Search

Background Faltering of growth in early life has been recognized as a public health challenge among Indian babies. A two-day consultation on growth faltering in early infancy was organized to examine the data and evidence on identification and management of early growth failure and to identify knowledge gaps and future areas of research. The consultation was supported by the Biotechnology Industry Research Assistance Council (BIRAC), the Indian Academy of Pediatrics (Nutrition Chapter), Vardhman Mahavir Medical College and Safdarjung Hospital, and the Society for Applied Studies. It brought together researchers, clinicians, policy makers and program managers.

Background Kangaroo mother care (KMC) can substantially enhance overall survival of low birthweight babies. In a large randomized controlled trial, we recently showed that supporting mothers to provide community initiated KMC (ciKMC) can reduce mortality among infants up to 180 days of life by 25% (hazard ratio (HR) 0.75). With the current analysis, we aimed to explore if ciKMC promotion leads to increased inequity in survival. Methods In the trial we randomized 8402 low birthweight babies to a ciKMC (4480 babies) and a control (3922 babies) arm, between 2015 and 2018 in Haryana, India. We estimated the difference in concentration indices, which measure inequality, between babies in the ciKMC and control arms for survival until 180 days of life. Further, we compared the effect of ciKMC promotion across subgroups defined by socioeconomic status, caste, maternal literacy, infant’s sex, and religion. Results Our intervention did not increase survival inequity, as the concentration index in the ciKMC arm of the trial was 0.05 (95% CI -0.07 to 0.17) lower than in the control arm. Survival impact was higher among those belonging to the lower two wealth quintiles, those born to illiterate mothers and those belonging to religions other than Hindu. Conclusions We found that ciKMC promotion did not increase inequity in survival associated with wealth. The beneficial impact of ciKMC tended to be larger among vulnerable groups. Supporting mothers to provide KMC at home to low birthweight babies will not increase and could indeed reduce inequities in infant survival. Trial registration ClinicalTrials.gov, NCT02653534. Registered January 12, 2016—Retrospectively registered.

Highlights • Prelicensure trials of ROTAVAC® not powered to assess risk of intussusception. • During ROTAVAC® rollout we assessed risk of intussusception in infants in 3 states. • No increased risk of intussusception within 21 days of 1st and 2nd dose. • No increased risk of intussusception within 21 days of any single dose or all 3 doses., Background Pre-licensure trials of ROTAVAC® were not adequately powered to assess risk of intussusception, a rare adverse event associated with other rotavirus vaccines in some settings. We examined the risk of intussusception after ROTAVAC® vaccination among Indian infants during pilot rollout of the vaccine in the public health system in three states - Himachal Pradesh, Maharashtra and Tamil Nadu. Methods Passive surveillance for intussusception was set up in 35 sentinel health facilities covering 26.3 million population in the three states under monitoring of an Interministerial-Interagency Steering Committee. Clinical and immunization data were collected by independent teams. An expert committee blinded to vaccination status, classified intussusception cases using Brighton criteria. The self-controlled case-series method was used to estimate risk of intussusception (Brighton Level 1) after ROTAVAC® vaccination. Results 151 intussusception cases were included in the analysis. The relative incidence (incidence during the risk period compared to the control period) 1–21 days after doses 1 and 2 combined was 1.56 (95% CI, 0.0–5.28) and that for three doses combined was 1.88 (95% CI, 0.76–4.30). Attributable risk 1–21 days after doses 1 and 2 combined was 0.11 (95% CI, 0.0–0.25) and that for 3 doses combined was 0.42 (95% CI, 0.0–0.70) per 100,000 doses. Conclusions No increased risk of intussusception within 21 days of receipt of the first two doses combined or all 3 doses combined of ROTAVAC® was detected.

Summary Background Coverage of kangaroo mother care remains very low despite WHO recommendations for its use for babies with low birthweight in health facilities for over a decade. Initiating kangaroo mother care at the community level is a promising strategy to increase coverage. However, knowledge of the efficacy of community-initiated kangaroo mother care is still lacking. We aimed to assess the effect of community-initiated kangaroo mother care provided to babies weighing 1500–2250 g on neonatal and infant survival. Methods In this randomised controlled, superiority trial, undertaken in Haryana, India, we enrolled babies weighing 1500–2250 g at home within 72 h of birth, if not already initiated in kangaroo mother care, irrespective of place of birth (ie, home or health facility) and who were stable and feeding. The first eligible infants in households were randomly assigned (1:1) to the intervention (community-initiated kangaroo mother care) or control group by block randomisation using permuted blocks of variable size. Twins were allocated to the same group. For second eligible infants in the same household as an enrolled infant, if the first infant was assigned to the intervention group the second infant was also assigned to this group, whereas if the first infant was assigned to the control group the second infant was randomly assigned (1:1) to the intervention or control group. Mothers and infants in the intervention group were visited at home (days 1–3, 5, 7, 10, 14, 21, and 28) to support kangaroo mother care (ie, skin-to-skin contact and exclusive breastfeeding). The control group received routine care. The two primary outcomes were mortality between enrolment and 28 days and between enrolment and 180 days. Analysis was by intention to treat and adjusted for clustering within households. The effect of the intervention on mortality was assessed with person-time in the denominator using Cox proportional hazards model. This study is registered with ClinicalTrials.gov , NCT02653534 and NCT02631343 , and is now closed to new participants. Findings Between July 30, 2015, and Oct 31, 2018, 8402 babies were enrolled, of whom 4480 were assigned to the intervention group and 3922 to the control group. Most births (6837 [81·4%]) occurred at a health facility, 36·2% (n=3045) had initiated breastfeeding within 1 h of birth, and infants were enrolled at an average of about 30 h (SD 17) of age. Vital status was known for 4470 infants in the intervention group and 3914 in the control group at age 28 days, and for 3653 in the intervention group and 3331 in the control group at age 180 days. Between enrolment and 28 days, 73 infants died in 4423 periods of 28 days in the intervention group and 90 deaths in 3859 periods of 28 days in the control group (hazard ratio [HR] 0·70, 95% CI 0·51–0·96; p=0·027). Between enrolment and 180 days, 158 infants died in 3965 periods of 180 days in the intervention group and 184 infants died in 3514 periods of 180 days in the control group (HR 0·75, 0·60–0·93; p=0·010). The risk ratios for death were almost the same as the HRs (28-day mortality 0·71, 95% CI 0·52– 0·97; p=0·032; 180-day mortality 0·76, 0·60–0·95; p=0·017). Interpretation Community-initiated kangaroo mother care substantially improves newborn baby and infant survival. In low-income and middle-income countries, incorporation of kangaroo mother care for all infants with low birthweight, irrespective of place of birth, could substantially reduce neonatal and infant mortality. Funding Research Council of Norway and University of Bergen.

