Tick Bite Co-Infections:

I am really tired, so relax. Take what you understand and later……. I will not be too long.

Bacteria:

Borrelia burgdorferi, Bartonella henselae, Erlichia, Mycoplasma fermentans

I wish to show you a case report about a patient of mine who was co-infected with Bartonella henselae - a gram-negative bacterium known since 1993 and it was separated from the Rickettsia group.

Transmission:

Known ways are through ticks and also cats. Other ways could be blood and body fluids but there is no publication about it
When an illness or bacterium is detected, so you have first publication. That was in 1993. Everyone was happy to know which bacterium was responsible for the ‘Cat Scratch disease’. Now there are more and more publications about it and Bartonella is now well accepted.

Now is there a relevance of Bartonella henselae?: (in tick-borne disease)
For this I have collected and sent all ticks from my patients in 2002, and they were sent to the MDL laboratory for PCR testing and I have done all tests Borrelia burgdorferi, Babesia microti, Mycoplasma fermentans, Bartonella, Erlichia and Rickettsia, but not all tests for each tick. Work did confirm the results of Dr. Mordechai. And probably the ticks are more infested with Bartonella than Borrelia and from nine ticks we had ,we had two ticks with both Borrelia burgdorferi and Bartonella henselae and that is important.

Case Report:

34 year old woman, she has a dog and works in the garden - whole summer. In 1999 she had Erythema migrans chronicum (Emc or Em) – for which she was given 200mgx2per day Doxycycline for 8 weeks and she recovered.
History - she has had endometriosis, and following on a hysterectomy had laparoscopy revised endometrium in 1994. Last year (2002), in March she got an acute disease with headache, light and noise sensitivity, nausea, abdominal pain, diarrhoea, chills, low temperature, dysaesthesia, extreme fatigue, muscle and joint pain, thoracic pain and she was quickly worsening. It was crazy. She was very healthy then in several days she was very, very bad. So I had to send her to hospital. No diagnosis was done but all her tests were normal and all tests to explain the abdominal pain, urine, stool, cerebro-spinal fluid, all normal. All tests were normal.

So she came back from hospital as sick as before. So, because of Emc in her history, I performed blood tests – PCR and sent them to MDL. I repeated the CSF. And the laboratory diagnosis in US for tick-borne disease in CSF – PCR positive for Bartonella henselae and blood PCR had positive Bartonella henselae and positive Babesia microti. I show you the serology of this patient – very interesting things.

Serology:

In September 1999, moment she has the Emc, Elisa and I tested her antibodies and for IgG, she is negative and normally we would stop. I would stop making more tests, but she has ‘Lyme capture test’ very positive for all and the western blot test, and negative in the IgG. So she shows about two weeks after the Emc, very strong positive Lyme western blot IgM response for Borrelia garinii. All her bands were positive, especially band 41 and band 22, and all other bands also were positive. Later on I made a control, long after the therapy to have a new base and she went less positive in the ‘IgM Lyme capture test’ and negative in the western blot IgM, so I was very satisfied about my therapy.
But not at all a sign of a good therapy because last year (2002) when we repeated the serology tests at the time when she was very, very sick, we have also negative results. My diagnosis was severe generalised Tick-Borne Disease in the cns and several Bartonella, Babesia and Lyme and specific immune complexes were also positive.

The Hospital:

They diagnosed a pain syndome of unknown cause by a pathological personality. For this there are two different therapies. Mine is difficult, intravenous, takes a long time, has a high risk, complications, a combination therapy and it is not officially accepted.
Hospital has another one; pain therapy, a psychiatrist – it is cheap and well accepted, also they can refer her to another MD and the therapy is simpler.

But, we don’t have time to decide about the therapy because the patient was deteriorating more and more, she had terrible and increasing pain, more and more sopor(ific), with hemangiosis on her body, she could not speak two or three words, she was spotted with red hemangium. They were not bleeding or irritating but a hemangiosis - higher than the skin, we did biopsies about them. And she also had erythema of the face and mood lability, anxious behaviour and I could show you anxious and aggressive things she wrote, it was absolutely…..a poor, poor person.

