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Typhoid remains a major cause of illness and death globally. In this trial, the efficacy of a typhoid conjugate vaccine was assessed in children in Nepal. A total of 20,019 children were randomly assigned to receive either a TCV or a meningococcal A vaccine. The TCV was associated with a decrease of 81.6% in Salmonella Typhi bacteremia.

Background/aimsWe aimed to examine risk factors for corneal ulcer in a rural and peri-urban setting in Nepal.MethodsThis population-based matched case–control study was nested in a cluster randomised trial in 24 village development committees in Nepal. Incidence density sampling was used to match incident corneal opacity cases to controls, matching on time of opacity, age, sex and location. Cases and controls were invited to participate in a survey of risk factors for corneal ulcer. Risk factors were evaluated using conditional logistic regression to account for matching.ResultsOf the 540 participants with incident opacities identified in the trial, 433 were willing to participate in this substudy and matched to a control. Compared with controls, cases had lower odds of having any education vs no education (adjusted OR, aOR 0.60, 95% CI 0.39 to 0.94), working in non-manual labour occupations vs manual labour occupations (aOR 0.64, 95% CI 0.42 to 0.95) and preferring medical shops for ocular trauma versus eye care system centres (aOR 0.58, 95% CI 0.37 to 0.92). Cases had higher odds of protective goggle use versus no protection (aOR 3.8, 95% CI 1.3 to 11.0) and having an ocular injury vs none (aOR 7.7, 95% CI 4.3 to 13.6) compared with controls.ConclusionWe found ocular injury, manual labour and lower education to be strongly associated with the development of corneal ulcer. Given the persistent burden of corneal blindness in this area, prevention efforts could target efforts to increase access to care in areas where these factors are common.

Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country. We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to <2 years, 2 years to <18 years, and 18 years to 45 years), into one of four groups (A–D). Participants in groups A–C received a single dose (25 μg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 μg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A–C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A–C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of −10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098. Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A–D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A–C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A–C combined versus Vi-TT group D was 0·47% (97·5% CI −0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A–C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A–C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A–C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A–C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product. When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies. The Bill & Melinda Gates Foundation. For the Nepali translation of the abstract see Supplementary Materials section.

Respiratory syncytial virus (RSV) is the most important cause of viral pneumonia in children worldwide. A maternal vaccine may protect both the mother and infant from RSV illness. The epidemiology and clinical presentation of RSV in pregnant and postpartum women is not well-described. Data were collected from a prospective, randomized trial of influenza immunization in pregnant women in rural southern Nepal. Women were enrolled in their second trimester of pregnancy and followed until six months postpartum. Active weekly home-based surveillance for febrile respiratory illness was performed. Mid-nasal swabs collected with episodes of respiratory illness were tested for RSV by real-time polymerase chain reaction. RSV was detected in 14 (0.4%) illness episodes in 3693 women over 3554 person-years of surveillance from 2011-2014. RSV incidence was 3.9/1000 person-years overall, and 11.8/1000 person-years between September and December. Seven (50%) women sought care for RSV illness; none died. Of the 7 (50%) illness episodes during pregnancy, all had live births with 2 (29%) preterm births and a median birthweight of 3060 grams. This compares to 469 (13%) preterm births and a median birthweight of 2790 grams in women without RSV during pregnancy. Of the 7 mothers with postpartum RSV infection, RSV was detected in 4 (57%) of their infants. RSV was an uncommon cause of febrile respiratory illness in mothers during pregnancy in Nepal. These data will inform prevention and therapeutic strategies against RSV in resource-limited settings.

