Praziquantel has been used to treat schistosome infections since 1979 and currently is the only chemotherapeutic agent in production for this purpose, raising concerns about the potential for the emergence of drug resistance. In practice, 10–20% of infected patients will continue to excrete eggs after treatment. It is not understood to what degree this represents selection of a resistant population or incomplete elimination due to the presence of immature worms at the time of treatment. We used a population genetics approach to test whether or not persistent Schistosoma mansoni parasites were drawn from the same population as susceptible parasites. In this study, stool samples were collected from 96% of individuals in two small Brazilian communities (populations 482 and 367) and examined for S. mansoni eggs. The combined prevalence of S. mansoni infections in the villages was 41%. Total egg DNA was extracted from each sample and was genotyped at 15 microsatellite markers. Day-to-day variation of the infrapopulation from an individual human host was low (median differentiation using Jost’s D = 0.010), so that a single stool was representative of the genotypes present in stool eggs, at least in the short term. Average pairwise analysis of D among all pre-treatment infrapopulations suggested moderate differentiation (mean D = 0.082 and 0.122 for the two villages), whereas the pre-treatment component population differentiation between the two communities was 0.047. The differentiation of the component population remaining after treatment from the fully susceptible component population was low (mean D = 0.007 and 0.020 for the two villages), suggesting that the persistent parasites were not selected by praziquantel treatment. We will continue to follow these communities for evidence of selection or changes in population structure.
In general, the prevalence and genotype distribution of hepatitis C virus (HCV) are estimated based on the ambulatory clinic or hospital population. In the present work, a population-based study was conducted to estimate the prevalence of HCV infection in Salvador, Brazil. A total of 1308 serum samples were collected from 30 "sentinel areas", and the prevalence of HCV infection was determined by ELISA and confirmed by recombinant immunoblot assay and RT-PCR. The overall prevalence of HCV infection was 1.5% (20/1308). Prevalence was greater among those aged 35 years or older and those with more education. Genotype 3 was the most common (53.3%), followed by genotypes 1 (40%) and 2 (6.7%). These observations are different from those found in a prior survey of hospital and ambulatory patients in Salvador, who were most frequently infected with genotype 1, followed by genotypes 3 and 2, respectively.
To identify genes associated with the clinical presentation of dengue, 50 cases of probable or possible dengue hemorrhagic fever, 236 dengue fever and 236 asymptomatic infections were genotyped for 593 single nucleotide polymorphisms in 56 genes across the type 1 interferon response pathway as well as other important candidate genes. By single locus analysis comparing dengue hemorrhagic fever with dengue fever, 11 of the 51 markers with p<0.05 were in the JAK1 gene. Five markers were significantly associated by false discovery rate criteria (q<0.20 when p<6 × 10−4). The JAK1 single nucleotide polymorphisms showed differential distribution by ethnicity and ancestry consistent with epidemiologic observations in the Americas. The association remained significant after controlling for ancestry and income. No association was observed with markers in the gene encoding CD209 (DC-SIGN). An association between dengue hemorrhagic fever and JAK1 polymorphisms is in agreement with expression profiles showing generalized decreased type 1 interferon-stimulated gene expression in these patients.
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