Sushil Mathew John

Household food access and child malnutrition: Results from the eight-country MAL-ED study

BackgroundStunting results from decreased food intake, poor diet quality, and a high burden of early childhood infections, and contributes to significant morbidity and mortality worldwide. Although food insecurity is an important determinant of child nutrition, including stunting, development of universal measures has been challenging due to cumbersome nutritional questionnaires and concerns about lack of comparability across populations. We investigate the relationship between household food access, one component of food security, and indicators of nutritional status in early childhood across eight country sites.MethodsWe administered a socioeconomic survey to 800 households in research sites in eight countries, including a recently validated nine-item food access insecurity questionnaire, and obtained anthropometric measurements from children aged 24 to 60 months. We used multivariable regression models to assess the relationship between household food access insecurity and anthropometry in children, and we assessed the invariance of that relationship across country sites.ResultsAverage age of study children was 41 months. Mean food access insecurity score (range: 0–27) was 5.8, and varied from 2.4 in Nepal to 8.3 in Pakistan. Across sites, the prevalence of stunting (42%) was much higher than the prevalence of wasting (6%). In pooled regression analyses, a 10-point increase in food access insecurity score was associated with a 0.20 SD decrease in height-for-age Z score (95% CI 0.05 to 0.34 SD; p = 0.008). A likelihood ratio test for heterogeneity revealed that this relationship was consistent across countries (p = 0.17).ConclusionsOur study provides evidence of the validity of using a simple household food access insecurity score to investigate the etiology of childhood growth faltering across diverse geographic settings. Such a measure could be used to direct interventions by identifying children at risk of illness and death related to malnutrition.

Probiotics, antibiotics and the immune responses to vaccines

Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome.

Establishment of the MAL-ED Birth Cohort Study Site in Vellore, Southern India

The Indian Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) site is in Vellore, Tamil Nadu, in south India and is coordinated by the Christian Medical College, Vellore, which has many years of experience in establishing and following cohorts. India is a diverse country, and no single area can be representative with regard to many health and socioeconomic indicators. The site in Vellore is an urban semiorganized settlement or slum. In the study site, the average family size is 5.7, adults who are gainfully employed are mostly unskilled laborers, and 51% of the population uses the field as their toilet facility. Previous studies from Vellore slums have reported stunting in well over a third of children, comparable to national estimates. The infant mortality rate is 38 per 1000 live births, with deaths due mainly to perinatal and infectious causes. Rigorous staff training, monitoring, supervision and refinement of tools have been essential to maintaining the quality of the significantly large quantity of data collected. Establishing a field clinic within the site has minimized inconvenience to participants and researchers and enabled better rapport with the community and better follow-up. These factors contribute to the wealth of information that will be generated from the MAL-ED multisite cohort, which will improve our understanding of enteric infections and its interactions with malnutrition and development of young children.

50 years of tuberculosis control in India: Progress, pitfalls and the way forward

India established the National Tuberculosis Control Project (NTCP) 50 years ago and re-designed it as Revised NTCP (RNTCP) 19 years ago. Tuberculosis (TB) control was beset with obstacles — BCG vaccination was found ineffective in TB control in 1979; human immunodeficiency virus began spreading in India since 1984 with TB as the commonest opportunistic disease; multi-drug resistance was found to be prevalent since 1992. The World Health Organization declared TB as global emergency in 1993. Yet, RNTCP was extended to the whole nation very slowly, taking 13 years from inception. The first objective of RNTCP, namely 85% treatment success has been achieved and case-fatality had dropped by 90%. Still, TB burden continues to remain huge; about half the cases are not getting registered under RNTCP; pediatric TB is neglected; TB drains national economy of US

Use of antibiotics in children younger than two years in eight countries: A prospective cohort study

23 billion annually. Therefore, TB control is in urgent need of re-design and re-invigoration, with additional inputs and system re-organization to cover all such gaps. We highlight the need for Public Health infrastructure under which all vertical disease control projects such as RNTCP should be synergized for better efficiency and for establishing Public Health Surveillance for collecting denominator-based data on incidence and prevalence to guide course corrections. India ought to spend 3 to 5 times more on TB control than at present. Control needs clear epidemiologic definition and measurable parameters for monitoring the level of control over time. TB control is both a measure of, and a means to, socioeconomic development.

