Search

BACKGROUND To describe the pattern of gestational weight gain (GWG), derive reference centiles for GWG specific to North Indian population, and to compare the weight gain across different periods of gestation with the INTERGROWTH-21st reference. METHODS A prospective pregnancy (GARBH-Ini) cohort was initiated and followed between May 2015 and June 2019 in a district hospital, Gurguram, North India. GWG centile curves were modelled by Generalized Additive Models for Location, Scale and Shape method (n = 2844) and compared with INTERGROWTH-21st reference. The independent association of GWG with biological and social predictors was assessed using multivariable regression analysis. RESULTS Percentiles (3rd, 10th, 50th, 90th and 97th) for each completed week from 18-40 weeks of gestation were derived from smoothed centile curves. The median GWG across pregnancy during specific antenatal visits was 1.29 at 18, 4.44 at 26, 5.8 at 30 and 9.06 kg at 40 weeks of gestation. Nearly 26% of participants had GWG

Background Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity. Methods This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized–controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12–27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months. Results Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference: 0.050; 95% confidence interval: 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference: 0.062; 95% confidence interval: 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes. Conclusions Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Clinical and epidemiological characteristics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now widely available, but there are few data regarding longitudinal serology in large cohorts, particularly those from low-income and middle-income countries. We established an ongoing prospective cohort of 3,840 SARS-CoV-2-positive individuals according to RT-PCR in the Delhi-National Capital Region of India to document clinical and immunological characteristics during illness and convalescence. The immunoglobulin G (IgG) responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0 to 7 days, 10 to 28 days, and 6 to 10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates during the postinfection windows of 0 to 7 days, 10 to 28 days, and 6 to 10 weeks were 46%, 84.7%, and 85.3%, respectively (N = 743). The proportion with a serological response increased with the severity of coronavirus disease 2019 (COVID-19). All participants with severe disease, 89.6% with mild to moderate infection, and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values for the nasopharyngeal viral RNA RT-PCR of a subset of asymptomatic and symptomatic seroconverters were comparable (P = 0.48) to those of nonseroconverters (P = 0.16) (N = 169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 over a period of 10 weeks in South Asia. The low seropositivity of asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.

To describe the pattern of gestational weight gain (GWG), derive reference centiles for GWG specific to North Indian population, and to compare the weight gain across different periods of gestation with the INTERGROWTH-21st reference.A prospective pregnancy (GARBH-Ini) cohort was initiated and followed between May 2015 and June 2019 in a district hospital, Gurguram, North India. GWG centile curves were modelled by Generalized Additive Models for Location, Scale and Shape method (n = 2844) and compared with INTERGROWTH-21st reference. The independent association of GWG with biological and social predictors was assessed using multivariable regression analysis.Percentiles (3rd, 10th, 50th, 90th and 97th) for each completed week from 18-40 weeks of gestation were derived from smoothed centile curves. The median GWG across pregnancy during specific antenatal visits was 1.29 at 18, 4.44 at 26, 5.8 at 30 and 9.06 kg at 40 weeks of gestation. Nearly 26% of participants had GWG 10th centile at 18-20 weeks as per INTERGROWTH-21st reference and this increased to 45% at delivery. Significant predictors of GWG included maternal age, height, first trimester body mass index, parity, type of family, and use of clean fuel for cooking.These GWG percentiles will serve as a useful reference, particularly during the WHO recommended antenatal visit schedule for optimum pregnancy outcomes, for clinicians and researchers. Multiple independent biological and social predictors of GWG suggest that single interventions are unlikely to bridge the gap between general Indian population and international references.

