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Patients with SARS-CoV-2 infection have a wide spectrum of clinical presentations, from asymptomatic infection, to mild illness, to severe disease with recovery or fatal outcome. Immune correlates of protection are not yet clear. To understand the association between presence and titers of neutralizing antibodies (NAb) with recovery, we screened 82 COVID-19 patients classified in mild (n = 56) and severe (n = 26) disease groups on different days post onset of disease and 27 viral RNA–positive asymptomatic contacts examined within 1 week of the identification of index cases. Of 26 patients with severe disease, six died and 20 recovered. Anti-SARS-CoV-2 NAb levels in plasma and serum were measured using a plaque reduction neutralization test with live virus. The proportion of asymptomatic and symptomatic infections was 1:7.8 in males and 1:1 in females, with males predominating the severe disease group (21/26, 80.7%). At the time of presentation, NAb positivity and titers were comparable among groups with asymptomatic and mild infections. Notably, patients with severe disease exhibited higher NAb seropositivity and titers (25 of 26, 96.2%; 866 ± 188) than those in the mild category (39 of 56, 69.6%; 199 ± 50, P < 0.0001) and asymptomatic individuals (21 of 27, 77.8%; 124 ± 28, P = 0.0002). Within first 2 weeks of onset, NAb titers were significantly higher among patients with severe disease than those with mild presentation. Our data suggest that irrespective of fatal outcome, progression to disease severity was associated with induction of early and high levels of NAb. In our patient series, clinical disease, severity and fatality were predominantly seen in males. The role of NAbs in immunopathogenesis or protection needs to be defined.

In view of the rapidly progressing COVID-19 pandemic, our aim was to isolate and characterize SARS-CoV-2 from Indian patients. SARS-CoV-2 was isolated from nasopharyngeal swabs collected from the two members of a family without any history of (H/O) travel abroad. Both the virus isolates (8003 and 8004) showed CPE on day 3 post-inoculation, viral antigens by immunofluorescence assay and produced distinct, clear and uniform plaques. Infectious virus titers were 5 × 106 and 4 × 106 Pfu/ml by plaque assay and 107.5 and 107 by CPE-based TCID50/ml, respectively. Phylogenetic analysis grouped our isolates with the Italian strains. On comparison with Wuhan strain, 3 unique mutations were identified in nsp3 (A1812D), exonuclease (P1821S) of Orf1ab and spike protein (Q677H) regions, respectively. Both the viruses grouped with Italian strains of SARS-CoV-2 suggesting possible source being the virus imported from Italy. These fully characterized virus isolates will be useful in developing neutralization/virological assays for the evaluation of vaccines/antivirals.

Clinical trials are complicated, time-consuming and costly. From the initial screening, informed consent and recruitment of the participants’ to study completion, the sponsor must undertake a wide array of complex and closely monitored operations, complying with international standards for human subject research and local requirements. Conducting these studies in an underdeveloped country, with limited resources, infrastructure, and experience with regulated clinical trials adds to this complexity. The initial site selection, set up and preparatory activities for the clinical trial are crucial to minimizing the risks to both participants and to successful completion during the subsequent study execution. In this paper, we describe the experience and lessons learned of building clinical trial site capacity in terms of infrastructure and human resource development for a Phase III vaccine clinical trial. We believe that sharing the experience of setting up a clinical trial in a resource-limited country will enable other entities contemplating clinical research in these countries, to prepare and plan ahead, to minimize the impact of barriers, and to contribute to bringing more studies to the countries where people live with the burden of vaccine-preventable, poverty-associated diseases.

Background & objectives: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) continues to be a devastating pandemic. This study was aimed at performance assessment of SARS-CoV-2 IgM and IgG ELISAs, and investigation of their utility for patient diagnosis and sero-epidemiologic investigations. Methods: Serum/plasma samples from COVID-19 patients or asymptomatic contacts (n=180) and healthy donors (n=90) were tested in parallel using two commercial IgM ELISAs (Erbalisa and Inbios), and four IgG ELISAs (Kavach, Euroimmun, Erbalisa and Inbios) along with an indigenous β-propiolactone inactivated virus-based ELISA (IRSHA-IgG-ELISA). Plaque reduction neutralization test (PRNT) was used as reference test. Results: Among 180 COVID-19 patients, 125 tested positive by PRNT. Inbios-IgM-ELISA showed sensitivity (Se)/specificity (Sp)/positive predictive value (PPV)/negative predictive value (NPV) of 93.6/97.8/98.4/94.4 per cent in relation to PRNT, and performed better than Erbalisa-IgM-ELISA (Se: 48%, Sp: 95.6%, PPV: 95.2%, NPV: 65.2%). During the first week of disease, only 47.4 per cent of the COVID-19 patients tested IgM positive by Inbios-IgM-ELISA, detection improving at two weeks and beyond (~86-100%). Among IgG tests, Inbios-IgG-ELISA ranked first in terms of sensitivity (83.2%), followed by IRSHA (64.8%), Euroimmun (64%), Erbalisa (57.6%) and Kavach (56%) tests. For all IgG tests, sensitivity improved during the third (73.9-95.7%) and fourth week (100%) of illness. The specificity (96.7-100%) and PPV (96.2-100%) of all IgG tests were high; NPV ranged between 71.9 and 87.1 per cent with Inbios-IgG-ELISA scoring highest. Interpretation & conclusions: Our results show that IgM detection by the current, most sensitive ELISAs cannot replace molecular diagnosis, but may aid as a supplement test. The available IgG tests are suitable for serosurveys for the assessment of previous virus exposure.

