Stephen P Luby’s research while affiliated with Stanford University and other places

Background: Hospital-acquired neonatal infections are increasingly caused by antibiotic-resistant bacteria. It is unknown to what extent home-based births, which account for nearly a third of deliveries in Bangladesh, may also result in exposure to antibiotic-resistant bacteria. Methods: We enrolled mothers who delivered at home and their newborns from a rural community in Bangladesh during April-June, 2022. Within 2-7 days after delivery, we collected vaginal and rectal swabs from mothers and rectal swabs from the newborns. Swabs were cultured on chromogenic culture media selective for extended-spectrum β-lactamase-producing bacteria (ESBL-PB) and carbapenem-resistant bacteria (CRB). Demographic and risk factor data were collected via surveys. Birth attendants who facilitated the deliveries were interviewed regarding infection prevention practices. We performed descriptive analyses to identify potential risk factors associated with colonization. Results: Of the 50 mothers enrolled, the median age was 23 years (range 18 to 26). Thirty-eight (76%) mothers had at least one antenatal care visit. Only one mother reported hospitalization during pregnancy, and 4 reported antibiotic use during pregnancy. Following delivery, 47 (94%) mothers were colonized with ESBL-PB, and 37 (74%) were colonized with CRB. Of the newborns, 36 (72%) were colonized with ESBL-PB, and 27 (54%) were colonized with CRB. No associations were found with any perinatal exposures, though all households reported incomes below the international poverty level. Of the 9 birth attendants were able to be interviewed, 7 (78%) reported performing hand hygiene before delivery, and 8 (89%) reported glove use during the delivery. Attendants reported cleaning equipment shared across deliveries with soap and water and using boiled water for delivery (89%, n=8). Conclusions: Women and newborns in this rural population were frequently colonized with both ESBL-PB and CRB following home deliveries. This demonstrates the importance of community-based antibiotic-resistant bacterial transmission and need for further understanding community exposures driving antibiotic resistance.

Soil floors are common in low-income countries and can harbor contamination from unsafely managed human and animal fecal waste. Soil/dust ingestion directly from floors or indirectly via hands, drinking water and food can significantly contribute to children’s ingestion of fecal organisms. We assessed if finished (e.g., concrete) floors are associated with lower E. coli contamination in the domestic environment in rural Bangladesh. We collected samples from 1864 households over 3.5 years, including stored drinking water, child and caregiver hand rinses, courtyard soil, food, and flies (n=24,118 samples), and enumerated E. coli using IDEXX Quanti-Tray/2000. Controlling for potential confounders (socio-demographics, water/sanitation status, animal ownership), households with finished floors had slightly lower log10-transformed E. coli counts (Δlog10= -0.10 (-0.20, 0.00)) and prevalence (prevalence ratio=0.90 (0.83, 0.98)) on child hands than households with soil floors; floor material was not associated with contamination levels in other sample types. Finished floors were associated with lower E. coli contamination of child hands, food and stored drinking water following periods of higher rainfall and temperature, and lower E. coli contamination of child hands in households with more domestic animals. Measures to control enteric infections in low-income countries should test flooring improvements to reduce exposure to fecal contamination.

Ascariasis affects up to 1.2 billion people globally, with a significant burden in low-income regions. Despite high prevalence and substantial morbidity, existing monitoring and intervention strategies are insufficient due to sample extraction and quantification inaccuracies. This review underscores the need for enhanced environmental monitoring to improve Ascaris egg remediation and reduce disease incidence. We critically reviewed existing environmental monitoring practices and explored advanced technologies like lab-on-a-disk for rapid detection and quantification of Ascaris eggs. A meta-analysis and meta-regression of studies on Ascaris egg recovery revealed significant variability in recovery rates, with the best methods achieving less than 60% efficiency. Advanced imaging analyses and lab-on-a-disk technologies show promise for rapid detection and viability assessment. By identifying gaps in current methodologies, we recommend more effective environmental interventions. The review incorporated high-quality data adhering to PRISMA guidelines, ensuring comprehensive coverage of the latest methodologies. Integrating improved detection methods and environmental control strategies can significantly reduce ascariasis incidence, especially in endemic regions. Future efforts should focus on refining these technologies and validating their application in real-world settings for sustainable disease control.