Clinical and epidemiological characteristics of SARS-CoV-2 infection are now widely available, but there are few data on longitudinal serology in large cohorts, particularly from low-and middle-income countries. We established an ongoing prospective cohort of 3840 SARS-CoV-2 RT-PCR positive individuals in the Delhi-National Capital Region of India, to document clinical and immunological characteristics during illness and convalescence. The IgG responses to the receptor binding domain (RBD) and nucleocapsid were assessed at 0-7, 10-28 days and 6-10 weeks after infection. The clinical predictors of seroconversion were identified by multivariable regression analysis. The seroconversion rates in the post-infection windows of 0–7 days, 10–28 days and 6–10 weeks were 46%, 84.7% and 85.3% respectively (n=782). The proportion with a serological response increased with severity of COVID-19 disease. All participants with severe disease, 89.6% with mild to moderate infection and 77.3% of asymptomatic participants had IgG antibodies to the RBD antigen. The threshold values in the nasopharyngeal viral RNA RT-PCR in a subset of asymptomatic and symptomatic seroconverters were comparable (p value: 0.48), with similar results among non-seroconverters (p value: 0.16) (n=169). This is the first report of longitudinal humoral immune responses to SARS-CoV-2 infection over a period of ten weeks from South Asia. The low seropositivity in asymptomatic participants and differences between assays highlight the importance of contextualizing the understanding of population serosurveys.SummaryWe measured anti-SARS-CoV-2 RBD and NC protein IgG in a multi-hospital-based prospective cohort from northern India up to ten weeks post-infection. The lower seroconversion rate among asymptomatic RT-PCR positive participants has public health significance particularly for interpreting community seroprevalence estimates.

SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein’s receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential. Detection of IgG antibodies, rather than IgM or total antibodies, against RBD is likely to play a larger role in understanding antibody-mediated protection and vaccine response. Here we describe a rapid and stable RBD-based IgG ELISA test obtained through extensive optimization of the assay components and conditions. The test showed a specificity of 99.79% (95% CI: 98.82–99.99%) in a panel of pre-pandemic samples (n = 470) from different groups, i.e., pregnancy, fever, HCV, HBV, and autoantibodies positive. Test sensitivity was evaluated using sera from SARS-CoV-2 RT-PCR positive individuals (n = 312) and found to be 53.33% (95% CI: 37.87–68.34%), 80.47% (95% CI: 72.53–86.94%), and 88.24% (95% CI: 82.05–92.88%) in panel 1 (days 0–13), panel 2 (days 14–20) and panel 3 (days 21–27), respectively. Higher sensitivity was achieved in symptomatic individuals and reached 92.14% (95% CI: 86.38–96.01%) for panel 3. Our test, with a shorter runtime, showed higher sensitivity than parallelly tested commercial ELISAs for SARS-CoV-2-IgG, i.e., Euroimmun and Zydus, even when equivocal results in the commercial ELISAs were considered positive. None of the tests, which are using different antigens, could detect anti-SARS-CoV-2 IgGs in 10.5% RT-PCR positive individuals by the fourth week, suggesting the lack of IgG response.

Nucleic acid real-time PCR test has become the main diagnostic tool for SARS‐CoV‐2 infection, and there are also drawbacks to these real-time PCR test kits. Additionally, it has reported high false-negative rates. A reliable and rapid test method is urgently required to briskly detect antibody response in a large number of infected patients and ensure prompt care for patients. Therefore, we report here a Luminex bead based multiplexed immunoassay to serologically diagnose the SARS-CoV2 infection and detect IgM and IgG response in COVID-19 patients. The technology can provide sensitive and specific detection using a low amount of serum samples in high-throughput screening platforms.

