Therapy

Dr. med. Uwe Auf der Strasse

Chronisch aktive Toxoplasmose: Therapie

For entering Toxoplasmosis therapy I refer to basic research (40, 41) and use parts of my book, only the original chapter is a bit more extensive. First, in order not to be misunderstood: 

 

This chapter is not supposed to replace consultation with a physician. The presented therapies are available only by prescription from a doctor. Selftreatment is strongly discouraged. All liability of the author for personal injury, property or financial damage will be declined.

 

A second important note is, that patients with immune deficiencies or undergoing an immune-suppressive/immune-modulating therapy, for example following organ transplants, during cancer treatment or under certain antirheumatic drugs have a high risk, and should therefore be observed very closely or even better be treated in hospital. In these patients, the prescription of pyrimethamine (Daraprim) or sulfadiazine must only be undertaken with utmost care. 

 

A third note is, that the dosages presented here do not refer to patients with pronounced symptoms of Fibromyalgia or ME/CFS. In these cases, as well as in patients whose psyche is affected severely by toxoplasmosis, it is advisable to use a reduced dosis and to increase the Toxoplasma treatment slowly. 

 

1) Cases with suspected chronic active Toxoplasmosis

If in some cases even a Toxoplasma LTT (see "Next Steps") does not indicate a chronic active Toxoplasmosis, although the combination of symptoms might be very typical for this course of the disease. A thorough exclusion of other causes of the disease should be performed (please read as well the "Update Juli 2020" on page 6 of this website). If these diagnostic measures show normal results, it can be useful  to take Clindamycin as a probatory treatment for approximately one week. The effectiveness of this antibiotic as a monotherapy has been proven in 1993 (9).   It has been seen in almost all cases in which Clindamycine was effective within the first 7-10 days, that further significant improvements were achieved  by prescribing a combination therapy. This procedure is not in contradiction to basic research, because to my knowledge, no lab method has been proven to be 100% reliable in confirming or excluding chronic active toxoplasmosis.

In cases of an ineffective probatory clindamycin treatment, a combination therapy will be of no use, most of the times. Alltogether, the decision to take a probatory treatment should be considered carefully, and I recommend to inform thoroughly and consult with your doctor before taking this step.

In cases of pronounced symptoms or a very long disease duration it is advisable to prescribe not more than 3 x 300mg clindamycin at first, since in some cases an initial worsening of symptoms in the first 3 – 4 days with a temporary increase in fatigue and muscular pains may occur. In all other cases, a dosage of 2 x 600mg for a duration of 7 – 10 days has proven its worth. Most patients describe significant improvements already within the first week of treatment, which generally shows noticeable symptom reductions on the checklist. 

 

In some cases, Clindamycine may, as other antibiotics, trigger bouts of diarrhoea due to the elimination of useful beneficial intestinal microorganisms. This risk can be reduced by parallel ingestion of a saccharomyces boulardii preparation twice daily. Should diarrhoea occur, increased care is to be taken and the practitioner has to be consulted. In case of doubt, the clindamycin administration has to be stopped.

 

2) Cases with confirmed chronic active Toxoplasmosis

 

In these cases, the checklist indicates a high risk for chronic active Toxoplasmosis, and a positive Toxoplasma LTT result or, in rare cases, a positive Toxoplasma IgM confirm the diagnosis.

 

A good symptom reduction during a 7-10 day  probatory treatment, while Toxoplasma LTT and IgM are negative, is also a strong argument for this diagnosis, though not offering definitive proof. Until 3/2020 I have found this combination in approximately 20 cases - and they have been treated successfully.  

 

If a chronic active Toxoplasmosis has been confirmed a combination therapy is prescribed for about 3-4 weeks, depending on the effectiveness,  in very severe cases, up to 10 weeks. It should only be stopped when all symptoms of an active toxoplasmosis have been eliminated almost completely. During this therapy, kidney and liver values, blood count and folic acid level should be monitored. A combination of 3 drugs is usually employed.

 

The following two drugs are part of each combination of 3 drugs. Several different antibiotics can be used as the third partner in these combinations of three drugs.

 

Pyrimethamine

 

(Brand-name Daraprim) is used in a dosage of 25mg 2x1 tablet per day. The drug is approved as a treatment against toxoplasmosis in combination with certain antibiotics. Pyrimethamine suppresses an enzyme which is essential for the supply of the vital folic acid. The resulting deficiency in folic acid damages Toxoplasma significantly.  Beware however, as it is vitally important to ingest folinic acid (calcium folinate) during the administration of this drug!!  This is necessary because otherwise the human organism would suffer from a folacin impoverishment at the same time, and this could cause life-threatening side-effects. This leads us to the next drug.

