Lyme Disease in the news thanks to Total Essex covering a story on Ruth Black. here
As many local newspapers do not keep these stories on line indefinitely I will copy and post below.
HUTTON: Mum Ruth Black left virtually bed bound as NHS 'fails to identify illness'
By editorial@gazettenews.co.uk
A WOMAN has accused the NHS of ruining her life, after medics failed to identify a debilitating illness which left her virtually bed-bound.
Mum-of-two Ruth Black, 34, spent eight months battling the symptoms of Lyme disease, but only diagnosed the condition after research on the internet.
She is now receiving treatment for the disease but fears it could take her up to a decade to recover.
"My experience with the NHS was horrific," Ruth said.
"They have cost me my health and left me with a chronic condition which could have been easily treated if it had been diagnosed earlier.
"I was a very lively, healthy woman before I became ill.
"It has completely devastated my life."
Ruth, who lives in Hutton with husband Cliff and sons Jamie, 6, and Lewis, who is 20 months old, fell ill in March 2010.
This prompted a series of visits to her GP over the next few months and trips to hospitals in Romford and Basildon.
Ruth said: "My first symptoms were just general tiredness.
"I felt exhausted and disorientated and was coming out in fevers. Then I started to get bad back pain, but I didn't think about it as I thought it was due to my carrying Lewis around."
However, as the weeks wore on, her symptoms became worse.
"I started itching like crazy and I had severe pain in my muscles.
"My skin was burning and it felt like I had been doused in petrol."
After a range of tests, including a brain scan and blood tests, Ruth gave up on the NHS and decided to visit a private hospital.
But she still could not get a diagnosis and so decided to turn to the internet for help.
"The more I researched, the more my illness seemed to fit a condition called Lyme disease," Ruth said. "The bizarre thing was that I had already been tested for Lyme disease via the NHS and privately."
During her research, she found the tests used by the NHS to diagnose Lyme disease are "very disputed".
She also eventually found a private clinic in Hertfordshire which diagnosed her with the condition in November last year.
However, because of the time it took to identify the illness, it is now chronic, meaning Ruth could take a long time to recover.
"It is a very, very slow process," she said. "I know people that have been on treatment for ten years and they are still not right."
Ruth is now taking antibiotics but, in another blow, is not eligible to receive them free on the NHS.
As a result, she now has to spend around £350 a month on drugs and other supplements.
She said: "The fact I am now left paying for all the treatment is a very bitter pill to swallow."
Cliff, 51, added: "It is difficult enough for people to battle against this horrendous illness without having to battle the establishment as well.
"This has impacted on our family, and I cannot understand how people are subjected to the lack of care and understanding that is required from our so-called health professionals."
Dr Kannan Athreya, 44, has been a GP at The Surgery in Mount Avenue, Shenfield, since 1996.
He told the Gazette that the internet could be a "useful tool" for helping people diagnose their illness, but stressed that it could also have its pitfalls.
"It is a very useful tool provided you know how to use it," he said.
A spokesman for Queen's Hospital, in Romford, said: "We have not had any contact from Mrs Black regarding the treatment she received.
"Lyme disease can be very difficult to diagnose, with tests often only showing an infection once the disease is advanced.
"If Mrs Black chooses to contact us we will, of course, look into her complaint."
A spokesman for Basildon Hospital said: "All patients brought to A&E as emergencies are given thorough investigation and treatment according to the symptoms they present.
"Sometimes it is appropriate for A&E to treat patients for immediate symptoms and then discharge back to their GP."
Meanwhile, NHS South West Essex, which runs GP services in Brentwood, said: "We cannot comment on this case without a review of the patient's case notes."
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However perhaps even more telling are the comments left on this article:-
I had no idea this was such a big problem but the messages on this website would seem to suggest so. Very interesting and I'm glad it has been brought to my attention.
Unamit, Chelmsford
commented on 11-Feb-2011 01:01
Lyme (Borrelia) infection is usually caught from infected ticks, which are found everywhere, as they are carried by birds and all domestic animals and wildlife. Hosts for ticks can be any small animal, like hedgehogs, so allotments often comprise hot-spots for Lyme.
Even if you remove the tick before it has time to transmit Lyme, you can still get serious co-infections from the tick, such as Bartonella ("cat-scratch fever"). Babesia is a malaria-like infection. There¿s a list of other infections including Ehrlichia, Mycoplasma and others which may not yet be recognised in the UK like Tick-Borne Encephalitis.
Lyme Disease can be transmitted by other biting insects like stable-flies, fleas, lice, mites - and can be transmitted from a mother to her offspring, either via the placenta or through the milk. Or like its cousin syphilis, by sexual contact. It appears to be a major cause of autism in children and also Alzheimer's.
The scary thing about Lyme (Borrelia) infection is its effects on the body. It can mimic virtually every other disease. The bacterium itself is the most sophisticated known to man. Being a corkscrew-shape spirochaete it resembles its relatives like Leptospira (Weil's Disease) caught from rat's urine, and Syphilis, but it has many more genes and plasmids to generate its outer surface proteins (OSP's) so it can change its coat to avoid detection by the body's immune system. Which is a reason why we get negative blood tests, as our current blood tests (serology) are very primitive and only pick up antibodies generated by our immune systems in response to OSP's presented to it.
Simple bacteria often move around by being driven by a rotating filament attached to one end, that acts just like an outboard motor, spins and moves the bacterium. Borrelia has a bundle of flagellae wrapped around its cellular contents, which act like an "inboard motor" and drive the bacterium in a corkscrew manner which enables it to penetrate every cell in the body.
Classically it penetrates the cartilage of joints and causes an arthritis that appears to move from joint to joint, so-called "migratory arthritis", and which occurs even in young children. In fact it was first characterised because of an outbreak of arthritis in children. Its main effect is to penetrate nerves and disrupt them, technically "neuro-borreliosis". Facial nerves are attacked and you get classic Bell's Palsy with droopy eyelids and jaw. This can spread to the intestine and cause signs of constipation and colic, known as Bell's Palsy of the Gut. It can affect nerves feeding glands so there are many effects like diabetes & thyroid problems. Many people recover from allergic situations when treated for Lyme.
If a suspected Lyme infection is treated within the first few (4 to 6) weeks of the actual infection, with reasonably high doses of even simple penicillin, it may be eliminated. But many people don't know whether they've been bitten, let alone when, as they may not have the classic tick-bite "bull's eye" rash, said to be unique to Lyme.
Once the bacteria have penetrated deep into the tissues - they prefer the low oxygen levels found in cartilage, tendon, etc - they can be difficult to reach with antibiotics. High doses and long courses are absolutely essential. Rotating antibiotics can help.
The bacterium can also hide away in the form of cysts, coccal and CWD (mycoplasmal) forms, and in biofilms where they are neither recognised by the immune system nor touchable by antibiotics - just the same as Syphilis and Tuberculosis. But once established, you may have the infection for life, and you can only control, perhaps never cure it, even with repeated courses of antibiotics.
One myth is that all antibiotics have potentially serious side effects, such as you may develop an allergy to penicillin. None of the side effects are unconquerable and are often worth the risk considering the life destroying effects of Lyme Disease.
It is normal to prescribe long-term antibiotics for certain well-known diseases like TB, Brucellosis, Syphilis and even acne. Lyme is at least as important as these.
The problem of resistant bacteria, like MRSA in hospitals, has everything to do with the hospital environment and hygiene and very little to do with the use of antibiotics.
In fact, it is "under-treatment" of infections by doctors that has allowed resistant organisms to survive. If they used higher doses and longer courses in the first place, the organisms would not have had a chance to develop resistance.
Drug resistance in Lyme doesn't seem to be a problem when antibiotics are rotated properly - it's co-infections like Babesia that cause the problems. Rarely does Borrelia come on its own. Ticks often transmit other bugs, called "co-infections". Babesia is a malaria-like parasite that only responds to anti-malarials.
Laurence Swift (retired vet), Herne Bay, Kent, ENGLAND
commented on 10-Feb-2011 19:40
For anyone struck down with the many and varied symptoms of this debilitating disease it can be a very frightening experience excerbated by the ignorance about diagnosis and required treatment which varies considerably across the country. Fortunately when I was struck down,bedridden and finally hospitalised in 2008 I was in the right area to get a confirmed diagnosis and treatment to enable my to regain nearly but not all my pre illness health.
This illness should not be a postcode lottery for if diagnosed and treated in the early stages it prevents the extreme and debilitaing symptoms which for some can be permanent.
It needs to be recognised across the board no matter which part of the uk you live in.
My own local authority have a web page dedicated to tick awareness, Lyme disease and associated issues and yet my county council appear ignorant because on a secret shopper phone call to them I hit a brick wall- I ask how can this be.?
Every organisation, health authority, outdoor workers employer, countryside user, park control authorities, etc etc etc needs to be clued up on lyme disease ,the risks, the precautions and what to do if you think you may have had a tick bite regardless of whether the tick is carrying the borrellia bacteria. ( even IF you see a tick attached, many are seed size,it won't tell you it carries the bacteria!)
Simple precautions can help to eliminate the risk from contracting lyme disease but unfortunately it is often long after a bite, which a victim may not even been aware of, before symptoms start and they may not always be associated with lyme and a tick bite.
Finally to the gentleman who in a earlier comment wrote 'oh shut up' I sincerely hope you/family member/friend never get infected by lyme because I can assure you it would definately make you change your attitude.
Sue Mitchell, West Sussex
commented on 10-Feb-2011 19:02
Thank you to Ruth and the Essex Chronicle. Ruth's story is very similar to my own. I had decades of illness before I finally got the right diagnosis.
Years ago I started to get episodes of flu-like illnesses and a sort of brain fog and fatigue that rest or sleep wouldn't shift. I'd recover from each one and feel fine, but a few weeks later I'd be ill again. Doctors told me I'd probably picked up a virus, or I had post-viral syndrome, or it was caused by stress, or I was working too hard and needed a holiday. As the years went by my health very gradually deteriorated further. I saw numerous GPs and I was referred to different specialists in the NHS, including an infectious diseases specialist who told me I was suffering from anxiety and I wasn't ill at all.
Each time I was prescribed a short course of antibiotics I felt much better, but when I finished it I'd become ill again.
At one point I was admitted to hospital and given a blood transfusion when my blood count suddenly crashed for apparently no reason, but no diagnosis was offered.
I carried on trying to lead as normal a life as possible, but eventually I became so ill I could barely function and I was diagnosed by the NHS with CFS. By then I was also having repeated migraine and vomiting attacks, dreadful cramps in my legs and feet, I'd developed loud tinnitus, I seemed to have become dyslexic and my balance was poor. I was very weak, but out of desperation I managed to do a little research on the internet and kept coming up with Lyme Disease as a match for my symptoms.
I found the Lyme Disease Action, BADA-UK and Eurolyme websites and they have been a great source of information and support. I discovered a specialist private clinic that treats Lyme Disease and it's through their expertise that I discovered I have 3 strains of Lyme Disease and 2 other infections ticks often carry.
My health is finally improving for the first time in years thanks to their treatment, but it will take a long time for me to regain anything approaching normal health after so many decades of untreated neurological infections.
My life has been completely derailed by this awful illness. I'm paying for my treatment myself, having sold my home, as the NHS has declined to fund my treatment costs. It is indeed a bitter pill to swallow.
Lesley, Hertfordshire
commented on 10-Feb-2011 11:25
do shut up George
Anon, Maldon commented on 10-Feb-2011 08:20
I too have Lyme disease, confirmed by blood tests from laboratories in the USA and Germany. I cannot access care for my condition on the NHS and like Ruth have to pay privately for my treatment and antibiotics.I have now been in treatment for nearly 2 years and still have days when I am overwhelmed by fatigue and have to stay in bed. However, I am also now having days when I can function well.
The neglect of patients with Lyme disease is disgraceful.
I worked for the NHS for 14 years and was proud to do so. However, I now feel completely let down by the organisation I once thought so highly of.
The NHS needs to educate their staff about Lyme disease and get up to speed with accurate diagnosis and treatment.
The numbers of infected patients are increasing year on year.
Catherine, UK
commented on 09-Feb-2011 20:36
Another one, thank you very much to Ruth and Essex Chronicle for publishing this story.
One day, just one day, someone will eventually join the dots and realise this is a major problem.
How many people are trying to 'manage' their symptoms under the ME, CFS, Fibromyalgia, etc. labels when really they should be continuing to look for the cause and treating that?
If there are any doctors reading this, I would be very grateful if you would take some time to look up the many reams of research from very well-respected experts out there and stop assuming we don't have Lyme in the UK. Your patients will thank you for it.
So, stop hiding away from it just because it's political, let's get it out there!
Jan, Ipswich
commented on 09-Feb-2011 15:53
Is there no Dr House in the house ?
George, Chelmsford
commented on 09-Feb-2011 15:17
Ruth's story is like so many more here in the UK and sadly that also includes children who after all are the most vulnerable.
There is not one Paediatrician in the UK who has bothered to throughly understand this disease.
Our doctors are advised by the HPA who say that the IDSA guidelines are authoritive and yet there is a considerable body of evidence on this emerging disease that contradicts those guidelines. http://www.ilads.org/lyme_disease/lyme_slides.html
Ben Luft's research sequenced the Genome and he found that some strains of Borrelia are simple and easy to cure whilst others are more complex and harder to treat.(Of course in the UK we have other species which further complicates things)
Then Ben Luft says about the many co infections that can also be transmitted by the bite of the tick.
(We need to stop and consider that in their early stages these ticks will have fed on vermin and other small mammals before injecting that blood and infections into us.)
Luft presented at the following Workshop. Congress mandated the NIH to hold a workshop on the state of the science in Lyme Disease and other tick borne illnesses this was held by the Institute of Medicine and can be watched at the videocast here
http://www.tvworldwide.com/events/iom/101011/
This leaves those watching in no doubt as to the complexities of tick borne illness, it is far too early to be imposing restrictive treatment practises.
I was fortunate in having a very thinking GP although it took 5 doctors and 3 Rheumatologists 4 years to diagnose me with Lyme Disease.
It was a chance course of antibiotics which improved my symptoms and led GP to suspect Lyme Disease, I had attended the surgery at the time of bites, bulls eye rashes, summer flu and migrating arthralgias ( all red flags for Lyme Disease).
As my symptoms progressed I was diagnosed with Fibromyalgia, ME/CFS, Arthritis, Muscle Weakness, Musculoskeletal Disease and then Polymyalgia Rheumatica and unfortunately put on steroids which are contra indicated if you are fighting a bacterial infection.
There have been several other patients diagnosed with Lyme Disease now at my surgery and in my locality near Guildford, once doctors start to look they will find.
I am 100% recovered now but it has been a very long struggle, I was Retired early from the Civil Service on Ill health grounds, at my worst I had difficulty standing from a chair and walking across a room and for 3 1/2 years had difficulty walking up or down stairs properly now I have no pain or disability and can garden and cycle again. How amazing is that.
There is important information available through UK charity at www.lymediseaseaction.org.uk
This is a Medical disgrace of International proportions because everyone cow tows to a small group of biased doctors who wrote the outdated and much contested IDSA Lyme Disease Guidelines, guidelines which were based more on the opinions of those who receive significant financial rewards from their involvement with Lyme Disease and not on all the scientific evidence available.
The makers of the test kits used in the UK Trinity Biotech say that a negative test can not be used to rule out Lyme Disease, it's an antibody test!! and yet Doctors are not made aware of this and therefore say to patients you can't have Lyme.
What they fail to know is that the tests can miss up to 50% of cases.
Imagine spending the rest of your life with a painful, debilitating and crippling illness when just simple oral antibiotics can restore your health if it is found to be a bacterial infection Lyme Disease and co infections.
Joanne Drayson, Guildford Surrey
commented on 09-Feb-2011 14:48
The situation with Lyme disease is dreadful, and not just in the UK, although perhaps our country has had the worst deal in Europe as far as warning signs to the general public go.
At least in Germany and other EU countries, GPs surgeries have warning posters. Why don't we?
In the Netherlands, 65,000 people signed a petition last year demanding treatment for chronic sufferers, and a public health strategy to combat new infections.
Here in the UK a similar petition is under weigh, here at:http://www.ipetitions.com/petition/uklymepetition/and I urge everyone to take a look at the signatures and comments, and see that Ruth's story is being repeated all over the country. And please sign to support us!
Only those with private funds are being treated properly.
Many people with Lyme don't know they have it - but they may be diagnosed as having Multiple Sclerosis type symptoms, ME or Chronic Fatigue Syndrome, Parkinson's type symptoms, jaw and dental symptoms, strange optical problems, even dementia, and mental health problems.
Lyme was first recognised as being endemic in the UK in 1989, but only a few people know what a tick looks like or that its bite is painless and the newly-hatched baby ticks are as small as a poppy seed.
Why this has been kept so hush-hush is very puzzling, as each day there will be more people infected because they had no idea that Lyme is in Britain.
My own GPs practice head said "It's only in deer ticks" and that such ignorance exists in GPs is incredible - Lyme is carried by the sheep tick, and by vole ticks and mouse ticks and bird ticks, and you can get bitten in your own back garden or a park in a city.
A big "Thank you" to Ruth and your paper for bringing this state of affairs into the public eye, because each article like this, in the absence of a government strategy, may help hundreds or thousand of people to learn about Lyme.
I myself was left for 20 years before I had a diagnosis, being labelled instead as having post viral fatigue then ME and Fibromyalgia. I am now trying to survive on state benefits having sold my house long ago, and I cannot afford any treatment at all.
I worked and contributed until I was 38 years old, paying my taxes and National Insurance, only to be left infected with a disease worse than AIDS and syphilis and TB combined.
The symptoms seem to move around the body, and many people have Fibromyalgia pains, but some might have palpitations, or even a stroke or heart weakening as a result of Lyme and the other bacteria and viruses carried in ticks.
The infection can lie dormant for a month or even longer after the bite. It's a hard disease to diagnose, but the health services are doing none of us any favours by playing down the fact that Lyme is not rare at all, and by also saying their tests are 100% accurate, when all of the scientific literature has said again and again that the tests are very variable and just cannot be relied on to say whether the person has the disease or not.
Even the test kit manufacturers say this. But the Lyme testing labs do not pass that information on to any doctors, not even the top infectious disease doctors as far as I know.
This is a scandal which has been simmering under the horizon for 40 years and it needs top thinking directed at the problem rather than the pretence that there is no problem.
Denise Longman MSc, Lowestoft Suffolk
commented on 09-Feb-2011 12:17
Showing posts with label Bells Palsy. Show all posts
Showing posts with label Bells Palsy. Show all posts
Friday, 11 February 2011
Tuesday, 30 November 2010
TIME TO EDUCATE OUR NHS CONSULTANTS
I don't generally post personal stories of patients with Lyme disease but this one particularly touched me.
With permission I am only going to post a small section of it but do go to the full details here
Apart from highlighting patients' struggle with the disease and getting a diagnosis for their multi system problems it so highlights the crass comments our 'esteemed' medical professionals come out with, it is time they were taken to task over their behaviour and held to account for their comments to patients when clearly they are not informed of the complexities of Tick borne illness. Lyme Disease and the many co infections that can also affect us.
***************************************************************************** the ----establishment had so badly let me down and basically left me for dead at 36 years old !!
I went to London to the Infectious Disease clinic and the journey itself was hard as I am so poorly.
We were seen and told from the offset that, "we were there to listen to his opinion and that we would not be discussing Lyme until we had heard what he had to say" and i felt like a naughty schoolgirl that had been pulled up in front of the headmaster and was really tired of being treated so awfully when I was sick .
He asked about where I had traveled to tropically and then in Europe and then in the UK.... I reeled of the list of many places as I had travelled to all of these in my youth through bar work.
He then said "well you haven't been anywhere that is tick endemic and so its not Lyme" ..I, this time, had no patience to argue ,as the last time had taught me I was banging my head up a brick wall so I just sat there and silently disagreed with him in my head.
So he preceded to examine me which was very different to the previous 20 or so examinations I'd had by other doctors...and consisted of my lymph glands down my body and my spleen....he had said he would check my eyes as I was wearing the sunglasses but after he had done his tests he told me to go back and sit down and did not again look at toenails,rash or the eyes .
My husband then played him the video footage of me and my attack ...he watched about 10 seconds of it and said" that's enough "and then showed him the positive test results and he asked ..".who done these..."my husband replied "Igenex" and he said "well i can get a positive result for any test I want if I send it to the right place "and then told me that the "Americans are all mental and blame every symptom they have on Lyme" ....he said "don't get fixated with Lyme "...
to which I replied "I'm not fixated ..its just I have every symptom ..even definitive ones of Lyme ..positive test results that are non biased .. and the most important thing is ...if its not then what is it ??..
because I have seen nearly 20 doctors now ...who either tell me they don't know.. or we can tell you what its not ...or its a headache.... or a stiff neck ... or I may never get a diagnosis for this...or the last doctor who had the cheek to tell me there was NOTHING wrong with me...or its all in your head ....so believe me, I'm not fixated, I just haven't even been given anything else that it realistically could be ...and the fact that this is capable of evading normal routine tests, which is what's happened with me is surely proof enough to give antibiotic treatment a go
""He then said that, as this is an infectious disease clinic then he was going to run 3 tests of diseases that are of African nature..... and although the timing is out as to when I should have got ill with these after my return from Africa..... and the chances of me having them are next to none... he needed to rule them out anyway ....
to which I agreed ,but wondered why this wasn't checked for in the hospital on my admission on that first night ..as they were made fully aware of the fact we had not long returned from a tropical country and they did tell my husband that all possibilities had been checked for ...
Then we had the punchline delivered to us..in a very sinister way indeed ... considering he had just told me that if he wanted to ,then he could get a positive result for any test if he sent it to the right place.
..one of the tests that he was running was for an African borne disease that's VERY ,VERY RARE.. but the only treatment for it is to pump arsenic into your blood ..which results in 3 out of 5 death rate anyway...
I couldn't believe it ...one of the possible options that he'd managed to come up with rather than even acknowledging there is even a slight chance that it might be Lyme was of a rare disease that you had hardly any chance of surviving from the treatment..
.and it had sounded more like a threat ...
and I wondered why he had no worries about putting arsenic into me but I was having such a tough time getting antibiotics ..
I had also, before I'd found Lyme gone through, like I said every disease going ..and had studied African diseases especially hard, as we had spent a lot of time in Africa in the last two years and the symptoms and timing didn't match any of the diseases. .
So I'd agreed to his tests (or death sentence )that he had given me... and then I continued talking about Lyme .
This is when I believe ...he used the sentence that it had taken the doctors all these months to come up with ...of how to get around this situation, without actually telling me they would not treat me long term.
He said I am going to put you on a course of doxycycline for 3 weeks..if you get better then it was Lyme and you are cured...if not then it wasn't Lyme.
Here's how this interprets ...3 weeks course of doxycycline does treat and cure Lyme disease if caught in the early stages ..ie after the bite of an infected tick ..or the trademark rash being present ...after that if left untreated it grows in your body and will eventually turn into stage 2 which is harder to treat... and if still not detected it will go to stage 3 ...when it crosses the blood borne barrier and enters the brain and internal organs and this is where I am at and is extremely difficult to treat
and the NHS are not willing to invest the time or money to see if long term IV antibiotics make a difference...even though it has been proved by real people suffering with the disease at late stage... who have had to raise money and sell there homes .beg and borrow to find theirself a LLMD (Lyme Literate Medical Doctor) who specialises in the treatment of Lyme and its co infections and understands the complexity of the disease and of the treatment plan ,for life .
This is the aim of this appeal... I need to find myself a LLMD who will treat me and this will be outside the NHS and possibly outside the UK ...
Thankyou for reading my story ..please educate yourself and your family and friends on Lyme....... because if I can stop this happening to someone else it will do some good ...please if you are on facebook join the group that was my daughters idea and my husband set up ...called Would you pay a £1 to help save my mummy's life?..pass it on to your friends and ask them to pass it on and so on ...the more people that join ..the more awareness there is and it also gives my little girl some hope and makes us not feel not so totally alone in this situation http://www.facebook.com/profile.php?id=1109650270&ref=search#!/group.php?gid=134675306560444&ref=mf thankyou so much if you would like to donate click on the link below or if you would like to send a cheque ..please make payable to ...The Sonia Smith Appeal Fund 29 St Johns Rd
Bletchley
Milton Keynes
MK3 5DU
England
or for further queries contact soniasmithappeal@aol.com
****************************************************************
Initially Sonia was admitted to hospital with a suspected Brain Tumour or stroke but when tests showed nothing she was dismissed with 'It's all in your head' despite symptoms of paralysis, Bells Palsy, verbal stuttering and difficulties speaking, light and sound sensitivity to mention just a few of her symptoms.
As most of us find with Lyme Disease here in the UK like elsewhere in the World getting diagnosis even with positive Igenex tests is no guarantee that NHS will treat with antibiotics. Quite remarkable that this ID specialist would consider IV arsenic for some rare African Disease and yet simple antibiotics even oral antibiotics have significantly improved the lives of many patients with a clinical diagnosis of Lyme Disease let alone a serological diagnosis.
