Inverse probability weighted estimators of vaccine effects accommodating partial interference and censoring.

Estimating population-level effects of a vaccine is challenging because there may be interference, that is, the outcome of one individual may depend on the vaccination status of another individual. Partial interference occurs when individuals can be partitioned into groups such that interference occurs only within groups. In the absence of interference, inverse probability weighted (IPW) estimators are commonly used to draw inference about causal effects of an exposure or treatment. Tchetgen Tchetgen and VanderWeele proposed a modified IPW estimator for causal effects in the presence of partial interference. Motivated by a cholera vaccine study in Bangladesh, this paper considers an extension of the Tchetgen Tchetgen and VanderWeele IPW estimator to the setting where the outcome is subject to right censoring using inverse probability of censoring weights (IPCW). Censoring weights are estimated using proportional hazards frailty models. The large sample properties of the IPCW estimators are derived, and simulation studies are presented demonstrating the estimators' performance in finite samples. The methods are then used to analyze data from the cholera vaccine study.

Estimating exposure to neighborhood crime by race and ethnicity for public health research.

BACKGROUND: Police-reported crime data (hereafter "crime") is routinely used as a psychosocial stressor in public health research, yet few studies have jointly examined (a) differences in crime exposure based on participant race and ethnicity, (b) differences in measures of crime exposure, and (c) considerations for how exposure to police is captured in police-recorded crime data. We estimate neighborhood exposure to crime and discuss the implications of structural differences in exposure to crime and police based on race and ethnicity. METHODS: Using GPS coordinates from 1188 participants in the Newborn Epigenetics Study, we estimated gestational exposure to crime provided by the Durham, North Carolina, Police Department within (a) 800 m and (b) the Census block group of residence. We controlled for non-overlapping spatial boundaries in crime, Census, residential, and police data to report crime spatial (crime per km2) and population (crime per 1000 people per km2) density. RESULTS: We demonstrate dramatic disparities in exposure to crime based on participant race and ethnicity and highlight variability in these disparities based on the type of crime and crime measurement method chosen. CONCLUSIONS: Public health researchers should give thoughtful consideration when using police-reported crime data to measure and model exposure to crime in the United States, as police-reported data encompasses joint exposure to police and crime in the neighborhood setting.

Randomization inference with general interference and censoring.

Interference occurs between individuals when the treatment (or exposure) of one individual affects the outcome of another individual. Previous work on causal inference methods in the presence of interference has focused on the setting where it is a priori assumed that there is "partial interference," in the sense that individuals can be partitioned into groups wherein there is no interference between individuals in different groups. Bowers et al. (2012, Political Anal, 21, 97-124) and Bowers et al. (2016, Political Anal, 24, 395-403) consider randomization-based inferential methods that allow for more general interference structures in the context of randomized experiments. In this paper, extensions of Bowers et al. that allow for failure time outcomes subject to right censoring are proposed. Permitting right-censored outcomes is challenging because standard randomization-based tests of the null hypothesis of no treatment effect assume that whether an individual is censored does not depend on treatment. The proposed extension of Bowers et al. to allow for censoring entails adapting the method of Wang et al. (2010, Biostatistics, 11, 676-692) for two-sample survival comparisons in the presence of unequal censoring. The methods are examined via simulation studies and utilized to assess the effects of cholera vaccination in an individually randomized trial of 73 000 children and women in Matlab, Bangladesh.

The Where and How for Reaching Transgender Women and Men Who Have Sex with Men with HIV Prevention Services in Guatemala.

This study aims to describe the transgender women and men who have sex with men (MSM) missed through venue-based sampling and illustrate how data on venues can be used to prioritize service delivery. Respondent-driven sampling (RDS) and time-location sampling (TLS) were used concurrently in 2010 for behavioral surveillance among MSM and transgender women in Guatemala City. RDS recruits who did not frequent venues (n = 106) were compared to TLS recruits (n = 609). TLS participants recruited at different types of venues were compared. RDS recruits who did not frequent venues were less educated, less likely to identify as gay, more likely to have concurrent partners and female sexual partners. Participants recruited at NGOs, saunas, hotels, streets and parks had more partners, were more likely to receive money for sex or have concurrent partners. Prevention programs for MSM and transgender women should characterize social venues and people that frequent them and improve service coverage through venues and social networks.

