Malaria vectors and transmission dynamics in Goulmoun, a rural city in south-western Chad

<p>Abstract</p> <p>Background</p> <p>Knowledge of some baseline entomological data such as Entomological Inoculation Rates (EIR) is crucially needed to assess the epidemiological impact of malaria control activities directed either against parasites or vectors. In Chad, most published surveys date back to the 1960's. In this study, anopheline species composition and their relation to malaria transmission were investigated in a dry Sudanian savannas area of Chad.</p> <p>Methods</p> <p>A 12-month longitudinal survey was conducted in the irrigated rice-fields area of Goulmoun in south western Chad. Human landing catches were performed each month from July 2006 to June 2007 in three compounds (indoors and outdoors) and pyrethrum spray collections were conducted in July, August and October 2006 in 10 randomly selected rooms. Mosquitoes belonging to the <it>Anopheles gambiae </it>complex and to the <it>An. funestus </it>group were identified by molecular diagnostic tools. <it>Plasmodium falciparum </it>infection and blood meal sources were detected by ELISA.</p> <p>Results</p> <p>Nine anopheline species were collected by the two sampling methods. The most aggressive species were <it>An. arabiensis </it>(51 bites/human/night), <it>An. pharoensis </it>(12.5 b/h/n), <it>An. funestus </it>(1.5 b/h/n) and <it>An. ziemanni </it>(1.3 b/h/n). The circumsporozoite protein rate was 1.4% for <it>An. arabiensis</it>, 1.4% for <it>An. funestus</it>, 0.8% for <it>An. pharoensis </it>and 0.5% for <it>An. ziemanni</it>. Malaria transmission is seasonal, lasting from April to December. However, more than 80% of the total EIR was concentrated in the period from August to October. The overall annual EIR was estimated at 311 bites of infected anophelines/human/year, contributed mostly by <it>An. arabiensis </it>(84.5%) and <it>An. pharoensis </it>(12.2%). <it>Anopheles funestus </it>and <it>An. ziemanni </it>played a minor role. Parasite inoculation occurred mostly after 22:00 hours but around 20% of bites of infected anophelines were distributed earlier in the evening.</p> <p>Conclusion</p> <p>The present study revealed the implication of <it>An. pharoensis </it>in malaria transmission in the irrigated rice fields of Goulmoun, complementing the major role played by <it>An. arabiensis</it>. The transmission period did not depend upon irrigation. Correct use of insecticide treated nets in this area may be effective for vector control although additional protective measures are needed to prevent pre-bedtime exposure to the bites of infected anophelines.</p

Constraints on Nucleon Decay via "Invisible" Modes from the Sudbury Neutrino Observatory

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to ``invisible'' modes, such as n -> 3 nu. The analysis was based on a search for gamma-rays from the de-excitation of the residual nucleus that would result from the disappearance of either a proton or neutron from O16. A limit of tau_inv > 2 x 10^{29} years is obtained at 90% confidence for either neutron or proton decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton decay modes and 400 times more stringent than similar neutron modes.Comment: Update includes missing efficiency factor (limits change by factor of 2) Submitted to Physical Review Letter

Patterns of Selection in Anti-Malarial Immune Genes in Malaria Vectors: Evidence for Adaptive Evolution in LRIM1 in Anopheles arabiensis

Co-evolution between Plasmodium species and its vectors may result in adaptive changes in genes that are crucial components of the vector's defense against the pathogen. By analyzing which genes show evidence of positive selection in malaria vectors, but not in closely related non-vectors, we can identify genes that are crucial for the mosquito's resistance against Plasmodium.We investigated genetic variation of three anti-malarial genes; CEC1, GNBP-B1 and LRIM1, in both vector and non-vector species of the Anopheles gambiae complex. Whereas little protein differentiation was observed between species in CEC1 and GNBP-B1, McDonald-Kreitman and maximum likelihood tests of positive selection show that LRIM1 underwent adaptive evolution in a primary malaria vector; An. arabiensis. In particular, two adjacent codons show clear signs of adaptation by having accumulated three out of four replacement substitutions. Furthermore, our data indicate that this LRIM1 allele has introgressed from An. arabiensis into the other main malaria vector An. gambiae.Although no evidence exists to link the adaptation of LRIM1 to P. falciparum infection, an adaptive response of a known anti-malarial gene in a primary malaria vector is intriguing, and may suggest that this gene could play a role in Plasmodium resistance in An. arabiensis. If so, our data also predicts that LRIM1 alleles in An. gambiae vary in their level of resistance against P. falciparum

