Oral rehydration therapy: the simple solution for saving lives.
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Child↗
Biomedical subjects
M K Bhan
Publications and source records attributed to M K Bhan.
Quantitative evaluation of rotaviral antigenemia in children with acute rotaviral diarrhea.
BACKGROUND: Rotaviral antigen and RNA have recently been identified in the serum of patients with rotaviral gastroenteritis, but the roles they play in disease remains undetermined. METHODS: Rotaviral antigen and RNA were quantified by enzyme-linked immunosorbant assay and by quantitative reverse-transcription polymerase chain reaction in stool and serum specimens from children with rotaviral diarrhea (n=102), children with nonrotaviral diarrhea (n=40), and nondiarrheal control children (n=30). RESULTS: Rotaviral antigenemia was detected in 64%, 3%, and 0% of the children with rotaviral diarrhea, the children with nonrotaviral diarrhea, and the nondiarrheal control children, respectively. The level of rotaviral antigen in serum was approximately 2x10(2) -fold lower than that in stool, and a moderate correlation was observed between the 2 levels. Rotaviral RNA was detected in 93% of the antigen-positive serum specimens. The median number of RNA copies in serum was approximately 1 x 10(5) -fold lower than that in stool, and no correlation was observed between the 2 levels. Serum levels of both antigen and RNA were inversely associated with baseline titers of rotaviral serum immunoglobulin G (P<.01). Antigenemia was also associated with G1 serotype. CONCLUSIONS: Rotaviral antigenemia and viremia were common in children with rotaviral diarrhea, but antigen and RNA levels in serum were substantially lower than those in stool. Antigenemia was associated with infection with G1 strains and with low baseline titers of rotaviral serum antibody.
Antigens, Viral↗
Polymorphism in L-selectin, E-selectin and ICAM-1 genes in Asian Indian pediatric patients with celiac disease.
Celiac disease (CD) follows an autoimmune course in which both genetic and environmental factors contribute to its development. A strong association with HLA class II molecules, predominantly HLA-DQ2, has been reported in most ethnic groups with CD. The aim of this study was to determine if genetic polymorphisms in L-selectin, E-selectin, and intercellular adhesion molecule-1 (ICAM-1) have any correlation with CD. We investigated 5 mutations, namely F206L in L-selectin, S128R and L554F in E-selectin, and G241R and K469E in ICAM-1, in 37 North Indian pediatric patients with CD. A significant increase in allele frequencies of 128R of E-selectin and the associated genotype SR was observed in patients. No significant differences were observed in the F206L polymorphism of L-selectin, or the G241R and E469K polymorphisms in the ICAM-1 gene in CD. This study illustrates that selectin gene polymorphism might contribute to the genetic background of CD and invites further investigation relevant to understanding the mechanisms underlying the immunopathogenesis of this autoimmune disease.
Alleles↗
Safety and immunogenicity of two live attenuated human rotavirus vaccine candidates, 116E and I321, in infants: results of a randomised controlled trial.
We evaluated safety and immunogenicity of two orally administered human rotavirus vaccine candidates 116E and I321. Ninety healthy infants aged 8 weeks received a single dose of 116E (10(5)FFu (florescence focus units)), I321 (10(5)FFu) or placebo. There were no significant differences in the number of adverse events. Fever was reported by 6/30, 1/30 and 5/30 in the 116E, I321 and placebo groups; the corresponding figures for diarrhoea were 5/30, 8/29 and 3/30. Serum IgA seroconversion rates were 73%, 39% and 20% in the 116E, I321 and placebo groups, respectively. Vaccine virus was shed on days 3, 7 or 28 in 11/30 infants of the 116E and none in the other two groups. The 116E strain is attenuated, clinically safe and highly immunogenic with a single dose.
Double-Blind Method↗
Incidence of severe rotavirus diarrhea in New Delhi, India, and G and P types of the infecting rotavirus strains.
