Publications by authors named "Alan E Hubbard"

106 Publications

Epigenetic aging biomarkers and occupational exposure to benzene, trichloroethylene and formaldehyde.

Environ Int 2021 Sep 21;158:106871. Epub 2021 Sep 21.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Rockville, MD 20850, USA.

Epigenetic aging biomarkers are associated with increased morbidity and mortality. We evaluated if occupational exposure to three established chemical carcinogens is associated with acceleration of epigenetic aging. We studied workers in China occupationally exposed to benzene, trichloroethylene (TCE) or formaldehyde by measuring personal air exposures prior to blood collection. Unexposed controls matched by age and sex were selected from nearby factories. We measured leukocyte DNA methylation (DNAm) in peripheral white blood cells using the Infinium HumanMethylation450 BeadChip to calculate five epigenetic aging clocks and DNAmTL, a biomarker associated with leukocyte telomere length and cell replication. We tested associations between exposure intensity and epigenetic age acceleration (EAA), defined as the residuals of regressing the DNAm aging biomarker on chronological age, matching factors and potential confounders. Median differences in EAA between exposure groups were tested using a permutation test with exact p-values. Epigenetic clocks were strongly correlated with age (Spearman r > 0.8) in all three occupational studies. There was a positive exposure-response relationship between benzene and the Skin-Blood Clock EAA biomarker: median EAA was -0.91 years in controls (n = 44), 0.78 years in workers exposed to <10 ppm (n = 41; mean benzene = 1.35 ppm; p = 0.034 vs. controls), and 2.10 years in workers exposed to ≥10 ppm (n = 9; mean benzene = 27.3 ppm; p = 0.019 vs. controls; p = 0.0021). In the TCE study, control workers had a median Skin-Blood Clock EAA of -0.54 years (n = 71) compared to 1.63 years among workers exposed to <10 ppm of TCE (n = 27; mean TCE = 4.22 ppm; p = 0.035). We observed no evidence of EAA associations with formaldehyde exposure (39 controls, 31 exposed). Occupational benzene and TCE exposure were associated with increased epigenetic age acceleration measured by the Skin-Blood Clock. For TCE, there was some evidence of epigenetic age acceleration for lower exposures compared to controls. Our results suggest that some chemical carcinogens may accelerate epigenetic aging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envint.2021.106871DOI Listing
September 2021

City-wide school-located influenza vaccination: A retrospective cohort study.

Vaccine 2021 10 14;39(42):6302-6307. Epub 2021 Sep 14.

Division of Epidemiology & Biostatistics, University of California, Berkeley, CA, United States.

Background: We measured the effectiveness of a city-wide school-located influenza vaccination (SLIV) program implemented in over 102 elementary schools in Oakland, California.

Methods: We conducted a retrospective cohort study among Kaiser Permanente Northern California (KPNC) members of all ages residing in either the intervention or a multivariate-matched comparison site from September 2011 - August 2017. Outcomes included medically attended acute respiratory illness (MAARI), influenza hospitalization, and Oseltamivir prescriptions. We estimated difference-in-differences (DIDs) in 2014-15, 2015-16, and 2016-17 using generalized linear models and adjusted for race, ethnicity, age, sex, health plan, and language.

Results: Pre-intervention member characteristics were similar between sites. The proportion of KPNC members vaccinated for influenza by KPNC or the SLIV program was 8-11% higher in the intervention site than the comparison site during the intervention period. Among school-aged children, SLIV was associated with lower Oseltamivir prescriptions per 1,000 (DIDs: -3.5 (95% CI -5.5, -1.5) in 2015-16; -4.0 (95% CI -6.5, -1.6) in 2016-17) but not with other outcomes. SLIV was associated with lower MAARI per 1,000 in adults 65 + years (2014-15: -13.2, 95% CI -23.2, -3.2; 2015-16: -21.5, 95% CI -31.1, -11.9; 2016-17: -13.0, 95% CI -23.2, -2.9). There were few significant associations with other outcomes among adults.

Conclusions: A city-wide SLIV intervention was associated with higher influenza vaccination coverage, lower Oseltamivir prescriptions in school-aged children, and lower MAARI among people over 65 years, suggesting possible indirect effects of SLIV among older adults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vaccine.2021.08.099DOI Listing
October 2021

Telomere length is associated with growth in children in rural Bangladesh.

Elife 2021 09 8;10. Epub 2021 Sep 8.

Division of Epidemiology and Biostatistics, School of Public Health, University of California, Berkeley, Berkeley, United States.

Background: Previously, we demonstrated that a water, sanitation, handwashing, and nutritional intervention improved linear growth and was unexpectedly associated with shortened childhood telomere length (TL) (Lin et al., 2017). Here, we assessed the association between TL and growth.

Methods: We measured relative TL in whole blood from 713 children. We reported differences between the 10th percentile and 90th percentile of TL or change in TL distribution using generalized additive models, adjusted for potential confounders.

Results: In cross-sectional analyses, long TL was associated with a higher length-for-age Z score at age 1 year (0.23 SD adjusted difference in length-for-age Z score [95% CI 0.05, 0.42; FDR-corrected p-value = 0.01]). TL was not associated with other outcomes.

Conclusions: Consistent with the , our previous trial findings support an adaptive role for telomere attrition, whereby active TL regulation is employed as a strategy to address 'emergency states' with increased energy requirements such as rapid growth during the first year of life. Although short periods of active telomere attrition may be essential to promote growth, this study suggests that a longer overall initial TL setting in the first 2 years of life could signal increased resilience against future telomere erosion events and healthy growth trajectories.

Funding: Funded by the Bill and Melinda Gates Foundation.

Clinical Trial Number: NCT01590095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7554/eLife.60389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494482PMC
September 2021

Acute myocardial infarction associated with abacavir and tenofovir based antiretroviral drug combinations in the United States.

AIDS Res Ther 2021 09 6;18(1):57. Epub 2021 Sep 6.

Division of Epidemiology, School of Public Health, University of California Berkeley, Berkeley, CA, USA.

Introduction: Although individual antiretroviral drugs have been shown to be associated with elevated cardiovascular disease (CVD) risk, data are limited on the role of antiretroviral drug combinations. Therefore, we sought to investigate CVD risk associated with antiretroviral drug combinations.

Methods: Using an administrative health-plan dataset, risk of acute myocardial infarction (AMI) associated with current exposure to antiretroviral drug combinations was assessed among persons living with HIV receiving antiretroviral therapy (ART) across the U.S. from October 2009 through December 2014. To account for confounding-by-indication and for factors simultaneously acting as causal mediators and confounders, we applied inverse probability of treatment weighted marginal structural models to longitudinal data of patients.

