Anju Sinha

Zinc Supplementation in Young Children with Acute Diarrhea in India

BACKGROUNDnIn developing countries the duration and severity of diarrheal illnesses are greatest among infants and young children with malnutrition and impaired immune status, both factors that may be associated with zinc deficiency. In children with severe zinc deficiency, diarrhea is common and responds quickly to zinc supplementation.nnnMETHODSnTo evaluate the effects of daily supplementation with 20 mg of elemental zinc on the duration and severity of acute diarrhea, we conducted a double-blind, randomized, controlled trial involving 937 children, 6 to 35 months of age, in New Delhi, India. All the children also received oral rehydration therapy and vitamin supplements.nnnRESULTSnAmong the children who received zinc supplementation, there was a 23 percent reduction (95 percent confidence interval, 12 percent to 32 percent) in the risk of continued diarrhea. Estimates of the likelihood of recovery according to the day of zinc supplementation revealed a reduction of 7 percent (95 percent confidence interval, -9 percent to +22 percent) in the risk of continued diarrhea during days 1 through 3 and a reduction of 38 percent (95 percent confidence interval, 27 percent to 48 percent) after day 3. When zinc supplementation was initiated within three days of the onset of diarrhea, there was a 39 percent reduction (95 percent confidence interval, 7 percent to 61 percent) in the proportion of episodes lasting more than seven days. In the zinc-supplementation group there was a decrease of 39 percent (95 percent confidence interval, 6 percent to 70 percent) in the mean number of watery stools per day (P = 0.02) and a decrease of 21 percent (95 percent confidence interval, 10 percent to 31 percent) in the number of days with watery diarrhea. The reductions in the duration and severity of diarrhea were greater in children with stunted growth than in those with normal growth.nnnCONCLUSIONnFor infants and young children with acute diarrhea, zinc supplementation results in clinically important reductions in the duration and severity of diarrhea.

Typhoid fever in children aged less than 5 years

BACKGROUNDnCalculation 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.nnnMETHODSnA 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.nnnFINDINGSn63 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.nnnINTERPRETATIONnOur 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.

Association between Helicobacter pylori Infection and Increased Risk of Typhoid Fever

Helicobacter pylori infection has been reported to increase the risk of cholera. This nested case-control study was conducted to determine whether H. pylori infection is associated with occurrence of typhoid fever. Eighty-three case subjects of culture-proven typhoid fever were identified through a 1-year surveillance of subjects aged 0-40 years in an urban slum. Two age- and sex-matched neighborhood control subjects were concurrently selected for each case subject. Serum anti-H. pylori immunoglobulin G antibodies were measured in case and neighborhood control subjects. For determining other risk factors, 2 additional community control subjects per case were selected. There was a significant association between the presence of serum anti-H. pylori immunoglobulin G antibodies and typhoid fever (adjusted odds ratio, 2.03; 95% confidence interval, 1.02-4.01). Illiteracy, being part of a nuclear family, nonuse of soap, and consumption of ice cream were also associated with a significantly greater risk of typhoid fever. This study provides the first empiric evidence that H. pylori infection is associated with an increased risk of typhoid fever.

Changes in cause-specific neonatal and 1–59-month child mortality in India from 2000 to 2015: a nationally representative survey

