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According to the 2018 WHO R&D Blueprint, Nipah virus (NiV) is a priority disease, and the development of a vaccine against NiV is strongly encouraged. According to criteria used to categorize zoonotic diseases, NiV is a stage III disease that can spread to people and cause unpredictable outbreaks. Since 2001, the NiV virus has caused annual outbreaks in Bangladesh, while in India it has caused occasional outbreaks. According to estimates, the mortality rate for infected individuals ranges from 70 to 91%. Using immunoinformatic approaches to anticipate the epitopes of the MHC-I, MHC-II, and B-cells, they were predicted using the NiV glycoprotein and nucleocapsid protein. The selected epitopes were used to develop a multi-epitope vaccine construct connected with linkers and adjuvants in order to improve immune responses to the vaccine construct. The 3D structure of the engineered vaccine was anticipated, optimized, and confirmed using a variety of computer simulation techniques so that its stability could be assessed. According to the immunological simulation tests, it was found that the vaccination elicits a targeted immune response against the NiV. Docking with TLR-3, 7, and 8 revealed that vaccine candidates had high binding affinities and low binding energies. Finally, molecular dynamic analysis confirms the stability of the new vaccine. Codon optimization and in silico cloning showed that the proposed vaccine was expressed to a high degree in Escherichia coli. The study will help in identifying a potential epitope for a vaccine candidate against NiV. The developed multi-epitope vaccine construct has a lot of potential, but they still need to be verified by in vitro & in vivo studies. [ABSTRACT FROM AUTHOR]

Background: Globally, undernutrition is the leading cause of mortality among under-five children. Bangladesh and India were in the top ten countries in the world for under-five mortality. The aim of the study was to investigate the nutritional status of Bengali under-five children. Methods: Data on 25938 under-five children were retrieved from the Bangladesh Demographic and Health Survey 2017–18 (BDHS) and the National Family Health Survey of India 2015–16 (NFHS-4). Stunting, wasting, underweight and thinness were considered to understand the nutritional status of under-five children. Binary logistic regression was used to identify associated factors of undernutrition among children. Results: Over one-quarter of Bengali under-five children were found to be suffering from the problem of stunting (31.9%) and underweight (28.1%), while other nutritional indicators raised serious concern and revealed inter-country disparities. In the cases of wasting, underweight and thinness, the mean z-scores and frequency differences between Bangladesh and India were significant. The nutritional status of Bengali under-five children appeared to have improved in Bangladesh compared to India. Child undernutrition had significant relations with maternal undernutrition in both countries. Girls in Bangladesh had slightly better nutritional status than boys. In Bangladesh, lack of formal education among mothers was a leading cause of child undernutrition. Stunting and underweight coexist with low household wealth index in both counties. Conclusions: The research revealed that various factors were associated with child undernutrition in Bengalis. It has been proposed that programmes promoting maternal education and nutrition, along with household wealth index be prioritised. The study recommends that the Governments of Bangladesh and India should increase the budget for health of children so as to reach the sustainable development goals. [ABSTRACT FROM AUTHOR]

Background: As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding: We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance: There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. [ABSTRACT FROM AUTHOR]

