Impact of Vaccination With the SCB-2019 Coronavirus Disease 2019 Vaccine on Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Household Contact Study in the Philippines.

BACKGROUND: An exploratory household transmission study was nested in SPECTRA, the phase 2/3 efficacy study of the adjuvanted recombinant protein-based COVID-19 vaccine SCB-2019. We compared the occurrence of confirmed COVID-19 infections between households and household contacts of infected SPECTRA placebo or SCB-2019 recipients. METHODS: SPECTRA participants at 8 study sites in the Philippines who developed real-time reverse transcriptase-polymerase chain reaction (rRT-PCR)-confirmed COVID-19 were contacted by a study team blinded to assignment of index cases to vaccine or placebo groups to enroll in this household transmission study. Enrolled households and household contacts were monitored for 3 weeks using rRT-PCR and anti-SARS-CoV-2 N-antigen IgG/IgM testing to detect new COVID-19 infections. RESULTS: One hundred fifty-four eligible COVID-19 index cases (51 vaccinees, 103 placebo) were included. The secondary attack rate per household for symptomatic COVID-19 infection was 0.76% (90% CI: .15-3.90%) if the index case was an SCB-2019 vaccinee compared with 5.88% (90% CI: 3.20-10.8%) for placebo index cases, a relative risk reduction (RRR) of 79% (90% CI: -28% to 97%). The RRR of symptomatic COVID-19 per household member was similar: 84% (90% CI: 28-97%). The impact on attack rates in household members if index cases were symptomatic (n = 130; RRR = 80%; 90% CI: 7-96%) or asymptomatic (n = 24; RRR = 100%; 90% CI: -76% to 100%) was measurable but the low numbers undermine the clinical significance. CONCLUSIONS: In this prospective household contact study vaccination with SCB-2019 reduced SARS-CoV-2 transmission compared with placebo in households and in household members independently of whether or not index cases were symptomatic.

Rotavirus Vaccine Trials in International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) and Future Use of the Vaccine in Bangladesh.

Safe and effective rotavirus vaccines (RVs) are needed to reduce the enormous public health burden of rotavirus illness in developing countries. Vaccination is critical for effective control of rotavirus infection since it cannot be prevented with improvements in water and sanitation. The International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) has completed several groundbreaking RV trials (Phase I-Phase IV). The safety, immunogenicity, efficacy, and effectiveness of different RVs were evaluated among both urban and rural populations. In this study, we present the results, policy implications, and lessons learned for successful implementation of these trials as well as future directions for rotavirus vaccination in Bangladesh.

Raising the case of hepatitis E: Report from the 2nd international HEV symposium.

The 2nd International Hepatitis E Virus Symposium was held on April 28 and 29, 2023, in London, UK. The conference was hosted by the International Vaccine Institute and brought together key clinicians, researchers, and private and public stakeholders for a dedicated forum on hepatitis E virus (HEV). The scientific program spanned multiple facets of HEV, from updates on clinical research and diagnostic advances to vaccine development. The conference highlighted presentations on several critical HEV vaccine studies that will greatly impact the field, including the largest effectiveness study of Hecolin vaccine outside of China and the first reactive mass-vaccination campaign in South Sudan. This report summarizes information shared at the convening and offers perspectives on the steps forward for hepatitis E.

Assessing the mucosal intestinal and systemic humoral immunity of sequential schedules of inactivated poliovirus vaccine and bivalent oral poliovirus vaccine for essential immunization in Bangladesh: An open-label, randomized controlled trial.

In 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) recommended introduction of at least one inactivated poliovirus vaccine (IPV) dose in essential immunization programs. We evaluated systemic humoral and intestinal mucosal immunity of a sequential IPV-bivalent oral poliovirus vaccine (bOPV) schedule compared with a co-administration IPV + bOPV schedule in an open-label, randomized, controlled, non-inferiority, inequality trial in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomized to either: (A) IPV and bOPV at 6 and bOPV at 10 and 14 weeks (IPV + bOPV-bOPV-bOPV); or (B) IPV at 6 and bOPV at 10 and 14 weeks (IPV-bOPV-bOPV). Of 456 participants enrolled and randomly assigned during May-August 2015, 428 (94%) were included in the modified intention-to-treat analysis (arm A: 211, arm B: 217). Humoral immune responses did not differ at 18 weeks between study arms: type 1 (98% versus 96%; p = 0.42), type 2 (37% versus 39%; p = 0.77), and type 3 (97% versus 93%; p = 0.07). Virus shedding one week after the bOPV challenge dose in arm B was non-inferior to arm A (type 1 difference = -3% [90% confidence interval: -6 - 0.4%]; type 3 difference: -3% [-6 to -0.2%]). Twenty-six adverse events including seven serious adverse events were reported among 25 participants including one death; none were attributed to study vaccines. An IPV-bOPV-bOPV sequential schedule induced comparable systemic humoral immunity to all poliovirus types and types 1 and 3 intestinal mucosal immunity as an IPV + bOPV-bOPV-bOPV co-administration schedule.