Summary Background Documentation of the demographic and geographical details of changes in cause-specific neonatal (younger than 1 month) and 1–59-month mortality in India can guide further progress in reduction of child mortality. In this study we report the changes in cause-specific child mortality between 2000 and 2015 in India. Methods Since 2001, the Registrar General of India has implemented the Million Death Study (MDS) in 1·3 million homes in more than 7000 randomly selected areas of India. About 900 non-medical surveyors do structured verbal autopsies for deaths recorded in these homes. Each field report is assigned randomly to two of 404 trained physicians to classify the cause of death, with a standard process for resolution of disagreements. We combined the proportions of child deaths according to the MDS for 2001–13 with annual UN estimates of national births and deaths (partitioned across Indias states and rural or urban areas) for 2000–15. We calculated the annual percentage change in sex-specific and cause-specific mortality between 2000 and 2015 for neonates and 1–59-month-old children. Findings The MDS captured 52u2008252 deaths in neonates and 42u2008057 deaths at 1–59 months. Examining specific causes, the neonatal mortality rate from infection fell by 66% from 11·9 per 1000 livebirths in 2000 to 4·0 per 1000 livebirths in 2015 and the rate from birth asphyxia or trauma fell by 76% from 9·0 per 1000 livebirths in 2000 to 2·2 per 1000 livebirths in 2015. At 1–59 months, the mortality rate from pneumonia fell by 63% from 11·2 per 1000 livebirths in 2000 to 4·2 per 1000 livebirths in 2015 and the rate from diarrhoea fell by 66% from 9·4 per 1000 livebirths in 2000 to 3·2 per 1000 livebirths in 2015 (with narrowing girl–boy gaps). The neonatal tetanus mortality rate fell from 1·6 per 1000 livebirths in 2000 to less than 0·1 per 1000 livebirths in 2015 and the 1–59-month measles mortality rate fell from 3·3 per 1000 livebirths in 2000 to 0·3 per 1000 livebirths in 2015. By contrast, mortality rates for prematurity or low birthweight rose from 12·3 per 1000 livebirths in 2000 to 14·3 per 1000 livebirths in 2015, driven mostly by increases in term births with low birthweight in poorer states and rural areas. 29 million cumulative child deaths occurred from 2000 to 2015. The average annual decline in mortality rates from 2000 to 2015 was 3·3% for neonates and 5·4% for children aged 1–59 months. Annual declines from 2005 to 2015 (3·4% decline for neonatal mortality and 5·9% decline in 1–59-month mortality) were faster than were annual declines from 2000 to 2005 (3·2% decline for neonatal mortality and 4·5% decline in 1–59-month mortality). These faster declines indicate that India avoided about 1 million child deaths compared with continuation of the 2000–05 declines. Interpretation To meet the 2030 Sustainable Development Goals for child mortality, India will need to maintain the current trajectory of 1–59-month mortality and accelerate declines in neonatal mortality (to >5% annually) from 2015 onwards. Continued progress in reduction of child mortality due to pneumonia, diarrhoea, malaria, and measles at 1–59 months is feasible. Additional attention to low birthweight is required. Funding National Institutes of Health, Disease Control Priorities Network, Maternal and Child Epidemiology Estimation Group, and University of Toronto.BACKGROUNDnDocumentation of the demographic and geographical details of changes in cause-specific neonatal (younger than 1 month) and 1-59-month mortality in India can guide further progress in reduction of child mortality. In this study we report the changes in cause-specific child mortality between 2000 and 2015 in India.nnnMETHODSnSince 2001, the Registrar General of India has implemented the Million Death Study (MDS) in 1·3 million homes in more than 7000 randomly selected areas of India. About 900 non-medical surveyors do structured verbal autopsies for deaths recorded in these homes. Each field report is assigned randomly to two of 404 trained physicians to classify the cause of death, with a standard process for resolution of disagreements. We combined the proportions of child deaths according to the MDS for 2001-13 with annual UN estimates of national births and deaths (partitioned across Indias states and rural or urban areas) for 2000-15. We calculated the annual percentage change in sex-specific and cause-specific mortality between 2000 and 2015 for neonates and 1-59-month-old children.nnnFINDINGSnThe MDS captured 52u2008252 deaths in neonates and 42u2008057 deaths at 1-59 months. Examining specific causes, the neonatal mortality rate from infection fell by 66% from 11·9 per 1000 livebirths in 2000 to 4·0 per 1000 livebirths in 2015 and the rate from birth asphyxia or trauma fell by 76% from 9·0 per 1000 livebirths in 2000 to 2·2 per 1000 livebirths in 2015. At 1-59 months, the mortality rate from pneumonia fell by 63% from 11·2 per 1000 livebirths in 2000 to 4·2 per 1000 livebirths in 2015 and the rate from diarrhoea fell by 66% from 9·4 per 1000 livebirths in 2000 to 3·2 per 1000 livebirths in 2015 (with narrowing girl-boy gaps). The neonatal tetanus mortality rate fell from 1·6 per 1000 livebirths in 2000 to less than 0·1 per 1000 livebirths in 2015 and the 1-59-month measles mortality rate fell from 3·3 per 1000 livebirths in 2000 to 0·3 per 1000 livebirths in 2015. By contrast, mortality rates for prematurity or low birthweight rose from 12·3 per 1000 livebirths in 2000 to 14·3 per 1000 livebirths in 2015, driven mostly by increases in term births with low birthweight in poorer states and rural areas. 29 million cumulative child deaths occurred from 2000 to 2015. The average annual decline in mortality rates from 2000 to 2015 was 3·3% for neonates and 5·4% for children aged 1-59 months. Annual declines from 2005 to 2015 (3·4% decline for neonatal mortality and 5·9% decline in 1-59-month mortality) were faster than were annual declines from 2000 to 2005 (3·2% decline for neonatal mortality and 4·5% decline in 1-59-month mortality). These faster declines indicate that India avoided about 1 million child deaths compared with continuation of the 2000-05 declines.nnnINTERPRETATIONnTo meet the 2030 Sustainable Development Goals for child mortality, India will need to maintain the current trajectory of 1-59-month mortality and accelerate declines in neonatal mortality (to >5% annually) from 2015 onwards. Continued progress in reduction of child mortality due to pneumonia, diarrhoea, malaria, and measles at 1-59 months is feasible. Additional attention to low birthweight is required.nnnFUNDINGnNational Institutes of Health, Disease Control Priorities Network, Maternal and Child Epidemiology Estimation Group, and University of Toronto.

