Christian L. Coles

Impact of supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in southern India

Abstract Objective To assess the impact of supplementing newborn infants with vitamin A on mortality at age 6 months. Design Community based, randomised, double blind, placebo controlled trial. Setting Two rural districts of Tamil Nadu, southern India. Participants 11 619 newborn infants allocated 24 000 IU oral vitamin A or placebo on days 1 and 2 after delivery. Main outcome measure Primary outcome measure was mortality at age 6 months. Results Infants in the vitamin A group had a 22% reduction in total mortality (95%confidence interval 4% to 37%) compared with those in the placebo group. Vitamin A had an impact on mortality between two weeks and three months after treatment, with no additional impact after three months. Conclusion Supplementing newborn infants with vitamin A can significantly reduce early infant mortality.

Exposure to indoor biomass fuel and tobacco smoke and risk of adverse reproductive outcomes, mortality, respiratory morbidity and growth among newborn infants in south India

BACKGROUND Exposure to indoor air pollution due to open burning of biomass fuel is common in low- and middle-income countries. Previous studies linked this exposure to an increased risk of respiratory illness, low birth weight (LBW) and other disorders. We assessed the association between exposure to biomass fuel sources and second-hand tobacco smoke (SHTS) in the home and adverse health outcomes in early infancy in a population in rural south India. METHODS A population-based cohort of newborns was followed from birth through 6 months. Household characteristics were assessed during an enrolment interview including the primary type of cooking fuel and smoking behaviour of household residents. Follow-up visits for morbidity were carried out every 2 weeks after delivery. Infants were discharged at 6 months when anthropometric measurements were collected. RESULTS 11 728 live-born infants were enrolled and followed, of whom 92.3% resided in households that used wood and/or dung as a primary source of fuel. Exposure to biomass fuel was associated with an adjusted 49% increased risk of LBW, a 34% increased incidence of respiratory illness and a 21% increased risk of 6-month infant mortality. Exposed infants also had 45 and 30% increased risks of underweight and stunting at 6 months. SHTS exposure was also associated with these adverse health outcomes except for attained growth. CONCLUSIONS Open burning of biomass fuel in the home is associated with significant health risks to the newborn child and young infant. Community-based trials are needed to clarify causal connections and identify effective approaches to reduce this burden of illnesses.

Pneumococcal nasopharyngeal colonization in young South Indian infants.

BACKGROUND Streptococcus pneumoniae is the most frequent bacterial cause of morbidity and mortality in young children. Bacteria carried in the nasopharynx of healthy children reflect the prevalent strains circulating in the community. METHODS We recruited 464 newborns from a rural area in South India with endemic vitamin A deficiency. Nasopharyngeal specimens were collected from each infant at ages 2, 4 and 6 months. RESULTS Fifty-four percent of study infants were colonized by age 2 months, with 64.1 and 70.2% carriage prevalence at ages 4 and 6 months, respectively. The odds of carriage at 2 months were significantly increased in female infants, infants living in a household in which 20 or more cigarettes were smoked each day, infants whose mothers had less than 1 year of schooling and infants fed colostrum. At age 4 months infants having 2 or more siblings <5 years of age were at significantly increased risk of carriage. At age 6 months none of the potential risk factors examined achieved statistical significance, but maternal night blindness increased the risk of colonization 3-fold. The odds of carrying a PncCRM197 vaccine serotype were increased among infants born to mothers who experienced night blindness during pregnancy. The most prevalent serogroups/types during the first 6 months of life were 6, 9, 10, 11, 14, 15, 19, 23 and 33, accounting for 76.7% of all serotyped isolates. CONCLUSIONS South Indian infants experience high rates of pneumococcal carriage during the first 6 months of life, which may partially explain their increased risk for pneumonia.

