Child Neurodevelopment After Multidomain Interventions From Preconception Through Early Childhood: The WINGS Randomized Clinical Trial.

Importance: Multidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions. Objective: To evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment. Design, Setting, and Participants: In this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial's secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2000, through February 25, 2022. Interventions: Health, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods. Main Outcomes and Measures: Cognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool. Results: The mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group. Conclusions and Relevance: Multidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children's development warrant further evaluation. Trial Registration: Clinical Trials Registry-India CTRI/2017/06/008908.

International network of cancer genome projects.

The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.

Impact of a package of health, nutrition, psychosocial support, and WaSH interventions delivered during preconception, pregnancy, and early childhood periods on birth outcomes and on linear growth at 24 months of age: factorial, individually randomised controlled trial.

OBJECTIVE: To determine the effect of integrated and concurrent delivery of health, nutrition, water, sanitation and hygiene (WaSH), and psychosocial care interventions during the preconception period alone, during pregnancy and early childhood, and throughout preconception, pregnancy, and early childhood on birth outcomes and linear growth at 24 months of age compared with routine care. DESIGN: Individually randomised factorial trial. SETTING: Low and middle income neighbourhoods of Delhi, India. PARTICIPANTS: 13 500 women were randomised to receive preconception interventions (n=6722) or routine care (n=6778). 2652 and 2269 pregnant women were randomised again to receive pregnancy and early childhood interventions or routine care. The analysis of birth outcomes included 1290 live births for the preconception, pregnancy, and early childhood interventions (group A), 1276 for the preconception intervention (group B), 1093 for the pregnancy and early childhood interventions (group C), and 1093 for the control (group D). Children aged 24 months by 30 June 2021 were included in the 24 month outcome analysis (453 in group A, 439 in B, 293 in C, and 271 in D). INTERVENTIONS: Health, nutrition, psychosocial care and support, and WaSH interventions were delivered during preconception, pregnancy, and early childhood periods. MAIN OUTCOME MEASURES: The primary outcomes were low birth weight, small for gestational age, preterm, and mean birth weight. At 24 months, the outcomes were mean length-for-age z scores and proportion stunted. Three prespecified comparisons were made: preconception intervention groups (A+B) versus no preconception intervention groups (C+D); pregnancy and early childhood intervention groups (A+C) versus routine care during pregnancy and early childhood (B+D) and preconception, pregnancy, and early childhood interventions groups (A) versus control group (D). RESULTS: The proportion with low birth weight was lower in the preconception intervention groups (506/2235) than in the no preconception intervention groups (502/1889; incidence rate ratio 0.85, 98.3% confidence interval 0.75 to 0.97; absolute risk reduction -3.80%, 98.3% confidence interval -6.99% to -0.60%). The proportion with low birth weight was lower in the pregnancy intervention groups (502/2096) than in the no pregnancy intervention groups (506/2028) but the upper limit of the confidence interval crossed null effect (0.87, 0.76 to 1.01; -1.71%, -4.96% to 1.54%). There was a larger effect on proportion with low birth weight in the group that received interventions in the preconception and pregnancy periods (267/1141) compared with the control group (267/934; 0.76, 0.62 to 0.91; -5.59%, -10.32% to -0.85%). The proportion stunted at 24 months of age was substantially lower in the pregnancy and early childhood intervention groups (79/746) compared with the groups that did not receive these interventions (136/710; 0.51, 0.38 to 0.70; -8.32%, -12.31% to -4.32%), and in the group that received preconception, pregnancy, and early childhood interventions (47/453) compared with the control group (51/271; 0.49, 0.32 to 0.75; -7.98%, -14.24% to -1.71%). No effect on stunting at 24 months was observed in the preconception intervention groups (132/892) compared with the no preconception intervention groups (83/564). CONCLUSIONS: An intervention package delivered during preconception, pregnancy, and early childhood substantially reduced low birth weight and stunting at 24 months. Pregnancy and early childhood interventions alone had lower but important effects on birth outcomes and 24 month outcomes. Preconception interventions alone had an important effect on birth outcomes but not on 24 month outcomes. TRIAL REGISTRATION: Clinical Trial Registry-India CTRI/2017/06/008908.

Comparison of Ready-to-Use Therapeutic Food with cereal legume-based khichri among malnourished children.

