[KATHMANDU] Researchers in Nepal have found that miltefosine, the drug of choice in treating visceral leishmaniasis, or 'kala azar', is losing effectiveness.
A year-long study of 120 kala azar patients admitted to the B. P. Koirala Institute of Health Sciences (BPKIHS) in eastern Nepal showed declining cure rates — from an initial 96 per cent to 83 per cent after six months, and 73 per cent after one year — according to a report published last month (20 February) in Clinical Infectious Diseases.
Previous studies from Bangladesh and India showed showed the drug was beginning to fail.
Given the implications of reduced drug efficacy in treating kala azar, considered the most deadly parasitic disease after malaria, researchers are calling for closer monitoring of patients on miltefosine.
- Oral drug against ‘kala azar’ shows higher failure rates
- Antibiotic resistance to main drug ruled out
- Researchers worry as drugs options against kala azar limited
In 2005, when the three South Asian countries launched a leishmaniasis elimination drive they had adopted orally administered miltefosine as the first line of treatment.
"The problem with leishmaniasis is that we have a very limited number of drugs," says Jean-Claude Dujardin, co-author of the report and professor at the Institute of Tropical Medicine, Antwerp.
Miltefosine is convenient because it can be given to patients orally, says Suman Rijal, lead author and professor at the department of internal medicine at BPKIHS.
Alternatives include intramuscular injections of paromomycin and intravenously administered liposomal amphotericin B. The latter is effective but expensive, needs to be kept cool throughout the year and is not yet registered for use in Nepal, Rijal tells SciDev.Net.
Some large-scale public health studies are looking into the potential of combination therapy, and a 2010 paper published in PLOS Neglected Tropical Diseases identified paromomycin-miltefosine as the most cost-effective combination strategy.
"It is true that there is a problem with miltefosine, with nearly one-fourth of the patients not cured by it, but based on that we cannot simply say, 'OK throw away that drug and we’ll use another drug,' " Dujardin tells SciDev.Net. "We first need to understand the reason for the failure."
The study ruled out drug resistance and re-infection from a new strain. None of the patients who relapsed were HIV-positive and all took their medications correctly.
The only useful lead in finding a reason for drug's failure was higher risk of relapse for children under 12, which may require adjustments in dosage. Researchers were also alerted to the possibility of infection by virulent 'super parasites' among suspects for failing leishmaniasis drug efficacy capable of getting past the human immune system.
"But, for the moment, it is really a mystery why miltefosine is not working that well," said Dujardin.