Epidemiologic, genetic, and clinical associations among phenotypically distinct populations of Leishmania (Viannia) in Colombia.

Phenotypic characterization of 511 strains of Leishmania, subgenus Viannia, isolated from Colombian patients was conducted based on electrophoretic polymorphisms of 13 isoenzymes. Ninety-one Colombian strains of L. braziliensis were the most heterogeneous, constituting seven zymodemes while 397 L. panamensis and 22 L. guyanensis strains yielded five and three zymodemes, respectively. Phosphogluconate dehydrogenase, nucleoside hydrolase, and superoxide dismutase were the most polymorphic enzymes in this collection of strains, and together with glucose-6-phosphate dehydrogenase, allowed the discrimination of the three aforementioned species. Hierarchical cluster analysis of the zymodemes using Jaccard's coefficient of similarities revealed two clusters, one constituted by L. braziliensis zymodemes, and another by three subgroups consisting of zymodemes of L. panamensis closely related to the species reference strain, another consisting of L. guyanensis zymodemes, and a third group distinguished by new electromorphs of proline iminopeptidase and aspartate aminotransferase that reacted with the L. panamensis-specific monoclonal antibody B-11. Multiple zymodemes of L. panamensis and L. guyanensis were found to be sympatrically transmitted in foci along the Pacific coast. Leishmania braziliensis variants were ubiquitous throughout the territory of Colombia; L. panamensis was prevalent in the western region and L. guyanensis was prevalent in the Orinoco and Amazon river basins in the eastern half of the country. Distinct zymodemes of L. panamensis predominated in the northern and southern regions of the Pacific coast. Nine zymodemes of all three species were isolated from mucosal lesions. Zymodeme 1.1 of L. braziliensis had the highest frequency of mucosal involvement (10% of the cases), and disease caused by this zymodeme had the longest mean time of evolution (31 months; P = 0.002). In addition to being useful in describing epidemiologic relationships, the intraspecific heterogeneity of strains of the Viannia subgenus within and among foci can be used to understand such fundamental questions as the pathogenicity of different populations of parasites, and the induction of cross-protection against related parasites.

The relationship of Leishmania braziliensis subspecies and immune response to disease expression in New World leishmaniasis.

Multivariate analyses of clinical presentation, subspecies identity of the causal organism, and the Leishmania-specific immune response parameters (indirect fluorescent antibody test [IFAT], cutaneous delayed type hypersensitivity [DTH], and in vitro lymphocyte transformation [LT]) of 441 patients with tegumentary leishmaniasis were used to examine the human host-parasite interaction in L. braziliensis infection. Mucocutaneous disease (P less than .002) and L. braziliensis braziliensis infection (P less than .001) were independently associated with significantly higher IFAT titers and cutaneous DTH than were cutaneous disease or L. braziliensis panamensis infection. Lesion size was also correlated with IFAT titer (P. less than .001). Although time of lesion evolution was highly correlated with all parameters, differences associated with subspecies and disease form were independent of lesion duration (three-way analysis of variance). In contrast with the cutaneous DTH response, the in vitro lymphocyte proliferative response to Leishmania antigen did not correlate with disease form and only weakly with infecting subspecies when time of evolution and subspecies were controlled. The association of mucosal disease presentation with a particular subspecies and the independent correlation of both variables with heightened IFAT titers and cutaneous DTH to Leishmania antigen supports the possibility of immune mechanisms of pathogenesis in human tegumentary leishmaniasis.

Divergent isoenzyme profiles of sylvatic and domiciliary Trypanosoma cruzi in the eastern plains, piedmont, and highlands of Colombia.

Fifty-four stocks of Trypanosoma cruzi from vectors, mammalian reservoirs, and infected humans were characterized by enzyme electrophoresis in starch gels using Brazilian zymodeme reference strains (Z1, X-10; Z2, ESM; Z3, CAN-3) as standards. Colombian stocks were collected in three ecologically and epidemiologically distinct settings. Thirteen enzymes were included in the evaluation. Sixteen different phenotypic profiles or "zymodemes" were evident and generated three groups of closely related stocks: a sylvatic Z1-like group, a domiciliary Z1-like group, and a sylvatic Z3-like group. The number of zymodemes observed in foci of sylvatic transmission was greater than in foci of domiciliary transmission. Modified ecologic conditions associated with agriculture and the consequent reduction of biologic diversity may account for the observed pattern of zymodeme distribution and heterogeneity. The phenotypic similarity between the principal sylvatic group of stocks and domiciliary stocks contrasts with the extensive differences observed between the domestic Z2 zymodeme and sylvatic Z1 and Z3 zymodemes in Brazil and Chile.

Lack of enzyme polymorphism in Trypanosoma rangeli stocks from sylvatic and domiciliary transmission cycles in Colombia.

Although Trypanosoma rangeli is biologically and morphologically distinct from Trypanosoma cruzi, these two hemoflagellates are epidemiologically linked. We report the results of enzyme electrophoretic studies of T. rangeli stocks isolated from sylvatic and domiciliary Rhodnius prolixus, and infected humans inhabiting foci in which T. cruzi was sympatrically transmitted. T. rangeli stocks displayed electrophoretically detectable polymorphism for only a single enzyme, isocitrate dehydrogenase (ICD), in contrast with the marked phenotypic heterogeneity previously reported among the T. cruzi stocks. The relatively restricted diversity manifested by stocks from different geographic sites and ecologic habitats may reflect the existence of distinctive biologic or genetic constraints influencing T. cruzi and T. rangeli transmission.

Mucocutaneous leishmaniasis in Colombia: Leishmania braziliensis subspecies diversity.

It is generally held that with rare exception Leishmania braziliensis braziliensis is the parasite responsible for the metastatic development of mucocutaneous leishmaniasis in the New World. Yet the infrequency of mucocutaneous disease compared with cutaneous manifestations, and the difficulty of isolating parasites from mucocutaneous lesions have restricted the study of the organisms involved. We here report the biologic, isoenzymatic, and monoclonal antibody specificity characteristic of eight Leishmania isolates obtained from the mucosal lesions of the same number of patients. Individually and collectively, the identifying criteria implicate at least two L. braziliensis subspecies as etiologic agents of mucocutaneous leishmaniasis in Colombia and suggest that a spectrum of intrinsically distinguishable organisms may be involved in this disease form.