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M K Bhan

Publications and source records attributed to M K Bhan.

At least 37 records · Page 2Linked to original sources

Pneumococcal pulmonary infection, septicaemia and survival in young zinc-depleted mice.

The aim of the present study was to explore whether mice fed a diet low in Zn (2.0 mg Zn/kg diet) for a relatively short period of time were more prone to severe Streptococcus pneumoniae infection than mice fed a normal diet (25 mg elemental Zn/kg). The Zn-deficient mice were compared with mice in two Zn-adequate control groups; one pair-fed and another with free access to the diet. After 2 weeks feeding, the mice were infected intranasally under anaesthesia with a suspension containing about 10(7) pneumococci. Clinical status was observed every day and blood samples were examined for S. pneumoniae every second day for a week. All infected mice examined carried the infecting strain intranasally. The survival time and time before positive blood culture were significantly shorter in the Zn-depleted group than in the pair-fed Zn-adequate group (hazard ratios 15.6 and 3.2, and respectively). At the end of the observation period, ten of the twelve mice in the Zn-deficient group were dead while one of twelve and two of twelve were dead in the two Zn-adequate control groups. This study shows that even acutely-induced Zn deficiency dramatically increases the risk of serious pneumococcal infection in mice.

Animals↗

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.

Administration, Oral↗

Food supplementation with encouragement to feed it to infants from 4 to 12 months of age has a small impact on weight gain.

It is unclear whether a substantial decline in malnutrition among infants in developing countries can be achieved by increasing food availability and nutrition counseling without concurrent morbidity-reducing interventions. The study was designed to determine whether provision of generous amounts of a micronutrient-fortified food supplement supported by counseling or nutritional counseling alone would significantly improve physical growth between 4 and 12 mo of age. In a controlled trial, 418 infants 4 mo of age were individually randomized to one of the four groups and followed until 12 mo of age. The first group received a milk-based cereal and nutritional counseling; the second group monthly nutritional counseling alone. To control for the effect of twice-weekly home visits for morbidity ascertainment, similar visits were made in one of the control groups (visitation group); the fourth group received no intervention. The median energy intake from nonbreast milk sources was higher in the food supplementation group than in the visitation group by 1212 kJ at 26 wk (P < 0.001), 1739 kJ at 38 wk (P < 0.001) and 2257 kJ at 52 wk (P < 0.001). The food supplementation infants gained 250 g (95% confidence interval: 20--480 g) more weight than did the visitation group. The difference in the mean increment in length during the study was 0.4 cm (95% confidence interval: -0.1--0.9 cm). The nutritional counseling group had higher energy intakes ranging from 280 to 752 kJ at different ages (P < 0.05 at all ages) but no significant benefit on weight and length increments. Methods to enhance the impact of these interventions need to be identified.

Body Height↗

Great diversity of group A rotavirus strains and high prevalence of mixed rotavirus infections in India.

We previously observed a marked diversity of rotavirus strains and a high prevalence of the uncommon serotype G9 in a small survey of rotavirus strains collected from six centers in India. In the present study, we characterized a larger collection of strains from children hospitalized with severe diarrhea in seven Indian cities between 1996 and 1998. A total of 287 strains were G and P genotyped by reverse transcription-PCR, and some were further characterized by electropherotyping and subgrouping. Of the four strains common globally, three were found in only 43% of samples (P[8], G1, 15%; P[4], G2, 22%; P[8], G4, 6%), whereas G9 strains made up 17% of the total. Three different G9 strains were present: a P[8], G9 strain, which displayed the long electropherotype and subgroup II VP6 specificity, and two P[6], G9 strains, one with the long electropherotype and subgroup II specificity and the other with the short electropherotype and subgroup I specificity. Marked diversity was observed among strains collected from different cities and collected over time. Of the 253 strains that were fully typed, 54 (21%) had a mixed G or P genotype. Serotype G2 strains were detected more often in infections caused by single strains than in mixed infections (P < 0.05), whereas serotype G1 strains were found more often in mixed infections than in infections caused by single strains (P < 0.05). The diversity of rotavirus strains and the high prevalence of mixed infections confirm trends reported earlier and help to better characterize the strains of rotavirus circulating in India. Vaccines under development should clearly target G9 strains, and G9 should be included as one of the common global serotypes.