Background: The VL elimination strategy requires cost-effective tools for case detection and management. This intervention study tests the yield, feasibility and cost of 4 different active case detection (ACD) strategies (camp, index case, incentive and blanket approach) in VL endemic districts of India, Nepal and Bangladesh. Methodology/Principal Findings: First, VL screening (fever more than 14 days, splenomegaly, rK39 test) was performed in camps. This was followed by house to house screening (blanket approach). An analysis of secondary VL cases in the neighborhood of index cases was simulated (index case approach). A second screening round was repeated 4–6 months later. In another sub-district in India and Nepal, health workers received incentives for detecting new VL cases over a 4 month period (incentive approach). This was followed by house screening for undetected cases. A total of 28 new VL cases were identified by blanket approach in the 1st screening round, and used as ACD gold standard. Of these, the camp approach identified 22 (sensitivity 78.6%), index case approach identified 12 (sensitivity – 42.9%), and incentive approach identified 23 new VL cases out of 29 cases detected by the house screening (sensitivity – 79.3%). The effort required to detect a new VL case varied (blanket approach – 1092 households, incentive approach – 978 households; index case approach – 788 households had to be screened). The cost per new case detected varied (camp approach $21 – $661; index case approach $149 – $200; incentive based approach $50 – $543; blanket screening $112 – $629). The 2nd screening round yielded 20 new VL cases. Sixty and nine new PKDL cases were detected in the first and second round respectively. Conclusions/Significance: ACD in the VL elimination campaign has a high yield of new cases at programme costs which vary according to the screening method chosen. Countries need the right mix of approaches according to the epidemiological profile, affordability and organizational feasibility. Author Summary: For the elimination of any infectious disease (i.e., reduction of the burden of a serious public health problem to a minor problem which can be managed by the general health services) the right mix of public health tools has to be identified for the early detection and successful treatment of new cases as well as effective vector control (in the case of vector borne diseases) at affordable costs. The paper provides a powerful example of evidence building for cost-effective early case detection in the visceral leishmaniasis elimination initiative of Bangladesh, India and Nepal. It compares the camp approach (mobile teams testing in chronic fever camps for spleen enlargement and rapid diagnostic tests) with the index case approach (screening for new cases in the neighbourhood of reported visceral leishmaniasis patients) and the incentive based approach (where basic health workers receive an allowance for detecting a new case) using subsequent house-to-house screening for the identification of the real number of un-detected cases. By applying a mix of different study methods and an itinerate research process to identify the most effective, feasible and affordable case detection method, under different environmental conditions, recommendations could be developed which help governments in shaping their visceral leishmaniasis elimination strategy. [ABSTRACT FROM AUTHOR]

Background: Child undernutrition is a burden and the leading cause of child mortality in low-and middle-income countries like Bangladesh and India. Currently, this issue is a matter of great concern, inasmuch as achieving the Sustainable Development Goals (SDGs). The study intends to determine the factors of child undernutrition using a single composite index of anthropometric failure (CIAF) among the Bengali population. Methods: Unit level data on 14055 under 5 children were extracted from the Bangladesh Demographic and Health Survey 2017–18 (BDHS) and the 4th National Family Health Survey of India (NFHS-4). To understand child undernutrition and generate CIAF, data on height-for-age (stunting), weight-for-height (wasting), and weight-for-age (underweight) were used by WHO guidelines. These three undernutrition indicators were combined into a single undernutrition indicator called anthropometric failure (anth-failure) using the CIAF concept. Explanatory factors of anth-failure included data on maternal health, socio-demographic and birth-related variables. Differences of frequency were determined by Z-proportional and Chi-square tests; predictors of anth-failure were determined by binary logistic regression. Cut off point of p-value was taken as 0.05 to test the significance. Results: Inter-country disparities were revealed, about half of Bengali children in India and two-fifths in Bangladesh being prone to anth-failure. Stunting and underweight were more prevalent in both countries than wasting. Maternal undernutrition, lack of maternal education, and poor wealth index were common factors of anth-failure for both countries. Children in Bangladesh developed anth-failure after the end of breastfeeding period, indicating a lack of nutritious food. Lack of antenatal care was another significant factor in Bangladesh. In India, the first child suffered from anth-failure due to lack of maternal education. Conclusions: This study provides a better understanding of multifactorial impact on child undernutrition. It is proposed that the emphasis should be on initiatives that improve maternal education and nutrition, child food security, boost household wealth index, and enhance mothers' access to health care. The study strongly recommends that the governments of Bangladesh and India invest financially in preventing child malnutrition, which will contribute to achieving the first four SDGs. [ABSTRACT FROM AUTHOR]

Background: Pregnancy is a time of major psychological changes making pregnant women more susceptible to depression and anxiety. Prevalence is higher among women living in Bangladesh, India and Pakistan, compared to high-income countries, due to poor understanding and lack of mental health integration within antenatal care. Antenatal depression/anxiety is associated with adverse outcomes including postnatal depression, low birth weight and impaired fetal development. Existing systematic reviews provided only limited information on the social determinants of antenatal depression/anxiety in these South Asian countries. Objective: This review aimed to identify, synthesise and appraise the evidence on the social determinants associated with antenatal depression and anxiety in women living in Bangladesh, India and Pakistan. Methods: We searched five databases (MEDLINE, Embase, PsycINFO, Scopus, Web of Science) and PROSPERO. Observational studies published between 1st January 2000 and 4th January 2021 were included if they were in the English language, used validated tools for measuring depression/anxiety in pregnant women and reported statistical associations or raw numbers. Summary estimates were obtained using random-effects model. Heterogeneity and publication bias was measured using the I2 statistic and Egger's test, respectively. This review was registered on PROSPERO (reference: CRD42020167903). Results: We included 34 studies (with 27,379 women). Meta-analysis of Adjusted Odds Ratios (AOR) found that Intimate partner violence (AOR 2.48, 95% CI 1.41–4.33), unplanned pregnancy (AOR 1.53, 95% CI 1.28–1.83), male gender preference (AOR 3.06, 95% CI 1.40–6.72) and poor relationship with in-laws (AOR 2.69, 95% CI 1.25–5.80) were significantly associated with antenatal depression/anxiety. Conclusion: The review identified a complex range of social determinants of antenatal depression and anxiety in Bangladesh, India and Pakistan. Screening tools to identify pregnant women at high risk should be integrated within antenatal care to prevent adverse outcomes. Knowledge of these social determinants will inform the development of such screening tools and interventions. [ABSTRACT FROM AUTHOR]