Salmonella typhi is a causative organism for typhoid fever. Free Vi capsular polysaccharide (Vi) is licensed for use as vaccine for typhoid fever in individuals 2 years of age and older, which has limited memory response. There is dire need of protein or peptide as conjugate partner with Vi polysaccharide to improve shortcomings of Vi vaccine. Prediction of immunogenic peptide was deduced by program T sites. Carbodiimide mediated conjugation of Vi polysaccharide with OmpCp was performed utilizing ADH as linker. Immune response of Vi-conjugates along with control group was tested in mice. Ig and IgG antibodies against Vi polysaccharide was measured by ELISA. Two immunodominant regions (loop number 3a and 7) with high content of T-cell epitopes from OmpC was selected and synthesized. Vi poly/OmpCp ratios in Vi-conjugates were ~0.43–0.65. Vi polysaccharide alone elicited very low levels of Vi antibody without any booster effect. Vi-conjugate evoked 20-fold higher immune response compared to free Vi. Further, adequate levels of IgG antibodies were induced only by the Vi-conjugate suggesting that T-helper cells had been induced. Our data suggest that selected short peptide (OmpCp)as a carrier with Vi polysaccharide is assumed to be a promising molecule for candidate vaccine for typhoid fever.

Changing epidemiology, rapid urbanization, and rising expectations of populations are creating new challenges and opportunities for India's primary healthcare system. A group of primary care experts, practitioners, and researchers got together to design key elements of primary healthcare models for the future that would address these challenges and make use of emergent opportunities in rural and urban India. Based on experiences and evidence from India and across the globe shared in the consultation, the article lays out a vision and components of India's primary healthcare for future. It provides answers to questions such as how will healthcare be financed and organized, what mechanisms will assure quality of services, who will provide primary healthcare, and what role will technology have. Finally, it provides an agenda for primary healthcare practitioners and researchers to translate this vision into action.

The aim of this study was to examine the association between vitamin D deficiency and anemia status among young children in the resource-poor setting of northern urban India.We used data from a randomized controlled trial of daily supplementation with folic acid, vitamin B25-Hydroxyvitamin-D (25 OHD) concentration was measured for 960 (96%) children. Of the children, 331 (34.5%) were vitamin-D deficient (10 ng/mL). Approximately 70% of the enrolled children were anemic, with ∼46% having moderate (Hgb 7-9.9 g/dL) and 24% mild (Hgb 10-10.9 g/dL) anemia. There was no association between vitamin D and anemia status after adjusting for confounders; however, the risk for moderate anemia was significantly higher among vitamin D-deficient children than those who were vitamin-D replete (relative risk, 1.58; 95% confidence interval, 1.09-2.31).Vitamin D deficiency was associated with moderate anemia among young children and the effect was independent of iron deficiency. The causal association of vitamin D deficiency with anemia risk remains debatable. The role of vitamin D in risk for anemia needs to be examined in further studies.

Background: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration. Because ROTAVAC®, a WHO prequalified vaccine, was derived from the 116E neonatal strain, we evaluated the immunogenicity and safety of ROTAVAC® without buffer and ROTAVAC® with buffer in a phase 4, multicentre, single-blind, randomized clinical trial in healthy infants in India. Methods: 900 infants, approximately 6, 10 and 14 weeks of age, were assigned to 3 groups to receive ROTAVAC® (0.5 mL dose) orally: (i) 2.5 mL of citrate-bicarbonate buffer 5 minutes prior to administration of ROTAVAC® (Group I), (ii) ROTAVAC®, alone, without any buffer (Group II), or (iii) ROTAVAC®, mixed with buffer immediately before administration (Group III). Non–inferiority was compared among the groups for differences in serological responses (detected by serum anti-rotavirus IgA) and safety. Results: Geometric mean titers post vaccination at day 84 (28 days after dose 3) were 19.6 (95%CI: 17.0, 22.7), 20.7 (95%CI: 17.9, 24) and 19.2 (95%CI: 16.8, 22.1) for groups I, II and III respectively. Further, seroconversion rates and distribution of adverse events were similar among groups. Conclusions: Administration of ROTAVAC® at a 0.5 mL dose volume without buffering agent was shown to be well tolerated and immunogenic. Given the homologous nature of the strain, it is plausible that ROTAVAC® replicates well and confers immunity even without buffer administration.

Background The period from conception to two years of life denotes a critical window of opportunity for promoting optimal growth and development of children. Poor nutrition and health in women of reproductive age and during pregnancy can negatively impact birth outcomes and subsequent infant survival, health and growth. Studies to improve birth outcomes and to achieve optimal growth and development in young children have usually tested the effect of standalone interventions in pregnancy and/or the postnatal period. It is not clearly known whether evidence-based interventions in the different domains such as health, nutrition, water sanitation and hygiene (WASH) and psychosocial care, when delivered together have a synergistic effect. Further, the effect of delivery of an intervention package in the pre and peri-conception period is not fully understood. This study was conceived with an aim to understand the impact of an integrated intervention package, delivered across the pre and peri-conception period, through pregnancy and till 24 months of child age on birth outcomes, growth and development in children. Methods An individually randomized controlled trial with factorial design is being conducted in urban and peri-urban low- to mid-socioeconomic neighbourhoods in South Delhi, India. 13,500 married women aged 18 to 30 years will be enrolled and randomized to receive either the pre and peri-conception intervention package or routine care (first randomization). Interventions will be delivered until women are confirmed to be pregnant or complete 18 months of follow up. Once pregnancy is confirmed, women are randomized again (second randomization) to receive either the intervention package for pregnancy and postnatal period or to routine care. Newborns will be followed up till 24 months of age. The interventions are delivered through different study teams. Outcome data are collected by an independent outcome ascertainment team. Discussion This study will demonstrate the improvement that can be achieved when key factors known to limit child growth and development are addressed together, throughout the continuum from pre and peri-conception until early childhood. The findings will increase our scientific understanding and provide guidance to nutrition programs in low- and middle-income settings. Trial registration Clinical Trial Registry – India #CTRI/2017/06/008908; Registered 23 June 2017, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies

Background Government of India and the World Health Organization have guidelines for outpatient management of young infants 0–59 days with signs of Possible Serious Bacterial Infection (PSBI), when referral is not feasible. Implementation research was conducted to identify facilitators and barriers to operationalizing these guidelines. Methods Himachal Pradesh government implemented the guidelines in program settings supported by Centre for Health Research and Development, Society for Applied Studies. The strategy included community sensitization, skill enhancement of Accredited Social Health Activists (ASHA), Auxiliary Nurse Midwives (ANMs) and Medical Officers (MOs) to identify PSBI and treat when referral was not feasible. The research team collected information on facilitators and barriers. A technical support unit provided training and oversight. Findings Among 1997 live births from June 2017 to January 2019, we identified 160 cases of PSBI in young infants resulting in a coverage of 80%, assuming an incidence of 10%. Of these,29(18.1%) had signs of critical illness (CI), 92 (57.5%) had clinical severe infection (CSI), 5 (3.1%)had severe pneumonia (only fast breathing in young infants 0–6 days), while 34 (21%) had pneumonia (only fast breathing in young infants 7–59 days). Hospital referral was accepted by 48/160 (30%), whereas 112/160 (70%) were treated with the simplified treatment regimens at primary level facilities. Of the 29 infants with CI, 18 (62%) accepted referral; 26 (90%) recovered while 3 (10%) who had accepted referral, died. Of the 92 infants who had CSI, 86 (93%) recovered, 65 (71%) received simplified treatment and one infant who had accepted referral, died. All the five infants who had severe pneumonia, recovered; 3 (60%) had received simplified treatment. Of the 34 pneumonia cases, 33 received simplified treatment of which 5 (15%) failed treatment; two out of these 5 died. Overall, 6/160 infants died (case-fatality-rate 3.4%); 2 in the simplified treatment (case-fatality-rate 1.8%) and 4 in the hospital group (case-fatality-rate 8.3%). Delayed identification and care-seeking by families and health system weaknesses like manpower gaps and interrupted supplies were challenges in implementation. Conclusions Implementation of the guidelines in program settings is possible and acceptable. Scaling up would require creating community awareness, early identification and appropriate care-seeking, strengthening ASHA home-visitation program, building skills and confidence of MOs and ANMs, uninterrupted supplies and a dependable referral system.