A total of 62,475 children <5 years old from a defined population of approximately 500,000 children and adults from slums in New Delhi, India, were assessed for 1 year by means of passive surveillance, to identify children who were hospitalized for diarrhea. The incidence of severe rotavirus diarrhea was estimated, and the G and P types of the infecting rotavirus strains were determined and were correlated with the clinical severity of diarrhea. Of 584 children who were hospitalized with diarrhea, 137 (23.5%) had rotavirus detected in stool specimens (incidence of rotavirus diarrhea-associated hospitalizations, 337 hospitalizations/100,000 children <5 years of age). Most cases of diarrhea (98%) occurred during the first 2 years of life, peaking at 9-11 months of age. Rotavirus-associated diarrhea occurred year-round but was predominant in winter. Among the strains that could be G-typed, G1 was the most common serotype, followed by G9 and G2; 10% of cases of diarrhea were due to mixed G-type infections. Common strains identified in the present surveillance study were P[8]G1, P[4]G2, P[8]G9, P[6]G1, P[6]G9, and P[6]G3. Children infected with G1 strains had a greater risk of developing more-severe cases of diarrhea than did children infected with other rotavirus strains (odds ratio, 2.95; 95% confidence interval, 1.3-6.67).
Adult↗
Variability pattern and correlation studies in Silybum marianum Gaertn.
Phenotypic and genotypic coefficient of variability, heritability in broad sense and genetic advance were determined investigating the characters of 15 accessions of Silybum marianum. Seed yield/plant and number of capsules/plant had highest estimates of genotypic variation, heritability and genetic advance which suggest that direct selection for these traits is suitable for the improvement of this crop. Number of capsules/plant had a significant positive correlation with the number of branches/plant and leaf length (r=0.3398, 0.7547), whereas seed yield/plant had a positive significant correlation with leaf length, stem diameter, capsule diameter and silymarin content (r=0.6830, 0.3140, 0.3484, 0.2925).
Genetic Variation↗
Possible role of neonatal infection with the asymptomatic reassortant rotavirus (RV) strain I321 in the decrease in hospital admissions for RV diarrhea, Bangalore, India, 1988-1999.
We sought to determine the proportion of rotavirus (RV) infections among children with severe diarrhea in Bangalore, India, and to determine the role of neonatal infection with the asymptomatic RV strain I321 in protection against subsequent RV diarrhea. At 2 major hospitals, there was a >42% decrease in diarrhea-specific admissions during the study period. At 6 hospitals, asymptomatic infections were found in 25%-50% of neonates, when screening was performed randomly, and in >58% of neonates, when screening was performed daily, with the majority of infections occurring within the first 7 days of life. All the RVs found in asymptomatic neonates were strain I321. A 24-month follow-up of a cohort of 44 children who had been neonatally infected with strain I321 and 28 children who had not (control group) revealed comparable rates of RV detection but a marked decrease in the number of RV diarrhea episodes in the strain I321-infected group (2.3%), compared with the control group (39.3%) (P<.0001). This preliminary study suggests a possible association between neonatal infection with strain I321 and protection against subsequent RV illness.
Age Factors↗
Zinc supplementation for four months does not affect plasma copper concentration in infants.
AIM: The aim of the present study, which was undertaken as a sub-study within a randomized controlled trial of zinc supplementation, was to evaluate the effect of prolonged zinc supplementation on copper status as assessed by hematological markers. METHODS: Plasma copper and zinc were estimated at baseline and after 120 d of supplementation in a randomly selected infant subset (115) of the children. Of these, 61 children were in a zinc group (Z) getting 10 mg of elemental zinc, and 54 were in a control group (C) getting supplement without zinc. RESULTS: Baseline plasma zinc was comparable in the two groups; post-supplementation zinc was significantly higher (Z 93.0 +/- 3.6 vs C 60.6 +/- 8.0) in the zinc supplementation group. There was no significant difference in the mean/median copper levels between the zinc and control groups. The percentage of children with plasma copper <100 microg/dl was also not significantly different between groups (baseline Z 14.8%, C 11.1%; post-supplementation Z 18.0%, C 11.1%). There were no differences between the zinc and control groups after 120 d of supplementation in hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), or number of lymphocytes or granulocytes. CONCLUSION: Zinc supplementation of 10 mg/d for 4 mo in this study did not affect copper status, as assessed by plasma copper concentration and hematological parameters, diagnostics of copper deficiency.
