Evidence of health system resilience in primary health care for preventing under-five mortality in Rwanda and Bangladesh: Lessons from an implementation study during the Millennium Development Goal period and the early period of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic led to disruptions of health service delivery in many countries; some were more resilient in either limiting or rapidly responding to the disruption than others. We used mixed methods implementation research to understand factors and strategies associated with resiliency in Rwanda and Bangladesh, focussing on how evidence-based interventions targeting amenable under-five mortality that had been used during the Millennium Development Goal (MDG) period (2000-15) were maintained during the early period of COVID-19. Methods: We triangulated data from three sources - a desk review of available documents, existing quantitative data on evidence-based intervention coverage, and key informant interviews - to perform a comparative analysis using multiple case studies methodology, comparing contextual factors (barriers or facilitators), implementation strategies (existing from 2000-15, new, or adapted), and implementation outcomes across the two countries. We also analysed which health system resiliency capabilities were present in the two countries. Results: Both countries experienced many of the same facilitators for resiliency of evidence-based interventions for children under five, as well as new, pandemic-specific barriers during the early COVID-19 period (March to December 2020) that required targeted implementation strategies in response. Common facilitators included leadership and governance and a culture of accountability, while common barriers included movement restrictions, workload, and staff shortages. We saw a continuity of implementation strategies that had been associated with success in care delivery during the MDG period, including data use for monitoring and decision-making, as well as building on community health worker programmes for community-based health care delivery. New or adapted strategies used in responding to new barriers included the expanded use of digital platforms. We found implementation outcomes and strong resilience capabilities, including awareness and adaptiveness, which were related to pre-existing facilitators and implementation strategies (continued and new). Conclusions: The strategies and contextual factors Rwanda and Bangladesh leveraged to build 'everyday resilience' before COVID-19, i.e. during the MDG period, likely supported the maintained delivery of the evidence-based interventions targeting under-five mortality during the early stages of the pandemic. Expanding our understanding of pre-existing factors and strategies that contributed to resilience before and during the pandemic is important to support other countries' efforts to incorporate 'everyday resilience' into their health systems.

Does the implementation of revised American College of Cardiology and American Heart Association (ACC/AHA) guidelines improve the identification of stillbirths and preterm births in hypertensive pregnancies: a population-based cohort study from South Asia and sub-Saharan Africa.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a significant cause of maternal mortality worldwide. The classification and treatment of hypertension in pregnancy remain debated. We aim to compare the effectiveness of the revised 2017 ACC/AHA blood pressure threshold in predicting adverse pregnancy outcomes. METHODS: We conducted a secondary data analysis of the Alliance for Maternal and Newborn Health Improvement (AMANHI) biorepository study, including 10,001 pregnant women from Bangladesh, Pakistan, and Tanzania. Blood pressure was measured using validated devices at different antenatal care visits. The blood pressure readings were categorized as: normal blood pressure (systolic blood pressure (sBP) < 120 mm Hg and diastolic blood pressure (dBP) < 80 mm Hg), elevated blood pressure (sBP 120-129 and dBP < 80), stage 1 hypertension (sBP 130-139 or dBP 80-89, or both), and stage 2 hypertension (sBP ≥ 140 or dBP ≥ 90, or both). We estimated risk ratios for stillbirths and preterm births, as well as diagnostic test properties of both the pre-existing JNC7 (≥ 140/90) and revised ACC/AHA (≥ 130/80) thresholds using normal blood pressure as reference group. RESULTS: From May 2014 to June 2018, blood pressure readings were available for 9,448 women (2,894 in Bangladesh, 2,303 in Pakistan, and 4,251 in Tanzania). We observed normal blood pressure in 70%, elevated blood pressure in 12.4%, stage 1 hypertension in 15.2%, and stage 2 hypertension in 2.5% of the pregnant women respectively. Out of these, 310 stillbirths and 9,109 live births were recorded, with 887 preterm births. Using the ACC/AHA criteria, the stage 1 hypertension cut-off revealed 15.3% additional hypertension diagnoses as compared to JNC7 criteria. ACC/AHA defined hypertension was significantly associated with stillbirths (RR 1.8, 95% CI 1.4, 2.3). The JNC 7 hypertension cut-off of ≥ 140/90 was significantly associated with a higher risk of preterm births (RR 1.6, 95% CI 1.2, 2.2) and stillbirths (RR 3.6, 95% CI 2.5, 5.3). Both criteria demonstrated low sensitivities (8.4 for JNC-7 and 28.1 for ACC/AHA) and positive predictive values (11.0 for JNC7 and 5.2 for ACC/AHA) in predicting adverse outcomes. CONCLUSION: The ACC/AHA criteria (≥ 130/80) identified additional cases of hypertension but had limited predictive accuracy for stillbirths and preterm births, highlighting the ongoing need for improved criteria in managing pregnancy-related hypertension.

