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1.  Revisiting Community Case Management of Childhood Pneumonia: Perceptions of Caregivers and Grass Root Health Providers in Uttar Pradesh and Bihar, Northern India 
PLoS ONE  2015;10(4):e0123135.
Community-acquired pneumonia (CAP) is the leading cause of under-five mortality globally with almost one-quarter of deaths occurring in India.
To identify predisposing, enabling and service-related factors influencing treatment delay for CAP in rural communities of two states in India. Factors investigated included recognition of danger signs of CAP, health care decision making, self-medication, treatment and referral by local practitioners, and perceptions about quality of care.
Qualitative research employing case studies (CS) of care-seeking, key informant interviews (KII), semi-structured interviews (SSI) and focus group discussions (FGD) with both video presentations of CAP signs, and case scenarios. Interviews and FGDs were conducted with parents of under-five children who had suffered CAP, community health workers (CHW), and rural medical practitioners (RMP).
From September 2013 to January 2014, 30 CS, 43 KIIs, 42 SSIs, and 42 FGDs were conducted. Recognition of danger signs of CAP among caregivers was poor. Fast breathing, an early sign of CAP, was not commonly recognized. Chest in-drawing was recognized as a sign of serious illness, but not commonly monitored by removing a child’s clothing. Most cases of mild to moderate CAP were brought to RMP, and more severe cases taken to private clinics in towns. Mothers consulted local RMP directly, but decisions to visit doctors outside the village required consultation with husband or mother-in-law. By the time most cases reached a public tertiary-care hospital, children had been ill for a week and treated by 2-3 providers. Quality of care at government facilities was deemed poor by caregivers.
To reduce CAP-associated mortality, recognition of its danger signs and the consequences of treatment delay needed to be better recognized by caregivers, and confidence in government facilities increased. The involvement of RMP in community based CAP programs needs to be investigated further given their widespread popularity.
PMCID: PMC4405201  PMID: 25898211
2.  Association of Adiponectin Gene Polymorphism with Adiponectin Levels And Risk for Insulin Resistance Syndrome 
Adiponectin is an abundant adipose tissue–derived protein with anti-atherogenic, anti-inflammatory and antidiabetic properties. Plasma adiponectin levels are decreased in obesity, type 2 diabetes, and coronary artery disease and low adiponectin levels also predict insulin resistance (IR).
Case-control study in which 642 male and female subjects were participated from the North Indian population. Lipid, insulin, leptin and adiponectin level were estimated using standard protocols by commercially available test kits. Single nucleotide polymorphisms +45T>G and +276G>T of the AMP1 (adiponectin) gene was genotyped by polymerase chain reaction restriction fragment length polymorphism method.
Levels of adiponectin, insulin, homeostasis model assessment-IR index (HOMA-IR index), systolic blood pressure and fat mass showed significant differences between male and female subjects. Serum adiponectin level showed highly significant association with both the +45 and the +276 genotypes. The common haplotype triglyceride (TG) showed a significantly lower adiponectin value than other haplotypes (P = 0.0001). A clear trend of decreasing adiponectin levels per copy of the common haplotype was observed. Nonobese insulin sensitive subjects showed a higher adiponectin value (P = 0.0006) than nonobese insulin resistant subjects. The values of blood pressure, adiponectin, insulin, HOMA-IR, total-cholesterol, and low-density lipoprotein-cholesterol significantly associated with TG haplotype.
We observed the very strong association of the adiponectin 45-276 genotypes and haplotypes with adiponectin levels in healthy north Indian population and TG haplotypes also associated with metabolic parameters of the IR syndrome.
PMCID: PMC4410438  PMID: 25949781
Adiponectin; AMP1; haplotype; insulin resistance; polymorphism
3.  Multicenter case–control study protocol of pneumonia etiology in children: Global Approach to Biological Research, Infectious diseases and Epidemics in Low-income countries (GABRIEL network) 
BMC Infectious Diseases  2014;14:635.
Data on the etiologies of pneumonia among children are inadequate, especially in developing countries. The principal objective is to undertake a multicenter incident case–control study of <5-year-old children hospitalized with pneumonia in developing and emerging countries, aiming to identify the causative agents involved in pneumonia while assessing individual and microbial factors associated with the risk of severe pneumonia.