Child↗

Molecular characterization of serotype G9 rotavirus strains from a global collection.

Between 1992 and 1998, serotype G9 human rotavirus (RV) strains have been detected in 10 countries, including Thailand, India, Brazil, Bangladesh, Malawi, Italy, France, the United States, the United Kingdom, and Australia, suggesting the possible emergence of the fifth common serotype worldwide. Unlike the previously characterized reference G9 strains (i.e., WI61 and F45), the recent G9 isolates had a variety of gene combinations, raising questions concerning their origin and evolution. To identify the progenitor strain and examine the on-going evolution of the recent G9 strains, we characterized by genetic and antigenic analyses 16 isolates obtained from children with diarrhea in India, Bangladesh, the United States, and Malawi. Specifically, we sequenced their VP7 and NSP4 genes and compared the nucleotide (nt) and deduced amino acid sequences with the reference G9 strains. To identify reassortment, we examined the products of five gene segments; VP4, VP7, and NSP4 genotypes (genes 4, 9, and 10); subgroups (gene 6); electropherotypes (gene 11); and the genogroup profiles of all of the recent G9 isolates. Sequence analysis of the VP7 gene indicated that the recent U.S. P[6],G9 strains were closely related to the Malawian G9 strains (>99% nt identity) but distinct from G9 strains of India ( approximately 97% nt identity), Bangladesh ( approximately 98% nt identity), and the reference strains ( approximately 97% nt identity). Phylogenetic analysis identified a single cluster for the U.S. P[6],G9 strains that may have common progenitors with Malawian P[6],G9 strains whereas separate lineages were defined for the Indian, Bangladeshi, and reference G9 strains. Northern hybridization results indicated that all 11 gene segments of the Malawian P[6],G9 strains hybridized with a probe derived from a U.S. strain of the same genotype and may have the same progenitor, different from the Indian G9 strains, whereas the Bangladesh strains may have evolved from the U.S. G9 progenitors. Overall, our findings suggest that much greater diversity among the newly identified G9 strains has been generated by reassortment between gene segments than through the accumulation of mutations in a single gene.

Antigens, Viral↗

Prognostic factors for persistent diarrhoea managed in a community setting.

Two hundred and five cases (mean age 13.4, SD 9.5) of persistent diarrhoea (PD) of 14-28 days duration, attending an urban slum clinic and treated according to standard WHO guidelines, were monitored at weekly intervals to obtain an estimate of treatment failure rates and to identify its clinical predictors. Vitamin and micronutrients (daily 2RDA) were additionally provided. Only 9 (8.2%) of 109 children with criteria for hospital care accepted in-patient care. Weight gain was considered inadequate if the daily increment between enrollment and day 7 of follow up was < 10 g at age 0-3 months, < 5 g at 4-6 months, and any weight loss for those older than 6 months. Recovery was considered delayed if diarrhoea ceased 7 days after enrollment. Overall, 28.3% cases had inadequate weight gain and 25.6% had delayed recovery. The non-breast milk calorie intake was 11.2% during infancy and 40.6% at later ages of the recommended intakes. In a logistic regression model, initial watery stool frequency greater than median (adjusted OR 2.30, p = 0.01), age < or = 6 months (adjusted OR 2.24, p = 0.04) and low consumption of micronutrient mixture (adjusted OR 2.62, p = 0.01) were associated with an increased risk of delayed recovery. In a Cox proportional hazards model for time to recovery from diarrhoea, low consumption of the micronutrient mixture and age < or = 6 months reduced the chances of recovery by 29% and 37% respectively. Low consumption of the prescribed micronutrient mixture (adjusted OR 2.21, p = 0.04), fever (adjusted OR 1.91, p = 0.05) and diarrhoea continuing beyond study day 7 (adjusted OR 2.29, p = 0.03) increased the risk of inadequate weight gain. Breast feeding status and animal milk consumption did not influence weight gain or recovery. Due to the low compliance for advised hospitalisation, approaches for care at community level itself need to be evolved. Focus should be on increasing the overall dietary intake and provision of generous but safe amount of micronutrients; our findings do not support need for routine elimination of animal milk. The efficacy of individual micronutrients needs evaluation in controlled trials.