Human health risk assessment of heavy metals in vegetables of Bangladesh.

This study aims to evaluate the heavy metal concentration in fifteen species of vegetables as well as associated health risk. Atomic absorption spectrometry is used to assess heavy metals. The mean concentrations of Pb, Cd, Cr, Ni and Fe in vegetables were 4.78, 0.713, 9.266, 0.083, 5.06 mg/kg/fw exceeding the reference value of FAO/WHO indicating unsafe to consumption. Based on principal component analysis, the Pb, Cr, Ni and Fe are from same sources. Health risk was estimated in terms of estimated daily intake (EDI), target hazard quotient, hazard index (HI) and cancer risk (CR). The EDI values of metals except Cr were found to be lower than maximum tolerable daily intake (MTDI). The total THQs of metals were > 1 indicating non-carcinogenic health risk. The individual HI values for vegetables except potato (0.831) and total HI values were found to be > 1 (94.747). The TCR of Pb, Cd and Cr were > 1.0E-04 which indicating carcinogenic risk. Fruit and pod vegetables contribute much in carcinogenic risk for Pb and Cr whereas fruit, root and stems vegetables for Cd. The study revealed potential human health risk associated with the consumption of different types of vegetables in Bangladeshi adult population that might assist the regulatory bodies to develop new strategies to minimize the risk to human.

A survey on the knowledges, attitudes, behaviours and practices of goat farmers about peste des petits ruminants disease in goats at Haor and bordered areas in Sylhet district of Bangladesh.

BACKGROUND: Contagious and economically devastating, peste des petits ruminants (PPR) is a viral disease affecting goats and sheep, causing significant losses in livestock productivity and posing a threat to food security and rural livelihoods worldwide. OBJECTIVES: This study was conducted to assess the status of goat farmer's knowledge, attitude and practice (KAP) about PPR disease at Sylhet district of Bangladesh. METHODS: A comprehensive cross-sectional survey, conducted over 11 weeks, targeted 130 goat owners. Following a pilot study with 20 farmers, a set of 17 validated questions on PPR KAP was validated. Data collection was performed through face-to-face interviews by a trained team using KOBO Toolbox, with interpretation of responses based on established thresholds for knowledge (>65%), attitude (>75%) and practice (>70%). RESULTS: Overall, 67.7% of participants demonstrated a good level of knowledge about PPR disease. Males exhibited 1.42 times higher odds of knowledge compared to females (odds ratio = 1.42). The middle age group (31-45 years) showed significantly higher knowledge levels (83.3%, p < 0.001). Within this age group, positive practice levels were also notably higher (54.8%). Those with a higher secondary education background exhibited the most positive practice levels (>80%). Participants whose additional income came from non-governmental organization employment showed a higher positive practice level (71.4%), 1.46 times higher than other income sources. CONCLUSION: Strategic interventions should prioritize female farmers, educational empowerment and collaboration with non-governmental organizations to bolster livestock health and rural livelihoods in Bangladesh as part of national PPR control strategy to fulfil the goals of Office International des Epizooties/World Organization for Animal Health (OIE/WOAH) and Food and Agriculture Organization (FAO) PPR eradication by 2030.

Soil bacteriome diversity and composition of rooftop and surface gardens in urban and peri-urban areas of Bangladesh.