BackgroundSpike protein domains are being used in various serology-based assays to detect prior exposure to SARS-CoV-2 virus. However, there has been limited comparison of human antibody titers against various spike protein antigens among COVID-19 infected patients.MethodsWe compared four spike proteins (RBD, S1, S2 and a stabilized spike trimer (ST)) representing commonly used antigens for their reactivity to human IgG antibodies using indirect ELISA in serum from COVID-19 patients and pre-2020 samples. ST ELISA was also compared against the EUROIMMUN IgG ELISA test. Further, we estimated time appropriate IgG and IgA seropositivity rates in COVID-19 patients using a panel of sera samples collected longitudinally from the day ofonset of symptoms (DOS).ResultsAmong the four spike antigens tested, the ST demonstrated the highest sensitivity (86.2%; 95% CI: 77.8-91.7%), while all four antigens showed high specificity to COVID-19 sera (94.7-96.8%). 13.8% (13/94) of the samples did not show seroconversion in any of the four antigen-based assays. In a double-blinded head-to-head comparison, ST based IgG ELISA displayed a better sensitivity (87.5%, 95%CI: 76.4-93.8%) than the EUROIMMUN IgG ELISA (67.9%, 95% CI: 54.8-78.6%). Further, in ST-based assays, we found 48% and 50% seroconversion in the first six days (from DOS) for IgG and IgA antibodies, respectively, which increased to 84% (IgG) and 85% (IgA) for samples collected ≥22 days DOS.ConclusionsComparison of spike antigens demonstrates that spike trimer protein is a superior option as an ELISA antigen for COVID-19 serology.HighlightsSpike trimer displays the highest antibody titer in SARS-CoV-2 infections among spike protein antigens.Spike trimer IgG ELISA displays a sensitivity of 50% within six days and 86.2% after 14 days from onset of symptoms.IgA and IgG responses to spike trimer antigen were comparable and concomitant in time after infection.16% (IgG) and 15% (IgA) of COVID-19 RT-PCR positive patients did not seroconvert even after 21 days from onset of symptoms.

BackgroundBacterial infections account for a significant proportion of neonatal and infant mortality globally. We aimed to identify predictors of death in infants with probable serious bacterial infection (PSBI) defined as signs/symptoms of possible serious bacterial infection along with baseline C-reactive protein (CRP) ≥12 mg/l.MethodsWe did a secondary analysis using the data collected from 700 infants with PSBI who participated in a randomized controlled trial in India in which zinc or placebo was given in addition to the standard antibiotics. Logistic regression was used to estimate the associations between relevant variables and death within 21 days.ResultsThose infants who were fed cow's milk or formula before the illness episode had 3.7-fold (95% confidence interval (CI) 1.5-9.3) and 5.3-fold (95% CI 2.0-13.6) higher odds of death, respectively. Lethargy (odds ratio (OR) 2.4, 95% CI 1.1-5.4) and CRP (OR 1.9, 95% CI 1.1-3.3) were also independent predictors of death. In the model including only clinical features, female gender (OR 2.25, 95% CI 1.0-5.0), abdominal distention (3.7, 95% CI 1.1-12.3), and bulging fontanelle (5.8, 95% CI 1.1-30.5) were also independent predictors for death.ConclusionFormula or cow milk feeding prior to the illness, lethargy at the time of presentation, and high serum CRP levels predicted death in infants with PSBI.

Memory T and B lymphocyte numbers are thought to be regulated by recent and cumulative microbial exposures. We report here that memory-phenotype lymphocyte frequencies in B, CD4 and CD8 T-cells in 3-monthly serial bleeds from healthy young adult humans were relatively stable over a 1-year period, while recently activated -B and -CD4 T cell frequencies were not, suggesting that recent environmental exposures affected steady state levels of recently activated but not of memory lymphocyte subsets. Frequencies of memory B and CD4 T cells were not correlated, suggesting that variation in them was unlikely to be determined by cumulative antigenic exposures. Immunophenotyping of adult siblings showed high concordance in memory, but not of recently activated lymphocyte subsets, suggesting genetic regulation of memory lymphocyte frequencies. To explore this possibility further, we screened effector memory (EM)-phenotype T cell frequencies in common independent inbred mice strains. Using two pairs from these strains that differed predominantly in either CD4EM and/or CD8EM frequencies, we constructed bi-parental bone marrow chimeras in F1 recipient mice, and found that memory T cell frequencies in recipient mice were determined by donor genotypes. Together, these data suggest cell-autonomous determination of memory T niche size, and suggest mechanisms maintaining immune variability.