An Assessment of Wastage Multiplier Factor (WMF) and Percent Wastage of Vaccines during Routine Immunization Under the Universal Immunization Programme (UIP), Government of India (GOI)

At the inception of the UIP, the wastage and the WMF were built into the programme based on the guidelines of WHO/UNICEF. Indian Council of Medical Research (ICMR) conducted a study through its network of five Human Reproductive Research Centres (HRRCs) in 10 districts of four states of India to estimate the wastage and the wastage multiplier factor for the six vaccines currently being used under the UIP, GOI. Objectives: (i) To determine the amount of wastage of vaccines being used under UIP, (ii) To determine the reasons of wastage of vaccine, and (iii) To suggest methods for reducing the wastage of vaccine. Methods: The study was conducted through the network of five HRRCs in ten districts located in four states of India. Wastage at the point of administration of vaccine was estimated. Results and conclusion: WMF and % wastage were calculated separately for each of the six vaccines for each district. The estimated % wastage and its range, the estimated WMF and its range for DPT, DT, TT, OPV, BCG and Measles was respectively 38.9 (12.8-69.7), 1.64 (1.15-3.31); 39.1 (27.3-61.4), 1.64 (1.38-2.59); 48.0 (20.9-67.1), 1.92 (1.26-3.04); 52.7 (22.1-75.7), 2.12 (1.28-4.12); 49.3 (30.3-70.2), 1.97 (1.43-3.36); 38.7 (20.8-50.1), 1.39 (1.26- 2.00). The estimated % wastage of five of the six vaccines namely, DPT, DT, TT, OPV and Measles was found to be significantly higher than what is assumed in the UIP (p<0.0001). Among all the other reasons for wastage of vaccines, “Residual vaccine left in the vial” was the most frequently reported reason for wastage of vaccines. Therefore, vials of variable size with house to house campaign were recommended to minimize wastage of vaccines in UIP.

Divergent trends in ischaemic heart disease and stroke mortality in India from 2000 to 2015: a nationally representative mortality study

Summary Introduction India accounts for about a fifth of cardiovascular deaths globally, but nationally representative data on mortality trends are not yet available. In this nationwide mortality study, we aimed to assess the trends in ischaemic heart disease and stroke mortality over 15 years using the Million Death Study. Methods We determined national and subnational cardiovascular mortality rates and trends by sex and birth cohort using cause of death ascertained by verbal autopsy from 2001 to 2013 among 2·4 million households. We derived mortality rates for ischaemic heart disease and stroke by applying mortality proportions to UN mortality estimates for India and projected the rates from 2000 to 2015. Findings Cardiovascular disease caused more than 2·1 million deaths in India in 2015 at all ages, or more than a quarter of all deaths. At ages 30–69 years, of 1·3 million cardiovascular deaths, 0·9 million (68·4%) were caused by ischaemic heart disease and 0·4 million (28·0%) by stroke. At these ages, the probability of dying from ischaemic heart disease increased during 2000–15, from 10·4% to 13·1% in men and 4·8% to 6·6% in women. Ischaemic heart disease mortality rates in rural areas increased rapidly and surpassed those in urban areas. By contrast, the probability of dying from stroke decreased from 5·7% to 5·0% in men and 5·0% to 3·9% in women. A third of premature stroke deaths occurred in the northeastern states, inhabited by a sixth of India’s population, where rates increased significantly and were three times higher than the national average. The increased mortality rates of ischaemic heart disease nationally and stroke in the northeastern states were higher in the cohorts of adults born in the 1970s onwards, than in earlier decades. A large and growing proportion of the ischaemic heart disease nationally and stroke deaths in high-burden states reported earlier diagnosis of cardiovascular disease, but low medication use. Interpretation The unexpectedly diverse patterns of cardiovascular mortality require investigation to identify the role of established and new cardiovascular risk factors. Secondary prevention with effective and inexpensive long-term treatment and adult smoking cessation could prevent substantial numbers of premature deaths. Without progress against the control of cardiovascular disease in India, global goals to reduce non-communicable diseases by 2030 will be difficult to achieve. Funding Fogarty International Center of the US National Institutes of Health, Dalla Lana School of Public Health, University of Toronto, Indian Council of Medical Research, and the Disease Control Priorities.