BackgroundThere is a growing interest in the life course approach for the prevention, early detection and subsequent management of morbidity in women of reproductive age to ensure optimal health and nutrition when they enter pregnancy. Reliable estimates of such morbidities are lacking. We report the prevalence of health or nutrition-related morbidities, specifically, anemia, undernutrition, overweight and obesity, sexually transmitted infections (STIs) or reproductive tract infections (RTIs), diabetes or prediabetes, hypothyroidism, hypertension, and depressive symptoms, during the preconception period among women aged 18 to 30 years.MethodsA cross-sectional study was conducted among 2000 nonpregnant married women aged 18 to 30 years with no or one child who wished to have more children in two low- to middle-income urban neighborhoods in Delhi, India, in the context of a randomized controlled trial. STIs and RTIs were measured by symptoms and signs, blood pressure by a digital device, height by stadiometer and weight by a digital weighing scale. A blood specimen was taken to screen for anemia, diabetes, thyroid disorders and syphilis. Maternal depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analysis was performed to identify sociodemographic factors associated with individual morbidity.ResultsOverall, 58.7% of women were anemic; 16.5%, undernourished; 26%, overweight or obese; 13.2%, hypothyroid; and 10.5% with both symptoms and signs of STIs/RTIs. There was an increased risk of RTI/STI symptoms and signs in undernourished women and an increased risk of diabetes or prediabetes in overweight or obese women. An increased risk of undernutrition was also observed in women from lower categories of wealth quintiles. A decreased risk of moderate to severe anemia was seen in overweight women and those who completed at least secondary education.ConclusionsOur findings show a high burden of undernutrition, anemia, RTIs, hypothyroidism and prediabetes among women in the study. This information will aid policymakers in planning special programs for women of reproductive age.

Background Childhood diarrhea deaths have declined more than 80% from 1980 to 2015, in spite of an increase in the number of children in low- and middle-income countries (LMIC). Possible drivers of this remarkable accomplishment can guide the further reduction of the half million annual child deaths from diarrhea that still occur. Methods We used the Lives Saved Tool, which models effects on mortality due to changes in coverage of preventive or therapeutic interventions or risk factors, for 50 LMIC to determine the proximal drivers of the diarrhea mortality reduction. Results Diarrhea treatment (oral rehydration solution [ORS], zinc, antibiotics for dysentery and management of persistent diarrhea) and use of rotavirus vaccine accounted for 49.7% of the diarrhea mortality reduction from 1980 to 2015. Improvements in nutrition (stunting, wasting, breastfeeding practices, vitamin A) accounted for 38.8% and improvements in water, sanitation and handwashing for 11.5%. The contribution of ORS was greater from 1980 to 2000 (58.0% of the reduction) than from 2000 to 2015 (30.7%); coverage of ORS increased from zero in 1980 to 29.5% in 2000 and more slowly to 44.1% by 2015. To eliminate the remaining childhood diarrhea deaths globally, all these interventions will be needed. Scaling up diarrhea treatment and rotavirus vaccine, to 90% coverage could reduce global child diarrhea mortality by 74.1% from 2015 levels by 2030. Adding improved nutrition could increase that to 89.1%. Finally, adding increased use of improved water sources, sanitation and handwashing could result in a 92.8% reduction from the 2015 level. Conclusions Employing the interventions that have resulted in such a large reduction in diarrhea mortality in the last 35 years can virtually eliminate remaining childhood diarrhea deaths by 2030.

Background India has achieved 86% reduction in the number of under-five diarrheal deaths from 1980 to 2015. Nonetheless diarrhea is still among the leading causes of under-five deaths. The aim of this analysis was to study the contribution of factors that led to decline in diarrheal deaths in the country and the effect of scaling up of intervention packages to address the remaining diarrheal deaths. Methods We assessed the attribution of different factors and intervention packages such as direct diarrhea case management interventions, nutritional factors and WASH interventions which contributed to diarrhea specific under-five mortality reduction (DSMR) during 1980 to 2015 using the Lives Saved Tool (LiST). The potential impact of scaling up different packages of interventions to achieve universal coverage levels by year 2030 on reducing the number of remaining diarrheal deaths were estimated. Results The major factors associated with DSMR reduction in under-fives during 1980 to 2015, were increase in ORS use, reduction in stunting prevalence, improved sanitation, changes in age appropriate breastfeeding practices, increase in the vitamin-A supplementation and persistent diarrhea treatment. ORS use and reduction in stunting were the two key interventions, each accounting for around 32% of the lives saved during this period. Scaling up the direct diarrhea case management interventions from the current coverage levels in 2015 to achieve universal coverage levels by 2030 can save around 82 000 additional lives. If the universal targets for nutritional factors and WASH interventions can be achieved, an additional 23 675 lives can potentially be saved. Conclusions While it is crucial to improve the coverage and equity in ORS use, an integrated approach to promote nutrition, WASH and direct diarrhea interventions is likely to yield the highest impact on reducing the remaining diarrheal deaths in under-five children.

Executive summaryDespite dramatic improvements in survival, nutrition, and education over recent decades, today’s children face an uncertain future. Climate change, ecological degradation, migrating populations, conflict, pervasive inequalities, and predatory commercial practices threaten the health and future of children in every country. In 2015, the world’s countries agreed on the Sustainable Development Goals (SDGs), yet nearly 5 years later, few countries have recorded much progress towards achieving them. This Commission presents the case for placing children, aged 0–18 years, at the centre of the SDGs: at the heart of the concept of sustainability and our shared human endeavour. Governments must harness coalitions across sectors to overcome ecological and commercial pressures to ensure children receive their rights and entitlements now and a liveable planet in the years to come.

Burden and risk factors for wasting in the first 6 months of life among Indian children are not well documented. We used data from India's National Family Health Survey 4 to estimate the prevalence of severe wasting (weight for length < -3 SD) among 18,898 infants under 6 months of age. We also examined the association of severe wasting with household, maternal, and child-related factors using multivariable logistic regression analysis. Prevalence of severe wasting among infants less than 6 months of age was 14.8%, ranging from 3.5 to 21% across states. Low birth weight (

Background South Asia contributes substantially to global low birth weight population (i.e. those with birth weight

Objectives We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India. Methods We analysed a sample of 190,898 women from India’s National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation. Results In India, 21% of pregnant women utilised full ANC, ranging from 2.3–65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government’s Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father’s participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation. Conclusions Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child’s father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India’s maternal health program. Electronic supplementary material The online version of this article (10.1186/s12884-019-2473-6) contains supplementary material, which is available to authorized users.