Postpartum depression is the most common mental health problem among women of childbearing age in resource-poor countries. Poor maternal mental health is linked with both acute and chronic negative effects on the growth and development of the child. This study aimed to assess the prevalence and factors associated with depressive symptoms among postpartum mothers in the lowland region in southern Nepal. A hospital-based analytical cross-sectional study was conducted from 1st July to 25th August 2019 among 415 randomly selected postpartum mothers attending the child immunization clinic at Narayani hospital. The postpartum depressive symptoms were measured using the validated Nepalese version of the Edinburg Postnatal Depression Scale (EPDS). The data were entered into EpiData software 3.1v and transferred into Stata version 14.1 (StataCorp LP, College Station, Texas) for statistical analyses. To identify the correlates, backward stepwise binary logistic regression models were performed separately for the dichotomized outcomes: the presence of postpartum depressive symptoms. The statistical significance was considered at p-value <0.05 with 95% confidence intervals (CIs). Among the total 415 study participants, 33.7% (95% CI: 29.2-38.5%) of postpartum mothers had depressive symptoms. Study participant's whose family monthly income <150 USD compared to ≥150 USD (aOR = 13.76, 95% CI: 6.54-28.95), the husband had migrated for employment compared to not migrated (aOR = 8.19, 95% CI:4.11-15.87), nearest health facility located at more than 60 minutes of walking distance (aOR = 4.52, 95% CI: 2.26-9.03), delivered their last child by cesarean section compared to normal (vaginal) delivery (aOR = 2.02, 95% CI: 1.12-3.59) and received less than four recommended antenatal care (ANC) visits (aOR = 2.28, 95% CI:1.25-4.15) had higher odds of depressive symptoms. Participants who had planned pregnancy (aOR = 0.44, 95% CI: 0.25-0.77) were associated with 56% lower odds of depressive symptoms. One-third of the mothers suffered from postpartum depressive symptoms. The participant's husband migrated for employment, family income, distance to reach a health facility, delivery by cesarean section, not receiving recommended ANC visits, and plan of pregnancy were independent predictors for postpartum depressive symptoms. The study results warranted the urgency for clinical diagnosis of PPD and implementation of preventive package in study settings. Mental health education to pregnant women during ANC visits and proper counseling during the antepartum and postpartum period can also play a positive role in preventing postpartum depression.

Annually, an estimated 2.3 million infants die within their first month of life, primarily in sub-Saharan Africa and South Asia. Infections, including sepsis are among the major contributors to these deaths. Effective interventions added to standard antimicrobial therapy can reduce sepsis mortality. A recent meta-analysis suggests that adjunct zinc treatment of young infants with sepsis could reduce case fatality risk. This study evaluated the efficacy of zinc as an adjunct to antibiotics in young infants with suspected sepsis, defined as clinical severe infection (CSI). We conducted a randomized, double-blind, placebo-controlled trial across seven hospitals in India and Nepal from February 28, 2017, to February 22, 2022. Infants aged 3-59 days hospitalized with suspected sepsis, defined as CSI, adapted from the WHO Integrated Management of Childhood Illness (IMCI) criteria, were randomly assigned to receive 10 mg of elemental zinc daily or placebo orally for 14 days, in addition to standard of care. The primary outcomes were death during hospitalization and death within 12 weeks after enrollment. Among 3,153 enrolled infants (1,203 [38%] females), the median age at enrollment was 25 days (interquartile range 13-41 days), and the mean weight was 2.9 kg (standard deviation 0.8). During the hospital stay, 64 (4.1%) of 1,576 infants died in the zinc arm compared to 77 (4.9%) of 1,577 in the placebo arm (relative risk [RR] 0.83 (95% CI [0.60, 1.15]; p = 0.267)). Among those who completed 12 weeks of follow-up, 140 of 1,554 infants (9.0%) died in the zinc arm, and 133 of 1,550 (8.6%) in the placebo arm (RR 1.05 (95% CI [0.84, 1.32]; p = 0.674)). Adverse events were similar across trial arms, except for a slight increase in vomiting in the zinc arm; no events were attributed to the intervention. The main limitation of the study is that it was underpowered due to lower-than-anticipated event rates and a shortfall in the achieved sample size. In this setting, we found little evidence for an effect of adjunct zinc therapy on young infants with CSI on the risk of dying during hospitalization or for the subsequent 3 months. Our findings contrast previous studies that used more specific case definitions. This underscores the need for further RCTs to evaluate the effect of zinc in young infant sepsis before it can be recommended in treatment guidelines. Clinical Trials Registry-India (CTRI/2017/02/007966) on February 27, 2017, and Universal Trial Number is U1111-1187-6479.