Despite high level vaccination and the availability of two different types of vaccines, whole cell (wP) and acellular vaccines (aP), the resurgence of pertussis has been reported in many countries. Antigenic variation within circulating and vaccine strains is the most documented reason reported for the resurgence of pertussis. Research on genetic divergence among circulating and vaccine strains has largely been reported in countries using aP vaccines. There are inadequate data available for antigenic variation in

Background: Many risk factors contribute to high morbidity and mortality due to childhood pneumonia. Mostly the risk factors are modifiable and related to behavior. Imparting knowledge to mothers about risk factors, early recognition of danger signs and importance of timely seeking health care is an accepted strategy for control. Aims & Objectives: To assess improvement in knowledge and perceptions about childhood pneumonia, risk factors and hand washing skills among mothers after sequential use of different media. Materials & Methods: This community based, pre and post assessment study was conducted in eight randomly clusters from two districts. Specially field supervisors assessed mothers for their ‘knowledge’, ‘perceptions’ and ‘skills’ about nutrition including breast feeding and malnutrition, indoor pollution, pneumonia and hand washing. Knowledge was assessed pertaining to all four aspects, perception was assessed for first three and skills were assessed only for hand washing. Three rounds of BCC using pictorial booklet, audio-visual film and flash cards consequently were completed, spread over about one year. Marks pertaining knowledge, perceptions about risk factors of childhood pneumonia and hand washing skills etc. were separately measured. Results: A total of 1,321 mothers participated. The mean pre-test marks were 22.31 out of 38 marks which significantly improved and retained to 35.24 after undergoing three BCC rounds. Highly significant improvements, 2.27 times in hand washing skills to 1.15 times for knowledge about indoor air pollution was observed. Conclusions: Consecutive use of different media at appropriate interval spread over a long period certainly yields desired results at diverse places.

Improving health education of the mother by providing community-based interventions is known to help control pneumonia.To determine the effect of behavior change communication (BCC) activities for mothers in reducing the incidence of childhood pneumonia.Open-label cluster randomized controlled trial.Urban slums and villages in two districs of Maharashtra.Under-five children and their mothers from households in the randomly selected 16 clusters out of total 45 clusters, stratified into Pune and Sangli districts and further into rural and urban areas before randomization.Three forms of BCC activities were imparted, viz., interactive sessions of education using pictorial mothers' booklet, screening of a audio-visual film, and virtual hand wash demonstration and use of flashcard. Routine care under the National health program was provided by the Accredited Social Health Activists (ASHA) workers in both the arms.The primary outcome was pneumonia as per the IMNCI criteria assessed during fortnightly visits of the ASHA/anganwadi workers to the houses of under-five children, who received at least one follow-up visit in a period of one year.The incidence of pneumonia in 1993 and 1987 under-five children in the intervention and control arm was 0.80 and 0.48 episodes per child per year, respectively (P=0.03).BCC for mothers is not sufficient to reduce the incidence of childhood pneumonia.

Acute respiratory infections (ARIs) continue to be the most important cause of morbidity and mortality among under-five children. Some demographic and environmental factors are associated with ARIs among under-five children. This study was conducted with the objective to estimate the prevalence of ARIs among under-five children in the rural areas and densely populated urban slum areas in Maharashtra, India and to assess the association of the selected sociodemographic and household environmental factors with ARI. This study was conducted in 16 selected clusters from the rural areas and densely populated urban slum areas of the two districts in Maharashtra, India. Structured and validated proforma was used for collecting the data on the sociodemographic and household environmental risk factors. A total of 3,671 under-five children were surveyed. The prevalence of ARIs for the preceding month was 50.4%. It was higher among the children living in the rural areas (54.2%) compared to the children living in the urban areas (46.7%) (p = 0.01). The prevalence of ARIs was reported to be 51.4 and 49.4% in boys and girls, respectively. In the multivariate analysis, the researchers found that living in rural areas (p = 0.01) and parental smoking (p = 0.04) were significantly associated with the ARIs. An intervention such as reducing parental smoking habits at the household level may reduce ARIs.