Distance to testing sites and its association with timing of HIV diagnosis.

Early HIV diagnosis enables prompt treatment initiation, thereby contributing to decreased morbidity, mortality, and transmission. We aimed to describe the association between distance from residence to testing sites and HIV disease stage at diagnosis. Using HIV surveillance data, we identified all new HIV diagnoses made at publicly funded testing sites in central North Carolina during 2005-2013. Early-stage HIV was defined as acute HIV (antibody-negative test with a positive HIV RNA) or recent HIV (normalized optical density <0.8 on the BED assay for non-AIDS cases); remaining diagnoses were considered post-early-stage HIV. Street distance between residence at diagnosis and (1) the closest testing site and (2) the diagnosis site was dichotomized at 5 miles. We fit log-binomial models using generalized estimating equations to estimate prevalence ratios (PR) and robust 95% confidence intervals (CI) for post-early-stage diagnoses by distance. Models were adjusted for race/ethnicity and testing period. Most of the 3028 new diagnoses were black (N = 2144; 70.8%), men who have sex with men (N = 1685; 55.7%), and post-early-stage HIV diagnoses (N = 2010; 66.4%). Overall, 1145 (37.8%) cases traveled <5 miles for a diagnosis. Among cases traveling ≥5 miles for a diagnosis, 1273 (67.6%) lived <5 miles from a different site. Residing ≥5 miles from a testing site was not associated with post-early-stage HIV (adjusted PR, 95% CI: 0.98, 0.92-1.04), but traveling ≥5 miles for a diagnosis was associated with higher post-early HIV prevalence (1.07, 1.02-1.13). Most of the elevated prevalence observed in cases traveling ≥5 miles for a diagnosis occurred among those living <5 miles from a different site (1.09, 1.03-1.16). Modest increases in post-early-stage HIV diagnosis were apparent among persons living near a site, but choosing to travel longer distances to test. Understanding reasons for increased travel distances could improve accessibility and acceptability of HIV services and increase early diagnosis rates.

Temporal trends in syphilis and gonorrhea incidences in guangdong province, china.

The high burden of syphilis in China presents a unique opportunity to examine temporal trends. This study used wavelet transformation and Fourier analysis to assess the presence of temporal oscillations in the incidence of syphilis among adults, gonorrhea, and congenital syphilis over 11 years in China's largest province. This study found a significant annual oscillation trend in the incidence of adult syphilis, consistent with a peak during July-September, which was 4-fold higher than the trough, which occurred during January-March. A similar but dampened trend was observed in the incidence of gonorrhea, and no trend was observed for the incidence of congenital syphilis. Further research on the temporal oscillation of the incidence of syphilis is needed.

Assessing effects of cholera vaccination in the presence of interference.

Interference occurs when the treatment of one person affects the outcome of another. For example, in infectious diseases, whether one individual is vaccinated may affect whether another individual becomes infected or develops disease. Quantifying such indirect (or spillover) effects of vaccination could have important public health or policy implications. In this article we use recently developed inverse-probability weighted (IPW) estimators of treatment effects in the presence of interference to analyze an individually-randomized, placebo-controlled trial of cholera vaccination that targeted 121,982 individuals in Matlab, Bangladesh. Because these IPW estimators have not been employed previously, a simulation study was also conducted to assess the empirical behavior of the estimators in settings similar to the cholera vaccine trial. Simulation study results demonstrate the IPW estimators can yield unbiased estimates of the direct, indirect, total, and overall effects of vaccination when there is interference provided the untestable no unmeasured confounders assumption holds and the group-level propensity score model is correctly specified. Application of the IPW estimators to the cholera vaccine trial indicates the presence of interference. For example, the IPW estimates suggest on average 5.29 fewer cases of cholera per 1000 person-years (95% confidence interval 2.61, 7.96) will occur among unvaccinated individuals within neighborhoods with 60% vaccine coverage compared to neighborhoods with 32% coverage. Our analysis also demonstrates how not accounting for interference can render misleading conclusions about the public health utility of vaccination.

