Experimental infection of the neotropical malaria vector Anopheles darlingi by human patient-derived Plasmodium vivax in the Peruvian Amazon

Malaria transmission from humans to mosquitoes is modulated by human host immune factors. Understanding mechanisms by which the human host response may impair parasite infectivity for mosquitoes has direct implications for the development of transmission-blocking vaccines. We hypothesized that despite a low transmission intensity of malaria in the Peruvian Amazon region of Iquitos, transmission-blocking immunity against Plasmodium vivax might be common, given an unexpectedly high proportion of asymptomatic parasitemic individuals in this region. To test this hypothesis, the ability of symptomatic P. vivax malaria patients to experimentally infect wild-caught outbred Anopheles darlingi mosquitoes was tested using the indirect membrane feeding technique. Only half (52/102) of P. vivax parasitemic patients successfully infected mosquitoes. Transmitters were more likely to have gametocytes (OR 6.35, P = 0.003), high parasitemia (OR 3.79, P = 0.024), and, in terms of basic clinical parameters, a slower pulse rate (mean ± SD: 82.3 ± 12.3 versus 88.7 ± 13.5, P = 0.016) than non-transmitters. Log10 gametocytemia and log10 real-time reverse transcriptase Pvs25 PCR quantifying gametocytes were significantly and positively correlated with oocyst counts (correlation coefficient 0.505, R2 = 0.26, P = 0.001). These experiments are the first to establish a system of determining transmission patterns in experimental infection of outbred natural neotropical malaria vectors in the Amazon region. Patients with P. vivax inefficiently infect outbred An. darlingi mosquitoes, raising the possibility that some degree of naturally occurring transmission-blocking immunity is present on a population basis in the Peruvian Amazon, an area of low intensity of malaria transmission

High frequency of Polio-like Enterovirus C strains with differential clustering of CVA-13 and EV-C99 subgenotypes in a cohort of Malawian children

Enteroviruses (EVs) are among the most commonly detected viruses infecting humans worldwide. Although the prevalence of EVs is widely studied, the status of EV prevalence in sub-Saharan Africa remains largely unknown. The objective of our present study was therefore to increase our knowledge on EV circulation in sub-Saharan Africa. We obtained 749 fecal samples from a cross-sectional study conducted on Malawian children aged 6 to 60 months. We tested the samples for the presence of EVs using real time PCR, and typed the positive samples based on partial viral protein 1 (VP1) sequences. A large proportion of th

High frequency and diversity of parechovirus A in a cohort of Malawian children

Parechoviruses (PeVs) are highly prevalent viruses worldwide. Over the last decades, several studies have been published on PeV epidemiology in Europe, Asia and North America, while information on other continents is lacking. The aim of this study was to describe PeV circulation in a cohort of children in Malawi, Africa. A total of 749 stool samples obtained from Malawian children aged 6 to 60 months were tested for the presence of PeV by real-time PCR. We performed typing by phylogenetic and Basic Local Alignment Search Tool (BLAST) analysis. PeV was found in 57% of stool samples. Age was signifcantly associated with PeV positivity (p = 0.01). Typing by phylogenetic analysis resulted in 15 diferent types, while BLAST typing resulted in 14 diferent types and several indeterminate strains. In total, six strains showed inconsistencies in typing between the two methods. One strain, P02-4058, remained untypable by all methods, but appeared to belong to the recently reclassifed PeV-A19 genotype. PeV-A1, -A2 and -A3 were the most prevalent types (26.8%, 13.8% and 9.8%, respectively). Both the prevalence and genetic diversity found in our study were remarkably high. Our data provide an important contribution to the scarce data available on PeV epidemiology in Africa

Measurement of the Atmospheric Muon Spectrum from 20 to 3000 GeV

The absolute muon flux between 20 GeV and 3000 GeV is measured with the L3 magnetic muon spectrometer for zenith angles ranging from 0 degree to 58 degree. Due to the large exposure of about 150 m2 sr d, and the excellent momentum resolution of the L3 muon chambers, a precision of 2.3 % at 150 GeV in the vertical direction is achieved. The ratio of positive to negative muons is studied between 20 GeV and 500 GeV, and the average vertical muon charge ratio is found to be 1.285 +- 0.003 (stat.) +- 0.019 (syst.).Comment: Total 32 pages, 9Figure

The Somatic Mutation Paradigm in Congenital Malformations: Hirschsprung Disease as a Model

Patients with Hirschsprung disease (HSCR) do not always receive a genetic diagnosis after routine screening in clinical practice. One of the reasons for this could be that the causal mutation is not present in the cell types that are usually tested-whole blood, dermal fibroblasts or saliva-but is only in the affected tissue. Such mutations are called somatic, and can occur in a given cell at any stage of development after conception. They will then be present in all subsequent daughter cells. Here, we investigated the presence of somatic mutations in HSCR patients. For this, whole-exome sequencing and copy number analysis were performed in DNA isolated from purified enteric neural crest cells (ENCCs) and blood or fibroblasts of the same patient. Variants identified were subsequently validated by Sanger sequencing. Several somatic variants were identified in all patients, but causative mutations for HSCR were not specifically identified in the ENCCs of these patients. Larger copy number variants were also not found to be specific to ENCCs. Therefore, we believe that somatic mutations are unlikely to be identified, if causative for HSCR. Here, we postulate various modes of development following the occurrence of a somatic mutation, to describe the challenges in detecting such mutations, and hypothesize how somatic mutations may contribute to 'missing heritability' in developmental defects