Background An estimated 2.7 of the 5.9 million deaths in children under 5 years of age occur in the neonatal period. Severe infections contribute to almost a quarter of these deaths. Mortality due to severe infections in developing country settings is substantial despite antibiotic therapy. Effective interventions that can be added to standard therapy for severe infections are required to reduce case fatality. Methods/Design This is a double-blind randomized placebo-controlled parallel group superiority trial to investigate the effect of zinc administered orally as an adjunct to standard therapy to infants aged 3 days up to 2 months (59 days) hospitalized with clinical severe infection, that will be undertaken in seven hospitals in Delhi, India and Kathmandu, Nepal. In a 1:1 ratio, we will randomly assign young infants to receive 10 mg of elemental zinc or placebo orally in addition to the standard therapy for a total of 14 days. The primary outcomes hospital case fatality, which is death due to any cause and at any time after enrolment while hospitalized for the illness episode, and extended case fatality, which encompasses the period until 12 weeks after enrolment. Discussion A previous study showed a beneficial effect of zinc in reducing the risk of treatment failure, as well as a non-significant effect on case fatality. This study was not powered to detect an effect on case fatality, which this current study is. If the results are consistent with this earlier trial, we would have provided strong evidence for recommending zinc as an adjunct to standard therapy for clinical severe infection in young infants. Trial registration Universal Trial Number: U1111-1187-6479, Clinical Trials Registry – India: CTRI/2017/02/007966 : Registered on February 27, 2017.

The induction of CD80 on podocytes has been shown in animal models of podocyte injury and in certain cases of nephrotic syndrome. In a lipopolysaccharide (LPS)-induced mouse model of albuminuria, we have recently shown a signalling axis of LPS-myeloid cell activation-TNFα production-podocyte CD80 induction-albuminuria. Therefore, in this report, we investigated the cellular and molecular consequences of TNFα addition and CD80 expression on cultured podocytes. A murine podocyte cell line was used for TNFα treatment and for over-expressing CD80. Expression and localization of various podocyte proteins was analysed by reverse transcriptase-polymerase chain reaction, western blotting and immunofluorescence. HEK293 cells were used to biochemically characterize interactions. Podocytes treated with LPS in vitro did not cause CD80 upregulation but TNFα treatment was associated with an increase in CD80 levels, actin derangement and poor wound healing. Podocytes stably expressing CD80 showed actin derangement and co-localization with Neph1. CD80 and Neph1 interaction was confirmed by pull down assays of CD80 and Neph1 transfected in HEK293 cells. Addition of TNFα to podocytes causes CD80 upregulation, actin reorganization and podocyte injury. Overexpressed CD80 and Neph1 interact via their extracellular domain. This interaction implies a mechanism of slit diaphragm disruption and possible use of small molecules that disrupt CD80-Neph1 interaction as a potential for treatment of nephrotic syndrome associated with CD80 upregulation.

Background: Despite the benefits of exclusive breastfeeding (EBF), exposure to HIV from breast milk has relegated EBF to an option only when formula feeding is not affordable, feasible, safe, and sustainable. Mixed feeding remains the norm in sub-Saharan Africa. Objective: We evaluated whether the duration of EBF was associated with mortality and HIV infection in children followed to ≤5 y of age. Methods: A total of 690 mother-infant pairs from the Trial of Vitamins with information on infant feeding, HIV status, and at least one visit in the first year were included in the analysis. The duration of EBF was defined in months as a time-varying covariate at each follow-up visit. Associations of the duration of EBF with mortality, HIV infection, and HIV infection or death were estimated by using Cox proportional hazards models and Kaplan-Meier survival curves. Results: A 1-mo increase in EBF was associated with a 49% reduction in early infant mortality in the first 6 mo of life (RR: 0.51; 95% CI: 0.28, 0.93) and a nonsignificant 15% reduction in risk of HIV infection or death (RR: 0.85; 95% CI: 0.71, 1.01; P = 0.07) over the first 5 y of life. EBF was not associated with HIV infection (RR: 0.93; 95% CI: 0.76, 1.15). Conclusion: Longer EBF by HIV-positive mothers was associated with reduced mortality in the first 6 mo of life without increased HIV infection, which makes EBF the best option for women who cannot sustain exclusive formula feeding. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT00197743","term_id":"NCT00197743"}}NCT00197743.

