October 25, 2013
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Treatment failure may be result of Leishmania parasites' greater infectivity

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According to a study published in mBio, an online journal of the American Society for Microbiology, relapses after treatment for Leishmania infection may be due to a greater infectivity of the parasite rather than drug resistance, as has been previously thought.

Visceral leishmaniasis is a parasitic disease that affects 400,000 people a year, and 1 in 10 die of the disease. Visceral leishmaniasis is difficult to treat, partly because many patients who take the suggested drug, miltefosine, relapse after treatment. Drug resistance was thought to be the cause of failure of miltefosine, but recent study results show that may not be the case. Researchers said parasites in patients who relapse after treatment have a greater infectivity than parasites from patients who were treated successfully. Essentially, there is a more dangerous form of the visceral leishmaniasis parasite.

“Parasites from relapsed patients show an increased capacity to infect host cells,” study researcher Manu Vanaerschot, postdoctoral researcher at Institute of Tropical Medicine, Antwerp, Belgium, said in a press release. The researchers said it is unknown whether miltefosine treatment causes the increased infectivity of the parasite or if parasites with greater infectivity are unaffected by treatment.

The study of the presence of visceral leishmaniasis in the Indian subcontinent offers more perspective on the issue of relapse after treatment. In Indian patients, 6.8% redevelop symptoms of the disease within 6 months after miltefosine treatment, and 20% of Nepalese patients relapse within 12 months. According to a press release, parasites collected from patients before and after treatment were fingerprinted and appeared to be close genetic matches, indicating that these patients are not re-infected with new parasites, but carry the same strain that initially infected them before treatment. Other studies revealed that parasites from relapsed patients were sensitive to miltefosine, so the failure of treatment was not due to drug resistance, as previously thought.

The precise link between infectivity and treatment failure is not known, the researchers said, but they theorize that parasites with greater infectivity might cause a greater parasite load, making the case more difficult to treat. Parasites’ ability to evade treatment has not been ruled out — it is possible the infection can hide in parts of the body the drug cannot reach, such as the skin.

Disclosure: The authors report no relevant financial disclosures.