Molecular mechanisms for environmentally induced and evolutionarily rapid redistribution (plasticity) of meiotic recombination

It has long been known (circa 1917) that environmental conditions, as well as speciation, can affect dramatically the frequency distribution of Spo11/Rec12-dependent meiotic recombination. Here, by analyzing DNA sequence-dependent meiotic recombination hotspots in the fission yeast Schizosaccharomyces pombe, we reveal a molecular basis for these phenomena. The impacts of changing environmental conditions (temperature, nutrients, and osmolarity) on local rates of recombination are mediated directly by DNA site-dependent hotspots (M26, CCAAT, and Oligo-C). This control is exerted through environmental condition-responsive signal transduction networks (involving Atf1, Pcr1, Php2, Php3, Php5, and Rst2). Strikingly, individual hotspots modulate rates of recombination over a very broad dynamic range in response to changing conditions. They can range from being quiescent to being highly proficient at promoting activity of the basal recombination machinery (Spo11/Rec12 complex). Moreover, each different class of hotspot functions as an independently controlled rheostat; a condition that increases the activity of one class can decrease the activity of another class. Together, the independent modulation of recombination rates by each different class of DNA site-dependent hotspots (of which there are many) provides a molecular mechanism for highly dynamic, large-scale changes in the global frequency distribution of meiotic recombination. Because hotspot-activating DNA sites discovered in fission yeast are conserved functionally in other species, this process can also explain the previously enigmatic, Prdm9-independent, evolutionarily rapid changes in hotspot usage between closely related species, subspecies, and isolated populations of the same species.     

Characterising co-infections with Plasmodium spp., Mansonella perstans or Loa loa in asymptomatic children,adults and elderly people living on Bioko Island using nucleic acids extracted from malaria rapid diagnostic tests

BackgroundRegular and comprehensive epidemiological surveys of the filarial nematodes Mansonella perstans and Loa loa in children, adolescents and adults living across Bioko Island, Equatorial Guinea are lacking. We aimed to demonstrate that blood retained on malaria rapid diagnostic tests, commonly deployed for malaria surveys, could be used as a source of nucleic acids for molecular based detection of M. perstans and L. loa. We wanted to determine the positivity rate and distribution of filarial nematodes across different age groups and geographical areas as well as to understand level of co-infections with malaria in an asymptomatic population.MethodologyM. perstans, L. loa and Plasmodium spp. parasites were monitored by qPCR in a cross-sectional study using DNA extracted from a subset malaria rapid diagnostic tests (mRDTs) collected during the annual malaria indicator survey conducted on Bioko Island in 2018.Principal findingsWe identified DNA specific for the two filarial nematodes investigated among 8.2% (263) of the 3214 RDTs screened. Positivity rates of M. perstans and L. loa were 6.6% and 1.5%, respectively. M. perstans infection were more prominent in male (10.5%) compared to female (3.9%) survey participants. M. perstans parasite density and positivity rate was higher among older people and the population living in rural areas. The socio-economic status of participants strongly influenced the infection rate with people belonging to the lowest socio-economic quintile more than 3 and 5 times more likely to be L. loa and M. perstans infected, respectively. No increased risk of being co-infected with Plasmodium spp. parasites was observed among the different age groups.Conclusions/SignificanceWe found otherwise asymptomatic individuals were infected with M. perstans and L. loa. Our study demonstrates that employing mRDTs probed with blood for malaria testing represents a promising, future tool to preserve and ship NAs at room temperature to laboratories for molecular, high-throughput diagnosis and genotyping of blood-dwelling nematode filarial infections. Using this approach, asymptomatic populations can be reached and surveyed for infectious diseases beyond malaria.     

Sachet water consumption as a risk factor for cholera in urban settings: Findings from a case control study in Kinshasa,Democratic Republic of the Congo during the 2017–2018 outbreak

BackgroundBehavioural risk factors for cholera are well established in rural and semi-urban contexts, but not in densely populated mega-cities in Sub-Saharan Africa. In November 2017, a cholera epidemic occurred in Kinshasa, the Democratic Republic of the Congo, where no outbreak had been recorded for nearly a decade. During this outbreak, we investigated context-specific risk factors for cholera in an urban setting among a population that is not frequently exposed to cholera.Methodology/Principal findingsWe recruited 390 participants from three affected health zones of Kinshasa into a 1:1 matched case control study. Cases were identified from cholera treatment centre admission records, while controls were recruited from the vicinity of the cases’ place of residence. We used standardized case report forms for the collection of socio-demographic and behavioural risk factors. We used augmented backward elimination in a conditional logistic regression model to identify risk factors.The consumption of sachet water was strongly associated with the risk of being a cholera case (p-value 0.019), which increased with increasing frequency of consumption from rarely (OR 2.2, 95% CI 0.9–5.2) to often (OR 4.0, 95% CI 1.6–9.9) to very often (OR 4.1, 95% CI 1.0–16.7). Overall, more than 80% of all participants reported consumption of this type of drinking water. The risk factors funeral attendance and contact with someone suffering from diarrhoea showed a p-value of 0.09 and 0.08, respectively. No socio-demographic characteristics were associated with the risk of cholera.Conclusions/SignificanceDrinking water consumption from sachets, which are sold informally on the streets in most Sub-Saharan African cities, are an overlooked route of infection in urban cholera outbreaks. Outbreak response measures need to acknowledge context-specific risk factors to remain a valuable tool in the efforts to achieve national and regional targets to reduce the burden of cholera in Sub-Saharan Africa.