Soil microbiome science, rapidly evolving, predominantly focuses on field crop soils. However, understanding garden soil microbiomes is essential for enhancing food production sustainability in garden environments. This study aimed to unveil the bacteriome diversity and composition in rooftop garden soils (RGS) and surface garden soils (SGS) across urban (Dhaka North and Dhaka South City Corporations) and peri-urban (Gazipur City Corporation) areas of Dhaka Division, Bangladesh. We analyzed 11 samples, including six RGS and five SGS samples from 11 individual gardens using 16S rRNA (V3-V4 region) gene-based amplicon sequencing. A total of 977 operational taxonomic units (OTUs), including 270 and 707 in RGS and SGS samples, respectively, were identified. The observed OTUs were represented by 21 phyla, 45 classes, 84 orders, 173 families, and 293 genera of bacteria. Alpha diversity indices revealed significantly higher bacterial diversity in SGS samples (p = 0.01), while beta diversity analyses indicated distinct bacteriome compositions between RGS and SGS samples (p = 0.028, PERMANOVA). Despite substantial taxonomic variability between sample categories, there was also a considerable presence of shared bacterial taxa. At the phylum level, Bacilliota (61.14%), Pseudomonadota (23.42%), Actinobacteria (6.33%), and Bacteroidota (3.32%) were the predominant bacterial phyla (comprising > 94.0% of the total abundances) in both types of garden soil samples. Of the identified genera, Bacillus (69.73%) and Brevibacillus (18.81%) in RGS and Bacillus (19.22%), Methylophaga (19.21%), Acinetobacter (6.27%), Corynebacterium (5.06%), Burkholderia (4.78%), Paracoccus (3.98%) and Lysobacter (2.07%) in SGS were the major bacterial genera. Importantly, we detected that 52.90% of genera were shared between RGS and SGS soil samples. Our data reveal unique and shared bacteriomes with probiotic potential in soil samples from both rooftop and surface gardens. Further studies should explore the functional roles of shared bacterial taxa in garden soils and how urban environmental factors affect microbiome composition to optimize soil health and sustainable food production.

Folate deficiency in pregnancy and the risk of preterm birth: A nested case-control study.

Background: Preterm birth (PTB) and its complications are important public health problems. Its aetiology is multifactorial and involves both modifiable and non-modifiable factors. Among the modifiable risk factors, micronutrient deficiencies, including maternal folate deficiency, are increasingly being studied in PTB. In this study, we estimated the prevalence of folate deficiency during pregnancy and examined its association with PTB among rural Bangladeshi women. Methods: We conducted a nested case-control study using data from a population-based cohort of 3000 pregnant women who were enrolled between 8 and 19 weeks of gestation following ultrasound confirmation of gestational age. Sociodemographic, epidemiologic, clinical, and pregnancy outcomes data were collected through home visits, while blood samples were collected at enrolment and 24-28 weeks of gestation during pregnancy. We included all women who delivered preterm (defined as live births <37 weeks of gestation) as cases (n = 235) and a random sample of women having a term birth as controls (n = 658). The main exposure was folate concentrations in maternal serum during 24-28 weeks of pregnancy. We categorised women into folate deficient (<3 ng/mL) and not deficient (≥3 ng/mL). We then performed multivariable logistic regression analysis to examine the association between maternal folate levels and PTB, adjusting for relevant covariates. Results: Thirty-eight per cent of the enrolled pregnant women were folate deficient. Maternal serum folate deficiency was significantly associated with PTB (adjusted OR (aOR) = 1.73; 95% confidence interval (CI) = 1.27-2.36). The risk of PTB was also higher among women who were of short stature (aOR = 1.83; 95% CI = 1.27-2.63), primiparous (aOR = 1.60; 95% CI = 1.15-2.22), and had exposure to passive smoking (aOR = 1.54; 95% CI = 1.02-2.31). Conclusions: The prevalence of folate deficiency was high among pregnant women in rural Bangladesh, and folate deficiency was significantly associated with an increased risk of preterm birth.

Anaemia among adolescent girls, pregnant and lactating women in the southern rural region of Bangladesh: Prevalence and risk factors.

