Asymptomatic Plasmodium parasitemia and the ecology of malaria transmission.

The American journal of tropical medicine and hygiene (Impact Factor: 2.74). 07/2002; 66(6):639-40.
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    ABSTRACT: Previous data have suggested that regulatory T cells (Tregs) balance protective immune responses with immune mediated pathology in malaria. This study aimed to determine to test the hypothesis that Treg proportions or absolute levels are associated with parasitaemia and malaria symptoms. Treg cells were quantified by flow cytometry as CD4+ CD25+, Foxp3+, CD127low T cells. Three patient groups were assessed: patients with symptomatic Plasmodium falciparum malaria (S), subjects with asymptomatic P. falciparum parasitaemia (AS) and uninfected control individuals (C). S, AS and C groups had similar absolute numbers and percentage of Tregs (3.9%, 3.5% and 3.5% respectively). Levels of parasitaemia were not associated with Treg percentage (p = 0.47). Neither relative nor absolute regulatory T cell numbers were found to be associated with malaria-related symptomatology in this study. Immune mechanisms other than Tregs are likely to be responsible for the state of asymptomatic P. falciparum parasitaemia in the Peruvian Amazon; but further study to explore these mechanisms is needed.
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    ABSTRACT: Molecular tools to distinguish strains of Plasmodium vivax are important for studying the epidemiology of malaria transmission. Two sets of markers—tandem repeat (TR) polymorphisms and MSP3a—were used to study Plasmodium vivax in patients in the Peruvian Amazon region of Iquitos. Of 110 patients, 90 distinct haplotypes were distinguished using 9 TR markers. An MSP3a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) using HhaI and AluI revealed 8 and 9 profiles, respectively, and 36 profiles when analyzed in combination. Combining TR and PCR-RFLP markers, 101 distinct molecular profiles were distinguished among these 110 patients. Nine TR markers arrayed along a 100 kB stretch of a P. vivax chromosome containing the gene for circumsporozoite protein showed non-linear linkage disequilibrium (I SA = 0.03, P = 0.001). These findings demonstrate the potential use of TR markers for molecular epidemiology studies.
    The American journal of tropical medicine and hygiene 01/2012; 86(4):580-586. · 2.74 Impact Factor
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    ABSTRACT: Nitric oxide (NO) is a proposed component of malaria pathogenesis and the inducible nitric oxide synthase gene (NOS2) has been associated to malaria susceptibility. We analyzed the role of NOS2 polymorphisms on NO bioavailability and on susceptibility to infection, Plasmodium carrier status and clinical malaria. Two distinct West African sample collections were studied: a population-based collection of 1,168 apparently healthy individuals from the Príncipe Island and a hospital-based cohort of 269 Angolan children. We found that two NOS2 promoter SNP alleles associated to low NO plasma levels in non-infected individuals were also associated to reduced risk of pre-erythrocytic infection as measured anti-CSP antibody levels (6.25E-04<P<7.57E-04). In contrast, three SNP alleles within the NOS2 cistronic region conferring increased NO plasma levels in asymptomatic carriers were strongly associated to risk of parasite carriage (8.00E-05<P<7.90E-04). Notwithstanding, three SNP alleles in this region protected from cerebral malaria (7.90E-4<P<4.33E-02). Cohesively, the results revealed a dual genetic control of NO bioavailability afforded by NOS2 depending on the infection status. NOS2 promoter variants operate in non-infected individuals to decrease both NO bioavailability and susceptibility to pre-erythrocytic infection. Conversely, NOS2 cistronic variants (namely, rs6505469) operate in infected individuals to increase NO bioavailability and confer increased susceptibility to unapparent infection but protect from cerebral malaria. These findings corroborate the hypothesis that NO anti-inflammatory properties impact on different steps of malaria pathogenesis, explicitly by favoring infection susceptibility and deterring severe malaria syndromes.
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