Mass Distribution of Azithromycin for Trachoma Control Is Associated With Increased Risk of Azithromycin-Resistant Streptococcus pneumoniae Carriage in Young Children 6 Months After Treatment

BACKGROUND Emerging evidence suggests that the mass distribution of azithromycin for trachoma control (MDA) may increase circulation of macrolide resistance in bacteria associated with severe pediatric infections in treated communities. METHODS We examined the effect of MDA on nasopharyngeal carriage of antibiotic-resistant Streptococcus pneumoniae among 1015 young children living in rural Tanzania. MDA with a single dose of oral azithromycin was provided in 4 of 8 communities where trachoma prevalence was ≥10%. Isolates were tested for susceptibility to azithromycin (AZM) and commonly used antibiotics by disk diffusion and Etest. We calculated the proportion of antibiotic-resistant S. pneumoniae carriage at baseline and again 1, 3, and 6 months after treatment, and at comparable intervals in the untreated villages. RESULTS The proportion of AZM-resistant isolates was similar between groups at baseline (MDA: 35.8% vs non-MDA: 35.4%), however, this proportion was greater in the MDA group in all subsequent surveys. At 6 months, the percentage of AZM-resistant isolates was significantly higher in the MDA group (81.9% vs 46.9%, P < .001). The odds of AZM-resistant carriage was 5-fold greater in the MDA group (odds ratio, 4.95 [95% confidence interval, 3.23-7.61]). The proportion of isolates clinically resistant to AZM (minimum inhibitory concentration ≥16 µg/mL) was also significantly greater in the MDA group at 6 months (35.3% vs 12.4%, P < .006). CONCLUSIONS Mass distribution of a single dose of oral azithromycin for trachoma was associated with increased circulation of macrolide-resistant S. pneumoniae carriage among young children in the 6 months following treatment. It is crucial that changes in antibiotic resistance patterns and their clinical significance in the treatment of severe pediatric infections be assessed in future MDA trials.

Breast-feeding initiation time and neonatal mortality risk among newborns in South India

Objective:To examine the association between breast-feeding initiation time and neonatal mortality in India, where breast-feeding initiation varies widely from region to region.Study Design:Data were collected as part of a community-based, randomized, placebo-controlled trial of the impact of vitamin A supplementation in rural villages of Tamil Nadu, India. Multivariate binomial regression analysis was used to estimate the association between neonatal mortality and breast-feeding initiation time (<12 h, 12 to 24 h, >24 h) among infants surviving a minimum of 48 h.Result:Among 10 464 newborns, 82.1% were first breast-fed before 12 h, 13.8% were breast-fed between 12 and 24 h, and 4.1% were breast-fed after 24 h. After adjusting for birth weight, gestational age and other covariates, late initiators (>24 h) were at ∼78% higher risk of death (relative risk=1.78 (95% confidence interval (CI)=1.03 to 3.10)). There was no difference in mortality risk when comparing babies fed in the first 12 h compared with the second 12 h after birth.Conclusion:Late (>24 h) initiation of breast-feeding is associated with a higher risk of neonatal mortality in Tamil Nadu. Emphasis on breast-feeding promotion programs in low-resource settings of India where early initiation is low could significantly reduce neonatal mortality.

Association of Mass Treatment with Azithromycin in Trachoma-Endemic Communities with Short-Term Reduced Risk of Diarrhea in Young Children

A cohort study was designed to assess the impact of mass distribution of azithromycin (MDA) for trachoma control on incidence over six months of pediatric diarrhea in eight communities in rural Tanzania. A single dose of azithromycin was offered to all residents in four communities, where trachoma prevalence was ≥ 10%. Four geographically matched communities had trachoma prevalences < 10% and did not receive MDA. All randomly selected children (n = 1036) were followed-up for six months post-MDA with bi-weekly surveillance at home. In the 0-1-month and 1-3-month periods, MDA exposure was associated with a 39% (rate ratio = 0.61, 95% confidence interval = 0.39-0.95) and 24% (rate ratio = 0.76, 95% confidence interval = 0.54-1.07) lower risk of diarrhea, respectively, compared with those unexposed, after adjustment for clustering and covariates. By the 3-6-month period, diarrhea incidence was comparable between groups. Thus, MDA was associated with a short-term reduction in diarrheal morbidity in children.

Risk factors for antibiotic-resistant E. coli in children in a rural area

We surveyed antimicrobial susceptibility in faecal Escherichia coli in primary schoolchildren in rural Tamil Nadu, India. Resistance profiles of E. coli samples from local water sources were also obtained. We investigated sociodemographic characteristics as risk factors for resistance and local paediatric prescription patterns. In 119 stool samples, carriage of resistance to 1 antibiotic was 63% and multiple drug resistance was 32%. Resistance outcomes were associated with school of attendance, having a sibling attend the same school, younger age, and less crowded households. Eight of nine water samples were resistant to > or =1 antibiotic. Recent history of medication use was not associated with resistance carriage. Resistance patterns may have been influenced by local paediatric prescription patterns and veterinary antibiotic use. Frequent, low-cost surveillance of commensal resistance can guide development of locally appropriate treatment guidelines. School-based hygiene programmes should be considered as means of limiting the spread of antibiotic resistance.