Anaemia is a major public health concern in developing countries, particularly among children, adolescents, and women of reproductive age. The study aimed to assess the anaemia status among adolescent girls, pregnant, and lactating women with their contributing factors in the southern rural regions of Bangladesh. This cross-sectional study was conducted among 400 adolescent girls, 375 pregnant, and 375 lactating women using a multistage cluster-random sampling technique. Anaemia was measured through haemoglobin concentration in blood capillaries collected with a Hemocue 301 machine. Multinomial logistic regression was used to determine the factors associated with anaemia. The average age of pregnant and lactating women was 24 years and 15.2 years for girls. Overall, the prevalence of anaemia was 50% among pregnant women, 46% among lactating women, and 38% among adolescent girls. The risk of anaemia among adolescent girls was higher among non-Muslim (aOR = 2.13, 95%CI:1.05-4.31), belonged to families having >5 members (aOR = 2.24, 95%CI:1.16-4.31) while exposure to media reduced their risk (aOR = 0.33, 95%CI:0.15-0.74). Pregnant women who consumed a diversified diet, washed their hands after toilet, and received ≥4 ANC visits had a lower likelihood of developing anaemia. Lactating women who were employed, consumed a diversified diet, washed their hands before preparing food, and after toilet, had been exposed to media, received ≥4 ANC visits, and consumed ≥90 IFA, had a lower risk of developing anaemia. However, anaemia was more likely to be associated with lactating women who were non-Muslim (aOR = 3.75; 95%CI:1.26-11.22). The high prevalence of anaemia emphasizes the need to reconsider the existing strategy for the prevention and control of micronutrient deficiencies in Bangladesh.

Experience and side effects of COVID-19 vaccine uptake among university students: a cross-sectional survey study.

Introduction: Many people expressed concern over coronavirus vaccinations' reliability and side effects. This research aimed to assess university students' perceptions and experiences regarding the side effects of the COVID-19 vaccines in Bangladesh. Method: We conducted an online cross-sectional survey to collect responses from university students vaccinated with any vaccines administered in Bangladesh between November 2021 to April 2022. Bangladeshi university students over the age of 18 and having an internet connection was included in the study. A binary logistic regression analysis along with Pearson's Chi-square test were used to identify COVID-19 vaccine-related side effects predictors after receiving the first dose. Results: A total of 1,176 participants responded voluntarily to the online study, and most were vaccinated. More than half of the participants received the Sinopharm vaccine (56.5%), while others received Covishield (8.9%), Moderna (7.3%), and Pfizer (5.8%) vaccine. Around 32% of the participants reported side effects after receiving the first dose of the vaccine, including pain and edema (78.4%), body temperature (20.3%), and headache (14.5%), while a few experienced allergy, anxiety, and uneasy feelings. About 17% of the participants reported experiencing side effects after the second dose of the vaccine, including pain and edema (7.5%), body temperature (8.8%), and headache (7.3%). Most side effects were significantly associated with the Moderna vaccine (p < 0.001). Female students and those previously infected with COVID-19 were significantly associated with the side effects after taking the first dose of the vaccine. Conclusion: We found that side effects are mild and did not pose a significant challenge to Bangladesh's effort in managing and reducing the risk associated with the COVID-19 pandemic.

Autonomic Dysfunction in Amyotrophic Lateral Sclerosis - A Case-Control Study.

INTRODUCTION: This study aimed to explore autonomic nervous system involvement in amyotrophic lateral sclerosis (ALS) patients by evaluating sympathetic skin response (SSR). MATERIALS AND METHODS: The study included 35 sporadic (ALS) patients (cases), and 35 healthy age and sex-matched participants (controls) aged <60 years. SSR was recorded in the electrophysiology lab of the Neurology Department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh. Patients with diseases associated with peripheral or autonomic neuropathy were excluded. Prolonged latency (delayed SSR) or an absent response was considered abnormal SSR. RESULTS: SSR was found to be abnormal in 17 (48.6 %) ALS cases, with an absent response in the upper limbs of six cases (17.1%). Abnormal SSR was more prevalent in the lower limbs, with 33 (94.3%) and 20 (57.1%) cases having a delayed or absent response, respectively. In comparison, SSR was normal in all control participants (P-value <0.05). Abnormal SSR was significantly more common in the lower limbs of ALS cases with bulbar palsy than those without bulbar palsy (P-value=0.04). There was no association of SSR with disease severity and duration. CONCLUSION: ALS is significantly associated with abnormal SSR, indicating autonomic nervous system involvement. There could also be an association between bulbar palsy and abnormal SSR among ALS patients. Further studies should be carried out to determine the association of abnormal SSR with disease severity, duration, and type.