Known Symptoms of Bartonella henselae infection:

Hemangiosis infectuosa. I can show you pictures later. There is lymphadenitis in Cat Scratch disease with big lymphatic nodes swelling in the axils (armpits), and they are very smooth not hard, big and red and warm. Encephalitis is known and also septic infection and endocarditis and also an infection that gives no symptoms.

Here we have the main symptoms of Lyme Disease but not all. No enough space but we know this! (Dr. Meer shows a long list).

Open question is now, what happens when all the infections are together in one patient? What is the influence on the immune system? What about the disturbance of antibody production by different infections together? Do they influence together or influence on one on another? What about treatment? Treat them all together or one after the other? All this is not answered in the literature, so it is empiric treatment, and yes, we draw upon our own experience. What can we do?

Therapy and Follow-Up:

What can we do? Antibiotics working against Borrelia burgdorferi and Bartonella Henselae. .
The only three antibiotics that are working all at the same time are Claforan, Citromax (Azithromycin) and Doxycycline.
What about Babesia? That’s the three that we use.
And what about what is working against the Bartonella? Ciproxin (on this) more than the three others.
And now what we did (in this case history):
I give you the list of what we have tried. (Dr. Meer shows a long list of medicines). In 2002 Between May and June of this year.
I begin with intra-venous Ciproxin for 40 days because it is an acute infection. There is Bartonella infection in the CSF and first I have to bring that down.
Second decision was to eliminate or reduce the Babesia. Difficult - long term. I performed short courses of this, when I have done this, then I stop for six weeks because of the awful Herxheimer. And Cipro is more toxic, so in the first part of treatment she had worse symptoms including neurological symptoms – and I had to explain that to her before therapy, so it was a very hard therapy for her, and for me. In the early morning I gave infusions and she would lie in the Office morning and in the evening came back. She had very bad veins - patient needing intravenous therapy has worst veins (not good). So we decide to put in intravenous catheter, it works outside the hospital, so she was freer for treatment. I decided to give Doxycycline because it’s also anti-inflammatory and I hoped not too much toxic side-effects. But she was so sick and at first it was not working very well, so I added 2 weeks Mefloquine also.
But we had to stop because of neurotoxic effects and then…? So we tried Claforan and I had to stop this after 2 weeks because she had generalised urticaria. It was very, very difficult.

So we had a break of therapy – because I wished to know if the side effects were an allergy to the medication or from the a pseudo-allergy of the skin and a very strong Herxheimer. We took the risk of the worsening over the two months because I tested also by T-lymphocyte stimulating tests.
We did this for all medications usable in this case (she has ten or fifteen medications tested). And no allergy was found to the drugs. – absolutely no allergy.

So, I decided to make complete other plan because she is so sick. If I restarted the same thing – it would be the same. So I used an old TB drug, Rifampicin with Riamet (Artemisia usually against Protozoals) . (Something against TBD and together with something against protozoal). I decided to try a pulse therapy. Three days Rifampicin in very,very low doses, so not to have too much Herxheimer. (This for) three days a week, in the other days I gave her Riamet and on the other day we have a holiday. This therapy for ten weeks , then again three weeks with intravenous Ciproxin and this time much better tolerated, and now she is under intravenous Doxycycline.

Vitamins Supplements:

There are many other supplements and things to try such as physiotherapy. Many other things in therapy.
We are doing all these things. I thought you like to know mainly how I am dealing with antibiotics. Maybe too much about antibiotics and not enough about other therapies? But we use all these things also.

Therapy and Follow-Up:
Best Therapy - Ciproxin and Mefloquine – but I couldn’t give this because of side effects and Herxheimer. (In this patient). Claforan… was similar.
And the best improvement for a long time was Rifampicin.
Patient is a good deal better now and we can relax a bit.

Today she is working again, she has had a raise in weight, pain significantly better and important improvement of neuropsychiatric symptoms, but her strength is low and she has no stress tolerance. The Herxheimer reaction has disappeared. Now I am more free to give medication without a strong Herxheimer - we go step by step, and all PCRs of tick-borne disease went negative.

