Louise C Ivers’s research while affiliated with Harvard Medical School and other places

Background Killed whole-cell oral cholera vaccines (kOCVs) are a standard prevention and control measure in cholera endemic areas, outbreaks, and humanitarian emergencies. Recently, new evidence has emerged and the ways in which the vaccines are used have changed. An updated synthesis of evidence on kOCV protection, is needed. Methods We systematically searched for randomized trials and observational studies that reported estimates of protection against confirmed cholera conferred by kOCVs. Eligible studies in English, French, Spanish or Chinese published through March 8, 2024, were included. Data on efficacy and effectiveness were extracted as were the number of doses, duration of follow-up, and age group. Efficacy and effectiveness estimates were summarized separately using random effects models to estimate protection by time since vaccination; meta-regression models were used to estimate protection, by dose, as a function of time since vaccination. Findings Twenty-three publications from five randomized controlled trials and ten observational studies were included. Average two-dose efficacy one-year post-vaccination was 55% (95%CI: 46-62%), declining to 44% (95%CI: 25-59%) four years post-vaccination. Average two-dose effectiveness was 69% (95%CI: 58-78%) one-year post-vaccination declining to 47% (95%CI: 9-70%) four years post-vaccination. Only one randomized trial assessed one-dose efficacy and found sustained protection for two years (52%; 95%CI 8-75%). Average one-dose effectiveness one year after vaccination was 60% (95%CI: 51-68%) and 47% (95%CI: 34-58%) after two years. Through age-group specific meta-analysis average 2-dose efficacy in children under five years old was half that of older individuals. Interpretation Two doses of kOCV provide protection against medically-attended cholera for at least four years post-vaccination. One-dose of kOCV provides protection for at least two years post-vaccination, but wanes faster than that of two doses. Children under five are less protected by kOCVs compared to those 5 years and older regardless of the number of doses received. Funding Bill and Melinda Gates Foundation

Objective The effects of sanitation and hygiene interventions on the gut microbiome and enteric pathogen burden are not well understood. We measured the association between free chlorine residue (FCR) levels in drinking water, microbiome composition, and stool enteric pathogens in infants and young children in Haiti. Methods FCR levels were measured in household drinking water and enteric pathogen burden was evaluated using multiplex RT-PCR of stool among 131 children from one month to five years of age living in Mirebalais, Haiti. Microbiome profiling was performed using metagenomic sequencing. Results Most individuals lived in households with undetectable FCR measured in the drinking water (112/131, 86%). Detection of enteric pathogen DNA in stool was common and did not correlate with household water FCR. The infant microbiome in households with detectable FCR demonstrated reduced richness (fewer total number of species, P = 0.04 Kruskall–Wallis test) and less diversity by Inverse Simpson measures (P = 0.05) than households with undetectable FCR. Infants in households with a detectable FCR were more likely to have abundant Bifidobacterium. Using in vitro susceptibility testing, we found that some Bifidobacterium species were resistant to chlorine. Conclusions FCR in household drinking water did not correlate with enteric pathogen burden in our study.

Background: Tuberculosis is a leading cause of death worldwide, and food insecurity is known to negatively influence health outcomes through multiple pathways. Few studies have interrogated the relationship between food insecurity and tuberculosis outcomes, particularly independent of nutrition. Methods: We conducted a prospective cohort study of adults initiating first-line treatment for clinically suspected or microbiologically confirmed drug-sensitive tuberculosis at a rural referral center in Haiti. We administered a baseline questionnaire, collected clinical data, and analyzed laboratory samples. We used logistic regression models to estimate the relationship between household food insecurity (Household Hunger Scale) and treatment failure or death. We accounted for exclusion of patients lost to follow-up using inverse probability of censoring weighting and adjusted for measured confounders and nutritional status using inverse probability of treatment weighting. Results: We enrolled 257 participants (37% female) between May 2020 and March 2023 with a median age (interquartile range) of 35 (25-45) years. Of these, 105 (41%) had no hunger in the household, 104 (40%) had moderate hunger in the household, and 48 (19%) had severe hunger in the household. Eleven participants (4%) died, and 6 (3%) had treatment failure. After adjustment, food insecurity was significantly associated with subsequent treatment failure or death (odds ratio 5.78 [95% confidence interval, 1.20-27.8]; P = .03). Conclusions: Household food insecurity at tuberculosis treatment initiation was significantly associated with death or treatment failure after accounting for loss to follow-up, measured confounders, and nutritional status. In addition to the known importance of undernutrition, our findings indicate that food insecurity independently affects tuberculosis treatment outcomes in Haiti.