Summary Background Serious bacterial infections are a major cause of death in early infancy in developing countries. Inexpensive and accessible interventions that can add to the effect of standard antibiotic treatment could reduce infant mortality. We measured the effect of zinc as an adjunct to antibiotics in infants with probable serious bacterial infection. Methods In this randomised, double-blind, placebo-controlled trial, we enrolled infants aged 7–120 days with probable serious bacterial infection at three hospitals in New Delhi, India, between July 6, 2005, and Dec 3, 2008. With computer-generated sequences, we randomly assigned infants in permuted blocks of six, stratified by whether patients were underweight or had diarrhoea at enrolment, to receive either 10 mg of zinc or placebo orally every day in addition to standard antibiotic treatment. The primary outcome was treatment failure, which was defined as a need to change antibiotics within 7 days of randomisation, or a need for intensive care, or death at any time within 21 days. Participants and investigators were masked to treatment allocation. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00347386. Findings 352 infants were randomly assigned to receive zinc and 348 to placebo. 332 given zinc and 323 given placebo could be assessed for treatment failure. Significantly fewer treatment failures occurred in the zinc group (34 [10%]) than in the placebo group (55 [17%]; relative risk reduction 40%, 95% CI 10–60, p=0·0113; absolute risk reduction 6·8%, 1·5–12·0, p=0·0111). Treatment of 15 (95% CI eight to 67) infants with zinc would prevent one treatment failure. Ten infants receiving zinc died compared with 17 given placebo (relative risk 0·57, 0·27–1·23, p=0·15). Interpretation Zinc could be given as adjunct treatment to reduce the risk of treatment failure in infants aged 7–120 days with probable serious bacterial infection. Funding Department of Biotechnology, Government of India; the European Commission; the Meltzer Foundation; and the Research Council of Norway.

To compare immune phenotypes across two geographic and ethnic communities, we examined umbilical cord blood by flow cytometry and Luminex in parallel cohorts of 53 newborns from New Delhi, India, and 46 newborns from Stanford, California. We found that frequencies of a B cell subset suggested to be B-1-like, and serum IgM concentration were both significantly higher in the Stanford cohort, independent of differences in maternal age. While serum IgA levels were also significantly higher in the Stanford cohort, IgG1, IgG2, and IgG4 were significantly higher in the New Delhi samples. We found that neutrophils, plasmacytoid dendritic cells, CD8+ T cells, and total T cells were higher in the U.S. cohort, while dendritic cells, patrolling monocytes (CD14dimCD16+), natural killer cells, CD4+ T cells, and naïve B cells were higher in the India cohort. Within the India cohort, we also identified cell types whose frequency was positively or negatively predictive of occurrence of infection(s) in the first six months of life. Monocytes, total T cells, and memory CD4+ T cells were most prominent in having an inverse relationship with infection. We suggest that these data provide impetus for follow-up studies linking phenotypic differences to environmental versus genetic factors, and to infection outcomes.

Limited resources for hospitalized treatment of India’s nearly 8 million children with severe acute malnutrition (SAM) make community management of SAM a priority. Capability to produce sufficient quantities of Ready to Use Therapeutic Food (RUTF) is one component of preparedness for community management of SAM. Production of RUTF is a simple process that consists of grinding, mixing and packaging using widely available equipment. Nitrogen flush packaging increases shelf life to 2 years though it is the most expensive and slowest step of the production process. Being a therapeutic product, quality and safety must be ensured including aflatoxin measurement and estimation of micronutrient and macronutrient content consistently. RUTF can be made in India in several production models — (i) Dairy cooperatives and private manufacturers can produce large quantities to meet regional requirements, (ii) small and niche food manufacturers can produce smaller volumes but have a major presence in most parts of India; and (iii) “hand made” RUTF can be made by “village industries” for immediate local consumption. All the ingredients and equipment for RUTF are widely available in India — RUTF is already being produced in India for export. Concerns from various sections of society will need to be heard before community management of SAM using therapeutic, processed nutritional products can begin. Despite apprehensions about processed RUTFs or the sections of the public health community that press for its use, withholding alternative treatment for one of the largest killers of India’s children must not be the option. It is time public health/ medical communities and civil society come together to make effective community management of SAM an immediate reality.