A multicenter case–control study, based on the GABRIEL network, is ongoing. Ten study sites are located in 9 countries over 3 continents: Brazil, Cambodia, China, Haiti, India, Madagascar, Mali, Mongolia, and Paraguay. At least 1,000 incident cases and 1,000 controls will be enrolled and matched for age and date. Cases are hospitalized children <5 years with radiologically confirmed pneumonia, and the controls are children without any features suggestive of pneumonia. Respiratory specimens are collected from all enrolled subjects to identify 19 viruses and 5 bacteria. Whole blood from pneumonia cases is being tested for 3 major bacteria. S. pneumoniae-positive specimens are serotyped. Urine samples from cases only are tested for detection of antimicrobial activity. The association between procalcitonin, C-reactive protein and pathogens is being evaluated. A discovery platform will enable pathogen identification in undiagnosed samples.
This multicenter study will provide descriptive results for better understanding of pathogens responsible for pneumonia among children in developing countries. The identification of determinants related to microorganisms associated with pneumonia and its severity should facilitate treatment and prevention.
PMCID: PMC4272811  PMID: 25927410
Pneumonia; Children; Case–control; Etiology; Developing and emerging countries
4.  ADAM Metallopeptidase Domain 33 (ADAM33): A Promising Target for Asthma 
Mediators of Inflammation  2014;2014:572025.
Over the last few years, a significant progress has been made in understanding the role of a disintegrin and metalloproteinase 33 (ADAM33) in asthma. The previous observations for the association with asthma have been replicated in over 33 different population samples worldwide. We and others have performed association analysis and meta-analysis and provided further evidence that several polymorphisms in the ADAM33 are risk factors for asthma, especially in the Asian population. Further, several studies have suggested that alterations in epigenetic marks alter the patterns of DNA methylation of ADAM33 and result in potentially adverse biological effects. Finally, while the biological activities of ADAM33 are as yet unknown, ADAM33 may play a possible role in airway remodeling because of its high expression in epithelium, myo/fibroblasts, and airway smooth muscle cells (ASMCs) and its role in promoting angiogenesis and stimulating cell proliferation and differentiation. Thus, ADAM33 represents a promising target for asthma. However, further investigations are clearly needed to discover functional ADAM33 gene polymorphisms and the role of genetic/epigenetic factors in conferring genetic susceptibility to environmental exposure induced asthma as well as biological function in asthma. This, in turn, will unlock the possibility of ADAM33 as a target for asthma therapy.
PMCID: PMC4003756  PMID: 24817794
5.  Hypoadiponectinemia in Obesity: Association with Insulin Resistance 
Obesity is risk factor for insulin resistance, diabetes, and other chronic diseases. Adiponectin, an adipose-specific protein with antiatherogenic and antiinflammatory effects, were found to be associated with obesity, type 2 diabetes, and insulin resistance. Our aim to identify possible relationships between circulating adiponectin and obesity as well as obesity related phenotypes. A total of 642, obese and non-obese individuals were included in this cross-sectional study. Hormone and glucose levels were estimated using standard protocols. The adiponectin levels showed a significant decrease with increasing quartiles of insulin resistance index. Subjects in lowest quartile of adiponectin level had a significantly higher risk than those in the highest quartile, with higher body mass index, waist circumference, blood pressure, percentage body fat, fat mass, fasting insulin, insulin resistance index, total cholesterol (p < 0.001), low density lipoprotein–cholesterol (p = 0.001), very low density lipoprotein–cholesterol (p = 0.002), and Triglyceride (p = 0.002). The present study indicates that adiponectin is significantly associated with obesity, insulin resistance and other obesity related phenotypes.
PMCID: PMC3613499  PMID: 24426202
Adiponectin; Insulin resistance; Obesity; Phenotypes; Body mass index
6.  Performance criteria for verbal autopsy-based systems to estimate national causes of death: development and application to the Indian Million Death Study 
BMC Medicine  2014;12:21.
Verbal autopsy (VA) has been proposed to determine the cause of death (COD) distributions in settings where most deaths occur without medical attention or certification. We develop performance criteria for VA-based COD systems and apply these to the Registrar General of India’s ongoing, nationally-representative Indian Million Death Study (MDS).
