Racecadotril in the Management of Rotavirus and Non-rotavirus Diarrhea in Under-five Children: Two Randomized, Double-blind, Placebo-controlled Trials.

Objective: To study the effect of racecadotril on reduction in the duration of acute rotavirus and non-rotavirus diarrhea. Design: Two randomized double-blind placebo-controlled trials Setting: Community-based trial in an urban area in Vellore, hospital-based trial at a secondary hospital in Vellore Participants: 199 and 130 3-59 month old children in the community- and hospital-based trials, respectively. Methods: Racecadotril (1.5 mg/kg/dose, thrice a day for three days) or placebo were given to manage acute diarrhea in both trials. Main outcome measure: Median duration of diarrhea. Results: Among 124 children completing the hospital trial, the median duration of diarrhea was 25 h in both arms (P=0.5); median total stool weight was 74 g/kg and 53.5 g/kg in racecadotril group and placebo group, respectively (P=0.4); and average fluid intake per day was 3.6 mL/kg/h and 3mL/kg/h in racecadotril and placebo arms, respectively (P=0.3). Among rotavirus-positive children, median duration of diarrhea was 26.9 h and 30.2 h in racecadotril and placebo arms, respectively (P=0.7). In the community, 196 completed the trial, the median duration of diarrhea was 2 days for both arms (P=0.8) and rotavirus positive children had similar outcomes with median diarrheal duration of 3 d in both arms (P=0.4). Conclusion: Treatment with racecadotril did not reduce diarrheal duration, stool volume or the requirement for fluid replacement in children with acute gastroenteritis, both with and without rotavirus infection.

Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India, 2014 and Updates on Immunization.

Justification: There is a need to review/revise recommendations about existing vaccines in light of recent developments in the field of vaccinology. Process: Following an IAP ACVIP meeting on April 19 and 20, 2014, a draft of revised recommendations for the year 2014 and updates on certain vaccine formulations was prepared and circulated among the meeting participants to arrive at a consensus. Objectives: To review and revise recommendations for 2014 Immunization timetable for pediatricians in office practice and issue statements on certain new and existing vaccine formulations. Recommendations: The major changes in the 2014 Immunization Timetable include two doses of MMR vaccine at 9 and 15 months of age, single dose recommendation for administration of live attenuated H2 strain hepatitis A vaccine, inclusion of two new situations in ‘high-risk category of children’ in context with ‘pre-exposure prophylaxis’ of rabies, creation of a new slot at 9-12 months of age for typhoid conjugate vaccine for primary immunization, and recommendation of two doses of human papilloma virus vaccines with a minimum interval of 6 months between doses for primary schedule of adolescent/ preadolescent girls aged 9-14 years. There would not be any change to the committee’s last year’s (2013) recommendations on pertussis vaccination and administration schedule of monovalent human rotavirus vaccine. There is no need of providing additional doses of whole-cell pertussis vaccine to children who have earlier completed their primary schedule with acellular pertussis vaccine-containing products. A brief update on the new Indian Rotavirus vaccine, 116E is also provided. The committee has reviewed and offered its recommendations on the currently available pentavalent vaccine (DTwP+Hib+Hepatitis-B) combinations in Indian market. The comments and footnotes for several vaccines are also updated and revised.

Indian Academy of Pediatrics (IAP) Recommended Immunization Schedule for Children Aged 0 through 18 years – India, 2013 and Updates on Immunization.