Results: Over 114,417 person-years (n = 73,071 persons) of ART exposure, 602 cases of AMI occurred at an event rate of 5.26 (95% CI: 4.86, 5.70)/1000 person-years. Of the 14 antiretroviral drug combinations studied, persons taking abacavir-lamivudine-darunavir had the highest incidence rate (IR: 11/1000; 95% CI: 7.4-16.0) of AMI. Risk (HR; 95% CI) of AMI was elevated for current exposure to abacavir-lamivudine-darunavir (1.91; 1.27-2.88), abacavir-lamivudine-atazanavir (1.58; 1.08-2.31), and tenofovir-emtricitabine-raltegravir (1.35; 1.07-1.71). Tenofovir-emtricitabine-efavirenz was associated with reduced risk (0.65; 0.54-0.78). Abacavir-lamivudine-darunavir was associated with increased risk of AMI beyond that expected of abacavir alone, likely attributable to darunavir co-administration. We did not find an elevated risk of AMI when abacavir-lamivudine was combined with efavirenz or raltegravir.

Conclusion: The antiretroviral drug combinations abacavir-lamivudine-darunavir, abacavir-lamivudine-atazanavir and tenofovir-emtricitabine-raltegravir were found to be associated with elevated risk of AMI, while tenofovir-emtricitabine-efavirenz was associated with a lower risk. The AMI risk associated with abacavir-lamivudine-darunavir was greater than what was previously described for abacavir, which could suggest an added risk from darunavir. The results should be confirmed in additional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12981-021-00383-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419948PMC
September 2021

Exposure to arsenic at different life-stages and DNA methylation meta-analysis in buccal cells and leukocytes.

Environ Health 2021 07 9;20(1):79. Epub 2021 Jul 9.

Division of Environmental Health Sciences, School of Public Health, University of California, 2121 Berkeley Way, Room 5302, Berkeley, Berkeley, CA, 94720, USA.

Background: Arsenic (As) exposure through drinking water is a global public health concern. Epigenetic dysregulation including changes in DNA methylation (DNAm), may be involved in arsenic toxicity. Epigenome-wide association studies (EWAS) of arsenic exposure have been restricted to single populations and comparison across EWAS has been limited by methodological differences. Leveraging data from epidemiological studies conducted in Chile and Bangladesh, we use a harmonized data processing and analysis pipeline and meta-analysis to combine results from four EWAS.

Methods: DNAm was measured among adults in Chile with and without prenatal and early-life As exposure in PBMCs and buccal cells (N = 40, 850K array) and among men in Bangladesh with high and low As exposure in PBMCs (N = 32, 850K array; N = 48, 450K array). Linear models were used to identify differentially methylated positions (DMPs) and differentially variable positions (DVPs) adjusting for age, smoking, cell type, and sex in the Chile cohort. Probes common across EWAS were meta-analyzed using METAL, and differentially methylated and variable regions (DMRs and DVRs, respectively) were identified using comb-p. KEGG pathway analysis was used to understand biological functions of DMPs and DVPs.

Results: In a meta-analysis restricted to PBMCs, we identified one DMP and 23 DVPs associated with arsenic exposure; including buccal cells, we identified 3 DMPs and 19 DVPs (FDR < 0.05). Using meta-analyzed results, we identified 11 DMRs and 11 DVRs in PBMC samples, and 16 DMRs and 19 DVRs in PBMC and buccal cell samples. One region annotated to LRRC27 was identified as a DMR and DVR. Arsenic-associated KEGG pathways included lysosome, autophagy, and mTOR signaling, AMPK signaling, and one carbon pool by folate.

Conclusions: Using a two-step process of (1) harmonized data processing and analysis and (2) meta-analysis, we leverage four DNAm datasets from two continents of individuals exposed to high levels of As prenatally and during adulthood to identify DMPs and DVPs associated with arsenic exposure. Our approach suggests that standardizing analytical pipelines can aid in identifying biological meaningful signals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12940-021-00754-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8272372PMC
July 2021

Longitudinal Effects of a Sanitation Intervention on Environmental Fecal Contamination in a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Environ Sci Technol 2021 06 4;55(12):8169-8179. Epub 2021 Jun 4.

Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, North Carolina 27695, United States.

Household latrine access generally is not associated with reduced fecal contamination in the environment, but its long-term effectiveness has not been measured. We conducted an environmental assessment nested within the WASH Benefits Bangladesh randomized controlled trial (NCT01590095). We quantified and fecal coliforms in samples of stored drinking water, child hands, mother hands, soil, and food among a random sample of households from the sanitation and control arms of the trial. Samples were collected during eight quarterly visits approximately 1-3.5 years after intervention initiation. Overall, there were no substantial differences in environmental fecal contamination between households enrolled in the sanitation and control arms. Statistically significant reductions were found in stored water and child hands after pooling across sampling rounds, but the effects were small and not consistent across rounds. In addition, we assessed potential effect modification of intervention effects by follow-up time, season, wealth, community-level latrine density and coverage, population density, and domestic animal ownership. While the intervention had statistically significant effects within some subgroups, there were no consistent patterns of effect modification. Our findings support a growing consensus that on-site latrines are insufficient to prevent fecal contamination in the rural household environment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.1c01114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213058PMC
June 2021

Ensemble machine learning for the prediction of patient-level outcomes following thyroidectomy.

Am J Surg 2021 Aug 3;222(2):347-353. Epub 2020 Dec 3.

University of California, San Francisco, Section of Endocrine Surgery, San Francisco, United States.

Background: Accurate prediction of thyroidectomy complications is necessary to inform treatment decisions. Ensemble machine learning provides one approach to improve prediction.

Methods: We applied the Super Learner (SL) algorithm to the 2016-2018 thyroidectomy-specific NSQIP database to predict complications following thyroidectomy. Cross-validation was used to assess model discrimination and precision.

Results: For the 17,987 patients undergoing thyroidectomy, rates of recurrent laryngeal nerve injury, post-operative hypocalcemia prior to discharge or within 30 days, and neck hematoma were 6.1%, 6.4%, 9.0%, and 1.8%, respectively. SL improved prediction of thyroidectomy-specific outcomes when compared with benchmark logistic regression approaches. For postoperative hypocalcemia prior to discharge, SL improved the cross-validated AUROC to 0.72 (95%CI 0.70-0.74) compared to 0.70 (95%CI 0.68-0.72; p < 0.001) when using a manually curated logistic regression algorithm.

Conclusion: Ensemble machine learning modestly improves prediction for thyroidectomy-specific outcomes. SL holds promise to provide more accurate patient-level risk prediction to inform treatment decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjsurg.2020.11.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172667PMC
August 2021

Internal replication of computational workflows in scientific research.

Gates Open Res 2020 17;4:17. Epub 2020 Jun 17.

Division of Epidemiology & Biostatistics, University of California, Berkeley, Berkeley, CA, 94720, USA.