Objectives Low birth weight (LBW) is a risk factor for neonatal mortality and morbidity. It is important to examine whether this risk persists beyond neonatal period. The current secondary data analysis aimed to examine association of birth weight with mortality, hospitalisation and breast feeding practices during infancy. Design Data from a large randomised controlled trial of neonatal vitamin A supplementation (Neovita) trial were used. Log binomial model was applied to assess association between birth weight and mortality, hospitalisation and breast feeding practices. Setting Rural Haryana, North India. Participants Newborns recruited in the primary intervention trial that aimed to evaluate the effect of single-dose oral vitamin A supplementation on mortality in the first 6 months of life. Results We recruited a total of 44 984 infants, of which 10 658 (23.7%) were born LBW, that is, birth weight less than 2500 g. In the neonatal period, LBW babies had four times higher risk of mortality (relative risk (RR) 3.92; 95% CI 3.33 to 4.66) compared with normal birthweight babies. In the postneonatal period, the risk was two times higher (RR 1.92; 95% CI 1.71 to 2.15); even higher in those with birth weight

AIM To conduct implementation research in integrated community case management (ICCM) of childhood pneumonia, diarrhoea and fever by promoting accredited social health activists as treatment providers and generate lessons for upscaling this approach. METHODS In this one-sample study, 49 Accredited Social Health Activists were trained in ICCM. Community awareness and demand generation activities undertaken included announcements, pamphlets and posters. Supplies of medicines and supervision of activists were maintained throughout the 10-month implementation period. Three cross-sectional surveys were conducted in households with children aged 2-59 months for documenting two-week prevalence of illnesses and care-seeking practices. Focus group discussions and in-depth interviews were carried out with mothers/grandmothers and activists for documenting perceptions about health activists as treatment providers. RESULTS One third of pneumonia (113/334) and one quarter of diarrhoea (102/408) cases at end-line were treated by Accredited Social Health Activists. Proportion of households seeking care from private providers (mostly unqualified) reduced significantly from baseline to endline (81-56% for diarrhoea, p

Background Low birth weight (LBW) infants constitute a vulnerable subset of infants with impaired immunity in early life. In India, there is scarcity of studies that focus on immunization practices in such infants. This analysis aimed to examine immunization practices in LBW infants with the intention to identify areas requiring intervention. Methods Data on immunization status of LBW infants enrolled in an individually randomized, double-masked, placebo-controlled trial of neonatal vitamin A supplementation were analysed. Study outcomes were full immunization by one year of age and delayed vaccination with DPT1 and DPT3. Multivariable logistic regression was performed to identify factors associated with the outcome(s). Findings Out of 10 644 LBW infants enrolled in trial, immunization data were available for 10 517 (98.8%). Less than one-third (29.7%) were fully immunized by one year of age. Lowest wealth quintile (adjusted odds ratio (AOR) 0.39, 95% confidence interval (CI) 0.32-0.47), Muslim religion (AOR 0.41, 95% CI 0.35-0.48) and age of mother

A phase III randomized double-blind placebo-controlled trial was conducted in the urban neighborhoods of Delhi to assess whether Oral Rotavirus Vaccine ROTAVAC® interferes with the immune response to childhood vaccines when coadministered. Infants aged 6 weeks were randomized to receive three doses of either ROTAVAC® or placebo along with childhood vaccines: Oral Polio Vaccine and vaccines against Diphtheria, Pertussis, Tetanus, Hepatitis B and Haemophilus influenza type b given as Pentavalent at 6, 10, 14 weeks of age. Blood specimens were collected from all infants at baseline and 4 weeks post dose 3 to assess the immune response to antigens in Oral Polio Vaccine, Pentavalent and ROTAVAC® vaccines. Non-inferiority of immune response to all vaccine components of the childhood vaccines when ROTAVAC® was administered concurrently was demonstrated. Non-inferior immune responses to childhood vaccines were evaluated based on the seroprotective levels of antibodies against polio types 1, 2, and 3, Diphtheria toxoid, Tetanus toxoid, Haemophilus influenza type b anti- polyribosyl ribitol phosphate antibodies and Hepatitis B antibodies; and the Geometric Mean Concentration for Pertussis. The proportion of infants who seroconverted (≥4 fold rise) was 38.6% in the ROTAVAC® group and 12.2% in the placebo group. The frequency and severity of immediate adverse events, adverse events and serious adverse events were similar in both groups. None of the five reported deaths were considered to be related to the ROTAVAC® and no case of intussusception meeting Brighton Diagnostic Certainty Level I criteria was reported. This study demonstrated that ROTAVAC® can be safely administered with childhood vaccines without interfering with the immune response to the antigens contained in these vaccines.

Rotavirus is the leading cause of severe gastroenteritis in young children worldwide and is responsible for around 100,000 deaths in India annually. Vaccination against rotavirus (RV) is a high priority: ‘ROTAVAC’ an indigenous vaccine will soon be licensed in India. Surveillance to determine the impact of vaccines on emerging RV strains is required. In this study we compared the pattern of RV strains circulating in Delhi over a 5 year period with the strains over the past 12 years. The most commonly detected G genotypes were G1 (22.4%), G2 (17.2%), and G9 (25.2%) with P[4] (25.5%), P[6] (20%) and P[8] (16.9%) specificity. G12 genotype was found to be the fourth common G-type with 14.8% prevalence. Among the G–P combinations; G1P[8], G2P[4], G9P[8] and G12P[6] were detected at 7.2%, 7.2%, 5.2% and 10%, respectively. Of note, G9P[4] and G2P[6] that were rarely detected during 2000–2007 in Delhi, were observed quite frequently with prevalence of 6.5% and 3.4%, respectively. In total, 16 different G–P combinations were detected in the present study demonstrating the rich diversity of rotavirus strains in Delhi. Our data from the 12 year period indicate wide circulation of G1 and G9 genotypes in combination with P[8], G2 with P[4] and G12 with P[6] with high frequency of RV strains having rare G–P combinations in Delhi. Since the indigenous vaccine ‘ROTAVAC’ has a monovalent formulation, the impact of vaccines on strains and the effect of strain diversity on the efficacy of the vaccine should be monitored.

