Biomedical subjects

M K Bhan

Publications and source records attributed to M K Bhan.

At least 19 recordsLinked to original sources

PubMed2003

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed1999

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↗

PubMed1999

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↗

PubMed1999

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↗