OBJECTIVE: To compare the acceptability and energy intake of Ready-to-Use Therapeutic Food (RUTF) with cereal legume based khichri among malnourished children. DESIGN: An acceptability trial with cross-over design. SETTING: Urban low to middle socioeconomic neighbor-hoods in Delhi. SUBJECTS: 31 children aged > or =6 to < or =36 months with malnutrition, defined as Weight for height (WHZ) < -2 to > or = -3 SD, with no clinical signs of infection or edema. INTERVENTION: Children were offered weighed amounts of RUTF and khichri in unlimited amounts for 2 days, one meal of each on both days. Water was fed on demand. Caregivers interviews and observations were conducted on the second day. OUTCOME MEASURES: Acceptability of RUTF compared to khichri based on direct observation and energy intake for test and control meals. RESULTS: The proportion of children who accepted RUTF eagerly was 58% as against 77% for khichri. 42% children on RUTF and 23% on khichri accepted the meal but not eagerly. The median (IQR) energy intake over the two day period in children aged 6 to 36 months from RUTF was 305 (153, 534) kcal, and from khichri was 242 (150, 320) kcal (P=0.02). CONCLUSION: RUTF and khichri were both well accepted by study children. The energy intake from RUTF was higher due to its extra energy density.

Emergence of G12 rotavirus strains in Delhi, India, in 2000 to 2007.

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

Mid upper arm circumference as a predictor of risk of mortality in children in a low resource setting in India.

OBJECTIVE: In this secondary analysis of data from an intervention trial, we assessed the performance of Mid Upper Arm Circumference (MUAC) as a predictor of mortality in children aged 6-59 months from Delhi, India, one year after their initial MUAC measurements were taken. Additionally, we assessed MUAC as an absolute value and MUAC z-scores as predictors of risk of mortality. METHODS: In the trial, children were screened using MUAC prior to referral to the study clinic. These children were revisited a year later to ascertain their vital status. Baseline MUAC and MUAC z-scores were used to categorize children as severely (MUAC <115 mm, MUAC z-score <-3SD) or moderately (MUAC 115 to <125 mm, MUAC z-score <-2SD) malnourished. The proportion of malnutrition, risk of mortality, relative risk estimates, positive predictive value and area under the curve (AUC) by MUAC and MUAC z-scores were calculated. RESULTS: In the resurvey, the first 36159 children of the 48635 in the initial survey were contacted. Of these, vital status of 34060 (94.2%) was available. The proportion of severe malnutrition by MUAC (<115 mm) was 0.5% with an associated mortality of 4.7% over a one year period and an attributable mortality of 13% while the proportion of the severe malnutrition by MUAC z-score (<-3SDwas 0.9% with an associated mortality of 2.2%. CONCLUSIONS: MUAC is a significant predictor of subsequent mortality in under-five children. In settings where height measurement is not feasible, MUAC can be used as a screening tool for identifying severely malnourished children for management.

Typhoid and paratyphoid fever.

Typhoid fever is estimated to have caused 21.6 million illnesses and 216,500 deaths globally in 2000, affecting all ages. There is also one case of paratyphoid fever for every four of typhoid. The global emergence of multidrug-resistant strains and of strains with reduced susceptibility to fluoroquinolones is of great concern. We discuss the occurrence of poor clinical response to fluoroquinolones despite disc sensitivity. Developments are being made in our understanding of the molecular pathogenesis, and genomic and proteomic studies reveal the possibility of new targets for diagnosis and treatment. Further, we review guidelines for use of diagnostic tests and for selection of antimicrobials in varying clinical situations. The importance of safe water, sanitation, and immunisation in the presence of increasing antibiotic resistance is paramount. Routine immunisation of school-age children with Vi or Ty21a vaccine is recommended for countries endemic for typhoid. Vi vaccine should be used for 2-5 year-old children in highly endemic settings.

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.

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).

Plasma zinc as a predictor of diarrheal and respiratory morbidity in children in an urban slum setting.