Summary Background Rotavirus is the most common cause of severe dehydrating gastroenteritis in developing countries. Safe, effective, and affordable rotavirus vaccines are needed in these countries. We aimed to assess the efficacy and tolerability of a monovalent human-bovine rotavirus vaccine for severe rotavirus gastroenteritis in low-resource urban and rural settings in India. Methods We did a randomised double-blind, placebo-controlled, multicentre trial at three sites in Delhi (urban), Pune (rural), and Vellore (urban and rural) between March 11, 2011, and Nov 5, 2012. Infants aged 6–7 weeks were randomly assigned (2:1), via a central interactive voice or web response system with a block size of 12, to receive either three doses of oral human-bovine natural reassortant vaccine (116E) or placebo at ages 6–7 weeks, 10 weeks, and 14 weeks. Infants' families, study investigators, paediatricians in referral hospitals, laboratory staff, and committee members were all masked to treatment allocation. The primary outcome was incidence of severe rotavirus gastroenteritis (≥11 on the Vesikari scale). Efficacy outcomes and adverse events were ascertained through active surveillance. Analysis was by intention to treat and per protocol. The trial is registered with Clinical Trial Registry–India (CTRI/2010/091/000102) and ClinicalTrials.gov (NCT01305109). Findings 4532 infants were assigned to receive the 116E vaccine and 2267 to receive placebo, of whom 4354 (96%) and 2187 (96%) infants, respectively, were included in the primary per-protocol efficacy analysis. 71 events of severe rotavirus gastroenteritis were reported in 4752 person-years in infants in the vaccine group compared with 76 events in 2360 person-years in those in the placebo group; vaccine efficacy against severe rotavirus gastroenteritis was 53·6% (95% CI 35·0–66·9; p=0·0013) and 56·4% (36·6–70·1; p Interpretation Monovalent human-bovine (116E) rotavirus vaccine is effective and well tolerated in Indian infants. Funding Department of Biotechnology and the Biotechnology Industry Research Assistance Council, Government of India; Bill & Melinda Gates Foundation to PATH, USA; Research Council of Norway; UK Department for International Development; National Institutes of Health, Bethesda, USA; and Bharat Biotech International, Hyderabad, India.

Low‐birthweight (LBW) infants are at an increased risk of stunting and poor linear growth. The risk might be additionally higher in these infants when born to short mothers. However, this hypothesis has been less explored. The objective of this secondary data analysis was to determine the risk of linear growth faltering and difference in linear growth velocity in LBW infants born to short mothers (

Background Vitamin-D deficiency has been linked with impaired development in animal studies; however, the evidence from human studies is scanty. Evidence as to whether vitamin-D deficiency during early childhood affects growth is also limited and conflicting. We examined the extent to which vitamin-D deficiency (

Background Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this paper, we examined the extent to which vitamin-D deficiency (

Vaccines against important enteric pathogens such as rotavirus and poliovirus have shown lower efficacy in some populations. The application of new technologies and diverse scientific disciplines are needed to realize the promise of truly universal and effective solutions to combat those and other enteric diseases.

In the present investigation we molecularly characterized nontypeable rotavirus strains previously identified during surveillance in New Delhi, India. The majority of strains were demonstrated to belong to genotype G1 (54.5%) or P[8] (77.8%) on the basis of nucleotide sequencing of fragments from their VP7 and VP4 genes. The other genotypes detected included G2, G8, G9, G12, and P[4]. A G8P[6] strain, strain DS108, was detected for the first time in northern India. The VP7 gene of DS108 was most homologous with the VP7 gene of a bovine G8 strain, strain A5 (98.9%), indicating its bovine parentage. In contrast, the VP4 gene had a high degree of nucleotide sequence homology (92.9% to 99.1%) with the VP4 genes of human P[6] strains. The VP6 gene and nonstructural genes (NSP1 to NSP3 and NSP5) were most homologous with the VP6 gene and nonstructural genes of human rotaviruses belonging to the DS1 genogroup. Interestingly, the NSP4 gene of DS108 clustered within genotype E6 that until now had only two representative strains, both with G12P[6] specificity (strains RV176-00 and N26-02). Together, these results indicate that G8 strain DS108 belongs to the DS1 genogroup and could be the result of the acquisition of the VP7, VP4, and NSP4 genes by a human G2P[4] strain from more than one donor, similar to the evolution of G12P[6] strain RV176-00. The present study highlights the importance of characterizing multiple genes of nontypeable rotavirus strains to detect novel strains and get a more complete picture of rotavirus evolution.

Background A rotavirus vaccine previously licensed in the United States was withdrawn because it caused intussusception. Data on background intussusception rates in developing countries are required to plan pre- and postlicensure safety studies for new rotavirus vaccines. Also, it is unclear whether natural rotavirus infection is associated with intussusception. Methods Passive surveillance for intussusception in a large, well-defined, poor, urban population in Delhi, India, was conducted in 2 phases. Intussusception was confirmed by ultrasonography or surgery. Fecal samples obtained from patients with intussusception at study hospitals (irrespective of their residence in study areas) and healthy control subjects were tested for rotavirus with use of enzyme immunoassay. If available, resected intestinal tissue samples were tested for rotavirus with use of immunohistochemistical analysis and reverse-transcription polymerase chain reaction. Results The incidence of intussusception requiring hospitalization was 17.7 cases per 100,000 infant-years of follow-up (95% confidence interval, 5.9-41.4 cases per 100,000 infant-years). Detection rates of rotavirus in stool samples did not differ significantly between case patients and control subjects (4 of 42 case patients vs 6 of 92 control subjects), and no evidence of rotavirus was detected in any of the 22 patients with intussusception for whom intestinal tissue samples were available. Conclusions The incidence of intussusception among Indian infants appears to be lower than that reported in other middle- and high-income countries. Natural rotavirus infection does not appear to be a major cause of intussusception in Indian infants.

Background: Low-birth-weight infants may have impaired zinc status, but little is known about the effect of zinc supplementation. Objective: The objective was to investigate the effect of daily zinc supplementation on morbidity and anthropometric status in hospitalborn, low-birth-weight infants. Design: In a double-blind, randomized, placebo-controlled trial, 2052 hospital-born term infants with a birth weight 2500 g were randomly assigned to receive zinc or placebo. The zinc group received elemental zinc: 5 mg/d for those infants between ages 2 wk and 6 mo and 10 mg/d for those infants aged .6 mo. All-cause hospitalizations, prevalence of diarrhea, acute lower respiratory tract infections, visits to health care providers, weights, and lengths were ascertained at 3, 6, 9, and 12 mo of age. Results: The supplement was consumed for .85% of the follow-up period. Mean plasma zinc at 12 mo of age was higher in the zinc group (100.2 lg/dL) than in the control group (73.3 lg/dL) (difference in means: 26.9; 95% CI: 19.6, 34.2). The 24-h and 7-d prevalence of diarrhea and acute lower respiratory tract infections was similar at 3, 6, 9, and 12 mo. Care-seeking for illness was significantly lower in the zinc group (difference in proportions: 25.7; 95% CI: 29.9, 21.4; P , 0.05) at 9 mo. The numbers of hospitalizations, weights, and lengths were all similar at all 4 assessments. Conclusion: Hospital-born, term, low-birth-weight infants do not seem to benefit substantially from zinc supplementation that meets the Recommended Dietary Allowance for zinc in terms of morbidity or physical growth during infancy in this setting. This trial was registered at www.clinicaltrials.gov as NCT00272142. Am J Clin Nutr 2009;90:385‐91.

