Population genetic analyses were conducted using samples of Aedes aegypti from 14 localities in the north, southeast, northeast, and central regions of Brazil. An 852-bp region of the mitochondrial DNA cytochrome oxidase I (COI) gene was used in the analyses. Ten haplotypes were observed, and cluster analyses revealed 2 groups (lineages) separated by 8 fixed mutations, suggesting that the Brazilian Ae. aegypti populations probably came from East and West Africa, with evidence of multiple introductions, one related to Group 1 and two related to Group 2. Considering all samples, genetic and geographic distances were significantly correlated (r(2) = 0.332; P = 0.038), supporting the isolation by distance (IBD) model, but no correlation was detected for any particular region, which is consistent with human migrations and trade exchanges. Genetic distances (pairwise F(ST) and Nm values), AMOVA, and cluster analyses indicated a deep genetic structure for the Brazilian Ae. aegypti, probably resulting from several factors: multiple introductions associated with distinct lineages, geographic differentiation (IBD), passive dispersal patterns, control activities, extinction and recolonization events, and genetic drift.
As phagocytosis is the first line of defense against malaria, we developed a
phagocytosis assay with Plasmodium vivax (P.
vivax) merozoites that can be applied to evaluate vaccine
candidates. Briefly, after leukocyte removal with loosely packed cellulose
powder in a syringe, P. vivax trophozoites matured to the
merozoite-rich schizont stages in the presence of the E64 protease inhibitor.
The Percoll gradient-enriched schizonts were chemically disrupted to release
merozoites that were submitted to merozoite opsonin-dependent phagocytosis in
two phagocytic lines with human and mouse antibodies against the N- and
C-terminus of P. vivax Merozoite Surface Protein-1
(Nterm-PvMSP1 and MSP119). The resulting assay is simple and
efficient for use as a routine phagocytic assay for the evaluation of merozoite
stage vaccine candidates.
Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.
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