Margaret Pinder

Durham University | DU · School of Biological and Biomedical Sciences

Normal respiratory rates (RR) for children under five in the tropics are well-documented, but data for older children are limited. This study tracked RR changes with age and examined associations with nutritional status and environmental factors. We monitored rural Gambian children aged 6 months to 14 years, recording RR during home visits twice we...

Background: Although ranges of normal respiratory rates (RR) have been described for children under five years old living in the tropics, there are few datasets recording rates in older children. The present study was designed to capture the changes in RR with age and to examine its association with nutritional status and environmental factors. Met...

Rural houses in sub-Saharan Africa are typically hot and allow malaria mosquitoes inside. We assessed whether passive or active ventilation can reduce house entry of malaria mosquitoes and cool a bedroom at night in rural Gambia. Two identical experimental houses were used: one ventilated and one unventilated (control). We evaluated the impact of (...

Background The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should pro...

Background: The housing stock of rural sub-Saharan Africa is changing rapidly. With millions of new homes required over the coming decades, there is an opportunity to protect residents by screening homes from malaria mosquitoes. This study, undertaken in the Upper River Region of The Gambia, explores local perceptions of what a good house should pr...

Background: In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bed net (ITN) at night. Whether the colour of a metal roof affects indoor temperature and human c...

Most malaria infections in sub-Saharan Africa are acquired indoors, thus finding effective ways of preventing mosquito house entry should reduce transmission. Since most malaria mosquitoes fly less than 1 m from the ground, we tested whether raising buildings off the ground would prevent the entry of Anopheles gambiae , the principal African malari...

In sub-Saharan Africa, cooler houses would increase the coverage of insecticide-treated bednets, the primary malaria control tool. We examined whether improved ventilation, using windows screened with netting, cools houses at night and reduces malaria mosquito house entry in The Gambia. Identical houses were constructed, with badly fitting doors th...

Background In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. We aimed to assess whether children in The Gambia received an incremental benefit from improved housing, where current best practice of insecticide-treated nets, indoor residual spraying, seasonal malaria chemoprevention in chi...

Background In rural sub-Saharan Africa, thatch roofs are being replaced by metal roofs. Metal roofing, however, increases indoor temperatures above human comfort levels, and thus makes it more likely that residents will not use an insecticide-treated bednet (ITN) at night. We assessed whether the colour of a metal roof affects indoor temperature an...

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background African houses are frequently too hot and uncomfortable to use a bed net at night. Indoor thermal comfort is often evaluated by measuring temperature and humidity, ignoring ventilation. This study explored ways to measure ventilation in single-roomed rural Gambian houses during the malaria transmission season and evaluated build...

Background: Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly, and where respondents answer what they think the recorder may want to hear. Sleeping under a long-lasting insecticidal net (LLIN) is an important intervention for malar...

Abstract Background Long-lasting insecticidal nets (LLINs) treated with pyrethroids are the foundation of malaria control in sub-Saharan Africa. Rising pyrethroid resistance in vectors, however, has driven the development of alternative net formulations. Here the durability of polyethylene nets with a novel combination of a pyrethroid, permethrin,...

Background Recording behaviours that have the potential to impact health can be doubly challenging if the behaviour takes place in private spaces that cannot be observed directly and where there is potential for social desirability bias, i.e. where the respondent may give an answer that they think the recorder wants to hear. Sleeping under a long-l...

In The Gambia, metal-roof houses were hotter during the day than thatched-roof houses. After 24 h, the mortality of Anopheles gambiae, the principal African malaria vector, was 38% higher in metal-roof houses than thatched ones. During the day, mosquitoes in metal-roof houses moved from the hot roof to cooler places near the floor, where the temper...

Bio-Detection Dogs (BDDs) are used in some high-income countries as a diagnostic intervention, yet little is known about their potential in low/middle-income countries with limited diagnostic resources. This exploratory study investigated the opportunities and implications of deploying BDDs as a mobile diagnostic intervention to identify people wit...

Introduction: Unprecedented improvements in housing are occurring across much of rural sub-Saharan Africa, but the consequences of these changes on malaria transmission remain poorly explored. We examined how different typologies of rural housing affect mosquito house entry and indoor climate. Methods: Five typologies of mud-block houses were co...

Despite compelling evidence that modern housing protects against malaria, houses in endemic areas are still commonly porous to mosquitoes. The protective efficacy of four prototype screened doors and two windows designs against mosquito house entry, their impact on indoor climate, as well as their use, durability and acceptability was assessed in a...