Differential serum cytokine responses to inactivated and live attenuated seasonal influenza vaccines

Despite vaccine efforts, influenza outbreaks pose a significant threat to global public health. There are two commercially available seasonal influenza vaccines in the United States: the trivalent inactivated vaccine (TIV), delivered parenterally, and the live attenuated influenza vaccine (LAIV), delivered intranasally. Although both vaccines are generally efficacious, the immunologic mechanisms which contribute to protective immunity are incompletely understood. Thus, we investigated the protracted effects of TIV and LAIV on serum cytokine profiles at 14 and 28 days post-vaccination (when antibody titers are peak) in healthy adults over two influenza seasons. Vaccination with TIV was associated with a small, yet significant, decrease in the levels of both IL-8 and TNF-α at 14 and 28 days post-vaccination. LAIV, however, had no impact on serum cytokine levels. Similarly, analysis of serum antibody titers indicated that TIV recipients had a significantly higher sero-response rate compared to LAIV recipients, as has been previously shown. Finally, we examined the relationship between baseline serum cytokine levels and antibody responses to TIV (LAIV recipients were excluded due to the poor sero-response rate). Interestingly, in TIV recipients pre-vaccination levels of IL-8 were higher in sero-responders compared to non-responders. Collectively, these data suggest that cytokines may influence vaccine outcomes and indicate that parenteral immunization with TIV induces a sustained, systemic cytokine response which lasts for weeks.

Mass distribution of azithromycin for trachoma control is associated with short-term reduction in risk of acute lower respiratory infection in young children.

Background: We evaluated the effect of a single mass distribution of azithromycin for trachoma on the risk of acute lower respiratory infection (ALRI) during a 6-month period among young children living in 8 communities in rural Tanzania. Methods: In 8 communities, a cohort of randomly selected children (n = 1036) was followed for incidence of ALRI episodes. Mass treatment for trachoma using a single dose of oral azithromycin was provided in 4 of the 8 communities where trachoma prevalence was .10%. All children were followed with biweekly surveillance at home for 6 months. Incidence of ALRI episodes was calculated for 0 to 1 month, 1 to 3 months, and 3 to 6 months posttreatment and in comparable time points in the nontreated villages. Results: In the multivariate analysis, living in a MDA village was associated with a 38% (rate ratio 5 0.62, 95% confidence interval [CI] = 0.43–0.91) decreased risk of ALRI in the 0- to 1-month follow-up period as compared with those in the untreated communities after adjusting for covariates and clustering. There were no significant differences in ALRI incidence by exposure status in the 1- to 3-month (rate ratio = 0.91, 95% CI = 0.69–1.20) and in the 3- to 6-month (rate ratio = 1.00, 95% CI = 0.76–1.30) follow-up periods. Conclusions: Mass distribution of a single dose of oral azithromycin for trachoma is associated with a significant short-term reduction in ALRI morbidity among young children.

Prevalence of Small-for-Gestational-Age and Its Mortality Risk Varies by Choice of Birth-Weight-for-Gestation Reference Population

Background We use data from rural Nepal and South India to compare the prevalence of small-for-gestational-age (SGA) and neonatal mortality risk associated with SGA using different birth-weight-for-gestation reference populations. Methods We identified 46 reference populations in low-, middle-, and high-income countries, of which 26 met the inclusion criteria of being commonly cited and having numeric 10th percentile cut points published. Those reference populations were then applied to populations from two community-based studies to determine SGA prevalence and its relative risk of neonatal mortality. Results The prevalence of SGA ranged from 10.5% to 72.5% in Nepal, and 12.0% to 78.4% in India, depending on the reference population. Females had higher rates of SGA than males using reference populations that were not sex specific. SGA prevalence was lowest when using reference populations from low-income countries. Infants who were both preterm and SGA had much higher mortality risk than those who were term and appropriate-for-gestational-age. Risk ratios for those who are both preterm and SGA ranged from 7.34–17.98 in Nepal and 5.29–11.98 in India, depending on the reference population. Conclusions These results demonstrate the value of a common birth-weight-for-gestation reference population that will facilitate comparisons of SGA prevalence and mortality risk across research studies.