Receipt of hepatitis E vaccine and fetal loss in rural Bangladesh: further analysis of a double-blind, cluster-randomised, controlled trial.

BACKGROUND: Vaccination constitutes an attractive control measure for hepatitis E virus (HEV), a major cause of maternal and perinatal mortality globally. Analysis of pregnant participants in an effectiveness trial of the HEV vaccine HEV239 showed possible HEV239-associated fetal losses. We aimed to conduct a detailed analysis of this safety signal. METHODS: In a double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomly allocated (1:1) to two vaccine groups, in which non-pregnant women aged 16-39 years received either HEV239 (HEV239 group) or Hepa-B (a hepatitis B vaccine; control group). We implemented weekly surveillance for pregnancy detection, and follow-up of pregnancies once every 2 weeks, using physician-confirmed diagnoses to evaluate fetal loss outcomes (miscarriage [spontaneous abortion], stillbirth, and elective termination). Data from a parallel system of reproductive health surveillance in Matlab were used to clarify study diagnoses when necessary. Miscarriage was assessed only among participants whose first positive pregnancy test and vaccination date (for whichever dose was closest to the date of last menstrual period [LMP]) were before 20 weeks' gestation. We defined the following analysis periods of interest: from 90 days before the LMP until the pregnancy outcome (the proximal period); from the LMP date until the pregnancy outcome (the pregnancy period); from 90 days before the LMP until the LMP date (90 days pre-LMP period); and from enrolment until 90 days before the LMP (the distal period). Both Poisson and Cox regression models were used to assess the associations between receipt of HEV239 and fetal loss outcomes. The trial was registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Among the 19 460 non-pregnant participants enrolled in the trial, 5011 were identified as having pregnancies within 2 years following vaccination and met the criteria for analysis (2407 in the HEV239 group and 2604 in the control group). Among participants vaccinated in the proximal period and evaluated for miscarriage, miscarriage occurred in 54 (8·9%) of 607 in the HEV239 group and 32 (4·5%) of 719 in the control group (adjusted relative risk [aRR] 2·0 [95% CI 1·3-3·1], p=0·0009). Similarly, the risk of miscarriages was increased in the HEV239 group versus the control group among participants inadvertently vaccinated during pregnancy (22 [10·5%] miscarriages among 209 participants in the HEV239 group vs 14 [5·3%] of 266 in the control group; aRR 2·1 [95% CI 1·1-4·1], p=0·036) and among those vaccinated within 90 days pre-LMP (32 [8·0%] of 398 vs 18 [4·0%] of 453; 1·9 [1·1-3·2], p=0·013). No increased risk of miscarriage was observed in those who received HEV239 in the distal period (93 [5·6%] of 1647 vs 80 [4·5%] of 1773; 1·3 [0·8-1·9], p=0·295). Stillbirth and elective termination showed no increased risk among women administered HEV239 versus those administered Hepa-B in any of the analysis periods. INTERPRETATION: HEV239 given shortly before or during pregnancy was associated with an elevated risk of miscarriage. This association poses a possible safety concern for programmatic use of HEV239 in women of childbearing age. FUNDING: Research Council of Norway and Innovax.

Do Oral Cholera Vaccine and Water, Sanitation, and Hygiene Combine to Provide Greater Protection Against Cholera? Results From a Cluster-Randomized Trial of Oral Cholera Vaccine in Kolkata, India.

