Resistance to treatment in Kala-azar: speciation of isolates from northeast India.

Abstract

Abstract. Kala-azar in India is becoming increasingly difficult to treat, which may be due to the presence of species other than Leishmania donovani; Leishmania tropica was reported to cause the same clinical syndrome in the area. Over the past 3 years, we have collected samples from 241 patients with visceral leishmaniasis from across the region. Of the 189 isolates that grew on diphasic medium, 159 were successfully transferred to liquid medium for typing. Clinically, 80% of these were resistant to antimony. Lipophosphoglycan-specific monoclonal antibodies were used to distinguish the 2 species by agglutination of promastigotes; all 159 were shown to be L. donovani. Eightythree isolates were confirmed to be L. donovani by isoenzyme analysis, by amplification of kinetoplast DNA, or both, in comparison with multiple reference strains; none were L. tropica. Thus, the rising incidence of clinical resistance to treatment is unlikely to be due to a different species causing kala-azar in north Bihar.

Leishmania tropica (Kinetoplastida: Trypanosomatidae) - a perplexing parasite

“…These reports raise the question whether L. tropica is the causative agent of visceral leishmaniasis in other areas, but recent reports of drug resistant visceral leishmaniasis in India have failed to find any evidence of this parasite (Thakur et al 2001, Sundar et al 2001.…”

Drug Resistance in Leishmaniasis

“…Even in this geographical region a variation in Sb(V) sensitivity occurs with significant drug resistance at the epicenter of the epidemic and a high level of sensitivity only 200 miles away (144). This resistance is so far unique to L. donovani; all isolates from a large number of refractory as well as responding patients in India were identified as this species (146,149).…”

“…Although the in vitro data suggest that increasing the dose of Sb(V) could overcome the unresponsiveness, even the current doses produce unacceptable toxicity and further increase in the quantity of drug could seriously jeopardize the safety of the patients (146 (146), but evidence of their existence in field isolates from refractory patients has yet to be found. Although an amplicon was observed in a few isolates from Sb-refractory patients, the significance of this observation has yet to be determined (134).…”

“…A similar potential for resistance to develop exists in East Africa, especially in Sudan, another anthroponotic focus of VL with intense transmission, where poverty, illiteracy, and poor health care facilities portend misuse of the drug and consequent emergence of resistance. Resistance seems to be a feature of intensive transmission of anthroponotic L. donovani as epidemic turns to endemic in foci where Sb(V) has been used as monotherapy for long periods, often with poor supervision and compliance (146,147). In other parts of the world, Sb(V) continues to be effective (34,156).…”

Detection, Differentiation, and Quantitation of Pathogenic Leishmania Organisms by a Fluorescence Resonance Energy Transfer-Based Real-Time PCR Assay

“…Since these groups are associated with distinct clinical courses, our test may allow prediction of the clinical manifestations that a patient will develop. Furthermore, in selected situations, the combination of a certain melting point group with an unusual clinical course can allow identification of highly virulent strains (e.g., recurrent VL caused by L. tropica in India [37]). Early clinical decisions can be based on these data.…”