All these consultants in denial should listen to the recent presentations at the Institute of Medicine Workshop showing how complex all these tick borne diseases are to test for let alone to treat. Click here
With permission I am only going to post a small section of it but do go to the full details here
Apart from highlighting patients' struggle with the disease and getting a diagnosis for their multi system problems it so highlights the crass comments our 'esteemed' medical professionals come out with, it is time they were taken to task over their behaviour and held to account for their comments to patients when clearly they are not informed of the complexities of Tick borne illness. Lyme Disease and the many co infections that can also affect us.
***************************************************************************** the ----establishment had so badly let me down and basically left me for dead at 36 years old !!
I went to London to the Infectious Disease clinic and the journey itself was hard as I am so poorly.
We were seen and told from the offset that, "we were there to listen to his opinion and that we would not be discussing Lyme until we had heard what he had to say" and i felt like a naughty schoolgirl that had been pulled up in front of the headmaster and was really tired of being treated so awfully when I was sick .
He asked about where I had traveled to tropically and then in Europe and then in the UK.... I reeled of the list of many places as I had travelled to all of these in my youth through bar work.
He then said "well you haven't been anywhere that is tick endemic and so its not Lyme" ..I, this time, had no patience to argue ,as the last time had taught me I was banging my head up a brick wall so I just sat there and silently disagreed with him in my head.
So he preceded to examine me which was very different to the previous 20 or so examinations I'd had by other doctors...and consisted of my lymph glands down my body and my spleen....he had said he would check my eyes as I was wearing the sunglasses but after he had done his tests he told me to go back and sit down and did not again look at toenails,rash or the eyes .
My husband then played him the video footage of me and my attack ...he watched about 10 seconds of it and said" that's enough "and then showed him the positive test results and he asked ..".who done these..."my husband replied "Igenex" and he said "well i can get a positive result for any test I want if I send it to the right place "and then told me that the "Americans are all mental and blame every symptom they have on Lyme" ....he said "don't get fixated with Lyme "...
to which I replied "I'm not fixated ..its just I have every symptom ..even definitive ones of Lyme ..positive test results that are non biased .. and the most important thing is ...if its not then what is it ??..
because I have seen nearly 20 doctors now ...who either tell me they don't know.. or we can tell you what its not ...or its a headache.... or a stiff neck ... or I may never get a diagnosis for this...or the last doctor who had the cheek to tell me there was NOTHING wrong with me...or its all in your head ....so believe me, I'm not fixated, I just haven't even been given anything else that it realistically could be ...and the fact that this is capable of evading normal routine tests, which is what's happened with me is surely proof enough to give antibiotic treatment a go
""He then said that, as this is an infectious disease clinic then he was going to run 3 tests of diseases that are of African nature..... and although the timing is out as to when I should have got ill with these after my return from Africa..... and the chances of me having them are next to none... he needed to rule them out anyway ....
to which I agreed ,but wondered why this wasn't checked for in the hospital on my admission on that first night ..as they were made fully aware of the fact we had not long returned from a tropical country and they did tell my husband that all possibilities had been checked for ...
Then we had the punchline delivered to us..in a very sinister way indeed ... considering he had just told me that if he wanted to ,then he could get a positive result for any test if he sent it to the right place.
..one of the tests that he was running was for an African borne disease that's VERY ,VERY RARE.. but the only treatment for it is to pump arsenic into your blood ..which results in 3 out of 5 death rate anyway...
I couldn't believe it ...one of the possible options that he'd managed to come up with rather than even acknowledging there is even a slight chance that it might be Lyme was of a rare disease that you had hardly any chance of surviving from the treatment..
.and it had sounded more like a threat ...
and I wondered why he had no worries about putting arsenic into me but I was having such a tough time getting antibiotics ..
I had also, before I'd found Lyme gone through, like I said every disease going ..and had studied African diseases especially hard, as we had spent a lot of time in Africa in the last two years and the symptoms and timing didn't match any of the diseases. .
So I'd agreed to his tests (or death sentence )that he had given me... and then I continued talking about Lyme .
This is when I believe ...he used the sentence that it had taken the doctors all these months to come up with ...of how to get around this situation, without actually telling me they would not treat me long term.
He said I am going to put you on a course of doxycycline for 3 weeks..if you get better then it was Lyme and you are cured...if not then it wasn't Lyme.
Here's how this interprets ...3 weeks course of doxycycline does treat and cure Lyme disease if caught in the early stages ..ie after the bite of an infected tick ..or the trademark rash being present ...after that if left untreated it grows in your body and will eventually turn into stage 2 which is harder to treat... and if still not detected it will go to stage 3 ...when it crosses the blood borne barrier and enters the brain and internal organs and this is where I am at and is extremely difficult to treat
and the NHS are not willing to invest the time or money to see if long term IV antibiotics make a difference...even though it has been proved by real people suffering with the disease at late stage... who have had to raise money and sell there homes .beg and borrow to find theirself a LLMD (Lyme Literate Medical Doctor) who specialises in the treatment of Lyme and its co infections and understands the complexity of the disease and of the treatment plan ,for life .
This is the aim of this appeal... I need to find myself a LLMD who will treat me and this will be outside the NHS and possibly outside the UK ...
Thankyou for reading my story ..please educate yourself and your family and friends on Lyme....... because if I can stop this happening to someone else it will do some good ...please if you are on facebook join the group that was my daughters idea and my husband set up ...called Would you pay a £1 to help save my mummy's life?..pass it on to your friends and ask them to pass it on and so on ...the more people that join ..the more awareness there is and it also gives my little girl some hope and makes us not feel not so totally alone in this situation http://www.facebook.com/profile.php?id=1109650270&ref=search#!/group.php?gid=134675306560444&ref=mf thankyou so much if you would like to donate click on the link below or if you would like to send a cheque ..please make payable to ...The Sonia Smith Appeal Fund 29 St Johns Rd
Bletchley
Milton Keynes
MK3 5DU
England
or for further queries contact soniasmithappeal@aol.com
****************************************************************
Initially Sonia was admitted to hospital with a suspected Brain Tumour or stroke but when tests showed nothing she was dismissed with 'It's all in your head' despite symptoms of paralysis, Bells Palsy, verbal stuttering and difficulties speaking, light and sound sensitivity to mention just a few of her symptoms.
As most of us find with Lyme Disease here in the UK like elsewhere in the World getting diagnosis even with positive Igenex tests is no guarantee that NHS will treat with antibiotics. Quite remarkable that this ID specialist would consider IV arsenic for some rare African Disease and yet simple antibiotics even oral antibiotics have significantly improved the lives of many patients with a clinical diagnosis of Lyme Disease let alone a serological diagnosis.
All these consultants in denial should listen to the recent presentations at the Institute of Medicine Workshop showing how complex all these tick borne diseases are to test for let alone to treat. Click here
Wednesday, 10 November 2010
CLINICAL DIAGNOSIS - SAY MAKERS OF LYME DISEASE TEST KITS
Trinity Biotech make the test kits for Lyme Disease used here in the UK.
It is interesting to read their recently updated website here
Lyme disease is a multisystem disease caused by the spirochete Borrelia burgdorferi (1). The disease has been documented in Europe since early this century. It was documented in the United States during an epidemic in 1975 among children in Old Lyme Connecticut who demonstrated arthritic symptoms. Steere, et al. recognized the disease as a unique clinical entity (2,3). The symptoms of Lyme disease have been mistaken with many diseases including: juvenile rheumatoid arthritis, lupus erythematosis, multiple sclerosis, Bell’s palsy, rheumatic fever, Reiter's Syndrome, myocarditis and viral meningitis (4).
The spirochete is transmitted by ticks of the genus Ixodes from animal reservoirs such as deer, mice, dogs, horses and birds. The ticks are commonly found on vegetation in endemic regions especially in wooded areas common to the animal reservoir. The incidence of human infection coincides with the tick season from May through September (3,5).
Although the symptoms of Lyme Disease are varied and sometimes unclear, three distinct phases of the disease are recognized. Early manifestations include a single or multiple rash called erythema migrans (EM), a meningitis stage during the next weeks to months is often seen. Late manifestations are recognized to include arthritis or neurologic signs and symptoms. In asymptomatic or subclinical cases, symptoms of infection may not be evident until the later stages of disease (5).
Isolation of B. burgdorferi in culture is definitive evidence of active infection, but is not practical. Detection of specific antibodies is practical but an indirect marker of exposure. Patients produce IgM antibodies within a few weeks of the appearance of EM. Although only IgM antibodies may be detectable during the first month, IgG antibodies increase in most patients after approximately one month. Detectable levels of both IgG and IgM may persist for years (5,6).
B. burgdorferi strains exhibit considerable antigenic variation. Patients often develop early antibodies to the flagellar antigen which can be cross reactive. Patients in the early stage of disease and a portion of patients with late manifestations may not have detectable antibodies. Early antimicrobial treatment, after appearance of EM may lead to diminished antibody concentrations. Serologic tests have been shown to have low sensitivity and specificity and, therefore, cannot be relied upon for establishing a diagnosis of Lyme disease (6,7,8).
The Second National Conference on Serological Diagnosis of Lyme disease (1994) recommended the use of a two-tier test system for Lyme serology in which positive and equivocal samples from a sensitive first-tier test must be further tested by a more specific method such as Western blot (second tier). Positive results in the second tier test provide supportive evidence of exposure to B. burgdorferi which could support a clinical diagnosis of Lyme disease but should not be used as a criterion for diagnosis (9).
***********************************************************
I don't think this could be put much clearer - negative tests can not be used to rule out the patient having Lyme Disease.
Why then are there so many doctors and consultants still telling patients here in the UK you don't have Lyme Disease your test result was negative?
Well I think the answer is that they are told this incorrect information from the 'expert' or certainly that was the case for me when I consulted a Rheumatologist who was taking an interest in Lyme Disease, he quoted this expert.
Thankfully for me I had a GP who had seen my amazing recovery on antibiotics, from being severely incapacitated with arthritis and muscle weakness and so continued to treat me on long term antibiotics despite the advice issued by our Health Protection Agency 'expert' who said she should stop giving me antibiotics. I continued to recover and can enjoy a normal life once more.
We need more doctors and consultants to be allowed to think for themselves and not be dictated to by a narrow definition which has insufficient basis to be used to restrict diagnosis and treatment of this emerging complex illness.
Whilst the science continues to emerge over this complex illness it is important to do our own research so that we can discuss with our doctors the best treatments for us, bearing in mind our doctors are often too busy to spend the time needed to read the abundant scientific research that shows that for some of us a short course of antibiotics is just not adequate.
It is interesting to read their recently updated website here
Lyme disease is a multisystem disease caused by the spirochete Borrelia burgdorferi (1). The disease has been documented in Europe since early this century. It was documented in the United States during an epidemic in 1975 among children in Old Lyme Connecticut who demonstrated arthritic symptoms. Steere, et al. recognized the disease as a unique clinical entity (2,3). The symptoms of Lyme disease have been mistaken with many diseases including: juvenile rheumatoid arthritis, lupus erythematosis, multiple sclerosis, Bell’s palsy, rheumatic fever, Reiter's Syndrome, myocarditis and viral meningitis (4).
The spirochete is transmitted by ticks of the genus Ixodes from animal reservoirs such as deer, mice, dogs, horses and birds. The ticks are commonly found on vegetation in endemic regions especially in wooded areas common to the animal reservoir. The incidence of human infection coincides with the tick season from May through September (3,5).
Although the symptoms of Lyme Disease are varied and sometimes unclear, three distinct phases of the disease are recognized. Early manifestations include a single or multiple rash called erythema migrans (EM), a meningitis stage during the next weeks to months is often seen. Late manifestations are recognized to include arthritis or neurologic signs and symptoms. In asymptomatic or subclinical cases, symptoms of infection may not be evident until the later stages of disease (5).
Isolation of B. burgdorferi in culture is definitive evidence of active infection, but is not practical. Detection of specific antibodies is practical but an indirect marker of exposure. Patients produce IgM antibodies within a few weeks of the appearance of EM. Although only IgM antibodies may be detectable during the first month, IgG antibodies increase in most patients after approximately one month. Detectable levels of both IgG and IgM may persist for years (5,6).
B. burgdorferi strains exhibit considerable antigenic variation. Patients often develop early antibodies to the flagellar antigen which can be cross reactive. Patients in the early stage of disease and a portion of patients with late manifestations may not have detectable antibodies. Early antimicrobial treatment, after appearance of EM may lead to diminished antibody concentrations. Serologic tests have been shown to have low sensitivity and specificity and, therefore, cannot be relied upon for establishing a diagnosis of Lyme disease (6,7,8).
The Second National Conference on Serological Diagnosis of Lyme disease (1994) recommended the use of a two-tier test system for Lyme serology in which positive and equivocal samples from a sensitive first-tier test must be further tested by a more specific method such as Western blot (second tier). Positive results in the second tier test provide supportive evidence of exposure to B. burgdorferi which could support a clinical diagnosis of Lyme disease but should not be used as a criterion for diagnosis (9).
***********************************************************
I don't think this could be put much clearer - negative tests can not be used to rule out the patient having Lyme Disease.
Why then are there so many doctors and consultants still telling patients here in the UK you don't have Lyme Disease your test result was negative?
Well I think the answer is that they are told this incorrect information from the 'expert' or certainly that was the case for me when I consulted a Rheumatologist who was taking an interest in Lyme Disease, he quoted this expert.
Thankfully for me I had a GP who had seen my amazing recovery on antibiotics, from being severely incapacitated with arthritis and muscle weakness and so continued to treat me on long term antibiotics despite the advice issued by our Health Protection Agency 'expert' who said she should stop giving me antibiotics. I continued to recover and can enjoy a normal life once more.
We need more doctors and consultants to be allowed to think for themselves and not be dictated to by a narrow definition which has insufficient basis to be used to restrict diagnosis and treatment of this emerging complex illness.
Whilst the science continues to emerge over this complex illness it is important to do our own research so that we can discuss with our doctors the best treatments for us, bearing in mind our doctors are often too busy to spend the time needed to read the abundant scientific research that shows that for some of us a short course of antibiotics is just not adequate.
Thursday, 28 October 2010
UK ADVICE ON LYME DISEASE
PATIENT UK article on Lyme Disease link here
Lyme Disease
This disease was formally described following the investigation of a collection of patients with rashes and swollen joints occurring in Lyme, Connecticut in 1975, and acquired the name 'Lyme disease' (Lyme arthritis) in 1977.1 The various rashes, however, had been recognised many years previously, as had their association with neurological problems.
Lyme disease is caused by a tick-borne spirochaete, Borrelia burgdorferi2 and others. The infectious spirochetes are transmitted to humans through the bite of certain Ixodes spp. ticks.
The disease is caused by the infection and the body's immune response to infection. Different strains of Borrelia spp. cause different clinical manifestations of Lyme disease and this explains differences between the disease in Europe and the disease in the USA.
Although there is a rising incidence this is likely to be due to better detection and surveillance.3 It is still a rare disease.
Pathophysiology
The spirochete responsible is transmitted from host to host by Ixodes spp. or deer ticks. Understanding the life cycle of these organisms gives better understanding of the epidemiology, other clinical aspects and prevention of Lyme disease.
The Ixodes tick:
Is made up of different species, found in different areas of the world. For example:
Ixodes persulcatus and Ixodes ricinus (European ticks), Ixodes scapularis, Ixodes pacificus.
Emerges in a larval form in the summer and feeds just once on a host animal (often a mouse).
In the spring the larva becomes a nymph and feeds, again only once, from a similar animal host. Humans can be victims in the nymph stage (85% of tick bites in humans occur at this time in spring and early summer).
In the autumn the adult tick finally emerges to feed on deer, again just once. Humans can be hosts at this stage (15% of tick bites in humans are at this stage and occur in the autumn).
The spirochete responsible:
Is transmitted by the tick. The tick must have fed on a host significantly infected with spirochete to pass on the infection to man.
Once it infects, the tick has to go through a particular cycle of multiplication and dissemination to salivary glands within the tick before it can be passed on to the animal victim. Hence a tick must be attached for 2-3 days to a person before infection can be passed on.
Once the spirochete infects the host there may be one of several consequences:
The infection is cleared by host defences. This means the person will have had no clinical manifestations, be asymptomatic but seropositive.
The organism spreads by direct invasion. This is believed to be a feature in early disease. For example, erythema migrans is thought to result from the inflammatory response to direct invasion of the organism in the skin.
The organism excites an immune response in the host which causes a variety of clinical manifestations around the body. In such cases there is no evidence of direct bacterial invasion. Host factors (immunological and genetic) are associated with development of disease in this form. For example, HLA- DR4 and HLA- DR2 are associated with such disease. The manifestations of Lyme disease are also related to the particular Borrelia spp. strain involved. Particular strains are found in different countries. For example:
B. burgdorferi garnii, found in Europe, is associated with neurological disease.
B. burgdorferi afzelii from Europe is associated with acrodermatitis chronica atrophicans.
B. burgdorferi sensu stricto is found on the East Coast of the USA.
B. burgdorferi predominates in the USA4 with an associated pattern of musculoskeletal complications.
B. valaisiana has a relatively high prevalence in British ticks, and does not appear to be associated with manifestations of disseminated borreliosis, which may explain the low incidence of Lyme borreliosis in the UK.
Lyme disease is now becoming global and mixed infections are becoming recognised.
Epidemiology
In the UK, areas where infection is acquired include:
Exmoor
The New Forest
The South Downs
Parts of Wiltshire and Berkshire
Thetford Forest
The Lake District
The Yorkshire moors
The Scottish Highlands
About 20% of confirmed cases are reported to have been acquired abroad:3
The USA
France
Germany
Austria
Scandinavia
Eastern Europe
Laboratory-confirmed reports of Lyme borreliosis have risen steadily since reporting began in 1986. Several factors have contributed to the observed increase, including increased awareness of the disease, access to diagnostic facilities, more sensitive diagnostic methods, the enhanced surveillance scheme (introduced in 1996) and, since 2000, more complete reporting of cases.3 Other possible factors producing a real increase include changes in the geographical ranges of I. ricinus both in the UK and Europe (successive mild winters), more recreational travel to high endemic areas and the increasing popularity of activity holidays (walking, trekking and mountain biking).3
Over 3,000 reports of Lyme borreliosis have been received since 1986, almost 2,800 of which have been reported since the introduction of enhanced surveillance in 1997.3
Mean annual incidence rates for laboratory-confirmed cases have risen from 0.06 per 100,000 total population for the period 1986 to 1992, to 0.64 cases per 100,000 total population in 2002, to 1.1 cases per 100,000 total population in 2005.3 The highest rates in the USA are 69.9 cases per 100,000 persons in Connecticut.
Lyme disease occurs in temperate regions of North America, Europe, and Asia.
In some countries of Europe, the incidence of Lyme disease has been estimated to be over 100 per 100,000 people a year.
Lyme disease infection has occurred in northern forested regions of Russia, in China, and in Japan.
It has not been found in tropical areas or in the southern hemisphere.
Risk of infection is greater if the tick is attached for more than 24 hours.
There is a rise in reported cases in autumn, but the peak occurs in spring and summer.
It is not possible to separate false-positive antibody tests from asymptomatic infection. In endemic areas as many as 10% of the population may have positive serology without any history of symptoms.
Cases of Lyme disease are lowest in urban areas in the eastern states of the USA.
In the USA there are peaks in incidence in the 5-9 year age group and the 50-54 year age group.
Presentation
It should be remembered that some infected people will have no symptoms. In Europe as many as 64% of patients with Lyme disease do not remember being bitten by the often innocuous tick. The presentation depends on the stage of disease at the time of presentation. For example:
Early Lyme Disease (Stage 1 or localised disease):
The characteristic manifestation is erythema migrans:
A circular rash at the site of the infectious tick attachment that radiates from the bite, within 2-40 days.
It expands over a period of days to weeks in 80-90% of people with Lyme disease.
It may be the only manifestation of disease in one third of patients.
In most patients there is only one episode of erythema migrans but, in about 20%, there are recurrent episodes.
About 40% of patients have multiple lesions (not the result of multiple bites).
Pyrexia, arthritis, musculoskeletal symptoms and local lymphadenopathy may occur in about two thirds of patients but one third of patients will develop no further symptoms.
Disseminated Lyme disease (or stage 2 disease ). This disseminated stage is still considered to be early infection and occurs weeks to months later, with:
Flu-like illness, oligoarthralgia (60%). Typically, with myalgia, multiple erythema migrans and sometimes systemic upset. Malaise and fatigue are very marked (particularly in the USA where 80% of patients are affected - about double that recorded in Europe).
Intermittent inflammatory arthritis:
This is more common in the USA.
In Europe joint pains are less often associated with inflammation.
Untreated episodes last about a week.
Most patients have at least 2 or 3 episodes and, even untreated, these resolve over a a few years.
Central nervous system disorders (15%):
These include facial (and other cranial nerve) palsies. These are the most common neurological manifestations in Europe and the USA.
Meningism and meningitis may occur alone or with other neurological manifestations. It is usually at the mild end of the spectrum but can be more severe.
Mild encephalitis producing malaise and fatigue.
Peripheral mononeuritis
Lymphocytic meningoradiculitis (or Bannwarth's syndrome which is more common in Europe than the USA).
Cardiovascular problems (10%):
This usually presents with syncopal episodes associated with fever.
Manifestations include transient atrioventricular block, myocarditis, or chronic dilated cardiomyopathy.
Occasionally hepatitis, orchitis, uveitis and panophthalmitis.
Lymphocytomas:
These are bluish-red nodular lesions infiltrated with lymphocytes.
They typically appear on the earlobe or nipple.
They occur in Europe but not the USA.
Late manifestations of Lyme disease (or stage 3 disease):
Untreated or inadequately treated Lyme disease can cause late disseminated manifestations weeks to months after infection. These late manifestations typically include prolonged arthritis, polyneuropathy, encephalopathy and symptoms consistent with fibromyalgia.
Chronic lyme arthritis - a chronic erosive arthropathy typically involving the knees.
Acrodermatitis chronica atrophicans . This is a bluish discolouration (normally on the lower leg over extensor surfaces) signifying epidermal atrophy, usually with mild sensory neuropathy and myalgia. It is generally seen in Europe not the USA.
Chronic neurological syndromes . Generally these appear to be more common in Europe. These include chronic neuropathies (usually with paraesthesia and occasionally with pain but not with motor deficit). They may even present as chronic fatigue syndromes, spastic paraparesis or depression.
Differential diagnosis
Chronic Lyme disease can be indistinguishable from fibromyalgia and chronic fatigue syndrome and in the assessment of these illnesses B. burgdorferi infection should be considered.
Noninfectious:
Urticaria
Gout
Psoriatic arthritis
Thyroid disease
Degenerative arthritis
Metabolic disorders (vitamin B12 deficiency, diabetes)
Heavy metal toxicity
Vasculitis
Systemic lupus erythematosus
Psychiatric disorders
Localised infections:
Gonococcal arthritis
Meningitis
Infections which can mimic certain aspects of the typical multisystem illness seen in chronic Lyme disease include:
Viral infections, for example:
Parvovirus B19
West Nile virus infection
Bacterial infections, for example:
Relapsing fever
Syphilis
Leptospirosis
Mycoplasma
Infective endocarditis
Investigations5
When to test and when to refer?
It is useful to have clear guidance on when to test and when to refer.
In all cases of suspected Lyme disease seek further advice on when and how to investigate from one or more sources. The following sources of advice are suggested:5
A microbiologist
An infectious diseases consultant
The Lyme Borreliosis Unit
In patients with erythema migrans:
Testing is not usually necessary with a history of tick bite (or possible exposure).
This characteristic rash with a history of tick bite or exposure is enough to make a diagnosis.
In primary care, testing should be considered:
With erythema migrans but with no tick bite (or tick exposure) and no other features of Lyme disease.
When there is isolated unilateral facial palsy (as with Bell's palsy) and Lyme disease needs excluding because of a history of tick bite (or tick exposure).
In patients with other neurological symptoms, joint or cardiac symptoms:
Test in primary care only after specialist advice.
Usually such patients require hospital admission or urgent specialist assessment.
What test?
There is currently no definitive test. Lyme disease is a clinical diagnosis and tests should be used to support clinical judgement. The most useful tests are antibody detection tests. The only national guidelines for testing come from the US Centers for Disease Control and Prevention (CDC).6 They recommend a 2-step testing process:
Lyme disease symptoms (other than erythema migrans) - take a blood sample for antibodies to B. burgdorferi. But note:
If negative and the sample is within 2 weeks of symptoms, repeat the test after 2 weeks.5
The enzyme immunoassay has a high false positive rate (low specificity) and can be positive with other conditions (for example, glandular fever, syphilis, rheumatoid arthritis and some autoimmune conditions).5
If positive or borderline by antibody testing using enzyme immunoassay, then retest using immunoblot or Western blotting to confirm the positive result.
Antibody testing in patients with erythema migrans is unhelpful because the rash develops before the antibodies.
Serology:
Serology may help in cases of endemic exposure where there are clinical features suggestive of disseminated disease.3
Serology - enzyme-linked immunosorbent assay (ELISA) - remains negative for several weeks in the initial phase, but is usually positive in serum and CSF in the disseminated stage. False positives may occur with other spirochaete infections.