Maternal betel quid use during pregnancy and child growth: a cohort study from rural Bangladesh.

BACKGROUND: Chewing betel quid (BQ) - a preparation commonly containing areca nut and slaked lime wrapped in betel leaf - is entrenched in South Asia. Although BQ consumption during pregnancy has been linked to adverse birth outcomes, its effect on postnatal growth remains largely unexplored. OBJECTIVE: We examined the associations of BQ use during pregnancy with children's height-for-age and body mass index-for-age z-scores (HAZ and BAZ, respectively) and fat and fat-free mass along with sex-based differences in association in rural Bangladesh. METHODS: With a prospective cohort design, we assessed BQ use among mothers enrolled in the Preterm and Stillbirth Study, Matlab (n = 3140) with a structured questionnaire around early third trimester. Children born to a subset of 614 women (including 134 daily users) were invited to follow-up between October 2021 and January 2022. HAZ and BAZ were calculated from anthropometric assessment, and fat and fat-free mass were estimated using bioelectric impedance. Overall and sex-specific multiple linear regression models were fitted. RESULTS: Growth data were available for 501 children (mean age 4.9 years): 43.3% of them were born to non-users, 35.3% to those using prior to or less-than-daily during the survey, and 21.3% to daily users. No statistically significant associations were observed after adjusting for sex, parity, maternal height and education, and household wealth. CONCLUSIONS: There was no effect of BQ use during pregnancy on postnatal growth in this study. Longitudinal studies following up those born to heavy users beyond childhood are warranted for capturing long-term implications of prenatal BQ exposure.

Main findings: In this cohort study, no association was observed between maternal betel quid use during pregnancy and children's growth around five years of age.Added knowledge: Although catch-up growth among those born to heavy users may have attenuated any negative impact of prenatal exposure to betel quid on postnatal growth, such catch-up growth often involves greater acquisition and a more centralized distribution of body fat and insulin resistance later in life; leading to a potential heightening of cardiometabolic risk.Global health impact for policy and action: Given that betel quid consumption during pregnancy remains socially acceptable across south and south-east Asia, this study highlights the need for following up those born to betel quid users beyond childhood for capturing long-term health implications of prenatal betel quid exposure.

Geospatial variation in dietary patterns and their association with heart disease in Bangladeshi population: Evidence from a nationwide survey.

Heart disease is a significant public health threat, and its burden is increasing worldwide. Recent evidence suggests that dietary pattern is a key modifiable factor for heart disease. Research regarding dietary patterns and heart disease in Bangladesh with their spatial variability is limited. In this study, the spatial variation and relationship between dietary patterns and heart disease among Bangladeshi people was investigated. The country-representative Household Income and Expenditure Survey 2016 dataset was used, and a total of 77,207 participants aged 30 years and over were included. A principal component analysis was conducted to derive the dietary patterns. Both statistical and spatial analyses were performed. The overall prevalence of heart disease was 3.6%, with a variation of 0.6% to 10.4% across districts of Bangladesh. Three major dietary patterns, named "festival pattern", "pickles and fast foods pattern", and "rice and vegetable pattern" were identified, accounting for 25.2% of the total dietary variance. Both the dietary pattern and heart disease rate varied across the region. A higher risk of heart disease was persistent in the western-south, southern, central, and eastern regions, as was greater adherence to the "festival pattern" and "pickles and fast foods pattern." After adjusting for confounders, participants with the highest adherence to the "rice and vegetable pattern" were associated with a lower likelihood of developing heart disease (AOR: 0.78, 95% CI: 0.64-0.95, p <0.05), while the highest adherence to the "pickles and fast foods pattern" was associated with a higher likelihood of developing heart disease (AOR: 1.50, 95% CI: 1.27-1.76, p <0.001). The spatial disparities in the prevalence of heart disease and dietary patterns underscore the significance of prioritizing intervention at the district level, especially in the western-south, southern, central, and eastern regions, to control the rising heart disease trends in Bangladesh.

