MulticlonalLeishmania braziliensisPopulation Structure and Its Clinical Implication in a Region of Endemicity for American Tegumentary Leishmaniasis

Abstract

In Corte de Pedra (CP), northeastern Brazil, Leishmania braziliensis causes three distinct forms of American tegumentary leishmaniasis (ATL). To test the hypothesis that strain polymorphism may be involved in this disease spectrum and accurately characterize the parasite population structure in CP, we compared one L. major, two non-CP L. braziliensis, one CP L. amazonensis, and 45 CP L. braziliensis isolates, obtained over a 10-year period from localized cutaneous, mucosal, and disseminated leishmaniasis patients, with randomly amplified polymorphic DNA (RAPD). Electrophoretic profiles were mostly unique across species. All typing protocols revealed polymorphism among the 45 CP L. braziliensis isolates, which displayed eight different RAPD patterns and greater than 80% overall fingerprint identity, attesting to the adequacy of the tools to assess strain variability in CP's geographically limited population of parasites. The dendrogram based on the sum of RAPD profiles of each isolate unveiled nine discrete typing units clustered into five clades. Global positioning showed extensive overlap of these clades in CP, precluding geographic sequestration as the mechanism of the observed structuralization. Finally, all forms of ATL presented a statistically significant difference in their frequencies among the clades, suggesting that L. braziliensis genotypes may be accompanied by specific disease manifestation after infection.

Ecology of the Leishmania Species in the Guianan Ecoregion Complex

“…However, isolates from different polymorphic species show plesiomorphic similarities in their enzymatic or genetic profiles, suggesting that they may have originated from one primary sylvatic enzootic form. 80,81 Globally, although L. (V.) braziliensis [82][83][84][85][86][87][88][89][90] and in a lesser extent L. (V.) amazonensis 85,91 were shown to be highly polymorphic, L. (V.) naiffi, 45,82,83 L. (V.) guyanensis, 46,83,88 and L. (L.) deanei 92 were shown to have less diversity. Leishmania (V.) lainsoni was shown to be more invariant.…”

Endemic Tegumentary Leishmaniasis in Brazil: Correlation between Level of Endemicity and Number of Cases of Mucosal Disease

“…Different studies using polymorphic markers, in an attempt to define genetic profiles, and biochemical and molecular characteristics of parasite populations have failed to establish a correlation between these profiles and clinical expression of MCL. [10][11][12][13][14][15] Leishmania ( Viannia ) braziliensis , one of seven dermotropic Leishmania species found in Brazil, is responsible for localized, multiple, or disseminated cutaneous lesions and for the secondary effects in the mucosa. This species is broadly distributed in South and Central America and is predominant outside the Amazon region of Brazil, including rural and peri-urban areas.…”

Genetic risk factors for human susceptibility to infections of relevance in dermatology

“…In the earlier of these studies, a multiclonal population structure among L. braziliensis isolates from an area with high endemicity for ATL in the northeastern Brazilian state of Bahia was described. 60 More importantly, that study revealed a statistically significant association between clinical outcome of leishmaniasis and parasite genotypes. Coupled with the observations from Saravia et al mentioned above, these findings indicate a major role for the intra-species variability among these microorganisms with regard to form of the disease, paralleling the strong relationship between species of Leishmania and form of leishmaniasis.…”

“…61 It was remarkable that the distributions of ML and DL overlapped those of the clones of the parasite that were associated with these diseases in that previous study, indicating that the L. brazilliensis genetic content may also influence other complex phenotypes like geographic distribution of form of leishmaniasis within an affected region. 60 …”