Zinc supplementation has been consistently shown to reduce the incidence of childhood pneumonia, but its effect on the course of pneumonia when administered as an adjunct to antibiotic therapy is still unclear. Three trials published to date have shown mixed results, and a recent trial from India raises the possibility that zinc may be detrimental in some circumstances. Study sites and designs differ, particularly in the timing of zinc treatment and in determining recovery from pneumonia, which can explain the differences in study findings. Serum zinc concentrations are unreliable indicators of zinc status, particularly during acute infectious illnesses. Subgroup analyses, especially using serum zinc levels, must be cautioned against. Future studies are needed that are large enough to be sufficiently powered to accommodate larger treatment failure rates, an issue that ongoing trials will hopefully address.

Zinc deficiency is common in children from developing countries due to lack of intake of animal foods, high dietary phytate content, inadequate food intake and increased fecal losses during diarrhea. Zinc has a fundamental role in cellular metabolism, with profound effects on the immune system and the intestinal mucosa. Zinc supplementation has shown significant benefits in prevention and treatment of diarrhea and pneumonia. Routine zinc supplementation given to low birth weight babies for a year has resulted in substantial reduction in mortality. Zinc deficiency may have adverse effects on physical growth and neurodevelopment. WHO Task Force, 2001, and the National task Force of IAP has recommended use of zinc in the treatment of diarrhea. It is also recommended as part of standard case management in persistent diarrhea and in those with severe malnutrition. Further evidence is required for qualifying its use in treatment of other infective diseases like pneumonia and malaria. Improved dietary quality & intake, food fortification and cultivation of zinc dense plants are some ways of mitigating zinc deficiency.

Background While infections are a major cause of neonatal mortality in India even in full-term neonates, this is an especial problem in the large proportion (~20%) of neonates born underweight (or small-for-gestational-age; SGA). One potential contributory factor for this susceptibility is the possibility that immune system maturation may be affected along with intrauterine growth retardation. Methods In order to examine the possibility that differences in immune status may underlie the susceptibility of SGA neonates to infections, we enumerated the frequencies and concentrations of 22 leukocyte subset populations as well as IgM and IgA levels in umbilical cord blood from full-term SGA neonates and compared them with values from normal-weight (or appropriate-for-gestational-age; AGA) full-term neonates. We eliminated most SGA-associated risk factors in the exclusion criteria so as to ensure that AGA-SGA differences, if any, would be more likely to be associated with the underweight status itself. Results An analysis of 502 such samples, including 50 from SGA neonates, showed that SGA neonates have significantly fewer plasmacytoid dendritic cells (pDCs), a higher myeloid DC (mDC) to pDC ratio, more natural killer (NK) cells, and higher IgM levels in cord blood in comparison with AGA neonates. Other differences were also observed such as tendencies to lower CD4:CD8 ratios and greater prominence of inflammatory monocytes, mDCs and neutrophils, but while some of them had substantial differences, they did not quite reach the standard level of statistical significance. Conclusions These differences in cellular lineages of the immune system possibly reflect stress responses in utero associated with growth restriction. Increased susceptibility to infections may thus be linked to complex immune system dysregulation rather than simply retarded immune system maturation.

BACKGROUND AND AIM: The World Health Organization recommends oral zinc (tablets or syrups) as adjunct therapy with oral rehydration solution (ORS) for acute childhood diarrhea. Mixing zinc with ORS can be an attractive approach for simultaneous provision of these 2 effective interventions. This double-masked randomized controlled trial evaluated the efficacy of ORS containing 40 mg/L elemental zinc per liter (zinc-ORS) in reducing stool weight and duration of diarrhea. PATIENTS AND METHODS: Five hundred northern Indian children ages 1 to 35 months with diarrhea

Zinc supplementation has been consistently shown to reduce the incidence of childhood pneumonia, but its effect on the course of pneumonia when administered as an adjunct to antibiotic therapy is still unclear. Three trials published to date have shown mixed results, and a recent trial from India raises the possibility that zinc may be detrimental in some circumstances. Study sites and designs differ, particularly in the timing of zinc treatment and in determining recovery from pneumonia, which can explain the differences in study findings. Serum zinc concentrations are unreliable indicators of zinc status, particularly during acute infectious illnesses. Subgroup analyses, especially using serum zinc levels, must be cautioned against. Future studies are needed that are large enough to be sufficiently powered to accommodate larger treatment failure rates, an issue that ongoing trials will hopefully address.