Background: Oral cholera vaccine (OCV) and incremental improvements in household water, sanitation, and hygiene (WASH) within cholera-endemic areas can reduce cholera risk. However, we lack empiric evaluation of their combined impact. Methods: We evaluated a cluster-randomized, placebo-controlled trial of OCV (Shanchol) in Kolkata, India. The study population included 108 777 individuals, and 106 879 nonpregnant individuals >1 year of age were eligible to receive 2 doses of OCV or placebo. We measured cholera risk in all household members assigned to OCV vs placebo and in all members of households with "Better" vs "Not Better" WASH, where WASH was classified according to validated criteria. Protection was measured by Cox proportional hazard models. Results: Residence in an OCV household was associated with protective effectiveness (PE) of 54% (95% CI, 42%-64%; P < .001) and was similar regardless of Better (PE, 57%; 95% CI, 26%-75%; P = .002) or Not Better (PE, 53%; 95% CI, 40%-64%; P < .001) household WASH. Better WASH household residence was associated with PE of 30% (95% CI, 5%-48%; P = .023) and was similar in OCV (PE, 24%; 95% CI, -26% to 54%; P = .293) and placebo (PE, 29%; 95% CI, -3% to 51%; P = .069) households. When assessed conjointly, residence in OCV households with Better WASH was associated with the greatest PE against cholera at 69% (95% CI, 49%-81%; P < .001). Conclusions: These findings suggest that the combination of a vaccine policy and improved WASH reduces cholera risk more than either would alone, although the magnitude of either intervention was not affected by the other. Future randomized trials investigating OCV and WASH interventions separately and together are recommended to further understand the interaction between OCV and WASH.

Mental health status among chronic disease patients in Bangladesh during the COVID-19 Pandemic: Findings from a cross-sectional study.

Context: The COVID-19 epidemic has had a substantial influence on the mental health of chronic disease patients. However, there is a scarcity of research on them in Bangladesh. Aims: This study aims to explore the prevalence of and identify the risk factors for depression, anxiety, and stress symptoms during the COVID-19 pandemic among people with chronic diseases in Bangladesh. Materials and Methods: This cross-sectional study involving face-to-face and telephone interviews was carried out among Bangladeshi people diagnosed with chronic diseases between September and November 2020. The total sample size was 878, and a convenient sampling technique was used. Logistic regression analysis was performed to investigate potential influencing factors for depression, anxiety, and stress. Results: The mean age of respondents was 50.10 years. Among them, 35.0%, 36.0%, and 29.0% suffered from depression, anxiety, and stress symptoms, respectively. In multivariable logistic regression, depression had a significant positive association with higher age (≥60 years), lower income, rural residency, and loss of close family members due to COVID-19. Anxiety had a significant positive association with higher age (≥40 years), lower education, lower income, rural residency, and loss of close family members due to COVID-19. Stress had a significant positive association with higher age (≥40 years), no income, rural residency, and loss of close family members due to COVID-19. Conclusion: It is urgent to consider the risk of developing mental health distress among chronic disease patients, especially aged people, by health service providers and generate effective programs for emergency situations.

Indirect effectiveness of a novel SARS-COV-2 vaccine (SCB-2019) in unvaccinated household contacts in the Philippines: A cluster randomised analysis.

BACKGROUND: Though observational evidence supports indirect effects of SARS-CoV-2 vaccines, randomised experiments are lacking. To address this gap, the double-blinded, prospective follow-up of the household contacts (HHCs) of Philippine participants of the individually-randomised, placebo-controlled trial of the adjuvanted-subunit protein COVID-19 vaccine, SCB-2019, (EudraCT, 2020-004272-17; ClinicalTrials.gov, NCT04672395) was analyzed in a cluster-randomised fashion. METHODS: Over an eight-week period, HHCs were followed by rRT-PCR and paired rapid antibody tests (RATs) to detect symptomatic (SCI, primary) and all (ACI, secondary) SARS-CoV-2 infection. A standard analysis estimated the indirect effectiveness of SCB-2019 for each endpoint, excluding HHC RAT-positive at enrollment. A secondary analysis employed enzyme-linked immunosorbent assay (ELISA) results to correct for suspected bias. FINDINGS: SCB-2019 (N = 3470) and placebo (N = 3225) exposed HHCs contributed to at least one analysis. The standard analysis estimated that SCB-2019 reduced the risk of SCI by 83% (95% confidence/credible interval [CI: 32% to 96%), with no effect against ACI. The bias-corrected relative risk reduction was 97% (95% CI: 74% to 100%) for SCI and 79% (95% CI: 14% to 96%) for ACI, with an estimated one SARS-CoV-2 infection prevented per 4.8 households where one member received SCB-2019. INTERPRETATION: SCB-2019 demonstrated bias-corrected indirect effectiveness against SARS-CoV-2 infection among HHC, even at a modest coverage level in the household (approximately 25%). Further research into the indirect effects of SARS-CoV-2 vaccines is needed to optimize the impact of limited doses in low and middle-income settings.