Failures to reproduce research findings across scientific disciplines from psychology to physics have garnered increasing attention in recent years. External replication of published findings by outside investigators has emerged as a method to detect errors and bias in the published literature. However, some studies influence policy and practice before external replication efforts can confirm or challenge the original contributions. Uncovering and resolving errors before publication would increase the efficiency of the scientific process by increasing the accuracy of published evidence. Here we summarize the rationale and best practices for internal replication, a process in which multiple independent data analysts replicate an analysis and correct errors prior to publication. We explain how internal replication should reduce errors and bias that arise during data analyses and argue that it will be most effective when coupled with pre-specified hypotheses and analysis plans and performed with data analysts masked to experimental group assignments. By improving the reproducibility of published evidence, internal replication should contribute to more rapid scientific advances.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12688/gatesopenres.13108.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403855PMC
June 2020

Evaluation of a city-wide school-located influenza vaccination program in Oakland, California, with respect to vaccination coverage, school absences, and laboratory-confirmed influenza: A matched cohort study.

PLoS Med 2020 08 18;17(8):e1003238. Epub 2020 Aug 18.

Division of Epidemiology and Biostatistics, University of California, Berkeley, Berkeley, California, United States of America.

Background: It is estimated that vaccinating 50%-70% of school-aged children for influenza can produce population-wide indirect effects. We evaluated a city-wide school-located influenza vaccination (SLIV) intervention that aimed to increase influenza vaccination coverage. The intervention was implemented in ≥95 preschools and elementary schools in northern California from 2014 to 2018. Using a matched cohort design, we estimated intervention impacts on student influenza vaccination coverage, school absenteeism, and community-wide indirect effects on laboratory-confirmed influenza hospitalizations.

Methods And Findings: We used a multivariate matching algorithm to identify a nearby comparison school district with pre-intervention characteristics similar to those of the intervention school district and matched schools in each district. To measure student influenza vaccination, we conducted cross-sectional surveys of student caregivers in 22 school pairs (2017 survey, N = 6,070; 2018 survey, N = 6,507). We estimated the incidence of laboratory-confirmed influenza hospitalization from 2011 to 2018 using surveillance data from school district zip codes. We analyzed student absenteeism data from 2011 to 2018 from each district (N = 42,487,816 student-days). To account for pre-intervention differences between districts, we estimated difference-in-differences (DID) in influenza hospitalization incidence and absenteeism rates using generalized linear and log-linear models with a population offset for incidence outcomes. Prior to the SLIV intervention, the median household income was $51,849 in the intervention site and $61,596 in the comparison site. The population in each site was predominately white (41% in the intervention site, 48% in the comparison site) and/or of Hispanic or Latino ethnicity (26% in the intervention site, 33% in the comparison site). The number of students vaccinated by the SLIV intervention ranged from 7,502 to 10,106 (22%-28% of eligible students) each year. During the intervention, influenza vaccination coverage among elementary students was 53%-66% in the comparison district. Coverage was similar between the intervention and comparison districts in influenza seasons 2014-2015 and 2015-2016 and was significantly higher in the intervention site in seasons 2016-2017 (7%; 95% CI 4, 11; p < 0.001) and 2017-2018 (11%; 95% CI 7, 15; p < 0.001). During seasons when vaccination coverage was higher among intervention schools and the vaccine was moderately effective, there was evidence of statistically significant indirect effects: The DID in the incidence of influenza hospitalization per 100,000 in the intervention versus comparison site was -17 (95% CI -30, -4; p = 0.008) in 2016-2017 and -37 (95% CI -54, -19; p < 0.001) in 2017-2018 among non-elementary-school-aged individuals and -73 (95% CI -147, 1; p = 0.054) in 2016-2017 and -160 (95% CI -267, -53; p = 0.004) in 2017-2018 among adults 65 years or older. The DID in illness-related school absences per 100 school days during the influenza season was -0.63 (95% CI -1.14, -0.13; p = 0.014) in 2016-2017 and -0.80 (95% CI -1.28, -0.31; p = 0.001) in 2017-2018. Limitations of this study include the use of an observational design, which may be subject to unmeasured confounding, and caregiver-reported vaccination status, which is subject to poor recall and low response rates.

Conclusions: A city-wide SLIV intervention in a large, diverse urban population was associated with a decrease in the incidence of laboratory-confirmed influenza hospitalization in all age groups and a decrease in illness-specific school absence rate among students in 2016-2017 and 2017-2018, seasons when the vaccine was moderately effective, suggesting that the intervention produced indirect effects. Our findings suggest that in populations with moderately high background levels of influenza vaccination coverage, SLIV programs are associated with further increases in coverage and reduced influenza across the community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pmed.1003238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433855PMC
August 2020

Child defecation and feces management practices in rural Bangladesh: Associations with fecal contamination, observed hand cleanliness and child diarrhea.

PLoS One 2020 20;15(7):e0236163. Epub 2020 Jul 20.

Department of Forestry and Environmental Resources, North Carolina State University, Raleigh, NC, United States of America.

Child open defecation is common in low-income countries and can lead to fecal exposure in the domestic environment. We assessed associations between child feces management practices vs. measures of contamination and child diarrhea among households with children <5 years in rural Bangladesh. We visited 360 households quarterly and recorded caregiver-reported diarrhea prevalence, and defecation and feces disposal practices for children <5 years. We examined caregiver and child hands for visible dirt and enumerated E. coli in child and caregiver hand rinse and stored drinking water samples. Safe child defecation (in latrine/potty) and safe feces disposal (in latrine) was reported by 21% and 23% of households, respectively. Controlling for potential confounders, households reporting unsafe child defecation had higher E. coli prevalence on child hands (prevalence ratio [PR] = 1.12, 1.04-1.20) and in stored water (PR = 1.12,1.03-1.21). Similarly, households reporting unsafe feces disposal had higher E. coli prevalence on child hands (PR = 1.11, 1.02-1.21) and in stored water (PR = 1.10, 1.03-1.18). Effects on E. coli levels were similar. Children in households with unsafe defecation and feces disposal had higher diarrhea prevalence but the associations were not statistically significant. Our findings suggest that unsafe child feces management may present a source of fecal exposure for young children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236163PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371197PMC
September 2020

Comparison of multi-parallel qPCR and double-slide Kato-Katz for detection of soil-transmitted helminth infection among children in rural Bangladesh.

PLoS Negl Trop Dis 2020 04 24;14(4):e0008087. Epub 2020 Apr 24.

Division of Epidemiology & Biostatistics, University of California, Berkeley, Berkeley, California, United States of America.

There is growing interest in local elimination of soil-transmitted helminth (STH) infection in endemic settings. In such settings, highly sensitive diagnostics are needed to detect STH infection. We compared double-slide Kato-Katz, the most commonly used copromicroscopic detection method, to multi-parallel quantitative polymerase chain reaction (qPCR) in 2,799 stool samples from children aged 2-12 years in a setting in rural Bangladesh with predominantly low STH infection intensity. We estimated the sensitivity and specificity of each diagnostic using Bayesian latent class analysis. Compared to double-slide Kato-Katz, STH prevalence using qPCR was almost 3-fold higher for hookworm species and nearly 2-fold higher for Trichuris trichiura. Ascaris lumbricoides prevalence was lower using qPCR, and 26% of samples classified as A. lumbricoides positive by Kato-Katz were negative by qPCR. Amplicon sequencing of the 18S rDNA from 10 samples confirmed that A. lumbricoides was absent in samples classified as positive by Kato-Katz and negative by qPCR. The sensitivity of Kato-Katz was 49% for A. lumbricoides, 32% for hookworm, and 52% for T. trichiura; the sensitivity of qPCR was 79% for A. lumbricoides, 93% for hookworm, and 90% for T. trichiura. Specificity was ≥ 97% for both tests for all STH except for Kato-Katz for A. lumbricoides (specificity = 68%). There were moderate negative, monotonic correlations between qPCR cycle quantification values and eggs per gram quantified by Kato-Katz. While it is widely assumed that double-slide Kato-Katz has few false positives, our results indicate otherwise and highlight inherent limitations of the Kato-Katz technique. qPCR had higher sensitivity than Kato-Katz in this low intensity infection setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0008087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202662PMC
April 2020

Predictors of Enteric Pathogens in the Domestic Environment from Human and Animal Sources in Rural Bangladesh.