Background: India has the second-highest number of under-five deaths in any country in the world. WHO and the Government of India recommended the rollout of preconception care (PCC) to reduce maternal and child mortality. However, very few countries, including India, have started a comprehensive package of PCC services. It implies that women, mainly from rural and tribal areas, are not aware of PCC. PCC has been rolled out through the government health system in two blocks of Nashik district in Maharashtra state, India, among all women who desire to be pregnant within 1 year. This project is the first of its kind in India. To assess basic perceptions, knowledge, and behavior of women on PCC before the implementation of the project, focus group discussions (FGDs) were carried out. The authors think that the finding may help to develop strategies for behavioral change communication.Methods: From each of the four blocks, two villages having subcenter were selected for conducting FGD. A house-to-house survey was conducted by Accredited Social Health Activist (ASHA) to enlist women who desire a baby in 1 year and invite them to subcenter for FGDs, which were conducted in June 2018.Results: A total of 76 women having a mean age of 23.97 years participated in the FGDs. Most of them (46.05%) had completed 10 years of education. About 50% of pregnancies were planned. The decision about the timing of the first pregnancy is influenced by the mother-in-law. Women knew that they should not conceive before 20 years of age, and their suboptimal weight may have an adverse impact on the health of the newborn. There are many myths about food like “hot and cold foods” and “forbidden food” etc. Women had some knowledge about the adverse effects of tobacco and alcohol; very few consumed these. Most of them did not practice behaviors or accessed services related to PCC.Conclusions: Women neither have the knowledge nor adopt behaviors or accessed services related to PCC. Roll out of PCC among them may help in further reduction of maternal and neonatal morbidity and mortality in India.

BackgroundThe preconception phase of women’s life cycle is critical but comparatively ignored. The presence of health risks is judged as hazardous to the wellbeing of women and their offspring. This study aimed to estimate the prevalence of various pregnancy outcomes and assess the association between certain risk factors and adverse outcomes.MethodsAs a part of a preconception care intervention project, a baseline survey was conducted in four blocks of Nashik District, India. In this population-based cross-sectional analytical study, we compared cases in the study group (randomly selected one tribal and one non-tribal block) with those of the control group (one tribal and one non-tribal block). A comparison was also made between the tribal and non-tribal blocks in each group. All women who had a pregnancy outcome in the preceding 12 months (01 April 2017 to 31 March 2018) were interviewed. Trained Accredited Social Health Activists conducted the survey under the direct supervision of Auxiliary Nurse Midwives and Medical Officers. Multivariate analysis was carried out to find the adjusted prevalence ratio of having a particular adverse outcome because of the prespecified potential risk factors.ResultsA total of 9307 women participated in the study. The prevalence of adverse pregnancy outcomes was as follows: abortion in 4.1%, stillbirth in 1.7%, preterm birth in 4.1%, low birth weight in 13.2%, and congenital physical defect in 2.8%. Prevalence of parental consanguinity, pre-existing maternal illness at conception, heavy work during the last six months of pregnancy, tobacco consumption, alcohol consumption, direct exposure to pesticides and domestic violence during pregnancy was 18.5, 2.2, 18.7, 5.6, 0.5, 2.3, and 0.8% respectively. Risk factors associated with abortion included pre-existing illness and heavy work in the last six months of the pregnancy. Consanguinity, tobacco consumption during pregnancy and pre-existing illness were identified as risk factors for stillbirth. Significant risk factors of low birth weight were heavy work in the last six months of pregnancy, pre-existing illness and residence in a tribal area.ConclusionThere is a need to emphasize on maternal behaviour, including tobacco consumption, and heavy work during pregnancy, as well as on parental consanguinity and pre-existing maternal illnesses, in order to achieve the best possible pregnancy outcomes.

Respiratory syncytial virus (RSV) causes significant infant mortality worldwide and a vaccine may be available soon. This study determined age-stratified anti-RSV antibody positivity (enzyme-linked immunosorbent assay [ELISA]) at Pune, India (cord blood-85 years). Antibody positivity declined from 100% at birth to 71.3% (3 months), and 0.7% (6 months). A significant rise was noted at 15 months (16%), 16 to 24 months (64.5%) and 4 years (95.2%) with concomitant IgM-anti-RSV positivity indicative of recent infection. Antibody decline was higher in infants born preterm than full-term. Across subsequent age groups including the elderly, antibody positivity was similar and comparable, suggestive of repeated exposure to the virus. Early protection/vaccination is essential for the infant population.

A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency.This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards.Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related.The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®.Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].

Background Immunization of children with vaccines against Measles, Mumps, Rubella, and Varicella (MMRV) is practiced globally with varied recommendations. In India, measles vaccine is administered alone or as MMR at 9 months age. Varicella vaccine is not routinely used. Immunization age is a function of disappearance of maternal antibodies and natural exposure of the children to the pathogens. In view of the measles-WHO-initiative, we aimed to assess if the current immunization age for measles is still valid. In addition, the kinetics of IgG and IgM antibodies against rubella, mumps and varicella viruses was also examined. Methods This cross-sectional study was conducted at a tertiary care hospital in Pune, India. A total of 600 children, 150 each in 6-month/9-month (no vaccination) and 12-month/15-month (minimum 4 weeks post-measles-vaccine) cohorts were included. History of these infections and birth status (term/preterm) was recorded. All serum samples were screened for IgG-anti-MMRV-antibodies while IgG-positives were tested for specific IgM antibodies (ELISA). Results At 6-months, the prevalence of MMRV antibodies was 4.7%, 2.7%, 10.7%, 5.3% respectively depicting disappearance of maternal antibodies in majority of the children. Birth status did not influence antibody positivity. Despite vaccination at ∼9-months, >25% children were still susceptible to measles virus at the age of 12/15-months. The ratio of clinical:subclinical infections was 4:10 (measles) and 12:1 (varicella). All the mumps/rubella IgM positives (1 and 2 respectively) represented subclinical infections. Conclusion Demonstration of early disappearance of maternal antibodies against MMRV viruses leading to the risk of these infections at an early age emphasize need for early immunization of Indian children. Suboptimal response to measles vaccine needs to be seriously addressed especially in view of the WHO’s initiative for measles eradication.