Geographic analysis of individual and environmental risk factors for hypospadias births.

BACKGROUND: Hypospadias is a relatively common birth defect affecting the male urinary tract. We explored the etiology of hypospadias by examining its spatial distribution in North Carolina and the spatial clustering of residuals from individual and environmental risk factors. METHODS: We used data collected by the North Carolina Birth Defects Monitoring Program from 2003 to 2005 to estimate local Moran's I statistics to identify geographic clustering of overall and severe hypospadias, using 995 overall cases and 16,013 controls. We conducted logistic regression and local Moran's I statistics on standardized residuals to consider the contribution of individual variables (maternal age, maternal race/ethnicity, maternal education, smoking, parity, and diabetes) and environmental variables (block group land cover) to this clustering. RESULTS: Local Moran's I statistics indicated significant clustering of overall and severe hypospadias in eastern central North Carolina. Spatial clustering of hypospadias persisted when controlling for individual factors, but diminished somewhat when controlling for environmental factors. In adjusted models, maternal residence in a block group with more than 5% crop cover was associated with overall hypospadias (odds ratio = 1.22; 95% confidence interval = 1.04-1.43); that is living in a block group with greater than 5% crop cover was associated with a 22% increase in the odds of having a baby with hypospadias. Land cover was not associated with severe hypospadias. CONCLUSION: This study illustrates the potential contribution of mapping in generating hypotheses about disease etiology. Results suggest that environmental factors including proximity to agriculture may play some role in the spatial distribution of hypospadias. Birth Defects Research (Part A) 100:887-894, 2014. © 2014 Wiley Periodicals, Inc.

Multilevel and spatial analysis of syphilis in Shenzhen, China, to inform spatially targeted control measures.

OBJECTIVES: The present study investigates the varied spatial distribution of syphilis cases in Shenzhen, China, and explores the individual-, neighbourhood- and district-level factors affecting the distribution. METHODS: This study uses spatial analysis and multi-level generalised estimating equations to explore the spatial distribution of reported syphilis cases among individuals in Shenzhen, Guangdong Province, China. The spatial distribution of primary/secondary and latent cases was investigated using the Moran's I-statistic. Primary/secondary syphilis cases were compared with all syphilis cases using a three-level model with individual (n=6496), neighbourhood (n=55) and district (n=6) levels. RESULTS: A total of 6496 syphilis cases were reported in 2009 with 35.8% primary and secondary syphilis cases. Both primary/secondary syphilis cases (Moran's I value=0.33, p<0.01) and latent syphilis cases (Moran's I value=0.19, p<0.01) showed significant spatial clustering at the neighbourhood level. Adjusting for the number of reporting hospitals, the best model found that the following characteristics were associated with primary/secondary syphilis infection: individuals who are younger in age (p=0.003), male (p<0.001), migrant labourers (p=0.047) and those who live in districts with a higher gross domestic product (p<0.001). CONCLUSIONS: There is substantial clustering of primary and secondary syphilis cases at the neighbourhood level in Shenzhen, suggesting the need for greater STD health service provision in these clustered neighbourhoods. Spatially targeted syphilis control measures may be useful to optimise testing, treatment and partner services.

Gestational exposure to neighborhood police-reported crime and early childhood blood pressure in Durham, NC.

Gestational exposure to police-reported crime is associated with adverse birth outcomes, but no previous research has evaluated the effects of gestational crime exposure on early childhood health or attempted to disentangle the health effects of neighborhood crime from the effects of neighborhood policing. Using data from 672 Newborn Epigenetics Study participants, we evaluate the effects of gestational exposure to violent crime and racialized drug policing on early childhood blood pressure. We demonstrate that violence and drug policing are consistently associated with increased blood pressure among children born to Black participants but not White or Latinx participants.

