ICMR-DBT Guidelines for Evaluation of Probiotics in Food.

There has been an increased influx of probiotic products in the Indian market during the last decade. However, there has been no systematic approach for evaluation of probiotics in food to ensure their safety and efficacy. An initiative was, therefore, taken by the Indian Council of Medical Research (ICMR) along with the Department of Biotechnology (DBT) to formulate guidelines for regulation of probiotic products in the country. These guidelines define a set of parameters required for a product/strain to be termed as ‘probiotic’. These include identification of the strain, in vitro screening for probiotic characteristics, animal studies to establish safety and in vivo animal and human studies to establish efficacy. The guidelines also include requirements for labeling of the probiotic products with strain specification, viable numbers at the end of shelf life, storage conditions, etc., which would be helpful to the consumers to safeguard their own interest.

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 ³6 to £36 months with malnutrition, defined as Weight for height (WHZ) <–2 to ³–3 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.

Diffuse intra-abdominal fibromatosis-report of a new entity with review of literature.

Fibromatosis, arare non-neoplastic spindle cell proliferation of unknown aetiology, can occur anywhere in the body. Though extra-abdominal sites are commonly involved, intra-abdominal fibromatosis has also been described. Described herein is an unusual case of diffuse intra-abdominal fibromatosis in a 9-year-old boy, who could not be salvaged despite extensive medical management.

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.

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.

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.

Chlamydia trachomatis infection among pregnant women: prevalence and prenatal importance.

BACKGROUND: Chlamydia trachomatis infection in pregnant women is suspected to result in low birth-weight and premature infants. We conducted studies to ascertain the prevalence of this infection among pregnant women in our setting and whether its presence is a risk factor for low birth-weight or prematurity. METHODS: In the first study, 94 pregnant women between 26 and 30 weeks of gestation were screened for infection with Chlamydia trachomatis. The second investigated a cohort of 172 pregnant women presenting in spontaneous labour. The infection status was related to perinatal outcome in terms of birth-weight and gestation. In both the studies, Chlamydia trachomatis infection was diagnosed using the Chlamydiazyme test performed on endocervical swabs. RESULTS: The prevalence of Chlamydia trachomatis infection in mid-pregnancy and at labour was 17% (16/94) and 18.6% (32/172), respectively. Women with infection were relatively older than those without it [mean (SD) age: 26.6 (4.5) years v. 24.8 (3.6) years, p = 0.01]. The mean (SD) birth-weight [2869 (611) g v. 2814 (496) g], gestation [38.5 (2.6) weeks v. 38.3 (2.0) weeks], and incidence of low birth-weight [18.7% v. 20.7%] as well as prematurity [9.4% v. 10.7%] were similar among neonates born to women with or without infection. Neonates born to infected mothers experienced purulent conjunctivitis more frequently than those born to non-infected mothers [12.5% v. 2.8%, p = 0.04]. CONCLUSION: Chlamydia trachomatis is a relatively common infection in pregnant women. However, it was not associated with either low birth-weight or prematurity.

Lessons learnt from Diarrheal Diseases Control Program and implications for the future.

The national Diarrheal Disease Control Program was launched with the aim of improving the knowledge and practice of appropriate case management among caretakers of young children as well as health care providers. The National Family Health Survey (1992-3) revealed that 42.7% of mothers knew about ORS packets and 25.9% had ever used them. ORS use rates in children who suffered from diarrhea during the previous two weeks varied from 8.3% in Rajasthan to 50.1% in West Bengal. These findings represent substantial accomplishment, and also are a reminder that we still have to reach more than half of the households. Further analysis of the NFHS data showed that exposure to electronic mass media had a significant impact on mothers' awareness about ORS packets (56% in exposed, 32% in unexposed) and ORT use rates (38% in exposed, 25% in unexposed). In this review, future strategies for increasing the impact of the program are discussed. These include involvement of licensed and unlicensed medical practitioners, greater use of the electronic mass media, ORS standardization, greater focus on poorly performing states and resolving residual issues in the case management of diarrhea in malnourished children and infants under 6 months of age.

Histologic chorioamnionitis & its association with prematurity in a hospital-based study.

This prospective study was undertaken to study the occurrence of histologic chorioamnionitis and determine its association with prematurity; and to assess whether colonization of the genital tract of pregnant women by genital mycoplasmas or Chlamydia trachomatis is a risk factor for histologic chorioamnionitis. A total of 268 women with singleton pregnancies of over 26 weeks gestation were subjected to high vaginal cultures of genital mycoplasmas and endocervical specimens for chlamydia antigen. Placental histopathology was performed on multiple sections. Histologic chorioamnionitis was documented in 22.4 per cent (60/208) placentae. Genital tract colonization with Ureaplasma urealyticum or C. trachomatis was not a risk factor for histologic chorioamnionitis. Neonates born in association with histologic chorioamnionitis had a mean birth weight 111 g lower than those born without this lesion (2626.9 +/- 702 g vs 2737.8 +/- 500 g, NS). The relative risk (95% confidence interval) of prematurity in the presence of histologic chorioamnionitis was 1.49 (0.87-2.53). Analysis of linear trend in proportions for prevalence of histologic chorioamnionitis with decreasing gestation showed a significant association (P = 0.047, 1-tail). These results taken together suggest that histologic chorioamnionitis may be a risk factor of prematurity, but of only a modest magnitude.

