Background Despite the success of rotavirus vaccines over the last decade, rotavirus remains a leading cause of severe diarrheal disease among young children. Further progress in reducing the burden of disease is inhibited, in part, by vaccine underperformance in certain settings. Early trials suggested that oral poliovirus vaccine (OPV), when administered concomitantly with rotavirus vaccine, reduces rotavirus seroconversion rates after the first rotavirus dose with modest or nonsignificant interference after completion of the full rotavirus vaccine course. Our study aimed to identify a range of individual-level characteristics, including concomitant receipt of OPV, that affect rotavirus vaccine immunogenicity in high- and low-childmortality settings, controlling for individual- and country-level factors. Our central hypothesis was that OPV administered concomitantly with rotavirus vaccine reduced rotavirus vaccine immunogenicity. Methods and findings Pooled, individual-level data from GlaxoSmithKline's Phase II and III clinical trials of the monovalent rotavirus vaccine (RV1), Rotarix, were analyzed, including 7,280 vaccinated infants (5-17 weeks of age at first vaccine dose) from 22 trials and 33 countries/territories (5 countries/territories with high, 13 with moderately low, and 15 with very low child mortality). Two standard markers for immune response were examined including antirotavirus immunoglobulin A (IgA) seroconversion (defined as the appearance of serum antirotavirus IgA antibodies in subjects initially seronegative) and serum antirotavirus IgA titer, both collected approximately 4-12 weeks after administration of the last rotavirus vaccine dose. Mixed-effect logistic regression and mixed-effect linear regression of log-transformed data were used to identify individual- and country-level predictors of seroconversion (dichotomous) and antibody titer (continuous), respectively. Infants in high-child-mortality settings had lower odds of seroconverting compared with infants in low-child-mortality settings (odds ratio [OR] = 0.48, 95% confidence interval [CI] 0.43-0.53, p < 0.001). Similarly, among those who seroconverted, infants in high-child-mortality settings had lower IgA titers compared with infants in low-child-mortality settings (mean difference [β] = 0.83, 95% CI 0.77-0.90, p < 0.001). Infants who received OPV concomitantly with both their first and their second doses of rotavirus vaccine had 0.63 times the odds of seroconverting (OR = 0.63, 95% CI 0.47-0.84, p = 0.002) compared with infants who received OPV but not concomitantly with either dose. In contrast, among infants who seroconverted, OPV concomitantly administered with both the first and second rotavirus vaccine doses was found to be positively associated with antirotavirus IgA titer (β = 1.28, 95% CI 1.07-1.53, p = 0.009). Our findings may have some limitations in terms of generalizability to routine use of rotavirus vaccine because the analysis was limited to healthy infants receiving RV1 in clinical trial settings. Conclusions Our findings suggest that OPV given concomitantly with RV1 was a substantial contributor to reduced antirotavirus IgA seroconversion, and this interference was apparent after the second vaccine dose of RV1, as with the original clinical trials that our reanalysis is based on. However, our findings do suggest that the forthcoming withdrawal of OPV from the infant immunization schedule globally has the potential to improve RV1 performance.

Background: Despite Colombia's robust well-child visits program, Colombian children and mothers still suffer from anemia, especially in populations of lower socioeconomic status. In this study, we aimed to quantify the prevalence and risk factors among mothers and their children attending their well-child visits in Apartadó, a municipality in the Urabá region of the Colombian Caribbean. Methods: There were 100 mother–child pairs enrolled in this secondary data-analysis study from a health facility in the municipality of Apartadó, Urabá, Colombia, during well-child visits. Self-reported data included child illnesses in the past two weeks (diarrheal, fever, or respiratory symptoms), child feeding practices (breastfeeding, complementary feeding), child vaccinations, and demographic characteristics (mother’s and child’s age, mother’s education, marital status, race, and child sex) and socioeconomic status. Mother and child anthropometry data were collected via standardized weight and height measurements. Mother or child anemia status was collected via a blood test. Chi-squared tests and multivariable logistic regression were used to assess associations between risk factors and anemia. Result: The anemia prevalence in children (74%) and mothers (47%) was higher than the Colombian national prevalence. Reported child comorbidities in the preceding two weeks were not significantly associated with child anemia and included respiratory illnesses (60%), fever (46%), and diarrhea (30%). Stunting (8%) was not significantly associated with anemia. Wasting (0%) was not observed in this study. Reported child breastfeeding and complementary feeding were also not significantly associated with child anemia. In adjusted models, the child's significant risk factors for anemia included the mother's "Mestiza" race (OR: 4.681; 95% CI: 1.258, 17.421) versus the Afro-Colombian race. Older children (25–60 months) were less likely to develop anemia than younger (6–24 months) children (OR: 0.073; 95% CI: 0.015, 0.360). Conclusions: The finding of high anemia prevalence in this study advances our understanding of child and maternal anemia in populations of low socioeconomic status where health care is regularly accessed through well-child programs.