Ethnic density and preterm birth in African-, Caribbean-, and US-born non-Hispanic black populations in New York City.

Segregation studies suggest that the health of blacks in the United States is poorer in majority-black compared with mixed-race neighborhoods. However, segregation studies have not examined black immigrants, who may benefit from social support and country-of-origin foods in black immigrant areas. The authors used 1995-2003 New York City birth records and a spatial measure of ethnic density to conduct a cross-sectional investigation of the risks of preterm birth for African-, Caribbean-, and US-born non-Hispanic black women associated with neighborhood-level African-, Caribbean-, and US-born non-Hispanic black density, respectively. Preterm birth risk differences were computed from logistic model coefficients, comparing neighborhoods in the 90th percentile of ethnic density with those in the 10th percentile. African black preterm birth risks increased with African density, especially in more deprived neighborhoods, where the risk difference was 6.1 per 1,000 (95% confidence interval: 1.9, 10.2). There was little evidence of an ethnic density effect among non-Hispanic black Caribbeans. Among US-born non-Hispanic blacks, an increase in preterm birth risk associated with US-born black density was observed in more deprived neighborhoods only (risk difference = 12.5, 95% confidence interval: 6.6, 18.4). Ethnic density seems to be more strongly associated with preterm birth for US-born non-Hispanic blacks than for non-Hispanic black immigrants.

Sex work, discrimination, drug use and violence: a pattern for HIV risk among transgender sex workers compared to MSM sex workers and other MSM in Guatemala.

The risk of HIV infection is higher among transgender women and cisgender men who have sex with men (MSM) compared to the general population due in part to social and contextual factors. This study aimed to determine the prevalence and association of alcohol and drug abuse, discrimination and violence among transgender sex workers compared to cisgender male sex workers and cisgender men who had not received money for sex in Guatemala City. In 2010, transgender women and cisgender men who had had sex with men or transgender women were recruited into a cross-sectional behavioural survey. Among transgender women, 86% received money for sex in the past year. Transgender sex workers were more likely to use drugs and binge drink, three times as likely to be discriminated against and eight times as likely to be forced to have sex compared to non-sex worker men. Male sex workers were twice as likely to use illicit drugs or experience physical violence and six times as likely to experience forced sex compared to non-sex worker men. Transgender and male sex workers would benefit from harm reduction for substance use, violence prevention, response and strategies to mitigate discrimination.

Evidence of localized clustering of gastroschisis births in North Carolina, 1999-2004.

Examining the geographic distribution of birth defects can be useful in exploratory etiologic research. Identification of clusters of certain defects may uncover possible environmental or socio-economic risk factors and assist with the generation of hypotheses about underlying causes of these conditions. In North Carolina, the prevalence of gastroschisis, a serious abdominal wall defect, has increased over the past decade and anecdotal evidence from clinicians suggests the possibility of clustering of this condition. This study uses a spatial scan statistic to identify the location and extent of clusters of gastroschisis births in North Carolina between 1999 and 2004. Data on cases of gastroschisis were obtained from the North Carolina Birth Defect Monitoring Program (NCBDMP) and control births were chosen from all resident live births without birth defects contained in the North Carolina composite linked birth files. The clusters were controlled for five major risk factors (maternal age, race, parity, Medicaid status, maternal smoking) to ensure that the clusters were not artifacts of unequal population distribution. Results indicate a localized cluster of gastroschisis in the rural southern Piedmont of North Carolina which persists even after controlling for all major risk factors. Adjusting for these risk factors shifted the location of the cluster substantially, demonstrating the importance of adjusting for underlying population distribution. Since clusters persisted after adjusting for individual-level risk factors, environmental contaminants may explain the excess of gastroschisis cases. This study is among the first to assess spatial clustering of gastroschisis using GIS methods. This study also demonstrates the importance of controlling for covariates in spatial analysis and illustrates the usefulness of the spatial scan statistic in exploratory etiologic research.

