Spatial and temporal dynamics of malaria transmission in rural western Kenya

ABSTRACT: BACKGROUND: Understanding the impact of reducing Plasmodium falciparum malaria transmission requires estimates of the relationship between health outcomes and exposure to infectious mosquitoes. However, measures of exposure such as mosquito density and entomological inoculation rate (EIR) are generally aggregated over large areas and time periods, biasing the outcome-exposure relationship. There are few studies examining the extent and drivers of local variation in malaria exposure in endemic areas. METHODS: We describe the spatio-temporal dynamics of malaria transmission intensity measured by mosquito density and EIR in the KEMRI/CDC health and demographic surveillance system using entomological data collected during 2002-2004. Geostatistical zero inflated binomial and negative binomial models were applied to obtain location specific (house) estimates of sporozoite rates and mosquito densities respectively. Model-based predictions were multiplied to estimate the spatial pattern of annual entomological inoculation rate, a measure of the number of infective bites a person receive per unit of time. The models included environmental and climatic predictors extracted from satellite data, harmonic seasonal trends and parameters describing space-time correlation. RESULTS: Anopheles gambiae s.l was the main vector species accounting for 86% (n=2309) of the total collected mosquitoes with the remainder being Anopheles funestus. Sixty eight percent (757/1110) of the surveyed houses had no mosquitoes. Distance to water bodies, vegetation and day temperature were significantly associated with mosquito density. Overall annual point estimates of EIR were 6.7, 9.3 and 9.6 infectious bites per annum for 2002, 2003 and 2004 respectively. Monthly mosquito density and EIR varied over the study period peaking in May during the wet season. The predicted and observed densities and EIR showed a strong seasonal and spatial pattern over the study area. CONCLUSIONS: Spatio-temporal maps of malaria transmission intensity obtained in this study are not only useful in understanding variability in malaria epidemiology over small areas but also provides a high resolution exposure surface that can be used to analyse the impact of malaria exposure on mortalit

‘Forgotten Europeans’: transnational minority activism in the age of European integration

YesThis article examines transnational activism by coalitions of national minorities in Europe from the early 20th century to the present, setting this within the broader ‘security versus democracy dilemma’ that continues to surround international discussions on minority rights. Specifically, we analyse two organisations – the European Nationalities Congress (1925–1938) and the Federal Union of European Nationalities (1949–) – which, while linked, have never been subject to a detailed comparison based on primary sources. In so far as comparisons do exist, they present these bodies in highly negative terms, as mere fronts for inherently particularistic nationalisms that threaten political stability, state integrity and peace. Our more in‐depth analysis provides a fresh and more nuanced perspective: it shows that, in both cases, concepts of European integration and ‘unity in diversity’ have provided the motivating goals and frameworks for transnational movements advocating common rights for all minorities and seeking positive interaction with the interstate world

Protein interaction mapping with ribosome-displayed using PLATO ORF libraries

Identifying physical interactions between proteins and other molecules is a critical aspect of biological analysis. Here we describe PLATO, an in vitro method for mapping such interactions by affinity enrichment of a library of full-length open reading frames displayed on ribosomes, followed by massively parallel analysis using DNA sequencing. We demonstrate the broad utility of the method by identifying known and new interacting partners of LYN kinase, patient autoantibodies and the small molecules gefitinib and dasatinib

An Analysis of Pregnancy-Related Mortality in the KEMRI/CDC Health and Demographic Surveillance System in Western Kenya

Background Pregnancy-related (PR) deaths are often a result of direct obstetric complications occurring at childbirth. Methods and Findings To estimate the burden of and characterize risk factors for PR mortality, we evaluated deaths that occurred between 2003 and 2008 among women of childbearing age (15 to 49 years) using Health and Demographic Surveillance System data in rural western Kenya. WHO ICD definition of PR mortality was used: “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the cause of death”. In addition, symptoms and events at the time of death were examined using the WHO verbal autopsy methodology. Deaths were categorized as either (i) directly PR: main cause of death was ascribed as obstetric, or (ii) indirectly PR: main cause of death was non-obstetric. Of 3,223 deaths in women 15 to 49 years, 249 (7.7%) were PR. One-third (34%) of these were due to direct obstetric causes, predominantly postpartum hemorrhage, abortion complications and puerperal sepsis. Two-thirds were indirect; three-quarters were attributable to human immunodeficiency virus (HIV/AIDS), malaria and tuberculosis. Significantly more women who died in lower socio-economic groups sought care from traditional birth attendants (p = 0.034), while less impoverished women were more likely to seek hospital care (p = 0.001). The PR mortality ratio over the six years was 740 (95% CI 651–838) per 100,000 live births, with no evidence of reduction over time (χ2 linear trend = 1.07; p = 0.3). Conclusions These data supplement current scanty information on the relationship between infectious diseases and poor maternal outcomes in Africa. They indicate low uptake of maternal health interventions in women dying during pregnancy and postpartum, suggesting improved access to and increased uptake of skilled obstetric care, as well as preventive measures against HIV/AIDS, malaria and tuberculosis among all women of childbearing age may help to reduce pregnancy-related mortality

Application of a synthetic human proteome to autoantigen discovery through PhIP-Seq

In this study, we improve on current autoantigen discovery approaches by creating a synthetic representation of the complete human proteome, the T7 “peptidome” phage display library (T7-Pep), and use it to profile the autoantibody repertoires of individual patients. We provide methods for 1) designing and cloning large libraries of DNA microarray-derived oligonucleotides encoding peptides for display on bacteriophage, and 2) analysis of the peptide libraries using high throughput DNA sequencing. We applied phage immunoprecipitation sequencing (PhIP-Seq) to identify both known and novel autoantibodies contained in the spinal fluid of three patients with paraneoplastic neurological syndromes. We also show how our approach can be used more generally to identify peptide-protein interactions and point toward ways in which this technology will be further developed in the future. We envision that PhIP-Seq can become an important new tool in autoantibody analysis, as well as proteomic research in general