Performance criteria include a low ill-defined proportion of deaths before old age; reproducibility, including consistency of COD distributions with independent resampling; differences in COD distribution of hospital, home, urban or rural deaths; age-, sex- and time-specific plausibility of specific diseases; stability and repeatability of dual physician coding; and the ability of the mortality classification system to capture a wide range of conditions.
The introduction of the MDS in India reduced the proportion of ill-defined deaths before age 70 years from 13% to 4%. The cause-specific mortality fractions (CSMFs) at ages 5 to 69 years for independently resampled deaths and the MDS were very similar across 19 disease categories. By contrast, CSMFs at these ages differed between hospital and home deaths and between urban and rural deaths. Thus, reliance mostly on urban or hospital data can distort national estimates of CODs. Age-, sex- and time-specific patterns for various diseases were plausible. Initial physician agreement on COD occurred about two-thirds of the time. The MDS COD classification system was able to capture more eligible records than alternative classification systems. By these metrics, the Indian MDS performs well for deaths prior to age 70 years. The key implication for low- and middle-income countries where medical certification of death remains uncommon is to implement COD surveys that randomly sample all deaths, use simple but high-quality field work with built-in resampling, and use electronic rather than paper systems to expedite field work and coding.
Simple criteria can evaluate the performance of VA-based COD systems. Despite the misclassification of VA, the MDS demonstrates that national surveys of CODs using VA are an order of magnitude better than the limited COD data previously available.
PMCID: PMC3912490  PMID: 24495287
Verbal autopsy; Physician-certified verbal autopsy; Cause of death statistics; Vital statistics; India
7.  Correction: Diarrhea, Pneumonia, and Infectious Disease Mortality in Children Aged 5 to 14 Years in India 
PLoS ONE  2013;8(11):10.1371/annotation/65b7652d-fad0-4595-90b1-77f9685cf25f.
PMCID: PMC3838729
8.  Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial 
Lancet  2013;381(9876):1478-1486.
In north India many pre-school children are underweight, many have intestinal worms, and 2–3% die at ages 1·0–6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality.
Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at age 1·0–6·0 years [the primary outcome]). This trial is registered at, NCT00222547.
Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0–6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI −0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0–6·0 years during the 5-year study were 3·00 (SE 0·07) albendazole versus 3·16 (SE 0·09) control, difference 0·16 (SE 0·11, mortality ratio 0·95, 95% CI 0·89 to 1·02, p=0·16), suggesting absolute risks of dying between ages 1·0 and 6·0 years of roughly 2·5% albendazole versus 2·6% control. No specific cause of death was significantly affected.
Existing ICDS village staff can be organised to deliver simple pre-school interventions sustainably for many years at low cost, but regular deworming had little effect on mortality in this lightly infected pre-school population.
UK Medical Research Council, USAID, World Bank (albendazole donated by GlaxoSmithKline).
PMCID: PMC3647147  PMID: 23498850
9.  Vitamin A supplementation every 6 months with retinol in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial 
Lancet  2013;381(9876):1469-1477.
In north India, vitamin A deficiency (retinol <0·70 μmol/L) is common in pre-school children and 2–3% die at ages 1·0–6·0 years. We aimed to assess whether periodic vitamin A supplementation could reduce this mortality.
Participants in this cluster-randomised trial were pre-school children in the defined catchment areas of 8338 state-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks (clusters) were cluster-randomly allocated in Oxford, UK, between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of retinol effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial vitamin A to sample blood (for retinol assay, technically reliable only after mid-study), examine eyes, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at ages 1·0–6·0 years [the primary outcome]). This trial is registered at, NCT00222547.
Estimated compliance with 6-monthly retinol supplements was 86%. Among 2581 versus 2584 children surveyed during the second half of the study, mean plasma retinol was one-sixth higher (0·72 [SE 0·01] vs 0·62 [0·01] μmol/L, increase 0·10 [SE 0·01] μmol/L) and the prevalence of severe deficiency was halved (retinol <0·35 μmol/L 6% vs 13%, decrease 7% [SE 1%]), as was that of Bitot's spots (1·4% vs 3·5%, decrease 2·1% [SE 0·7%]). Comparing the 36 retinol-allocated versus 36 control blocks in analyses of the primary outcome, deaths per child-care centre at ages 1·0–6·0 years during the 5-year study were 3·01 retinol versus 3·15 control (absolute reduction 0·14 [SE 0·11], mortality ratio 0·96, 95% CI 0·89–1·03, p=0·22), suggesting absolute risks of death between ages 1·0 and 6·0 years of approximately 2·5% retinol versus 2·6% control. No specific cause of death was significantly affected.