Adequate nutrition is essential during the lactation period for better maternal and child health outcomes. Although food insecurity and dietary monotony (defined as less diverse diet), two important determinants of undernutrition, are endemic in the rural mountains of Nepal, insufficiently examined and assessed for risk factors in mothers during lactation, a life stage of high nutritional demand. This study aimed to assess the status and factors associated with food insecurity and dietary diversity among lactating mothers residing in the mountains of Nepal. A community-based cross-sectional study was conducted in an urban municipality in the mountainous Bajhang District of far-western Nepal. The sampling frame and strategy led to 417 randomly selected lactating mothers. Household Food Insecurity Access Scale (HFIAS) and the tool \"Minimum Dietary Diversity for Women\" developed by the Food and Agriculture Organization were used to measure food insecurity and dietary diversity, respectively. Additional information on socio-demographics and risk factors were collected. Multivariable logistics regression assessed correlates of study outcomes. Overall, 54% of the households were food insecure, and over half (53%) of the mothers had low dietary diversity. Food insecurity status (mild food insecurity AOR = 10.12, 95% CI = 4.21-24.34; moderate food insecurity AOR = 8.17, 95% CI = 3.24-20.59, and severe food insecurity AOR = 10.56, 95% CI = 3.92-28.43) were associated with higher odds of dietary monotony. Likewise, participants with lower dietary diversity were 8.5 times more likely to be food insecure than those with higher dietary diversity (AOR = 8.48, 95% CI = 3.76-19.14). The monthly income of the family was positively associated with food insecurity. Participants' (AOR = 3.92 95%CI = 1.76-8.71) or spouses' (AOR = 2.90, 95% CI = 1.07-7.85) unemployment was associated with higher odds of being food insecure. Likewise, owning a cultivable land (AOR = 0.49, 95% CI = 0.28-0.84) and participant's unemployment status (AOR = 5.92, 95% CI = 3.02-11.63), were significantly associated with increased odds of dietary monotony. The observed food insecurity and poor dietary diversity among lactating mothers, the correlates associated with these outcomes, may help local stakeholders to identify local health needs and subgroups for targeted interventions. Socioeconomically disadvantaged mothers should be specifically targeted for relevant programs and policies.

This placebo-controlled randomized trial in rural Nepal found that maternal influenza vaccination in either the second or third trimester of pregnancy provided similar birth outcomes and protection from influenza in infancy. Abstract Background Maternal influenza vaccination protects mothers and their infants in low resource settings, but little is known about whether the protection varies by gestational age at vaccination. Methods Women of childbearing age in rural southern Nepal were surveilled for pregnancy, consented and randomized to receive maternal influenza vaccination or placebo, with randomization stratified on gestational age (17-25 or 26-34 weeks). Enrollment occurred in 2 annual cohorts, and vaccinations occurred from April 2011 through September 2013. Results In sum, 3693 women consented and enrolled, resulting in 3646 live births. Although cord blood antibody titers and the rise in maternal titers were generally greater when women were vaccinated later in pregnancy, this was not statistically significant. The incidence risk ratio (IRR) for maternal influenza in pregnancy through 6 months postpartum was 0.62 (95% confidence interval [CI]: 0.35, 1.10) for those vaccinated 17-25 weeks gestation and 0.89 (95% CI: 0.39, 2.00) for those 26-34 weeks. Infant influenza IRRs were 0.73 (95% CI: 0.51, 1.05) for those whose mothers were vaccinated earlier in gestation, and 0.63 (95% CI: 0.37, 1.08) for those later. Relative risks (RR) for low birthweight were 0.83 (95% CI: 0.71, 0.98) and 0.90 (95% CI: 0.72, 1.12) for 17-25 and 26-34 weeks gestation at vaccination, respectively. IRRs did not differ for small-for-gestational age or preterm. No RRs were statistically different by timing of vaccine receipt. Conclusions Vaccine efficacy did not vary by gestational age at vaccination, making maternal influenza immunization programs easier to implement where women present for care late in pregnancy. Clinical Trials Registration NCT01034254