 

Calcium folinate

 

Capsules with 15mg and tablets with 6.35mg are available. The ingestion of 1 capsule of calcium folinate 15mg every second day usually leads to a slight increase of the folic acid level under Daraprim therapy. One tablet with 6.35mg can be ingested daily as an alternative. The folic acid level must be monitored, as I have noted. Beware: cheaper folic acid may under no circumstance be used as a substitute for calcium folinate. It would be inefficient in this case and the resulting folacin impoverishment would be dangerous !! (55)

 

Antibiotics that can be combined with Daraprim and calcium folinate 

Sulfadiazine

 

500mg 4x1 up to 4x2 tablets per day is an antibiotic from the group of sulphonamides and may therefore not be used in patients with sulphonamide allergies. The effectiveness derives from a suppression of the production of folic acid, so it supplements the effectiveness of pyrimethamine (Daraprim) substantially. Sulfadiazine is only approved as a treatment against toxoplasmosis in combination with pyrimethamine and Calicum foliate. I usually prescribe only 4 tablets a day, and in some cases, when side effects occur, only 3 tablets per day.

Clindamycine 

 

3x300mg or 2x600mg, its effectivity is almost equivalent to sulfadiazine (40). I sometimes directly prescribe it as combination partner first, if it proves a good effectiveness in the 7-10 days initial phase without causing side-effects. Headaches, which frequently occur under Sulfadiazine, rarely occur under clindamycin.

 

Cotrimoxazole 

 

960mg 2x1 is another alternative. It also contains a sulphonamide and belongs to the same group as Sulfadiazine. It is a combination drug of sulfamethoxazole and trimethoprim. There is less risk for antibiotics-induced diarrhoea than under clindamycin.

 

 

Spiramycine 

 

1.5 mio 4x1 up to 3x2 can be obtained under the brandname “Rovamycine”, it belongs to the group of makrolides. My impression is that it is somewhat more effective than clindamycin in terms of peripheral symptoms when used as monotherapy, so it can be used it for initial treatment in case of clindamycin intolerance. Unfortunately, a disadvantage is its poor penetration across the blood-brain barrier, therefore it is not very effective in the central nervous system. A significant improvement of neurological symptoms should only be expected in combination with Daraprim - in my experience, however, this combination is not well tolerated in all cases. Depending on the body weight, 4 x 1 to 3 x 2 tablets of 1.5 million units are prescribed.

                                                                ..........................................

These are the tried and tested therapies, which are available in our daily practice and which help us to achieve our goal, which is the almost complete reduction of toxoplasmosis symptoms. More intensive progressions of the disease may require higher dosages, potentially other drug combinations and a longer duration of therapy (40, 41). See also pages 188 – 201.

 

It is imperative to monitor the patient in the course of therapy in frequent consultations, I found 10-day intervals to be appropriate. This serves to find out about potential side-effects or losses of effectiveness, and to adjust or change the therapy accordingly. This is needed in about 30% of all cases. In some cases a “revolving” therapy in intervals of 5 days has to be considered and by doing so the adaption of Toxoplasma to the therapy can be effectively avoided. (see also "Case report" on this website) This will be discussed in 12.4. on pages 200 and 201 as “revolving therapy concept”.

Please take note, that the healing process is best monitored by documenting the development of the symptoms, because the LTT value mirrors the reactivity of our immune system against Toxoplasma, but it is not directly linked to the intensity of the disease. Nevertheless, in many cases the LTT shows  higher values when the disease causes pronounced symptoms, and in most cases it decreases significantly after a successful treatment, but there are exceptions.

Addendum 3/2021:  With rotating therapy, the medication is varied every 5 days according to a fixed scheme. The success is based on the fact that the aforementioned adaptation processes of Toxoplasma require at least 5 days. If the medication is varied on the 6th day, Toxoplasma are confronted with a change in therapy at a point in time at which their adaptation process has not yet been completed - they are therefore constantly forced to make new adaptations.

Since this form of therapy is very reliable and puts, in my experience,  less strain on the intestinal microbiome, I now almost exclusively prescribe revolving therapies, including in those cases whose documentations can be found under the menu item "Case Reports".

Unfortunately Toxoplasma are very resilient and at the moment, complete eradication is beyond our scope and thus relapses (recurrences) are possible. The risk of a relapse has to be communicated to every patient, because in case of a renewed Toxoplasma activity it is essential to start a treatment again as soon as possible.

 

 

Prophylaxis of relapses

As mentioned above, Relapses (recurrences) cannot be fully avoided. There are no guidelines for the prevention of recurrences, only personal experience. The following procedures have proven to be effective:

 

1. In the first block of treatment the medication needs to be taken continuously every day until the patient is free from symptoms; this usually takes between 4 and 6 weeks. In some cases a revolving therapy has to be applied (see p. 200 and 201 and "case report" on this website) .

 

2. For a period of one month, the last successful combination therapy is taken on two treatment days per week (e.g. Wednesday and Sunday).

 

3. For a period of a second month, the last successful combination therapy is taken once per week.

 

It is sometimes sensible to vary this schedule slightly in patients with very severe or very lengthy progressions of the disease. In the first month of relapse prevention, treatment would be taken on 3 days per week and in the second month on 2 days per week. This therapeutic scheme is worth all the effort, as in my experience a relapse happens after that type of prophylaxis much later or not at all.

Addendum 3/2021:  If a revolving therapy is used, the combination of Therapy  should also be changed regulary during the recurrence prophylaxis in order to avoid an adaptation of Toxoplasma and maintain a constant effectivity of the therapy. To achieve this, a weekly change of the drug combination is sufficient, since even with 3 therapy days per week (for example Monday / Wednesday / Friday) the same combination is not administered for more than 5 days.