Plasmodium falciparum transmission and aridity: a Kenyan experience from the dry lands of Baringo and its implications for Anopheles arabiensis control

<p>Abstract</p> <p>Background</p> <p>The ecology of malaria vectors particularly in semi-arid areas of Africa is poorly understood. Accurate knowledge on this subject will boost current efforts to reduce the burden of malaria in sub-Saharan Africa. The objective of this study was to describe the dynamics of malaria transmission in two model semi-arid sites (Kamarimar and Tirion) in Baringo in Kenya.</p> <p>Methods</p> <p>Adult mosquitoes were collected indoors by pyrethrum spray collections (PSC) and outdoors by Centers for Disease Control (CDC) light traps and identified to species by morphological characteristics. Sibling species of <it>Anopheles gambiae </it>complex were further characterized by rDNA. PCR and enzyme-linked immuno-sorbent assays (ELISA) were used to test for <it>Plasmodium falciparum </it>circumsporozoite proteins and host blood meal sources respectively.</p> <p>Results</p> <p><it>Anopheles arabiensis </it>was not only the most dominant mosquito species in both study sites but also the only sibling species of <it>An. gambiae s.l. </it>present in the area. Other species identified in the study area were <it>Anopheles funestus</it>, <it>Anopheles pharoensis </it>and <it>Anopheles coustani</it>. For Kamarimar but not Tirion, the human blood index (HBI) for light trap samples was significantly higher than for PSC samples (Kamarimar, 0.63 and 0.11, Tirion, 0.48 and 0.43). The HBI for light trap samples was significantly higher in Kamarimar than in Tirion while that of PSC samples was significantly higher in Tirion than in Kamarimar. Entomological inoculation rates (EIR) were only detected for one month in Kamarimar and 3 months in Tirion. The number of houses in a homestead, number of people sleeping in the house, quality of the house, presence or absence of domestic animals, and distance to the animal shelter and the nearest larval habitat were significant predictors of <it>An. arabiensis </it>occurrence.</p> <p>Conclusion</p> <p>Malaria transmission in the study area is seasonal with <it>An. arabiensis </it>as the dominant vector. The fact this species feeds readily on humans and domestic animals suggest that zooprophylaxis may be a plausible malaria control strategy in semi-arid areas of Africa. The results also suggest that certain household characteristics may increase the risk of malaria transmission.</p

Low linkage disequilibrium in wild Anopheles gambiae s.l. populations

<p>Abstract</p> <p>Background</p> <p>In the malaria vector <it>Anopheles gambiae</it>, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD). For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs) to be genotyped to represent the majority of the genomic information. Here, we aim to determine LD in wild <it>An. gambiae s.l</it>. populations in 4 genes potentially involved in mosquito immune responses against pathogens (<it>Gambicin</it>, <it>NOS</it>, <it>REL2 </it>and <it>FBN9</it>) using previously published and newly generated sequences.</p> <p>Results</p> <p>The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species) of the <it>An. gambiae </it>complex. In all tested genes and species, LD between SNPs was low: even at short distances (< 200 bp), most SNP pairs gave an r²< 0.3. Mean r²ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance.</p> <p>Conclusions</p> <p>These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.</p

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Development of an online p38α mitogen-activated protein kinase binding assay and integration of LC–HR-MS

A high-resolution screening method was developed for the p38α mitogen-activated protein kinase to detect and identify small-molecule binders. Its central role in inflammatory diseases makes this enzyme a very important drug target. The setup integrates separation by high-performance liquid chromatography with two parallel detection techniques. High-resolution mass spectrometry gives structural information to identify small molecules while an online enzyme binding detection method provides data on p38α binding. The separation step allows the individual assessment of compounds in a mixture and links affinity and structure information via the retention time. Enzyme binding detection was achieved with a competitive binding assay based on fluorescence enhancement which has a simple principle, is inexpensive, and is easy to interpret. The concentrations of p38α and the fluorescence tracer SK&F86002 were optimized as well as incubation temperature, formic acid content of the LC eluents, and the material of the incubation tubing. The latter notably improved the screening of highly lipophilic compounds. For optimization and validation purposes, the known kinase inhibitors BIRB796, TAK715, and MAPKI1 were used among others. The result is a high-quality assay with Z′ factors around 0.8, which is suitable for semi-quantitative affinity measurements and applicable to various binding modes. Furthermore, the integrated approach gives affinity data on individual compounds instead of averaged ones for mixtures