The association between low initial plasma zinc concentration and risk of morbidity over the subsequent 3 mo was examined in a cohort of 116 children aged 12-59 mo recovering from acute diarrhea. Children with low initial plasma zinc (< or = 8.4 micromol/L) had more episodes of diarrhea [risk ratio (RR): 1.47; 95% CI: 1.03, 2.49) and severe diarrhea, defined as passage of > or = 5 liquid stools in a 24-h period, (RR: 1.70; 95% CI: 1.06, 2.72) than did children with normal plasma zinc (> 8.4 micromol/L). The mean prevalence rate of diarrhea associated with fever was 4 times higher in the zinc-deficient group (P = 0.01). Overall, the difference in the number of episodes of acute lower respiratory tract infections (ALRIs) between the two groups was not statistically significant (RR: 1.76; 95% CI: 0.88-3.53) but the mean prevalence rate of ALRIs was 3.5 times higher in children with low plasma zinc (P = 0.05). The increased risk of diarrhea and ALRIs episodes in zinc-deficient children was larger in boys than in girls. These results show that children with low plasma zinc concentrations are at risk for increased diarrheal and respiratory morbidity.

Efficacy of zinc supplementation in reducing the incidence and prevalence of acute diarrhea--a community-based, double-blind, controlled trial.

A community-based, double-blind, randomized trial was conducted in a population of low socioeconomic status in urban India to determine whether daily zinc supplementation reduces the incidence and prevalence of acute diarrhea, especially in those with zinc deficiency. Children 6-35 mo of age were randomly assigned to zinc (n = 286) and control (n = 293) groups and received a supplement daily for 6 mo. Zinc gluconate (10 mg elemental Zn) was given, with both zinc and control groups also receiving multivitamins. The primary outcome measures determined by home visits every fifth day and physician examinations were the number of acute diarrheal episodes (incidence) and total diarrheal days (prevalence). Zinc supplementation had no effect in children 6-11 mo old. In children aged > 11 mo there was significantly less diarrhea in the zinc group. In boys > 11 mo old, supplementation resulted in a 26% (95% CI: 13%, 38%) lower diarrheal incidence and a 35% (95% CI: 20%, 50%) lower prevalence. In zinc-supplemented girls > 11 mo of age, the incidence was 17% (95% CI: 2%, 30%) lower and the prevalence was 19% (95% CI: 4%, 47%) lower. Overall, zinc supplementation resulted in a 17% (95% CI: 1%, 30%) lower diarrheal incidence in children with plasma zinc concentrations < 9.18 mumol/L at enrollment and a 33% (95% CI: 6%, 52%) lower incidence in children with concentrations < 50 mumol/L. In conclusion, zinc supplementation had a significant effect on acute diarrheal morbidity in children > 11 mo old and in children with low plasma zinc concentrations.

Community-based controlled trial of dietary management of children with persistent diarrhea: sustained beneficial effect on ponderal and linear growth.

BACKGROUND: Uncontrolled hospital-based studies in developing countries have reported promising results of dietary rehabilitation of children with persistent diarrhea. OBJECTIVE: The objective was to determine the immediate and long-term effects of a dietary supplement and micronutrients given to children with persistent diarrhea during the episode and for 1 wk during convalescence. DESIGN: The study was open, controlled, and community-based and was conducted in a periurban area in Guinea-BISSAU: Children <3 y of age with persistent diarrhea were identified during weekly household visits. The children randomly assigned to the treatment and control groups were examined by a physician and all medical conditions were treated. The children in the treatment group were offered home-based dietary treatment consisting of locally available foods and micronutrient supplements. RESULTS: There were 141 episodes of persistent diarrhea during the study: 70 in the treatment group (in 58 children) and 71 in the control group (in 62 children). During the intervention period (median: 17 d), weight gain in the treatment group exceeded that of the control group by 61.5 g/wk (95% CI: 49.2, 73.8), whereas there was no significant difference in linear growth on the basis of knee-heel length. At a median follow-up period of 6.6 mo after the intervention was stopped, weight gain in the treatment group exceeded that of the control group by 12.5 g/wk (95% CI: 7.7, 17.3); knee-heel length was 7.5 mm/y (4.8, 10.2) greater and total length was 0.65 cm/y (0.11, 1.19) greater in the treatment group. CONCLUSION: Therapeutic feeding and micronutrient supplementation had an immediate and sustained beneficial effect on growth in children with persistent diarrhea.

Efficacy of milk-based diets in persistent diarrhea: a randomized, controlled trial.