Doubly Robust Estimation in Observational Studies with Partial Interference.

Interference occurs when the treatment (or exposure) of one individual affects the outcomes of others. In some settings it may be reasonable to assume individuals can be partitioned into clusters such that there is no interference between individuals in different clusters, i.e., there is partial interference. In observational studies with partial interference, inverse probability weighted (IPW) estimators have been proposed of different possible treatment effects. However, the validity of IPW estimators depends on the propensity score being known or correctly modeled. Alternatively, one can estimate the treatment effect using an outcome regression model. In this paper, we propose doubly robust (DR) estimators which utilize both models and are consistent and asymptotically normal if either model, but not necessarily both, is correctly specified. Empirical results are presented to demonstrate the DR property of the proposed estimators, as well as the efficiency gain of DR over IPW estimators when both models are correctly specified. The different estimators are illustrated using data from a study examining the effects of cholera vaccination in Bangladesh.

Determinants of environmental styrene exposure in Gulf coast residents.

BACKGROUND: In a previous study of exposure to oil-related chemicals in Gulf coast residents, we measured blood levels of volatile organic compounds. Levels of styrene were substantially elevated compared to a nationally representative sample. We sought to identify factors contributing to these levels, given the opportunities for styrene exposure in this community. METHODS: We measured blood styrene levels in 667 Gulf coast residents and compared participants' levels of blood styrene to a nationally representative sample. We assessed personal and environmental predictors of blood styrene levels using linear regression and predicted the risk of elevated blood styrene (defined as above the National Health and Nutrition Examination Survey 95th percentile) using modified Poisson regression. We assessed exposure to styrene using questionnaire data on recent exposure opportunities and leveraged existing databases to assign ambient styrene exposure based on geocoded residential location. RESULTS: These Gulf coast residents were 4-6 times as likely as the nationally representative sample to have elevated blood styrene levels. The change in styrene (log ng/mL) was 0.42 (95% CI: 0.34, 0.51) for smoking, 0.34 (0.09, 0.59) for time spent in vehicles and 1.10 (0.31, 1.89) for boats, and -0.41 (-0.73, -0.10) for fall/winter blood draws. Residential proximity to industrial styrene emissions did not predict blood styrene levels. Ambient styrene predicted elevated blood styrene in subgroups. CONCLUSIONS: Personal predictors of increasing blood styrene levels included smoking, vehicle emissions, and housing characteristics. There was a suggestive association between ambient and blood styrene. Our measures of increased regional exposure opportunity do not fully explain the observed elevated blood styrene levels in this population.

Environmental Styrene Exposure and Sensory and Motor Function in Gulf Coast Residents.

BACKGROUND: Although styrene is an established neurotoxicant at occupational exposure levels, its neurotoxicity has not been characterized in relation to general population exposures. Further, occupational research to date has focused on central nervous system impairment. OBJECTIVE: We assessed styrene-associated differences in sensory and motor function among Gulf coast residents. METHODS: We used 2011 National Air Toxics Assessment estimates of ambient styrene to determine exposure levels for 2,956 nondiabetic Gulf state residents enrolled in the Gulf Long-term Follow-up Study, and additionally measured blood styrene concentration in a subset of participants 1 to 2 y after enrollment ([Formula: see text]). Participants completed an enrollment telephone interview and a comprehensive test battery to assess sensory and motor function during a clinical follow-up exam 2 to 4 y later. Detailed covariate information was ascertained at enrollment via telephone interview. We used multivariate linear regression to estimate continuous differences in sensory and motor function, and log-binomial regression to estimate prevalence ratios for dichotomous outcomes. We estimated associations of both ambient and blood styrene exposures with sensory and motor function, independently for five unique tests. RESULTS: Those participants in the highest 25% vs. lowest 75% of ambient exposure and those in the highest 10% vs. lowest 90% of blood styrene had slightly diminished visual contrast sensitivity. Mean vibrotactile thresholds were lower among those in the highest vs. lowest quartile of ambient styrene and the highest 10% vs. lowest 90% of blood styrene ([Formula: see text] log microns; 95% CI: [Formula: see text], [Formula: see text] and [Formula: see text] log microns; 95% CI: [Formula: see text], [Formula: see text], respectively). The highest vs. lowest quartile of ambient styrene was associated with significantly poorer postural stability, and (unexpectedly) with significantly greater grip strength. DISCUSSION: We observed associations between higher styrene exposure and poorer visual, sensory, and vestibular function, though we did not detect associations with reduced voluntary motor system performance. Associations were more consistent for ambient exposures, but we also found notable associations with measured blood styrene. https://doi.org/10.1289/EHP3954.