Modelling climate impacts on paediatric sepsis incidence and severity in Bangladesh.

Background: Sepsis is a leading cause of paediatric mortality worldwide, disproportionately affecting children in low- and middle-income countries. The impacts of climate change on the burden and outcomes of sepsis in low- and middle-income countries, particularly in paediatric populations, remain poorly understood. We aimed to assess the associations between climate variables (temperature and precipitation) and paediatric sepsis incidence and mortality in Bangladesh, one of the countries most affected by climate change. Methods: We conducted retrospective analyses of patient-level data from the International Centre for Diarrhoeal Disease Research, Bangladesh, and environmental data from the National Oceanic and Atmospheric Administration. Using random forests, we assessed associations between sepsis incidence and sepsis mortality with temperature and precipitation between 2009-22. Results: A nonlinear relationship between temperature and sepsis incidence and mortality was identified. The lowest incidence occurred at an optimum temperature of 26.6°C with a gradual increase below and a sharp rise above this temperature. Higher precipitation levels showed a general trend of increased sepsis incidence. A similar distribution for sepsis mortality was identified with an optimum temperature of 28°C. Conclusions: Findings suggest that environmental temperature and precipitation play a role in paediatric sepsis incidence and sepsis mortality in Bangladesh. As children are particularly vulnerable to climate impacts, it is important to consider climate change in health care planning and resource allocation, especially in resource-limited settings, to allow for surge capacity planning during warmer and wetter seasons. Further prospective research from more globally representative data sets will provide more robust evidence on the nature of the relationships between climate variables and paediatric sepsis worldwide.

Cost-effectiveness of seasonal influenza vaccination in WHO-defined high-risk populations in Bangladesh.

Background: Bangladesh carries a substantial health and economic burden of seasonal influenza, particularly among the World Health Organization (WHO)-defined high-risk populations. We implemented a modelling study to determine the cost-effectiveness of influenza vaccination in each of five high-risk groups (pregnant women, children under five years of age, adults with underlying health conditions, older adults (≥60 years), and healthcare personnel) to inform policy decisions on risk group prioritisation for influenza vaccination in Bangladesh. Methods: We implemented a Markov decision-analytic model to estimate the impact of influenza vaccination for each target risk group. We obtained model inputs from hospital-based influenza surveillance data, unpublished surveys, and published literature (preferentially from studies in Bangladesh, followed by regional and global ones). We used quality-adjusted life years (QALY) as the health outcome of interest. We also estimated incremental cost-effectiveness ratios (ICERs) for each risk group by comparing the costs and QALY of vaccinating compared to not vaccinating each group, where the ICER represents the additional cost needed to achieve one year of additional QALY from a given intervention. We considered a willingness-to-pay threshold (ICER) of less than one gross domestic product (GDP) per capita as highly cost-effective and of one to three times GDP per capita as cost-effective (per WHO standard). For Bangladesh, this threshold ranges between USD 2462 and USD 7386. Results: The estimated ICERs were USD -99, USD -87, USD -4, USD 792, and USD 229 per QALY gained for healthcare personnel, older adults (≥60), children aged less than five years, adults with comorbid conditions, and pregnant women, respectively. For all risk groups, ICERs were below the WHO willingness-to-pay threshold for Bangladesh. Vaccinating pregnant women and adults with comorbid conditions was highly cost-effective per additional life year gained, while vaccinating healthcare personnel, older adults (≥60), and children under five years were cost-saving per additional life year gained. Conclusions: Influenza vaccination to all target risk groups in Bangladesh would be either cost-saving or cost-effective, per WHO guidelines of GDP-based thresholds.

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.

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.

Foodborne bacteria in milk and milk products along the water buffalo milk chain in Bangladesh.