Spatial and temporal clustering of typhoid fever in an urban slum of Dhaka City: Implications for targeted typhoid vaccination.

BACKGROUND: Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce. METHODS: We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models. RESULTS: We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection. CONCLUSION: In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.

Safety and effectiveness of a recombinant hepatitis E vaccine in women of childbearing age in rural Bangladesh: a phase 4, double-blind, cluster-randomised, controlled trial.

BACKGROUND: Hepatitis E virus (HEV) leads to high mortality in pregnant women in low-income countries. We aimed to evaluate the safety of a HEV vaccine and its effectiveness in preventing hepatitis E during pregnancy. METHODS: In this phase 4, double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomised 1:1 to receive HEV239 (a recombinant HEV vaccine) or a control vaccine (Hepa-B, a hepatitis B vaccine), using block randomisation with random number tables and blocks of size eight, stratified by cluster population size. Eligible non-pregnant women (aged 16-39 years) were vaccinated intramuscularly on day 0, at 1 month, and at 6 months, and followed up for 2 years after the last immunisation. The primary endpoint was hepatitis E in the pregnant, per-protocol population (those who received all three doses within 2 days of the scheduled dates), while safety was a secondary endpoint, assessed in the intention-to-treat (ITT) population (participants who received at least one dose). Solicited adverse events were recorded for the first 7 days after each dose, and unsolicited events until 2 years after a participant's final dose. Pregnancy-related safety outcomes were assessed in the pregnant ITT population. This study is registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Between Oct 2, 2017, and Feb 28, 2019, 19 460 participants were enrolled and received either HEV239 (9478 [48·7%] participants, 33 clusters) or Hepa-B (9982 [51·3%] participants, 34 clusters), of whom 17 937 (92·2%) participants received three doses and 17 613 (90·5%) were vaccinated according to protocol (8524 [48·4%] in the HEV239 group and 9089 [51·6%] in the control group). No pregnant participants were confirmed to have hepatitis E in either treatment group. HEV239 showed a mild safety profile, similar to Hepa-B, with no difference in the proportion of solicited adverse events between groups and no severe solicited events. Pain was the most common local symptom (1215 [12·8%] HEV239 recipients and 1218 [12·2%] Hepa-B recipients) and fever the most common systemic symptom (141 [1·5%] HEV239 recipients and 145 [1·5%] Hepa-B recipients). None of the serious adverse events or deaths were vaccine related. Among pregnant participants, the HEV239 group had a higher risk of miscarriage (136 [5·7%] of 2407 pregnant participants) compared with the control group (102 [3·9%] of 2604; adjusted odds ratio 1·54 [95% CI 1·15-2·08]). INTERPRETATION: The effectiveness of HEV239 in pregnant women remains uncertain. HEV239 was safe and well tolerated in non-pregnant women, but findings regarding miscarriage warrant further investigation. FUNDING: Research Council of Norway; Innovax.

Using Dried Blood Spots to Quantitatively Detect Anti-SARS-CoV-2 IgG Antibodies by ELISA: A Validation Study.

SARS-CoV-2 serological testing is useful to determine seroprevalence, epidemiological trends, and the extent of transmission. The collection and transport of serum samples can be logistically challenging, especially in remote underserved areas. Dried blood spots (DBSs) would allow easier sample collection and logistical handling compared with standard serum collection, particularly for extensive and repeated SARS-CoV-2 serosurveys. We evaluated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the IgG ELISA (Wantai, Beijing, China) using DBSs against sera for the quantitative detection of SARS-CoV-2 IgG antibody. The IgG ELISA was used to test paired sera and DBSs obtained from individuals with recent virologically confirmed COVID-19 illness and banked paired sera and DBSs collected before the COVID-19 pandemic. We found that 100/100 (100%) seropositive samples were positive using DBSs, and 193/194 (99%) seronegative samples were negative using DBSs. Compared with sera, the DBS method had a 100% sensitivity, 99% specificity, 99% PPV, and 100% NPV. Use of DBSs for SARS-CoV-2 household or population serosurveys may be considered in situations with limitations in sample collection, shipment, and storage.