Polymerase chain reaction (PCR) may identify very small numbers of spirochaetes in samples, and may influence decisions about whether to treat asymptomatic individuals with positive serology. Usually, however, PCR techniques are not helpful because of the uncertain correlation between positive results and the presence of live organisms in biological fluids.
Management
Discuss management with microbiologist and/or hospital specialists. The early use of antibiotics can prevent persistent, recurrent, and refractory Lyme disease. Antibiotics shorten clinical course and progression. The duration of therapy should be guided by clinical response, rather than by an arbitrary treatment course but guidance is offered.5 Generally speaking, long courses of antibiotics may be required (2-4 weeks or longer).
Management at a glance:
Tick bite- remove tick and consider a single-dose oral antibiotic in high-risk cases (not recommended routinely in UK-acquired tick bites)3
Skin manifestations - (erythema migrans) oral regimen 14-21 days
Arthritis - oral regimen for 30 days, repeated IV if the oral course is unsuccessful
Neuroborreliosis - oral regimen 30 days for all except encephalitis and encephalopathy
Encephalitis/encephalopathy - IV regimen for 28 days
Fibromyalgia - no evidence of benefit from trials with oral or IV treatment
Jarisch-Herxheimer reaction may occur soon after treatment is initiated.
Oral drug therapies for erythema migrans alone can be started in primary care. These are appropriate when:
There is no evidence of neurological, cardiac, or joint involvement.
Patients are not pregnant or breast-feeding.
Doxycycline (and tetracycline), amoxicillin, azithromycin, cefuroxime, and clarithromycin have similar favourable results in studies. For many Lyme disease patients, there is no clear advantage of parenteral therapy.
The following antibiotic regimens have been suggested:5
Adults:
First choice is doxycycline (100 mg twice-daily for 14 days) or amoxicillin (500 mg three times daily for 14 days).7. Some recommend 3 weeks course.6
If both doxycycline and amoxicillin are contra-indicated, use cefuroxime (500 mg twice-daily for 14 days) unless there is a history of anaphylaxis with a penicillin.
When a bacterial cellulitis cannot be excluded use 14 days of either co-amoxiclav alone (500/125 mg three times daily) or cefuroxime axetil alone (500 mg twice-daily) or amoxicillin (500 mg three times daily) with flucloxacillin (500 mg four times daily for 7 to14 days).
Children:
12 years of age or older, give 14 days of either amoxicillin (50 mg/kg per day in three divided doses) or doxycycline (100 mg twice-daily).
Less than 12 years of age, give 14 days of amoxicillin (50 mg/kg per day in three divided doses).
If both doxycycline and amoxicillin are contra-indicated give 14 days of cefuroxime axetil (30 mg/kg/day in two divided doses) unless there is a history of anaphylaxis with a penicillin.
When erythema migrans is indistinguishable from bacterial cellulitis, give 14 days of either co-amoxiclav, cefuroxime axetil or amoxicillin with flucloxacillin in age-appropriate doses.
Intravenous antibiotics are used in severe cases (for example, encephalitis, meningitis, optic neuritis, joint effusions, and heart block); or where there is failure of oral medications - in patients with persistent, recurrent, or refractory Lyme disease. Ceftriaxone, cefotaxime, and penicillin are commonly used intravenous antibiotics. The precise regime will depend on the individual situation but high doses of antibiotics, combination of antibiotics, sequential regimes and prolonged duration (one month or longer) are advocated.
Surgical synovectomy should be reserved for knee pain failing antibiotic treatment. Intra-articular steroid injection may be useful for persistent knee pain but runs the risk of masking persistent infection.
Treatment of Lyme arthritis - cefotaxime, ceftriaxone, doxycycline and amoxicillin plus probenecid are all effective.
Treatment of late neurological Lyme disease - Cefotaxime has been shown to improve neuropathy in patients with late Lyme disease. Intravenous ceftriaxone has been shown to be effective in Lyme encephalopathy.8 Other studies have shown no benefit of antibiotic for late neurological Lyme disease.
A temporary pacemaker may be required where there are carditis and conduction defects.
Prophylactic treatment of tick bite
Prophylactic antibiotics after Ixodes scapularis tick bites in Lyme disease endemic areas in North America have been shown to reduce the risk of developing clinical Lyme disease.9 This article in the New England Journal of Medicine suggests that a single dose of 200 mg of doxycycline within 72 hours of tick removal can prevent Lyme disease developing. The risk in the UK is such that use of prophylactic antibiotics is not recommended. It might be considered in very exceptional circumstances - for example, when a person travelling from an endemic area discovers a tick which has been attached for more than 48 hours.
Prognosis
Lyme disease is rarely fatal.
However, untreated Lyme disease can result in arthritis (50% of untreated people), meningitis or neuropathies (15% of untreated people), carditis (5-10% of untreated people with erythema migrans) and, rarely, encephalopathy. Over 90% of facial palsies due to Lyme disease resolve spontaneously, and most cases of Lyme carditis resolve without sequelae.10
The natural disease course of European borreliosis is not well defined and the effect of antibiotic treatment is unclear.11 There are no UK studies on the outcome of treatment.
Long-term sequelae also include poor concentration and fatigue.10
Recovery is often incomplete if the disease presents late.
Prevention
Measures to reduce infection in areas associated with ticks:
Wear long hair under a hat.
Keep to the middle of paths and avoid unnecessary brushes with foliage where ticks loiter waiting for the next passing mammal.
Avoid wooded areas where possible. Mowed grass areas are less likely to have ticks in them.
Keep legs and arms covered (wear trousers inside socks).
Use insect repellent for humans.
Use tick collars for pets (they can get Lyme disease) and inspect for (and remove) any ticks.
Inspect skin regularly during the day in at-risk areas (especially the groin, axillae and hairline). Remember ticks are unlikely to transmit Lyme disease until attached for several days.
If bitten by a tick:
Remove the tick:
Clean the surrounding skin with disinfectant to prevent bacterial infection.
Gently remove by grasping close to mouth parts with forceps (tweezers).12 The safest, quickest and most reliable method of removal is by using forceps applied to the tick as close to the skin as possible and removed with steady traction (and not twisting).13
Fragments of the mouthparts may be left in the skin, but these are small and rarely cause any problems, especially if the skin is disinfected before and after the procedure.
Note: cigarettes and glowing match heads or suffocating the tick with various agents (for example, petroleum jelly or solvents) are not recommended.13
If tweezers are not available, to avoid delay, find a cotton thread and tie a single loop of cotton around the tick's mouthparts, as close to the skin as possible and pull gently upwards and outwards.
Routine prophylaxis after tick bites is not currently recommended in the UK.3 However, in endemic areas, prophylaxis should be considered if there is a high risk of infection.9
Note: if the tick-bite area does not heal promptly or becomes painful, antibiotics may be necessary to treat other bacteria. Check for a spreading red patch, especially one that appears between 3 and 30 days after removal of the tick. However, remember that the risk of developing Lyme borreliosis from a tick bite is small, even in heavily infested areas and most doctors prefer not to treat patients with antibiotics unless they develop symptoms.13
A vaccine was licensed for use in the USA but later removed from the market.
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Document references
Steere AC, Malawista SE, Snydman DR, et al; Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7-17. [abstract]
Burgdorfer W, Barbour AG, Hayes SF, et al; Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317-9. [abstract]
Lyme borreliosis/Lyme disease, Health Protection Agency
No authors listed; Lyme disease--United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2004 May 7;53(17):365-9. [abstract]
Lyme disease, Clinical Knowledge Summaries (January 2010)
Wormser GP, Dattwyler RJ, Shapiro ED, et al; The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134. Epub 2006 Oct 2.; (reviewed 22/4/2010 by IDSA - no changes made to guidelines) [abstract]
British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)
Logigian EL, Kaplan RF, Steere AC; Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999 Aug;180(2):377-83. [abstract]
Nadelman RB, Nowakowski J, Fish D, et al; Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001 Jul 12;345(2):79-84. [abstract]
Seltzer EG, Gerber MA, Cartter ML, et al; Long-term outcomes of persons with Lyme disease. JAMA. 2000 Feb 2;283(5):609-16. [abstract]
Dinser R, Jendro MC, Schnarr S, et al; Antibiotic treatment of Lyme borreliosis: what is the evidence? Ann Rheum Dis. 2005 Apr;64(4):519-23. [abstract]
Correct Method of Tick Removal, Borreliosis and Associated Diseases Awareness UK Website.
EUCALB - European Union Concerted Action on Lyme Borreliosis; A pan-European information site supported by an advisory board comprising an expert group of physicians and biologists from across Europe.
Acknowledgements EMIS is grateful to Dr Richard Draper for writing this article and to Dr Colin Tidy for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2010.
Document ID: 7004
Document Version: 8
Document Reference: bgp442
Last Updated: 30 Jun 2010
Planned Review: 29 Jun 2013
Lyme Disease
This disease was formally described following the investigation of a collection of patients with rashes and swollen joints occurring in Lyme, Connecticut in 1975, and acquired the name 'Lyme disease' (Lyme arthritis) in 1977.1 The various rashes, however, had been recognised many years previously, as had their association with neurological problems.
Lyme disease is caused by a tick-borne spirochaete, Borrelia burgdorferi2 and others. The infectious spirochetes are transmitted to humans through the bite of certain Ixodes spp. ticks.
The disease is caused by the infection and the body's immune response to infection. Different strains of Borrelia spp. cause different clinical manifestations of Lyme disease and this explains differences between the disease in Europe and the disease in the USA.
Although there is a rising incidence this is likely to be due to better detection and surveillance.3 It is still a rare disease.
Pathophysiology
The spirochete responsible is transmitted from host to host by Ixodes spp. or deer ticks. Understanding the life cycle of these organisms gives better understanding of the epidemiology, other clinical aspects and prevention of Lyme disease.
The Ixodes tick:
Is made up of different species, found in different areas of the world. For example:
Ixodes persulcatus and Ixodes ricinus (European ticks), Ixodes scapularis, Ixodes pacificus.
Emerges in a larval form in the summer and feeds just once on a host animal (often a mouse).
In the spring the larva becomes a nymph and feeds, again only once, from a similar animal host. Humans can be victims in the nymph stage (85% of tick bites in humans occur at this time in spring and early summer).
In the autumn the adult tick finally emerges to feed on deer, again just once. Humans can be hosts at this stage (15% of tick bites in humans are at this stage and occur in the autumn).
The spirochete responsible:
Is transmitted by the tick. The tick must have fed on a host significantly infected with spirochete to pass on the infection to man.
Once it infects, the tick has to go through a particular cycle of multiplication and dissemination to salivary glands within the tick before it can be passed on to the animal victim. Hence a tick must be attached for 2-3 days to a person before infection can be passed on.
Once the spirochete infects the host there may be one of several consequences:
The infection is cleared by host defences. This means the person will have had no clinical manifestations, be asymptomatic but seropositive.
The organism spreads by direct invasion. This is believed to be a feature in early disease. For example, erythema migrans is thought to result from the inflammatory response to direct invasion of the organism in the skin.
The organism excites an immune response in the host which causes a variety of clinical manifestations around the body. In such cases there is no evidence of direct bacterial invasion. Host factors (immunological and genetic) are associated with development of disease in this form. For example, HLA- DR4 and HLA- DR2 are associated with such disease. The manifestations of Lyme disease are also related to the particular Borrelia spp. strain involved. Particular strains are found in different countries. For example:
B. burgdorferi garnii, found in Europe, is associated with neurological disease.
B. burgdorferi afzelii from Europe is associated with acrodermatitis chronica atrophicans.
B. burgdorferi sensu stricto is found on the East Coast of the USA.
B. burgdorferi predominates in the USA4 with an associated pattern of musculoskeletal complications.
B. valaisiana has a relatively high prevalence in British ticks, and does not appear to be associated with manifestations of disseminated borreliosis, which may explain the low incidence of Lyme borreliosis in the UK.
Lyme disease is now becoming global and mixed infections are becoming recognised.
Epidemiology
In the UK, areas where infection is acquired include:
Exmoor
The New Forest
The South Downs
Parts of Wiltshire and Berkshire
Thetford Forest
The Lake District
The Yorkshire moors
The Scottish Highlands
About 20% of confirmed cases are reported to have been acquired abroad:3
The USA
France
Germany
Austria
Scandinavia
Eastern Europe
Laboratory-confirmed reports of Lyme borreliosis have risen steadily since reporting began in 1986. Several factors have contributed to the observed increase, including increased awareness of the disease, access to diagnostic facilities, more sensitive diagnostic methods, the enhanced surveillance scheme (introduced in 1996) and, since 2000, more complete reporting of cases.3 Other possible factors producing a real increase include changes in the geographical ranges of I. ricinus both in the UK and Europe (successive mild winters), more recreational travel to high endemic areas and the increasing popularity of activity holidays (walking, trekking and mountain biking).3
Over 3,000 reports of Lyme borreliosis have been received since 1986, almost 2,800 of which have been reported since the introduction of enhanced surveillance in 1997.3
Mean annual incidence rates for laboratory-confirmed cases have risen from 0.06 per 100,000 total population for the period 1986 to 1992, to 0.64 cases per 100,000 total population in 2002, to 1.1 cases per 100,000 total population in 2005.3 The highest rates in the USA are 69.9 cases per 100,000 persons in Connecticut.
Lyme disease occurs in temperate regions of North America, Europe, and Asia.
In some countries of Europe, the incidence of Lyme disease has been estimated to be over 100 per 100,000 people a year.
Lyme disease infection has occurred in northern forested regions of Russia, in China, and in Japan.
It has not been found in tropical areas or in the southern hemisphere.
Risk of infection is greater if the tick is attached for more than 24 hours.
There is a rise in reported cases in autumn, but the peak occurs in spring and summer.
It is not possible to separate false-positive antibody tests from asymptomatic infection. In endemic areas as many as 10% of the population may have positive serology without any history of symptoms.
Cases of Lyme disease are lowest in urban areas in the eastern states of the USA.
In the USA there are peaks in incidence in the 5-9 year age group and the 50-54 year age group.
Presentation
It should be remembered that some infected people will have no symptoms. In Europe as many as 64% of patients with Lyme disease do not remember being bitten by the often innocuous tick. The presentation depends on the stage of disease at the time of presentation. For example:
Early Lyme Disease (Stage 1 or localised disease):
The characteristic manifestation is erythema migrans:
A circular rash at the site of the infectious tick attachment that radiates from the bite, within 2-40 days.
It expands over a period of days to weeks in 80-90% of people with Lyme disease.
It may be the only manifestation of disease in one third of patients.
In most patients there is only one episode of erythema migrans but, in about 20%, there are recurrent episodes.
About 40% of patients have multiple lesions (not the result of multiple bites).
Pyrexia, arthritis, musculoskeletal symptoms and local lymphadenopathy may occur in about two thirds of patients but one third of patients will develop no further symptoms.
Disseminated Lyme disease (or stage 2 disease ). This disseminated stage is still considered to be early infection and occurs weeks to months later, with:
Flu-like illness, oligoarthralgia (60%). Typically, with myalgia, multiple erythema migrans and sometimes systemic upset. Malaise and fatigue are very marked (particularly in the USA where 80% of patients are affected - about double that recorded in Europe).
Intermittent inflammatory arthritis:
This is more common in the USA.
In Europe joint pains are less often associated with inflammation.
Untreated episodes last about a week.
Most patients have at least 2 or 3 episodes and, even untreated, these resolve over a a few years.
Central nervous system disorders (15%):
These include facial (and other cranial nerve) palsies. These are the most common neurological manifestations in Europe and the USA.
Meningism and meningitis may occur alone or with other neurological manifestations. It is usually at the mild end of the spectrum but can be more severe.
Mild encephalitis producing malaise and fatigue.
Peripheral mononeuritis
Lymphocytic meningoradiculitis (or Bannwarth's syndrome which is more common in Europe than the USA).
Cardiovascular problems (10%):
This usually presents with syncopal episodes associated with fever.
Manifestations include transient atrioventricular block, myocarditis, or chronic dilated cardiomyopathy.
Occasionally hepatitis, orchitis, uveitis and panophthalmitis.
Lymphocytomas:
These are bluish-red nodular lesions infiltrated with lymphocytes.
They typically appear on the earlobe or nipple.
They occur in Europe but not the USA.
Late manifestations of Lyme disease (or stage 3 disease):
Untreated or inadequately treated Lyme disease can cause late disseminated manifestations weeks to months after infection. These late manifestations typically include prolonged arthritis, polyneuropathy, encephalopathy and symptoms consistent with fibromyalgia.
Chronic lyme arthritis - a chronic erosive arthropathy typically involving the knees.
Acrodermatitis chronica atrophicans . This is a bluish discolouration (normally on the lower leg over extensor surfaces) signifying epidermal atrophy, usually with mild sensory neuropathy and myalgia. It is generally seen in Europe not the USA.
Chronic neurological syndromes . Generally these appear to be more common in Europe. These include chronic neuropathies (usually with paraesthesia and occasionally with pain but not with motor deficit). They may even present as chronic fatigue syndromes, spastic paraparesis or depression.
Differential diagnosis
Chronic Lyme disease can be indistinguishable from fibromyalgia and chronic fatigue syndrome and in the assessment of these illnesses B. burgdorferi infection should be considered.
Noninfectious:
Urticaria
Gout
Psoriatic arthritis
Thyroid disease
Degenerative arthritis
Metabolic disorders (vitamin B12 deficiency, diabetes)
Heavy metal toxicity
Vasculitis
Systemic lupus erythematosus
Psychiatric disorders
Localised infections:
Gonococcal arthritis
Meningitis
Infections which can mimic certain aspects of the typical multisystem illness seen in chronic Lyme disease include:
Viral infections, for example:
Parvovirus B19
West Nile virus infection
Bacterial infections, for example:
Relapsing fever
Syphilis
Leptospirosis
Mycoplasma
Infective endocarditis
Investigations5
When to test and when to refer?
It is useful to have clear guidance on when to test and when to refer.
In all cases of suspected Lyme disease seek further advice on when and how to investigate from one or more sources. The following sources of advice are suggested:5
A microbiologist
An infectious diseases consultant
The Lyme Borreliosis Unit
In patients with erythema migrans:
Testing is not usually necessary with a history of tick bite (or possible exposure).
This characteristic rash with a history of tick bite or exposure is enough to make a diagnosis.
In primary care, testing should be considered:
With erythema migrans but with no tick bite (or tick exposure) and no other features of Lyme disease.
When there is isolated unilateral facial palsy (as with Bell's palsy) and Lyme disease needs excluding because of a history of tick bite (or tick exposure).
In patients with other neurological symptoms, joint or cardiac symptoms:
Test in primary care only after specialist advice.
Usually such patients require hospital admission or urgent specialist assessment.
What test?
There is currently no definitive test. Lyme disease is a clinical diagnosis and tests should be used to support clinical judgement. The most useful tests are antibody detection tests. The only national guidelines for testing come from the US Centers for Disease Control and Prevention (CDC).6 They recommend a 2-step testing process:
Lyme disease symptoms (other than erythema migrans) - take a blood sample for antibodies to B. burgdorferi. But note:
If negative and the sample is within 2 weeks of symptoms, repeat the test after 2 weeks.5
The enzyme immunoassay has a high false positive rate (low specificity) and can be positive with other conditions (for example, glandular fever, syphilis, rheumatoid arthritis and some autoimmune conditions).5
If positive or borderline by antibody testing using enzyme immunoassay, then retest using immunoblot or Western blotting to confirm the positive result.
Antibody testing in patients with erythema migrans is unhelpful because the rash develops before the antibodies.
Serology:
Serology may help in cases of endemic exposure where there are clinical features suggestive of disseminated disease.3
Serology - enzyme-linked immunosorbent assay (ELISA) - remains negative for several weeks in the initial phase, but is usually positive in serum and CSF in the disseminated stage. False positives may occur with other spirochaete infections.
Polymerase chain reaction (PCR) may identify very small numbers of spirochaetes in samples, and may influence decisions about whether to treat asymptomatic individuals with positive serology. Usually, however, PCR techniques are not helpful because of the uncertain correlation between positive results and the presence of live organisms in biological fluids.
Management
Discuss management with microbiologist and/or hospital specialists. The early use of antibiotics can prevent persistent, recurrent, and refractory Lyme disease. Antibiotics shorten clinical course and progression. The duration of therapy should be guided by clinical response, rather than by an arbitrary treatment course but guidance is offered.5 Generally speaking, long courses of antibiotics may be required (2-4 weeks or longer).
Management at a glance:
Tick bite- remove tick and consider a single-dose oral antibiotic in high-risk cases (not recommended routinely in UK-acquired tick bites)3
Skin manifestations - (erythema migrans) oral regimen 14-21 days
Arthritis - oral regimen for 30 days, repeated IV if the oral course is unsuccessful
Neuroborreliosis - oral regimen 30 days for all except encephalitis and encephalopathy
Encephalitis/encephalopathy - IV regimen for 28 days
Fibromyalgia - no evidence of benefit from trials with oral or IV treatment
Jarisch-Herxheimer reaction may occur soon after treatment is initiated.
Oral drug therapies for erythema migrans alone can be started in primary care. These are appropriate when:
There is no evidence of neurological, cardiac, or joint involvement.
Patients are not pregnant or breast-feeding.
Doxycycline (and tetracycline), amoxicillin, azithromycin, cefuroxime, and clarithromycin have similar favourable results in studies. For many Lyme disease patients, there is no clear advantage of parenteral therapy.
The following antibiotic regimens have been suggested:5
Adults:
First choice is doxycycline (100 mg twice-daily for 14 days) or amoxicillin (500 mg three times daily for 14 days).7. Some recommend 3 weeks course.6
If both doxycycline and amoxicillin are contra-indicated, use cefuroxime (500 mg twice-daily for 14 days) unless there is a history of anaphylaxis with a penicillin.
When a bacterial cellulitis cannot be excluded use 14 days of either co-amoxiclav alone (500/125 mg three times daily) or cefuroxime axetil alone (500 mg twice-daily) or amoxicillin (500 mg three times daily) with flucloxacillin (500 mg four times daily for 7 to14 days).
Children:
12 years of age or older, give 14 days of either amoxicillin (50 mg/kg per day in three divided doses) or doxycycline (100 mg twice-daily).
Less than 12 years of age, give 14 days of amoxicillin (50 mg/kg per day in three divided doses).
If both doxycycline and amoxicillin are contra-indicated give 14 days of cefuroxime axetil (30 mg/kg/day in two divided doses) unless there is a history of anaphylaxis with a penicillin.
When erythema migrans is indistinguishable from bacterial cellulitis, give 14 days of either co-amoxiclav, cefuroxime axetil or amoxicillin with flucloxacillin in age-appropriate doses.
Intravenous antibiotics are used in severe cases (for example, encephalitis, meningitis, optic neuritis, joint effusions, and heart block); or where there is failure of oral medications - in patients with persistent, recurrent, or refractory Lyme disease. Ceftriaxone, cefotaxime, and penicillin are commonly used intravenous antibiotics. The precise regime will depend on the individual situation but high doses of antibiotics, combination of antibiotics, sequential regimes and prolonged duration (one month or longer) are advocated.
Surgical synovectomy should be reserved for knee pain failing antibiotic treatment. Intra-articular steroid injection may be useful for persistent knee pain but runs the risk of masking persistent infection.
Treatment of Lyme arthritis - cefotaxime, ceftriaxone, doxycycline and amoxicillin plus probenecid are all effective.
Treatment of late neurological Lyme disease - Cefotaxime has been shown to improve neuropathy in patients with late Lyme disease. Intravenous ceftriaxone has been shown to be effective in Lyme encephalopathy.8 Other studies have shown no benefit of antibiotic for late neurological Lyme disease.
A temporary pacemaker may be required where there are carditis and conduction defects.
Prophylactic treatment of tick bite
Prophylactic antibiotics after Ixodes scapularis tick bites in Lyme disease endemic areas in North America have been shown to reduce the risk of developing clinical Lyme disease.9 This article in the New England Journal of Medicine suggests that a single dose of 200 mg of doxycycline within 72 hours of tick removal can prevent Lyme disease developing. The risk in the UK is such that use of prophylactic antibiotics is not recommended. It might be considered in very exceptional circumstances - for example, when a person travelling from an endemic area discovers a tick which has been attached for more than 48 hours.
Prognosis
Lyme disease is rarely fatal.
However, untreated Lyme disease can result in arthritis (50% of untreated people), meningitis or neuropathies (15% of untreated people), carditis (5-10% of untreated people with erythema migrans) and, rarely, encephalopathy. Over 90% of facial palsies due to Lyme disease resolve spontaneously, and most cases of Lyme carditis resolve without sequelae.10
The natural disease course of European borreliosis is not well defined and the effect of antibiotic treatment is unclear.11 There are no UK studies on the outcome of treatment.
Long-term sequelae also include poor concentration and fatigue.10
Recovery is often incomplete if the disease presents late.
Prevention
Measures to reduce infection in areas associated with ticks:
Wear long hair under a hat.
Keep to the middle of paths and avoid unnecessary brushes with foliage where ticks loiter waiting for the next passing mammal.
