Alternative regimens for multi-drug therapy (MDT) in leprosy

Ref.: CLeprosy Mailing List – February 10^th, 2010

Ref.: Alternative regimens for multi-drug therapy (MDT) in leprosy

From: Ben Naafs, Munnekeburen, The Netherlands

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Dear Salvatore,

Concerning alternatives for MDT.

Resistance is not often seen, though it was expected, with the known dapsone resistance and the widespread use of Rifampicine. It is however important to be aware that this may occur, and that one should have possibilities to prove it. Some surveillance system therefore should be in place.

Diane Lockwood mentions (LML Jan. 27^th, 2010) scores of side-effects up to 50% quoting a paper of Patricia Deps from Brazil . I may be a bad observer, but I have hardly seen that many side effects. (Neither in the Netherlands , nor in Africa or Brazil )

Dapsone

Yes, haemolytic anaemia may occur on dapsone, independent of the G6PD status. I have seen this mainly in patients with Nordic or Celtic Caucasian background. I hardly saw it in Africans or Ethiopians. When it occurred it was usually because of the dose; 100 mg dapsone standard in MDT may be to high for people below 70kg bodyweight and a lower dose should be considered. The haemolysis is dose dependent. This lower dose could replace an other drug with more or not yet known side effects. Do not forget that dapsone is an immuno-modulator and may prevent type 1 leprosy reactions.

Allergic reactions may occur and the dapsone syndrome as well. But those are rare. Liver function disturbances are often wrongly attributed to dapsone. Methaemoglobinaemia is common but dose dependent and mostly does not interfere with the patients daily life. Gastrointestinal problems are also diagnosed, but mostly by people who look for it and are biased. Psychological problems are rare but sleeplessness may occur, but a lower dose and early morning intake may take care of this.

Rifampicine

Rifampicine side effects occur nearly only with a daily dose and than may cause infaust reactions. The flu-syndrome is hardly ever seen and if seen it is seen in patients who take their rifampicine irregular.

Clofazimine

Clofazimine has gastro-abdominal side effects, especially when one focuses on it. But again, this is in general, dose dependent, as is the discoloration. Minocycline is a good alternative, but it also has a number of side effects, in my experience more than clofazimine. I have not been able to confirm the protective effect of minocycline on type 2 reactions as suggested by Gelber.

Rifampicin, ofloxacine and minocycline (ROM)

Indeed ROM is a possibility, but one misses than the inhibitory effect of dapsone for type 1 and clofazimine for type 2 reactions. Little is yet known about the effectivity in daily use.

Rifampicine resistance

I have treated a few rifampicine resistant patients with either clarithromycine or ofloxacin or both. I have seen good results and no side effects. But I use both drugs also for other conditions and than see side effects. Resistance to components or side-effects attributable to components of MDT may occur, but I wonder whether alternatives have less.

In the past 25 years I have noticed one big problem, which makes me weary: often when an problem with a drug or treatment is emphasized, an alternative is in the pipeline, which is usually more expensive. People other than the patient benefit from the advertised problem, researchers, politicians or manufactures.

With kind regards,

Dr Ben Naafs

PS

The last remark is definitely not directed against Dr Gilead's question which was genuine and needed a proper and honest answer as is given by the other responders. The remark is a “cri de coeur” which occurred to me writing my comments.