OBJECTIVE: Previous studies have shown increased stool output when children with persistent diarrhea (PD) received milk as the predominant source of nutrition. METHODS: We evaluated the efficacy of milk given in modest amounts as a part of a mixed diet in children with PD. One hundred sixteen children 3 to 24 months of age with diarrhea for between 14 days and 12 weeks were allocated to milk-based (n = 60) or milk-free (n = 56) cereal dietary regimens. The two diets were isocaloric (86.9 calories/100 g for < or = 9 months; 95.6 cal/100 g for > 9 months) consisting of puffed rice cereal, sugar, and oil differing in only their source of protein, which was either milk or egg white, respectively. An average of 30% of the calories were constituted by milk in the milk-cereal diet. Both diets were offered at the rate of 150 kcal/kg per day. Children receiving milk-cereal consumed an average of 1.9 g/kg lactose per day. RESULTS: The baseline characteristics in the two groups were similar. Comparable amounts of diet were consumed in both groups. The milk-cereal group did not have higher median (range) stool output (g/kg/h) compared with the milk-free group during a 0- to 48-hour (milk-cereal, 1.7 [0.2 to 8.7]; milk-free, 1.5 [0.1 to 6.6]) or 0- to 120-hour (milk-cereal, 1.6 [0.4 to 7.2]; milk-free, 1.3 [0.1 to 7.6]) period. The percentage of weight gain was similar in the two groups, and there were no significant differences in the duration of diarrhea. Overall, 23 children had treatment failures, 10 (17%) in the milk-cereal and 13 (23.6%) in the milk-free groups. CONCLUSIONS: Our findings suggest that modest intakes of milk are well tolerated as a part of mixed diet during PD.

Effect of zinc supplementation on observed activity in low socioeconomic Indian preschool children.

OBJECTIVES: To investigate whether supplementation of zinc in preschool children is associated with improvement in observed activity levels. METHODS: On 2 consecutive days, we performed 5-hour observations with momentary time sampling (instant activity every 10 minutes) in children selected from an ongoing double-blind, randomized trial of zinc supplementation. The study was conducted in Kalkaji, a low-socioeconomic urban population of New Delhi with high diarrheal incidence and rates of malnutrition. A total of 93 children (48 zinc and 45 control) 12 to 23 months of age from an ongoing community-based, randomized, controlled trial received supplements for at least 1 month before study; 71% had received supplementation for more than 120 days. Zinc gluconate (10 mg of elemental zinc) was given daily, with both zinc and control groups receiving vitamins A, B1, B2, B6, D3, and E and niacinamide in addition. RESULTS: Outcomes were percentages of time spent in each of five activity levels and two groups representing high and low movement and overall rating by two activity scores. Children in the zinc group spent 72% more time performing activities in the high-movement group. Among the zinc-supplemented children, the activity rating by the children's activity rating score was 12% higher and by the energy expenditure score was 8.3% higher than in the control group. CONCLUSIONS: In conclusion, zinc supplementation, given along with selected vitamins, was associated with significantly greater activity levels in children. The relationship between the activity increase and locomotor development needs to be investigated, as do the long-term implications of zinc supplementation in terms of developmental status and school performance.

Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial.

BACKGROUND: Increased acute lower respiratory infection incidence, severity, and mortality are associated with malnutrition, and reduced immunological competence may be a mechanism for this association. Because zinc deficiency results in impaired immunocompetence and zinc supplementation improves immune status, we hypothesized that zinc deficiency is associated with increased incidence and severity of acute lower respiratory infection. METHODS: We evaluated the effect of daily supplementation with 10 mg of elemental zinc on the incidence and prevalence of acute lower respiratory infection in a double-blind, randomized, controlled trial in 609 children (zinc, n = 298; control, n = 311) 6 to 35 months of age. Supplementation and morbidity surveillance were done for 6 months. RESULTS: After 120 days of supplementation, the percentage of children with plasma zinc concentrations <60 microg/dL decreased from 35.6% to 11.6% in the zinc group, whereas in the control group it increased from 36.8% to 43.6%. Zinc-supplemented children had 0.19 acute lower respiratory infection episodes/child/year compared with 0.35 episodes/child/year in the control children. After correction for correlation of data using generalized estimating equation regression methods, there was a reduction of 45% (95% confidence interval, 10% to 67%) in the incidence of acute lower respiratory infections in zinc-supplemented children. CONCLUSIONS: A dietary zinc supplement resulted in a significant reduction in respiratory morbidity in preschool children. These findings suggest that interventions to improve zinc intake will improve the health and survival of children in developing countries.