Background: The Surveillance for Enteric Fever in Asia Project (SEAP) conducted blood culture surveillance for Salmonella enterica serotype Typhi (S. Typhi) and Paratyphi (S. Paratyphi) to provide an evidence base for prevention and control measures in Bangladesh, Nepal, and Pakistan. Methods: From October 2020 to September 2022, we conducted prospective clinical surveillance and retrospective laboratory surveillance at health facilities in Dhaka, Bangladesh; Kathmandu and Kavrepalanchok, Nepal; and Karachi, Pakistan. Patients were eligible if they were outpatients with three or more days of fever in the last week. In Nepal and Pakistan, inpatients were eligible if they had suspected or confirmed enteric fever; in Bangladesh, only inpatients with confirmed enteric fever were enrolled. Patients with blood culture–confirmed enteric fever identified by hospital laboratories and laboratory network sites were also enrolled. Patients completed interviews and medical records were reviewed and abstracted. All enrolled patients had blood cultures performed. Antibiograms were performed to characterize drug sensitivity. We summarized the data descriptively. Findings: A total of 17,593 patients were enrolled from 19 facilities. Of these, 8410 patients had culture-confirmed enteric fever. Case counts in all countries decreased in the early stages of the COVID-19 pandemic, but increased over time in Bangladesh and Pakistan. Case counts remained low throughout the study period in Nepal. In all countries, typhoid was more common than paratyphoid; the proportion of paratyphoid cases ranged from 8.4% in Pakistan to 16% in Nepal. Extensively drug-resistant typhoid was common in Pakistan (69%), but was not detected in Bangladesh or Nepal. Interpretation: Cases of enteric fever decreased during the COVID-19 pandemic, though it is not clear how much of this decrease relates to true changes in transmission versus health-seeking behavior. Funding: This project was funded by the Gates Foundation through INV-008335.

Background Hepatitis E virus (HEV) is endemic in many resource-poor countries. Despite an available vaccine, data on HEV-associated mortality are scarce, hindering informed decisions. This study aims to estimate the population-based rate of HEV-specific mortality in Bangladesh. Methods During December 2014 to September 2017, we conducted surveillance in 6 tertiary hospitals in Bangladesh. Patients aged ≥14 years with acute jaundice were recruited, tested for IgM anti-HEV, and followed up postdischarge. A mortality survey in the hospital catchment areas identified deaths associated with acute jaundice, including maternal deaths, stillbirths, and neonatal deaths delivered by a mother with acute jaundice during pregnancy, as confirmed by 2 independent physicians reviewing verbal autopsy data. Results Out of 1925 patients with acute jaundice enrolled in the surveillance hospitals, 302 died, with 28 (9%) testing positive for IgM anti-HEV. In the hospital catchment areas, the team identified 587 jaundice-associated deaths, including 25 maternal deaths. Combining hospital-based surveillance and mortality survey data, the study estimated 986 (95% CI, 599–1338) HEV-associated deaths annually among individuals aged ≥14 years in Bangladesh, including 163 (95% CI, 57–395) maternal deaths. Additionally, 279 (95% CI, 101–664) stillbirths and 780 (95% CI, 365–1297) neonatal deaths were attributed to HEV infection annually. Conclusions Prior Global Burden of Disease studies presented wildly varying modeling estimates of HEV-associated annual deaths, ranging from 50 000 in 2013 to 1932 in 2019. This study is the first to directly measure population-based estimates of mortality in Bangladesh, which can be used to determine the cost-effectiveness of hepatitis E vaccination and other interventions.

Shorter telomere length (TL) is associated with an increased risk for developing chronic or age-related diseases in adults. The process of telomere shortening is accelerated in response to stress and is well characterized in adult populations from high-income countries. Prior studies suggest the relationship between stress, shorter TL, and disease risk initiates in early life. Nested within the WASH Benefits Bangladesh trial, we examined associations between parental stressors, including maternal exposure to intimate partner violence (IPV), maternal depressive symptoms, and parental perceived stress, and child TL in rural Bangladesh. We measured whole blood relative TL in 660 children at median age 14 months and 702 children at median age 28 months. We estimated mean differences between the 25th and 75th percentile or absence and presence of each exposure using generalized additive models. IPV during pregnancy was associated with more TL attrition between 14 and 28 months (− 0.32 (95% CI − 0.64, − 0.01), p-value 0.05). This association was not significant after correction for multiple comparisons. Other parental psychosocial stressors were not associated with child TL outcomes at 14 or 28 months of age in rural Bangladesh. Telomere biology during early-life development may vary across settings.