In the agricultural setting, core global food safety elements, such as hand hygiene and worker furlough, should reduce the risk of norovirus contamination on fresh produce. However, the effect of these practices has not been characterized. Using a quantitative microbial risk model, we evaluated the individual and combined effect of farm-based hand hygiene and worker furlough practices on the maximum risk of norovirus infection from three produce commodities (open leaf lettuce, vine tomatoes, and raspberries). Specifically, we tested two scenarios where a harvester's and packer's norovirus infection status was: 1) assumed positive; or 2) assigned based on community norovirus prevalence estimates. In the first scenario with a norovirus-positive harvester and packer, none of the individual interventions modeled reduced produce contamination to below the norovirus infectious dose. However, combined interventions, particularly high handwashing compliance (100%) and efficacy (6 log10 virus removal achieved using soap and water for 30 s), reduced produce contamination to <1–82 residual virus. Translating produce contamination to maximum consumer infection risk, 100% handwashing with a 5 log10 virus removal was necessary to achieve an infection risk below the threshold of 0.032 infections per consumption event. When community-based norovirus prevalence estimates were applied to the harvester and packer, the single interventions of 100% handwashing with 3 log10 virus removal (average 0.02 infection risk per consumption event) or furlough of the packer (average 0.03 infection risk per consumption event) reduced maximum infection risk to below the 0.032 threshold for all commodities. Bundled interventions (worker furlough, 100% glove compliance, and 100% handwashing with 1-log10 virus reduction) resulted in a maximum risk of 0.02 per consumption event across all commodities. These results advance the evidence-base for global produce safety standards as effective norovirus contamination and risk mitigation strategies.

Essential food workers experience elevated risks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection due to prolonged occupational exposures in food production and processing areas, shared transportation (car or bus), and employerprovided shared housing. Our goal was to quantify the daily cumulative risk of SARS-CoV-2 infection for healthy susceptible produce workers and to evaluate the relative reduction in risk attributable to food industry interventions and vaccination. We simulated daily SARSCoV- 2 exposures of indoor and outdoor produce workers through six linked quantitative microbial risk assessment (QMRA) model scenarios. For each scenario, the infectious viral dose emitted by a symptomatic worker was calculated across aerosol, droplet, and fomitemediated transmission pathways. Standard industry interventions (2-m physical distancing, handwashing, surface disinfection, universal masking, ventilation) were simulated to assess relative risk reductions from baseline risk (no interventions, 1-m distance). Implementation of industry interventions reduced an indoor worker's relative infection risk by 98.0% (0.020; 95% uncertainty interval [UI], 0.005 to 0.104) from baseline risk (1.00; 95% UI, 0.995 to 1.00) and an outdoor worker's relative infection risk by 94.5% (0.027; 95% UI, 0.013 to 0.055) from baseline risk (0.487; 95% UI, 0.257 to 0.825). Integrating these interventions with twodose mRNA vaccinations (86 to 99% efficacy), representing a worker's protective immunity to infection, reduced the relative infection risk from baseline for indoor workers by 99.9% (0.001; 95% UI, 0.0002 to 0.005) and outdoor workers by 99.6% (0.002; 95% UI, 0.0003 to 0.005). Consistent implementation of combined industry interventions, paired with vaccination, effectively mitigates the elevated risks from occupationally acquired SARS-CoV-2 infection faced by produce workers. IMPORTANCE This is the first study to estimate the daily risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across a variety of indoor and outdoor environmental settings relevant to food workers (e.g., shared transportation [car or bus], enclosed produce processing facility and accompanying breakroom, outdoor produce harvesting field, shared housing facility) through a linked quantitative microbial risk assessment framework. Our model has demonstrated that the elevated daily SARS-CoV-2 infection risk experienced by indoor and outdoor produce workers can be reduced below 1% when vaccinations (optimal vaccine efficacy, 86 to 99%) are implemented with recommended infection control strategies (e.g., handwashing, surface disinfection, universal masking, physical distancing, and increased ventilation). Our novel findings provide scenario-specific infection risk estimates that can be utilized by food industry managers to target high-risk scenarios with effective infection mitigation strategies, which was informed through more realistic and context-driven modeling estimates of the infection risk faced by essential food workers daily. Bundled interventions, particularly if they include vaccination, yield significant reductions (.99%) in daily SARS-CoV-2 infection risk for essential food workers in enclosed and open-air environments.