Background Cardiovascular diseases (CVD) are the main cause of mortality in low- and middle-income countries like Nepal. Different risk factors usually cluster and interact multiplicatively to increase the risk of developing acute cardiovascular events; however, information related to clustering of CVD risk factors is scarce in Nepal. Therefore, we aimed to determine the prevalence of CVD risk factors with a focus on their clustering pattern in a rural Nepalese population. Methods A community-based cross-sectional study was conducted among residents aged 40 to 80 years in Lamjung District of Nepal in 2014. A clustered sampling technique was used in steps. At first, four out of 18 wards were chosen at random. Then, one person per household was selected randomly ( n  = 388). WHO STEPS questionnaires (version 2.2) were used to collect data. Chi-square and independent t-test were used to test significance at the level of p  < 0.05. Results A total 345 samples with complete data were analyzed. Smoking [24.1% (95% CI: 19.5–28.6)], harmful use of alcohol [10.7% (7.4–13.9)], insufficient intake of fruit and vegetable [72% (67.1–76.6)], low physical activity [10.1% (6.9–13.2)], overweight and obesity [59.4% (54.2–64.5)], hypertension [42.9% (37.6–48.1)], diabetes [16.2% (14.0–18.3)], and dyslipidemia [56.0% (53.0–58.7)] were common risk factors among the study population. Overall, 98.2% had at least one risk factor, while 2.0% exhibited six risk factors. Overall, more than a half (63.4%) of participants had at least three risk factors (male: 69.4%, female: 58.5%). Age [OR: 2.3 (95% CI: 1.13–4.72)] and caste/ethnicity [2.0 (95% CI: 1.28–3.43)] were significantly associated with clustering of at least three risk factors. Conclusions Cardiovascular risk factors and their clustering were common in the rural population of Nepal. Therefore, comprehensive interventions against all risk factors should be immediately planned and implemented to reduce the future burden of CVD in the rural population of Nepal.

Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years. 90% of deliveries in the poorest quintile of households happen at home. We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates. We pair-matched 42 geopolitical clusters in Makwanpur district, Nepal, selected 12 pairs randomly, and randomly assigned one of each pair to intervention or control. In each intervention cluster (average population 7000), a female facilitator convened nine women's group meetings every month. The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them. We monitored birth outcomes in a cohort of 28931 women, of whom 8% joined the groups. The primary outcome was neonatal mortality rate. Other outcomes included stillbirths and maternal deaths, uptake of antenatal and delivery services, home care practices, infant morbidity, and health-care seeking. Analysis was by intention to treat. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN31137309. From 2001 to 2003, the neonatal mortality rate was 26·2 per 1000 (76 deaths per 2899 livebirths) in intervention clusters compared with 36·9 per 1000 (119 deaths per 3226 livebirths) in controls (adjusted odds ratio 0·70 [95% CI 0·53–0·94]). Stillbirth rates were similar in both groups. The maternal mortality ratio was 69 per 100000 (two deaths per 2899 livebirths) in intervention clusters compared with 341 per 100000 (11 deaths per 3226 livebirths) in control clusters (0·22 [0·05–0·90]). Women in intervention clusters were more likely to have antenatal care, institutional delivery, trained birth attendance, and hygienic care than were controls. Birth outcomes in a poor rural population improved greatly through a low cost, potentially sustainable and scalable, participatory intervention with women's groups.