Cholestatic jaundice due to congenital Toxoplasma gondii infection.

A case of congenital toxoplasmosis manifesting as hepatosplenomegaly and cholestatic jaundice in a 4 month old child is reported. To the best of our knowledge this is the first report of cholestatic jaundice due to congenital toxoplasmosis from India. The child was successfully treated with sulphadiazine and pyremethamine combination.

Effect of zinc supplementation on cell-mediated immunity and lymphocyte subsets in preschool children.

OBJECTIVE: In a zinc supplementation trial (with a significant impact on diarrheal morbidity), to evaluate effect of zinc supplementation on cellular immune status before and after 120 days of supplementation. DESIGN: A double blind, randomized controlled trial with immune assessment at baseline and after 120 days on supplement. SETTING: Community based study in an urban slum population. SUBJECTS: Randomly selected children (zinc 38, control 48), had a Multitest CMI skin test at both times. In 66 children (zinc 22, control 34), proportions of CD3, CD4, CD8, CD16, CD20 cells and the CD/CD8 ratio were also estimated using a whole blood lysis method and flowcytometry. INTERVENTION: Zinc gluconate to provide elemental zinc 10 mg daily and 20 mg during diarrhea. MAIN OUTCOME RESULTS: Regarding CMI, the percentage of anergic or hypoergic children (using induration score) decreased from 67% to 47% in the zinc group, while in the control group it remained unchanged (73% vs 71%) (p = 0.05). The percentage of children deteriorating between first and second tests was significantly lower in the zinc group (13% vs 33%, p = 0.03). Regarding lymphocyte subsets, the zinc group had a significantly higher rise in the geometric means of CD3 (25%, p = 0.02), CD4 (64% p = 0.001), and CD4/CD8 ratio (73% p = 0.004) with no difference in CD8 and CD20. The rise in CD4 was significantly higher in the zinc as compared to the control group; the ratio of geometric means was 1.45 (95% CI, 1.03-2.01). CONCLUSION: Zinc supplementation improves cellular immune status, which may have been one of the mechanisms for observed impact of zinc supplementation on diarrheal morbidity.

Epidemiology & management of persistent diarrhoea in children of developing countries.

Diarrhoea that begins acutely but lasts longer than two weeks is defined to be persistent. Revised estimates in developing countries including India showed that acute diarrhoea accounts for 35 per cent, dysentery 20 per cent and non-dysenteric persistent diarrhoea (PD) for 45 per cent of total diarrhoeal deaths. PD also often changes marginal malnutrition to more severe forms. Factors that increase the risk of acute diarrhoea becoming persistent have been identified in India and other developing countries. These include antecedent malnutrition, micronutrient deficiency particularly for zinc and vitamin A, transient impairment in cell mediated immunity, infection with entero aggregative Escherichia coli and cryptosporidium, sequential infection with different pathogens and lack of exclusive breast feeding during the initial four months of life particularly use of bovine milk. Several issues regarding the management of persistent diarrhoea in hospitalized children in India have been resolved. Diets providing modest amounts of milk mixed with cereals are well tolerated. In those who fail on such diets providing carbohydrate as a mixture of cereals and glucose or sucrose hasten recovery. The role of antimicrobial agents and individual micronutrients in PD is currently being investigated. A management algorithm appropriate for India and other developing countries has been developed and found to substantially reduce case fatality in hospital settings to about 2-3 per cent. Recent epidemiological and clinical research related to persistent diarrhoea is also reviewed.

Reduced-osmolarity oral rehydration salts solution multicentre trial: implications for national policy.

World Health Organization (WHO) recommended standard ORS solution has sodium (90 mmol/L) and glucose (111 mmol/L) almost in the ratio of 1:1 and a total osmolarity of 311 mmol/L. There are concerns that the sodium or glucose concentration and the overall osmolarity in the formulation is not appropriate. Therefore, the efficacy of standard and reduced-osmolarity ORS solutions in young children with acute diarrhea was evaluated in a recent WHO supervised multicentre trial conducted in India (New Delhi), Brazil, Mexico and Peru. The implications of trial results are discussed. In non-cholera diarrhea, both the standard and reduced osmolarity ORS solutions were effective in achieving clinical rehydration. The stool output was 39% higher in the standard ORS solution group as compared to the reduced-osmolarity ORS solution group. The duration of diarrhea was 22% higher in the standard ORS solution group. The risk of requiring supplementary intravenous infusion was increased in children treated with standard ORS solution [relative risk 1.4 (0.9-2.4)]; this benefit was not observed in Indian patients due to high breast feeding rate. The mean sodium concentration at 24 hours after admission was lower in the reduced osmolarity ORS solution group [135 (134-136) vs 138 (136-139), p < 0.01). The low osmolarity ORS deserves to be evaluated in adult cholera to determine its efficacy and any excess hyponatreamia. Meanwhile, it is reassuring that the WHO formulation was effective and its use was not associated with hypenatremia even in young children. Efforts must continue to be made to promote WHO-ORS while research to improve it further is welcome.