Epidemiology of drug-resistant Kala-Azar in India and neighboring countries

Abstract

Sodium stibogluconate (SSG), a pentavalent antimonial compound administered parenterally at a daily dose of 10 mg/kg for 10 days has been the first-line treatment for kala-azar on the Indian subcontinent for more than 70 years, with a cure rate of >∈90%. However, in the 1970s and early 1980s this regimen failed to cure an appreciable percentage of kala-azar cases from the hyper endemic Indian state of Bihar. In 1982 and 1990, the World Health Organization recommended a higher and prolonged dosage regimen for use in resistant zones of Indian kala-azar. But by the year 2000, even these stronger treatments failed to cure as many as 60% of cases. Even in the districts of Nepal bordering Bihar, the efficacy rate declined to 59.9%. Diamidine compounds were used extensively in SSG-resistant cases in Bihar between the late 1970s and 2003. The cure rate when 10-12 injections were given remained at 98.2% until the late 1980s. However, by the 1990s longer treatment was required, and the efficacy rate declined while the incidence of serious toxicities increased. Thus, the use of this drug was discontinued. Among the drugs administered orally, miltefosine was found highly effective in the treatment of kala-azar in different phases of trials in India, with a cure rate of 94%. But the cure rate declined to 82-87% in outpatients. Paromomycin, administered intramuscularly for 21 days, was found to have a cure rate of 94% in different phases of trials in India. It has been registered in India since August 2006, and is a potential first-line drug. Amphotericin B or its liposomal compound (AmBisome) remains the most potent drug with a cure rate of 98-100% in all resistant cases of kala-azar. To counter the problem of drug resistance, particularly in patients of kala-azar co-infected with HIV, a combination therapy of two potent drugs or alternatively two courses of AmBisome is recommended.