Serological Response to Early Measles Vaccination

Abstract Objective To describe the frequency and factors associated with antibiotic use in early childhood, and estimate the proportion of diarrhoea and respiratory illnesses episodes treated with antibiotics. Methods Between 2009 and 2014, we followed 2134 children from eight sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa and the United Republic of Tanzania, enrolled in the MAL-ED birth cohort study. We documented all antibiotic use from mothers’ reports at twice-weekly visits over the children’s first two years of life. We estimated the incidence of antibiotic use and the associations of antibiotic use with child and household characteristics. We described treatment patterns for diarrhoea and respiratory illnesses, and identified factors associated with treatment and antibiotic class. Findings Over 1 346 388 total days of observation, 16 913 courses of antibiotics were recorded (an incidence of 4.9 courses per child per year), with the highest use in South Asia. Antibiotic treatment was given for 375/499 (75.2%) episodes of bloody diarrhoea and for 4274/9661 (44.2%) episodes of diarrhoea without bloody stools. Antibiotics were used in 2384/3943 (60.5%) episodes of fieldworker-confirmed acute lower respiratory tract illness as well as in 6608/16742 (39.5%) episodes of upper respiratory illness. Penicillins were used most frequently for respiratory illness, while antibiotic classes for diarrhoea treatment varied within and between sites. Conclusion Repeated antibiotic exposure was common early in life, and treatment of non-bloody diarrhoea and non-specific respiratory illnesses was not consistent with international recommendations. Rational antibiotic use programmes may have the most impact in South Asia, where antibiotic use was highest.

Paradigm shift for tuberculosis control in high prevalence countries

This study compares the persistence of measles IgG antibody in 239 children vaccinated at 6-8 months of age with 76 children vaccinated after 8 months of age. Among the children vaccinated prior to 9 months, 49 per cent of the children between 16 and 44 months and 33 per cent of children over 54 months had levels of measles IgG antibody conventionally considered protective. Among the children older than 48 months, 67 per cent of children vaccinated before 9 months and 13 per cent of children vaccinated after 8 months had antibody levels below the conventionally accepted protective levels of 0.2 IU/ml. Older children had lower antibody levels than younger children. Measles immunization before 9 months with the standard titer Edmonston-Zagreb vaccine has not provided a large proportion of under-five children with protective levels of measles IgG antibody. A significant proportion of children vaccinated at the currently recommended age also had suboptimal levels. It is difficult to protect the majority of the measles-susceptible population with a single dose regardless of the immunization schedule used. A second dose of measles vaccine may be necessary to increase the herd immunity.

Early Antibiotic Exposure in Low-resource Settings is Associated with Increased Weight in The First Two Years of Life

Tuberculosis (TB) was described a global emergency in 1994 (World Health Organization 1994) but its control strategy has not improved since then. Globally, the estimated number of incident cases of TB increased from 9.24 to 9.27 millions between 1990 and 2007, of which 86% are in Asia and Africa (WHO 2009). Three factors are involved in the TB burden: population growth tends to increase, but secular trend and control efforts tend to reduce the number of incident cases. Their sum total has been estimated to be a meagre <1% annual decline of cases. The estimated incidence (per 100 000) was 142 in 2004 and 139 in 2007 (World Health Organization 2009). At this rate, the Millennium Development Goal (MDG) to reduce by half TB prevalence and death by 2015 (compared to 1990 levels) will be missed by a disappointingly huge margin. Poverty is both determinant and consequence of TB. Hence the MDG of poverty reduction also depends on TB control. The annual loss due to TB morbidity in India alone has been estimated at US