Background: The health of women during the preconception phase though critical, is a comparatively ignored part in her life cycle. The presence of health risks is judged as hazardous to the wellbeing of women and their forthcoming progeny. The study aimed to estimate the prevalence of various pregnancy outcomes and assess the association between various risk factors and adverse outcomes. Methods: It was a population-based cross-sectional analytical study. The study was carried out in Nashik District, having a large mountainous area. It included two randomly selected blocks, one tribal and one nontribal, in which interventions were planned in the later stage. For comparison, two adjacent blocks, one tribal and one nontribal, were also included. All women who had a pregnancy outcome in the preceding 12 months (01 April 2017 to 31 March 2018) were interviewed. Trained Accredited Social Health Activists under the direct supervision of Auxiliary Nurse Midwives and Medical Officers conducted the survey. Multivariate analysis was carried out to find the adjusted risk ratio of having a particular adverse outcome because of the specified potential risk factors.Results: A total of 9,307 women participated in the study. The prevalence of adverse pregnancy outcomes was abortion 4.1%; stillbirth 1.6%; preterm birth 4.1%; LBW 11.2%; congenital physical defect 2.6%. Prevalence of consanguineous marriage, heavy work during the last six months of pregnancy, pre-existing illness, tobacco consumption, direct exposure to pesticides and domestic violence during pregnancy was 17.6%; 16.9%; 2.2%; 5.6%; 2.3%; and 0.8%, respectively. Risk factors that were significantly associated with abortion include existing illness at the time of conception and performing heavy work in the last six months of pregnancy. Consanguinity, tobacco consumption during pregnancy and pre-existing illness were identified as risk factors for stillbirth. Significant risk factors of LBW were heavy work in the last six months of pregnancy, pre-existing illness and residence in a tribal area. Conclusion: The survey showed that risk factors differentially affect outcomes of pregnancy. Preconception and antenatal care should include counselling about consanguineous marriages, identifying and managing a pre-existing illness, avoiding tobacco consumption in the prenatal and natal period, and avoiding heavy work during pregnancy.

Childhood vaccination plays critical role in protecting infants from several dreaded diseases. Of the global 15 million preterm (PT) infants with compromised immune system born annually, India contributes to >3.5 million. Generation of adequate vaccine-induced immune response needs to be ensured of their protection. Immune response of Indian PT (n = 113) and full-term (FT, n = 80) infants to pentavalent vaccine administered as per the national recommendation was studied. Antibody titers against component antigens of pentavalent vaccine, immune cells profiling (T and B cells, monocytes and dendritic cells) and plasma cytokines were determined pre- and post-vaccination. Additionally, cell-mediated recall immune responses to pentavalent antigens were evaluated after short time antigenic exposure to infant PBMCs. Irrespective of gestational age (GA), all the infants developed adequate antibody response against tetanus, diphtheria, and protective but lower antibody levels for Haemophilus influenzae type-b and hepatitis B in preterm infants. Lower (~74%) protective antibody response to pertussis was independent of gestational age. PT-infants exhibited lower frequencies of CD4 T cells/dendritic cells/monocytes, increased plasma IL-10 levels and lower proliferation of central and effector memory T cells than in term-infants. Proliferative central memory response of FT-infants without anti-pertussis antibodies suggests protection from subsequent infection. Responder/non-responder PT-infants lacked immunological memory and could be infected with Bordetella. For hepatitis B, the recall response was gestational age-dependent and antibody status-independent. Humoral/cellular immune responses of PT-infants were dependent on the type of the immunogen. Preterm infants born before 32 weeks of gestation may need an extra dose of pentavalent vaccine for long lived robust immune response.

Background: Preconception phase in women though critical is comparatively ignored. The presence of risk factors affects well-being of the woman and her forthcoming progeny. The objectives of the study were to measure the prevalence of various risk factors among women and their comparison between blocks.Methods: This was a community based cross-sectional study in two tribal and two non-tribal blocks in Nasik district, Maharashtra, India. The study included women desiring conception within one year. Trained Accredited Social Health Activists collected information through house-to-house visits using a validated interview schedule. They recorded anthropometric measures of women in a standard manner. Results: The study enlisted 7,875 women desiring pregnancy soon. The mean age of women was 23.19 (+3.71) years and 16% of them were adolescents. Women's illiteracy was higher in tribal areas than non-tribal (p+3.51) and higher proportion (40.5%) of women from tribal areas were having BMIConclusions: Health risks namely younger age, illiteracy, high parity, consumption of tobacco, low protein and calories intake were found to be prevalent and the risks were significantly more among tribal women. “Continuum of care” must include preconception care.