DEVTA contradicts the expectation from other trials that vitamin A supplementation would reduce child mortality by 20–30%, but cannot rule out some more modest effect. Meta-analysis of DEVTA plus eight previous randomised trials of supplementation (in various different populations) yielded a weighted average mortality reduction of 11% (95% CI 5–16, p=0·00015), reliably contradicting the hypothesis of no effect.
UK Medical Research Council, USAID, World Bank (vitamin A donated by Roche).
PMCID: PMC3647148  PMID: 23498849
10.  Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children 
Background & objectives:
Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance.
Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens.
A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively).
Interpretation & conclusions:
Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.
PMCID: PMC3724251  PMID: 23703338
Haemophilus influenzae type B; meningitis; surveillance
11.  Increased expression of ADAM33 protein in asthmatic patients as compared to non-asthmatic controls 
Background & objectives:
ADAM33 is a member of a family of genes that encode membrane-anchored proteins with a disintegrin and a metalloprotease domain, primarily expressed in lung fibroblasts and bronchial smooth muscle cells. ADAM33 has been identified as a risk factor for asthma and is known as a gene associated with airway remodelling. The present study was conducted with the aims to investigate the expression of ADAM33 protein in patients of asthma and non-asthmatic controls, and to assess if the expression of ADAM33 protein relates with severity of asthma.
A total of 35 subjects, including 27 patients with asthma and eight non-asthmatic controls were included using Global Initiative for Asthma guidelines 2005. Bronchial biopsy tissues were collected and paraffin sections were made to store all study samples. Immunohistochemistry was performed using standardized protocol.
An increase in expression of ADAM33 protein was observed in the epithelium, smooth muscle and mesenchymal cells of asthma cases when compared to controls but there was no relationship with severity of asthma.
Interpretation & conclusions:
A higher expression of ADAM33 protein was seen in asthma patients compared to controls. Large prospective studies need to be done with adequate study design to confirm these preliminary finding.
PMCID: PMC3705658  PMID: 23640557
ADAM33 protein expression; asthma; bronchial biopsy; immunohistochemistry; severity of asthma
12.  Cytokine Gene Polymorphism in Idiopathic Nephrotic Syndrome Children 
The pathogenesis of idiopathic nephrotic syndrome is not completely understood. We postulate that cytokine gene polymorphisms may influence susceptibility or clinical course in Idiopathic Nephrotic Syndrome. Polymorphisms of IL-4, IL-6, and TNF-α cytokines were investigated in 150 children with Idiopathic Nephrotic Syndrome and 569 healthy controls by using polymerase chain reaction and restriction fragment length polymorphism. On comparing patient with controls strong association were found for IL-6, TNF-α and IL-4 at allelic level (IL-6-G174C (G vs. C): P = <0.001; OR = 6.33, TNF-α-G308A (G vs. A): P = <0.001; OR = 1.99, IL-4-C590T (C vs. T): P = 0.048; OR = 1.38). Further when SR group was compared with SS group significant association was found at genotypic level in all the studied genetic polymorphisms. Studied cytokine gene polymorphisms may influence susceptibility to idiopathic nephrotic syndrome and might affect steroid response in INS patients.
PMCID: PMC3162962  PMID: 22754196
Idiopathic nephrotic syndrome; IL-6; IL-4; TNF-α; PCR; RFLP
13.  Association of CFTR gene mutation with bronchial asthma 
Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.
PMCID: PMC3385229  PMID: 22664493
Asthma; CFTR; cystic fibrosis; heterozygous; modifier genes; phenotype
14.  Socio Demographic Determinants and Knowledge, Attitude, Practice: Survey of Family Planning 
Understanding of family planning scenario among different societies and communities, which by and large reside in urban slum and rural areas, might prove useful in increasing family planning acceptance by them and decreasing population growth.
To assess the sociodemographic determinants and KAP of family planning among urban slum and rural areas of Lucknow.