Effects of elevated blood lead levels in preschool children in urban Vellore

3 billion (Government of India 2009). A radical re-think and paradigm shift are essential for TB control, especially in high prevalence countries. There are several reasons why TB has not been controlled by current efforts. Control has to be defined in such a manner that its trajectory can be monitored over time; currently no such monitoring is included in the TB control program in many countries (John 2000). Ideally any infectious disease control requires primary prevention (reduction of the incidence of infection). An additional approach is secondary prevention—in the case of TB, reduction of frequency of latent infection progressing to pulmonary TB. The natural history of TB begins in individuals with primary infection. Pulmonary TB is the infectious form of disease with shedding of mycobacteria into the environment, leading to fresh infections. Much reliance was once placed on BCG vaccination of infants for primary and secondary prevention. However, a large vaccine trial in India showed that BCG did not provide either benefit (Tuberculosis Research Centre 1999). Thus the current control program relies solely on rapid microbiological cure of pulmonary TB so as to reduce the intensity and duration of mycobacterial shedding. These cannot be quantified to monitor control trajectory. There is hardly another epidemiological model of infection-control solely by treatment of end-stage disease. The current guidelines of 70% case detection and 85% cure rates of pulmonary TB for control were based on mathematical modelling and not epidemiological evidence (Dye et al. 1998). While the cure rate can be monitored among detected cases (the denominator), the case detection rate cannot be monitored since the population-prevalence would be unknown except where case-notification or active search is practiced (Gonzales-Ochoa et al. 2009; Grange et al. 2009; Kritzinger et al. 2009). Even if truly 70% were detected through sputum-smear testing and 85% cured within a few weeks, would that reliably control primary infection rate in susceptible children? In high prevalence communities it will not, as shown in South Africa and in India (John 2008; Kritzinger et al. 2009). There is often an interval during which a person with pulmonary TB is not symptomatic but sheds mycobacteria into the environment. In highly endemic situations, much of the infection in contacts occurs before diagnosis and start of chemotherapy (Kamat et al. 1996). Microbiological cure takes a few more weeks. Meanwhile more new infections would have inevitably taken place. In high prevalence communities children may be exposed to more than one infectious individual. The probability of infection increases with repetitiveness of exposure (in household, neighborhood, school, etc.) and cumulative time of exposure (the function of age). Where prevalence is high, virtually every child is exposed; the likelihood of infection increases as infants grow through childhood to adolescence, as in south India and South Africa (John et al. 1971; Kritzinger et al. 2009). The experience from South Africa shows very high annual risk (rate) of tuberculosis infection Tropical Medicine and International Health doi:10.1111/j.1365-3156.2009.02392.x

Two Doses of Measles Vaccine: Are Some States in India Ready for It?

Objectives: The potential growth-promoting effects of antibiotics are not well understood among undernourished children in environments with high pathogen exposure. We aimed to assess whether early antibiotic exposure duration and class were associated with growth to 2 years of age across 8 low-resource sites in the MAL-ED birth cohort study. Methods: We followed 1954 children twice per week from birth to 2 years to record maternally reported antibiotic exposures and measure anthropometry monthly. We estimated the associations between antibiotic exposure before 6 months of age and weight-for-age and length-for-age (LAZ) z scores to 2 years. We assessed the impact of class-specific exposures and duration, and compared these results to effects of antibiotic exposures after 6 months of age. Results: Antibiotic use before 6 months of age was associated with increased weight from 6 months to 2 years, whereas associations with length were less consistent across sites and antibiotic classes. Compared to unexposed children, 2 or more courses of metronidazole, macrolides, and cephalosporins were associated with adjusted increases in weight-for-age of 0.24 (95% confidence interval (CI): 0.04, 0.43), 0.23 (95% CI: 0.05, 0.42), and 0.19 (95% CI: 0.04, 0.35) from 6 months to 2 years, respectively. Conclusions: Antibiotic use in low-resource settings was most associated with the ponderal growth of children who had multiple exposures to antibiotics with broad spectrum and anaerobic activity in early infancy. Opportunities for rational and targeted antibiotic therapy in low resource settings may also promote short-term weight gain in children, although longer-term physical growth and metabolic impacts are unknown.