Background: Newborn infections are responsible for approximately one-third of the estimated 4.0 million neonatal deaths that occur globally every year. Appropriately targeted research is required to guide investment in effective interventions, especially in low resource settings. Setting global priorities for research to address neonatal infections is essential and urgent. Methods: The Department of Child and Adolescent Health and Development of the World Health Organization (WHO/CAH) applied the Child Health and Nutrition Research Initiative (CHNRI) priority-setting methodology to identify and stimulate research most likely to reduce global newborn infection-related mortality by 2015. Technical experts were invited by WHO/CAH to systematically list and then use standard methods to score research questions according to their likelihood to (i) be answered in an ethical way, (ii) lead to (or improve) effective interventions, (iii) be deliverable, affordable, and sustainable, (iv) maximize death burden reduction, and (v) have an equitable effect in the population. The scores were then weighted according to the values provided by a wide group of stakeholders from the global research priority-setting network. Findings: On a 100-point scale, the final priority scores for 69 research questions ranged from 39 to 83. Most of the 15 research questions that received the highest scores were in the domain of health systems and policy research to address barriers affecting existing cost-effective interventions. The priority questions focused on promotion of home care practices to prevent newborn infections and approaches to increase coverage and quality of management of newborn infections in health facilities as well as in the community. While community-based intervention research is receiving some current investment, rigorous evaluation and cost analysis is almost entirely lacking for research on facility-based interventions and quality improvement. Interpretation: Given the lack of progress in improving newborn survival despite the existence of effective interventions, it is not surprising that of the top ranked research priorities in this article the majority are in the domain of health systems and policy research. We urge funding agencies and investigators to invest in these research priorities to accelerate reduction of neonatal deaths, particularly those due to infections.

The prospect that rotavirus diarrhea in children may soon be prevented by vaccines has placed a new priority on understanding the diversity of rotavirus strains and the mechanism by which these strains evolve over time. We have characterized a total of 465 rotavirus strains collected in North India from 2000 to 2007 for G and P types by reverse transcription-PCR and sequencing. The novel G12 rotavirus strains recently detected in other countries were first detected in India in 2001 and have emerged as the predominant strains in Delhi, India, during 2005 to 2007. While the VP7 sequence was highly homologous among G12 strains isolated in Delhi, suggesting recent emergence from a common ancestor, the strains had a diverse constellation of other gene segments, demonstrating substantial reassortment. For the entire period, the common rotavirus G types G1 (26%), G2 (25%), and G9 (14%) comprised 65% of the strains, and common P types, P[4] (19%), P[6] (22%), and P[8] (35%), comprised 76% of the total P types. Of note, we detected a high percentage of unusual (17%) strains and fecal specimens with mixed (12% G and 15% P) rotavirus infections having a variety of genomic constellations. For the first time, we identified two novel rotavirus strains with unusual G/P combinations, G2P[11] and G3P[11], in patients with diarrhea. The study highlights the great diversity among rotaviruses isolated from Indian children, the opportunity for genetic reassortment between strains, and the emergence of a novel G12 strain in our country. Due to the demonstrated effect of antigenic diversity on rotavirus vaccines, it will be important to continue careful monitoring of these strains as rotavirus vaccine programs are implemented in India.

Vitamin deficiencies are often part of malnutrition, which predisposes to acute lower respiratory tract infections.The objective was to measure the association between cobalamin and folate status and subsequent respiratory morbidity.A prospective cohort study was conducted in 2482 children aged 6-30 mo nested in a zinc supplementation trial. We measured plasma concentrations of folate, cobalamin, methylmalonic acid, and total homocysteine (tHcy) and followed the children for 4 mo.We observed 1176 episodes of acute lower respiratory tract infections. Children with folate concentrations in the lowest quartile (interquartile range: 6.4-20.0 nmol/L) had a 44% higher incidence [adjusted incidence rate ratio (IRR): 1.44; 95% CI: 1.23, 1.70] of acute lower respiratory tract infections than did children in the other 3 quartiles. For tHcy, the IRR was 1.24 (1.07, 1.40) in a comparison of those in the highest quartile with those in the other quartiles. Breastfeeding was associated with high folate concentrations and protection against subsequent respiratory tract infections. This protection was significantly and substantially reduced after adjustment for plasma folate concentrations at baseline. Compared with the children in the other 3 quartiles, the IRR for being in the lowest quartile of cobalamin was 1.13 (0.76, 1.03) and for being in the highest quartile of methylmalonic acid was 1.12 (0.96, 1.31).Poor folate status appears to be an independent risk factor for lower respiratory tract infections in young children. This study also suggests that the protective effect of breastfeeding is partly mediated by folate provided through breast milk.

Background A trial to evaluate the Integrated Management of Neonatal and Childhood Illness (IMNCI) strategy showed that the intervention resulted in lower infant mortality and improved infant care practices. In this paper, we present the results of a secondary analysis to examine the effect of the IMNCI strategy on inequities in health indicators. Methods The trial was a cluster–randomized controlled trial in 18 primary health centre areas. For this analysis, the population was divided into subgroups by wealth status (using Principal Component Analysis), religion and caste, education of mother and sex of the infant. Multiple linear regression analysis was used to examine inequity gradients in neonatal and post–neonatal mortality, care practices and care seeking, and the differences in these gradients between intervention and control clusters. Findings Inequity in post–neonatal infant mortality by wealth status was lower in the intervention as compared to control clusters (adjusted difference in gradients 2.2 per 1000, 95% confidence interval (CI) 0 to 4.4 per 1000, P = 0.053). The intervention had no effect on inequities in neonatal mortality. The intervention resulted in a larger effect on breastfeeding within one hour of birth in poorer families (difference in inequity gradients 3.0%, CI 1.5 to 4.5, P

Objectives: In a community randomized trial, we aimed to promote exclusive breastfeeding and appropriate complementary feeding practices in under-twos to ascertain the feasibility of using available channels for nutrition counselling, their relative performance and the relationship between intensity of counselling and behaviour change. We also assessed whether using multiple opportunities to impart nutrition education adversely affected routine activities. Methods: We conducted a community randomized, controlled effectiveness trial in rural Haryana, India, with four intervention and four control communities. We trained health and nutrition workers in the intervention communities to counsel mothers at multiple contacts on breastfeeding exclusively for 6 months and on appropriate complementary feeding practices thereafter. The intervention was not just training health and nutrition workers in counselling but included community and health worker mobilization. Findings: In the intervention group, about 32% of caregivers were counselled by traditional birth attendants at birth. The most frequent sources of counselling from birth to 3 months were immunization sessions (45.1%) and home visits (32.1%), followed closely by weighing sessions (25.5%); from 7 to 12 months, home visits (42.6%) became more important than the other two. An increase in the number of channels through which caregivers were counselled was positively associated with exclusive breastfeeding prevalence at 3 months (p = 0.002), consumption of milk/cereal gruel or mix use at 9 months (p = 0.004) and 18 months (p = 0.003), undiluted milk at 9 months (p

Lymphocyte subset estimations by flow cytometry in population-based studies require transportation of samples from the field site to the laboratory. As samples arrive late in the day they have to wait overnight before being processed. The effect of two possible approaches, sample storage for 24 h before staining and immediate staining with analysis after 24 h and 48 h were evaluated. Two sets of experiments were performed with EDTA (ethylenediamine tetra-acetate) anticoagulated peripheral blood. In the first experiment, after collection, each sample was divided into two portions. One portion was stained at the time of blood collection and the other 24 h later after keeping it at room temperature (38–45°C). In the second experiment, blood samples were stained within 1–2 h. Each sample was analyzed immediately upon completion of staining process and subsequently after 24 h and 48 h of storage at 4°C. Results suggest that blood collected in EDTA can be processed using whole blood lysis method, after storage at room temperature (38–45°C) for 24 h with some but not significant alteration in T-cell subsets. Storage at 4°C after staining for 24 h results in a lesser and insignificant loss of cells or alteration of T-cell subsets and may be the method of choice.