Study Design:
Cross sectional.
Bal Mahila Chikitsalaya, Aliganj, in urban and Primary Health Centre, Bakshi Ka Talaab, in rural area of Lucknow.
Study Period:
October 2008 to April 2009.
Materials and Methods:
Six hundred and eightytwo postpartum women (within 42 days of delivery) who came to these health facilities for their child's vaccination were interviewed, by a preformed and pretested schedule.
Maximum utilization of family methods were seen among Hindu women, women of age group 30 or more, parity four and more, educational level upto high school and above and those of higher socioeconomic class. Although overall residential area (urban or rural) of women had no influence on the practice of family planning by them and all of them were willing to adopt family planning methods in future, urban women were found to have a higher level of knowledge and attitude toward modern methods of family planning. Only 2.8% were unsure of preferred method for future use.
Family planning programs which effectively promotes the use of family planning methods, so that the trend toward increase in population could be arrested is the need of hour.
PMCID: PMC3893950  PMID: 24479000
Attitude; family planning; knowledge; practice; sociodemographic determinants
15.  Intravenous device associated blood stream staphylococcal infection in paediatric patients 
Background & objectives:
Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are major cause of morbidity and mortality. The present study was carried out to assess the frequency of staphylococcal IVD associated infections in a paediatric ward of a tertiary case hospital. Prevalence of resistance to commonly used antimicrobials in hospital acquired staphylococcal isolates was also tested.
Children admitted in paediatric wards with IVD for more than 48 h were enrolled. Blood, IVD tip at the time of removal, skin swab at the site of insertion of IVD and nasal swab were collected and cultured by standard protocol. All staphylococcal isolates from any source were analyzed for antimicrobial susceptibility by disk diffusion method. Genotyping matching of those staphylococcal isolates was done which were isolated from different sites of the same patient, but were phonotypically similar. Genotype of blood isolate was compared with genotype of isolate from nose/IVD/skin.
Staphylococcus aureus was the most frequent blood isolate (8.7%) followed by Candida (2.9%), coagulase negative staphylococci (CoNS 2.6%), Pseudomonas spp. (0.4%), Klebsiella spp. (0.3%) and Escherichia coli (0.1%). Isolation of microorganisms from blood was significantly higher in patients whose skin, IVD and nose were colonized by same microorganism (P<0.001). None of the staphylococcal isolate was found to be resistant to glycopeptides (vancomycin and teicoplanin). High penicillin and oxacillin resistance was present in both S. aureus (penicillin resistance; 76.8%, oxacillin resistance; 66.7%) and CoNS (penicillin resistance; 73.3%, oxacillin resistance; 60.0%). Among CoNS biotypes, S. haemolyticus was commonest blood isolate while S. epidermidis was commonest isolate from Skin/nose. Only 33.3 per cent of S. aureus blood stream infections and most of S. epidermidis and S. haemolyticus blood infections were IVD associated.
Interpretation & conclusions:
Staphylococci were the major causative agent of nosocomial blood stream infections. All episodes of septicaemia due to S. epidermidis and S. haemolyticus were IVD associated while only 1/3 of S. aureus septicaemia was IVD associated.
PMCID: PMC3181020  PMID: 21911972
Coagulase negative staphylococci; hospital acquired septicaemia; IVD associated staphylococcal septicaemia; Staphylococcus aureus
16.  Diarrhea, Pneumonia, and Infectious Disease Mortality in Children Aged 5 to 14 Years in India 
PLoS ONE  2011;6(5):e20119.
Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years.
A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001–03 in 1·1 million homes in India.
Infectious diseases accounted for 58% of all deaths among children aged 5 to 14 years. About 18% of deaths were due to diarrheal diseases, 10% due to pneumonia, 8% due to central nervous system infections, 4% due to measles, and 12% due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24·1 and 13·9 per 100 000 respectively. Mortality was nearly 50% higher in girls than in boys for both diarrheal diseases and pneumonia.
Approximately 60% of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea in particular, is much higher than previously estimated.
PMCID: PMC3101242  PMID: 21629660
17.  Role of ADAM33 gene and associated single nucleotide polymorphisms in asthma 
Allergy & Rhinology  2011;2(2):e63-e70.