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.

Oligonucleotide gene probes may detect enterotoxigenic Escherichia coli directly in fecal smears.

Diarrhoeal stools from 86 Indian children were examined for the presence of enterotoxigenic Escherichia coli (ETEC) by DNA hybridization on bacterial colonies as well as directly on fecal smears. Colony hybridization showed that 8 of the samples contained ETEC. Only in three of these specimens were all the colonies tested positive for ETEC. These samples were correctly identified by the stool smear hybridization assay. The remaining 5 specimens produced enterotoxigenic as well as nonenterotoxigenic colonies. These samples were all negative by the stool smear hybridization technique. Methodological improvements of the stool smear assay may provide a substantially simplified method for the otherwise cumbersome identification of ETEC.

Enteroaggregative Escherichia coli and Salmonella associated with nondysenteric persistent diarrhea.

A hospital-based case-control study including 92 children with diarrhea for longer than 14 days and 92 controls without gastrointestinal symptoms was performed to describe the association between the excretion of enteric pathogens and persistent diarrhea. In patients the most frequently isolated stool pathogens were enteroaggregative Escherichia coli (19.6%), nontyphoidal Salmonella spp. (17.4%), E. coli with diffuse adherence pattern (7.6%), G. lamblia (7.6%) and enterotoxigenic E. coli (5.4%). The excretion rates in patients were significantly greater than in controls only for nontyphoidal Salmonella spp. (P = 0.0006) and enteroaggregative E. coli (P = 0.016).

High prevalence of rotavirus infection among neonates born at hospitals in Delhi, India: predisposition of newborns for infection with unusual rotavirus.

Although rotavirus is the most common cause of diarrhea in children older than 3 months of age, neonatal infections, which are asymptomatic, have rarely been surveyed and have been identified in only a few discrete nosocomial outbreaks. After such a nosocomial outbreak of rotavirus infection among newborns at a hospital in Delhi, we screened infants born at five other nurseries in the immediate area to assess the prevalence of neonatal infections and to determine whether the unique neonatal rotavirus strain, 116E, previously identified in Delhi, was present in other settings. Infection was documented in 43 to 78% of hospitalized infants between 4 and 6 days of life born at five of the six hospitals. Infection with strains related to 116E were the most common, but other unusual strains and no strains common in the community were detected. In addition a shift in genotype was observed among specimens collected from two of these hospitals during a 2-year period. Our observation that neonatal rotavirus infections are more common than recognized previously would encourage the administration of rotavirus vaccines during the newborn period and suggests that the low efficacy of vaccines observed during trials in developing countries may be caused by early natural exposure of infants before immunization. The extraordinary predisposition of neonates for unusual rotavirus strains not commonly found in the community should encourage others to screen neonates for this infection, characterize the strains more fully and attempt to understand at a molecular level the unique relationship between the infecting strain type and the age of the host.

Role of enteric adenoviruses and rotaviruses in mild and severe acute enteritis.

The role of enteric-type adenoviruses and rotaviruses in mild and severe acute gastroenteritis was investigated among children younger than 5 years of age seeking treatment at an urban hospital (UH) and at a rural health center (RHC) in India. There were 330 children at the UH and 340 at the RHC; 319 and 315 age matched nondiarrheal children served as controls for the respective groups. Rotavirus was detected in 15.2% of 330 cases and 1.9% of 319 controls at the UH (P less than 0.001) and in 16.5% of 340 cases and 2.9% of 315 controls at the RHC (P less than 0.001). RV excretion was 3- to 5-fold more common in severe compared with mild diarrhea at the UH and at the RHC (P less than 0.001). The detection rate for enteric-type adenoviruses was similar in patients and controls, respectively, at the UH (0.9%; 2.5%) and RHC (3.8%; 2.5%). At the RHC adenovirus types other than 40 and 41 were excreted by 8.8% of the patients and by only 1.0% of the controls (P less than 0.001). It is possible that the diarrheagenic role of adenoviruses may not be restricted to types 40 and 41.