Background: Bangladesh, India, and Nepal aim for the elimination of Visceral Leishmaniasis (VL), a systemic parasitic infectious disease, as a public health problem by 2020. For decades, male patients have comprised the majority of reported VL cases in this region. By comparing this reported VL sex ratio to the one observed in population-based studies conducted in the Indian subcontinent, we tested the working hypothesis that mainly socio-cultural gender differences in healthcare-seeking behavior explain this gender imbalance. Methodology/Principal findings: We compared the observed sex ratio of male versus female among all VL cases reported by the health system in Nepal and in the two most endemic states in India with that observed in population-based cohort studies in India and Nepal. Also, we assessed male sex as a potential risk factor for seroprevalence at baseline, seroconversion, and VL incidence in the same population-based data. The male/female ratio among VL cases reported by the health systems was 1.40 (95% CI 1.37–1.43). In the population cohort data, the age- and study site-adjusted male to female risk ratio was 1.27 (95% CI 1.08–1.51). Also, males had a 19% higher chance of being seropositive at baseline in the population surveys (RR 1.19; 95% CI 1.11–1.27), while we observed no significant difference in seroconversion rate between both sexes at the DAT cut-off titer defined as the primary endpoint. Conclusions/Significance: Our population-based data show that male sex is a risk factor for VL, and not only as a socio-cultural determinant. Biological sex-related differences likely play an important role in the pathogenesis of this disease. Author summary: Visceral Leishmaniasis (VL) is a parasitic disease that is lethal if not treated timely and mainly affects impoverished populations. Bangladesh, India, and Nepal have targeted the elimination of this disease as a public health problem by 2020. The majority of VL patients attending the health services are male, and this is usually attributed to unequal access to health care for men and women in this sociocultural context. We analyzed two large datasets obtained in population surveillance projects, including regular door-to-door screening for VL, in India and Nepal. Thereby we minimized any potential differences in access to health care between both sexes, as every suspect VL case occurring in the community received a full diagnostic work-up, and the research project facilitated transport to treatment centers if needed. By comparing the observed sex ratio in the health services records with those of the population surveillance records, we aimed to reach meaningful conclusions about the pathway through which male gender exerts its leverage for increasing VL risk: socio-cultural determinants blocking women from accessing care (nurture) or biological factors (nature) making men more vulnerable to VL. Because in the population-based age adjusted-data, male VL cases were significantly more frequent than female, our findings strongly suggest that in the Indian subcontinent, biological differences between men and women play a more critical role in the pathogenesis of VL than previously assumed, and the observed male predominance in VL cases in health services cannot be explained by socio-cultural factors only. Moreover, data show that above the age of 14 years, males are seropositive more often than females and are at higher risk to develop VL disease. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends participatory learning and action (PLA) in women's groups to improve maternal and newborn health, particularly in rural settings with low access to health services. There have been calls to understand the pathways through which this community intervention may affect neonatal mortality. We examined the effect of women's groups on key antenatal, delivery, and postnatal behaviours in order to understand pathways to mortality reduction.Methods and Findings: We conducted a meta-analysis using data from 7 cluster-randomised controlled trials that took place between 2001 and 2012 in rural India (2 trials), urban India (1 trial), rural Bangladesh (2 trials), rural Nepal (1 trial), and rural Malawi (1 trial), with the number of participants ranging between 6,125 and 29,901 live births. Behavioural outcomes included appropriate antenatal care, facility delivery, use of a safe delivery kit, hand washing by the birth attendant prior to delivery, use of a sterilised instrument to cut the umbilical cord, immediate wrapping of the newborn after delivery, delayed bathing of the newborn, early initiation of breastfeeding, and exclusive breastfeeding. We used 2-stage meta-analysis techniques to estimate the effect of the women's group intervention on behavioural outcomes. In the first stage, we used random effects models with individual patient data to assess the effect of groups on outcomes separately for the different trials. In the second stage of the meta-analysis, random effects models were applied using summary-level estimates calculated in the first stage of the analysis. To determine whether behaviour change was related to group attendance, we used random effects models to assess associations between outcomes and the following categories of group attendance and allocation: women attending a group and allocated to the intervention arm; women not attending a group but allocated to the intervention arm; and women allocated to the control arm. Overall, women's groups practising PLA improved behaviours during and after home deliveries, including the use of safe delivery kits (odds ratio [OR] 2.92, 95% CI 2.02-4.22; I2 = 63.7%, 95% CI 4.4%-86.2%), use of a sterile blade to cut the umbilical cord (1.88, 1.25-2.82; 67.6%, 16.1%-87.5%), birth attendant washing hands prior to delivery (1.87, 1.19-2.95; 79%, 53.8%-90.4%), delayed bathing of the newborn for at least 24 hours (1.47, 1.09-1.99; 68.0%, 29.2%-85.6%), and wrapping the newborn within 10 minutes of delivery (1.27, 1.02-1.60; 0.0%, 0%-79.2%). Effects were partly dependent on the proportion of pregnant women attending groups. We did not find evidence of effects on uptake of antenatal care (OR 1.03, 95% CI 0.77-1.38; I2 = 86.3%, 95% CI 73.8%-92.8%), facility delivery (1.02, 0.93-1.12; 21.4%, 0%-65.8%), initiating breastfeeding within 1 hour (1.08, 0.85-1.39; 76.6%, 50.9%-88.8%), or exclusive breastfeeding for 6 weeks after delivery (1.18, 0.93-1.48; 72.9%, 37.8%-88.2%). The main limitation of our analysis is the high degree of heterogeneity for effects on most behaviours, possibly due to the limited number of trials involving women's groups and context-specific effects.Conclusions: This meta-analysis suggests that women's groups practising PLA improve key behaviours on the pathway to neonatal mortality, with the strongest evidence for home care behaviours and practices during home deliveries. A lack of consistency in improved behaviours across all trials may reflect differences in local priorities, capabilities, and the responsiveness of health services. Future research could address the mechanisms behind how PLA improves survival, in order to adapt this method to improve maternal and newborn health in different contexts, as well as improve other outcomes across the continuum of care for women, children, and adolescents. [ABSTRACT FROM AUTHOR]