For the assessment of vaccine-induced immune response and to understand the role of antibodies in neutralization, it is necessary to assess dynamics of various antibodies in patients with different clinical manifestations. This study aims to quantitate circulating levels of IgA/IgG and IgG subtypes induced at different days postonset of symptoms, in severe and nonsevere patients. For this, serum or plasma samples (n = 146) collected from 79 COVID-19 patients were used. Indirect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific IgA, IgG, and IgG subtype specific enzyme-linked immunosorbent assays (ELISAs) were performed. Antibody titers between severe and nonsevere patients were compared at different times postonset of clinical symptoms. Titers in ELISA were compared to neutralizing antibody (Nab) titers determined by plaque reduction neutralization test (PRNT). Over 75% patients were positive for IgA/IgG antibodies in the first week. The ELISA titers did not differ during the first week; however, severe disease exhibited raised titers thereafter. Nab titers correlated with the ELISA titers in mild presentation but not in severe disease. IgA and IgG1 antibodies correlated stronger with Nabs. The findings highlighted that IgA together with IgG play an important in SARS-CoV-2 neutralization. These results will prove useful in assessing efficacy of vaccines and understanding disease pathogenesis.

Introduction Infection with SARS‐CoV‐2 leads to a spectrum of symptoms. Understanding the basis for severity remains crucial for better management and therapy development. So far, older age, associated‐comorbidities, and IL‐6 have been associated with severity/mortality. Materials and Methodology As a primary step, we analyzed the frequency and functional profile of innate immune cells (NK cells/dendritic cells/monocytes) and adaptive immunity‐driving lymphocytes (B cells/T cells/follicular T helper cells) by flow cytometry. Sixty cases of SARS CoV‐2 infection (25 severe, 35 mild) and ten healthy subjects without SARS CoV‐2 IgG were included. Disease‐duration based analysis of immune profile was explored for early events differentiating the two disease forms. Neutralizing antibody titers were determined by PRNT. Results and Conclusion Disease severity was found to be associated with impaired maturation of mDCs and hyperactivation of NK, follicular T helper cells, and CD8 T cells. Lower IL‐21 receptor expression on memory B cells indicated an imbalance in IL‐21/IL‐21 R ratio. Lower BCMA positive plasmablast cells in severe cases did suggest a probable absence of long‐term humoral immunity. Multivariate analysis revealed a progressive association of PD‐1+CD4 T cells with PRNT50 titers. Thus, in addition to identifying probable prognostic markers for severity, our study emphasizes the definite need for in‐depth viral antigen‐specific functional analyses in a larger patient cohort and with multiple sampling., Understanding pathogenesis of severity in current SARS‐CoV2 pandemic is of prime importance. Another concern is the recent observations (including ours) of early, higher neutralizing antibody titers in severe disease. India is reporting >80,000/day for several weeks now. Identification of prognostic markers for severity may help identifying “extra‐care‐needed” patients. As a first step, this flow‐cytometry based study was planned to understand (1) differences in immunologic modulations in patients with mild and severe disease (2) if we can identify early events associated with severity (3) prognostic markers for severity (4) association of functionality of immune cells with higher antibody titers in severe disease.

Background: Being a long-term preventive measure, COVID-19 vaccines are used in global populations. In India, country-wide immunization drive was initiated in January 2021. Methods: To assess immune response of health-care-workers to COVISHIELD(n=187) and COVAXIN(n=21), blood samples collected pre-vaccination and 1month-post-1/post-2 dose, administered 28days apart, were tested for IgG-anti-SARS-CoV-2 (ELISA) and neutralizing (Nab, PRNT50) antibodies. Spike protein-specific T cells were quantitated by IFN-γ ELISPOT and Flow-cytometry-based Intra-cellular-secretion (ICS) for IFN-γ/IL2. Findings: Among pre-vaccination-antibody negative (pre-negatives, n=120) and positive (pre-positives, n=67) COVISHIELD recipients, %Nab seroconversion and median (IQR) Nab titers were 55.1%/95.6% and 16(IQR 2.5-36.3)/(64.5, IQR 34.5-154.2, p

BackgroundUndernutrition among under five children in India is a major public health problem. Despite India’s growth in the economy, the child mortality rate due to undernutrition is still high in both urban and rural areas. Studies that focus on urban slums are scarce. Hence the present study was carried out to assess the prevalence and determinants of undernutrition in children under five in Maharashtra, India.MethodsA community-based cross-sectional study was conducted in 16 randomly selected clusters in two districts of Maharashtra state, India. Data were collected through house to house survey by interviewing mothers of under five children. Total 2929 mothers and their 3671 under five children were covered. Multivariate logistic regression analysis was carried out to identify the determinants of child nutritional status seperately in urban and rural areas.ResultsThe mean age of the children was 2.38 years (±SD 1.36) and mean age of mothers was 24.25 years (± SD 6.37). Overall prevalence of stunting among children under five was 45.9%, wasting was 17.1 and 35.4% children were underweight. Prevalence of wasting, stunting and underweight were more seen in an urban slum than a rural area. In the rural areas exclusive breast feeding (p p = 0.001) were associated with wasting, children with birth order 2 or less than 2 were associated with stunting and exclusive breast feeding (p p p p p ConclusionsFactors like sex of the child, birth order,exclusive breast feeding,economic status of the family, type of family,acute diarrhea and maternal education have influence on nutritional status of the child. Improvement of maternal education will improve the nutritional status of the child. Strategies are needed to improve the economic status of the community.Trial registrationTrial registration number:CTRI/2017/12/010881; Registration date:14/12/2017. Retrospectively registered.