Background: Malnutrition is common in children in sub-Saharan Africa and is thought to increase the risk of infectious diseases, including malaria. The relationship between malnutrition and malaria was examined in a cohort of 6-59 month-old children in rural Gambia, in an area of seasonal malaria transmission. The study used data from a clinical t...

Background: Substantial reductions in malaria incidence in sub-Saharan Africa have been achieved with massive deployment of long-lasting insecticidal nets (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area with intense malaria transmission and highly pyrethroid-resistant vectors. We assessed the effectiveness of bednets...

Unfortunately, the original article [1] contained an error mistakenly carried forward by the Production department handling this article whereby some figures and their captions were interchanged. The correct figures (Figs. 1, 2, 3, 4, 5) and captions are presented in this erratum. The original article has also been updated to reflect this correctio...

Background: Insecticide resistance threatens malaria control in sub-Saharan Africa. Knockdown resistance to pyrethroids and organochlorines in Anopheles gambiae sensu lato (s.l.) is commonly caused by mutations in the gene encoding a voltage-gated sodium channel which is the target site for the insecticide. The study aimed to examine risk factors...

Single SNP association test results with adjustment for additive effect of G6PD+202.DOI: http://dx.doi.org/10.7554/eLife.15085.007

G6PDd score association test results.DOI: http://dx.doi.org/10.7554/eLife.15085.015

(A) Summary of study designs of contributing partner studies to MalariaGEN Consortial Project 1 (CP1). (B) Genotyped sample distribution. (C) Summary of 65 SNPs selected for analysis and successfully genotyped. (D) G6PD+202 female association test results. (E) G6PD+202 male association test results. (F) G6PD+202 all individuals association test res...

(A) SNP selection across G6PD region for genotyping. (B) SpectroDESIGNER assay design file for 135 G6PD locus SNPs in four multiplexes. (C) SpectroDESIGNER assay design file for 107 G6PD locus SNPs in four multiplexes. (D) SpectroDESIGNER assay design file for 68 G6PD locus SNPs in three multiplexes. DOI: http://dx.doi.org/10.7554/eLife.15085.020

Single SNP association test results.DOI: http://dx.doi.org/10.7554/eLife.15085.006

Background: In malaria-endemic areas, residents of modern houses have less malaria than those living in traditional houses. This study will determine if modern housing provides incremental protection against clinical malaria over the current best practice of long-lasting insecticidal nets (LLINs) and prompt treatment in The Gambia, determine the i...

Glucose-6-phosphate dehydrogenase (G6PD) deficiency exhibits considerable allelic heterogeneity which manifests with variable biochemical and clinical penetrance. It has long been thought that G6PD deficiency confers partial protection against severe malaria, however prior genetic association studies have disagreed with regard to the strength and s...

Recent reductions in malaria in sub-Saharan Africa have been associated with increased coverage with long-lasting insecticidal nets (LLINs). Pyrethroids are currently the only insecticide class used for treating nets, and the rapid increase in resistance to pyrethroids in vector mosquitoes may jeopardise future vector control. Nets containing a nov...

The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-...

Vector-borne diseases (VBDs) such as malaria, dengue, and leishmaniasis cause a high level of morbidity and mortality. Although vector control tools can play a major role in controlling and eliminating these diseases, in many cases the evidence base for assessing the efficacy of vector control interventions is limited or not available. Studies asse...

The effectiveness of pyrethroid-treated bednets for malaria control in sub-Saharan Africa is under threat because of high levels of resistance to pyrethroid insecticides in the vectors. Here we assess the durability of polyethylene nets with a novel combination of permethrin, a pyrethroid, with pyriproxyfen, an insect juvenile mimic (PPF-LLIN), in...

Although many malaria control programmes in sub-Saharan Africa use indoor residual spraying with long-lasting insecticidal nets (LLINs), the two studies assessing the benefit of the combination of these two interventions gave conflicting results. We aimed to assess whether the addition of indoor residual spraying to LLINs provided a significantly d...

Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. T...

Background. Analysis of genome-wide polymorphism in many organisms has potential to identify genes under recent selection. However, data on historical allele frequency changes are rarely available for direct confirmation. Methods. We genotyped single nucleotide polymorphisms (SNPs) in 4 Plasmodium falciparum drug resistance genes in 668 archived pa...

Malaria vector control is threatened by resistance to pyrethroids, the only class of insecticides used for treating bed nets. The second major vector control method is indoor residual spraying with pyrethroids or the organochloride DDT. However, resistance to pyrethroids frequently confers resistance to DDT. Therefore, alternative insecticides are...

In areas of declining malaria transmission such as in The Gambia, the identification of malaria infected individuals becomes increasingly harder. School surveys may be used to identify foci of malaria transmission in the community. The survey was carried out in May-June 2011, before the beginning of the malaria transmission season. Thirty two schoo...