Background: Globally, puerperal sepsis accounts for an estimated 8–12% of maternal deaths, but evidence is lacking on the extent to which clean delivery practices could improve maternal survival. We used data from the control arms of four cluster-randomised controlled trials conducted in rural India, Bangladesh and Nepal, to examine associations between clean delivery kit use and hand washing by the birth attendant with maternal mortality among home deliveries. Methods: We tested associations between clean delivery practices and maternal deaths, using a pooled dataset for 40,602 home births across sites in the three countries. Cross-sectional data were analysed by fitting logistic regression models with and without multiple imputation, and confounders were selected a priori using causal directed acyclic graphs. The robustness of estimates was investigated through sensitivity analyses. Results: Hand washing was associated with a 49% reduction in the odds of maternal mortality after adjusting for confounding factors (adjusted odds ratio (AOR) 0.51, 95% CI 0.28–0.93). The sensitivity analysis testing the missing at random assumption for the multiple imputation, as well as the sensitivity analysis accounting for possible misclassification bias in the use of clean delivery practices, indicated that the association between hand washing and maternal death had been over estimated. Clean delivery kit use was not associated with a maternal death (AOR 1.26, 95% CI 0.62–2.56). Conclusions: Our evidence suggests that hand washing in delivery is critical for maternal survival among home deliveries in rural South Asia, although the exact magnitude of this effect is uncertain due to inherent biases associated with observational data from low resource settings. Our findings indicating kit use does not improve maternal survival, suggests that the soap is not being used in all instances that kit use is being reported. [ABSTRACT FROM AUTHOR]

