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

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

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

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 that individuals can be partitioned into clusters such that there is no interference between individuals in different clusters, that is, there is partial interference. In observational studies with partial interference, inverse probability weighted (IPW) estimators have been something else different possible treatment effects. However, the validity of IPW estimators depends on the propensity score being known or correctly modelled. Alternatively, one can estimate the treatment effect using an outcome regression model. In this paper, we propose doubly robust (DR) estimators that 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 and 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

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 (n = 310). 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 (−0:13 log microns; 95% CI: −0:23, −0:03 and −0:39 log microns; 95% CI: −0:72, −0:05, 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

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 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

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

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 (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

Capsaicin-sensitive vagal afferent neurons contribute to the detection of pathogenic bacterial colonization in the gut

Vagal activation can reduce inflammation and disease activity in various animal models of intestinal inflammation via the cholinergic anti-inflammatory pathway. In the current model of this pathway, activation of descending vagal efferents is dependent on a signal initiated by stimulation of vagal afferents. However, little is known about how vagal afferents are activated, especially in the context of subclinical or clinical pathogenic bacterial infection. To address this question, we first determined if selective lesions of capsaicin-sensitive vagal afferents altered c-Fos expression in the nucleus of the solitary tract (nTS) after mice were inoculated with either Campylobacter jejuni or Salmonella typhimurium. Our results demonstrate that the activation of nTS neurons by intraluminal pathogenic bacteria is dependent on intact, capsaicin sensitive vagal afferents. We next determined if inflammatory mediators could cause the observed increase in c-Fos expression in the nTS by a direct action on vagal afferents. This was tested by the use of single-cell calcium measurements in cultured vagal afferent neurons. We found that tumor necrosis factor alpha (TNFα) and lipopolysaccharide (LPS) directly activate cultured vagal afferent neurons and that almost all TNFα and LPS responsive neurons were sensitive to capsaicin. We conclude that activation of the afferent arm of the parasympathetic neuroimmune reflex by pathogenic bacteria in the gut is dependent on capsaicin sensitive vagal afferent neurons and that the release of inflammatory mediators into intestinal tissue can be directly sensed by these neurons