Environ Sci Technol 2019 Sep 16;53(17):10023-10033. Epub 2019 Aug 16.

Department of Civil and Environmental Engineering , University of California , Berkeley , California 94720 , United States.

Fecal indicator organisms are measured to indicate the presence of fecal pollution, yet the association between indicators and pathogens varies by context. The goal of this study was to empirically evaluate the relationships between indicator , microbial source tracking markers, select enteric pathogen genes, and potential sources of enteric pathogens in 600 rural Bangladeshi households. We measured indicators and pathogen genes in stored drinking water, soil, and on mother and child hands. Additionally, survey and observational data on sanitation and domestic hygiene practices were collected. Log concentrations of indicator were positively associated with the prevalence of pathogenic genes in all sample types. Given the current need to rely on indicators to assess fecal contamination in the field, it is significant that in this study context indicator concentrations, measured by IDEXX Colilert-18, provided quantitative information on the presence of pathogenic in different sample types. There were no significant associations between the human fecal marker (HumM2) and human-specific pathogens in any environmental sample type. There was an increase in the prevalence of genes, any virulence gene, and the specific virulence genes with every log increase in the concentration of the animal fecal marker (BacCow) on mothers' hands. Thus, domestic animals were important contributors to enteric pathogens in these households.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b07192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727619PMC
September 2019

Human exposure to trichloroethylene is associated with increased variability of blood DNA methylation that is enriched in genes and pathways related to autoimmune disease and cancer.

Epigenetics 2019 11 26;14(11):1112-1124. Epub 2019 Jun 26.

Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville , MD , USA.

Human exposure to trichloroethylene (TCE) is linked to kidney cancer, autoimmune diseases, and probably non-Hodgkin lymphoma. Additionally, TCE exposed mice and cell cultures show altered DNA methylation. To evaluate associations between TCE exposure and DNA methylation in humans, we conducted an epigenome-wide association study (EWAS) in TCE exposed workers using the HumanMethylation450 BeadChip. Across individual CpG probes, genomic regions, and globally (i.e., the 450K methylome), we investigated differences in mean DNA methylation and differences in variability of DNA methylation between 73 control (< 0.005 ppm TCE), 30 lower exposed (< 10 ppm TCE), and 37 higher exposed ( 10 ppm TCE) subjects' white blood cells. We found that TCE exposure increased methylation variation globally (Kruskal-Wallis -value = 3.75e-3) and in 25 CpG sites at a genome-wide significance level (Bonferroni -value < 0.05). We identified a 609 basepair region in the gene promoter that exhibited hypomethylation with increased exposure to TCE (FWER = 1.20e-2). Also, genes that matched to differentially variable CpGs were enriched in the 'focal adhesion' biological pathway (-value = 2.80e-2). All in all, human exposure to TCE was associated with epigenetic alterations in genes involved in cell-matrix adhesions and interferon subtype expression, which are important in the development of autoimmune diseases; and in genes related to cancer development. These results suggest that DNA methylation may play a role in the pathogenesis of TCE exposure-related diseases and that TCE exposure may contribute to epigenetic drift.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15592294.2019.1633866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773405PMC
November 2019

Effects of water, sanitation, handwashing and nutritional interventions on soil-transmitted helminth infections in young children: A cluster-randomized controlled trial in rural Bangladesh.

PLoS Negl Trop Dis 2019 05 3;13(5):e0007323. Epub 2019 May 3.

Infectious Diseases & Geographic Medicine, Stanford University, Stanford, CA, United States of America.

Background: Soil transmitted helminths (STH) infect >1.5 billion people. Mass drug administration (MDA) effectively reduces infection; however, there is evidence for rapid reinfection and risk of potential drug resistance. We conducted a randomized controlled trial in Bangladesh (WASH Benefits, NCT01590095) to assess whether water, sanitation, hygiene and nutrition interventions, alone and combined, reduce STH in a setting with ongoing MDA.

Methodology/principal Findings: In 2012-2013, we randomized 720 clusters of 5551 pregnant women into water treatment, sanitation, handwashing, combined water+sanitation+handwashing (WSH), nutrition, nutrition+WSH (N+WSH) or control arms. In 2015-2016, we enrolled 7795 children, aged 2-12 years, of 4102 available women for STH follow-up and collected stool from 7187. We enumerated STH infections with Kato-Katz. We estimated intention-to-treat intervention effects on infection prevalence and intensity. Participants and field staff were not blinded; laboratory technicians and data analysts were blinded. Prevalence among controls was 36.8% for A. lumbricoides, 9.2% for hookworm and 7.5% for T. trichiura. Most infections were low-intensity. Compared to controls, the water intervention reduced hookworm by 31% (prevalence ratio [PR] = 0.69 (0.50,0.95), prevalence difference [PD] = -2.83 (-5.16,-0.50)) but did not affect other STH. Sanitation improvements reduced T. trichiura by 29% (PR = 0.71 (0.52,0.98), PD = -2.17 (-4.03,-0.38)), had a similar borderline effect on hookworm and no effect on A. lumbricoides. Handwashing and nutrition interventions did not reduce any STH. WSH and N+WSH reduced hookworm prevalence by 29-33% (WSH: PR = 0.71 (0.52,0.99), PD = -2.63 (-4.95,-0.31); N+WSH: PR = 0.67 (0.50,0.91), PD = -3.00 (-5.14,-0.85)) and marginally reduced A. lumbricoides. Effects on infection intensity were similar.

Conclusions/significance: In a low-intensity infection setting with MDA, we found modest but sustained hookworm reduction from water treatment and combined WSH interventions. Impacts were more pronounced on STH species with short vs. long-term environmental survival. Our findings suggest possible waterborne transmission for hookworm. Water treatment and sanitation improvements can augment MDA to interrupt STH transmission.

Trial Registration: NCT01590095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pntd.0007323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519840PMC
May 2019

Associations between High Temperature, Heavy Rainfall, and Diarrhea among Young Children in Rural Tamil Nadu, India: A Prospective Cohort Study.

Environ Health Perspect 2019 04;127(4):47004

1 School of Public Health, University of California , Berkeley, California, USA.

Background: The effects of weather on diarrhea could influence the health impacts of climate change. Children have the highest diarrhea incidence, especially in India, where many lack safe water and sanitation.