Controlling foodborne pathogens in buffalo milk is crucial for ensuring food safety. This study estimated the prevalence of nine target genes representing seven critical foodborne bacteria in milk and milk products, and identified factors associated with their presence in buffalo milk chain nodes in Bangladesh. One hundred and forty-three milk samples from bulk tank milk (n = 34), middlemen (n = 37), milk collection centers (n = 37), and milk product shops (n = 35) were collected and analyzed using RT-PCR. Escherichia (E.) coli, represented through yccT genes, was the most prevalent throughout the milk chain (81-97%). Chi-squared tests were performed to identify the potential risk factors associated with the presence of foodborne bacteria encoded for different genes. At the middleman level, the prevalence of E. coli was associated with the Mymensingh, Noakhali, and Bhola districts (P = 0.01). The prevalence of Listeria monocytogenes, represented through inlA genes, and Yersinia (Y.) enterocolitica, represented through yst genes, were the highest at the farm level (65-79%). The prevalence of both bacteria in bulk milk was associated with the Noakhali and Bhola districts (P < 0.05). The prevalence of Y. enterocolitica in bulk milk was also associated with late autumn and spring (P = 0.01) and was higher in buffalo-cow mixed milk than in pure buffalo milk at the milk collection center level (P < 0.01). The gene stx2 encoding for Shiga toxin-producing (STEC) E. coli was detected in 74% of the milk products. At the middleman level, the prevalence of STEC E. coli was associated with the use of cloths or tissues when drying milk containers (P = 0.01). Salmonella enterica, represented through the presence of invA gene, was most commonly detected (14%) at the milk collection center. The use of plastic milk containers was associated with a higher prevalence of Staphylococcus aureus, represented through htrA genes, at milk product shops (P < 0.05). These results suggest that raw milk consumers in Bangladesh are at risk if they purchase and consume unpasteurized milk.

Associations of hypertension and antenatal care-seeking with perinatal mortality: A nested case-control study in rural Bangladesh.

Maternal hypertension may be an underrecognized but important risk factor for perinatal death in low resource settings. We investigated the association of maternal hypertension and perinatal mortality in rural Bangladesh. This nested, matched case-control study used data from a 2019 cross-sectional survey and demographic surveillance database in Baliakandi, Bangladesh. We randomly matched each pregnancy ending in perinatal death with five pregnancies in which the neonate survived beyond seven days based on maternal age, education, and wealth quintile. We estimated associations of antenatal care-seeking and self-reported hypertension with perinatal mortality using conditional logistic regression and used median and interquartile ranges to assess the mediation of antenatal care by timing or frequency. Among 191 cases and 934 matched controls, hypertension prevalence was 14.1% among cases and 7.7% among controls. Compared with no diagnosis, the probability of perinatal death was significantly higher among women with a pre-gestational hypertension diagnosis (OR 2.90, 95% CI 1.29, 6.57), but not among women with diagnosis during pregnancy (OR 1.68, 95% CI 0.98, 2.98). We found no association between the number of antenatal care contacts and perinatal death (p = 0.66). Among women with pre-gestational hypertension who experienced a perinatal death, 78% had their first antenatal contact in the sixth or seventh month of gestation. Hypertension was more common among rural women who experience a perinatal death. Greater effort to prevent hypertension prior to conception and provide early maternity care to women with hypertension could improve perinatal outcomes in rural Bangladesh.

An insight into the vaginal microbiome of infertile women in Bangladesh using metagenomic approach.