Community Health Services↗

Current and future management of childhood diarrhoea.

Diarrhoea continues to have a devastating impact in infants and children. It is a major cause of retarded growth. Substantial declines in hospitalization rates and possibly in the mortality due to diarrhoea have occurred following the launch of programmes based on oral rehydration therapy, and yet about 1 million diarrhoea-related deaths occur each year in South-East Asia. The World Health Organization currently recommends oral rehydration therapy plus continued breast- and complementary feeding for children with diarrhoea, and antibiotics for dysentery or associated systemic infection. Although oral rehydration therapy has achieved substantial acceptance, physicians and families continue to prescribe and seek drug therapy to reduce diarrhoeal duration and severity. Research is aimed at developing improved oral rehydration salt solutions or identifying adjunct therapy that will provide substantial benefit in reducing stool output together with safety and selectivity of action. It must, however, be recognized that control of malnutrition is a key requirement to reduce the duration and severity of acute diarrhoea.

Child, Preschool↗

Typhoid fever in children aged less than 5 years.

BACKGROUND: Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. METHODS: A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. FINDINGS: 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. INTERPRETATION: Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.

Adolescent↗

Vitamin A administered with measles vaccine to nine-month-old infants does not reduce vaccine immunogenicity.

After a report of reduced seroconversion to measles in infants, aged 6 mo, given vitamin A with their measles vaccination, serious concerns were raised regarding the safety of the WHO's recommendation that infants be supplemented with vitamin A at the time of measles immunization. To determine the impact of coadministered vitamin A on the antibody response to measles vaccine given to infants aged 9 mo, the more common age for immunization in developing countries, we conducted a randomized, double-blind, placebo-controlled trial in an urban slum community in Delhi. Infants (618) were randomly allocated to receive 30 mg vitamin A or a placebo with the measles immunization. Antibodies to measles were measured by ELISA in serum samples obtained at before (baseline) and 12 wk after immunization. Overall, the seroconversion rates did not differ between vitamin A (89.5%) and placebo (87.6%) groups. There were no significant differences in the geometric mean titers in the two groups (ratio of geometric means, 1.19; 95% confidence interval, 0.97-1.46). Among malnourished infants, the geometric mean titer was significantly greater in the vitamin A group compared to the placebo group (ratio of geometric means, 1.57; 95% confidence interval, 1. 18-2.0), but seroconversion rates did not differ. There were no differences in seroconversion rates and geometric mean titers in the two study groups among the well-nourished children. These results indicate that 30 mg vitamin A does not reduce the immune response to the coadministered vaccine and, therefore, can be continued to be given safely in public health programs.

Antibody Formation↗

Community-based randomized controlled trial of reduced osmolarity oral rehydration solution in acute childhood diarrhea.

OBJECTIVE: The standard oral rehydration solution (ORS) recommended by WHO and UNICEF does not reduce the volume or frequency of stools or the length of the episode. Hospital-based studies from developing and developed countries and intestinal perfusion studies suggest a beneficial effect on water and sodium absorption with reduced osmolarity ORS as compared with standard ORS. We conducted a community-based study comparing the efficacy of reduced osmolarity ORS (224 mmol/l) with standard ORS (311 mmol/l) in acute childhood diarrhea in a West African community. METHODS: Infants and toddlers age 0 to 30 months having 738 episodes of diarrhea identified by weekly household visits were randomly assigned to treatment with either standard ORS (n = 376) or reduced osmolarity ORS (n = 362). The children were followed by daily home visits to assess ORS intake and clinical characteristics. Duration of diarrhea was compared by proportional hazards regression analysis, the hazard ratio being interpreted as the relative recovery rate between the children receiving the two types of ORS. Because earlier reports have suggested that weaning status might be an important modifier for the performance of reduced osmolarity ORS, the effect was assessed overall and as an interaction between type of ORS and weaning status and age. Maternal satisfaction was assessed in a paired analysis among mothers whose children participated at least twice in the study. RESULTS: In the overall analysis reduced osmolarity ORS was as efficacious as standard ORS as assessed by duration of diarrheal episode and total number of stool evacuations on Days 1 and 2. Non-breast-fed toddlers (i.e. children ages 12 to 30 months) treated with reduced osmolarity ORS had significantly shorter diarrheal episodes [1.14 days vs. 1.78 days with standard ORS; hazard ratio, 1.50; 95% confidence interval (CI), 1.07 to 2.09] and lower total number of stool evacuations on Days 1 and 2 (3.9 stool evacuations vs. 5.0 stool evacuations with standard ORS; ratio of geometric means, 0.77; 95% CI 0.60 to 1.01). No significant difference was found for breast-fed toddlers or for infants. There was no statistically significant difference in the ORS intake between the two treatment groups. The odds ratio for the mother preferring reduced osmolarity ORS to standard ORS was 1.92 (95% CI 0.97 to 3.85). CONCLUSIONS: Reduced osmolarity ORS was as efficacious as standard ORS. Non-breast-fed children treated with reduced osmolarity ORS had significantly shorter diarrheal episodes and a tendency toward lower stool frequency. These findings may be of importance, especially in developing countries where early weaning is common.