Combining data from genome-wide association studies (GWAS) conducted at different locations, using genotype imputation and fixed-effects meta-analysis, has been a powerful approach for dissecting complex disease genetics in populations of European ancestry. Here we investigate the feasibility of applying the same approach in Africa, where genetic d...

Example of cluster plot from Malawi cohort with outlying sets of individuals. (TIF)

Distribution of relatedness between most-related pairs. (TIF)

Comparison of logistic regression (SNPTEST) and mixed model (MMM) P values. (TIF)

SNPs showing highly divergent P values between logistic regression and mixed model scans. (TIF)

Comparison of meta-analysis P values versus Bayes factors under the fixed-effect model. (TIF)

Quantile-quantile plots of the region-based test in the three cohort and in the meta-analysis. The genomic control inflation factor is given in the title of the plots. (TIF)

Manhattan plot showing –log10 P values (thresholded at 10) for additive, dominant, heterozygote, recessive, and general models, and additive model conditional on the genotype at the sickle locus rs334, across all imputed SNPs. Meta-analysis P values for all three cohorts and for the East African cohorts are also shown for additive, dominant, recess...

The distribution of ethnic groups in Kenyan samples that were imputed with higher or lower quality (as defined by the red line in Figure S12). The difference in the two distributions is highly significant (Fisher's exact test, P = 4×10−4), suggesting that ethnic differences contribute to the bimodal distribution of imputation quality seen in Figure...

–log10(P values) for test of association using the mixed model. (TIF)

The distribution of imputation quality (measured by type2 r2) across imputed Kenyan samples. The red line is at r2 = 0.909, and is the minimum between the two peaks. (TIF)

Pre-imputation individual QC. (DOCX)

Top: signal of association in the HBB region after conditioning on the genotype at the known causal locus rs334. Bottom: signal of association in the ABO region after conditioning on the genotype at rs8176719. (TIF)

Example output from the imputation quality control pipeline for the Kenya imputation. a) per-SNP certainty (mean maximum posterior genotype call); b) per-SNP accuracy (type2 r2); c) per-individual type2 r2, averaged across segments; d) per-segment heterozygous call accuracy (proportion of true heterozygous calls that are correctly imputed with high...

Population-specific PCA analysis of Kenyan samples. (TIF)

a) Empirical distribution, across approximately 20,000 gene regions, of the maximum likelihood estimate of the eta parameter (see Text S2), for the region-based test. Overlaid (red line) is the assumed prior distribution under the alternative used to calculate Bayes factors in the region-based analysis. b) Scatter plot of the log10 combined Bayes F...

Post-imputation sample exclusions. (DOCX)

Genomic Inflation factors (λ) for logistic regression and mixed-model scans. (DOCX)

Enrichment of low region based test P values in three previously defined sets of regions. Each P value in the table results from a one-sided binomial test for an enrichment in the number of regions with empirical P value below the given threshold. The bottom row gives a summary of the distribution of the number of SNPs in each region. Note that the...

Manhattan plot showing –log10 P values (thresholded at 10) for additive, dominant, heterozygote, recessive, and general models, and additive model conditional on the genotype at the sickle locus rs334, across all non-excluded genotyped SNPs. Meta-analysis P values for all three cohorts and for the East African cohorts are also shown for additive, d...

Population-specific PCA analysis of Gambian samples. (TIF)

Population-specific PCA analysis of Malawian samples. (TIF)

Comparison of fixed, structured, correlated and independent-effect models at the ABO and HBB loci. The height of each bar represents the posterior probability that the corresponding model is true, under the assumption that one of the models is true. (TIF)

Details on the 3 study sites and genotyping platforms. (DOCX)

P values for correlation between the first 5 PCs and case/control status. (DOCX)

Supplementary statistical details. (PDF)

ROC curve showing empirical true positive rate (y-axis) against false positive rate (x-axis) for each method used to detect regional association (regional test with Fisher meta-analysis, regional test with Bayesian meta-analysis, best single-SNP frequentist meta-analysis in region, best single-SNP Bayes factor for each of the four choices of correl...

Pre-imputation SNP QC. (DOCX)

Regions showing most association in single-SNP and regional association test analyses. (XLSX)

Details of quality control. (DOCX)

Objective To explore ways of controlling Chrysomya putoria, the African latrine fly, in pit latrines. As pit latrines are a major source of these flies, eliminating these important breeding sites is likely to reduce village fly populations, and may reduce the spread of diarrhoeal pathogens. Methods We treated 24 latrines in a Gambian village: six...