AbstractIn Bihar state, India, the cure rate of antimonial compounds in the treatment of visceral leishmaniasis (VL) has declined from over 85% to less than 50%. This has been attributed to prolonged, widespread misuse of antimonials within the Indian private healthcare system. An alternative resistance hypothesis is that exposure to arsenic in drinking water in this region has resulted in antimony-resistant Leishmania parasites.
Leishmania donovani were serially passaged in mice exposed to environmentally-relevant levels of arsenic in drinking water. Arsenic accumulation in organs of these mice was proportional to exposure. After five passages, isolated parasites were refractory to SbV in drug sensitivity assays. Treatment of infected mice with SbV confirmed that these parasites retained resistance in vivo, supporting this hypothesis.
A retrospective field study on a cohort of antimony treated VL patients was performed in an arsenic contaminated area of Bihar to evaluate the presence of an increased risk of treatment failure and death in those exposed to arsenic. It demonstrated a significant increased risk of death from VL in arsenic exposed patients but did not indicate a significant relationship between arsenic exposure and antimonial treatment failure.
Collectively these data suggest that it is biochemically possible that arsenic contamination may have contributed to the development of antimonial resistance in Bihar although issues of underpower and the retrospective nature of our epidemiological study made it difficult to conclusively demonstrate this. Further research in to the relationships between arsenic exposure and antimonial treatment failure and death in the leishmaniases is warranted.
|Date of Award||2014|
|Supervisor||Alan Fairlamb (Supervisor)|