Avoid wooded areas where possible. Mowed grass areas are less likely to have ticks in them.
Keep legs and arms covered (wear trousers inside socks).
Use insect repellent for humans.
Use tick collars for pets (they can get Lyme disease) and inspect for (and remove) any ticks.
Inspect skin regularly during the day in at-risk areas (especially the groin, axillae and hairline). Remember ticks are unlikely to transmit Lyme disease until attached for several days.
If bitten by a tick:
Remove the tick:
Clean the surrounding skin with disinfectant to prevent bacterial infection.
Gently remove by grasping close to mouth parts with forceps (tweezers).12 The safest, quickest and most reliable method of removal is by using forceps applied to the tick as close to the skin as possible and removed with steady traction (and not twisting).13
Fragments of the mouthparts may be left in the skin, but these are small and rarely cause any problems, especially if the skin is disinfected before and after the procedure.
Note: cigarettes and glowing match heads or suffocating the tick with various agents (for example, petroleum jelly or solvents) are not recommended.13
If tweezers are not available, to avoid delay, find a cotton thread and tie a single loop of cotton around the tick's mouthparts, as close to the skin as possible and pull gently upwards and outwards.
Routine prophylaxis after tick bites is not currently recommended in the UK.3 However, in endemic areas, prophylaxis should be considered if there is a high risk of infection.9
Note: if the tick-bite area does not heal promptly or becomes painful, antibiotics may be necessary to treat other bacteria. Check for a spreading red patch, especially one that appears between 3 and 30 days after removal of the tick. However, remember that the risk of developing Lyme borreliosis from a tick bite is small, even in heavily infested areas and most doctors prefer not to treat patients with antibiotics unless they develop symptoms.13
A vaccine was licensed for use in the USA but later removed from the market.
--------------------------------------------------------------------------------
Document references
Steere AC, Malawista SE, Snydman DR, et al; Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three connecticut communities. Arthritis Rheum. 1977 Jan-Feb;20(1):7-17. [abstract]
Burgdorfer W, Barbour AG, Hayes SF, et al; Lyme disease-a tick-borne spirochetosis? Science. 1982 Jun 18;216(4552):1317-9. [abstract]
Lyme borreliosis/Lyme disease, Health Protection Agency
No authors listed; Lyme disease--United States, 2001-2002. MMWR Morb Mortal Wkly Rep. 2004 May 7;53(17):365-9. [abstract]
Lyme disease, Clinical Knowledge Summaries (January 2010)
Wormser GP, Dattwyler RJ, Shapiro ED, et al; The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2006 Nov 1;43(9):1089-134. Epub 2006 Oct 2.; (reviewed 22/4/2010 by IDSA - no changes made to guidelines) [abstract]
British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)
Logigian EL, Kaplan RF, Steere AC; Successful treatment of Lyme encephalopathy with intravenous ceftriaxone. J Infect Dis. 1999 Aug;180(2):377-83. [abstract]
Nadelman RB, Nowakowski J, Fish D, et al; Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001 Jul 12;345(2):79-84. [abstract]
Seltzer EG, Gerber MA, Cartter ML, et al; Long-term outcomes of persons with Lyme disease. JAMA. 2000 Feb 2;283(5):609-16. [abstract]
Dinser R, Jendro MC, Schnarr S, et al; Antibiotic treatment of Lyme borreliosis: what is the evidence? Ann Rheum Dis. 2005 Apr;64(4):519-23. [abstract]
Correct Method of Tick Removal, Borreliosis and Associated Diseases Awareness UK Website.
EUCALB - European Union Concerted Action on Lyme Borreliosis; A pan-European information site supported by an advisory board comprising an expert group of physicians and biologists from across Europe.
Acknowledgements EMIS is grateful to Dr Richard Draper for writing this article and to Dr Colin Tidy for earlier versions. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2010.
Document ID: 7004
Document Version: 8
Document Reference: bgp442
Last Updated: 30 Jun 2010
Planned Review: 29 Jun 2013
Monday, 6 September 2010
THE CASE FOR CHRONIC INFECTION
The Case For Chronic Infection: Evidential persistence of Borrelia species post antibiotic exposure in vivo and in vitro.
https://acrobat.com/#d=sbb-EmpQrQTgrPoezLGreg
Michael D. Parent
Introduction Summary:
There is an abundance of evidence demonstrating that Borrelia Burgdorferi, the causative agent of Lyme Disease, and related pathogenic species, can persist within specific body tissues and cells of various mammals despite adequate antibiotic therapy: ponies [93.5, 111.5], non-human primates [50, 86], dogs [65.5, 70, 80, 81, 82, 84], mice [44, 62, 88, 100, 107, 108, 110, 114], and humans [all others].
There is also abundant evidence that Borrelia Burgdorferi has evolved in a manner similar to other bacteria that evade the immune system via pleomorphic modification, in other words, the bacteria can change its shape beyond the conventional spirochetal form [45, 55, 61, 64, 90, 105, 109, 113].
L-forms, and cystic Borrelia have been identified in a number of studies [45, 68, 77, 87, 105, 109, 112, 113].
When these "forms" are exposed to the typical antibiotics, such as Penicillin family antibiotics or Doxycycline, they are unaffected. When the antibiotic is removed from the environment, the bacterium will alter its form once more, morphing back into a spiral form, allowing ongoing mobility [45, 68, 87, 90, 105, 109].
I have taken the time to "bold" the conclusions and various other aspects that clearly indicate a deviation from the point of view given by a number of physicians and researchers who deny the possibility of ongoing chronic infection within the human host.
The current guidelines issued by the Infectious Disease Society Of America (IDSA) are consistently used to dismiss further discussion regarding the subject of persistence. The guidelines are titled: “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis” Clinical Infectious Diseases 2006; 43:1089–134.
Patients who receive a diagnosis of Lyme Disease, either based on clinical observation and/or objective indicators often improve with antibiotic therapy [1, 4, 18, 19, 26, 33, 66].
However, if they have been undiagnosed and untreated for Lyme Disease for a long period of time, it often takes longer courses of antibiotics beyond those currently recommended to see progress in symptom reduction [15, 66, 73, 93, 105].
The U.S. National Institute Of Health funded a number of randomized double-blind placebo-controlled trials (RCT) regarding the long term treatment of Lyme Disease.
However, these RCT's were 3 months in duration or less.
Patients with documented medical records indicating Chronic Lyme Disease or a Lyme-Like Illness who have been untreated often do not see meaningful improvement until after 4-6 months of treatment, and even still, the improvements are modest initially in many patients and may require an ongoing open ended treatment regimen with antibiotics [66, 93].
It is well understood and agreed upon universally that the more time Borrelia Burdorferi has had to disseminate into various ligaments, bones, collagen, muscles, and other tissues, then the higher the probability of ongoing complications or symptoms post-antibiotic therapy.
Presently, studies indicate that antibiotics can not access many of the areas that Borrelia Burgdorferi disseminates to unless the bacterium itself leaves the safe haven of a Fibroblast skin cell [11, 22, 23, 24, 25, 29, 35, 52, 64, 70, 72, 80, 81, 84, 94], or synovial tissue cells and fluid [1, 7, 9, 31, 34, 37, 42, 60, 61, 69, 70, 71, 102].
Introductory Conclusion:
Therefore, we have studies demonstrating abundant persistence.
We have National Institute Of Health funded studies that do not treat patients long enough to confirm whether the treatment really is effective or not.
The short term studies we do have contradict other studies as well as those based on clinical reports from health care providers treating these patients with antibiotics beyond the currently accepted time frame.
It is unwise for the IDSA to claim that long-term antibiotic therapy doesn't work when you've only performed a study for 3 months, when the vast majority of the patients in the study have had the infection for many years and require at least 3-6 months of oral antibiotic before clinical improvements are seen.
IV antibiotics may demonstrate minor to moderate symptomatic improvement after 1- 3 months, but if that treatment is only given for 3 months and then discontinued, then it will be equally ineffective and the symptoms will return to pre-treatment levels. Coincidentally, that's exactly what happened in Dr. Brian Fallon's study. Some symptoms improved, but then returned upon discontinuing therapy.
I have discussed merely one specific possibility for the failure of patients to thrive and improve during the currently available randomized double-blind placebo-controlled clinical trials (RCT). Dr. Daniel J. Cameron writes in the Journal Of Medical Hypothesis that a number of limitations exist within the currently structured (RCTs), that strongly support the position I've laid forth. Med Hypotheses. 2009 Jun;72(6):688-91. Epub 2009 Mar 5. Insufficient evidence to deny antibiotic treatment to chronic Lyme disease patients. First Medical Associates, Medicine, 175 Main Street, Mount Kisco, NY 10549, USA. Cameron@LymeProject.com
"Evidence for the hypothesis: There are eight limitations that support the hypothesis: (1) the power of the evidence is inadequate to draw definite conclusions, (2) the evidence is too heterogeneous to make strong recommendations, (3) the risk to an individual of facing a long-term debilitating illness has not been considered, (4) the risk to society of a growing chronically ill population has not been considered, (5) treatment delay has not been considered as a confounder, (6) co-infections have not been considered as a confounder, (7) the design of RCTs did not address the range of treatment options in an actual practice, and (8) the findings cannot be generalized to actual practice. Implications of the hypothesis: This hypothesis suggests that physicians should consider the limitations of the evidence before denying antibiotic treatment for Chronic Lyme Disease (CLD). Physicians who deny antibiotic treatment to CLD patients might inform their patients that there are some clinicians who disagree with that position, and then offer to refer them for a second opinion to a doctor who could potentially present a different point of view. The hypothesis also suggests that health care insurers should consider the limitations of the evidence before adopting policies that routinely deny antibiotic treatment for CLD patients and should expand coverage of CLD to include clinical discretion for specific clinical situations."
There is more than enough information to justify at least a neutral position in respect to whether Borrelia Burgdorferi and related infectious species persist in human beings despite the Infectious Disease Society Of America's recommendations. Due to this uncertainty, treating physicians can not conclusively deny that persistence in human beings may be more problematic than assumed.
The scientific studies available on Lyme Disease contradict each other to a significant degree. Many study authors state in no uncertain terms that the discussion of Lyme Disease is a closed case. I disagree. The evidence disagrees. The Chief Medical Officer in the United Kingdom echoed the sentiments of the IDSA in 2009 stating: "There is no biological evidence of symptomatic chronic Lyme disease amongst those who have received the recommended treatment regimen." - CMO, Autum 2009, Issue 49, pg. 4. The IDSA states: "To date, there is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease." - Clin Infect Dis 2006 Nov 1;43(9):1089-134
Skepticism is the heart of science. Cynicism is the death of reason.
The following studies are organized by year, page, and study title within the Study table index.
Study Table Index:
1986 page 18
Ann Intern Med. 1986 Jun;104,6:798-800. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM.
1986 page18
J Am Acad Dermatol. 1986 Sep;15,3:459-63.Treating erythema chronicum migrans of Lyme disease. Berger BW.
1987 page 18
Arthritis Rheum. 1987 Apr;30,4:448-50.Failure of tetracycline therapy in early Lyme disease. Dattwyler RJ, Halperin JJ.
1987 page 19
Arthritis Rheum. 1987 Jun;30,6:705-8. Lyme meningoencephalitis: report of a severe, penicillin-re sistant case. Diringer MN, Halperin JJ, Dattwyler RJ.
1988 page 19
Pediatr Infect Dis J. 1988 Apr;7,4:286-9. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
1988 page 19
Ann N Y Acad Sci. 1988;539:346-51. Treatment of erythema chronicum migrans of Lyme disease. Berger BW. Department of Dermatology, New York University School of Medicine, New York 10016.
1988 page 20
Arthritis Rheum. 1988 Apr;31,4:487-95. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue. Steere AC, Duray PH, Butcher EC.
1988 page 20
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Am J Clin Pathol. 1989 Jan;91,1:95 7. Spirochetes in the spleen of a patient with chronic Lyme disease. Cimmino MA, Azzolini A, Tobia F, Pesce CM Istituto Scientifico di Medicina Interna, Università di Genova, Italy.
1989 page 22
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J Neurol. 1993 May;240,5:278-83. Borrelia burgdorferi myositis: report of eight patients. Reimers CD, de Koning J, Neubert U, Preac-Mursic V, Koster JG, Müller-Felber W, Pongratz DE, Duray PH.
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Arthritis Rheum. 1993 Nov;36,11:1621 6. Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Häupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schönherr U, Kalden JR, Burmester GR.
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1993 page 32
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J Clin Microbiol. 1994 Mar;32,3:715-20.Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. Kuiper H, van Dam AP, Spanjaard L, de Jongh BM, Widjojokusumo A, Ramselaar TC, Cairo I, Vos K, Dankert J. Department of Medical Microbiology, Academic Medical Centre, University Hospital, University of Amsterdam, The Netherlands.
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JAMA. 1996 Jun 5; 275,21, :1657-60. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. K rause PJ, Telford SR 3rd, Spielman A, Sikand V, Ryan R, Christianson D, Burke G, Brassard P, Pollack R, Peck J, Persing DH.
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Antimicrob Agents Chemother. 1996 Jun;40,6:1552-4. Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin. Brouqui P, Badiaga S, Raoult D. Unité des Rickettsies, Faculté de Médecine, Centre National de la Recherche Scientifique, Marseille, France.
1996 45
Infection. 1996 Sep-Oct;24,5:347-53.Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Bayer ME, Zhang L, Bayer MH. Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
1996 45
Hum Pathol. 1996 Oct;27,10:1025-34.Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms. Nanagara R, Duray PH, Schumacher HR Jr. Allergy-Immunology-Rheumatology Division, Department of Medicine, Faculty of Medicine, KhonKaen University, Thailand.
1996 46
Rheumatol Int. 1996;16,3:125-32.Intracellular persistence of Borrelia burgdorferi in human synovial cells. Girschick HJ, Huppertz HI, Rüssmann H, Krenn V, Karch H.
1996 47
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1996 47
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1996 48
Am J Dermatopathol. 1996 Dec;18,6:571-9. Heterogeneity of Borrelia burgdorferi in the skin. Aberer E, Kersten A, Klade H, Poitschek C, Jurecka W.
1997 48
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1997 49
J Clin Microbiol. 1997 January; 35(1): 111–116. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment. R K Straubinger, B A Summers, Y F Chang, and M J Appel Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. rks4@cornell.edu
1997 49
Clin Infect Dis. 1997 Jul;25 Suppl 1:S52-6. Tetracycline therapy for chronic Lyme disease. Donta ST.
1997 50
Clin Infect Dis. 1997 Jul;25 Suppl 1:S64-70.Why is chronic Lyme borreliosis chronic? Aberer E, Koszik F, Silberer M.
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American College of Rheumatology, Vol 40,9, Branigan P; Rao J; 1997 PCR evidence for Borrelia burgdorferi DNA in synovium in absence of positive serology. Suppl, Rao J; Gerard H; Sept, p.S270 Hudson A; Williams W; Arayssi T; Pando J; Bayer M; Rothfuss S; .PCR evidence for Borrelia has been identified in synovial biopsies of patients with clinical pictures that had not initially suggested Lyme disease. Clayburne G; Sieck M; Schumacher HR.
1997 51
Journal of Spirochetal & Tick-borne Diseases, Vol. 4, No. 1/2 Two lessons from the canine model of Lyme Disease: migration of Borrelia burgdorferi in tissues and persistence after antibiotic treatment. Straubinger RK; 1997 Straubinger AF; Jacobson RH; Chang Y; Summer BA;
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Ann Rheum Dis. 1998 Feb;57,2:118-21.Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Priem S, Burmester GR, Kamradt T, Wolbart K, Rittig MG, Krause A.
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Med J Aust. 1998 May 18;168,10:500-2. Comment in: Med J Aust. 1998 May 18;168,10:479-80. Culture-positive Lyme borreliosis. Hudson BJ, Stewart M, Lennox VA, Fukunaga M, Yabuki M, Macorison H, Kitchener-Smith J.
1998 52
Acta Clin Belg. 1998 Jun;53,3:178-83.Lyme borreliosis--a review of the late stages and treatment of four cases. Petrovic M, Vogelaers D, Van Renterghem L, Carton D, De Reuck J, Afs chrift M. Department of Internal Medicine, University Hospital Ghent, Belgium.
1998 53
Eur J Clin Microbiol Infect Dis. 1998 Oct;17,10:715-9.Comparison of oral cefixime and intravenous ceftriaxone followed by oral amoxicillin in disseminated Lyme borreliosis. Oksi J, Nikoskelainen J, Viljanen MK. Department of Medicine, Turku University Central Hospital, Finland.
1998 53
Neurology. 1998 Nov;51,5:1489-91. Comment in: Neurology. 1999 Sep 11;53,4:895-6. Clinical and serologic follow-up in patients with neuroborreliosis. Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R.
1998 54
Infection. 1998 Nov-Dec; 26,6:364-7.A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated. Phillips SE, Mattman LH, Hulínská D, Moayad H. Greenwich Hospital, CT 06830, USA.
1998 54
Klin Monatsbl Augenheilkd. 1998 Dec;213,6:351-4. Pars plana vitrectomy in Borrelia burgdorferi endophthalmitis [Article in German] Meier P, Blatz R, Gau M, Spencker FB, Wiedemann P.
1999 55
Ann Med. 1999 Jun; 3,3:225-32. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK.
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Zentralbl Bakteriol. 1999 Jul;289,3:301-18. Persistence of Borrelia garinii and Borrelia afzelii in patients with Lyme arthritis. Hulínská D, Votýpka J, Valeso vá M.
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J Infect Dis. 2000 Mar;181,3:1069-81. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: An experimental study. Straubinger RK, Straubinger AF, Summers BA, Jacobson RH.
2000 57
J Clin Microbiol. 2000 Jun; 38,6, :2191-9. PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-Day postinfection period. Straubinger RK. James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. rks4@cornell.edu
2001 59
Br J Dermatol. 2001 Feb;144,2:387-92. Is olation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Breier F, Khanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, Tappeiner G.
2001 59
Epidemiol Mikrobiol Imunol. 2001 Feb;50,1:10-6.Persistence of Borrelia burgdorferi sensu lato in patients with Lyme borreliosis [Article in Czech] Honegr K, Hulínská D, Dostál V, Gebouský P, Hanková E, Horácek J, Vyslouzil L, Havlasová J. Infekcní klinika, Fakultní nemocnice, Hradec Králové.
2001 60
Ann Neurol. 2001 Sep;50,3, :330-8.Central and peripheral nervous system infection, immunity, and inflammation in the NHP model of Lyme borreliosis. Pachner AR, Cadavid D, Shu G, Dail D, Pachner S, Hodzic E, Barthold SW. Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark 07103, USA. pachner@umdnj.edu
2002 60
Wien Klin Wochenschr. 2002 Jul 31;114,13-14:574-9. Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS. Murgia R, Piazzetta C, Cinco M.
2002 61
Acta Neurol Scand. 2002 Oct;106(4):205-8. Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire follow-up study. Vrethem M, Hellblom L, Widlund M, Ahl M, Danielsson O, Ernerudh J, Forsberg P.
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J Infect Dis. 2002 Nov 15;186,10:1430-7. Epub 2002 Oct 23. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. Bockenstedt LK, Mao J, Hodzic E, Barthold SW, Fish D.
2002 62
Antimicrob Agents Chemother. 2002 Nov;46,11:3637-40. Erythromycin resistance in Borrelia burgdorferi. Terekhova D, Sartakova ML, Wormser GP, Schwartz I, Cabello FC.
2002 63
Przegl Epidemiol. 2002;56 Suppl 1:57-67.New aspects of the pathogenesis of lyme disease [Article in Polish] Zajkowska JM, Hermanowska-Szpakowicz T. Klinika Chorób Zakaźnych i Neuroinfekcji AM w Bia ymstoku.
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Neurology. 2003 Jun 24;60,12:1923-30. Comment in: Neurology. 2003 Jun 24;60,12:1888-9.Study and treatment of post Lyme di sease, STOP-LD: a randomized double masked clinical trial. Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, Dattwyler R, Chandler B.
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Med Sci Monit. 2003 Nov;9,11:PI136-42. Macrolide therapy of chronic Lyme Disease. Donta ST.
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Vet Microbiol. 2005 May 20;107(3-4):285-94 Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies. Chang YF, Ku YW, Chang CF, Chang CD, McDonough SP, Divers T, Pough M, Torres A. College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. yc42@cornell.edu
2005 65
Int J Antimicrob Agents. 2005 Jun;25,6:474-8. Susceptibility of Borrelia afzelii strains to antimicrobial agents. Ruzić-Sabljić E, Podreka T, Maraspin V, Strle F.
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Int J Med Microbiol. 2006 May;296 Suppl 40:233-41. Epub 2006 Mar 10.Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance. Hunfeld KP, Ruzić-Sabljić E, Norris DE, Kraiczy P, Strle F. Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany. K.Hunfeld@em.uni-frankfurt.de
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Eur J Pediatr. 2006 Jun;165,6:420-1. Epub 2006 Mar 4. Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104. Hendrickx G, Demanet C, Vandenplas Y. Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. g.hendrickx@st-anna.nl
2006 67
Int J Immunopathol Pharmacol. 2006 Jul-Sep;19,3:545-9. In vitro susceptibility of isolates of Borrelia burgdorferi s.l. to antimicrobial agents. Santino I, Scazzocchio F, Ciceroni L, Ciarrocchi S, Sessa R, Del Piano M. Department of Public Health Sciences, La Sapienza University, Rome, Italy. iolanda.santino@uniroma1.it
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Microbes Infect. 2006 Nov-Dec; 8,14-15:2832-40. Epub 2006 Sep 22.Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi. Livengood JA, Gilmore RD Jr.
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Acta Radiologica, Volume 48, Issue 7 2007 , pages 755 - 762 Brain Magnetic Resonance Imaging Does Not Contribute to the Diagnosis of Chronic Neuroborreliosis. Aalto A, Sjöwall J, Davidsson L, Forsberg P, Smedby O. Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anne.aalto@imv.liu.se
2007 69
Pol Merkur Lekarski. 2007 Apr;22,130:275-9. Related Articles, Concentrations of pro-inflammatory cytokines IFN-gamma, IL-6, IL-12 and IL-15 in serum and cerebrospinal fluid in patients with neuroborreliosis undergoing antibiotic treatment. Article in Polish. Pancewicz SA, Kondrusik M, Zajkowska J, Grygorczuk S. Akademia Medyczna w Bialymstoku, Klinika Chorób Zakaznych i Neuroinfekcji.20spancewicz@interia.pl
2007 69
J Infect Dis. 2007 May 15;195,10:1489-96. Epub 2007 Apr 6.Anti-tumor necrosis factor-alpha treatment activates Borrelia burgdorferi spirochetes 4 weeks after ceftriaxone treatment in C3H/He mice. Yrjänäinen H, Hytönen J, Song XY, Oksi J, Hartiala K, Viljanen MK. Department of Medical Microbiology, University of Turku, Turku, 20520, Finland. heta.yrjanainen@utu.fi
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Adv Med Sci. 2007;52:174-8. Concentration of TGF-beta1 in the supernatant of peripheral blood mononuclear cells cultures from patients with early disseminated and chronic lyme borreliosis. Grygorczuk S, Chmielewski T, Zajkowska J, Swierzbińska R, Pancewicz S, Kondrusik M, Tylewska-Wierzbanowska S, Hermanowska-Szpakowicz T. Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, ul. Zurawia 14, 15-540 Białystok, Poland. neuroin@amb.edu.pl
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Rheumatol Int. 2007 Sep;27,11:1091-3. Epub 2007 Apr 4. Seronegative Lyme arthritis. Holl-Wieden A, Suerbaum S, Girschick HJ. Children's hospital, Section of Pediatric Rheumatology, Immunology and Infectious diseases, University of Wuerzburg, Josef-Schneider-Str. 2, 97090 Wuerzburg, Germany.
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Pol Merkur Lekarski. 2007 Sep;23,135:174-8. Concentration of soluble forms of selectins in serum and in cerebrospinal fluid in group of patients with neuroborreliosis--a preliminary study Moniuszko AM, Pancewicz SA, Ko ndrusik M, Zajkowska J, Grygorczuk S, Swierzbińska R. Akademia Medyczna w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji.
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Volume 358:428-431 January 24, 2008 Number An Appraisal of "Chronic Lyme Disease" To the Editor: Feder et al., Oct. 4 issue,
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Persistence of Borrelia burgdorferi Following Antibiotic Treatment in Mice Antimicrobial Agents and Chemotherapy, published online ahead of print on 3 March 2008 Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold
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Antimicrobial Agents and Chemotherapy, May 2008, p. 1728-1736, Vol. 52, No. 50066-4804 Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold*
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Pol Arch Med Wewn. 2008 May;118 5:314-7. : Neuroborreliosis with extrapyramidal symptoms: a case report. Biesiada G, Czapiel J, Sobczyk-Krupiarz I, Garlicki A, Mach T. Department of Infectious Diseases, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jagiellonian University School of Medicine, Kraków, Poland. gbiesiada@op.pl
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J Neuroinflammation. 2008 Sep 25;5:40. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL.