Background Health of women during preconception phase though critical is comparatively ignored period in her life cycle. Presence of health risks are judged as hazardous to well-being of women and her forthcoming progeny. The objective of the study was to measure the prevalence of health risks and its comparison between blocks.Methods A cross sectional study was conducted in two tribal and two non-tribal blocks in Nasik district, Maharashtra, India. Currently married women desiring conception within one year were included as study participants. Sample size was estimated to be 6,951. Data was collected by trained Accredited Social Health Activists using validated interview schedule. Anthropometric measures of women were recorded in standard manner. Body Mass Index criteria were used to assess the nutritional status.Results Mean age of women was 23.19 ± 3.71 years and 16% of them were adolescents. Illiteracy rate was higher in tribal than non-tribal women. Commonest reported occupation was farming. Despite being high parity and gravida status more tribal women desired pregnancy. Substance abuse was high among tribal women. Majority of women consumed meal with family members or with husband. Although 35% of women had low consumption of protein and calorie, yet most of them perceived to have abundant food.Conclusion Health risks namely younger age, illiteracy, farming with moderate to high-intensity work, high parity, low consumption of protein and calories and undernutrition were found to be prevalent and the risks were significantly more among tribal women. “Continuum of care” must include preconception care.

Background India has the highest number of under-five deaths in any country in the world. World Health Organization and Government of India recommended roll out of preconception care (PCC) for reduction of maternal and child mortality. However, very few countries including India have implemented a comprehensive package of PCC services. PCC has been rolled out among all women, who desire to be pregnant in one year through the government health system in two blocks of Nashik district of Maharashtra State, India. In order to assess the impact of PCC in these two blocks, baseline and post intervention studies (both quantitative and qualitative) on women’s knowledge and behaviour on PCC, their health status and pregnancy outcomes are planned in these two intervention blocks as well as in two control blocks. To assess women’s knowledge and behaviour on PCC before implementation of the project, focus group discussions (FGDs) were carried out as part of this impact assessment project.Methods From each of the four blocks, two villages having sub centre were selected for conducting FGD. A house to house survey was conducted by Accredited Social Health Activist (ASHA) to enlist women who desire a baby in one year. From the list, eight to twelve women were invited to sub centre for FGDs, which were conducted in June 2018.Results A total of 76 women having mean age 23.97 years participated in the FGDs. Most of them (46.05%) had completed 10 years of education. About 50% of pregnancies are planned. The decision about first pregnancy is influenced by the mother-in-law. Women knew that they should not conceive before 20 years of age and their inadequate weight may have adverse impact on the health of new-born. Women had some knowledge about adverse effects of tobacco and alcohol use, very few consumed these. Most of them did not practice behaviours or accessed services related to PCC.

Background: Undernutrition among under five children in India is a major public health problem. Despite India’s growth in the economy, the child mortality rate due to undernutrition is still high in both urban and rural areas. Studies that focus on urban slums are scarce. Hence the present study was carried out to assess the prevalence and determinants of undernutrition.Methods: A community-based cross-sectional study was conducted in 16 randomly selected clusters in two districts of Maharashtra state, India. Data were collected through the house to house survey by interviewing mothers of under five children. Logistic regression method was used for multivariate analysis to determine the association between the variables like sex of the child, type of family, the income of the family, birth order, exclusive breastfeeding, immunization status, ARI, diarrhea, maternal age, maternal education with outcome variables underweight, stunting and wasting.Results: Total 2929 mothers and their 3,671 under five children were covered. Prevalence of wasting, stunting and underweight were more seen in an urban slum than a rural area.Exclusive breastfeeding up to 6 months was the protective factor against wasting in both rural area (Adj OR=0.35,pConclusion: Undernutrition was related to the sex of the child, the economic status of the family, diarrhea (Past 1 month), and maternal education. Improvement of maternal education will improve the nutritional status of the child.The trial registration-This article is part of baseline data of the project, hence not related to trial registration. After baseline data principal investigator had done trial registration retrospectively.

