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Distinct Parasite Strain, Immune Responses Behind Unusual Leishmaniasis Cases in Brazil

NEW YORK (GenomeWeb) – A team from Brazil and the US has taken a genetic approach to understanding unusual clinical forms of leishmaniasis that have arisen recently.

Leishmaniasis is a parasitic disease caused by Leishmania braziliensis protozoans that are transmitted by sandfly bites. Four main forms have been documented in Brazil — from infections characterized by localized skin lesions to forms that have become more diffuse, disseminated to other parts of the body, or involve sores in mucosal tissues in the nose or other upper airway sites.

For their new analysis, published online today in PLOS Neglected Tropical Diseases, the researchers focused on yet another form of leishmaniasis, which has increasingly been described in northeastern Brazil. These so-called atypical cutaneous leishmaniasis (ACL) cases differ in their symptoms and often aren't amenable to typical leishmaniasis treatment with antimony-based drugs.

To get at the roots of these differences, the team used amplicon sequencing-based parasite genotyping coupled with patient immune response profiling, to assess samples from more than 100 individuals with or without ACL. The analyses indicated that ACL involves genetically distinct L. braziliensis strains that seem to prompt enhanced inflammatory responses in infected patients.

"We conclude that atypical cutaneous leishmaniasis in Northeast Brazil may be considered a clinical presentation per se, in part resulting from infection of human beings with distinct strains of L. braziliensis," senior author Albert Schriefer, an immunology researcher at the Federal University of Bahia, and his co-authors wrote. "Precise identification of ACL is important because it usually does not respond to drugs commonly used to treat leishmaniasis in Brazil, but readily responds to other treatment options available."

The team characterized SNPs in a L. braziliensis chromosome 28 region where parasite polymorphisms have been described in the past, searching for genetic changes linked to leishmaniasis patterns.

In 51 ACL cases and 51 more typical cutaneous leishmaniasis cases occurring in Brazil's Corte de Pedra region from 2005 to 2012, the researchers found that ACL cases involved more numerous skin lesions, tended to be more drug-resistant, and were marked by infections that lasted longer than typical leishmaniasis cases. They also saw signs that those with the ACL infections produced more inflammatory cytokines — an altered immune response relative to that described in individuals with typical leishmaniasis infections.

Genetically, the study's authors uncovered half a dozen L. braziliensis haplotypes, including four chromosome 28 haplotypes that turned up exclusively in the ACL cases. "The genotypic differences identified between isolates in the current study serve to expand our previous documentation that strain aligns with clinical disease form," they wrote, "indicating that parasite strain may also be a partial determinant of ACL."