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Microb Pathog. 2008 Sep 20. Borrelia burgdorferi expression of the bba64, bba65, bba66, and bba73 genes in tissues during persistent infection in mice. Gilmore RD Jr, Howison RR, Schmit VL, Carroll JA.
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Med Hypotheses. 2008;70,5:967-74. Epub 2007 Nov 5. The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders. Bransfield RC, Wulfman JS, Harvey WT, Usman AI.
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Journal of Veterinary Diagnostic Investigation Vol. 20 Issue 3, 321-324 Copyright © 2008 by the American Association of Veterinary Laboratory Diagnosticians: Validation of an in-clinic enzyme-linked immunosorbent assay kit for diagnosis of Borrelia burgdorferi infection in horses. Amy L. Johnson1, Thomas J. Divers and Yung-Fu Chang
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J Antimicrob Chemother. 2009 Jun;63 6:1163-72. Epub 2009 Apr 17. Assessment of methylthioadenosine/S-adenosylhomocysteine nucleosidases of Borrelia burgdorferi as targets for novel antimicrobials using a novel high-throughput method. Cornell KA, Primus S, Martinez JA, Parveen N.
2009 81
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18656-61. Epub 2009 Oct 20. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic tigecycline. Brorson Ø, Brorson SH, Scythes J, MacAllister J, Wier A, Margulis L.
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Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment HETA YRJÄNÄInen 1 , JUKKA HYTÖNen 1 , PAULIINA HARTIALA 1 , JARMO OKSI 2 and MATTI K. VILJANEN Departments of 1Medical Microbiology and Immunology and 2 Medicine, University of Turku, Turku, Finland
Evidential support for the case of Chronic Infection:
1: Ann Intern Med. 1986 Jun;104,6:798-800. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM.
Although indirect evidence suggests that chronic Lyme arthritis is caused by persistent infection with Borrelia burgdorferi, direct visualization has been lacking. We report the demonstration of B. burgdorferi from synovial fluid aspirated from the right knee of a 31-year-old man with Lyme arthritis for more than 1 year. After 6 days, culture medium inoculated with synovial fluid showed one motile and several nonmotile spirochetes. Direct immunofluorescence staining showed reactivity with anti-B. burgdorferi serum. Spirochetes were not seen in subcultured material. The patient's arthritis improved with high-dose intravenous penicillin. Identification of B. burgdorferi from the joint fluid of a patient with long-standing arthritis supports the concept that the arthritis is due to persistent infection.
2: J Am Acad Dermatol. 1986 Sep;15,3:459-63.Treating erythema chronicum migrans of Lyme disease. Berger BW.
The efficacy of antibiotic treatment of 117 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. Fifty-six patients with a minor form of the illness did not require retreatment and did not develop late manifestations following antibiotic treatment. Three pregnant patients were included in this group.Fourteen of sixty-one patients with a major form of the illness required retreatment, and five developed posttreatment late manifestations of Lyme disease consisting of Bell's palsy and persistent joint pain. Although the preferred antibiotic for treating erythema chronicum migrans of Lyme disease has not been conclusively established, tetracycline and penicillin proved effective. The use of probenecid plus penicillin may be of benefit to patients with the major form of the illness.
3: 1: Arthritis Rheum. 1987 Apr;30,4:448-50.Failure of tetracycline therapy in early Lyme disease. Dattwyler RJ, Halperin JJ.
We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migra ns with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.
4: Arthritis Rheum. 1987 Jun;30,6:705-8. Lyme meningoencephalitis: report of a severe, penicillin-re sistant case. Diringer MN, Halperin JJ, Dattwyler RJ.
Although Lyme disease frequently attacks the central nervous system, this involvement is rarely severe, and high-dose intravenous penicillin usually is adequate treatment. The patient we describe developed severe Lyme meningoencephalitis despite receiving a full course of penicillin, and his condition continued to deteriorate after reinstitution of this treatment. Intravenous chloramphenicol was used successfully and resulted in a substantial improvement.
5: Pediatr Infect Dis J. 1988 Apr;7,4:286-9. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
Department of Medicolegal Medicine, Dermatology and Microbiology, University of Munich, Federal Republic of Germany. "We now demonstrate B. burgdorferi in the brain and liver of a newborn whose mother had been treated with oral penicillin for LB [Lyme borreliosis] during the first trimester of pregnancy. ..The death of the newborn was probably due to a respiratory failure as a consequence of perinatal brain damage.”
6: Ann N Y Acad Sci. 1988;539:346-51. Treatment of erythema chronicum migrans of Lyme disease. Berger BW. Department of Dermatology, New York University School of Medicine, New York 10016.
Between June 1981 and July 1987 the efficacy of antibiotic treatment of 215 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. The principal antibiotics utilized to treat 161 patients through 1986 were varying doses of tetracycline, or penicillin alone or in combination with probenecid. Two of 8 0 patients with a minor form of the illness and 17 of 81 patients with a major form of the illness required retreatment. There were four patients who did not respond to retreatment with their original medication. A 15- to 30-day course of amoxicillin, 500 mg q.i.d., and probenecid, 500 mg q.i.d., or doxycycline, 100 mg t.i.d., and on three occasions ceftriaxone, 2-4 g/day i.v., were used to treat 54 patients in 1987. Although it is too early to judge the efficacy of treatment in these patients, increases in the incidence of Herxheimer reactions and drug eruptions were observed. Strict compliance with treatment protocols and the possibility of reactions to medications should be thoroughly discussed with patients.
7: 1: Arthritis Rheum. 1988 Apr;31,4:487-95. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue. Steere AC, Duray PH, Butcher EC.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Using monoclonal antibodies to spirochetal antigenes and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer s ubset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD-bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present. Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA-DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.
8: AMA. 1988 May 13;259,18:2737-9 Fatal adult respiratory distress syndrome in a patient with Lyme disease. Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A.
Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, PA 15213.
A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.
9: J Infect Dis. 1988 Oct;158,4:905-6. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. Schmidli J, Hunziker T, Moesli P, Schaad UB.
Attacks typically are intermittent and last from 3 days to 12 months. The knees are affected most often, but migratory arthritis is common and other large and small joints may be involved. Only very few Borrelia strains have been cultured from joint specimens worldwide However, a high percentage of patients with Lyme arthritis, 85%, have evidence of B burgdorferi DNA, detected by PCR, in the synovial fluid The local persistence of B burgdorferi in the joint over a long period of time might be related to the exacerbations of symptoms after chondrocyte cell transplantation. B burgdorferi is difficult to detect in synovial fluid, and cultures are positive only rarely
10: 1: N Engl J Med. 1988 Dec 1;319,22:1441-6. Comment in: N Engl J Med. 1989 May 11;320,19:1279-80.Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG.
Department of Medicine, State University of New York, School of Medicine, Stony Brook 11794-8161.
The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder.Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean, +/- SEM, stimulation index of 17.8 +/- 3.3, similar to that, 15.8 +/- 3.2, in 18 patients with chronic Lyme disease who had detectable antibodies. The T-cell response of both groups was greater than that of a control group of healthy subjects, 3.1 +/- 0.5; P less than 0.001.We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.
11: 1: Am J Clin Pathol. 1989 Jan;91,1:95 7. Spirochetes in the spleen of a patient with chronic Lyme disease. Cimmino MA, Azzolini A, Tobia F, Pesce CM Istituto Scientifico di Medicina Interna, Università di Genova, Italy.
A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.
12: 1: Conn Med. 1989 Jun;53,6:335-7. Treatment of Lyme disease. Schoen RT.
Lyme disease, a tick-transmitted spirochetal infection, can be divided into three stages that can overlap or occur alone. The goals of antibiotic therapy in stage one are to shorten the duration of early disease and to prevent the development of later stages20of the illness. This can usually be accomplished with oral antibiotic therapy. Later stages of the illness are frequently more difficult to treat, requiring prolonged oral or intravenous antibiotic therapy.
13: Infection. 1989 Jul-Aug;17,4:216-7. High-dose intravenous penicillin G does not prevent further progression in early neurological manifestation of Lyme borreliosis. Kohler J, Schneider H, Vogt A.
Neurologische Universitätsklinik und Poliklinik, Freiburg.
We report two cases of Lyme borreliosis, LB, with erythema migrans, EM, and simultaneous meningopolyneuritis with radicular pain and lymphocytic pleocytosis in the cerebrospinal fluid, CSF. EM and pain disappeared completely under high-dose penicillin G therapy within few a days. Pathological findings in CSF improved. Nevertheless, during and after therapy, neurological signs of LB developed: cranial nerve palsies as well as paresis of extremity muscles with radicular distribution.
14: 1: Dtsch Med Wochenschr. 1989 Oct 20;114,42:1602-6. Neuro-borreliosis or intervertebral disk prolapse? [Article in German] Dieterle L, Kubina FG, Staudacher T, Büdingen HJ.
Abteilung für Neurologie und klinische Neurophysiologie, St.-Elisabethen-Krankenhaus Ravensburg.
Between September 1986 and November 1988, 17 patients were hospitalized and treated for neuro-borreliosis. Ten of them had been admitted with suspected lumbar or cervical root or compression syndrome. Only four patients recalled a tick bite, only three an erythema migrans. Uni- or bilateral facial paresis was a prominent feature in six patients. Three of 14 patients had no IgG antibodies against Borrelia, either in serum or cerebrospinal fluid at the initial examination, two had positive titres in serum only. Despite antibiotic treatment, usually 10 mega U penicillin three times daily, six patients had a recurrence by April, 1989, treated with penicillin again or with twice daily 100 mg doxycycline or 2 g ceftriaxon. In four of them a residual painful polyneuropathy remains.
15: 1: Infection. 1989 Nov-Dec;17,6:355-9.Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. Neurologische Klinik Grosshadern, München, FR Germany.
The persistence of Borrelia burgdorferi in patients treated with antibiotics is described. The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B. burgdorferi in serum. Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients. B. burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B. burgdorferi.We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi.
[Persistence:] However, some patients later developed symptoms of the disease despite antibiotic treatment, 9-11. Because of these observations it has become questionable if a definite eradication of B. burgdorferi with antibiotics is possible, p.357. ..The central nervous system invasion by spirochetes and a persistence of Treponema pallidum after penicillin G therapy is common in neurosyphilis, 22,23, p.358.[Treatment:] In view of the hitherto failure of treatment, low CSF concentration of penicillin G, survival of B. burgdorferi in patients treated with antibiotics, the moderate penicillin G susceptibility o f the organism and unpredictable progression of the disease, it seems appropriate to treat patients with substantially larger doses of antibiotics and/or longer than is provided in present treatment regimens. p.358.[Seronegativity:] As shown, negative antibody-titers do not provide evidence for successful therapy; antibody-titers may become negative despite persistence.
16: Acta Trop. 1990 Dec;48, 2:89-94.Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi. MacDonald AB, Berger BW, Schwan TG.
Department of Pathology, Southampton Hospital, New York 11968.
Lyme borreliosis, a spirochetal infection caused by Borrelia burgdorferi, may become clinically active after a period of latency in the host.Active cases of Lyme disease may show clinical relapse following antibiotic therapy. The latency and relapse phenomena suggest that the Lyme disease spirochete is capable of survival in the host for prolonged periods of time. We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations. Some patients with Lyme borreliosis may require more than the currently recommended two to three week course of antibiotic therapy to eradicate strains of the spirochete which grow slowly.
17: Infect Immun. 1991 Feb;59,2:671-8. Intracellular localization of Borrelia burgdorferi within human endothelial cells. Ma Y, Sturrock A, Weis JJ.
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
The later stages of infection by the Lyme disease pathogen, Borrelia burgdorferi, are characterized by the persistence of the organism in individuals possessing a strong anti-Borrelia immune response. This suggests that the organism is sequestered in a tissue protected from the immune system of the host or there is a reservoir of the organism residing within the cells of the host. In this report, the ability of B. burgdorferi to gain entrance into human umbilical vein endothelial cells was explored as a model for invasion. Incubation of B. burgdorferi with human umbilical vein endothelial cells at ratios ranging from 200:1 to 5,000:1 resulted in the intracellular localization of 10 to 25% of B. burgdorferi in 24 h. The intracellular location of the spirochetes was demonstrated by the incorporation of radiolabeled B. burgdorferi into a trypsin-resistant compartment and was confirmed by double-immunofluorescence staining which differentiated intracellular from extracellular organisms. Actin-containing microfilaments were required for the intracellular localization, indica ting that the host cell participates in the internalization process. Activation of endothelial cells by agents known to increase the expression of several adhesion molecules had no effect on the interaction of B. burgdorferi with the endothelial monolayer. This indicates that the endothelial receptor for B. burgdorferi is constitutively expressed and that internalization is not dependent upon adhesion molecules whose expression is induced by inflammatory mediators. The demonstration of B. burgdorferi within endothelial cells suggest that intracellular localization may be a potential mechanism by which the organism escapes from the immune response of the host and may contribute to persistence of the organism during the later stages of Lyme disease.
18: 1991: Journal of Infectious Diseases, Feb;163,2:311-8 Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. Pfister HW, Preac-Mursic V, Wilske B, Schielke E, SÃrgel F, Einhäupl KM.
Neurological Department, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously, iv, every 24 h, n = 17, or cefotaxime, 2 g iv every 8 h, n = 16. Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 2 7 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid, CSF, 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime.However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.
19: Medicine, Baltimore. 1991 Mar;70,2:83-90. Lyme disease: clinical features, classification, and epidemiology in the upper midwest. Agger W, Case KL, Bryant GL, Callister SM.
Section of Infectious Disease, La Crosse Lutheran Hospital, Wisconsin.
Lyme disease can be classified using the terminology of syphilis. In this series of 95 cases from the upper midwest, early cases, defined as an illness of less than 2 months, were more likely to have lived in or recently visited a highly endemic area. Unlike late cases, early cases presented entirely in the nonwinter months, p less than .001. Early disease was further subdivided into primary and secondary disease. Ninety percent of primary and 43% of secondary cases had erythema migrans, while no late cases had active erythema migrans, p less than .001. Clinical manifestations of nonspecific inflammation, except for arthralgia, were more common in early than late disease, p less than .01. In secondary cases, monoarticular arthritis was slightly more common than polyarticular arthritis, with the reverse occurring in late disease, p less than .05. Indirect fluorescent antibody testing revealed a ratio of IgM to IgG antibodies to be helpful in distinguishing early from late disease. Antibacterial therapy in early, primary cases caused Jarisch-Herxheimer reaction 7% of the time. Despite longer and more frequent parenteral therapy, late Lyme disease frequently required retreatment, owing to poor clinical response, p less than .05.
19.5: N Engl J Med. 1991 Apr 18;324(16):1137. Chronic neurologic manifestations of Lyme disease. Logigian EL, Kaplan RF, Steere AC. Department of Neurology, Tufts University School of Medicine, Boston, MA 02111.
BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients, age range, 25 to 72 years, with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection. RESULTS. Of the 27 patients, 24, 89 percent, had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients,70 percent, had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue, 74 percent, headache, 48 percent, arthritis, 37 percent, and hearing loss, 15 percent. At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone, 2 g daily, 17 patients, 63 percent, had improvement; 6, 22 percent, had improvement but then relapsed; and 4,15 percent, had no change in their condition. CONCLUSIONS. Months to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis. These chronic neurologic abnormalities usually improve with antibiotic therapy.
20: Arthritis Rheum. 1991 Aug;34,8:1056-60. Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. Schoen RT, Aversa JM, Rahn DW, Steere AC.
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16, 80%, had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients, 20%, had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.
21: 1: Clin Exp Rheumatol. 1992 Jul-Aug;10,4:387-90. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Fraser DD, Kong LI, Miller FW.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
A 40-year-old white man with a several year history of various immunologic disorders, including anti-Jo-1 autoantibody positive dermatomyositis, developed clinical Lyme disease after being biten by a tick. The patient was treated with oral tetracycline and his initial symptoms resolved; however, he suffered an exacerbation of his muscle disease which was difficult to control despite cytotoxic therapy. Antibiotic therapy was reinstituted after Borrelia burgdorferi was detected in the patient's peripheral blood leukocytes by the polymerase chain reaction, PCR. All serologic, T-cell stimulation, and western blot analyses, however, were negative. The patient's disease responded to oral ampicillin, p robenecid therapy and concurrent cytotoxic therapy. Subsequent leukocyte PCR testing has been negative for the causative agent of Lyme disease. This case may provide an example of the in vivo immuno-modulatory effects of spirochetes in human autoimmune disease. In addition, this case emphasizes the potential clinical utility of PCR technology in evaluating the persistent sero-negative Lyme disease which may occur in immunocompromised individuals.
22: 1:20 J Infect Dis. 1992 Aug;166,2:440-4.Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. Georgilis K, Peacocke M, Klempner MS.
Department of Medicine, New England Medical Center, Boston, Massachusetts.
The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity.Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival.
23: J Am Acad Dermatol. 1993 Feb;28,2 Pt 2:312-4. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L.
Department of Medicine, Northern Westchester Hospital Center, Mount Kisco, NY.
Erythema migrans recurred in a patient 6 months after a course of treatment with minocycline for Lyme disease. Polymerase chain reaction on heparinized peripheral blood at that time demonstrated the presence of Borrelia burgdorferi-specific DNA. The patient was seronegative by Lyme enzyme-linked immunosorbent assay but showed suspicious bands on Western blot. Findings of a Warthin-Starry stain of a skin biopsy specimen of the eruption revealed a Borrelia-compatible structure. Reinfection was not believed to have occurred. Further treatment with minocycline led to resolution of the erythema migrans.
24: 1: J Infect Dis. 1993 May;167,5:1074-81.Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. Klempner MS, Noring R, Rogers RA.
Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111.
The ability of Borrelia burgdorferi to attach to and invade human fibroblasts was investigated by scanning electron and confocal microscopy. By scanning electron microscopy, B. burgdorferi were tightly adherent to fibroblast monolayers after 24-48 h but were eliminated from the cell surface by treatment with ceftriaxone, 1 microgram/mL, for 5 days. Despite the absence of visible spirochetes on the cell surface after antibiotic treatment, viable B. burgdorferi were isolated from lysates of the fibroblast monolayers. B. burgdorferi were observed in the perinuclear region within human fibroblasts by laser scanning confocal microscopy.Intracellular spirochetes specifically labeled with monoclonal anti-flagellin antibody were also identified by fluorescent laser scanning confocal microscopy. These observations suggest that B. burgdorferi can adhere to, penetrate, and invade human fibroblasts in organisms that remain viable.
25: Infection. 1993 Mar-Apr;21,2:83-8. Azithromycin versus doxycycli ne for treatment of erythema migrans: clinical and microbiological findings. Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V, Jereb M.
Department of Infectious Diseases, University Medical Center, Ljubljana, Slovenia.
The effectiveness of azithromycin and doxycycline in the treatment of erythema migrans was compared in a prospective randomized trial. One hundred seven adult patients with typical erythema migrans, examined in the Lyme Borreliosis Outpatients' Clinic, University Department of Infectious Diseases in Ljubljana, were included in the study. Fifty-five patients received azithromycin, 500 mg twice daily for the first day, followed by 500 mg once daily for four days, and 52 patients received doxycycline, 100 mg twice daily for 14 days. The mean duration of skin lesions after the beginning of treatment was 7.5 +/- 5.9 days, median value 5, range 2-28 days, in the azithromycin group and 11.4 +/- 7.8 days, median value 9, range 2 days--8 weeks, in the doxycycline group, p < kappa =" 0.54"> or = 1 month, only 7, 37 percent, had positive tests, P < n =" 43," n =" 38;" p =" 0.03;" p =" 0.03;" p =" 0.04," p =" 0.04." p =" 0.02," p =" 0.01," n =" 6]," n =" 4]," n =" 3]." p =" 0.03," p =" .002," p =" .03," p =" .04," p =" .02," p =" .004," p =" .04," p =" .01," n =" 10," p =" .06." n="97," n="86," n="15," p =" 0.001."> 4 mg/L. Comparison of MBC values after 3 and 6 weeks' incubation revealed comparable results for azithromycin and ceftriaxone while for amoxicillin, cefuroxime and doxycycline, some differences were found. In one of the patients from whom there were borrelia isolated before and after treatment with cefuroxime axetil, both isolates were resistant to cefuroxime. In the other two patients, the paired isolates were susceptible to the antibiotic used for therapy.
95: Int J Med Microbiol. 2006 May;296 Suppl 40:233-41. Epub 2006 Mar 10.Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance. Hunfeld KP, Ruzić-Sabljić E, Norris DE, Kraiczy P, Strle F. Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany. K.Hunfeld@em.uni-frankfurt.de
Erythema migrans, EM, develops at the site of the tick bite in 77-90% of Lyme borreliosis, LB, patients and is therefore a common manifestation of early disease.Clinical treatment failures have been reported in early LB cases for almost every suitable antimicrobial agent. The exact risk of resistance to antibiotic treatment in patients with EM, however, is not known and there are few published cases of culture-proven treatment failure. Moreover, currently available diagnostic techniques cannot reliably discriminate between possible reinfection, true endogenous relapse and co-infection with other tick-borne pathogens. These drawbacks together with the phenomenon of r esistance to therapy in individual patients undoubtedly contribute to the inconsistencies surrounding the optimal treatment regimens for LB and are often misinterpreted and misused to support prolonged antibiotic treatment regimens. The question for the underlying mechanisms of possible antimicrobial resistance in Borrelia burgdorferi sensu lato remains unresolved but a better understanding of such genetic or phenotypic mechanisms would be helpful for the treatment of LB and other spirochetal diseases. Investigations on this issue, at best, should start with borrelial isolates cultured from patients before the start of antibiotic therapy and again after the conclusion of treatment. This task, however, remains challenging insofar, as culture is rarely successful under routine laboratory conditions after antimicrobial therapy.Here, we review recent clinical and experimental data on treatment resistance in EM patients suggesting that, although rare, borrelial persistence does occur at the site of the infectious lesion after antibiotic treatment. Borrelial persistence, however, is unlikely to result from acquired resistance against antimicrobial agents that were used for initial specific chemotherapy.
96: Eur J Pediatr. 2006 Jun;165,6:420-1. Epub 2006 Mar 4. Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104. Hendrickx G, Demanet C, Vandenplas Y.
Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. g.hendrickx@st-anna.nl
We report on two patients with a persistent Lyme arthritis. In addition both had a peculiar disease history. The first patient had oligoarticular juvenile idiopathic arthritis in remission. Five months after an infected tick bite, she developed a relapse of arthritis in the same knee. We considered Lyme borreliosis as the possible trigger for this reactivation. The disease history of the second patient was that of a classical non-responder. After extensive antibiotic treatment osteolytic lesions became visible. MRI images suggested an erosive arthropathy and arthroscopy was used to investigate possible erosive arthritis. Studies on collected material made us consider the following hypothesis. Despite demonstration of a spirochete fragment in a synovial biopsy, the patient recovered without additional antibiotic treatment. Conclusion: delay of antibiotic treatment after appearance of erythema migrans may cause systemic spread of the antigen and predispose to Lyme arthritis. If intra-articular steroids are considered when spontaneous resolution of Lyme arthritis does not occur, magnetic resonance imaging of the affected joint, prior to administration, may provide additional information. The success of synovectomy may be related to removal of undegraded antigenic material which may prolong the inflammation.
97: Int J Immunopathol Pharmacol. 2006 Jul-Sep;19,3:545-9. In vitro susceptibility of isolates of Borrelia burgdorferi s.l. to antimicrobial agents. Santino I, Scazzocchio F, Ciceroni L, Ciarrocchi S, Sessa R, Del Piano M. Department of Public Health Sciences, La Sapienza University, Rome, Italy. iolanda.santino@uniroma1.it
In the present study, we investigate the in vitro antimicrobial activity of macrolides, beta-lactams and tetracycline against Borrelia burgdorferi s.l. clinical and tick isolates. Minimal inhibitory concentrations, MICs, were determined in normal growth condition and after pre-exposure of the strains to sub-MIC of the founder of each drug family. All the classes of tested antibiotics showed good antibacterial activity against all the borreliae isolates and there were no significant susceptibility differences among clinical and tick isolates. After pre-exposure of the strains to sub-MIC of erythromycin, cefoxitin and tetracycline, we observed that some strains of B. burgdorferi s.l. showed higher MIC values to both the pre-exposed drug and drugs of the same family. The less susceptibility of borreliae, in the last growth condition in vitro, could be one of the justifications of clinical results indicating the limited efficacy of these antibiotics in treatment of B. burgdoferi infections.
98: 1: Microbes Infect. 2006 Nov-Dec; 8,14-15:2832-40. Epub 2006 Sep 22.Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi. Livengood JA, Gilmore RD Jr.
Centers for Disease Control and Prevention, Divi sion of Vector-borne Infectious Diseases, 3150 Rampart Road, CSU Foothills Campus, Fort Collins, CO 80522, USA.
