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New parasite species causing drug-resistant disease in Brazil

The researchers plan to search for compounds (or existing drugs) that can kill the new parasite efficiently.

Melvin Sanicas
October 23, 2019 @ 2:14 pm

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A new species of parasite causing symptoms like visceral and cutaneous leishmaniasis but resistant to currently available treatments have been identified by researchers from Universidade Federal de São Carlos, Universidade Federal de Sergipe, Universidade de São Paulo, US National Institutes of Health, and Fundação Oswaldo Cruz in patients treated at the University Hospital in Aracaju, state of Sergipe in Brazil. At least one person has died from complications associated with infection by the parasite.

Phylogenomic analysis showed that the recently discovered parasite does not belong to the genus Leishmania, which comprises over 20 species of parasites that are transmitted to humans by the bites of the infected female phlebotomine sandfly – a tiny insect vector. There are three main forms of leishmaniasis: cutaneous, visceral (VL) or kala-azar, and mucocutaneous. VL is the most severe form of the disease and can be fatal if misdiagnosed or untreated. Cases of VL in Brazil account for >90% of annual reported cases in Latin America.

“From the phylogenetic standpoint, the species analyzed in this study is closer to Crithidia fasciculata, a mosquito parasite that cannot infect humans or other mammals. We managed to infect mice with it, and for this reason we believe it’s a new protozoan, which we propose to call Cridia sergipensis,” said João Santana da Silva, a professor at the University of São Paulo’s Ribeirão Preto Medical School (FMRP-USP).

The first case was confirmed in a 64-year-old man, first treated in 2011 for classic symptoms of visceral leishmaniasis: fever, enlarged spleen and liver, and decreased production of all types of blood cells (pancytopenia).

The patient was given the standard treatment and improved but suffered a relapse a few months later. He was then administered liposomal amphotericin B, the best drug available for these cases, responded, but suffered another relapse some months later. Unfortunately, the patient died after the relapses and an operation to remove his spleen, as recommended in severe cases that do not respond to treatment. A biopsy of the skin lesions found cells full of parasites, which were isolated and cryopreserved for analysis.

The group initially thought the patient had been infected atypically by Leishmania infantum but molecular tests available to identify this pathogen were all inconclusive in the analyses performed on the parasites isolated from the patient. They then opted to do a whole-genome analysis of the parasites isolated from the patient in order to find out exactly what they were dealing with.

The bioinformatics analysis that revealed the phylogenetic similarity between the new species and C. fasciculata was conducted by José Marcos Ribeiro at the National Institute of Allergy & Infectious Diseases (NIAID) and Sandra Regina Costa Maruyama, a researcher in the Department of Genetics and Evolution at the Federal University of São Carlos. The team also performed a whole-genome analysis of parasites isolated from two other patients in Aracaju who were not responding to treatment, confirming that they too belonged to the new species.

According to Maruyama, initial results gathered from an analysis of fragments of the genome identified as key to the characterization of the species suggest that most of the protozoans present in the isolates match the profile of Cridia sergipensis.

Maruyama and co-investigators would like to know whether Cridia sergipensis alone can cause severe and potentially fatal disease or whether the cases observed resulted from co-infection. Another research priority is to discover how Cridia sergipensis emerged and how it is transmitted to humans. The team also plans to search for compounds (or existing drugs) that can kill the new parasite efficiently.

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