Copper↗
Consensus Statement of IAP National Task Force: status report on management of acute diarrhea.
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Antiemetics↗
Racecadotril-is there enough evidence to recommend it for treatment of acute diarrhea?
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Antidiarrheals↗
Bacteriuria and urinary tract infections in malnourished children.
We prospectively examined the incidence of bacteriuria in malnourished patients between 6 months and 5 years of age. For each patient, a normally nourished control matched for age, sex, and presence of fever and diarrhea was included. Of 112 patients (65 boys), 55 had moderate and 57 had severe malnutrition; 43 had diarrhea and 35 had fever. Clean-catch and suprapubic urine specimens were examined microscopically and cultured. Significant bacteriuria was found in 17 (15.2%) malnourished and 2 (1.8%) control subjects ( P<0.01). The incidence of bacteriuria in malnourished and normally nourished subjects with fever was 28.6% and 5.7%, respectively ( P<0.05). The risk of bacteriuria increased significantly with the severity of malnutrition and in patients with diarrhea. Bacteriuria was associated with symptoms (70.6%) and elevated levels of acute-phase reactants (88.2%), indicating the presence of urinary tract infections (UTI) rather than asymptomatic colonization. Our observations show that malnourished children, particularly those with fever, are at risk for UTI. Urinalysis is useful for screening for UTI in these subjects. Urine culture should be performed in patients showing an abnormal urinalysis, and if the likelihood of detecting bacteriuria is high (as in patients with fever or diarrhea). Significant bacteriuria in malnourished subjects should be treated with appropriate antimicrobials.
Acute-Phase Proteins↗
Molecular characterization of serotype G2 and G3 human rotavirus strains that have an apparently identical electropherotype of the short RNA pattern.
The literature is conflicting whether or not rotavirus strains with different G serotype have an identical electropherotype. This is a contentious but an important issue because large parts of molecular epidemiological studies of rotaviruses have been based on the conception that a single strain of rotavirus can be defined by a single electropherotype. Here, we examined in detail by reverse-transcription PCR genotyping, electropherotyping, sequencing, and genogrouping using RNA--RNA hybridization three human rotavirus strains isolated in India that had apparently identical electropherotypes although one strain was typed as P[4], G3 while the other two typed as P[4], G2. These three strains showed an identical electropherotype on 7.5% and 12.5% polyacrylamide gels, but co-electrophoresis on a 10% gel demonstrated that segment 8 of the P[4], G3 strain migrated more slowly than the cognate segment of the P[4], G2 strains. Genogrouping assay and nucleotide sequencing provided evidence for the hypothesis that the P[4], G3 stain was an intergenogroup reassortant in which a P[4], G2 strain of the DS-1 genogroup had acquired the VP7 gene from an yet-unidentified concurrently circulating G3 strain. While electropherotyping remains a valuable asset for molecular epidemiology of rotaviruses, this study underscores the importance of co-electrophoresis under different electrophoretic conditions when pinpointing subtle differences.
Antigens, Viral↗
Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes.