Human infection by Borrelia burgdorferi, the etiological agent for Lyme disease, can result in serious acute and late-term disorders including neuroborreliosis, a degenerative condition of the peripheral and central nervous systems.To examine the mechanisms involved in the cellular pathogenesis of neuroborreliosis, we investigated the ability of B. burgdorferi to attach to and/or invade a panel of human neuroglial and cortical neuronal cells. In all neural cells tested, we observed B. burgdorferi in association with the cell by confocal microscopy. Further analysis by differential immunofluorescent staining of external and internal organisms, and a gentamicin protection assay demonstrated an intracellular localization of B. burgdorferi. A non-infectious strain of B. burgdorferi was attenuated in its ability to associate with these neural cells, suggesting that a specific borrelial factor related to cellular infectivity was responsible for the association. Cytopathic effects were not observed following infection of these cell lines with B. burgdorferi, and internalized spirochetes were found to be viable. Invasion of neural cells by B. burgdorferi provides a putative mechanism for the organism to avoid the host's immune response while potentially causing functional damage to neural cells during infection of the CNS.
98.5: Acta Radiologica, Volume 48, Issue 7 2007 , pages 755 - 762 Brain Magnetic Resonance Imaging Does Not Contribute to the Diagnosis of Chronic Neuroborreliosis. Aalto A, Sjöwall J, Davidsson L, Forsberg P, Smedby O. Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anne.aalto@imv.liu.se
BACKGROUND: Borrelia infections, especially chronic neuroborreliosis, NB, may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. PURPOSE: To evaluate brain magnetic resonance imaging, MRI, in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. MATERIAL AND METHODS: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1-, with and without gadolinium, T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery, FLAIR, imaging were used. RESULTS: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls, no significant difference. Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients, rho = 0.83, P<0.01, rho =" 0.61," x =" 42,3" x ="43," x =" 53,5" n="20;" n="5," n =" 220)">12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second "Great Imitator" (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = "cysts") by the antibiotic Tigecycline (TG; Wyeth), a glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged.
114: Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment HETA YRJÄNÄInen 1 , JUKKA HYTÖNen 1 , PAULIINA HARTIALA 1 , JARMO OKSI 2 and MATTI K. VILJANEN Departments of 1Medical Microbiology and Immunology and 2 Medicine, University of Turku, Turku, Finland
Correspondence to Heta Yrjänäinen, Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland. e-mail: heta.yrjanainen@utu.fi Copyright Journal compilation © 2010 APMIS
We have earlier shown that Borrelia burgdorferi-infected and ceftriaxone-treated mice have viable spirochetes in their body, since immunosuppressive treatment allows B. burgdorferi to be detected by culture. However, the niche of the persisting spirochetes remained unknown. In the present study, we analyzed the tissues of B. burgdorferi-infected and ceftriaxone-treated mice by culture and PCR to reveal the foci of persisting spirochetes. C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks, or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment. All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30–100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.
https://acrobat.com/#d=sbb-EmpQrQTgrPoezLGreg
Michael D. Parent
Introduction Summary:
There is an abundance of evidence demonstrating that Borrelia Burgdorferi, the causative agent of Lyme Disease, and related pathogenic species, can persist within specific body tissues and cells of various mammals despite adequate antibiotic therapy: ponies [93.5, 111.5], non-human primates [50, 86], dogs [65.5, 70, 80, 81, 82, 84], mice [44, 62, 88, 100, 107, 108, 110, 114], and humans [all others].
There is also abundant evidence that Borrelia Burgdorferi has evolved in a manner similar to other bacteria that evade the immune system via pleomorphic modification, in other words, the bacteria can change its shape beyond the conventional spirochetal form [45, 55, 61, 64, 90, 105, 109, 113].
L-forms, and cystic Borrelia have been identified in a number of studies [45, 68, 77, 87, 105, 109, 112, 113].
When these "forms" are exposed to the typical antibiotics, such as Penicillin family antibiotics or Doxycycline, they are unaffected. When the antibiotic is removed from the environment, the bacterium will alter its form once more, morphing back into a spiral form, allowing ongoing mobility [45, 68, 87, 90, 105, 109].
I have taken the time to "bold" the conclusions and various other aspects that clearly indicate a deviation from the point of view given by a number of physicians and researchers who deny the possibility of ongoing chronic infection within the human host.
The current guidelines issued by the Infectious Disease Society Of America (IDSA) are consistently used to dismiss further discussion regarding the subject of persistence. The guidelines are titled: “The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis” Clinical Infectious Diseases 2006; 43:1089–134.
Patients who receive a diagnosis of Lyme Disease, either based on clinical observation and/or objective indicators often improve with antibiotic therapy [1, 4, 18, 19, 26, 33, 66].
However, if they have been undiagnosed and untreated for Lyme Disease for a long period of time, it often takes longer courses of antibiotics beyond those currently recommended to see progress in symptom reduction [15, 66, 73, 93, 105].
The U.S. National Institute Of Health funded a number of randomized double-blind placebo-controlled trials (RCT) regarding the long term treatment of Lyme Disease.
However, these RCT's were 3 months in duration or less.
Patients with documented medical records indicating Chronic Lyme Disease or a Lyme-Like Illness who have been untreated often do not see meaningful improvement until after 4-6 months of treatment, and even still, the improvements are modest initially in many patients and may require an ongoing open ended treatment regimen with antibiotics [66, 93].
It is well understood and agreed upon universally that the more time Borrelia Burdorferi has had to disseminate into various ligaments, bones, collagen, muscles, and other tissues, then the higher the probability of ongoing complications or symptoms post-antibiotic therapy.
Presently, studies indicate that antibiotics can not access many of the areas that Borrelia Burgdorferi disseminates to unless the bacterium itself leaves the safe haven of a Fibroblast skin cell [11, 22, 23, 24, 25, 29, 35, 52, 64, 70, 72, 80, 81, 84, 94], or synovial tissue cells and fluid [1, 7, 9, 31, 34, 37, 42, 60, 61, 69, 70, 71, 102].
Introductory Conclusion:
Therefore, we have studies demonstrating abundant persistence.
We have National Institute Of Health funded studies that do not treat patients long enough to confirm whether the treatment really is effective or not.
The short term studies we do have contradict other studies as well as those based on clinical reports from health care providers treating these patients with antibiotics beyond the currently accepted time frame.
It is unwise for the IDSA to claim that long-term antibiotic therapy doesn't work when you've only performed a study for 3 months, when the vast majority of the patients in the study have had the infection for many years and require at least 3-6 months of oral antibiotic before clinical improvements are seen.
IV antibiotics may demonstrate minor to moderate symptomatic improvement after 1- 3 months, but if that treatment is only given for 3 months and then discontinued, then it will be equally ineffective and the symptoms will return to pre-treatment levels. Coincidentally, that's exactly what happened in Dr. Brian Fallon's study. Some symptoms improved, but then returned upon discontinuing therapy.
I have discussed merely one specific possibility for the failure of patients to thrive and improve during the currently available randomized double-blind placebo-controlled clinical trials (RCT). Dr. Daniel J. Cameron writes in the Journal Of Medical Hypothesis that a number of limitations exist within the currently structured (RCTs), that strongly support the position I've laid forth. Med Hypotheses. 2009 Jun;72(6):688-91. Epub 2009 Mar 5. Insufficient evidence to deny antibiotic treatment to chronic Lyme disease patients. First Medical Associates, Medicine, 175 Main Street, Mount Kisco, NY 10549, USA. Cameron@LymeProject.com
"Evidence for the hypothesis: There are eight limitations that support the hypothesis: (1) the power of the evidence is inadequate to draw definite conclusions, (2) the evidence is too heterogeneous to make strong recommendations, (3) the risk to an individual of facing a long-term debilitating illness has not been considered, (4) the risk to society of a growing chronically ill population has not been considered, (5) treatment delay has not been considered as a confounder, (6) co-infections have not been considered as a confounder, (7) the design of RCTs did not address the range of treatment options in an actual practice, and (8) the findings cannot be generalized to actual practice. Implications of the hypothesis: This hypothesis suggests that physicians should consider the limitations of the evidence before denying antibiotic treatment for Chronic Lyme Disease (CLD). Physicians who deny antibiotic treatment to CLD patients might inform their patients that there are some clinicians who disagree with that position, and then offer to refer them for a second opinion to a doctor who could potentially present a different point of view. The hypothesis also suggests that health care insurers should consider the limitations of the evidence before adopting policies that routinely deny antibiotic treatment for CLD patients and should expand coverage of CLD to include clinical discretion for specific clinical situations."
There is more than enough information to justify at least a neutral position in respect to whether Borrelia Burgdorferi and related infectious species persist in human beings despite the Infectious Disease Society Of America's recommendations. Due to this uncertainty, treating physicians can not conclusively deny that persistence in human beings may be more problematic than assumed.
The scientific studies available on Lyme Disease contradict each other to a significant degree. Many study authors state in no uncertain terms that the discussion of Lyme Disease is a closed case. I disagree. The evidence disagrees. The Chief Medical Officer in the United Kingdom echoed the sentiments of the IDSA in 2009 stating: "There is no biological evidence of symptomatic chronic Lyme disease amongst those who have received the recommended treatment regimen." - CMO, Autum 2009, Issue 49, pg. 4. The IDSA states: "To date, there is no convincing biologic evidence for the existence of symptomatic chronic B. burgdorferi infection among patients after receipt of recommended treatment regimens for Lyme disease." - Clin Infect Dis 2006 Nov 1;43(9):1089-134
Skepticism is the heart of science. Cynicism is the death of reason.
The following studies are organized by year, page, and study title within the Study table index.
Study Table Index:
1986 page 18
Ann Intern Med. 1986 Jun;104,6:798-800. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM.
1986 page18
J Am Acad Dermatol. 1986 Sep;15,3:459-63.Treating erythema chronicum migrans of Lyme disease. Berger BW.
1987 page 18
Arthritis Rheum. 1987 Apr;30,4:448-50.Failure of tetracycline therapy in early Lyme disease. Dattwyler RJ, Halperin JJ.
1987 page 19
Arthritis Rheum. 1987 Jun;30,6:705-8. Lyme meningoencephalitis: report of a severe, penicillin-re sistant case. Diringer MN, Halperin JJ, Dattwyler RJ.
1988 page 19
Pediatr Infect Dis J. 1988 Apr;7,4:286-9. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
1988 page 19
Ann N Y Acad Sci. 1988;539:346-51. Treatment of erythema chronicum migrans of Lyme disease. Berger BW. Department of Dermatology, New York University School of Medicine, New York 10016.
1988 page 20
Arthritis Rheum. 1988 Apr;31,4:487-95. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue. Steere AC, Duray PH, Butcher EC.
1988 page 20
AMA. 1988 May 13;259,18:2737-9 Fatal adult respiratory distress syndrome in a patient with Lyme disease. Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A.
1988 page 20
J Infect Dis. 1988 Oct;158,4:905-6. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. Schmidli J, Hunziker T, Moesli P, Schaad UB.
1988 page 21
N Engl J Med. 1988 Dec 1;319,22:1441-6. Comment in: N Engl J Med. 1989 May 11;320,19:1279-80.Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG.
1989 page 21
Am J Clin Pathol. 1989 Jan;91,1:95 7. Spirochetes in the spleen of a patient with chronic Lyme disease. Cimmino MA, Azzolini A, Tobia F, Pesce CM Istituto Scientifico di Medicina Interna, Università di Genova, Italy.
1989 page 22
Conn Med. 1989 Jun;53,6:335-7. Treatment of Lyme disease. Schoen RT.
1989 page 22
Infection. 1989 Jul-Aug;17,4:216-7. High-dose intravenous penicillin G does not prevent further progression in early neurological manifestation of Lyme borreliosis. Kohler J, Schneider H, Vogt A.
1989 page 22
Dtsch Med Wochenschr. 1989 Oct 20;114,42:1602-6. Neuro-borreliosis or intervertebral disk prolapse? [Article in German] Dieterle L, Kubina FG, Staudacher T, Büdingen HJ.
1989 page 23
Infection. 1989 Nov-Dec;17,6:355-9.Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. Neurologische Klinik Grosshadern, München, FR Germany.
1990 page 23
Acta Trop. 1990 Dec;48, 2:89-94.Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi. MacDonald AB, Berger BW, Schwan TG.
Department of Pathology, Southampton Hospital, New York 11968.
1991 page 24
Infect Immun. 1991 Feb;59,2:671-8. Intracellular localization of Borrelia burgdorferi within human endothelial cells. Ma Y, Sturrock A, Weis JJ.
1991page 24
1991: Journal of Infectious Diseases, Feb;163,2:311-8 Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. Pfister HW, Preac-Mursic V, Wilske B, Schielke E, SÃrgel F, Einhäupl KM.
1991 page 25
Medicine, Baltimore. 1991 Mar;70,2:83-90. Lyme disease: clinical features, classification, and epidemiology in the upper midwest. Agger W, Case KL, Bryant GL, Callister SM.
1991 page 25
N Engl J Med. 1991 Apr 18;324(16):1137. Chronic neurologic manifestations of Lyme disease. Logigian EL, Kaplan RF, Steere AC. Department of Neurology, Tufts University School of Medicine, Boston, MA 02111.
1991 page 26
Arthritis Rheum. 1991 Aug;34,8:1056-60. Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. Schoen RT, Aversa JM, Rahn DW, Steere AC.
1992 page 26
Clin Exp Rheumatol. 1992 Jul-Aug;10,4:387-90. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Fraser DD, Kong LI, Miller FW.
1992 page 27
J Infect Dis. 1992 Aug;166,2:440-4.Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. Georgilis K, Peacocke M, Klempner MS. Department of Medicine, New England Medical Center, Boston, Massachusetts.
1993 page 27
J Am Acad Dermatol. 1993 Feb;28,2 Pt 2:312-4. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L.
1993 page 27
J Infect Dis. 1993 May;167,5:1074-81.Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. Klempner MS, Noring R, Rogers RA.
1993 page 28
Infection. 1993 Mar-Apr;21,2:83-8. Azithromycin versus doxycycli ne for treatment of erythema migrans: clinical and microbiological findings. Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V, Jereb M.
1993 page 29
J Neurol. 1993 May;240,5:278-83. Borrelia burgdorferi myositis: report of eight patients. Reimers CD, de Koning J, Neubert U, Preac-Mursic V, Koster JG, Müller-Felber W, Pongratz DE, Duray PH.
1993 page 30
Arthritis Rheum. 1993 Nov;36,11:1621 6. Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Häupl T, Hahn G, Rittig M, Krause A, Schoerner C, Schönherr U, Kalden JR, Burmester GR.
1993 page 30
J Clin Neuroophthalmol. 1993 Sep;13,3:155-61; discussion 162. 59: First isolation of Borrelia burgdorferi from an iris biopsy. Preac-Mursic V, Pfister HW, Spiegel H, Burk R, Wilske B, Reinhardt S, Böhmer R.
1993 page 31
Cent Eur J Public Health. 1993 Dec;1,2:81-5. Electron microscopy and the polymerase chain reaction of spirochetes from the blood of patients with Lyme disease. Hulínská D, Krausová M, Janovská D, Rohácová H, Hancil J, Mailer H.
1993 page 32
Neurology. 1993 Dec;43,12:2705-7. Stroke due to Lyme disease. Reik L Jr. Department of Neurology, University of Connecticut Health Center, Farmington 06030-1845.
1994 page 32
N Engl J Med. 1994 Jan 27; 330,4:282-3.Detection of Borrelia burgdorferi DNA by polymerase chain reaction in synovial fluid from patients with Lyme arthritis. Nocton JJ, Dressler F, Rutledge BJ, Rys PN, Persing DH, Steere AC.
1994 page 33
J Clin Microbiol. 1994 Mar;32,3:715-20.Isolation of Borrelia burgdorferi from biopsy specimens taken from healthy-looking skin of patients with Lyme borreliosis. Kuiper H, van Dam AP, Spanjaard L, de Jongh BM, Widjojokusumo A, Ramselaar TC, Cairo I, Vos K, Dankert J. Department of Medical Microbiology, Academic Medical Centre, University Hospital, University of Amsterdam, The Netherlands.
1994 page 33
J Rheumatol. 1994 Mar;21,3:454-61. Lyme disease: an infectious and postinfectious syndrome.Asch ES, Bujak DI, Weiss M, Peterson MG, Weinstein A.
1994 page 34
Ann Intern Med. 1994 Mar 15;120,6:487-9. The persistence of spirochetal nucleic acids in active Lyme arthritis. Bradley JF, Johnson RC, Goodman JL.
1994 page 34
Ann Intern Med. 1994 Oct 15;121,8:560-7.The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Shadick NA, Phillips CB, Logigian EL, Steere AC, Kaplan RF, Berardi VP, Duray PH, Larson MG, Wright EA, Ginsburg KS, Katz JN, Liang MH.
1994 page 35
Infect. 1994 Nov;29,3:255-61.Treatment of late Lyme borreliosis. Wahlberg P, Granlund H, Nyman D, Panelius J, Seppälä I.
1994 page 36
Late complaints after erythema migrans Herta Klade, MD and Elizabeth Aberer, MD. JSTD 1994; 1:52-56.
1994 page 36
Borrelia burgdorferi - Seek and ye shall find. Expanding the envelope Kenneth Liegner, MD. JSTD 1994; 1:79-81.
1994 page 37
Psychiatric aspects of Lyme disease in children and adolescents: A community epidemiologic study in Westchester, New York Brian A. Fallon, MD, MPH; Hector Bird, MD; Christina Hoven, DrPH; Daniel Cameron, MD, MPH; Michael R. Liebowitz, MD; and David Shaffer, MD. JSTD 1994; 1:98-100.
1994 page 37
Persistence of Borrelia burgdorferi despite antibiotic treatment Michael A. Patmas, MD. JSTD 1994; 1:101.
1994 page 38
J Infect Dis. 1994 Nov;170,5:1312-6 Comment in: J Infect Dis. 1995 May;171,5:1379-80. Fate of Borrelia burgdorferi DNA in tissues of infected mice after antibiotic treatment. Malawista SE, Barthold SW, Persing DH. Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
1995 page 39
Antimicrob Agents Chemother. 1995 May;39,5:1127-33. Effects of penicillin, ceftriaxone, and doxycycline on morphology of Borrelia burgdorferi. Kersten A, Poitschek C, Rauch S, Aberer E.
1995 page 40
Persistent PCR positivity in a patient being treated for Lyme disease. Kornelia Keszler, MD and Richard C. Tilton, PhD. JSTD 1995; 2:57-58.
1995 page 40
Neuroborreliosis in Texas Audrey Stein Goldings, MD. JSTD 1995; 2:59-61.
1995 page 40
Vartiovaara I. 1995 Living with Lyme. Lancet, 345:842-4 A Finnish physician ’s account of his experiences that beginning with a tick bite in Vancouver in 1987.
1995 page 40
J Neuropsychiatry Clin Neurosci. 1995 Summer;7,3:345-7. Rapidly progressive frontal-type dementia associated with Lyme disease. Waniek C, Prohovnik I, Kaufman MA, Dwork AJ.
1995 page 41
Ann Neurol. 1995 Oct;38,4:667-9. Comment in: Ann Neurol. 1995 Oct;38,4:560-2.Neuroborreliosis in the nonhuman primate: Borrelia burgdorferi persists in the central nervous system. Pachner AR, Delaney E, O'Neill T.
1995 41
Eur Neurol. 1995;35,2:113-7. Comment in: Eur Neurol. 1996;36,6:394-5. Seronegative chronic relapsing neuroborreliosis.Lawrence C, Lipton RB, Lowy FD, Coyle PK.
1996 42
Infection. 1996 Jan-Feb;24,1:64-8. Azithromycin and doxycycline for treatment of Borrelia culture-positive erythema migrans. Strle F, Maraspin V, Lotric-Furlan S, Ruzić-Sabljić E, Cimperman J.
1996 42
Infection. 1996 Jan-Feb;24,1:9-16. Erratum in: Infection 1996 Mar-Apr;24,2:169.Kill kinetics of Borrelia burgdorferi and bacterial findings in relation to the treatment of Lyme borreliosis. Preac Mursic V, Marget W, Busch U, Pleterski Rigler D, Hagl S. Max v. Pettenkofer Institut, Ludwig-Maximilians-Universität München, Germany.
1996 43
Infection. 1996 Jan-Feb;24,1:73-5. Treatment failure in erythema migrans--a review. Weber K. Dermatologische Privatpraxis, München, Germany.
1996 43
Infection. 1996 May-Jun;24,3:218-26. Erratum in: Infection 1996 Jul-Aug;24,4:335. Formation and cultivation of Borrelia burgdorferi spheroplast-L-form variants. Mursic VP, Wanner G, Reinhardt S, Wilske B, Busch U, Marget W.
1996 44
JAMA. 1996 Jun 5; 275,21, :1657-60. Concurrent Lyme disease and babesiosis. Evidence for increased severity and duration of illness. K rause PJ, Telford SR 3rd, Spielman A, Sikand V, Ryan R, Christianson D, Burke G, Brassard P, Pollack R, Peck J, Persing DH.
1996 44
Antimicrob Agents Chemother. 1996 Jun;40,6:1552-4. Eucaryotic cells protect Borrelia burgdorferi from the action of penicillin and ceftriaxone but not from the action of doxycycline and erythromycin. Brouqui P, Badiaga S, Raoult D. Unité des Rickettsies, Faculté de Médecine, Centre National de la Recherche Scientifique, Marseille, France.
1996 45
Infection. 1996 Sep-Oct;24,5:347-53.Borrelia burgdorferi DNA in the urine of treated patients with chronic Lyme disease symptoms. A PCR study of 97 cases. Bayer ME, Zhang L, Bayer MH. Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
1996 45
Hum Pathol. 1996 Oct;27,10:1025-34.Ultrastructural demonstration of spirochetal antigens in synovial fluid and synovial membrane in chronic Lyme disease: possible factors contributing to persistence of organisms. Nanagara R, Duray PH, Schumacher HR Jr. Allergy-Immunology-Rheumatology Division, Department of Medicine, Faculty of Medicine, KhonKaen University, Thailand.
1996 46
Rheumatol Int. 1996;16,3:125-32.Intracellular persistence of Borrelia burgdorferi in human synovial cells. Girschick HJ, Huppertz HI, Rüssmann H, Krenn V, Karch H.
1996 47
Antimicrob Agents Chemother. 1996 Nov;40 11 :2632-6.In vivo activities of ceftriaxone and vancomycin against Borrelia spp in the mouse brain and other sites. Kazragis RJ, Dever LL, Jorgensen JH, Barbour AG.
1996 47
Brain. 1996 Dec;119, Pt 6:2143-54. Inflammatory brain changes in Lyme borreliosis. A report on three patients and review of literature. Oksi J, Kalimo H, Marttila RJ, Marjamäki M, Sonninen P, Nikoskelainen J, Viljanen MK.
1996 48
Am J Dermatopathol. 1996 Dec;18,6:571-9. Heterogeneity of Borrelia burgdorferi in the skin. Aberer E, Kersten A, Klade H, Poitschek C, Jurecka W.
1997 48
328: Semin Neurol. 1997 Mar;17,1:25-30.Peripheral nervous system Lyme borreliosis. Logigian EL.
1997 49
J Clin Microbiol. 1997 January; 35(1): 111–116. Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment. R K Straubinger, B A Summers, Y F Chang, and M J Appel Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. rks4@cornell.edu
1997 49
Clin Infect Dis. 1997 Jul;25 Suppl 1:S52-6. Tetracycline therapy for chronic Lyme disease. Donta ST.
1997 50
Clin Infect Dis. 1997 Jul;25 Suppl 1:S64-70.Why is chronic Lyme borreliosis chronic? Aberer E, Koszik F, Silberer M.
1997 51
American College of Rheumatology, Vol 40,9, Branigan P; Rao J; 1997 PCR evidence for Borrelia burgdorferi DNA in synovium in absence of positive serology. Suppl, Rao J; Gerard H; Sept, p.S270 Hudson A; Williams W; Arayssi T; Pando J; Bayer M; Rothfuss S; .PCR evidence for Borrelia has been identified in synovial biopsies of patients with clinical pictures that had not initially suggested Lyme disease. Clayburne G; Sieck M; Schumacher HR.
1997 51
Journal of Spirochetal & Tick-borne Diseases, Vol. 4, No. 1/2 Two lessons from the canine model of Lyme Disease: migration of Borrelia burgdorferi in tissues and persistence after antibiotic treatment. Straubinger RK; 1997 Straubinger AF; Jacobson RH; Chang Y; Summer BA;
1998 51
Ann Rheum Dis. 1998 Feb;57,2:118-21.Detection of Borrelia burgdorferi by polymerase chain reaction in synovial membrane, but not in synovial fluid from patients with persisting Lyme arthritis after antibiotic therapy. Priem S, Burmester GR, Kamradt T, Wolbart K, Rittig MG, Krause A.
1998 52
Med J Aust. 1998 May 18;168,10:500-2. Comment in: Med J Aust. 1998 May 18;168,10:479-80. Culture-positive Lyme borreliosis. Hudson BJ, Stewart M, Lennox VA, Fukunaga M, Yabuki M, Macorison H, Kitchener-Smith J.
1998 52
Acta Clin Belg. 1998 Jun;53,3:178-83.Lyme borreliosis--a review of the late stages and treatment of four cases. Petrovic M, Vogelaers D, Van Renterghem L, Carton D, De Reuck J, Afs chrift M. Department of Internal Medicine, University Hospital Ghent, Belgium.