Health Care-Seeking Behavior During Childhood Diarrheal Illness: Results of Health Care Utilization and Attitudes Surveys of Caretakers in Western Kenya, 2007-2010

We interviewed caretakers of 1,043 children 20,000 children on five separate subsequent occasions (May of 2009 to December 31, 2010) to assess healthcare seeking patterns for diarrhea. Diarrhea prevalence during the preceding 2 weeks ranged from 26% at baseline to 4–11% during 2009–2010. Caretakers were less likely to seek healthcare outside the home for infants (versus older children) with diarrhea (adjusted odds ratio [aOR] = 0.33, confidence interval [CI] = 0.12–0.87). Caretakers of children with reduced food intake (aOR = 3.42, CI = 1.37–8.53) and sunken eyes during their diarrheal episode were more likely to seek care outside home (aOR = 4.76, CI = 1.13–8.89). Caretakers with formal education were more likely to provide oral rehydration solution (aOR = 3.01, CI = 1.41–6.42) and visit a healthcare facility (aOR = 3.32, CI = 1.56–7.07). Studies calculating diarrheal incidence and healthcare seeking should account for seasonal trends. Improving caretakers' knowledge of home management could prevent severe diarrhea

ShoRAH: estimating the genetic diversity of a mixed sample from next-generation sequencing data

<p>Abstract</p> <p>Background</p> <p>With next-generation sequencing technologies, experiments that were considered prohibitive only a few years ago are now possible. However, while these technologies have the ability to produce enormous volumes of data, the sequence reads are prone to error. This poses fundamental hurdles when genetic diversity is investigated.</p> <p>Results</p> <p>We developed ShoRAH, a computational method for quantifying genetic diversity in a mixed sample and for identifying the individual clones in the population, while accounting for sequencing errors. The software was run on simulated data and on real data obtained in wet lab experiments to assess its reliability.</p> <p>Conclusions</p> <p>ShoRAH is implemented in C++, Python, and Perl and has been tested under Linux and Mac OS X. Source code is available under the GNU General Public License at <url>http://www.cbg.ethz.ch/software/shorah</url>.</p

Comparing verbal autopsy cause of death findings as determined by physician coding and probabilistic modelling: a public health analysis of 54 000 deaths in Africa and Asia.

BACKGROUND: Coverage of civil registration and vital statistics varies globally, with most deaths in Africa and Asia remaining either unregistered or registered without cause of death. One important constraint has been a lack of fit-for-purpose tools for registering deaths and assigning causes in situations where no doctor is involved. Verbal autopsy (interviewing care-givers and witnesses to deaths and interpreting their information into causes of death) is the only available solution. Automated interpretation of verbal autopsy data into cause of death information is essential for rapid, consistent and affordable processing. METHODS: Verbal autopsy archives covering 54 182 deaths from five African and Asian countries were sourced on the basis of their geographical, epidemiological and methodological diversity, with existing physician-coded causes of death attributed. These data were unified into the WHO 2012 verbal autopsy standard format, and processed using the InterVA-4 model. Cause-specific mortality fractions from InterVA-4 and physician codes were calculated for each of 60 WHO 2012 cause categories, by age group, sex and source. Results from the two approaches were assessed for concordance and ratios of fractions by cause category. As an alternative metric, the Wilcoxon matched-pairs signed ranks test with two one-sided tests for stochastic equivalence was used. FINDINGS: The overall concordance correlation coefficient between InterVA-4 and physician codes was 0.83 (95% CI 0.75 to 0.91) and this increased to 0.97 (95% CI 0.96 to 0.99) when HIV/AIDS and pulmonary TB deaths were combined into a single category. Over half (53%) of the cause category ratios between InterVA-4 and physician codes by source were not significantly different from unity at the 99% level, increasing to 62% by age group. Wilcoxon tests for stochastic equivalence also demonstrated equivalence. CONCLUSIONS: These findings show strong concordance between InterVA-4 and physician-coded findings over this large and diverse data set. Although these analyses cannot prove that either approach constitutes absolute truth, there was high public health equivalence between the findings. Given the urgent need for adequate cause of death data from settings where deaths currently pass unregistered, and since the WHO 2012 verbal autopsy standard and InterVA-4 tools represent relatively simple, cheap and available methods for determining cause of death on a large scale, they should be used as current tools of choice to fill gaps in cause of death data

Weekly miscarriage rates in a community-based prospective cohort study in rural western Kenya

Objective Information on adverse pregnancy outcomes is important to monitor the impact of public health interventions. Miscarriage is a challenging end point to ascertain and there is scarce information on its rate in low-income countries. The objective was to estimate the background rate and cumulative probability of miscarriage in rural western Kenya. Design This was a population-based prospective cohort. Participants and setting Women of childbearing age were followed prospectively to identify pregnancies and ascertain their outcomes in Siaya County, western Kenya. The cohort study was carried out in 33 adjacent villages under health and demographic surveillance. Outcome measure Miscarriage. Results Between 2011 and 2013, among 5536 women of childbearing age, 1453 pregnancies were detected and 1134 were included in the analysis. The cumulative probability was 18.9%. The weekly miscarriage rate declined steadily with increasing gestation until approximately 20 weeks. Known risk factors for miscarriage such as maternal age, gravidity, occupation, household wealth and HIV infection were confirmed. Conclusions This is the first report of weekly miscarriage rates in a rural African setting in the context of high HIV and malaria prevalence. Future studies should consider the involvement of community health workers to identify the pregnancy cohort of early gestation for better data on the actual number of pregnancies and the assessment of miscarriage