Comparing the effectiveness of bivalent and monovalent COVID-19 vaccines against COVID-19 infection during the winter season of 2022-2023: A real-world retrospective observational matched cohort study in the Republic of Korea.

OBJECTIVES: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. METHODS: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. RESULTS: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). CONCLUSION: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.

Better Existing Water, Sanitation, and Hygiene Can Reduce the Risk of Cholera in an Endemic Setting: Results From a Prospective Cohort Study From Kolkata, India.

Background: Global cholera control efforts rely heavily on effective water, sanitation, and hygiene (WASH) interventions in cholera-endemic settings. Methods: Using data from a large, randomized controlled trial of oral cholera vaccine conducted in Kolkata, India, we evaluated whether natural variations in WASH in an urban slum setting were predictive of cholera risk. From the control population (n = 55 086), baseline WASH data from a randomly selected "training subpopulation" (n = 27 634) were analyzed with recursive partitioning to develop a dichotomous ("better" vs "not better") composite household WASH variable from several WASH features collected at baseline, and this composite variable was then evaluated in a mutually exclusive "validation population" (n = 27 452). We then evaluated whether residents of better WASH households in the entire population (n = 55 086) experienced lower cholera risk using Cox regression models. Better WASH was defined by a combination of 4 dichotomized WASH characteristics including safe source of water for daily use, safe source of drinking water, private or shared flush toilet use, and always handwashing with soap after defecation. Results: Residence in better WASH households was associated with a 30% reduction in risk of cholera over a 5-year period (adjusted hazard ratio, 0.70 [95% confidence interval, .49-.99]; P = .048). We also found that the impact of better WASH households on reducing cholera risk was greatest in young children (0-4 years) and this effect progressively declined with age. Conclusions: The evidence suggests that modest improvements in WASH facilities and behaviors significantly modify cholera risk and may be an important component of cholera prevention and elimination strategies in endemic settings. Clinical Trials Registration. NCT00289224.

The interplay between WASH practices and vaccination with oral cholera vaccines in protecting against cholera in urban Bangladesh: Reanalysis of a cluster-randomized trial.

The current global initiative to end Cholera by 2030 emphasizes the use of oral cholera vaccine (OCV) combined with feasible household Water-Sanitation-Hygiene (WASH) interventions. However, little is known about how improved WASH practices and behaviors and OCV interact to reduce the risk of cholera. We reanalyzed two arms of a cluster-randomized trial in urban Bangladesh, to evaluate the effectiveness of OCV given as a 2-dose regimen. One arm (30 clusters, n = 94,675) was randomized to vaccination of persons aged one year and older with OCV, and the other arm (30 clusters, n = 80,056) to no intervention. We evaluated the prevention of cholera by household WASH, classified at baseline using a previously validated rule, and OCV over 2 years of follow-up. When analyzed by assignment to OCV clusters rather than receipt of OCV, in comparison to persons living in "Not Better WASH" households in the control clusters, reduction of severe cholera (the primary outcome) was similar for persons in "Not Better WASH" households in vaccine clusters (46%, 95% CI:24,62), for persons in "Better WASH" households in the control clusters (48%, 95% CI:25,64), and for persons in "Better WASH" households in the vaccine clusters (48%, 95% CI:16,67). In contrast, when analyzed by actual receipt of a complete OCV regimen, , in comparison to persons in "Not Better WASH" households in the control clusters, protection against severe cholera increased steadily from 39% (95% CI:13,58) in residents of "Better WASH" households in the control clusters to 57% (95% CI:35,72) in vaccinated persons in "Not Better WASH" households to 63% (95% CI:21,83) in vaccinated persons in "Better WASH" households. This analysis suggests that improved household WASH and OCV received may interact to provide greater protection against cholera. However, the divergence between findings related to intent to vaccinate versus those pertaining to actual receipt of OCV underscores the need for further research on this topic.

Association Among Household Water, Sanitation, and Hygiene (WASH) Status and Typhoid Risk in Urban Slums: Prospective Cohort Study in Bangladesh.