1998 53
Eur J Clin Microbiol Infect Dis. 1998 Oct;17,10:715-9.Comparison of oral cefixime and intravenous ceftriaxone followed by oral amoxicillin in disseminated Lyme borreliosis. Oksi J, Nikoskelainen J, Viljanen MK. Department of Medicine, Turku University Central Hospital, Finland.
1998 53
Neurology. 1998 Nov;51,5:1489-91. Comment in: Neurology. 1999 Sep 11;53,4:895-6. Clinical and serologic follow-up in patients with neuroborreliosis. Treib J, Fernandez A, Haass A, Grauer MT, Holzer G, Woessner R.
1998 54
Infection. 1998 Nov-Dec; 26,6:364-7.A proposal for the reliable culture of Borrelia burgdorferi from patients with chronic Lyme disease, even from those previously aggressively treated. Phillips SE, Mattman LH, Hulínská D, Moayad H. Greenwich Hospital, CT 06830, USA.
1998 54
Klin Monatsbl Augenheilkd. 1998 Dec;213,6:351-4. Pars plana vitrectomy in Borrelia burgdorferi endophthalmitis [Article in German] Meier P, Blatz R, Gau M, Spencker FB, Wiedemann P.
1999 55
Ann Med. 1999 Jun; 3,3:225-32. Borrelia burgdorferi detected by culture and PCR in clinical relapse of disseminated Lyme borreliosis. Oksi J, Marjamäki M, Nikoskelainen J, Viljanen MK.
1999 55
Zentralbl Bakteriol. 1999 Jul;289,3:301-18. Persistence of Borrelia garinii and Borrelia afzelii in patients with Lyme arthritis. Hulínská D, Votýpka J, Valeso vá M.
2000 56
J Infect Dis. 2000 Mar;181,3:1069-81. Status of Borrelia burgdorferi infection after antibiotic treatment and the effects of corticosteroids: An experimental study. Straubinger RK, Straubinger AF, Summers BA, Jacobson RH.
2000 57
J Clin Microbiol. 2000 Jun; 38,6, :2191-9. PCR-Based quantification of Borrelia burgdorferi organisms in canine tissues over a 500-Day postinfection period. Straubinger RK. James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. rks4@cornell.edu
2001 59
Br J Dermatol. 2001 Feb;144,2:387-92. Is olation and polymerase chain reaction typing of Borrelia afzelii from a skin lesion in a seronegative patient with generalized ulcerating bullous lichen sclerosus et atrophicus. Breier F, Khanakah G, Stanek G, Kunz G, Aberer E, Schmidt B, Tappeiner G.
2001 59
Epidemiol Mikrobiol Imunol. 2001 Feb;50,1:10-6.Persistence of Borrelia burgdorferi sensu lato in patients with Lyme borreliosis [Article in Czech] Honegr K, Hulínská D, Dostál V, Gebouský P, Hanková E, Horácek J, Vyslouzil L, Havlasová J. Infekcní klinika, Fakultní nemocnice, Hradec Králové.
2001 60
Ann Neurol. 2001 Sep;50,3, :330-8.Central and peripheral nervous system infection, immunity, and inflammation in the NHP model of Lyme borreliosis. Pachner AR, Cadavid D, Shu G, Dail D, Pachner S, Hodzic E, Barthold SW. Department of Neurosciences, UMDNJ-New Jersey Medical School, Newark 07103, USA. pachner@umdnj.edu
2002 60
Wien Klin Wochenschr. 2002 Jul 31;114,13-14:574-9. Cystic forms of Borrelia burgdorferi sensu lato: induction, development, and the role of RpoS. Murgia R, Piazzetta C, Cinco M.
2002 61
Acta Neurol Scand. 2002 Oct;106(4):205-8. Chronic symptoms are common in patients with neuroborreliosis -- a questionnaire follow-up study. Vrethem M, Hellblom L, Widlund M, Ahl M, Danielsson O, Ernerudh J, Forsberg P.
2002 62
J Infect Dis. 2002 Nov 15;186,10:1430-7. Epub 2002 Oct 23. Detection of attenuated, noninfectious spirochetes in Borrelia burgdorferi-infected mice after antibiotic treatment. Bockenstedt LK, Mao J, Hodzic E, Barthold SW, Fish D.
2002 62
Antimicrob Agents Chemother. 2002 Nov;46,11:3637-40. Erythromycin resistance in Borrelia burgdorferi. Terekhova D, Sartakova ML, Wormser GP, Schwartz I, Cabello FC.
2002 63
Przegl Epidemiol. 2002;56 Suppl 1:57-67.New aspects of the pathogenesis of lyme disease [Article in Polish] Zajkowska JM, Hermanowska-Szpakowicz T. Klinika Chorób Zakaźnych i Neuroinfekcji AM w Bia ymstoku.
2003 63
Neurology. 2003 Jun 24;60,12:1923-30. Comment in: Neurology. 2003 Jun 24;60,12:1888-9.Study and treatment of post Lyme di sease, STOP-LD: a randomized double masked clinical trial. Krupp LB, Hyman LG, Grimson R, Coyle PK, Melville P, Ahnn S, Dattwyler R, Chandler B.
2003 64
Med Sci Monit. 2003 Nov;9,11:PI136-42. Macrolide therapy of chronic Lyme Disease. Donta ST.
2005 65
Vet Microbiol. 2005 May 20;107(3-4):285-94 Antibiotic treatment of experimentally Borrelia burgdorferi-infected ponies. Chang YF, Ku YW, Chang CF, Chang CD, McDonough SP, Divers T, Pough M, Torres A. College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. yc42@cornell.edu
2005 65
Int J Antimicrob Agents. 2005 Jun;25,6:474-8. Susceptibility of Borrelia afzelii strains to antimicrobial agents. Ruzić-Sabljić E, Podreka T, Maraspin V, Strle F.
2006 66
Int J Med Microbiol. 2006 May;296 Suppl 40:233-41. Epub 2006 Mar 10.Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance. Hunfeld KP, Ruzić-Sabljić E, Norris DE, Kraiczy P, Strle F. Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany. K.Hunfeld@em.uni-frankfurt.de
2006 67
Eur J Pediatr. 2006 Jun;165,6:420-1. Epub 2006 Mar 4. Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104. Hendrickx G, Demanet C, Vandenplas Y. Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. g.hendrickx@st-anna.nl
2006 67
Int J Immunopathol Pharmacol. 2006 Jul-Sep;19,3:545-9. In vitro susceptibility of isolates of Borrelia burgdorferi s.l. to antimicrobial agents. Santino I, Scazzocchio F, Ciceroni L, Ciarrocchi S, Sessa R, Del Piano M. Department of Public Health Sciences, La Sapienza University, Rome, Italy. iolanda.santino@uniroma1.it
2006 68
Microbes Infect. 2006 Nov-Dec; 8,14-15:2832-40. Epub 2006 Sep 22.Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi. Livengood JA, Gilmore RD Jr.
2007 68
Acta Radiologica, Volume 48, Issue 7 2007 , pages 755 - 762 Brain Magnetic Resonance Imaging Does Not Contribute to the Diagnosis of Chronic Neuroborreliosis. Aalto A, Sjöwall J, Davidsson L, Forsberg P, Smedby O. Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anne.aalto@imv.liu.se
2007 69
Pol Merkur Lekarski. 2007 Apr;22,130:275-9. Related Articles, Concentrations of pro-inflammatory cytokines IFN-gamma, IL-6, IL-12 and IL-15 in serum and cerebrospinal fluid in patients with neuroborreliosis undergoing antibiotic treatment. Article in Polish. Pancewicz SA, Kondrusik M, Zajkowska J, Grygorczuk S. Akademia Medyczna w Bialymstoku, Klinika Chorób Zakaznych i Neuroinfekcji.20spancewicz@interia.pl
2007 69
J Infect Dis. 2007 May 15;195,10:1489-96. Epub 2007 Apr 6.Anti-tumor necrosis factor-alpha treatment activates Borrelia burgdorferi spirochetes 4 weeks after ceftriaxone treatment in C3H/He mice. Yrjänäinen H, Hytönen J, Song XY, Oksi J, Hartiala K, Viljanen MK. Department of Medical Microbiology, University of Turku, Turku, 20520, Finland. heta.yrjanainen@utu.fi
2007 70
Adv Med Sci. 2007;52:174-8. Concentration of TGF-beta1 in the supernatant of peripheral blood mononuclear cells cultures from patients with early disseminated and chronic lyme borreliosis. Grygorczuk S, Chmielewski T, Zajkowska J, Swierzbińska R, Pancewicz S, Kondrusik M, Tylewska-Wierzbanowska S, Hermanowska-Szpakowicz T. Department of Infectious Diseases and Neuroinfections, Medical University of Białystok, ul. Zurawia 14, 15-540 Białystok, Poland. neuroin@amb.edu.pl
2007 71
Rheumatol Int. 2007 Sep;27,11:1091-3. Epub 2007 Apr 4. Seronegative Lyme arthritis. Holl-Wieden A, Suerbaum S, Girschick HJ. Children's hospital, Section of Pediatric Rheumatology, Immunology and Infectious diseases, University of Wuerzburg, Josef-Schneider-Str. 2, 97090 Wuerzburg, Germany.
2007 71
Pol Merkur Lekarski. 2007 Sep;23,135:174-8. Concentration of soluble forms of selectins in serum and in cerebrospinal fluid in group of patients with neuroborreliosis--a preliminary study Moniuszko AM, Pancewicz SA, Ko ndrusik M, Zajkowska J, Grygorczuk S, Swierzbińska R. Akademia Medyczna w Białymstoku, Klinika Chorób Zakaźnych i Neuroinfekcji.
2008 72
Volume 358:428-431 January 24, 2008 Number An Appraisal of "Chronic Lyme Disease" To the Editor: Feder et al., Oct. 4 issue,
2008 75
Persistence of Borrelia burgdorferi Following Antibiotic Treatment in Mice Antimicrobial Agents and Chemotherapy, published online ahead of print on 3 March 2008 Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold
2008 75
Antimicrobial Agents and Chemotherapy, May 2008, p. 1728-1736, Vol. 52, No. 50066-4804 Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice Emir Hodzic, Sunlian Feng, Kevin Holden, Kimberly J. Freet, and Stephen W. Barthold*
2008 76
Pol Arch Med Wewn. 2008 May;118 5:314-7. : Neuroborreliosis with extrapyramidal symptoms: a case report. Biesiada G, Czapiel J, Sobczyk-Krupiarz I, Garlicki A, Mach T. Department of Infectious Diseases, Division of Gastroenterology, Hepatology, and Infectious Diseases, Jagiellonian University School of Medicine, Kraków, Poland. gbiesiada@op.pl
2008 76
J Neuroinflammation. 2008 Sep 25;5:40. Persisting atypical and cystic forms of Borrelia burgdorferi and local inflammation in Lyme neuroborreliosis. Miklossy J, Kasas S, Zurn AD, McCall S, Yu S, McGeer PL.
2008 77
Microb Pathog. 2008 Sep 20. Borrelia burgdorferi expression of the bba64, bba65, bba66, and bba73 genes in tissues during persistent infection in mice. Gilmore RD Jr, Howison RR, Schmit VL, Carroll JA.
2008 78
Med Hypotheses. 2008;70,5:967-74. Epub 2007 Nov 5. The association between tick-borne infections, Lyme borreliosis and autism spectrum disorders. Bransfield RC, Wulfman JS, Harvey WT, Usman AI.
2008 79
Journal of Veterinary Diagnostic Investigation Vol. 20 Issue 3, 321-324 Copyright © 2008 by the American Association of Veterinary Laboratory Diagnosticians: Validation of an in-clinic enzyme-linked immunosorbent assay kit for diagnosis of Borrelia burgdorferi infection in horses. Amy L. Johnson1, Thomas J. Divers and Yung-Fu Chang
2009 80
J Antimicrob Chemother. 2009 Jun;63 6:1163-72. Epub 2009 Apr 17. Assessment of methylthioadenosine/S-adenosylhomocysteine nucleosidases of Borrelia burgdorferi as targets for novel antimicrobials using a novel high-throughput method. Cornell KA, Primus S, Martinez JA, Parveen N.
2009 81
Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18656-61. Epub 2009 Oct 20. Destruction of spirochete Borrelia burgdorferi round-body propagules (RBs) by the antibiotic tigecycline. Brorson Ø, Brorson SH, Scythes J, MacAllister J, Wier A, Margulis L.
2010 81
Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment HETA YRJÄNÄInen 1 , JUKKA HYTÖNen 1 , PAULIINA HARTIALA 1 , JARMO OKSI 2 and MATTI K. VILJANEN Departments of 1Medical Microbiology and Immunology and 2 Medicine, University of Turku, Turku, Finland
Evidential support for the case of Chronic Infection:
1: Ann Intern Med. 1986 Jun;104,6:798-800. Borrelia burgdorferi in joint fluid in chronic Lyme arthritis. Snydman DR, Schenkein DP, Berardi VP, Lastavica CC, Pariser KM.
Although indirect evidence suggests that chronic Lyme arthritis is caused by persistent infection with Borrelia burgdorferi, direct visualization has been lacking. We report the demonstration of B. burgdorferi from synovial fluid aspirated from the right knee of a 31-year-old man with Lyme arthritis for more than 1 year. After 6 days, culture medium inoculated with synovial fluid showed one motile and several nonmotile spirochetes. Direct immunofluorescence staining showed reactivity with anti-B. burgdorferi serum. Spirochetes were not seen in subcultured material. The patient's arthritis improved with high-dose intravenous penicillin. Identification of B. burgdorferi from the joint fluid of a patient with long-standing arthritis supports the concept that the arthritis is due to persistent infection.
2: J Am Acad Dermatol. 1986 Sep;15,3:459-63.Treating erythema chronicum migrans of Lyme disease. Berger BW.
The efficacy of antibiotic treatment of 117 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. Fifty-six patients with a minor form of the illness did not require retreatment and did not develop late manifestations following antibiotic treatment. Three pregnant patients were included in this group.Fourteen of sixty-one patients with a major form of the illness required retreatment, and five developed posttreatment late manifestations of Lyme disease consisting of Bell's palsy and persistent joint pain. Although the preferred antibiotic for treating erythema chronicum migrans of Lyme disease has not been conclusively established, tetracycline and penicillin proved effective. The use of probenecid plus penicillin may be of benefit to patients with the major form of the illness.
3: 1: Arthritis Rheum. 1987 Apr;30,4:448-50.Failure of tetracycline therapy in early Lyme disease. Dattwyler RJ, Halperin JJ.
We describe the clinical courses of 5 patients with Lyme disease who developed significant late complications, despite receiving tetracycline early in the course of their illness. All 5 patients had been treated for erythema chronicum migra ns with a course of tetracycline that met or exceeded current recommendations. The late manifestations of Lyme disease included arthritis, cranial nerve palsy, peripheral neuropathy, chronic fatigue, and changes in mental function. Our findings suggest that the use of tetracycline at a dosage of 250 mg, 4 times a day for 10 days, as a treatment for early Lyme disease should be reconsidered. To determine optimal therapy for early Lyme disease, a study that compares an increased dosage of tetracycline with alternative treatments is indicated.
4: Arthritis Rheum. 1987 Jun;30,6:705-8. Lyme meningoencephalitis: report of a severe, penicillin-re sistant case. Diringer MN, Halperin JJ, Dattwyler RJ.
Although Lyme disease frequently attacks the central nervous system, this involvement is rarely severe, and high-dose intravenous penicillin usually is adequate treatment. The patient we describe developed severe Lyme meningoencephalitis despite receiving a full course of penicillin, and his condition continued to deteriorate after reinstitution of this treatment. Intravenous chloramphenicol was used successfully and resulted in a substantial improvement.
5: Pediatr Infect Dis J. 1988 Apr;7,4:286-9. Borrelia burgdorferi in a newborn despite oral penicillin for Lyme borreliosis during pregnancy. Weber K, Bratzke HJ, Neubert U, Wilske B, Duray PH.
Department of Medicolegal Medicine, Dermatology and Microbiology, University of Munich, Federal Republic of Germany. "We now demonstrate B. burgdorferi in the brain and liver of a newborn whose mother had been treated with oral penicillin for LB [Lyme borreliosis] during the first trimester of pregnancy. ..The death of the newborn was probably due to a respiratory failure as a consequence of perinatal brain damage.”
6: Ann N Y Acad Sci. 1988;539:346-51. Treatment of erythema chronicum migrans of Lyme disease. Berger BW. Department of Dermatology, New York University School of Medicine, New York 10016.
Between June 1981 and July 1987 the efficacy of antibiotic treatment of 215 patients with erythema chronicum migrans of Lyme disease was evaluated in terms of the necessity for retreatment and the prevention of the late manifestations of Lyme disease. The principal antibiotics utilized to treat 161 patients through 1986 were varying doses of tetracycline, or penicillin alone or in combination with probenecid. Two of 8 0 patients with a minor form of the illness and 17 of 81 patients with a major form of the illness required retreatment. There were four patients who did not respond to retreatment with their original medication. A 15- to 30-day course of amoxicillin, 500 mg q.i.d., and probenecid, 500 mg q.i.d., or doxycycline, 100 mg t.i.d., and on three occasions ceftriaxone, 2-4 g/day i.v., were used to treat 54 patients in 1987. Although it is too early to judge the efficacy of treatment in these patients, increases in the incidence of Herxheimer reactions and drug eruptions were observed. Strict compliance with treatment protocols and the possibility of reactions to medications should be thoroughly discussed with patients.
7: 1: Arthritis Rheum. 1988 Apr;31,4:487-95. Spirochetal antigens and lymphoid cell surface markers in Lyme synovitis. Comparison with rheumatoid synovium and tonsillar lymphoid tissue. Steere AC, Duray PH, Butcher EC.
Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut.
Using monoclonal antibodies to spirochetal antigenes and lymphoid cell surface markers, we examined the synovial lesions of 12 patients with Lyme disease, and compared them with rheumatoid synovium and tonsillar lymphoid tissue. The synovial lesions of Lyme disease patients and rheumatoid arthritis patients were similar and often consisted of the elements found in normal organized lymphoid tissue. In both diseases, T cells, predominantly of the helper/inducer s ubset, were distributed diffusely in subsynovial lining areas, often with nodular aggregates of tightly intermixed T and B cells. IgD-bearing B cells were scattered within the aggregates, and a few follicular dendritic cells and activated germinal center B cells were sometimes present. Outside the aggregates, many plasma cells, high endothelial venules, scattered macrophages, and a few dendritic macrophages were found. HLA-DR and DQ expression was intense throughout the lesions. In 6 of the 12 patients with Lyme arthritis, but in none of those with rheumatoid arthritis, a few spirochetes and globular antigen deposits were seen in and around blood vessels in areas of lymphocytic infiltration. Thus, in Lyme arthritis, a small number of spirochetes are probably the antigenic stimulus for chronic synovial inflammation.
8: AMA. 1988 May 13;259,18:2737-9 Fatal adult respiratory distress syndrome in a patient with Lyme disease. Kirsch M, Ruben FL, Steere AC, Duray PH, Norden CW, Winkelstein A.
Department of Medicine, Montefiore Hospital, University of Pittsburgh School of Medicine, PA 15213.
A dry cough, fever, generalized maculopapular rash, and myositis developed in a 67-year-old woman; she also had markedly abnormal liver function test results. Serologic tests proved that she had an infection of recent onset with Borrelia burgdorferi, the agent that causes Lyme disease. During a two-month course of illness, her condition remained refractory to treatment with antibiotics, salicylates, and steroids. Ultimately, fatal adult respiratory distress syndrome developed; this was believed to be secondary to Lyme disease.
9: J Infect Dis. 1988 Oct;158,4:905-6. Cultivation of Borrelia burgdorferi from joint fluid three months after treatment of facial palsy due to Lyme borreliosis. Schmidli J, Hunziker T, Moesli P, Schaad UB.
Attacks typically are intermittent and last from 3 days to 12 months. The knees are affected most often, but migratory arthritis is common and other large and small joints may be involved. Only very few Borrelia strains have been cultured from joint specimens worldwide However, a high percentage of patients with Lyme arthritis, 85%, have evidence of B burgdorferi DNA, detected by PCR, in the synovial fluid The local persistence of B burgdorferi in the joint over a long period of time might be related to the exacerbations of symptoms after chondrocyte cell transplantation. B burgdorferi is difficult to detect in synovial fluid, and cultures are positive only rarely
10: 1: N Engl J Med. 1988 Dec 1;319,22:1441-6. Comment in: N Engl J Med. 1989 May 11;320,19:1279-80.Seronegative Lyme disease. Dissociation of specific T- and B-lymphocyte responses to Borrelia burgdorferi. Dattwyler RJ, Volkman DJ, Luft BJ, Halperin JJ, Thomas J, Golightly MG.
Department of Medicine, State University of New York, School of Medicine, Stony Brook 11794-8161.
The diagnosis of Lyme disease often depends on the measurement of serum antibodies to Borrelia burgdorferi, the spirochete that causes this disorder.Although prompt treatment with antibiotics may abrogate the antibody response to the infection, symptoms persist in some patients. We studied 17 patients who had presented with acute Lyme disease and received prompt treatment with oral antibiotics, but in whom chronic Lyme disease subsequently developed. Although these patients had clinically active disease, none had diagnostic levels of antibodies to B. burgdorferi on either a standard enzyme-linked immunosorbent assay or immunofluorescence assay. On Western blot analysis, the level of immunoglobulin reactivity against B. burgdorferi in serum from these patients was no greater than that in serum from normal controls. The patients had a vigorous T-cell proliferative response to whole B. burgdorferi, with a mean, +/- SEM, stimulation index of 17.8 +/- 3.3, similar to that, 15.8 +/- 3.2, in 18 patients with chronic Lyme disease who had detectable antibodies. The T-cell response of both groups was greater than that of a control group of healthy subjects, 3.1 +/- 0.5; P less than 0.001.We conclude that the presence of chronic Lyme disease cannot be excluded by the absence of antibodies against B. burgdorferi and that a specific T-cell blastogenic response to B. burgdorferi is evidence of infection in seronegative patients with clinical indications of chronic Lyme disease.
11: 1: Am J Clin Pathol. 1989 Jan;91,1:95 7. Spirochetes in the spleen of a patient with chronic Lyme disease. Cimmino MA, Azzolini A, Tobia F, Pesce CM Istituto Scientifico di Medicina Interna, Università di Genova, Italy.
A 54-year-old man had intermittent evening fever, arthralgia, transient erythematous macular eruption on the skin, and splenomegaly of two year's duration. Immunofluorescence tests for Borrelia burgdorferi serum antibodies had positive results, but G-penicillin treatment was ineffective. Splenectomy with lymph node biopsy was performed to rule out lymphoproliferative disorders. Borrelia-like spirochetes were identified histologically in the spleen; this finding was consistent with persistence of B. burgdorferi organisms in inner organs in chronic Lyme disease.
12: 1: Conn Med. 1989 Jun;53,6:335-7. Treatment of Lyme disease. Schoen RT.
Lyme disease, a tick-transmitted spirochetal infection, can be divided into three stages that can overlap or occur alone. The goals of antibiotic therapy in stage one are to shorten the duration of early disease and to prevent the development of later stages20of the illness. This can usually be accomplished with oral antibiotic therapy. Later stages of the illness are frequently more difficult to treat, requiring prolonged oral or intravenous antibiotic therapy.
13: Infection. 1989 Jul-Aug;17,4:216-7. High-dose intravenous penicillin G does not prevent further progression in early neurological manifestation of Lyme borreliosis. Kohler J, Schneider H, Vogt A.
Neurologische Universitätsklinik und Poliklinik, Freiburg.
We report two cases of Lyme borreliosis, LB, with erythema migrans, EM, and simultaneous meningopolyneuritis with radicular pain and lymphocytic pleocytosis in the cerebrospinal fluid, CSF. EM and pain disappeared completely under high-dose penicillin G therapy within few a days. Pathological findings in CSF improved. Nevertheless, during and after therapy, neurological signs of LB developed: cranial nerve palsies as well as paresis of extremity muscles with radicular distribution.
14: 1: Dtsch Med Wochenschr. 1989 Oct 20;114,42:1602-6. Neuro-borreliosis or intervertebral disk prolapse? [Article in German] Dieterle L, Kubina FG, Staudacher T, Büdingen HJ.
Abteilung für Neurologie und klinische Neurophysiologie, St.-Elisabethen-Krankenhaus Ravensburg.
Between September 1986 and November 1988, 17 patients were hospitalized and treated for neuro-borreliosis. Ten of them had been admitted with suspected lumbar or cervical root or compression syndrome. Only four patients recalled a tick bite, only three an erythema migrans. Uni- or bilateral facial paresis was a prominent feature in six patients. Three of 14 patients had no IgG antibodies against Borrelia, either in serum or cerebrospinal fluid at the initial examination, two had positive titres in serum only. Despite antibiotic treatment, usually 10 mega U penicillin three times daily, six patients had a recurrence by April, 1989, treated with penicillin again or with twice daily 100 mg doxycycline or 2 g ceftriaxon. In four of them a residual painful polyneuropathy remains.