Costs:

I want to say something about the costs. For the patient, 1.3 years of treatment and not working. I think the costs of this are about100,000 Euros. Cost because of treatment and no working, but because insurance has to pay something like three or four thousand Euros each month. But she is 34 years old. She could have been disabled all her life, she could have had to go into a special institution because of not speaking and paralysed) and I think the costs of this would be two and half million Euros. And 1.5 million euros loss of (?public money). That makes 4 million Euros against 100, 000 Euros. I think it is important to make this cost comparison.

I have shown a case. I had a trouble to do it, a lot of complications in this patient – very difficult for this patient. Pain very difficult. A substance I was using, the gabapentin is very helpful in the pain therapy but there must be search about the medication and must change medication. Muscle spasms is a big,big problem of these Lyme Disease and co-infected patients, not only magnesium depletion and also the spasms are central problems which were treated by Malapar a medicine usually used against Parkinson symptoms.

We have now central nausea, skin allergies and intolerated Herxheimer, and the psychiatric symptoms.

I wish to say about the psychiatric symptoms: I say to patients to treat it also when they are very strong. This is because serotonin is very important in the brain not only to be well and happy but also to make a better immune function. Immune system also needs it, the serotonin in the brain regulates immune system in brain – a lot of people don’t know this. I tell them, they are not crazy or depressive but I need more help to make immune function the best possible in such a situation.

When do you have to search for co-infections when the Emc in spite of correct treatment (not only 100 mg Doxy for days) is still persistent, and Lyme symptoms persist in spite of treatment and by presence of special symptoms – extreme sweats, fever, chills.
And in each case chronicity of Lyme Disease or unexpected complications.

Erythema migrans chronicum: (Emc or Em)
When Emc is healed, and other important things about it:
Even before Emc the spirochaetes are in the cns, very, very important. The Elisa is still negative but the specific western blot can become positive several days after the bite before Emc is present. Now I do this for all patients. I do the western blot IgM when they have Emc and they are all positive
The person who is antibody converting cannot be predicted, we don’t say Emc is only healed when nothing to see. We don’t know – product of IgG. Only healed when you can’t feel it and no symptoms, that is most important.
In Ecm not only is there erythema, but it is also an induration.
There are Lyme spirochaetes, lymphocytes are there and you see it’s important to feel EMC and to compare with skin in other parts of the body - and you can feel the difference.
It is like the tuberculin test, the Mantoux, you have also to feel the induration and when you have still induration, you have to continue with the therapy – because there is the specific response of the lymphocytes and the patient must have no symptoms, no joint pain, nothing. Otherwise one must continue.
So control of Emc is obligatory. I treat Ecm treat for at least three weeks.

Special medical exams: (slide of other special tests that could be done) - the cytomegalo-virus, also a virus producing immune deficiency alone and Borrelia do this also. (If we have this). So we have two micro-organisms giving immune deficiency - so I treat a patient with this, even if no symptoms in the eye - I treat anyway because of the immune deficiency. Preventive controls very important for Lyme patients – because they have an immune deficiency disease. You have to control the Candida also.

That’s all the special tests I advise the doctors to do – the CD57s, NK cells, an indirect marker for intensitivity of the spirochaete activity - not specific for Borrelia. One laboratory does this for me (using flow cytometer). Possibly there is a genetic predisposition for the multiplication ability of a patient’s CD57 cells.

CD57 - just a little statistic, I go just through, only this, (a table) that’s all my chronic Lyme patients and here are the results in person of the NK cells.

Normal is 15- 20% of all lymphocytes but in Lyme Disease patients (majority of them) it is here and the middle value is 8%, so I think it can be an indicator.

Final remarks:

I have tried to show the complexity of the disease and that it must be recognised. The fight is hard and long but not without hope. Cost is high but diasability costs are higher. Tick-borne disease causes suffering not only for the individual patient but for the family, friends and colleagues of the patient. Tick-borne diseases extinguish the future of so many people.

We have to give the chronic patients (not only Lyme patients, but also diabetic patients and all chronic patients, all have a voice, the right of life and bring a new respect. They remind us of our proper limits and they help us stay humble.
We can learn from them, how to live such a difficult life, I hope for more fairness and engagement in the cause of tick-borne diseases. (ends)

A big thank you to my office team. I would not be here without them.

Dr. David Owen thanked Dr. Meer and expressed hope that the patient in question does well.