Objectives: In a prospective cohort of 1,284 children under 5 y of age from 900 households across 25 villages in rural Tamil Nadu, India, we examined whether high temperature and heavy rainfall was associated with increased all-cause diarrhea and water contamination.

Methods: Seven-day prevalence of diarrhea was assessed monthly for up to 12 visits from January 2008 to April 2009, and hydrogen sulfide ([Formula: see text]) presence in drinking water, a fecal contamination indicator, was tested in a subset of households. We estimated associations between temperature and rainfall exposures and diarrhea and [Formula: see text] using binomial regressions, adjusting for potential confounders, random effects for village, and autoregressive-1 error terms for study week.

Results: There were 259 cases of diarrhea. The prevalence of diarrhea during the 7 d before visits was 2.95 times higher (95% CI: 1.99, 4.39) when mean temperature in the week before the 7-d recall was in the hottest versus the coolest quartile of weekly mean temperature during 1 December 2007 to 15 April 2009. Diarrhea prevalence was 1.50 times higher when the 3 weeks before the diarrhea recall period included [Formula: see text] (vs. 0 d) with rainfall of [Formula: see text] (95% CI: 1.12, 2.02), and 2.60 times higher (95% CI: 1.55, 4.36) for heavy rain weeks following a 60-d dry period. The [Formula: see text] prevalence in household water was not associated with heavy rain prior to sample collection.

Conclusions: The results suggest that, in rural Tamil Nadu, heavy rainfall may wash pathogens that accumulate during dry weather into child contact. Higher temperatures were positively associated with diarrhea 1-3 weeks later. Our findings suggest that diarrhea morbidity could worsen under climate change without interventions to reduce enteric pathogen transmission through multiple pathways. https://doi.org/10.1289/EHP3711.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1289/EHP3711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785227PMC
April 2019

Dynamic multi-outcome prediction after injury: Applying adaptive machine learning for precision medicine in trauma.

PLoS One 2019 10;14(4):e0213836. Epub 2019 Apr 10.

Denver Health Medical Center and the University of Colorado; Denver, Colorado, United States of America.

Objective: Machine learning techniques have demonstrated superior discrimination compared to conventional statistical approaches in predicting trauma death. The objective of this study is to evaluate whether machine learning algorithms can be used to assess risk and dynamically identify patient-specific modifiable factors critical to patient trajectory for multiple key outcomes after severe injury.

Methods: SuperLearner, an ensemble machine-learning algorithm, was applied to prospective observational cohort data from 1494 critically-injured patients. Over 1000 agnostic predictors were used to generate prediction models from multiple candidate learners for outcomes of interest at serial time points post-injury. Model accuracy was estimated using cross-validation and area under the curve was compared to select among predictors. Clinical variables responsible for driving outcomes were estimated at each time point.

Results: SuperLearner fits demonstrated excellent cross-validated prediction of death (overall AUC 0.94-0.97), multi-organ failure (overall AUC 0.84-0.90), and transfusion (overall AUC 0.87-0.9) across multiple post-injury time points, and good prediction of Acute Respiratory Distress Syndrome (overall AUC 0.84-0.89) and venous thromboembolism (overall AUC 0.73-0.83). Outcomes with inferior data quality included coagulopathic trajectory (AUC 0.48-0.88). Key clinical predictors evolved over the post-injury timecourse and included both anticipated and unexpected variables. Non-random missingness of data was identified as a predictor of multiple outcomes over time.

Conclusions: Machine learning algorithms can be used to generate dynamic prediction after injury while avoiding the risk of over- and under-fitting inherent in ad hoc statistical approaches. SuperLearner prediction after injury demonstrates promise as an adaptable means of helping clinicians integrate voluminous, evolving data on severely-injured patients into real-time, dynamic decision-making support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0213836PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457612PMC
December 2019

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Environmental Enteric Dysfunction in Young Children: A Cluster-randomized, Controlled Trial in Rural Bangladesh.

Clin Infect Dis 2020 02;70(5):738-747

Department of Nutrition, University of California-Davis.

Background: We hypothesized that drinking water, sanitation, handwashing (WSH), and nutritional interventions would improve environmental enteric dysfunction (EED), a potential contributor to stunting.

Methods: Within a subsample of a cluster-randomized, controlled trial in rural Bangladesh, we enrolled pregnant women in 4 arms: control, WSH, child nutrition counseling plus lipid-based nutrient supplements (N), and nutrition plus WSH (N+WSH). Among the birth cohort, we measured biomarkers of gut inflammation (myeloperoxidase, neopterin), permeability (alpha-1-antitrypsin, lactulose, mannitol), and repair (regenerating gene 1β) at median ages 3, 14, and 28 months. Analysis was intention-to-treat.

Results: We assessed 1512 children. At age 3 months, compared to controls, neopterin was reduced by nutrition (-0.21 log nmol/L; 95% confidence interval [CI], -.37, -.05) and N+WSH (-0.20 log nmol/L; 95% CI, -.34, -.06) interventions; similar reductions were observed at 14 months. At 3 months, all interventions reduced lactulose and mannitol (-0.60 to -0.69 log mmol/L). At 28 months, myeloperoxidase was elevated in the WSH and nutrition arms (0.23-0.27 log ng/mL) and lactulose was higher in the WSH arm (0.30 log mmol/L; 95% CI, .07, .53).

Conclusions: Reductions in permeability and inflammation at ages 3 and 14 months suggest that the interventions promoted healthy intestinal maturation; however, by 28 months, the WSH and nutrition arms showed elevated EED biomarkers. These results underscore the importance of developing a better understanding of EED pathophysiology and targeting interventions early in childhood, when they are likely to have the largest benefit to intestinal health.

Clinical Trials Registration: NCT01590095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciz291DOI Listing
February 2020

Functional Profiling Identifies Determinants of Arsenic Trioxide Cellular Toxicity.

Toxicol Sci 2019 05;169(1):108-121

Department of Physiological Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.

Arsenic exposure is a worldwide health concern associated with an increased risk of skin, lung, and bladder cancer but arsenic trioxide (AsIII) is also an effective chemotherapeutic agent. The current use of AsIII in chemotherapy is limited to acute promyelocytic leukemia (APL). However, AsIII was suggested as a potential therapy for other cancer types including chronic myeloid leukemia (CML), especially when combined with other drugs. Here, we carried out a genome-wide CRISPR-based approach to identify modulators of AsIII toxicity in K562, a human CML cell line. We found that disruption of KEAP1, the inhibitory partner of the key antioxidant transcription factor Nrf2, or TXNDC17, a thioredoxin-like protein, markedly increased AsIII tolerance. Loss of the water channel AQP3, the zinc transporter ZNT1 and its regulator MTF1 also enhanced tolerance to AsIII whereas loss of the multidrug resistance protein ABCC1 increased sensitivity to AsIII. Remarkably, disruption of any of multiple genes, EEFSEC, SECISBP2, SEPHS2, SEPSECS, and PSTK, encoding proteins involved in selenocysteine metabolism increased resistance to AsIII. Our data suggest a model in which an intracellular interaction between selenium and AsIII may impact intracellular AsIII levels and toxicity. Together this work revealed a suite of cellular components/processes which modulate the toxicity of AsIII in CML cells. Targeting such processes simultaneously with AsIII treatment could potentiate AsIII in CML therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/toxsci/kfz024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6484884PMC
May 2019

Computer Algebra and Algorithms for Unbiased Moment Estimation of Arbitrary Order.