Background: Sepsis accounts for up to 15% of an estimated 3.3 million annual neonatal deaths globally. We used data collected from the control arms of three previously conducted cluster-randomised controlled trials in rural Bangladesh, India, and Nepal to examine the association between clean delivery kit use or clean delivery practices and neonatal mortality among home births. Methods and Findings: Hierarchical, logistic regression models were used to explore the association between neonatal mortality and clean delivery kit use or clean delivery practices in 19,754 home births, controlling for confounders common to all study sites. We tested the association between kit use and neonatal mortality using a pooled dataset from all three sites and separately for each site. We then examined the association between individual clean delivery practices addressed in the contents of the kit (boiled blade and thread, plastic sheet, gloves, hand washing, and appropriate cord care) and neonatal mortality. Finally, we examined the combined association between mortality and four specific clean delivery practices (boiled blade and thread, hand washing, and plastic sheet). Using the pooled dataset, we found that kit use was associated with a relative reduction in neonatal mortality (adjusted odds ratio 0.52, 95% CI 0.39-0.68). While use of a clean delivery kit was not always accompanied by clean delivery practices, using a plastic sheet during delivery, a boiled blade to cut the cord, a boiled thread to tie the cord, and antiseptic to clean the umbilicus were each significantly associated with relative reductions in mortality, independently of kit use. Each additional clean delivery practice used was associated with a 16% relative reduction in neonatal mortality (odds ratio 0.84, 95% CI 0.77-0.92). Conclusions: The appropriate use of a clean delivery kit or clean delivery practices is associated with relative reductions in neonatal mortality among home births in underserved, rural populations. [ABSTRACT FROM AUTHOR]

Background: In the Indian subcontinent, about 200 million people are at risk of developing visceral leishmaniasis (VL). In 2005, the governments of India, Nepal and Bangladesh started the first regional VL elimination program with the aim to reduce the annual incidence to less than 1 per 10,000 by 2015. A mathematical model was developed to support this elimination program with basic quantifications of transmission, disease and intervention parameters. This model was used to predict the effects of different intervention strategies. Methods and Findings: Parameters on the natural history of Leishmania infection were estimated based on a literature review and expert opinion or drawn from a community intervention trial (the KALANET project). The transmission dynamic of Leishmania donovani is rather slow, mainly due to its long incubation period and the potentially long persistence of parasites in infected humans. Cellular immunity as measured by the Leishmanin skin test (LST) lasts on average for roughly one year, and re-infection occurs in intervals of about two years, with variation not specified. The model suggests that transmission of L. donovani is predominantly maintained by asymptomatically infected hosts. Only patients with symptomatic disease were eligible for treatment; thus, in contrast to vector control, the treatment of cases had almost no effect on the overall intensity of transmission. Conclusions: Treatment of Kala-azar is necessary on the level of the individual patient but may have little effect on transmission of parasites. In contrast, vector control or exposure prophylaxis has the potential to efficiently reduce transmission of parasites. Based on these findings, control of VL should pay more attention to vector-related interventions. Cases of PKDL may appear after years and may initiate a new outbreak of disease; interventions should therefore be long enough, combined with an active case detection and include effective treatment. [ABSTRACT FROM AUTHOR]

Background: Pay-for-performance rewards health-care providers by paying them more if they succeed in meeting performance targets. A new contract for general practitioners in the United Kingdom represents the most radical shift towards pay-for-performance seen in any health-care system. The contract provides an important opportunity to address disparities in chronic disease management between ethnic and socioeconomic groups. We examined disparities in management of people with diabetes and intermediate clinical outcomes within a multiethnic population in primary care before and after the introduction of the new contract in April 2004.Methods and Findings: We conducted a population-based longitudinal survey, using electronic general practice records, in an ethnically diverse part of southwest London. Outcome measures were prescribing levels and achievement of national treatment targets (HbA1c < or = 7.0%; blood pressure [BP] < 140/80 mm Hg; total cholesterol < or = 5 mmol/l or 193 mg/dl). The proportion of patients reaching treatment targets for HbA1c, BP, and total cholesterol increased significantly after the implementation of the new contract. The extents of these increases were broadly uniform across ethnic groups, with the exception of the black Caribbean patient group, which had a significantly lower improvement in HbA1c (adjusted odds ratio [AOR] 0.75, 95% confidence interval [CI] 0.57-0.97) and BP control (AOR 0.65, 95% CI 0.53-0.81) relative to the white British patient group. Variations in prescribing and achievement of treatment targets between ethnic groups present in 2003 were not attenuated in 2005.Conclusions: Pay-for-performance incentives have not addressed disparities in the management and control of diabetes between ethnic groups. Quality improvement initiatives must place greater emphasis on minority communities to avoid continued disparities in mortality from cardiovascular disease and the other major complications of diabetes. [ABSTRACT FROM AUTHOR]