Asthma is a multifactorial disorder, primarily resulting from interactions between genetic and environmental factors. ADAM33 gene (located on chromosome 20p13) has been reported to play an important role in asthma. This review article is intended to include all of the publications, to date, which have assessed the association of ADAM33 gene polymorphisms as well as have shown the role of ADAM33 gene in airway remodeling and their expression with asthma. A PubMed search was performed for studies published between 1990 and 2010. The terms “ADAM33,” “ADAM33 gene and asthma,” and “ADAM33 gene polymorphisms” were used as search criteria. Based on available literature we can only speculate its role in the morphogenesis and functions of the lung. Fourteen studies conducted in different populations were found showing an association of ADAM33 gene polymorphisms with asthma. However, none of the single nucleotide polymorphisms (SNPs) of ADAM33 gene had found association with asthma across all ethnic groups. Because higher expression of ADAM33 is found in the fibroblast and smooth muscle cells of the lung, over- or underexpression of ADAM33 gene may result in alterations in airway remodeling and repair processes. However, no SNP of ADAM33 gene showed significant associations with asthma across all ethnic groups; the causative polymorphism, if any, still has to be identified.
PMCID: PMC3390120  PMID: 22852121
ADAM33; airway remodeling; association studies; asthma; bronchial hyperresponsiveness; chronic inflammatory disorder; multifactorial disorder; pathogenesis of asthma; positional cloning; single-nucleotide polymorphism
18.  Pharmacogenomics of pediatric asthma 
Indian Journal of Human Genetics  2010;16(3):111-118.
Asthma is a complex disease with multiple genetic and environmental factors contributing to it. A component of this complexity is a highly variable response to pharmacological therapy. Pharmacogenomics is the study of the role of genetic determinants in the variable response to therapy. A number of examples of possible pharmacogenomic approaches that may prove of value in the management of asthma are discussed below.
A search of PubMed, Google scholar, E-Medicine, BMJ and Mbase was done using the key words “pharmacogenomics of asthma”, “pharmacogenomics of β-agonist, glucocorticoids, leukotriene modifiers, theophylline, muscarinic antagonists in asthma”.
Presently, there are limited examples of gene polymorphism that can influence response to asthma therapy. Polymorphisms that alter response to asthma therapy include Arg16Gly, Gln27Glu, Thr164Ile for β-agonist receptor, polymorphism of glucocorticoid receptor gene, CRHR1 variants and polymorphism of LTC4S, ALOX5. Polymorphic variants of muscarinic receptors, PDE4 and CYP450 gene variants.
It was concluded that genetic variation can improve the response to asthma therapy. However, no gene polymorphism has been associated with consistent results in different populations. Therefore, asthma pharmacogenomic studies in different populations with a large number of subjects are required to make possible tailoring the asthma therapy according to the genetic characteristic of individual patient.
PMCID: PMC3009420  PMID: 21206697
Asthma; pharamacogenomics; polymorphism; variability in response
19.  Intestinal nematode infection and anaemia in developing countries 
BMJ : British Medical Journal  2007;334(7603):1065-1066.
Deworming and iron supplementation are cheap and effective
PMCID: PMC1877965  PMID: 17525401
20.  Factors Associated with Physician Agreement on Verbal Autopsy of over 27000 Childhood Deaths in India 
PLoS ONE  2010;5(3):e9583.
Each year, more than 10 million children younger than five years of age die. The large majority of these deaths occur in the developing world. The verbal autopsy (VA) is a tool designed to ascertain cause of death in such settings. While VA has been validated against hospital diagnosed cause of death, there has been no research conducted to better understand the factors that may influence individual physicians in determining cause of death from VA.
Methodology/Principal Findings
This study uses data from over 27,000 neonatal and childhood deaths from The Million Death Study in which 6.3 million people in India were monitored for vital status between 1998 and 2003. The main outcome variable was physician agreement or disagreement of category of death and the variables were assessed for association using the kappa statistic, univariate and multivariate logistic regression using a conceptual hierarchical model, and a sensitivity and specificity analysis using the final VA category of mortality as the gold standard. The main variables found to be significantly associated with increased physician agreement included older ages and male gender of the deceased. When taking into account confounding factors in the multivariate analysis, we did not find consistent significant differences in physician agreement based on the death being in a rural or urban area, at home or in a health care facility, registered or not, or the respondent's gender, religion, relationship to the deceased, or whether or not the respondent lived with the deceased.