BACKGROUND: Typhoid fever, or enteric fever, is a highly fatal infectious disease that affects over 9 million people worldwide each year, resulting in more than 110,000 deaths. Reduction in the burden of typhoid in low-income countries is crucial for public health and requires the implementation of feasible water, sanitation, and hygiene (WASH) interventions, especially in densely populated urban slums. OBJECTIVE: In this study, conducted in Mirpur, Bangladesh, we aimed to assess the association between household WASH status and typhoid risk in a training subpopulation of a large prospective cohort (n=98,087), and to evaluate the performance of a machine learning algorithm in creating a composite WASH variable. Further, we investigated the protection associated with living in households with improved WASH facilities and in clusters with increasing prevalence of such facilities during a 2-year follow-up period. METHODS: We used a machine learning algorithm to create a dichotomous composite variable ("Better" and "Not Better") based on 3 WASH variables: private toilet facility, safe drinking water source, and presence of water filter. The algorithm was trained using data from the training subpopulation and then validated in a distinct subpopulation (n=65,286) to assess its sensitivity and specificity. Cox regression models were used to evaluate the protective effect of living in "Better" WASH households and in clusters with increasing levels of "Better" WASH prevalence. RESULTS: We found that residence in households with improved WASH facilities was associated with a 38% reduction in typhoid risk (adjusted hazard ratio=0.62, 95% CI 0.49-0.78; P<.001). This reduction was particularly pronounced in individuals younger than 10 years at the first census participation, with an adjusted hazard ratio of 0.49 (95% CI 0.36-0.66; P<.001). Furthermore, we observed an inverse relationship between the prevalence of "Better" WASH facilities in clusters and the incidence of typhoid, although this association was not statistically significant in the multivariable model. Specifically, the adjusted hazard of typhoid decreased by 0.996 (95% CI 0.986-1.006) for each percent increase in the prevalence of "Better" WASH in the cluster (P=.39). CONCLUSIONS: Our findings demonstrate that existing variations in household WASH are associated with differences in the risk of typhoid in densely populated urban slums. This suggests that attainable improvements in WASH facilities can contribute to enhanced typhoid control, especially in settings where major infrastructural improvements are challenging. These findings underscore the importance of implementing and promoting comprehensive WASH interventions in low-income countries as a means to reduce the burden of typhoid and improve public health outcomes in vulnerable populations.

Evaluation of protection by COVID-19 vaccines after deployment in low and lower-middle income countries.

The availability and use of vaccines for the coronavirus disease 2019 (COVID-19) in low and middle-income countries (L/MICs) lags far behind more affluent countries, and vaccines currently used in L/MICs are predominantly of lower efficacy. As vaccines continue to be rolled out in L/MICs, successful control of COVID-19 by vaccines requires monitoring both of vaccine protection of vaccinees (effectiveness) and of the entire targeted populations, including vaccine herd protection of non-vaccinees (impact). To be of greatest relevance to L/MICs, there is the need to address the distinctive medical and demographic features of populations, health systems, and demography that may greatly affect vaccine performance in these settings. We identified 58 published studies that included 85 evaluations of the effectiveness of different COVID-19 vaccines globally. Only three were done in L/MICs, and no impact studies were identified in these settings. Post-deployment studies of the protection by COVID-19 vaccines rolled out in L/MICs constitute an important but currently neglected global priority.

Hepatitis E Virus (HEV) Synopsis: General Aspects and Focus on Bangladesh.

HEV is the most common cause of acute hepatitis globally. This review summarizes the latest knowledge on the epidemiology, clinical characteristics, testing, and treatment of HEV infection. We also focused on Bangladesh to highlight the distinct challenges and the possible remedies. In low-income settings, the virus is mainly transmitted between people by fecal contamination of drinking water causing large outbreaks, and sporadic cases. The disease is usually mild and self-limiting acute hepatitis. Still, pregnant women and their offspring in low-income countries are at particular risk for severe disease, with up to 20% maternal mortality. Despite the high burden of the disease, HEV remains a relatively neglected virus, with detection hampered by costly tests and a lack of suitable treatments. Molecular PCR diagnostics, together with ELISA antibody tests, remain the preferred methods for diagnosis of HEV; however, rapid bedside diagnostics are available and could offer a practical alternative, especially in low-income countries. One vaccine (HEV 239) is only available in China and Pakistan, as efficacy against the other genotypes remains uncertain. The effectiveness trial conducted in Bangladesh might lead the way in gathering more efficacy data and could, together with improved surveillance and raised awareness, dramatically reduce the global burden of HEV.