To examine the long-term infectivity of human norovirus in water, 13 study subjects were challenged at different time points with groundwater spiked with the prototype human norovirus, Norwalk virus. Norwalk virus spiked in groundwater remained infectious after storage at room temperature in the dark for 61 days (the last time point tested). The Norwalk virus-seeded groundwater was stored for 1,266 days and analyzed, after RNase treatment, by reverse transcription-quantitative PCR (RT-qPCR) to detect Norwalk virus RNA contained within intact capsids. Norwalk virus RNA within intact capsids was detected in groundwater for 1,266 days, with no significant log10 reduction throughout 427 days and a significant 1.10-log10 reduction by day 1266. Purified Norwalk virus RNA (extracted from Norwalk virus virions) persisted for 14 days in groundwater, tap water, and reagent-grade water. This study demonstrates that Norwalk virus in groundwater can remain detectable for over 3 years and can remain infectious for at least 61 days. (ClinicalTrials.gov identifier NCT00313404.)

Contamination of oysters with human noroviruses (HuNoV) constitutes a human health risk and may lead to severe economic losses in the shellfish industry. There is a need to identify a technology that can inactivate HuNoV in oysters. In this study, we conducted a randomized, double-blinded clinical trial to assess the effect of high hydrostatic pressure processing (HPP) on Norwalk virus (HuNoV genogroup I.1) inactivation in virus-seeded oysters ingested by subjects. Forty-four healthy, positive-secretor adults were divided into three study phases. Subjects in each phase were randomized into control and intervention groups. Subjects received Norwalk virus (8FIIb, 1.0 × 104 genomic equivalent copies) in artificially seeded oysters with or without HPP treatment (400 MPa at 25°C, 600 MPa at 6°C, or 400 MPa at 6°C for 5 min). HPP at 600 MPa, but not 400 MPa (at 6° or 25°C), completely inactivated HuNoV in seeded oysters and resulted in no HuNoV infection among these subjects, as determined by reverse transcription-PCR detection of HuNoV RNA in subjects' stool or vomitus samples. Interestingly, a white blood cell (granulocyte) shift was identified in 92% of the infected subjects and was significantly associated with infection (P = 0.0014). In summary, these data suggest that HPP is effective at inactivating HuNoV in contaminated whole oysters and suggest a potential intervention to inactivate infectious HuNoV in oysters for the commercial shellfish industry.

BACKGROUND In Bolivia, in 2008, the under-five mortality rate is 54 per 1000 live births. Diarrhea causes 15% of these deaths, and 40% of pediatric diarrhea-related hospitalizations are caused by rotavirus illness (RI). Rotavirus vaccination (RV), subsidized by international donors, is expected to reduce morbidity, mortality, and economic burden to the Bolivian state. Estimates of illness and economic burden of RI and their reduction by RV are essential to the Bolivian state’s policies on RV program financing. The goal of this report is to estimate the economic burden of RI and the cost-effectiveness of the RV program. METHODS To assess treatment costs incurred by the healthcare system, we abstracted medical records from 287 inpatients and 6,751 outpatients with acute diarrhea between 2005 and 2006 at 5 sentinel hospitals in 4 geographic regions. RI prevalence rates were estimated from 4 years of national hospital surveillance. We used a decision-analytic model to assess the potential cost-effectiveness of universal RV in Bolivia. RESULTS Our model estimates that, in a 5-year birth cohort, Bolivia will incur over US$3 million in direct medical costs due to RI. RV reduces, by at least 60%, outpatient visits, hospitalizations, deaths, and total direct medical costs associated with rotavirus diarrhea. Further, RV was cost-savings below a price of US$3.81 per dose and cost-effective below a price of US$194.10 per dose. Diarrheal mortality and hospitalization inputs were the most important drivers of rotavirus vaccine cost-effectiveness. DISCUSSION Our data will guide Bolivia’s funding allocation for RV as international subsidies change.