Factors influencing physician agreement/disagreement to the greatest degree are the gender and age of the deceased; specifically, physicians tend to be less likely to agree on a common category of death in female children and in younger ages, particularly neonates. Additional training of physician reviewers and continued adaptation of the VA itself, with a focus on gender and age of the deceased, may be useful in increasing rates of physician agreement in these groups.
PMCID: PMC2833201  PMID: 20221398
21.  Open letter to the leader of academic medicine 
BMJ : British Medical Journal  2007;334(7586):191-193.
As their campaign comes to a close, ICRAM presents a challenge to academic medicine's invisible leaders
PMCID: PMC1782025  PMID: 17255613
22.  Gender inequity and age-appropriate immunization coverage in India from 1992 to 2006 
A variety of studies have considered the affects of India's son preference on gender differences in child mortality, sex ratio at birth, and access to health services. Less research has focused on the affects of son preference on gender inequities in immunization coverage and how this may have varied with time, and across regions and with sibling compositions. We present a systematic examination of trends in immunization coverage in India, with a focus on inequities in coverage by gender, birth order, year of birth, and state.
We analyzed data from three consecutive rounds of the Indian National Family Health Survey undertaken between 1992 and 2006. All children below five years of age with complete immunization histories were included in the analysis. Age-appropriate immunization coverage was determined for the following antigens: bacille Calmette-Guérin (BCG), oral polio (OPV), diphtheria, pertussis (whooping cough) and tetanus (DPT), and measles.
Immunization coverage in India has increased since the early 1990s, but complete, age-appropriate coverage is still under 50% nationally. Girls were found to have significantly lower immunization coverage (p<0.001) than boys for BCG, DPT, and measles across all three surveys. By contrast, improved coverage of OPV suggests a narrowing of the gender differences in recent years. Girls with a surviving older sister were less likely to be immunized compared to boys, and a large proportion of all children were found to be immunized considerably later than recommended.
Gender inequities in immunization coverage are prevalent in India. The low immunization coverage, the late immunization trends and the gender differences in coverage identified in our study suggest that risks of child mortality, especially for girls at higher birth orders, need to be addressed both socially and programmatically.
Abstract in Hindi
See the full article online for a translation of this abstract in Hindi.
PMCID: PMC3226235  PMID: 19828061
23.  Care-seeking behavior and out-of-pocket expenditure for sick newborns among urban poor in Lucknow, northern India: a prospective follow-up study 
The state of Uttar Pradesh, India accounts for one-quarter of India's neonatal deaths and 8 percent of those worldwide. More than half (52%) of these deaths occur due to infections. In order to achieve Millennium Development Goal-4 of reducing child mortality by two-thirds by the year 2015, it is important to study factors which affect neonatal health. In Uttar Pradesh there is meager data for spending on health care in general and neonates in particular.
The study was conducted at an urban Reproductive and Child Health (RCH) center and a District hospital. Neonates were enrolled within 48 hours of birth and were followed-up once at 6 weeks ± 15 days at the OPD of the respective hospitals or at home. This study assessed (1) distribution of neonatal illnesses and different health providers sought (2) distribution of out-of-pocket expenditures by type of illness and type of health provider sought (3) socio-economic distribution of neonatal illnesses, care-seeking behavior and out-of-pocket expenditures. Per-protocol analysis was performed.
Five hundred and ten neonates were enrolled and 481(94.4%) were followed-up. Parents of 50.3% (242/481) neonates reported at least one symptom of illness. Of these 22.3% (107/481) neonates had illnesses with at least one reported Integrated Management of Neonatal and Childhood Illnesses (IMNCI) danger sign. Among IMNCI illnesses, point prevalence of septicemia was 6.2% and pneumonia was 5.2% while among non-IMNCI illnesses point prevalence of upper respiratory infection was 9.5%, and diarrhea was 7%. Community based non-government dispensers (NGDs) were leading health providers (37.6%). Mean monthly income of families was 2804 Indian Rupees (INR) (range: 800 to 14000; n = 510), where US$ 1 = 42 INR. Mean out-of-pocket expenditure on neonatal illness was 547.5 INR (range: 1 to 15000; n = 202) and mean out-of-pocket expenditure for hospitalization was 4993 INR (range: 41 to 15000; n = 17). All hospitalizations were for IMNCI illnesses. Neonates from lower income strata were less likely to receive any medical care (p < 0.0001) and were also less likely to be seen by a Government provider (p = 0.03).