Strengthening long-lasting insecticidal nets effectiveness monitoring using retrospective analysis of cross-sectional, population-based surveys across sub-Saharan Africa.

Bed nets averted 68% of malaria cases in Africa between 2000 and 2015. However, concerns over insecticide resistance, bed net durability and the effectiveness of long-lasting insecticidal nets (LLIN) are growing. To assess the effectiveness of LLINs of different ages and insecticides against malaria, we conducted a population-based, cross-sectional study using data from 162,963 children younger than 5 years of age participating in 33 Demographic and Health and Malaria Indicator Surveys conducted in 21 countries between 2009 and 2016. We used Bayesian logistic regression to estimate associations between LLIN age, insecticide type, and malaria. Children sleeping under LLINs the previous night experienced 21% lower odds of malaria infection than children who did not (odds ratio [OR] 0.79; 95% Uncertainty Interval [UI] 0.76-0.82). Nets less than one year of age exhibited the strongest protective effect (OR 0.75; 95% UI 0.72-0.79), and protection weakened as net age increased. LLINs containing different insecticides exhibited similar protection (ORdeltamethrin 0.78 [0.75-0.82]; ORpermethrin 0.79 [0.75-0.83]; ORalphacypermethrin 0.85 [0.76-0.94]). Freely-available, population-based surveys can enhance and guide current entomological monitoring amid concerns of insecticide resistance and bed net durability, and be used with locally-collected data to support decisions on LLIN redistribution campaign timing which insecticide to use.

Environmental styrene exposure and neurologic symptoms in U.S. Gulf coast residents.

BACKGROUND: Styrene is an established neurotoxicant at occupational levels, but effects at levels relevant to the general population have not been studied. We examined the neurologic effects of environmental styrene exposure among U.S. Gulf coast residents. METHODS: We used National Air Toxics Assessment (NATA) 2011 estimates of ambient styrene concentrations to assign exposure levels for 21,962 non-diabetic Gulf state residents, and additionally measured blood styrene concentration in a subset of participants (n = 874). Neurologic symptoms, as well as detailed covariate information, were ascertained via telephone interview. We used log-binomial regression to estimate prevalence ratios (PR) and 95% confidence intervals (95% CI) for cross-sectional associations between both ambient and blood styrene levels and self-reported neurologic symptoms. We estimated associations independently for ten unique symptoms, as well as for the presence of any neurologic, central nervous system (CNS), or peripheral nervous system (PNS) symptoms. We also examined heterogeneity of associations with estimated ambient styrene levels by race and sex. RESULTS: One-third of participants reported at least one neurologic symptom. The highest quartile of estimated ambient styrene was associated with one or more neurologic (PR, 1.12; 95% CI: 1.07,1.18), CNS (PR, 1.17; 95% CI: 1.11,1.25), and PNS (PR, 1.16; 95% CI: 1.09,1.25) symptom. Results were less consistent for biomarker analyses, but blood styrene level was suggestively associated with nausea (PR, 1.78; 95% CI: 1.04, 3.03). In stratified analyses, we observed the strongest effects among non-White participants. CONCLUSIONS: Increasing estimated ambient styrene concentration was consistently associated with increased prevalence of neurologic symptoms. Associations between blood styrene levels and some neurologic symptoms were suggestive. Environmental styrene exposure levels may be sufficient to elicit symptomatic neurotoxic effects.

