Unique Parasite Strain Causes Atypical Leishmaniasis Cases in Brazil

A recent study of patients with atypical cutaneous leishmaniasis (ACL) in northeast Brazil has shown that these cases are caused by distinct strains of Leishmania braziliensis. Luiz Henrique Guimarães, from the Federal University of Bahia, Salvador, Brazil, and colleagues, published the results of their study online in PLOS Neglected Tropical Diseases.

Leishmaniasis is a parasitic disease found in parts of the tropics and subtropics, as well as in southern Europe. It is caused by the protozoan organism Leishmania braziliensis, which is transmitted by the bites of phlebotomine sand flies.

“ACL found in Northeast Brazil is caused by distinct genotypes of [Leishmania (Viannia]) braziliensis and presents a cytokine profile that departs from that in classical CL [localized cutaneous leishmaniasis] patients,” the authors wrote. “We think that differences in antigenic contents among parasites may be in part responsible for the variation in cytokine responses and possibly immunopathology between CL and ACL.”

In the New World, Leishmania (Viannia) braziliensis is the main species of the organism that causes American tegumentary leishmaniasis (ATL), of which four main forms occur in Brazil: CL, mucosal leishmaniasis (ML), disseminated leishmaniasis (DL), and diffuse cutaneous leishmaniasis (DCL).

However, according to the authors, cases of atypical cutaneous leishmaniasis (ACL) have been increasingly reported in northeast Brazil that typically do not fit into any of the four categories of ATL. Previously, scientists have suspected that these atypical cases occurred in patients with underlying predisposing conditions, such as immunosuppression, chronic disease, or pregnancy. However, most patients with ACL do not have such underlying conditions.

With this in mind, the researchers conducted a study to better understand the differences between ACL and ATL. They collected clinical data, as well as samples of blood and skin, in order to examine the genetics of the parasite infecting each patient and the patients’ immune responses to the disease.

The results of the study showed that ACL involves genetically distinct L. braziliensis strains that seem to cause increased inflammatory responses in infected patients. Patients with ACL had significantly more lesions, especially above the waist, than those with CL had. The clinical course of ACL also lasted longer than CL did, and was more likely to be resistant to antimony-based treatment, which is the front-line treatment used in Brazil for leishmaniasis. The researchers found that, although almost 100% of initially refractory CL patients respond favourably to two courses of antimony therapy, more than 60% of those with ACL failed two courses of treatment.

They showed that cases of ACL in the northeast of Brazil are caused by a genetically distinct strain of L. braziliensis—the parasites that infected 62.5% of patients with ACL—had genetic variations seen only in these organisms that caused ACL, and not in those that caused CL. Levels of inflammatory cytokines in peripheral blood mononuclear cells also differed between patients with ACL and those with CL—patients with ACL had lower IFN-γ and higher IL-10 levels.

The authors suggested that this difference may favor parasite growth, and may also help to explain the exacerbated pathogenesis of ACL as well as its high rate of therapeutic failure.

"Precise identification of ACL is important because it usually does not readily respond to drugs commonly used to treat leishmaniasis in Brazil, but readily responds to other treatment options available," the authors concluded.

“These findings may contribute to our understanding of the pathogenesis of ACL, and ultimately to a more logical approach to management of this and other unusual forms of ATL.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.

Feature Picture Source: Dr. Martin D. Hicklin / Centers for Disease Control and Prevention