Acute Disease↗

Comparison of enzyme immunoassay and reverse transcriptase PCR for identification of serotype G9 rotaviruses.

While only four globally important rotavirus G serotypes (1 to 4) have been documented, many studies suggest that serotype G9 viruses may be widely distributed and more important than previously recognized. We have evaluated 10 serotype G9 rotavirus-neutralizing monoclonal antibodies (MAbs) directed to VP7, which bound by direct enzyme immunoassay (EIA) to P1A[8], G9 rotaviruses F45, WI61, and AU32, for their ability to recognize the New Delhi G9 rotavirus 116E. Only one MAb (MAb F45:1) bound to P[11], G9 virus 116E to a high titer by EIA. This MAb was incorporated into an indirect EIA for G serotyping, which was validated with prototype cultivable human rotaviruses of G types 1 to 4 and 9. The EIA was compared with genotyping by reverse transcriptase PCR (RT-PCR) under code for the determination of the G types of rotaviruses obtained from neonates in New Delhi, India. The sensitivities of RT-PCR and EIA (after two additional freeze-thaw cycles) for the typing of G9 rotaviruses were 91 and 86%, respectively, for 24 culture-adapted rotavirus strains. The untypeable culture-adapted rotavirus samples also were unreactive with VP7 group antigen-reactive MAb 60. After two additional freeze-thaw cycles, only 26 of 42 (62%) of stools containing rotavirus typed as G9 by RT-PCR were positive for G9 rotavirus by EIA. Stools containing rotavirus untypeable by EIA contained significantly less MAb 60-reactive VP7 antigen (P = 0. 0001) than the stools containing typeable rotavirus. Thus, RT-PCR genotyping was the more sensitive method for determination of G9 type, but a serotype was readily determined in rotavirus samples containing MAb 60-reactive VP7 antigen by an EIA that incorporates MAb F45:1.

Antibodies, Monoclonal↗

Serological diagnosis of celiac disease.

In developing countries like India, unlike in the West, diagnosis of celiac disease is a dilemma because the histological changes consistent with celiac disease may not be pathognomonic of the disease. We need clarity on how to use one or more of the serological antibodies, namely IgG and IgA anti-gliadin and IgA anti-endomysial antibodies as independent disease markers or as adjuncts to clinico-histological diagnosis. In this review, various possible algorithms have been discussed. The serological antibodies can be used as reliable screening tests to decide whom to biopsy and to interpret histological changes in our settings where malnutrition and intercurrent enteric infection are common.

Antibodies, Anti-Idiotypic↗

Association of genital mycoplasma colonization with low birth weight.

OBJECTIVE: This study was conducted to document the prevalence of maternal genital tract colonization by Ureaplasma urealyticum and Mycoplasma hominis, and to assess its association with low birth weight (LBW) and prematurity. METHODS: The high vaginal swabs of pregnant women in spontaneous labor after 26 weeks of gestation were cultured for U. urealyticum and M. hominis. Clinical details and perinatal outcomes including birth weight and gestation were documented. RESULTS: Of a total of 303 women enrolled, 148 (48.8%) had positive vaginal cultures for U. urealyticum, while only five (1.6%) grew M. hominis. The mean birth weight and the incidences of LBW and preterm neonates among ureaplasma positive and ureaplasma negative mothers were statistically comparable. CONCLUSIONS: U. urealyticum emerged as a common inhabitant of the lower genital tract of women in labor, being present in nearly half of them. Its presence was not a risk factor of LBW or prematurity. Maternal colonization with M. hominis was uncommon.