We sought to determine the proportion of rotavirus ( RV) infections among children with severe diarrhea in Bangalore, India, and to determine the role of neonatal infection with the asymptomatic RV strain I321 in protection against subsequent RV diarrhea. At 2 major hospitals, there was a >42% decrease in diarrhea-specific admissions during the study period. At 6 hospitals, asymptomatic infections were found in 25%-50% of neonates, when screening was performed randomly, and in >58% of neonates, when screening was performed daily, with the majority of infections occurring within the first 7 days of life. All the RVs found in asymptomatic neonates were strain I321. A 24-month follow-up of a cohort of 44 children who had been neonatally infected with strain I321 and 28 children who had not (control group) revealed comparable rates of RV detection but a marked decrease in the number of RV diarrhea episodes in the strain I321-infected group (2.3%), compared with the control group (39.3%) (P < .0001). This preliminary study suggests a possible association between neonatal infection with strain I321 and protection against subsequent RV illness.

AIM: The aim of the present study, which was undertaken as a sub-study within a randomized controlled trial of zinc supplementation, was to evaluate the effect of prolonged zinc supplementation on copper status as assessed by hematological markers. METHODS: Plasma copper and zinc were estimated at baseline and after 120 d of supplementation in a randomly selected infant subset (115) of the children. Of these, 61 children were in a zinc group (Z) getting 10 mg of elemental zinc, and 54 were in a control group (C) getting supplement without zinc. RESULTS: Baseline plasma zinc was comparable in the two groups; post-supplementation zinc was significantly higher (Z 93.0 +/- 3.6 vs C 60.6 +/- 8.0) in the zinc supplementation group. There was no significant difference in the mean/median copper levels between the zinc and control groups. The percentage of children with plasma copper

Seroconversion of immunoglobulin A (IgA) and immunoglobulin G (IgG) (> or =4-fold rise) to rotavirus nonstructural protein 4 (NSP4) was determined, by use of enzyme-linked immunosorbent assay with fusion proteins glutathione S-transferase (GST)-NSP4 from strains SA11 (A), 116E (B), and RRV (C), in 40 children with acute rotavirus gastroenteritis and in 30 with the same disease due to other pathogens. The IgG seroconversion rates in the rotavirus group were 67.5%, 70%, and 60% when recombinant (r) NSP4A, -B, and -C, respectively, were used as antigen in the assay, and, for rotavirus-uninfected children, rates were 10%, 13%, and 7%. IgA seroconversion occurred in 57%, 70%, and 50%, respectively, of children with rotavirus gastroenteritis; in rotavirus-uninfected children, 1 child each seroconverted to the different rNSP4s. Among 9 children infected with strain NSP4A, 7, 6, and 5 children showed IgG seroconversion, and, among 18 infected with NSP4A, -B, and -C, 16, 17, and 15, respectively, showed IgG seroconversion. Between NSP4A-infected and NSP4B-infected children, IgA responses were similar to IgG responses. In conclusion, significant NSP4-specific antibody response occurs in natural rotavirus infection, and the antibody response appears to be broad and heterotypic in nature.

Exclusive breastfeeding is recommended until age 6 months. We assessed the feasibility, effectiveness, and safety of an educational intervention to promote exclusive breastfeeding for this length of time in India.We developed the intervention through formative research, pair-matched eight communities on their baseline characteristics, and randomised one of each pair to receive the intervention and the other to no specific intervention. We trained health and nutrition workers in the intervention communities to counsel mothers for exclusive breastfeeding at multiple opportunities. We enrolled 1115 infants born in the 9 months after training-552 in the intervention and 473 in the control communities. Feeding at age 3 months, and anthropometry and of diarrhoea prevalence at age 3 months and 6 months were assessed. All analyses were by intention to treat.We assessed 483 and 412 individuals at 3 months in the intervention and control groups, respectively, and 468 and 412 at 6 months. At 3 months, exclusive breastfeeding rates were 79% (381) in the intervention and 48% (197) in the control communities (odds ratio 4.02, 95% CI 3.01-5.38, p0.0001). The 7-day diarrhoea prevalence was lower in the intervention than in the control communities at 3 months (0.64, 0.44-0.95, p=0.028) and 6 months (0.85, 0.72-0.99, p=0.04). The mean weights and lengths, and the proportion with weight-for-height or height-for-age Z scores of 2 or less, at age 3 months and 6 months did not differ much between groups. Intervention effect on exclusive breastfeeding, diarrhoeal morbidity, and anthropometry at age 6 months in the low-birthweight subgroup was similar to that for all births.Promotion of exclusive breastfeeding until age 6 months in a developing country through existing primary health-care services is feasible, reduces the risk of diarrhoea, and does not lead to growth faltering.

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

Objective: Vitamin A supplementation to mothers in the postpartum period and to their infants at routine immunization contacts is being considered to reduce vitamin A deficiency in infancy. This study was conducted to determine the impact of maternal and infant vitamin A supplementation on antibody response to oral polio vaccine (OPV). Design: Randomized, double blind, placebo-controlled trial. Interventions: Mothers in the intervention group received 60 mg retinol equivalent (RE) vitamin A 3–4 weeks after delivery and their infants 7.5 mg RE with each OPV dose at 6, 10 and 14 weeks of age. The control group mothers and their infants received a placebo at each of these contacts. Main outcomes: Geometric mean (GM) titer of neutralizing antibodies and proportion of children with protective titer to the three polioviruses at 26 weeks of age. Results: Vitamin A supplementation increased the proportion of infants with protective antibody titer against poliovirus type 1 (relative risk (RR) 1.15, 95% confidence interval (CI) 1.03–1.28) and the GM antibody titer (ratio of GM 1.55, 95% CI 1.03–2.31) following immunization. The proportion of infants with protective antibody titer against poliovirus type 2 (RR 0.99, 95% CI 0.94–1.05) or type 3 (RR 1.05, 95% CI 0.96–1.15) was not significantly different in vitamin A and placebo groups. The GM antibody titer for poliovirus type 2 (ratio of GM 0.99, 95% CI 0.64–1.54) or poliovirus type 3 (ratio of GM 1.10, 95% CI 0.69–1.75) also did not differ across groups. Conclusions: Vitamin A given to the mothers in the postpartum period and their infants with OPV did not interfere with the antibody response to any of the three polioviruses and enhanced the response to poliovirus type 1. Sponsorship: Division of Child Health and Development, WHO, Geneva, Norwegian Universities Committee for Development and Research and Indian Council of Medical Research, Panacea Biotec Ltd, India (provided the oral polio vaccine).