The role of human leukocyte antigen (HLA) DQ2 heterodimer (DQA1*0501-DQB1*0201) in presenting gluten peptides to effector T cells in celiac disease (CD) has been well documented. Because HLA-DQ2 is carried on DR3 haplotypes due to linkage disequilibrium, such haplotypes are encountered more frequently in patients with autoimmune disease. This study analyzed 35 North Indian children below 15 years of age and diagnosed to have CD as per the ESPGAN criteria, which included histopathologic alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of antiendomysial antibodies. The HLA class I and class II alleles were determined by polymerase chain reaction-sequence-specific primers, sequence-specific oligonucleotide probe, and reverse line strip molecular techniques. A statistically significant positive association of the disease with HLA-DRB1*03 (94.2% versus 22.1% in controls, chi(2) = 73.4, p = 7.54E-11), and a negative association with DRB1*15 (chi(2) = 7.4, p = 6.5E-03) and DRB1*13 alleles was observed. The HLA-DQB1*0201 was observed in all the 35 patients (100%), whereas the DQ2 heterodimer alpha(0)beta(0) occurred in 97.1% of CD patients (31.4% in double dose, 65.7% in single dose) and revealed significant deviation from healthy controls (chi(2) = 102.08, p = 7.56E-11). Further analysis revealed involvement of multiple DR3+ve haplotypes with CD in Indians, of which A26-B8-DR3 was the most common DR3 haplotype among patients (34.28%, chi(2) = 40.57, p = 2.65E-10) followed by Ax-B21-DR3 (11.4%) (chi(2) = 13.8, p = 2E-04) and the classical Caucasian haplotype A1-B8-DR3 (5.7%). The former two haplotypes are characteristic of Asian Indians and are involved in the development of CD. We conclude that the high risk DR3 haplotypes that play a crucial role in the development of CD are unique in Asian Indians. Detailed analysis of these haplotypes in Indian patients with autoimmune diseases may help understand the influence of other intervening genes within the major histocompatibility complex.
Adolescent↗
Effect of vitamin A administered at Expanded Program on Immunization contacts on antibody response to oral polio vaccine.
OBJECTIVE: Vitamin A supplementation to mothers in the postpartum period and to their infants at routine immunization contacts is being considered to reduce vitamin A deficiency in infancy. This study was conducted to determine the impact of maternal and infant vitamin A supplementation on antibody response to oral polio vaccine (OPV). DESIGN: Randomized, double blind, placebo-controlled trial. INTERVENTIONS: Mothers in the intervention group received 60 mg retinol equivalent (RE) vitamin A 3-4 weeks after delivery and their infants 7.5 mg RE with each OPV dose at 6, 10 and 14 weeks of age. The control group mothers and their infants received a placebo at each of these contacts. MAIN OUTCOMES: Geometric mean (GM) titer of neutralizing antibodies and proportion of children with protective titer to the three polioviruses at 26 weeks of age. RESULTS: Vitamin A supplementation increased the proportion of infants with protective antibody titer against poliovirus type 1 (relative risk (RR) 1.15, 95% confidence interval (CI) 1.03-1.28) and the GM antibody titer (ratio of GM 1.55, 95% CI 1.03-2.31) following immunization. The proportion of infants with protective antibody titer against poliovirus type 2 (RR 0.99, 95% CI 0.94-1.05) or type 3 (RR 1.05, 95% CI 0.96-1.15) was not significantly different in vitamin A and placebo groups. The GM antibody titer for poliovirus type 2 (ratio of GM 0.99, 95% CI 0.64-1.54) or poliovirus type 3 (ratio of GM 1.10, 95% CI 0.69-1.75) also did not differ across groups. CONCLUSIONS: Vitamin A given to the mothers in the postpartum period and their infants with OPV did not interfere with the antibody response to any of the three polioviruses and enhanced the response to poliovirus type 1.
Adult↗
Epidemiology of rotavirus in India.