Are better existing WASH practices in urban slums associated with a lower long-term risk of severe cholera? A prospective cohort study with 4 years of follow-up in Mirpur, Bangladesh.

OBJECTIVE: To investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly endemic. DESIGN, SETTING AND PARTICIPANTS: We assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the 'non-intervention' clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area. PRIMARY OUTCOME MEASURE: First severe cholera episode detected during follow-up period. METHODS: We applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary ('better', 'not better') composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between 'better' WASH households and severe cholera risk over 4 years in the entire study population. RESULTS: The 'better' WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of 'better' WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a 'better' WASH household and severe cholera persisted in all age groups. CONCLUSIONS: Salutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings. TRIAL REGISTRATION NUMBER: This article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.gov NCT01339845.

Cost of oral cholera vaccine delivery in a mass immunization program for children in urban Bangladesh.

Cholera poses a substantial health burden in the developing world due to both epidemic and endemic diseases. The World Health Organization recommends oral cholera vaccines for mass vaccination campaigns in addition to traditional prevention practices and treatments in resource-poor settings. In many developing countries like Bangladesh, the major challenge behind implementing mass vaccination campaigns concerns the affordability of the oral cholera vaccine (OCV). Vaccination of children with OCV is not only an impactful approach for controlling cholera at the population level and reducing childhood morbidity but is also considered more cost-effective than vaccinating all ages. The aim of the study was to estimate the cost of an OCV campaign for children from a societal perspective using empirical study. A total of 66,311 children aged 1 to 14 years old were fully vaccinated with two doses of the OCV Shanchol while 9,035 individuals received one dose of this vaccine. The estimated societal cost per individual for full vaccination was US$ 6.11, which includes the cost of vaccine delivery estimated at US$ 1.95. The cost per single dose was estimated at US$ 2.86. The total provider cost for full vaccination was estimated at US$ 6.01 and the recipient cost at US$ 0.10. Our estimation of OCV delivery costs for children was relatively higher than what was found in a similar mass OCV campaign for all age groups, indicating that there may be additional cost factors to consider in targeted vaccine campaigns. This analysis provides useful benchmarks for the possible costs related to delivery of OCV to children and future OCV cost-effectiveness models should factor in these possible cost disparities. Attempts to reduce the cost per dose are likely to have a greater impact on the cost of similar vaccination campaigns in many resource-poor settings.

Prevention of Typhoid Fever by Existing Improvements in Household Water, Sanitation, and Hygiene, and the Use of the Vi Polysaccharide Typhoid Vaccine in Poor Urban Slums: Results from a Cluster-Randomized Trial.

Modest improvements in household water, sanitation, and hygiene (WASH) and typhoid vaccination can reduce typhoid risk in endemic settings. However, empiric evaluation of their combined impact is lacking. A total of 62,756 persons residing in 80 clusters in a Kolkata slum were allocated randomly 1:1 to either the typhoid Vi polysaccharide (ViPS) vaccine or hepatitis A (Hep A) vaccine. Surveillance was conducted for 2 years before and 2 years after vaccination. We classified households as having "better" or "not better" WASH, and calculated the prevalence of better WASH households in clusters using previously validated criteria. We evaluated the protection by better household WASH, better household WASH prevalence, and ViPS vaccination against typhoid in all cluster members present at baseline using Cox proportional hazard models. Overall, ViPS vaccination was associated with a 55% (P < 0.001; 95% CI, 35-69) reduction of typhoid risk and was similar regardless of better WASH in the residence. Living in a better WASH household was associated with a typhoid risk reduction of 31% (P = 0.16; 95% CI, -16 to 59) overall. The reduction was 48% (P = 0.05; 95% CI, -1 to 73) in Hep A clusters, 6% (P = 0.85; 95% CI, -82 to 51) in ViPS clusters, and 57% (P < 0.05; 95% CI, 15-78) in the population during the 2 years preceding the trial. These findings demonstrate a preventive association of better household WASH in the non-ViPS population, but, unexpectedly, an absence of additional protection from ViPS by better WASH in the ViPS population. This analysis highlights the importance of assessing the combination of WASH in conjunction with typhoid vaccines, and has implications for the evaluation of new-generation typhoid conjugate vaccines.