Cogent Math Stat 2019 21;6(1). Epub 2019 Dec 21.

University of California, Berkeley, Division of Epidemiology and Biostatistics, Berkeley, CA 94720, USA.

While unbiased central moment estimators of lower orders (such as a sample variance) are easily obtainable and often used in practice, derivation of unbiased estimators of higher orders might be more challenging due to long math and tricky combinatorics. Moreover, higher orders necessitate calculation of estimators of powers and products that also amount to these orders. We develop a software algorithm that allows the user to obtain unbiased estimators of an arbitrary order and provide results up to the 6th order, including powers and products of lower orders. The method also extends to finding pooled estimates of higher central moments of several different populations ( for two-sample tests). We introduce an R package that calculates one- and two-sample estimates and generates intermediate results used to obtain these estimators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/25742558.2019.1701917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546107PMC
December 2019

Identification of gene expression predictors of occupational benzene exposure.

PLoS One 2018 9;13(10):e0205427. Epub 2018 Oct 9.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, NCI, NIH, DHHS, Bethesda, Maryland, United States of America.

Background: Previously, using microarrays and mRNA-Sequencing (mRNA-Seq) we found that occupational exposure to a range of benzene levels perturbed gene expression in peripheral blood mononuclear cells.

Objectives: In the current study, we sought to identify gene expression biomarkers predictive of benzene exposure below 1 part per million (ppm), the occupational standard in the U.S.

Methods: First, we used the nCounter platform to validate altered expression of 30 genes in 33 unexposed controls and 57 subjects exposed to benzene (<1 to ≥5 ppm). Second, we used SuperLearner (SL) to identify a minimal number of genes for which altered expression could predict <1 ppm benzene exposure, in 44 subjects with a mean air benzene level of 0.55±0.248 ppm (minimum 0.203ppm).

Results: nCounter and microarray expression levels were highly correlated (coefficients >0.7, p<0.05) for 26 microarray-selected genes. nCounter and mRNA-Seq levels were poorly correlated for 4 mRNA-Seq-selected genes. Using negative binomial regression with adjustment for covariates and multiple testing, we confirmed differential expression of 23 microarray-selected genes in the entire benzene-exposed group, and 27 genes in the <1 ppm-exposed subgroup, compared with the control group. Using SL, we identified 3 pairs of genes that could predict <1 ppm benzene exposure with cross-validated AUC estimates >0.9 (p<0.0001) and were not predictive of other exposures (nickel, arsenic, smoking, stress). The predictive gene pairs are PRG2/CLEC5A, NFKBI/CLEC5A, and ACSL1/CLEC5A. They play roles in innate immunity and inflammatory responses.

Conclusions: Using nCounter and SL, we validated the altered expression of multiple mRNAs by benzene and identified gene pairs predictive of exposure to benzene at levels below the US occupational standard of 1ppm.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0205427PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6177191PMC
March 2019

Effects of Single and Combined Water, Sanitation and Handwashing Interventions on Fecal Contamination in the Domestic Environment: A Cluster-Randomized Controlled Trial in Rural Bangladesh.

Environ Sci Technol 2018 11 11;52(21):12078-12088. Epub 2018 Oct 11.

School of Public Health , University of California , Berkeley , California 94720 , United States.

Water, sanitation, and hygiene interventions have varying effectiveness in reducing fecal contamination in the domestic environment; delivering them in combination could yield synergies. We conducted environmental assessments within a randomized controlled trial in Bangladesh that implemented single and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). After one and two years of intervention, we quantified fecal indicator bacteria in samples of drinking water (from source or storage), child hands, children's food and sentinel objects. In households receiving single water treatment interventions, Escherichia coli prevalence in stored drinking water was reduced by 50% and concentration by 1-log. E. coli prevalence in food was reduced by 30% and concentration by 0.5-log in households receiving single water treatment and handwashing interventions. Combined WSH did not reduce fecal contamination more effectively than its components. Interventions did not reduce E. coli in groundwater, on child hands and on objects. These findings suggest that WSH improvements reduced contamination along the direct transmission pathways of stored water and food but not along indirect upstream pathways. Our findings support implementing water treatment and handwashing to reduce fecal exposure through water and food but provide no evidence that combining interventions further reduces exposure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b05153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222549PMC
November 2018

Do Sanitation Improvements Reduce Fecal Contamination of Water, Hands, Food, Soil, and Flies? Evidence from a Cluster-Randomized Controlled Trial in Rural Bangladesh.

Environ Sci Technol 2018 11 12;52(21):12089-12097. Epub 2018 Oct 12.

School of Public Health , University of California , Berkeley , California 94720 , United States.

Sanitation improvements have had limited effectiveness in reducing the spread of fecal pathogens into the environment. We conducted environmental measurements within a randomized controlled trial in Bangladesh that implemented individual and combined water treatment, sanitation, handwashing (WSH) and nutrition interventions (WASH Benefits, NCT01590095). Following approximately 4 months of intervention, we enrolled households in the trial's control, sanitation and combined WSH arms to assess whether sanitation improvements, alone and coupled with water treatment and handwashing, reduce fecal contamination in the domestic environment. We quantified fecal indicator bacteria in samples of drinking and ambient waters, child hands, food given to young children, courtyard soil and flies. In the WSH arm, Escherichia coli prevalence in stored drinking water was reduced by 62% (prevalence ratio = 0.38 (0.32, 0.44)) and E. coli concentration by 1-log (Δlog = -0.88 (-1.01, -0.75)). The interventions did not reduce E. coli along other sampled pathways. Ambient contamination remained high among intervention households. Potential reasons include noncommunity-level sanitation coverage, child open defecation, animal fecal sources, or naturalized E. coli in the environment. Future studies should explore potential threshold effects of different levels of community sanitation coverage on environmental contamination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.est.8b02988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6222553PMC
November 2018

Machine learning without borders? An adaptable tool to optimize mortality prediction in diverse clinical settings.

J Trauma Acute Care Surg 2018 11;85(5):921-927

From the Department of Surgery (S.A.C., R.A.C., C.J.), University of California San Francisco, San Francisco, California; Department of Biostatistics (A.E.H.), University of California Berkeley, Berkeley, California; Division of General Surgery (M.H.), Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada; Littoral Regional Delegation of the Ministry of Public Health, Cameroon (F.N.D.-D.), Douala, Cameroon; Laquintinie Hospital of Douala, Douala, Cameroon (D.M., A.S.); Regional Hospital of Limbe, Limbe, Cameroon (A.C.M.); Catholic Hospital of Pouma, Pouma, Cameroon (P.N.); Department of Surgery (R.A.D.), University of California Los Angeles, Los Angeles, California; and Denver Health Medical Center and the University of Colorado, Denver, Colorado (M.J.C.).