The links between agriculture, Anopheles mosquitoes, and malaria risk in children younger than 5 years in the Democratic Republic of the Congo: a population-based, cross-sectional, spatial study.

BACKGROUND: The relationship between agriculture, Anopheles mosquitoes, and malaria in Africa is not fully understood, but it is important for malaria control as countries consider expanding agricultural projects to address population growth and food demand. Therefore, we aimed to assess the effect of agriculture on Anopheles biting behaviour and malaria risk in children in rural areas of the Democratic Republic of the Congo (DR Congo). METHODS: We did a population-based, cross-sectional, spatial study of rural children (<5 years) in the DR Congo. We used information about the presence of malaria parasites in each child, as determined by PCR analysis of dried-blood spots from the 2013-14 DR Congo Demographic and Health Survey (DHS). We also used data from the DHS, a longitudinal entomological study, and available land cover and climate data to evaluate the relationships between agriculture, Anopheles biting behaviour, and malaria prevalence. Satellite imagery was used to measure the percentage of agricultural land cover around DHS villages and Anopheles sites. Anopheles biting behaviour was assessed by Human Landing Catch. We used probit regression to assess the relationship between agriculture and the probability of malaria infection, as well as the relationship between agriculture and the probability that a mosquito was caught biting indoors. FINDINGS: Between Aug 13, 2013, and Feb 13, 2014, a total of 9790 dried-blood spots were obtained from the DHS, of which 4612 participants were included in this study. Falciparum malaria infection prevalence in rural children was 38·7% (95% uncertainty interval [UI] 37·3-40·0). Increasing exposure to agriculture was associated with increasing malaria risk with a high posterior probability (estimate 0·07, 95% UI -0·04 to 0·17; posterior probability [estimate >0]=0·89), with the probability of malaria infection increased between 0·2% (95% UI -0·1 to 3·4) and 2·6% (-1·5 to 6·6) given a 15% increase in agricultural cover, depending on other risk factors. The models predicted that large increases in agricultural cover (from 0% to 75%) increase the probability of infection by as much as 13·1% (95% UI -7·3 to 28·9). Increased risk might be due to Anopheles gambiae sensu lato, whose probability of biting indoors increased between 11·3% (95% UI -15·3 to 25·6) and 19·7% (-12·1 to 35·9) with a 15% increase in agriculture. INTERPRETATION: Malaria control programmes must consider the possibility of increased risk due to expanding agriculture. Governments considering initiating large-scale agricultural projects should therefore also consider accompanying additional malaria control measures. FUNDING: National Institutes of Health, National Science Foundation, Bill & Melinda Gates Foundation, President's Malaria Initiative, and Royster Society of Fellows at the University of North Carolina at Chapel Hill.

Computational identification of reassortments in avian influenza viruses.

The avian influenza virus (AIV) has eight genomic segments (hemagglutinin [HA], neuraminidase [NA], RNA polymerase subunit A [PA], RNA polymerase subunit B1 [PB1], RNA polymerase subunit B2 [PB2], nucleoprotein [NP], nonstructural gene [NS], and matrix protein [M]). The genetic reassortments, recombinations, and mutations lead to a rapid emergence of novel genotypes of the AIVs during their evolution. These emerging viruses provide a large reservoir for pandemic strains. Here we describe a novel computational strategy for genetic reassortment identification. In contrast to the traditional phylogenetic approaches, our method views the genotypes through the modules in networks. Genetic segments with short phylogenetic distance are grouped into modules. Our method is not limited to the number of sequences. We applied this method in reassortment identification of NP segments in H5N1 AIVs. We identified two new potential reassortments for H5N1 AIVs beyond the reported genotypes in literature.