School of Public Health

Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, yet few environmental risk factors have been identified. We previously found an association between early-life tobacco smoke exposure and frequency of somatic deletions of 8 leukemia driver genes among childhood ALL patients in the California Childhood Leukemia Study. To expand analysis genome-wide and examine potential mechanisms, we conducted tumor whole-genome sequencing in 35 ALL patients, including 18 with high prenatal tobacco exposure and 17 with low exposure as determined by established epigenetic biomarkers. High tobacco exposure patients had significantly more structural variants (P < .001) and deletions (P = .001) genome-wide than low exposure patients. Investigation of off-target RAG recombination revealed that 41% of deletions in the high tobacco exposure patients were putatively RAG-mediated (full RAG motif identified at one or both breakpoints) compared with only 21% in the low exposure group (P = .001). In a multilevel model, deletions in high tobacco exposure patients were 2.44-fold (95% CI:1.13-5.38) more likely to be putatively RAG-mediated than deletions in low exposure patients. No point mutational signatures were associated with prenatal tobacco exposure. Our findings suggest that early-life tobacco smoke exposure may promote leukemogenesis by driving development of somatic deletions in pre-leukemic lymphocytes via off-target RAG recombination.

Legacy effects describe the persistent, long-term impacts on an ecosystem following the removal of an abiotic or biotic feature. Redlining, a policy that codified racial segregation and disinvestment in minoritized neighborhoods, has produced legacy effects with profound impacts on urban ecosystem structure and health. These legacies have detrimentally impacted public health outcomes, socioeconomic stability, and environmental health. However, the collateral impacts of redlining on wildlife communities are uncertain. Here, we investigated whether faunal biodiversity was associated with redlining. We used home-owner loan corporation (HOLC) maps [grades A (i.e., "best" and "greenlined"), B, C, and D (i.e., "hazardous" and "redlined")] across four cities in California and contributory science data (iNaturalist) to estimate alpha and beta diversity across six clades (mammals, birds, insects, arachnids, reptiles, and amphibians) as a function of HOLC grade. We found that in greenlined neighborhoods, unique species were detected with less sampling effort, with redlined neighborhoods needing over 8,000 observations to detect the same number of unique species. Historically redlined neighborhoods had lower native and nonnative species richness compared to greenlined neighborhoods across each city, with disparities remaining at the clade level. Further, community composition (i.e., beta diversity) consistently differed among HOLC grades for all cities, including large differences in species assemblage observed between green and redlined neighborhoods. Our work spotlights the lasting effects of social injustices on the community ecology of cities, emphasizing that urban conservation and management efforts must incorporate an antiracist, justice-informed lens to improve biodiversity in urban environments.

Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation.

Diverse representation and inclusion are stated priorities for scientific institutions and professional societies, including the Society for Epidemiologic Research (SER). Prior studies have reported persistent underrepresentation and exclusion of marginalized groups across the sciences. We conducted a representation and inclusion survey among SER affiliates in 2021, following up on a similar 2018 survey. In 2021, we observed broad representation from diverse groups across multiple dimensions. However, across both surveys we found persistent underrepresentation of several marginalized groups, including Black or African American and Hispanic/Latinx people. Some groups reported feeling excluded in both the 2018 and 2021 surveys, and there was disproportionately high representation from a subset of higher-ranked US academic institutions. For several indicators of inclusion, perceptions of inclusion were more positive among White respondents compared to other respondents. Opportunities to work towards achieving SER’s diversity and inclusion aims include increasing outreach to epidemiology trainees and Minority Serving Institutions, addressing cultural and financial barriers to participation, and improving access for epidemiologists with disabilities. Iterative follow-up work with diversity and inclusion scholars could improve our understanding of barriers to diversity and inclusion within SER and, more broadly, the field of epidemiology.

Combined water, sanitation, and handwashing (WSH) interventions could reduce fecal contamination along more transmission pathways than single interventions alone. We measured Escherichia coli levels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a 2-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment with chlorine reduced E. coli in drinking water. A combined WSH intervention improved water quality by the same magnitude but did not affect E. coli levels on hands or toys. One potential explanation for the limited impact of the sanitation intervention (upgraded latrines) is failure to address dog and livestock fecal contamination. Small ruminant (goat or sheep) ownership was associated with increased E. coli levels in stored water and on child hands. Cattle and poultry ownership was protective against child stunting, and domesticated animal ownership was not associated with child diarrhea. Our findings do not support restricting household animal ownership to prevent child diarrheal disease or stunting but do support calls for WSH infrastructure that can more effectively reduce household fecal contamination.