Rotavirus is the leading cause of childhood diarrhea worldwide, causing an estimated 600,000 deaths each year. To assess the potential benefits of a national rotavirus immunization program in India, we analyzed 40 published studies of rotavirus that were conducted between 1976 and 1997 and included a total of approximately 13,000 Indian pediatric inpatients. Pediatric studies featuring 100 or more patients and lasting at least 12 months in duration and all neonatal studies were analyzed. Rotavirus was detected in a median of 18% of pediatric patients and 28% of neonates surveyed. Fifty percent of all children hospitalized with rotavirus by age 5 were hospitalized by the age of 6 months, 75% by the age of 9 months, and almost 100% by the age of 2 years. Rotavirus was most prevalent (31%) in children between 7 and 12 months of age, followed by children between 1 and 2 years of age (20%), and children < 7 months of age (13%). VP7 genotypes G1 and G2 were most commonly isolated although significant heterogeneity of serotypes was observed. P[11], G9 strains were most frequently isolated among neonates. In 1998; approximately 98,000 childhood deaths were caused by rotavirus. These data underscore the urgent need for safe and effective interventions against rotavirus such as vaccines. The significant diversity of rotavirus strains and young age of hospitalization pose unique challenges to the formulation of a rotavirus immunization program in India, but raise the possibility of utilizing a neonatal vaccine to provide effective coverage.
Child, Preschool↗
Selection of single chain variable fragments (scFv) against the glycoprotein antigen of the rabies virus from a human synthetic scFv phage display library and their fusion with the Fc region of human IgG1.
We have prepared human recombinant antibody molecules against the glycoprotein antigen of the rabies virus (GPRV) based on the single chain variable fragment (scFv) format. Anti-GPRV scFvs were selected from a human synthetic scFv phage display library with a repertoire of approximately 109 specificities. After three rounds of selection against the PV11 strain of the virus, 40% of the clones tested recognized the rabies antigen. Of the 20 positive clones that were sequenced, five distinct sequences were identified. These distinct scFvs were cloned into a mammalian expression vector carrying the human IgG1 Fc region. The specificity of the resulting scFv-Fc molecules for GPRV was established by ELISA, dot blot and western blot analyses and membrane immunofluorescence. Two of the scFv-Fc fusion proteins neutralized the PV11 strain in a standard in vivo neutralization assay where the virus was incubated with the scFv-Fc molecules before intracranial inoculation in mice. These anti-GPRV scFv-Fc molecules have the potential to be used as an alternative to the presently available HRIG, for use in post-exposure preventive treatment.
Amino Acid Sequence↗
Micronutrients as adjunct therapy of acute illness in children: impact on the episode outcome and policy implications of current findings.
Role of micronutrients namely vitamin A, zinc and folate, as adjunct therapy of illness episodes in children in developing countries have been discussed in the light of health policy. Apart from a selective review, attempts have been made to statistically combine results of several studies to address policy issues. In children, vitamin A supplementation during illness has (a) a profound effect in reducing mortality in measles, (b) possibly a significant effect in reducing persistent diarrhea episodes in children with acute diarrhea, and (c) no benefit in pneumonia. Use of large dose vitamin A is recommended during measles episodes but not in non-measles pneumonia. Its use in acute diarrhea is debatable but recommended in persistent diarrhea and in severe malnutrition as a component of a micronutrient mixture. Large dose vitamin A supplementation should be used with caution in young infants as there are unresolved concerns about its safety particularly, bulging fontanelle observed in infants when co-administered at immunization. In children, zinc supplementation during illness, (a) had a marked effect in reducing prolonged episodes and a modest effect on episode duration in acute diarrhea, (b) resulted in reduced rate of treatment failure and death in persistent diarrhea, (c) had no effect in measles and non-measles pneumonia, and (d) probably had a detrimental effect of increasing death rate when a large dose was used in severely malnourished children. The desirability of routine zinc supplementation therapy of undernourished children with acute diarrhea should be assessed further. Concerning policy, zinc supplementation as a component of a micronutrient mixture is recommended in the rehabilitation of severely malnourished children and in persistent diarrhea. However, recommendation for its routine use in all cases of acute diarrhea in children needs additional studies on effectiveness, cost, operations and safety. In two randomized controlled trials folate has been evaluated in acute and persistent diarrhea and found to have no beneficial effect. Folate is not recommended as adjunct therapy of diarrhea. Role of folate in preventing severe disease and/or death deserves further evaluation.
Acute Disease↗
Micronutrient deficiency in children.
Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to humans, the biology of deficiency as well as excess of micronutrients in humans must continue to be investigated with vigour.
Breeding↗