York University researchers are set to identify ways to help clinicians predict drug treatment outcomes for patients with visceral leishmaniasis in Brazil.
York scientists had previously shown that the absence of four particular genes in certain strains of Leishmania of infants parasite found in Brazil makes him less sensitive to an oral drug called miltefosine.
Absence of these genes correlates with drug resistance, which means Brazilian patients would benefit from a prognostic test, but to do this scientists first needed to identify what gene was involved. made the parasite resistant to the drug.
In a clinical trial using miltefosine treatment, 40% of patients relapsed within six months, but the presence of the genes in the parasite found in India, however, allowed that after a month of treatment the disease could be cured with a lower risk of relapse.
Due to its ‘failure’ in Brazil, the drug is not licensed in the country and therefore there is very little that can be done to manage the disease in patients, other than intravenous drugs which can be s prove to be a burden on the medical establishments who have to deliver it.
The team, together with colleagues from Universidade Federal do Piauí and Universidade Federal do Espírito Santo, have now taken the work a step further and identified the enzymes that make the difference between success and failure. of the treatment.
Juliana Brambilla Carnielli, Research Associate in the Department of Biology at the University of York, said: “Now that we have narrowed the search for a set of genes down to an enzyme, the potential for developing a blood test that can accurately predicting the patient’s outcome is more likely.
“There is no single treatment, and therefore a personalized medicine approach is needed, whereby a prognostic test to predict treatment success at the individual level can be provided.
“This disease affects people in India, Brazil, Africa and parts of Europe, so it’s really important that we better understand how the parasite lives in humans and responds to drugs. »
Leishmaniasis is a parasitic disease transmitted to humans by the bite of an infected female sandfly. With 50,000 to 90,000 new cases worldwide each year, it causes fever, severe weight loss, swollen spleen and liver, and anemia and can be fatal if left untreated.
The parasite first arrived in South America from Europe in the 1600s and has changed and adapted over time,
Jeremy Mottram, Professor of Pathogen Biology and Director of the York Biomedical Research Institute, said: “This latest finding means we are much closer to moving into clinical trials with patients in Brazil and understanding whether early prognostic tests in disease progression and appropriate medications could reduce the number of patients who relapse with the disease. »
Up to 2,500 patients presented with the disease in Brazil in 2019 with a case fatality rate of 9%, the highest recorded in the last 10 years, creating a significant burden on hospital resources.
The research is funded by an award from the MRC GCRF Foundation, MRC GCRF “A Global Network for Neglected Tropical Diseases” and the Fundação de Pesquisa do Estado do Espírito Santo — FAPES, Brazil, and is published in the journal eBioMédecine.
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