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Food insecurity is highly prevalent and linked to poorer diet and worse metabolic outcomes. Food insecurity can be stressful, and could elicit chronic psychological and physiological stress. In this study, we tested whether stress could be used to identify those at highest risk for worse diet and metabolic measures from food insecurity. Specifically, we hypothesized that cortisol (a physiological marker of stress) and perceived psychological stress would amplify the link between food insecurity and hyperpalatable food intake as well as metabolic measures. In a sample of 624 Black and White women aged 36-43 who participated in the NHLBI Growth and Health Study's midlife assessment, we assessed associations between food insecurity with hyperpalatable food intake (high fat + high sodium foods; high fat + high sugar foods; and high carbohydrate + high sodium foods), and metabolic measures (fasting glucose, insulin resistance, and waist circumference). We found that food insecurity was associated with higher levels of perceived stress (R² = 0.09), and greater intake of high fat + high sugar (hyperpalatable) foods (R² = 0.03). In those with higher cumulative cortisol (as indexed by hair cortisol), food insecurity was associated with higher levels of fasting glucose. Neither cortisol nor perceived stress moderated any other relationships, and neither variable functioned as a mediator in sensitivity analyses. Given these largely null findings, further research is needed to understand the role stress plays in the chronic health burdens of food insecurity.

INTRODUCTION: The U.S. safety net, which provides critical aid to households with low income, is composed of a patchwork of separate programs, and many people with low income benefit from accessing <1 program. However, little is known about multiprogram take-up, that is, participation conditioned on eligibility. This study examined individual and multiprogram take-up patterns and sociodemographic factors associated with multiprogram take-up of U.S. safety net programs. METHODS: The Assessing California Communities Experiences with Safety Net Supports study interviewed Californians and reviewed their 2019 tax forms between August 2020 and May 2021. Take-up of safety net programs was calculated among eligible participants (n=365), including the Earned Income Tax Credit; Supplemental Nutrition Assistance Program; the Special Supplemental Nutrition Program for Women, Infants, and Children; and Medicaid. Multivariable regressions identified sociodemographic factors associated with take-up of multiple programs. RESULTS: Take-up was highest for Medicaid (90.6%) and lowest for Supplemental Nutrition Assistance Program (57.5%). Among people who received benefits from at least 1 other program, take-up ranged from 81.7% to 84.8% for the Earned Income Tax Credit; 54.4%-62.0% for Supplemental Nutrition Assistance Program; 74.3%-80.1% for Special Supplemental Nutrition Program for Women, Infants, and Children; and 89.7%-98.1% for Medicaid. Having a lower income and being younger were associated with concurrent take-up of Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children. Among Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children recipients, having higher income, being older, and being primarily English speaking were associated with Earned Income Tax Credit take-up. CONCLUSIONS: Individual and multiprogram take-up vary between programs and by sociodemographic factors. Findings suggest opportunities to increase take-up of potentially synergistic programs by improving cross-program coordination, data sharing, and targeted recruitment of underenrolled subgroups (Supplemental Nutrition Assistance Program and Special Supplemental Nutrition Program for Women, Infants, and Children).

BACKGROUND: Type 2 diabetes elevates the risk of severe outcomes in COVID-19 patients, with multiple studies reporting higher case fatality rates. Metformin is a widely used medication for glycemic management. We hypothesize that improved adherence to metformin may lower COVID-19 post-infection mortality risk in this group. Utilizing data from the Mexican Social Security Institute (IMSS), we investigate the relationship between metformin adherence and mortality following COVID-19 infection in patients with chronic metformin prescriptions. METHODS: This is a retrospective cohort study consisting of 61,180 IMSS beneficiaries who received a positive polymerase chain reaction (PCR) or rapid test for SARS-CoV-2 and had at least two consecutive months of metformin prescriptions prior to the positive test. The hypothetical intervention is improved adherence to metformin, measured by proportion of days covered (PDC), with the comparison being the observed metformin adherence values. The primary outcome is all-cause mortality following COVID-19 infection. We defined the causal parameter using shift intervention, an example of modified treatment policies. We used the targeted learning framework for estimation of the target estimand. FINDINGS: Among COVID-19 positive patients with chronic metformin prescriptions, we found that a 5% and 10% absolute increase in metformin adherence is associated with a respective 0.26% (95% CI: -0.28%, 0.79%) and 1.26% (95% CI: 0.72%, 1.80%) absolute decrease in mortality risk. INTERPRETATION: Subject to the limitations of a real-world data study, our results indicate a causal association between improved metformin adherence and reduced COVID-19 post-infection mortality risk.