15: 1: Infection. 1989 Nov-Dec;17,6:355-9.Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis. Preac-Mursic V, Weber K, Pfister HW, Wilske B, Gross B, Baumann A, Prokop J. Neurologische Klinik Grosshadern, München, FR Germany.
The persistence of Borrelia burgdorferi in patients treated with antibiotics is described. The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B. burgdorferi in serum. Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients. B. burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B. burgdorferi.We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B. burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B. burgdorferi.
[Persistence:] However, some patients later developed symptoms of the disease despite antibiotic treatment, 9-11. Because of these observations it has become questionable if a definite eradication of B. burgdorferi with antibiotics is possible, p.357. ..The central nervous system invasion by spirochetes and a persistence of Treponema pallidum after penicillin G therapy is common in neurosyphilis, 22,23, p.358.[Treatment:] In view of the hitherto failure of treatment, low CSF concentration of penicillin G, survival of B. burgdorferi in patients treated with antibiotics, the moderate penicillin G susceptibility o f the organism and unpredictable progression of the disease, it seems appropriate to treat patients with substantially larger doses of antibiotics and/or longer than is provided in present treatment regimens. p.358.[Seronegativity:] As shown, negative antibody-titers do not provide evidence for successful therapy; antibody-titers may become negative despite persistence.
16: Acta Trop. 1990 Dec;48, 2:89-94.Clinical implications of delayed growth of the Lyme borreliosis spirochete, Borrelia burgdorferi. MacDonald AB, Berger BW, Schwan TG.
Department of Pathology, Southampton Hospital, New York 11968.
Lyme borreliosis, a spirochetal infection caused by Borrelia burgdorferi, may become clinically active after a period of latency in the host.Active cases of Lyme disease may show clinical relapse following antibiotic therapy. The latency and relapse phenomena suggest that the Lyme disease spirochete is capable of survival in the host for prolonged periods of time. We studied 63 patients with erythema migrans, the pathognomonic cutaneous lesion of Lyme borreliosis, and examined in vitro cultures of biopsies from the active edge of the erythematous patch. Sixteen biopsies yielded spirochetes after prolonged incubations of up to 10.5 months, suggesting that Borrelia burgdorferi may be very slow to divide in certain situations. Some patients with Lyme borreliosis may require more than the currently recommended two to three week course of antibiotic therapy to eradicate strains of the spirochete which grow slowly.
17: Infect Immun. 1991 Feb;59,2:671-8. Intracellular localization of Borrelia burgdorferi within human endothelial cells. Ma Y, Sturrock A, Weis JJ.
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132.
The later stages of infection by the Lyme disease pathogen, Borrelia burgdorferi, are characterized by the persistence of the organism in individuals possessing a strong anti-Borrelia immune response. This suggests that the organism is sequestered in a tissue protected from the immune system of the host or there is a reservoir of the organism residing within the cells of the host. In this report, the ability of B. burgdorferi to gain entrance into human umbilical vein endothelial cells was explored as a model for invasion. Incubation of B. burgdorferi with human umbilical vein endothelial cells at ratios ranging from 200:1 to 5,000:1 resulted in the intracellular localization of 10 to 25% of B. burgdorferi in 24 h. The intracellular location of the spirochetes was demonstrated by the incorporation of radiolabeled B. burgdorferi into a trypsin-resistant compartment and was confirmed by double-immunofluorescence staining which differentiated intracellular from extracellular organisms. Actin-containing microfilaments were required for the intracellular localization, indica ting that the host cell participates in the internalization process. Activation of endothelial cells by agents known to increase the expression of several adhesion molecules had no effect on the interaction of B. burgdorferi with the endothelial monolayer. This indicates that the endothelial receptor for B. burgdorferi is constitutively expressed and that internalization is not dependent upon adhesion molecules whose expression is induced by inflammatory mediators. The demonstration of B. burgdorferi within endothelial cells suggest that intracellular localization may be a potential mechanism by which the organism escapes from the immune response of the host and may contribute to persistence of the organism during the later stages of Lyme disease.
18: 1991: Journal of Infectious Diseases, Feb;163,2:311-8 Randomized comparison of ceftriaxone and cefotaxime in Lyme neuroborreliosis. Pfister HW, Preac-Mursic V, Wilske B, Schielke E, SÃrgel F, Einhäupl KM.
Neurological Department, Klinikum Grosshadern, University of Munich, Federal Republic of Germany.
In this prospective, randomized, open trial, 33 patients with Lyme neuroborreliosis were assigned to a 10-day treatment with either ceftriaxone, 2 g intravenously, iv, every 24 h, n = 17, or cefotaxime, 2 g iv every 8 h, n = 16. Of the 33 patients, 30 were eligible for analysis of therapeutic efficacy. Neurologic symptoms improved or even subsided in 14 patients of the cefotaxime group and in 12 patients of the ceftriaxone group during the treatment period. At follow-up examinations after a mean of 8.1 months, 17 of 2 7 patients examined were clinically asymptomatic. In one patient Borrelia burgdorferi was isolated from the cerebrospinal fluid, CSF, 7.5 months after ceftriaxone therapy. CSF antibiotic concentrations were above the MIC 90 level for B. burgdorferi in nearly all patients examined. Patients with Lyme neuroborreliosis may benefit from a 10-day treatment with ceftriaxone or cefotaxime.However, as 10 patients were symptomatic at follow-up and borreliae persisted in the CSF of one patient, a prolongation of therapy may be necessary.
19: Medicine, Baltimore. 1991 Mar;70,2:83-90. Lyme disease: clinical features, classification, and epidemiology in the upper midwest. Agger W, Case KL, Bryant GL, Callister SM.
Section of Infectious Disease, La Crosse Lutheran Hospital, Wisconsin.
Lyme disease can be classified using the terminology of syphilis. In this series of 95 cases from the upper midwest, early cases, defined as an illness of less than 2 months, were more likely to have lived in or recently visited a highly endemic area. Unlike late cases, early cases presented entirely in the nonwinter months, p less than .001. Early disease was further subdivided into primary and secondary disease. Ninety percent of primary and 43% of secondary cases had erythema migrans, while no late cases had active erythema migrans, p less than .001. Clinical manifestations of nonspecific inflammation, except for arthralgia, were more common in early than late disease, p less than .01. In secondary cases, monoarticular arthritis was slightly more common than polyarticular arthritis, with the reverse occurring in late disease, p less than .05. Indirect fluorescent antibody testing revealed a ratio of IgM to IgG antibodies to be helpful in distinguishing early from late disease. Antibacterial therapy in early, primary cases caused Jarisch-Herxheimer reaction 7% of the time. Despite longer and more frequent parenteral therapy, late Lyme disease frequently required retreatment, owing to poor clinical response, p less than .05.
19.5: N Engl J Med. 1991 Apr 18;324(16):1137. Chronic neurologic manifestations of Lyme disease. Logigian EL, Kaplan RF, Steere AC. Department of Neurology, Tufts University School of Medicine, Boston, MA 02111.
BACKGROUND AND METHODS. Lyme disease, caused by the tick-borne spirochete Borrelia burgdorferi, is associated with a wide variety of neurologic manifestations. To define further the chronic neurologic abnormalities of Lyme disease, we studied 27 patients, age range, 25 to 72 years, with previous signs of Lyme disease, current evidence of immunity to B. burgdorferi, and chronic neurologic symptoms with no other identifiable cause. Eight of the patients had been followed prospectively for 8 to 12 years after the onset of infection. RESULTS. Of the 27 patients, 24, 89 percent, had a mild encephalopathy that began 1 month to 14 years after the onset of the disease and was characterized by memory loss, mood changes, or sleep disturbance. Of the 24 patients, 14 had memory impairment on neuropsychological tests, and 18 had increased cerebrospinal fluid protein levels, evidence of intrathecal production of antibody to B. burgdorferi, or both. Nineteen of the 27 patients,70 percent, had polyneuropathy with radicular pain or distal paresthesias; all but two of these patients also had encephalopathy. In 16 patients electrophysiologic testing showed an axonal polyneuropathy. One patient had leukoencephalitis with asymmetric spastic diplegia, periventricular white-matter lesions, and intrathecal production of antibody to B. burgdorferi. Among the 27 patients, associated symptoms included fatigue, 74 percent, headache, 48 percent, arthritis, 37 percent, and hearing loss, 15 percent. At the time of examination, chronic neurologic abnormalities had been present from 3 months to 14 years, usually with little progression. Six months after a two-week course of intravenous ceftriaxone, 2 g daily, 17 patients, 63 percent, had improvement; 6, 22 percent, had improvement but then relapsed; and 4,15 percent, had no change in their condition. CONCLUSIONS. Months to years after the initial infection with B. burgdorferi, patients with Lyme disease may have chronic encephalopathy, polyneuropathy, or less commonly, leukoencephalitis. These chronic neurologic abnormalities usually improve with antibiotic therapy.
20: Arthritis Rheum. 1991 Aug;34,8:1056-60. Treatment of refractory chronic Lyme arthritis with arthroscopic synovectomy. Schoen RT, Aversa JM, Rahn DW, Steere AC.
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Of 20 patients who underwent arthroscopic synovectomy for refractory chronic Lyme arthritis of the knee, 16, 80%, had resolution of joint inflammation during the first month after surgery or soon thereafter, and they have remained well during the 3-8-year followup period. Three of these 16 patients who were more disabled preoperatively, still had mild functional limitation at long-term followup. The remaining 4 patients, 20%, had persistent or recurrent synovitis. We conclude that arthroscopic synovectomy is effective in treating chronic Lyme arthritis in patients in whom the disease does not respond to antibiotic therapy.
21: 1: Clin Exp Rheumatol. 1992 Jul-Aug;10,4:387-90. Molecular detection of persistent Borrelia burgdorferi in a man with dermatomyositis. Fraser DD, Kong LI, Miller FW.
National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.
A 40-year-old white man with a several year history of various immunologic disorders, including anti-Jo-1 autoantibody positive dermatomyositis, developed clinical Lyme disease after being biten by a tick. The patient was treated with oral tetracycline and his initial symptoms resolved; however, he suffered an exacerbation of his muscle disease which was difficult to control despite cytotoxic therapy. Antibiotic therapy was reinstituted after Borrelia burgdorferi was detected in the patient's peripheral blood leukocytes by the polymerase chain reaction, PCR. All serologic, T-cell stimulation, and western blot analyses, however, were negative. The patient's disease responded to oral ampicillin, p robenecid therapy and concurrent cytotoxic therapy. Subsequent leukocyte PCR testing has been negative for the causative agent of Lyme disease. This case may provide an example of the in vivo immuno-modulatory effects of spirochetes in human autoimmune disease. In addition, this case emphasizes the potential clinical utility of PCR technology in evaluating the persistent sero-negative Lyme disease which may occur in immunocompromised individuals.
22: 1:20 J Infect Dis. 1992 Aug;166,2:440-4.Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro. Georgilis K, Peacocke M, Klempner MS.
Department of Medicine, New England Medical Center, Boston, Massachusetts.
The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity.Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival.
23: J Am Acad Dermatol. 1993 Feb;28,2 Pt 2:312-4. Recurrent erythema migrans despite extended antibiotic treatment with minocycline in a patient with persisting Borrelia burgdorferi infection. Liegner KB, Shapiro JR, Ramsay D, Halperin AJ, Hogrefe W, Kong L.
Department of Medicine, Northern Westchester Hospital Center, Mount Kisco, NY.
Erythema migrans recurred in a patient 6 months after a course of treatment with minocycline for Lyme disease. Polymerase chain reaction on heparinized peripheral blood at that time demonstrated the presence of Borrelia burgdorferi-specific DNA. The patient was seronegative by Lyme enzyme-linked immunosorbent assay but showed suspicious bands on Western blot. Findings of a Warthin-Starry stain of a skin biopsy specimen of the eruption revealed a Borrelia-compatible structure. Reinfection was not believed to have occurred. Further treatment with minocycline led to resolution of the erythema migrans.
24: 1: J Infect Dis. 1993 May;167,5:1074-81.Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. Klempner MS, Noring R, Rogers RA.
Division of Geographic Medicine and Infectious Diseases, New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02111.
The ability of Borrelia burgdorferi to attach to and invade human fibroblasts was investigated by scanning electron and confocal microscopy. By scanning electron microscopy, B. burgdorferi were tightly adherent to fibroblast monolayers after 24-48 h but were eliminated from the cell surface by treatment with ceftriaxone, 1 microgram/mL, for 5 days. Despite the absence of visible spirochetes on the cell surface after antibiotic treatment, viable B. burgdorferi were isolated from lysates of the fibroblast monolayers. B. burgdorferi were observed in the perinuclear region within human fibroblasts by laser scanning confocal microscopy.Intracellular spirochetes specifically labeled with monoclonal anti-flagellin antibody were also identified by fluorescent laser scanning confocal microscopy. These observations suggest that B. burgdorferi can adhere to, penetrate, and invade human fibroblasts in organisms that remain viable.
25: Infection. 1993 Mar-Apr;21,2:83-8. Azithromycin versus doxycycli ne for treatment of erythema migrans: clinical and microbiological findings. Strle F, Preac-Mursic V, Cimperman J, Ruzic E, Maraspin V, Jereb M.
Department of Infectious Diseases, University Medical Center, Ljubljana, Slovenia.
The effectiveness of azithromycin and doxycycline in the treatment of erythema migrans was compared in a prospective randomized trial. One hundred seven adult patients with typical erythema migrans, examined in the Lyme Borreliosis Outpatients' Clinic, University Department of Infectious Diseases in Ljubljana, were included in the study. Fifty-five patients received azithromycin, 500 mg twice daily for the first day, followed by 500 mg once daily for four days, and 52 patients received doxycycline, 100 mg twice daily for 14 days. The mean duration of skin lesions after the beginning of treatment was 7.5 +/- 5.9 days, median value 5, range 2-28 days, in the azithromycin group and 11.4 +/- 7.8 days, median value 9, range 2 days--8 weeks, in the doxycycline group, p < kappa =" 0.54"> or = 1 month, only 7, 37 percent, had positive tests, P < n =" 43," n =" 38;" p =" 0.03;" p =" 0.03;" p =" 0.04," p =" 0.04." p =" 0.02," p =" 0.01," n =" 6]," n =" 4]," n =" 3]." p =" 0.03," p =" .002," p =" .03," p =" .04," p =" .02," p =" .004," p =" .04," p =" .01," n =" 10," p =" .06." n="97," n="86," n="15," p =" 0.001."> 4 mg/L. Comparison of MBC values after 3 and 6 weeks' incubation revealed comparable results for azithromycin and ceftriaxone while for amoxicillin, cefuroxime and doxycycline, some differences were found. In one of the patients from whom there were borrelia isolated before and after treatment with cefuroxime axetil, both isolates were resistant to cefuroxime. In the other two patients, the paired isolates were susceptible to the antibiotic used for therapy.
95: Int J Med Microbiol. 2006 May;296 Suppl 40:233-41. Epub 2006 Mar 10.Risk of culture-confirmed borrelial persistence in patients treated for erythema migrans and possible mechanisms of resistance. Hunfeld KP, Ruzić-Sabljić E, Norris DE, Kraiczy P, Strle F. Institute of Medical Microbiology, University Hospital of Frankfurt, Paul-Ehrlich Str. 40, D-60596 Frankfurt/Main, Germany. K.Hunfeld@em.uni-frankfurt.de
Erythema migrans, EM, develops at the site of the tick bite in 77-90% of Lyme borreliosis, LB, patients and is therefore a common manifestation of early disease.Clinical treatment failures have been reported in early LB cases for almost every suitable antimicrobial agent. The exact risk of resistance to antibiotic treatment in patients with EM, however, is not known and there are few published cases of culture-proven treatment failure. Moreover, currently available diagnostic techniques cannot reliably discriminate between possible reinfection, true endogenous relapse and co-infection with other tick-borne pathogens. These drawbacks together with the phenomenon of r esistance to therapy in individual patients undoubtedly contribute to the inconsistencies surrounding the optimal treatment regimens for LB and are often misinterpreted and misused to support prolonged antibiotic treatment regimens. The question for the underlying mechanisms of possible antimicrobial resistance in Borrelia burgdorferi sensu lato remains unresolved but a better understanding of such genetic or phenotypic mechanisms would be helpful for the treatment of LB and other spirochetal diseases. Investigations on this issue, at best, should start with borrelial isolates cultured from patients before the start of antibiotic therapy and again after the conclusion of treatment. This task, however, remains challenging insofar, as culture is rarely successful under routine laboratory conditions after antimicrobial therapy.Here, we review recent clinical and experimental data on treatment resistance in EM patients suggesting that, although rare, borrelial persistence does occur at the site of the infectious lesion after antibiotic treatment. Borrelial persistence, however, is unlikely to result from acquired resistance against antimicrobial agents that were used for initial specific chemotherapy.
96: Eur J Pediatr. 2006 Jun;165,6:420-1. Epub 2006 Mar 4. Persistent synovitis in two children with Lyme arthritis linked with HLA-DRB1*1104. Hendrickx G, Demanet C, Vandenplas Y.
Department of Paediatrics, Paediatric Orthopaedic and Rheumatology Unit, Academisch Ziekenhuis -Vrije Universiteit Brussel, Laarbeeklaan 101, 1090 Brussels, Belgium. g.hendrickx@st-anna.nl
We report on two patients with a persistent Lyme arthritis. In addition both had a peculiar disease history. The first patient had oligoarticular juvenile idiopathic arthritis in remission. Five months after an infected tick bite, she developed a relapse of arthritis in the same knee. We considered Lyme borreliosis as the possible trigger for this reactivation. The disease history of the second patient was that of a classical non-responder. After extensive antibiotic treatment osteolytic lesions became visible. MRI images suggested an erosive arthropathy and arthroscopy was used to investigate possible erosive arthritis. Studies on collected material made us consider the following hypothesis. Despite demonstration of a spirochete fragment in a synovial biopsy, the patient recovered without additional antibiotic treatment. Conclusion: delay of antibiotic treatment after appearance of erythema migrans may cause systemic spread of the antigen and predispose to Lyme arthritis. If intra-articular steroids are considered when spontaneous resolution of Lyme arthritis does not occur, magnetic resonance imaging of the affected joint, prior to administration, may provide additional information. The success of synovectomy may be related to removal of undegraded antigenic material which may prolong the inflammation.
97: Int J Immunopathol Pharmacol. 2006 Jul-Sep;19,3:545-9. In vitro susceptibility of isolates of Borrelia burgdorferi s.l. to antimicrobial agents. Santino I, Scazzocchio F, Ciceroni L, Ciarrocchi S, Sessa R, Del Piano M. Department of Public Health Sciences, La Sapienza University, Rome, Italy. iolanda.santino@uniroma1.it
In the present study, we investigate the in vitro antimicrobial activity of macrolides, beta-lactams and tetracycline against Borrelia burgdorferi s.l. clinical and tick isolates. Minimal inhibitory concentrations, MICs, were determined in normal growth condition and after pre-exposure of the strains to sub-MIC of the founder of each drug family. All the classes of tested antibiotics showed good antibacterial activity against all the borreliae isolates and there were no significant susceptibility differences among clinical and tick isolates. After pre-exposure of the strains to sub-MIC of erythromycin, cefoxitin and tetracycline, we observed that some strains of B. burgdorferi s.l. showed higher MIC values to both the pre-exposed drug and drugs of the same family. The less susceptibility of borreliae, in the last growth condition in vitro, could be one of the justifications of clinical results indicating the limited efficacy of these antibiotics in treatment of B. burgdoferi infections.
98: 1: Microbes Infect. 2006 Nov-Dec; 8,14-15:2832-40. Epub 2006 Sep 22.Invasion of human neuronal and glial cells by an infectious strain of Borrelia burgdorferi. Livengood JA, Gilmore RD Jr.
Centers for Disease Control and Prevention, Divi sion of Vector-borne Infectious Diseases, 3150 Rampart Road, CSU Foothills Campus, Fort Collins, CO 80522, USA.
Human infection by Borrelia burgdorferi, the etiological agent for Lyme disease, can result in serious acute and late-term disorders including neuroborreliosis, a degenerative condition of the peripheral and central nervous systems.To examine the mechanisms involved in the cellular pathogenesis of neuroborreliosis, we investigated the ability of B. burgdorferi to attach to and/or invade a panel of human neuroglial and cortical neuronal cells. In all neural cells tested, we observed B. burgdorferi in association with the cell by confocal microscopy. Further analysis by differential immunofluorescent staining of external and internal organisms, and a gentamicin protection assay demonstrated an intracellular localization of B. burgdorferi. A non-infectious strain of B. burgdorferi was attenuated in its ability to associate with these neural cells, suggesting that a specific borrelial factor related to cellular infectivity was responsible for the association. Cytopathic effects were not observed following infection of these cell lines with B. burgdorferi, and internalized spirochetes were found to be viable. Invasion of neural cells by B. burgdorferi provides a putative mechanism for the organism to avoid the host's immune response while potentially causing functional damage to neural cells during infection of the CNS.
98.5: Acta Radiologica, Volume 48, Issue 7 2007 , pages 755 - 762 Brain Magnetic Resonance Imaging Does Not Contribute to the Diagnosis of Chronic Neuroborreliosis. Aalto A, Sjöwall J, Davidsson L, Forsberg P, Smedby O. Division of Radiology, Department of Medicine and Care, Faculty of Health Sciences, Linköping University, Linköping, Sweden. anne.aalto@imv.liu.se
BACKGROUND: Borrelia infections, especially chronic neuroborreliosis, NB, may cause considerable diagnostic problems. This diagnosis is based on symptoms and findings in the cerebrospinal fluid but is not always conclusive. PURPOSE: To evaluate brain magnetic resonance imaging, MRI, in chronic NB, to compare the findings with healthy controls, and to correlate MRI findings with disease duration. MATERIAL AND METHODS: Sixteen well-characterized patients with chronic NB and 16 matched controls were examined in a 1.5T scanner with a standard head coil. T1-, with and without gadolinium, T2-, and diffusion-weighted imaging plus fluid-attenuated inversion recovery, FLAIR, imaging were used. RESULTS: White matter lesions and lesions in the basal ganglia were seen in 12 patients and 10 controls, no significant difference. Subependymal lesions were detected in patients down to the age of 25 and in the controls down to the age of 43. The number of lesions was correlated to age both in patients, rho = 0.83, P<0.01, rho =" 0.61," x =" 42,3" x ="43," x =" 53,5" n="20;" n="5," n =" 220)">12 species). Penicillin solution is one unfavorable condition that induces RBs. This antibiotic that inhibits bacterial cell wall synthesis cures neither the second "Great Imitator" (Lyme borreliosis) nor the first: syphilis. Molecular-microscopic techniques, in principle, can detect in animals (insects, ticks, and mammals, including patients) helices and RBs of live spirochetes. Genome sequences of B. burgdorferi and Treponema pallidum spirochetes show absence of >75% of genes in comparison with their free-living relatives. Irreversible integration of spirochetes at behavioral, metabolic, gene product and genetic levels into animal tissue has been documented. Irreversible integration of spirochetes may severely impair immunological response such that they persist undetected in tissue. We report in vitro inhibition and destruction of B. burgdorferi (helices, RBs = "cysts") by the antibiotic Tigecycline (TG; Wyeth), a glycylcycline protein-synthesis inhibitor (of both 30S and 70S ribosome subunits). Studies of the pleiomorphic life history stages in response to TG of both B. burgdorferi and Treponema pallidum in vivo and in vitro are strongly encouraged.
114: Persistence of borrelial DNA in the joints of Borrelia burgdorferi-infected mice after ceftriaxone treatment HETA YRJÄNÄInen 1 , JUKKA HYTÖNen 1 , PAULIINA HARTIALA 1 , JARMO OKSI 2 and MATTI K. VILJANEN Departments of 1Medical Microbiology and Immunology and 2 Medicine, University of Turku, Turku, Finland
Correspondence to Heta Yrjänäinen, Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland. e-mail: heta.yrjanainen@utu.fi Copyright Journal compilation © 2010 APMIS
We have earlier shown that Borrelia burgdorferi-infected and ceftriaxone-treated mice have viable spirochetes in their body, since immunosuppressive treatment allows B. burgdorferi to be detected by culture. However, the niche of the persisting spirochetes remained unknown. In the present study, we analyzed the tissues of B. burgdorferi-infected and ceftriaxone-treated mice by culture and PCR to reveal the foci of persisting spirochetes. C3H/HeN mice were infected via intradermal needle injection with B. burgdorferi s.s. N40. The mice were treated as follows: (i) short (5 days) and (ii) long (18 days) course of ceftriaxone at 2 weeks of infection and killed after either 10 or 30 weeks, or (iii) the mice received ceftriaxone for 5 days at 18 weeks of infection and were killed 21 weeks after the treatment. All samples of ceftriaxone-treated mice were culture negative, whereas all untreated controls were culture positive. Importantly, B. burgdorferi DNA was detected in the joints of 30–100% of the treated mice. In conclusion, these results combined with earlier results suggest that the joint or a tissue adjacent to the joint is the niche of persisting B. burgdorferi in ceftriaxone-treated mice.
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