Is there true Sb(V) resistance in Indian kala azar field isolates?

摘要

Visceral leishmaniasis (kala azar) is a serious health problem in the eastern states of Bihar and West Bengal. Leishmania donovani is the major causative agent of visceral leishmaniasis in India. The treatment of choice since long for kala azar has been the administration of a pentavalent antimony Sb(V) containing drug, sodium antimony gluconate (SAG). However, the focus is now shifting to the use of amphotericin B and the oral drug miltefosine. Resistance to antimony Sb(V) in Leishmania is widespread in several geographic regions, reaching epidemic proportions in parts of India. In Muzaffarpur, the epicentre of the outbreak, more than 60 percent of previously untreated patients are unresponsive to antimonials. A number of explanations for antimony treatment failures have been offered, like under-treatment due to premature termination of chemotherapy and immunologic or pharmacokinetic defects in the host. But is the parasite truly resistant to SAG, is a matter of concern and debate amongst Indian researchers. Although isolated studies have been carried out to confirm parasite resistance in Indian field isolates, no documented results can be found apart from a study carried out abroad, wherein Indian field isolates were collected from disease endemic areas between 1995 and 1998 from drug unresponsive and responsive patients. Unfortunately, these cultures are not available anywhere in India for Indian researchers to pursue further work towards unravelling mechanisms of resistance.