Justification: There is a need to review/revise recommendations about existing vaccines in light of recent developments in the field of vaccinology where new developments are taking place regularly at short intervals. Process: Following an IAP ACVIP meeting on 3rd and 4th August, 2013, a draft of revised recommendations for the year 2013 and updates on certain new vaccine formulations was prepared and circulated among the meeting participants to arrive at a consensus. Objectives: To review and revise recommendations for 2013 Immunization timetable for pediatricians in office practice and issue statements on new vaccine formulations. Recommendations: The major change in the 2013 Immunization timetable was made in the recommendations pertaining to pertussis immunization. Taking in to the consideration of recent outbreaks of pertussis in many industrialized countries using acellular pertussis (aP) vaccines and subsequent finding of faster waning of the same in comparison to whole-cell pertussis (wP) vaccines and superior priming with wP vaccines than aP vaccines, the committee has now recommended wP vaccines for the primary series of infant vaccination. Guidelines are now also issued on the preference/ selection of a particular aP vaccine in case it is not feasible to use wP vaccine, and use of Tdap vaccine during pregnancy. The administration schedule of monovalent human rotavirus vaccine, RV1 has been revised to 10 and 14 weeks from existing 6 and 10 weeks. Recommendation is made for the need of booster dose of live attenuated SA-14-14-2 JE vaccine. Updates and recommendations are issued on new typhoid conjugate vaccine, inactivated vero-cell culture derived SA-14- 14-2 JE vaccine, inactivated vero-cell derived Kolar strain, 821564XY JE vaccine, and new meningococcal conjugate vaccines. This year the recommended immunization schedule with range for persons aged 0 through 18 years is being published together instead of two separate schedules. A subcategory of ‘general instruction’ is added in footnotes. The comments and footnotes for several vaccines are revised and separate instructions for ‘routine vaccination’ and ‘catch-up vaccination’ are added in the footnotes section wherever applicable.

Birthweight Centile Charts from Rural Community-based Data from Southern India.

Objective: The objectives of the study were to estimate gestational age specific birthweight centiles from healthy pregnancies in a defined rural block and compare the under-two month mortality rates in those belonging to the lowest and highest centile groups. Design: Retrospective chart review. Setting: Routine data collected regarding all pregnancies, births and deaths occurring in Kaniyambadi, a rural block in Southern India, between 2003 to 2012. Subjects: All singleton live newborns of women without known major antenatal risk factors. Main outcome measures: Gestational age- and sex-specific birthweight centile curves were created using the LMS method. Mortality rates for the first two months of life were calculated for those in various centile groups. Results: The median birthweight at term was lower for the study subjects as compared to the median birth weights in the WHO child growth standards 2006, the US and the UK standards. Mortality rates for those with birthweights both below the 3rd centile as well as above the 97th centile higher than for those between 3rd and 97th centiles. Conclusions: While absolute values of birthweights were lower than the WHO 2006 child growth standards there was a J shaped curve of birthweight and mortality. This suggests that in a given population, mortality increases at extremes of birthweights, even if some of these birthweights may be considered normal by other standards.

Locally Made Ready-to-Use Therapeutic Food for Treatment of Malnutrition: A Randomized Controlled Trial.

Objective: To evaluate the effectiveness of a locally made ready-to-use therapeutic food (RUTF) in decreasing mild to moderate malnutrition. Design: A randomized open label, controlled trial. Setting: Pre-schools run by the Department of Community Health in Kaniyambadi administrative block, Vellore, India; duration of follow-up – 3 months from the date of recruitment. Participants: Pupils aged 18-60 months with Weight-for- Age ≤2 SD. Interventions: A locally produced energy-dense supplement (RUTF), and the current standard of care [teaching caregivers how to make a fortified cereal-milk supplement called High Calorie Cereal Milk (HCCM)]. Main outcome measures: Increase in weight-for-age status; increase in levels of plasma zinc, vitamin B12, serum albumin and haemoglobin. Results: The Mean (SD) weight gain at 3 months was higher in the RUTF group: RUTF (n=51): 0.54 kg; (SE = 0.05; 95% CI = 0.44 – 0.65) vs HCCM (n=45): 0.38 kg; (SE = 0.06; 95% CI = 0.25 – 0.51), P = 0.047. The weight gain per kilogram of body weight was directly proportional to the severity of malnutrition. Conclusions: Community-based treatment showed weight gain in both groups, the gain being higher with RUTF. Key words: India, Indigenous, Management, Malnutrition, Nutrition therapy.