Routinely collected testing data has been a vital resource for public health response during the COVID-19 pandemic and has revealed the extent to which Black and Hispanic persons have borne a disproportionate burden of SARS-CoV-2 infections and hospitalizations in the United States. However, missing race and ethnicity data and missed infections due to testing disparities limit the interpretation of testing data and obscure the true toll of the pandemic. We investigated potential bias arising from these two types of missing data through a case study in Holyoke, Massachusetts during the pre-vaccination phase of the pandemic. First, we estimated SARS-CoV-2 testing and case rates by race/ethnicity, imputing missing data using a joint modelling approach. We then investigated disparities in SARS-CoV-2 reported case rates and missed infections by comparing case rate estimates to estimates derived from a COVID-19 seroprevalence survey. Compared to the non-Hispanic white population, we found that the Hispanic population had similar testing rates (476 vs. 480 tested per 1,000) but twice the case rate (8.1% vs. 3.7%). We found evidence of inequitable testing, with a higher rate of missed infections in the Hispanic population compared to the non-Hispanic white population (77 vs. 58 infections missed per 1,000).

Background: Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied. Methods: We analyzed data from a cohort study of 165 ART-naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009-2013. 29 plasma biomarkers were measured pre-ART and four weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (Body Mass Index < 18.5 kg/m2), and clinical outcomes. Results: PCA identified 5 principal components (PCs) with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI 0.02 to 0.36) and post-ART (0.24, 95% CI 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, IL-12p40, VEGF, IL-1α, and IL-8, and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10, and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI 0.6 to 8.9) were associated with death in adjusted models. Discussion: We identified two distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and TB. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes.

Objectives The World Health Organization recommends the use of oral cholera vaccine (OCV) in cholera control efforts. Euvichol®, pre-qualified in 2015, is the leading component of the Global OCV stockpile, but data on its field effectiveness are limited. To evaluate Euvichol® vaccine effectiveness (VE), we conducted a case-control study between September 2018 to March 2020 following an OCV campaign in November 2017 in Haiti. Methods Cases were individuals with acute watery diarrhea. Stool samples were tested by culture and real-time polymerase chain reaction of the Vibrio cholerae ctxA gene. Cases were matched to four community controls without diarrhea by residence, enrollment time, age, and gender, and interviewed for sociodemographics, risk factors, and self-reported vaccination. Cholera cases were analyzed by conditional logistic regression in the VE study. Non-cholera diarrhea cases were analyzed in a bias-indicator study. Results We enrolled 15 cholera cases matched to 60 controls, and 63 non-cholera diarrhea cases matched to 249 controls. In the VE analysis, eight (53%) cases reported vaccination with any number of doses compared to 43 (72%) controls. Adjusted two-dose OCV VE was 69% (95% CI –71 to 94%). Conclusions Between 10-27 months after vaccination, Euvichol® was effective and similar to Shanchol™, suggesting that it can serve as one component of multi-sectoral comprehensive cholera control.

In Haiti in 2017, the prevalence of serum vibriocidal antibody titers against Vibrio cholerae serogroup O1 among adults was 12.4% in Cerca-la-Source and 9.54% in Mirebalais, suggesting a high recent prevalence of infection. Improved surveillance programs to monitor cholera and guide public health interventions in Haiti are necessary.