The development of monoclonal antibodies combined with flow cytometry has revolutionized the analysis of lymphocyte subsets. These newer methods using the Q-prep leucocyte preparation system require only 1–2 ml of blood as compared to 10 ml required traditionally. One of the main impediments in the use of this superior technology in Indian laboratories has been the high cost of reagents. This study evaluated methods to reduce the cost of assays. In the first experiment from 26 healthy subjects, 2ml venous blood samples in EDTA (ethylenediamine tetra-acetate) were obtained. Each sample was divided into two equal portions, one portion was stained using diluted monoclonal antibody, whereas the other portion was stained using standard concentrations of antibodies. In the second experiment, blood samples from 12 subjects were again divided into 2 portions; one portion of each pair was processed using commercial Q-prep reagents while the other portion was processed using our own reagents. In the first experiment, which evaluated use of a diluted antibody against the standard recommended concentrations, a 5-tube panel that estimated CD3, CD4, CD8, CD20 was used. In the second experiment CD3, CD4 and CD8 were estimated. The total cost per sample for a 5-panel estimation was however reduced from $39.11 to $1.10. Given the proven advantages of using a whole blood stain-lyse method for T cell subset estimations, its use should be encouraged in developing country settings. With the suggested methods the whole blood Q-prep could be performed at appreciably reduced costs, without loss in precision.

In The Lancet, fi ndings from Nita Bhandari and colleagues’ phase 3 clinical trial show the safety and effi cacy of the 116E rotavirus vaccine against severe rotavirus gastroenteritis in Indian infants. The vaccine has an effi cacy similar to that of two licensed oral rotavirus vaccines—RotaTeq (Merck) and Rotarix (GlaxoSmithKline) — when tested in low-income settings. However, the timeline of development has been unique and unconventional. The vaccine was not the product of a major multinational manufacturer, but rather, the result of work by team science, based in India. Team science called on the combined expertise and interests of highly diverse multinational groups of clinical and translational investigators from 13 institutions, all with the shared goal of development of a rotavirus vaccine in India that was not only safe and eff ective, but also aff ordable for use in India and other low-income countries (table). By working directly as a team and recruiting members with new skills as the vaccine development process evolved, many of the risks and expenses for research and development that would have been almost insurmountable for a local manufacturer were buff eted with fi nancial help from the public–private partnership between the Indian Government, the manufacturer (Bharat Biotech International), PATH (a non-profi t organisation supported by the Bill & Melinda Gates Foundation), and other academic institutions at diff erent phases of the development programme, and with technical support from various members of the team. The outcome is a vaccine that is so far safe and eff ective, and that will be accessible to the public sector in India for a maximum of US$1·00 per dose. As is frequently the case, development of this vaccine began when a pediatrician at the All India Institute of Medical Sciences, funded by a grant from India’s Department of Science and Technology, astutely noted that newborn babies were becoming infected with rotavirus in the hospital, but were not becoming sick; an observation made previously by Bishop and colleagues in Australia. The neonatal strain from India, 116E, turned out to be a naturally attenuated human–bovine reassortant virus that induced robust humoral and local immune responses and protected infants against severe diarrhoeal disease upon subsequent reinfection with rotavirus; properties that suggested its potential as a candidate vaccine. The 116E isolate was initially developed into a vaccine candidate by a team of Indian and American investigators supported through a bilateral collaborative initiative, the Indo-US Vaccine Action Program, hosted by the Government of India’s Department of Biotechnology, the Indian Council of Medical Research, and the US National Institute of Allergy and Infectious Diseases. In 1998, the Vaccine Action Program hosted a meeting to identify a manufacturing partner in India willing to develop the 116E candidate as a vaccine. The owner of Bharat Biotech International (a young biotech company with no licensed products at the time) came forward and committed his company to pursue this endeavour. The ability to prepare the manufacturer to develop the vaccine was made possible with generous support from the Bill & Melinda Gates Foundation and the Government of India’s Department of Biotechnology through a series of grants to PATH and to several partner Indian institutions. Scientists from the US Centers for Disease Control and Prevention, the National Institute of Allergy and Infectious Diseases, the Indian Institute of Science, and Stanford University provided the company with crucial technical assistance in specialties such as viral cultivation, and assay development and validation. The Bharat Biotech International team were a central part of the eff ort to develop a regulatory strategy, a commercial scale manufacturing process, and project management for product development, with strong support from PATH and the Department of Biotechnology, and with guidance from other partners. Bhandari and colleagues’ pivotal phase 3 fi eld trial was coordinated by the Society for Applied Studies, a community and child health research organisation experienced in undertaking complex community-based fi eld studies, and by PATH. The trial was done at three sites: the Society for Applied Studies in Delhi, KEM Hospital Research Centre in Pune, and the Christian Medical College in Vellore. The clinical assays were done at Translational Health Science and Technology Institute, with quality assurance aided by PATH. The Department of Biotechnology and PATH, together with site principal investigators and the clinical operations management unit, provided oversight through the project management committee. The outcome of this team eff ort was the development of a novel rotavirus vaccine. This vaccine is the fi rst totally new vaccine in recent memory to be developed entirely in India via a process that began with a key clinical observation, followed by basic virology, immunology, and epidemiology research, and progressing through product development to a licensed product. This process opposes the often cited bias from big pharma that local manufacturers cannot pursue independent research, develop good manufacturing practices, and produce a novel product. Cost is one of the most important determinants of a country’s ability and willingness to introduce a new vaccine and is a key motivation of the development programme. The two licensed vaccines have been Lancet 2014; 383: 2180–83

We previously observed a marked diversity of rotavirus strains and a high prevalence of the uncommon serotype G9 in a small survey of rotavirus strains collected from six centers in India. In the present study, we characterized a larger collection of strains from children hospitalized with severe diarrhea in seven Indian cities between 1996 and 1998. A total of 287 strains were G and P genotyped by reverse transcription-PCR, and some were further characterized by electropherotyping and subgrouping. Of the four strains common globally, three were found in only 43% of samples (P[8], G1, 15%; P[4], G2, 22%; P[8], G4, 6%), whereas G9 strains made up 17% of the total. Three different G9 strains were present: a P[8], G9 strain, which displayed the long electropherotype and subgroup II VP6 specificity, and two P[6], G9 strains, one with the long electropherotype and subgroup II specificity and the other with the short electropherotype and subgroup I specificity. Marked diversity was observed among strains collected from different cities and collected over time. Of the 253 strains that were fully typed, 54 (21%) had a mixed G or P genotype. Serotype G2 strains were detected more often in infections caused by single strains than in mixed infections ( P < 0.05), whereas serotype G1 strains were found more often in mixed infections than in infections caused by single strains ( P < 0.05). The diversity of rotavirus strains and the high prevalence of mixed infections confirm trends reported earlier and help to better characterize the strains of rotavirus circulating in India. Vaccines under development should clearly target G9 strains, and G9 should be included as one of the common global serotypes.

Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children