Background A previous cluster-randomized controlled trial in Bangladesh found that individual or combined water, handwashing, sanitation, and nutrition interventions during pregnancy and after birth improved developmental outcomes of children at 1 and 2 years of age. We aimed to determine if these intervention effects were sustained at school-age. Methods and Findings Pregnant women were enrolled between May 2012 and July 2013 and randomized into chlorinated drinking water (W); improved sanitation (S); handwashing with soap (H); combined WSH; nutrition counselling and provision of lipid-based supplements (N); combined WSH+N, or a passive control arm (C) (N=5,551). We followed-up enrolled mothers and children 5 years after intervention completion. Primary outcomes were child cognition, fine motor abilities, behaviour, school achievement, and executive function; secondary outcomes were maternal mental health and the home environment. We conducted intention to treat analyses using generalized linear models to determine unadjusted and adjusted comparisons between each arm and the control, accounting for pair-matching and block level clustering. Between September 2019 and February 2021, we re-enrolled 3,832 children. Children in the WSH+N, N, and S arms had improved cognitive scores on one or more domains compared to the control arm, with adjusted effect sizes between 0.10 (95%CI: 0.00, 0.20) and 0.15 (0.03, 0.27). Children in all arms except S had improved prosocial behaviour, with effect sizes between 0.21 (0.07, 0.34) and 0.33 (0.17, 0.49). No intervention effects were observed for fine motor, difficult behaviours, executive functioning, or school achievement. Maternal depressive symptoms were improved in the WSH+N, H, and N arms, and the stimulating home environment was improved in all intervention arms. Data collection for this study was interrupted by a 6-month pause at the start of the COVID-19 pandemic. Conclusions At 7 years of age, we found small, sustained impacts of early water, sanitation, hygiene, and nutrition interventions on child cognitive and social-emotional outcomes, the stimulating home environment, and maternal mental health. Future work to determine the mechanisms underlying these intervention effects will further inform the design of early interventions to improve child health and development. Trial registration Follow-up trial: ClinicalTrials.gov , NCT04443855 Original WASH-Benefits Bangladesh (WASH-B): ClinicalTrials.gov , NCT01590095

Background Fractional doses of vaccine to protect against COVID-19 offer the potential to expand vaccine availability, reduce side effects, and enhance vaccination campaign efficiency. This study aimed to assess the immune response and safety of fractional doses of SARS-CoV-2 booster vaccines compared to full doses in immunocompetent adults aged 18–60 who had previously received a full series of Sinovac, AZD1222 (AstraZeneca), or BNT162b2 (Pfizer/BioNTech). Methods This trial was structured as a parallel-group, double-blind, randomised Phase IV non-inferiority study, carried out in Campo Grande, Midwest, Brazil. After obtaining consent, eligible participants were randomised to one of 5–6 study arms, depending on their priming vaccine. Participants were followed for 21–60 days after vaccination through in-person visits and remote contact for blood collection and safety evaluation. Anti-spike binding IgG antibodies were measured by ELISA. The primary outcome was the difference in seroresponse rates between the full and fractional doses, with a non-inferiority threshold of 10%. Findings A total of 1451 participants were randomised and administered booster vaccines between 5 July and 3 October, 2022. A half dose of BNT162b2 met the non-inferiority threshold, compared to a full dose in the Sinovac and AZD1222 primed groups. Sinovac induced an inferior response compared to AZD1222 and BNT162b2 full or fractional dose boosters in participants primed with Sinovac. Fractional booster doses of BNT162b2 consistently resulted in higher seroresponse rates (ranging from 35.4% to 78.3%) compared to fractional boosters of AZD1222 (ranging from 10.0% to 44.7%) or a full dose of Sinovac (4.2%). Both full and fractional dose vaccines were generally well tolerated. Local and systemic adverse events occurred across all treatment arms in line with expectations, with nine serious adverse events reported, none of which were determined to be related to study vaccination. Interpretation Our data show that the immunogenicity of booster vaccines depends on the initial vaccine, baseline antibody levels, and the booster vaccine used. Fractional doses of BNT162b2 and AZD1222 were non-inferior to a full Sinovac booster in individuals primed with Sinovac. However, fractional doses of BNT162b2 were not non-inferior in BNT162b2-primed individuals, and AZD1222 fractional doses were only non-inferior in the AZD1222 priming arm. We advise against Sinovac as a booster. Fractional doses of BNT162b2 or AZD1222 remain practical alternatives for Sinovac-primed populations in resource-limited settings. Funding 10.13039/100016302Coalition for Epidemic Preparedness Innovations (CEPI)/10.13039/100004107Sabin Vaccine Institute.