Since more than half of the neonates have morbidity and out-of-pocket expenditure on neonatal illnesses often exceeds the family income of the lower strata of the low income group in the community, there is a need to either introduce health insurance scheme or subsidize health care for them. Also, since NGDs, half of which could be unqualified are leading health providers, qualified medical care-seeking for sick newborns should be promoted in urban Lucknow.
PMCID: PMC2676263  PMID: 19341473
24.  Gender Differences in Perception and Care-seeking for Illness of Newborns in Rural Uttar Pradesh, India 
Although gender-based health disparities are prevalent in India, very little data are available on care-seeking patterns for newborns. In total, 255 mothers were prospectively interviewed about their perceptions and action surrounding the health of their newborns in rural Uttar Pradesh, India. Perception of illness was significantly lower in incidence (adjusted odds ratio=0.56, 95% confidence interval 0.33-0.94) among households with female versus male newborns. While the overall use of healthcare providers was similar across gender, the average expenditure for healthcare during the neonatal period was nearly four-fold higher in households with males (Rs 243.3±537.2) compared to females (Rs 65.7±100.7) (p=0.07). Households with female newborns used cheaper public care providers whereas those with males preferred to use private unqualified providers perceived to deliver more satisfactory care. These results suggest that, during the neonatal period, care-seeking for girls is neglected compared to boys, laying a foundation for programmes and further research to address gender differences in neonatal health in India.
PMCID: PMC2761808  PMID: 19248649
Healthcare-seeking behaviour; Equity; Gender; Health expenditure; Healthcare-use; Neonatal health; Perceptions; Rural health; India
25.  Does 3-Day Course of Oral Amoxycillin Benefit Children of Non-Severe Pneumonia with Wheeze: A Multicentric Randomised Controlled Trial 
PLoS ONE  2008;3(4):e1991.
WHO-defined pneumonias, treated with antibiotics, are responsible for a significant proportion of childhood morbidity and mortality in the developing countries. Since substantial proportion pneumonias have a viral etiology, where children are more likely to present with wheeze, there is a concern that currently antibiotics are being over-prescribed for it. Hence the current trial was conducted with the objective to show the therapeutic equivalence of two treatments (placebo and amoxycillin) for children presenting with non-severe pneumonia with wheeze, who have persistent fast breathing after nebulisation with salbutamol, and have normal chest radiograph.
This multi-centric, randomised placebo controlled double blind clinical trial intended to investigate equivalent efficacy of placebo and amoxicillin and was conducted in ambulatory care settings in eight government hospitals in India. Participants were children aged 2–59 months of age, who received either oral amoxycillin (31–54 mg/Kg/day, in three divided doses for three days) or placebo, and standard bronchodilator therapy. Primary outcome was clinical failure on or before day- 4.
Principal Findings
We randomized 836 cases in placebo and 835 in amoxycillin group. Clinical failures occurred in 201 (24.0%) on placebo and 166 (19.9%) on amoxycillin (risk difference 4.2% in favour of antibiotic, 95% CI: 0.2 to 8.1). Adherence for both placebo and amoxycillin was >96% and 98.9% subjects were followed up on day- 4. Clinical failure was associated with (i) placebo treatment (adjusted OR = 1.28, 95% CI: 1.01 to1.62), (ii) excess respiratory rate of >10 breaths per minute (adjusted OR = 1.51, 95% CI: 1.19, 1.92), (iii) vomiting at enrolment (adjusted OR = 1.49, 95% CI: 1.13, 1.96), (iv) history of use of broncho-dilators (adjusted OR = 1.71, 95% CI: 1.30, 2.24) and (v) non-adherence (adjusted OR = 8.06, 95% CI: 4.36, 14.92).
Treating children with non-severe pneumonia and wheeze with a placebo is not equivalent to treatment with oral amoxycillin.
Trial Registration NCT00407394
PMCID: PMC2292255  PMID: 18431478

Results 1-25 (34)