Kala Azar/Visceral Leishmaniasis - Combination Drug Therapy Better Option for Its Treatment

Kala azar (Visceral Leishmaniasis) is a morbid disease caused by the parasitic protozoa   Leishmania donovani. About 165 million people are estimated to be at risk in India. Bihar is the worst affected state with 33 districts endemic. Kala azar lowers body’s immunity. Main clinical features include persistent fever, anemia, liver and spleen enlargement. If left untreated, it has high mortality. Pentavalent antimonial drugs are used worldwide to treat Kala azar. However these drugs are now ineffective in Bihar because of drug resistance leading to the use of amphotericin B as the standard treatment for Kala azar. The past two decades saw tremendous progress in management of the ailment. Effective treatment options like liposomal amphotericin B, miltefosine, andparomomycin were developed.

Therapy using a single drug, i.e. monotherapy leads to the development of drug resistance. The organism gains immunity rendering the drug ineffective. Emergence of drug resistance poses a severe threat to management of infections hence the concept of combination therapy has now been tested and shows promising results. The use of multiple drugs delays or reduces the incidence of resistance. Another advantage is that it causes fewer side effects since the duration of treatment required is decreased. Shorter treatment courses mean better adherence to therapy, lower cost, and reduced toxicity. A high efficacy can be maintained through this approach.

A recent trial tried to identify an effective and safe short-course combination treatment of visceral leishmaniasis in India. The following combinations were tried out:

• Liposomal amphotericin B and miltefosine
• Liposomal amphotericin B and paromomycin
• Miltefosine and paromomycin

The randomised controlled trial study was done at two sites in Bihar: Muzaffarpur (site of Kala-Azar Medical Research Center of Banaras Hindu University, Varanasi) and Patna (Rajendra Memorial Research Institute of Medical Sciences). The efficacy of the combination treatments (ie, definitive cure rate) was compared with the standard treatment (monotherapy).

The results of the study were published in The Lancet. All three combination treatments were found to be effective, and they were less toxic (particularly for the kidneys) and better tolerated than was the standard treatment with amphotericin B. The study did not try to find out which of the combinations works best. The choice of treatment depends on various factors like facilities available, acceptability, and costs. Miltefosine, for example is better avoided in pregnant women for fear of the detrimental effects on foetus. Drug combinations were also found to provide the advantage of shortening treatment duration from 21-28 days for monotherapy with paromomycin or miltefosine to 8-11 days with combinations.

The study was not devoid of limitations. The findings are significant though. Lower cost of treatment is indeed a boon for the poverty stricken districts that suffer disease burden. Reduced probability of development of resistant parasites, decreased duration of therapy, high efficiency and safety are advantages offered by combination regimens. Researchers believe that drug combinations are apt candidates that can replace monotherapy.

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Reference: The Lancet

Source-Medindia