Introduction: The dysbiosis of vaginal microbiota is recognized as a potential underlying factor contributing to infertility in women. This study aimed to compare the vaginal microbiomes of infertile and fertile women to investigate their relationship with infertility. Methods: Metagenomic analysis was conducted on samples from 5 infertile and 5 fertile individuals using both amplicon 16S and metagenomics shotgun sequencing methods. Results and discussion: In the infertile group, the bacterial community was primarily represented by three major bacterial genera: Lactobacillus (79.42%), Gardnerella (12.56%) and Prevotella (3.33%), whereas, the fertile group exhibited a more diverse composition with over 8 major bacterial genera, accompanied by significantly reduced abundance of Lactobacillus (48.79%) and Gardnerella (6.98%). At the species level, higher abundances of L. iners, L. gasseri and G. vaginalis were observed in the infertile group. Regarding the microbiome composition, only one fertile and two infertile subjects exhibited the healthiest Community State Types, CST-1, while CST-3 was observed among two infertile and one fertile subject, and CST-4 in three other fertile and one infertile subject. Overall, alpha diversity metrics indicated greater diversity and lower species richness in the control (fertile) group, while the infertile group displayed the opposite trend. However, beta-diversity analysis did not show distinct clustering of samples associated with any specific group; instead, it demonstrated CST-type specific clustering. Shotgun metagenomics further confirmed the dominance of Firmicutes, with a greater abundance of Lactobacillus species in the infertile group. Specifically, L. iners and G. vaginalis were identified as the most dominant and highly abundant in the infertile group. Fungi were only identified in the control group, dominated by Penicillium citrinum (62.5%). Metagenome-assembled genomes (MAGs) corroborated read-based taxonomic profiling, with the taxon L. johnsonii identified exclusively in disease samples. MAG identities shared by both groups include Shamonda orthobunyavirus, L. crispatus, Human endogenous retrovirus K113, L. iners, and G. vaginalis. Interestingly, the healthy microbiomes sequenced in this study contained two clusters, Penicillium and Staphylococcus haemolyticus, not found in the public dataset. In conclusion, this study suggests that lower species diversity with a higher abundance of L. iners, L. gasseri and G. vaginalis, may contribute to female infertility in our study datasets. However, larger sample sizes are necessary to further evaluate such association.

A First Record on Microplastic Ingestion by Tropical Estuarine Copepods of Bangladesh.

Microplastics (MPs) pollution is a profound problem around the world yet it's study on the effect on zooplankton including copepods are very limited. The study was conducted between January 2021 and January 2022 in the Lower Meghna Estuary to investigate MPs ingestion in two different family of copepod: Calanoid and Cyclopoid. A method of acid digestion along with Scanning Electron Microscope (SEM) was used to identify MPs ingested by copepods from the conducted area. However, three types of MPs namely fiber, fragment and foam were extracted from this copepod biomass. Fibers represent highest (> 50%) of the ingested MPs from both group of copepod that exceed fragments and foams in all sampling stations. The overall ingestion rate of Calanoid was found higher (0.084 ± 0.002 particles/individual) compared to the Cyclopoid group (0.077 ± 0.001 particles/individual). The results of the study have effectively illustrated that copepod, obtained from multiple sampling sites within the Lower Meghna Estuary, display a propensity to ingest MPs and subsequently endangering the food security of seafood industry.

Cervical cancer risk in association with TNF-alpha gene polymorphisms in Bangladeshi women.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) is among the vital pro-inflammatory cytokines that potentially exerts a significant influence on the immune response, hence potentially regulating the advancement of cervical lesions. OBJECTIVE: Our study objective was to examine the relationship between two single nucleotide polymorphisms (SNPs) (rs1799724 and rs1800629) of TNF-α and the risk of cervical cancer in women from Bangladesh. METHODS: We recruited 133 patients with cervical cancer and 126 healthy individuals for this study. Genotyping was performed using real-time PCR SNP genotyping assay. Multivariate logistic regression analysis was used to determine the odds ratio (OR) along with 95% confidence intervals (CI) and p-values. RESULTS: For rs1799724 (C > T) polymorphism, TT mutant homozygous genotype carried 3.26 times increased risk of developing cervical cancer (OR = 3.26, 95% CI = 1.15-9.28, p = 0.027). Polymorphism of rs1800629 (G > A) was also related to an elevated risk of cervical cancer. Individuals with the AG heterozygous genotype (OR = 2.85, 95% CI = 1.20-6.74, p = 0.017) and AA mutant homozygous genotype (OR = 4.55, 95% CI = 1.24-16.60, p = 0.022) also had a higher likelihood of having cervical cancer. Moreover, we found that injectable contraceptives increase the risk of cervical cancer. Individuals who smoked and/or had first-degree relatives with cancer were more likely to carry the risk allele, which increases the likelihood of developing cervical cancer. CONCLUSION: TNF-α polymorphisms in rs1799724 and rs1800629 increase the susceptibility of developing cervical cancer in women from Bangladesh.