Background: Mortality prediction aids clinical decision making and is necessary for quality improvement initiatives. Validated metrics rely on prespecified variables and often require advanced diagnostics, which are unfeasible in resource-constrained contexts. We hypothesize that machine learning will generate superior mortality prediction in both high-income and low- and middle-income country cohorts.

Methods: SuperLearner, an ensemble machine-learning algorithm, was applied to data from three prospective trauma cohorts: a highest-activation cohort in the United States, a high-volume center cohort in South Africa (SA), and a multicenter registry in Cameroon. Cross-validation was used to assess model discrimination of discharge mortality by site using receiver operating characteristic curves. SuperLearner discrimination was compared with standard scoring methods. Clinical variables driving SuperLearner prediction at each site were evaluated.

Results: Data from 28,212 injured patients were used to generate prediction. Discharge mortality was 17%, 1.3%, and 1.7% among US, SA, and Cameroonian cohorts. SuperLearner delivered superior prediction of discharge mortality in the United States (area under the curve [AUC], 94-97%) and vastly superior prediction in Cameroon (AUC, 90-94%) compared with conventional scoring algorithms. It provided similar prediction to standard scores in the SA cohort (AUC, 90-95%). Context-specific variables (partial thromboplastin time in the United States and hospital distance in Cameroon) were prime drivers of predicted mortality in their respective cohorts, whereas severe brain injury predicted mortality across sites.

Conclusions: Machine learning provides excellent discrimination of injury mortality in diverse settings. Unlike traditional scores, data-adaptive methods are well suited to optimizing precise site-specific prediction regardless of diagnostic capabilities or data set inclusion allowing for individualized decision making and expanded access to quality improvement programming.

Level Of Evidence: Prognostic and therapeutic, level II and III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TA.0000000000002044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225991PMC
November 2018

Elevated Levels of Organochlorine Pesticides in South Asian Immigrants Are Associated With an Increased Risk of Diabetes.

J Endocr Soc 2018 Aug 22;2(8):832-841. Epub 2018 May 22.

Department of Cardiology, Ealing Hospital, Middlesex, United Kingdom.

Objective: Rates of diabetes mellitus are higher in South Asians than in other populations and persist after migration. One unexplored cause may be higher exposure to persistent organic pollutants associated with diabetes in other populations. We compared organochlorine (OC) pesticide concentrations in South Asian immigrants and European whites to determine whether the disease was positively associated with OC pesticides in South Asians.

Research Design And Methods: South Asians of Tamil or Telugu descent (n = 120) and European whites (n = 72) were recruited into the London Life Sciences Population Study cohort. Blood samples as well as biometric, clinical, and survey data were collected. Plasma levels of -dichlorodiphenyldichloroethylene (DDE), - dichlorodiphenyltrichloroethane, -hexachlorohexane (HCH), and polychlorinated biphenyl-118 were analyzed by gas chromatography-mass spectrometry. South Asian cases and controls were categorized by binary exposure (above vs below the 50th percentile) to perform logistic regression.

Results: Tamils had approximately threefold to ninefold higher levels of OC pesticides, and Telugus had ninefold to 30-fold higher levels compared with European whites. The odds of exposure to -DDE above the 50th percentile was significantly greater in South Asian diabetes cases than in controls (OR: 7.00; 95% CI: 2.22, 22.06). The odds of exposure to -HCH above the 50th percentile was significantly greater in the Tamil cases than in controls (OR: 9.35; 95% CI: 2.43, 35.97).

Conclusions: South Asian immigrants have a higher body burden of OC pesticides than European whites. Diabetes mellitus is associated with higher -DDE and -HCH concentrations in this population. Additional longitudinal studies of South Asian populations should be performed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/js.2017-00480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6041775PMC
August 2018

Effects of Water, Sanitation, Handwashing, and Nutritional Interventions on Child Enteric Protozoan Infections in Rural Bangladesh: A Cluster-Randomized Controlled Trial.

Clin Infect Dis 2018 10;67(10):1515-1522

Infectious Diseases and Geographic Medicine, Stanford University, California.

Background: We evaluated effects of individual and combined water, sanitation, handwashing (WSH), and nutritional interventions on protozoan infections in children.

Methods: We randomized geographical clusters of pregnant women in rural Bangladesh into chlorinated drinking water, hygienic sanitation, handwashing, nutrition, combined WSH, nutrition plus WSH (N+WSH), or control arms. Participants were not masked. After approximately 2.5 years of intervention, we measured Giardia, Cryptosporidium, and Entamoeba histolytica prevalence and infection intensity by multiplex real-time polymerase chain reaction of child stool. Analysis was intention-to-treat.

Results: Between May 2012 and July 2013, we randomized 5551 pregnant women. At follow-up, among 4102 available women, we enrolled 6694 children into the protozoan assessment. We analyzed stool from 5933 children (aged ~31 months) for protozoan infections. Compared with 35.5% prevalence among controls, Giardia infection prevalence was lower in the sanitation (26.5%; prevalence ratio [PR], 0.75 [95% confidence interval {CI}, .64-.88]), handwashing (28.2%; PR, 0.80 [95% CI, .66-.96]), WSH (29.7%; PR, 0.83 [95% CI, .72-.96]), and N+WSH (26.7%; PR, 0.75 [95% CI, .64-.88]) arms. Water and nutrition interventions had no effect. Low prevalence of E. histolytica and Cryptosporidium (<2%) resulted in imprecise effect estimates.

Conclusions: Individual handwashing and hygienic sanitation interventions significantly reduced childhood Giardia infections, and there were no effects of chlorinated drinking water and nutrition improvements in this context. Combined WSH interventions provided no additional benefit. To reduce Giardia infection, individual WSH interventions may be more feasible and cost-effective than combined interventions in similar rural, low-income settings.

Clinical Trials Registration: NCT01590095.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciy320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206106PMC
October 2018

Effects of water quality, sanitation, handwashing, and nutritional interventions on child development in rural Kenya (WASH Benefits Kenya): a cluster-randomised controlled trial.

Lancet Child Adolesc Health 2018 Apr;2(4):269-280

Innovations for Poverty Action, New Haven, CT, USA; Center for International Policy Research and Evaluation, Mathematica Policy Research, Washington DC, USA.

Background: Poor nutrition and infectious diseases can prevent children from reaching their developmental potential. We aimed to assess the effects of improvements in water, sanitation, handwashing, and nutrition on early child development in rural Kenya.

