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The prevalence of enteric pathogen detection in children in low-income countries climbs rapidly between birth and 6 months of age. Few studies have tested whether improved household environmental and behavioral hygiene conditions protects infants from exposure to enteric pathogens spread via unhygienic human and animal sanitation conditions, especially during this early window of infancy. This cross-sectional study utilized enrollment survey data among households with 6 month old infants in Kisumu, Kenya participating in the Safe Start cluster-randomized controlled trial to estimate associations between household water access and treatment, animal vectors, sanitation access, hand washing practices, supplemental feeding, and flooring, with the outcomes of caregiver-reported 7-day diarrhea prevalence and sum count of different enteric viruses, bacteria, and parasites pathogens in infant stool. Then, we tested whether household environmental hygiene and behavioral practices moderated associations between infant exposure outcomes and latrine access and domestic animal co-habitation. We found that reported handwashing after handling animals and before eating were strongly associated with lower risk of caregiver-reported diarrhea, while owning and co-habitating with animals (versus no animals), living in a household with vinyl covered dirt floors (versus finished floors), and feeding infants cow milk (versus no milk) were strongly associated with pathogen detection in infants. Caregiver handwashing after child or self-defecation moderated the relationship between shared sanitation (vs private) sanitation access and infant exposure to pathogens such that handwashing had the greatest benefit for preventing pathogen exposure of infants in households with private latrines. In the absence of handwashing, access to private sanitation posed no benefits over shared latrines for protecting infants from exposure. Our evidence highlights eliminating animal co-habitation, improving flooring, improving post-defecation and food-related handwashing, and improving safety of cow milk sources and/or safe household storage of milk as interventions to prevent enteric pathogen exposure of infants less than 6 months age.Key QuestionsWhat is already known?The population prevalence of enteric infections and diarrhea climbs rapidly in the first year of life. Risk factors for pediatric infections include unhygienic human and animal sanitary conditions that introduce feces into the environment, as well as intermediate environmental and behavioral exposure pathways. Research examining the mitigating role of improved environmental and behavioral conditions in preventing infant exposure to human and animal sanitary conditions is limited.What are the new findings?Contact with domestic animals and feeding infants cow milk are leading risk factors for exposure to enteric pathogens by 6 months age in Kisumu, while handwashing after animal handling and before eating are protective factors against self-reported diarrhea. The benefits of access to a private improved latrine (versus shared) for protecting infants from pathogen exposure were conditional upon caregivers washing hands after defecation or child-defecation.What do the new findings imply?Interventions that keep animals out of infant living spaces and that improve food-related and post-defecation handwashing may be the most effective strategies for controlling the population prevalence of enteric infections in infants between birth and 6 months age in Kisumu and similar settings.

BackgroundCD20 depletion is a highly-effective treatment for relapsing multiple sclerosis that maintains B cells at low levels through six monthly dosing of 600mg ocrelizumab. This dosing schedule is associated with inhibition of seroconversion following SARS-CoV-2 vaccination, in contrast to the high levels of seroconversion following treatment with alemtuzumab and cladribine tablets. A number of emerging reports suggest that repopulation of 1-3% B cells facilitates seroconversion after CD20-depletion. The frequency of this occurring following repeated ocrelizumab treatment, after other DMT, and after treatment cessation is largely unknown.MethodsRelapse data, lymphocyte and CD19 B cell numbers were extracted from phase II ocrelizumab extension study (NCT00676715) data supplied by the manufacturer via the Vivli Inc, trial data-request portal. Repopulation data of oral cladribine from the phase III CLARITY study (NCT00213135) was supplied by the European Medicines Agency; and the alemtuzumab phase III CARE-MS I (NCT00530348) and CARE-MS II (NCT00548405) trial data were supplied by the manufacturer via the clinicalstudydatarequest.com portal.ResultsOnly 3-5% of people with MS exhibit 1% B cells at 6 months after the last infusion following 3-4 cycles of ocrelizumab, compared to 50-55% at 9 months, and 85-90% at 12 months. During this time relapses occurred at consistent disease breakthrough rates compared to people during standard therapy. In contrast most people (90-100%) exhibited more than 1% B cells during treatment with either cladribine or alemtuzumab.ConclusionsFew people repopulate peripheral B cells with standard ocrelizumab dosing, however an extending the dosing interval by 3-6 months may allow many more people to potentially seroconvert in the relative absence of excess relapse-activity. Most people demonstrate B cell repletion within 3 months of the last treatment of alemtuzumab and cladribine. This may help protect against severe COVID-19.