Objective To assess factors influencing perspectives on Brazil’s national Family Health Program (PSF) by exploring satisfaction with PSF units and home-visit community health agents and perceptions about PSF unit accessibility among frequent users (primary caretakers of children under age 5) in Vespasiano, Minas Gerais. Methods Data were collected though cross-sectional household surveys to determine programmatic and demographic factors affecting user satisfaction with the PSF. Multivariate logistic modeling was used to estimate users’ satisfaction with PSF units and agents and perceived access to PSF unit services. Chi-square and analysis of variance (ANOVA) tests were used to estimate statistical differences. Results The majority of caretakers were satisfied with both their PSF unit and their PSF community health agent and had received at least one monthly home visit from the health agent. Satisfaction with both the health agent and the unit was positively associated with perceived access to the unit and frequency of agent home visits. Caretakers who reported that their PSF agent made one or more home visits per month were more likely to perceive the PSF unit as being “accessible” (or “sometimes accessible”). Conclusions The current data are important indicators of population health in Minas Gerais, Brazil, and suggest that users’ satisfaction with the PSF and perceptions about its accessibility can be improved by ensuring that all households receive at least one health agent home visit per month. These results could be applied to other parts of Brazil or Latin America to improve understanding of user perceptions of health systems.

Objective In Latin America and the Caribbean, Bolivia has the third highest rate of mortality among children under five years of age (57 per 1 000), with 14.0% of under-five deaths attributable to diarrhea. Because a child’s world is predominantly controlled by and experienced through his or her mother, this investigation aims to understand what maternal dimensions may determine child diarrhea. Methods Variables were selected from the 2003 Bolivia Demographic and Health Survey to create indices of three maternal dimensions using principal components analysis: behavior and experience, access to care, and agency. The three indices were included in a logistic regression model while controlling for economic status, maternal education, and residence type. Results A total of 4 383 women who had children less than 5 years old were included in the final sample and 25.0% of mothers reported that their most recent born child had experienced an episode of diarrhea in the 2 weeks before the survey. Mothers with high levels of maternal agency or of high economic status were significantly less likely to report their child experienced an episode of diarrhea than women of low levels. Women with primary education were significantly more likely to report that their child experienced diarrhea than women with no education. Conclusions High levels of agency have a significant protective effect even when controlling for other factors. Increasing maternal agency could have a positive impact on child health in Bolivia, and future work should aim to understand what accounts for different levels of agency and how it may be strengthened.

Objective To analyze the strengths and limitations of the Family Health Strategy (ESF) from the perceptions of healthcare professionals and community. Methods Between June-August 2009, in the city of Vespasiano, Minas Gerais State, Southeastern Brazil, a questionnaire was applied to evaluate the ESF with 77 healthcare professionals and 293 caretakers of children under five. Health professional ESF training, community access to care, patient communication, and delivery of health education and pediatric care were of main interest in the evaluation. Logistic regression analysis was used to obtain odds ratios (OR) and 95% confidence intervals (CI). Results The majority of health care professionals reported their program training was insufficient in quantity, content and method of delivery. Caretakers and professionals identified similar weaknesses (services not accessible to the caretakers, lack of healthcare professionals, poor training for professionals) and strengths (community health worker-patient communications, provision of educational information, and pediatric care). Recommendations for improvement included: more doctors and specialists, more and better training, and scheduling improvements. Caretaker satisfaction with the ESF was found to be related to perceived benefits such as community health agent household visits (OR 5.8, 95%CI 2.8;12.1), good professional-patient relationships (OR 4.8, 95%CI 2.5;9.3), and family-focused health (OR 4.1, 95%CI 1.6;10.2); and perceived problems such as lack of personnel (OR 0.3, 95%CI 0.2;0.6), difficulty with access (OR 0.2, 95%CI 0.1;0.4), and poor quality of care (OR 0.3, 95%CI 0.1;0.6). Overall, 62% of caretakers reported being generally satisfied with the ESF services. Conclusions Identifying the limitations and strengths of the ESF from the healthcare professional and caretaker perspective may serve to advance primary community healthcare in Brazil.