Multi-center surveillance for pneumonia & meningitis among children (<2 yr) for Hib vaccine probe trial preparation in India.

Background & objectives: Severe clinical pneumonia and meningitis caused by Haemophilus influenzae type b in children less than 5 yr old is preventable by use of Hib vaccine. However, data on Hib burden in India are limited. To support an evidence-based decision for Hib vaccine introduction in India, a vaccine probe study was planned. This paper presents the results of the preparatory phase for such a study, which aimed to determine the feasibility of conducting a randomized vaccine probe study and to estimate the incidence of all causes of pneumonia and meningitis. The preparatory study included population-based, hospital-based and carriage surveillance. Methods: Children aged 18-24 months and were enrolled at PGIMER, Chandigarh, CMC, Vellore and NICED, Kolkata, from July 2005 to December 2006. At the time of enrollment, parents were informed about the signs and symptoms of pneumonia and meningitis, and were encouraged to take the child to study hospitals for treatment. Hospitalized children less than two years of age suspected of having pneumonia and/or meningitis were enrolled in study hospitals, whether or not they were from the cohort population. Patients were examined clinically and received chest radiograph for suspected cases of pneumonia or lumbar puncture for suspected cases of meningitis. Blood culture was done for both pneumonia and meningitis patients. Cerebrospinal fluid (CSF) was tested for biochemistry, culture, latex agglutination test and polymerase chain reaction. Nasopharyngeal swabs were collected from healthy children less than 2 yr of age at immunization clinics to estimate Hib carriage. Results: A cohort of 17,951 children were recruited for the population-based arm. The incidence of severe clinical pneumonia ranged from 2717 to 7890 per 100,000 child-years of observation; suspected meningitis ranged from 1971 to 2433 per 100,000 child-years of observation. In the hospital-based study 7/90 (7.8%), 29/98 (29.6%) and 38/181 (21.0%) of CSF samples with cell count ≥100 WBCs/mm3 were purulent at Chandigarh, Kolkata and Vellore respectively. Of these purulent CSF samples, Hib was detected in 2, 6 and 11 cases, respectively. The Hib nasopharyngeal carriage prevalence ranged from 6.0 - 7.6 per cent. Interpretation & conclusions: Incidence of severe clinical pneumonia is comparable with other studies from India but that of suspected meningitis is higher. Although rates of Hib meningitis cannot be calculated from a hospital-based study, there is evidence of Hib meningitis in these study settings. Hib carriage prevalence indicates that Hib is present and circulating in these study areas. There is a significant burden of pneumonia and meningitis among children in India. Continued strengthening of laboratory capacity and bacterial surveillance systems are necessary.

Retrospective Surveillance for Intussusception in Children Aged Less than Five Years in a South Indian Tertiary-care Hospital.

To facilitate the assessment of the safety profile of rotavirus vaccines effectively, baseline data on intussusception are important for comparison with intussusception rates following the introduction of vaccine. The aim of the study was to describe epidemiological and clinical features of intussusception in children aged less than five years in an Indian medical facility. Hospital data on intussusception for children discharged during 1 January 2001–30 June 2004 from the Christian Medical College Hospital, Vellore, India, were reviewed. Relevant information was extracted from medical records to classify cases according to the criteria of the Brighton Collaboration Intussusception Working Group. Complete review of medical records for clinical and demographic information was only performed for those cases fulfilling level 1 diagnostic certainty (definite intussusception) (Study ID 101245). During the surveillance period, 31 infants and children with definite intussusception were identified. The majority (61.2%) of the cases occurred in the first year of life. The male : female ratio was 3.4 : 1. Intussusception cases occurred round the year with no distinct seasonality. No intussusception-associated death was recorded. This study provides baseline data on intussusception in South India. Cases identified in the study were similar in presentation and demographics as those observed in other Asian settings. Prospective surveillance systems, using standardized case definitions will further increase the understanding of the aetiology and epidemiology of intussusception, especially as new rotavirus vaccines are made available.