Background and objectiveBirth weight and post-natal growth are important predictors of adult health. Preeclampsia (PE) is associated with low birth weight and may have long term effects on the health of the children. The current study aims to compare anthropometry and blood pressure between children of mothers with and without PE in an Indian cohort.MethodsWe studied children born to women with (PE; n = 211) and without preeclampsia (non-PE; n = 470) at Bharati Hospital, Pune, India. Anthropometry and blood pressure were measured in children at 3–7 years of age. Weight and height Z-scores were calculated using the WHO 2006 growth reference. Independent t-tests were used to compare means between the two groups, and associations between preeclampsia and child outcomes were analyzed using multiple linear regression, adjusting for potential confounders.ResultsWeight and height Z-scores (p = 0.04 and 0.008), and subscapular skinfold thickness (p = 0.03) were higher among children of PE compared with children of non-PE mothers. Systolic blood pressure was also higher in children of PE mothers (1.70 mmHg [95% CI 0.05, 2.90] p = 0.006). BMI and diastolic blood pressure did not differ between groups. In regression models adjusted for newborn weight and gestational age, current age and sex, and maternal height, BMI and socio-economic status, children of PE mothers had higher weight Z-score (0.27 SD [95%CI 0.06, 0.48] p = 0.01), height Z-score (0.28 SD [95%CI 0.09, 0.47] p = 0.005), and subscapular skinfold thickness (0.38 mm [95%CI 0.00, 0.76] p = 0.049). A trend for higher systolic blood pressure (1.59 mmHg [95%CI -0.02, 3.20] p = 0.053) in the children was also observed in the adjusted model. The difference in systolic blood pressure was attenuated after adjusting further for the child’s weight and height (1.09 mmHg [95%CI -0.48, 2.67] p = 0.17). There was no evidence of differences in effects between boys and girls.ConclusionChildren of PE mothers were taller and heavier, and had higher systolic blood pressure, partly explained by their increased body size, than children of non-PE mothers. In utero exposure to preeclampsia may increase the risk of future cardiovascular disease.

Background Undernutrition among under five children in India is a major public health problem. In India almost 60 million children are underweight. Despite India’s growth in economy, child mortality rate due to undernutrition is still high in both urban and rural area. Studies that focuses on undernutrition in urban slums are scarce. Hence present study was carried out to measure all forms of undernutrition like underweight, stunting and wasting. Methods A community based cross sectional study was conducted in 16 randomly selected clusters in two districts of Maharashtra state,India. All 2,929 mothers of under five children from these clusters were included in the study. Data was collected by house to house survey by interviewing mothers of underfive children.Odds ratio was calculated to determine association between the variables. Results Total 3,671 under five children were covered. Mean age of the children was 2.38 years (± SD 1.365).Stunting (45.9%) was found to be the commonest form of undernutrition among under five children, followed by underweight (35.4%), and wasting (17.1%). Sex of the child (urban slum; OR=1.32, rural area OR=1.63) birth order (rural area; OR= 0.47), immunization status (urban slum; OR=0.23) exclusive breast feeding (urban slum; OR=0.51), childhood infections like diarrhea(rural area OR= 1.69) acute respiratory tract infection (ARI) (rural area OR= 0.82), economic status of the family, (urban slum OR= 1.32), maternal age (P = 0.001)and maternal education(P

Background Hepatitis-A is an acute viral infection of the liver. Hepatitis-A virus has worldwide spread and is endemic in India. Though the disease is self-limiting in most cases, outbreaks are reported frequently from both developing and developed countries of the world. Severity and fatality occur more among infected symptomatic adults. The infection can be prevented with proper and timely immunization. This phase I, single arm, open label, multicenter trial was designed to assess the safety and immunogenicity of the inactivated hepatitis-A vaccine developed by Human Biologicals Institute when administered in a single dose in two age groups of healthy subjects. Methods This study was carried out in 55 subjects in two healthy age groups at two centers in India. Group A included subjects of 19–49 years and group B subjects of 12–18 years of age. Enrolled subjects received a single dose of inactivated hepatitis A vaccine. Blood samples were collected at baseline and 4–6 weeks after vaccination. Safety was assessed by collection and analysis of data on solicited and unsolicited adverse events and immunogenicity was assessed by estimating the seroconversion rate, seroprotection rate and the geometric mean titres of antibodies. Results Among the 55 subjects enrolled, 15 reported adverse events. No serious adverse event was reported. Pain at the injection site was the lone local adverse event. Systemic adverse events reported in Group A were: fatigue, headache, diarrhoea, fever, anorexia, nausea and upper respiratory tract infection, whereas there was no systemic event reported in Group B. There was 100% seroconversion and seroprotection and significant rise in antibody titre levels were observed in both the groups post vaccination. Conclusions This study found HBI inactivated hepatitis-A vaccine to be safe and highly immunogenic when administered as a single dose in adolescent and adult subjects.