Adult↗

Efficacy of milk versus yogurt offered as part of a mixed diet in acute noncholera diarrhea among malnourished children.

We compared the clinical outcome of acute diarrhea in 96 malnourished boys (aged 4 to 47 months) receiving full-strength milk compared with yogurt offered as part of a mixed diet. All had weight for height less than or equal to 80% of the National Centre for Health Statistics median. They were randomly assigned to receive milk formula (MF; 67 cal/100 ml) or yogurt formula (YF; prepared from the same milk formula) at the rate of 120 ml/kg body weight in seven divided feedings. Stool-reducing substances (> 1%) were detected more frequently in the MF group, and the differences were significant for day 3 of the study (p = 0.04). However, the geometric mean (95% confidence interval) of the total stool weights (gm/kg) during 0 to 72 hours (MF 128.8 [103, 161.4]; YF 110.9 [87, 142.2]) was comparable (p = 0.37) as was the median (range) duration of diarrhea (hours) (MF 45 [4, 183]; YF 52 [7, 173] p = 0.94). The treatment failure rates in the MF (8.2%) and YF (6.3%) groups were also similar (p = 0.67). The children consuming milk had higher median percent weight gain at the end of 72 hours of the study (p = 0.04) and at recovery (p = 0.02). Routine substitution of yogurt as small frequent feedings as an addition for semisolid food to malnourished children with acute diarrhea does not achieve any significant clinical benefit versus milk.

Acute Disease↗

Careseeking for illness in young infants in an urban slum in India.

Illness in infants in the first two months of life can take a precipitous life-threatening course, and requires timely and appropriate medical assessment and management. We conducted a focused ethnographic study of illness in young infants and associated careseeking practices in an urban slum in New Delhi, India, in order to identify the constraints in securing effective care for severe illness in this age group. The findings suggest that maternal recognition of illness is not a limiting factor in the use of health care services for sick young infants in this setting. Mothers respond to a number of important signs of illness, including changes in the young infant's sleeping or feeding behavior, and they are usually prompt in seeking care outside the home. They are not able, however, to discriminate among the many sources of health care available in this setting, and give preference to local unqualified private practitioners. Most practitioners, including qualified medical practitioners, display critical failures in the assessment and management of sick young infants. The continuity and effectiveness of care is further compromised by the caretakers' expectations of rapid cure, which result in discontinued treatment courses and frequent changes in practitioners, and by their reluctance to seek hospital care. The implications of these findings for the design of programs to reduce young infant mortality are discussed. In particular, the feasibility and acceptability of hospital referrals according to current program guidelines are called into question.

Adolescent↗

Nutrient absorption from a fat-enriched diet in young malnourished children: a randomized controlled trial.

A randomized, controlled trial was undertaken to compare nutrient absorption from low fat (22.2% energy as fat) and high fat (48% energy as fat)-containing mixed diets in 39 (26M, 13F) malnourished children aged < 2 y. Subjects of both dietary groups, standard (SDG, n = 18) and experimental (EDG, n = 21), were offered 184.5 ml of feeds/kg body weight/24 h that provided 146 kcal with the low fat diet and 216 kcal with the high fat diet, respectively. The baseline clinical and biochemical parameters and the volume of feeds consumed by the patients in the two groups were comparable. Thus, the subjects in the EDG were ingesting a mean (95% CI) of 50% (23.8%, 76.2%) extra energy than that eaten by the SDG. Coefficients of absorption of energy, nitrogen and carbohydrate were similar in the two dietary groups (p = 0.08-0.98). Median (binomial exact 95% CI) fat absorption among subjects receiving the high fat diet (96.3; 92.9, 98.6) was 7% more than in those consuming the low fat diet (89.3; 86.7, 94.1) (p = 0.01). Subjects of the EDG thus, retained almost 50% additional energy as compared to that by SDG.

Chi-Square Distribution↗

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.

Acute Disease↗