Methods: In this cluster-randomised controlled trial, we enrolled pregnant women in their second or third trimester from three counties (Kakamega, Bungoma, and Vihiga) in Kenya's western region, with an average of 12 households per cluster. Groups of nine geographically adjacent clusters were block-randomised, using a random number generator, into the six intervention groups (including monthly visits to promote target behaviours), a passive control group (no visits), or a double-sized active control group (monthly household visits to measure child mid-upper arm circumference). The six intervention groups were: chlorinated drinking water; improved sanitation; handwashing with soap; combined water, sanitation, and handwashing; improved nutrition through counselling and provision of lipid-based nutrient supplements; and combined water, sanitation, handwashing, and nutrition. Here we report on the prespecified secondary child development outcomes: gross motor milestone achievement assessed with the WHO module at year 1, and communication, gross motor, personal social, and combined scores measured by the Extended Ages and Stages Questionnaire (EASQ) at year 2. Masking of participants was not possible, but data assessors were masked. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.

Findings: Between Nov 27, 2012, and May 21, 2014, 8246 women residing in 702 clusters were enrolled. No clusters were lost to follow-up, but 2212 households with 2279 children were lost to follow-up by year 2. 5791 (69%) children were measured at year 1 and 6107 (73%) at year 2. At year 1, compared with the active control group, the combined water, sanitation, handwashing, and nutrition group had greater rates of attaining the standing with assistance milestone (hazard ratio 1·23, 95% CI 1·09-1·40) and the walking with assistance milestone (1·32, 1·17-1·50), and the handwashing group had a greater rate of attaining the standing alone milestone (1·15, 1·01-1·31). There were no differences when comparing the other intervention groups with the active control group on any of the motor milestone measures at year 1. At year 2, there were no differences among groups for the communication, gross motor, personal social, or combined EASQ scores.

Interpretation: The handwashing and combined water, sanitation, handwashing, and nutrition interventions might have improved child motor development after 1 year, although after 2 years there were no other differences between groups. Future research should examine ways to make community health and nutrition programmes more effective at supporting child development.

Funding: Bill & Melinda Gates Foundation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-4642(18)30025-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859215PMC
April 2018

A Randomized Controlled Trial to Measure Spillover Effects of a Combined Water, Sanitation, and Handwashing Intervention in Rural Bangladesh.

Am J Epidemiol 2018 08;187(8):1733-1744

School of Public Health, University of California, Berkeley, Berkeley, California.

Water, sanitation, and handwashing interventions may confer spillover effects on intervention recipients' neighbors by interrupting pathogen transmission. We measured geographically local spillovers in the Water Quality, Sanitation, and Handwashing (WASH) Benefits Study, a cluster-randomized trial in rural Bangladesh, by comparing outcomes among neighbors of intervention versus those of control participants. Geographically defined clusters were randomly allocated to a compound-level intervention (i.e., chlorinated drinking water, upgraded sanitation, and handwashing promotion) or control arm. From January 2015 to August 2015, in 180 clusters, we enrolled 1,799 neighboring children who were age matched to trial participants who would have been eligible for the study had they been conceived slightly earlier or later. After 28 months of intervention, we quantified fecal indicator bacteria in toy rinse and drinking water samples and measured soil-transmitted helminth infections and caregiver-reported diarrhea and respiratory illness. Neighbors' characteristics were balanced across arms. Detectable Escherichia coli prevalence in tubewell samples was lower for intervention participants' neighbors than control participants' (prevalence ratio = 0.83; 95% confidence interval: 0.73, 0.95). Fecal indicator bacteria prevalence did not differ between arms for other environmental samples. Prevalence was similar in neighbors of intervention participants versus those of control participants for soil-transmitted helminth infection, diarrhea, and respiratory illness. A compound-level water, sanitation, and handwashing intervention reduced neighbors' tubewell water contamination but did not affect neighboring children's health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwy046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6070113PMC
August 2018

Effects of water quality, sanitation, handwashing, and nutritional interventions on diarrhoea and child growth in rural Kenya: a cluster-randomised controlled trial.

Lancet Glob Health 2018 03 29;6(3):e316-e329. Epub 2018 Jan 29.

Division of Epidemiology, School of Public Health, University of California, Berkeley, CA, USA.

Background: Poor nutrition and exposure to faecal contamination are associated with diarrhoea and growth faltering, both of which have long-term consequences for child health. We aimed to assess whether water, sanitation, handwashing, and nutrition interventions reduced diarrhoea or growth faltering.

Methods: The WASH Benefits cluster-randomised trial enrolled pregnant women from villages in rural Kenya and evaluated outcomes at 1 year and 2 years of follow-up. Geographically-adjacent clusters were block-randomised to active control (household visits to measure mid-upper-arm circumference), passive control (data collection only), or compound-level interventions including household visits to promote target behaviours: drinking chlorinated water (water); safe sanitation consisting of disposing faeces in an improved latrine (sanitation); handwashing with soap (handwashing); combined water, sanitation, and handwashing; counselling on appropriate maternal, infant, and young child feeding plus small-quantity lipid-based nutrient supplements from 6-24 months (nutrition); and combined water, sanitation, handwashing, and nutrition. Primary outcomes were caregiver-reported diarrhoea in the past 7 days and length-for-age Z score at year 2 in index children born to the enrolled pregnant women. Masking was not possible for data collection, but analyses were masked. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01704105.

Findings: Between Nov 27, 2012, and May 21, 2014, 8246 women in 702 clusters were enrolled and randomly assigned an intervention or control group. 1919 women were assigned to the active control group; 938 to passive control; 904 to water; 892 to sanitation; 917 to handwashing; 912 to combined water, sanitation, and handwashing; 843 to nutrition; and 921 to combined water, sanitation, handwashing, and nutrition. Data on diarrhoea at year 1 or year 2 were available for 6494 children and data on length-for-age Z score in year 2 were available for 6583 children (86% of living children were measured at year 2). Adherence indicators for sanitation, handwashing, and nutrition were more than 70% at year 1, handwashing fell to less than 25% at year 2, and for water was less than 45% at year 1 and less than 25% at year 2; combined groups were comparable to single groups. None of the interventions reduced diarrhoea prevalence compared with the active control. Compared with active control (length-for-age Z score -1·54) children in nutrition and combined water, sanitation, handwashing, and nutrition were taller by year 2 (mean difference 0·13 [95% CI 0·01-0·25] in the nutrition group; 0·16 [0·05-0·27] in the combined water, sanitation, handwashing, and nutrition group). The individual water, sanitation, and handwashing groups, and combined water, sanitation, and handwashing group had no effect on linear growth.

Interpretation: Behaviour change messaging combined with technologically simple interventions such as water treatment, household sanitation upgrades from unimproved to improved latrines, and handwashing stations did not reduce childhood diarrhoea or improve growth, even when adherence was at least as high as has been achieved by other programmes. Counselling and supplementation in the nutrition group and combined water, sanitation, handwashing, and nutrition interventions led to small growth benefits, but there was no advantage to integrating water, sanitation, and handwashing with nutrition. The interventions might have been more efficacious with higher adherence or in an environment with lower baseline sanitation coverage, especially in this context of high diarrhoea prevalence.

Funding: Bill & Melinda Gates Foundation, United States Agency for International Development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2214-109X(18)30005-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809717PMC
March 2018
-->