Background Novel coronavirus disease 2019 (COVID-19) has rapidly spread across the entire globe causing a lot of fear among the masses India had more than 2,500 confirmed cases and more than 70 deaths at the time of submission of this article This is probably the first study from India on the knowledge, attitudes, and practices toward COVID-19 Presently, there is only 1 similar study from China Methods A cross-sectional observational study was performed in a tertiary care hospital in India to assess the knowledge, attitudes, and practices of the participants toward COVID-19 during the pandemic The participants had to answer a questionnaire in the language well understood by them It pertained to their basic knowledge about this disease, their attitudes, and correct practices The participants were either doctors, staff, patients, or relatives visiting the hospital Results Among the various age groups, the highest proportion (57 21%) of very good knowledge was in the 20 to 30 years age group Among the respondents, poor knowledge was seen in the patients Overall, 47 99% participants had an extremely optimistic attitude, whereas

Highlights • Development of indirect IgG ELISA using β-propiolactone-inactivated SARS-CoV-2. • Detection of anti-SARS-CoV-2 IgG during early disease phase. • Higher IgG seropositivity and OD values in COVID-19 patients with severe disease., Background Coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome – coronavirus-2 (SARS-CoV-2) continues to affect many countries and large populations. Serologic assays for antibody detection aid patient diagnosis and seroepidemiologic investigations. Methods An indirect IgG ELISA was developed indigenously using β-propiolactone (BPL) inactivated SARS-CoV-2. This assay was used for screening 200 healthy donor sera collected prior to COVID-19 emergence (2017–2019), 185 serum/plasma samples of confirmed COVID-19 patients (n = 137) and 57 samples of viral RNA positive asymptomatic contacts (n = 51). The IgG response was studied in relation to duration and severity of illness. Results The ELISA demonstrated 97 % specificity and IgG detection in >50 %, 80 %, 93.8 % and 100 % of the patients respectively during the first, second, third and fourth week of illness. IgG detection rate was higher in patients with severe disease (SD, 90.9 %) than those with mild disease (MD, 68.8 %) during the second week of illness (P = 0.027). IgG seropositivity among asymptomatic contacts was 64.7 %. IgG ELISA absorbance values were higher in SD than MD patients during the first 2 weeks of illness (P

The degree of transmission of hepatitis A virus (HAV) is inversely proportional to the socioeconomic status of a community. Serosurveys conducted at Pune, India during 1982-98 documented significant reduction in HAV exposure of paediatric, higher socioeconomic status (HSS) population. Anti-HAV positivity (ELISA) in age-stratified Pune population representing HSS and lower middle socioeconomic status (LMSS) (n = 1065) and infants till the age of 15 months (n = 690) was determined in 2017. Anti-HAV positivity in the LMSS population decreased significantly in 2017 while an increase was seen in the HSS category. The surprising rise in anti-HAV positivity in the HSS population reflected vaccine- and infection-induced antibodies while only infection-induced antibodies were present in the LMSS category. Lowest antibody prevalence in infants was at 12 months, the recommended age for hepatitis A vaccination. Improved hygiene and selective immunization practices impacted HAV exposure of the LMSS population. The data emphasize the need for hepatitis A vaccination irrespective of socioeconomic status.

A newly developed bovine-human reassortant pentavalent vaccine (BRV-PV, ROTASIIL®) was tested for its potential effect on the immunogenicity of concomitantly administered EPI vaccines in infants in a randomized controlled study in India.In this Phase III, multicenter, open label, randomized, controlled study, three doses of BRV-PV or two doses of Rotarix® and one dose of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were collected four weeks after the final vaccination to assess immune responses to all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 antibodies, non-interference was to be supported if the lower limit of the two-sided 90% confidence interval (CI) for the seroprotection rate difference for the BRV-PV group minus the Rotarix® group was10.0%. For pertussis antibodies, non-interference was to be supported if the lower limit of the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was0.5.A total of 1500 infants were randomized to either BRV-PV (1125 infants) or Rotarix® (375 infants), of which 1341 completed the study as per the protocol. More than 97% of subjects achieved seroprotective antibody titres against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in both groups. The difference in seroprotection rates between the BRV-PV group and the Rotarix® group for all these antibodies was less than 1%. The ratio of GMCs of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix® was 1.04 [90% CI: 0.90; 1.19].BRV-PV does not interfere with the immunogenicity of concomitantly administered routine infants vaccines.

Objectives Antibody persistence in children following three doses of primary vaccination with diphtheria, tetanus, whole-cell-pertussis (DTwP), hepatitis B, and Haemophilus influenzae type b (Hib) vaccines (SIIL Pentavac vaccine vs. Easyfive ® of Panacea Biotec), and response to the booster dose of DTwP–Hib (Quadrovax ® ) vaccine. Methods Children who completed their primary immunization were assessed for antibodies at 15–18 months of age, and then given a booster dose of DTwP–Hib vaccine. Reactogenicity and safety of the booster dose was evaluated. Results Both pentavalent vaccines demonstrated a good immune response at 15–18 months. Following the booster dose, all vaccinated subjects achieved protective titers against diphtheria, tetanus and Hib, whereas the response to pertussis antigen was ∼78%. Fever and irritability was noted in 24%, local pain in 51%, and swelling in 36% of the children following booster dose. Conclusions Primary immunization with either pentavalent vaccine induced an excellent immunity lasting till the second year of life. A booster dose with DTwP–Hib (Quadrovax ® ) vaccine effectuated a good anamnestic response to all vaccine components, being specially strong for Hib in children previously vaccinated with SIIL liquid pentavalent vaccine (Pentavac ® ). Also, the safety profile of SIIL quadrivalent vaccine (Quadrovax ® ) administered as booster dose was acceptable.