Jessica C. Seidman

Fecal markers of intestinal inflammation and permeability associated with the subsequent acquisition of linear growth deficits in infants.

Enteric infections are associated with linear growth failure in children. To quantify the association between intestinal inflammation and linear growth failure three commercially available enzyme-linked immunosorbent assays (neopterin [NEO], alpha-anti-trypsin [AAT], and myeloperoxidase [MPO]) were performed in a structured sampling of asymptomatic stool from children under longitudinal surveillance for diarrheal illness in eight countries. Samples from 537 children contributed 1,169 AAT, 916 MPO, and 954 NEO test results that were significantly associated with linear growth. When combined to form a disease activity score, children with the highest score grew 1.08 cm less than children with the lowest score over the 6-month period following the tests after controlling for the incidence of diarrheal disease. This set of affordable non-invasive tests delineates those at risk of linear growth failure and may be used for the improved assessments of interventions to optimize growth during a critical period of early childhood.

Assessment of Environmental Enteropathy in the MAL-ED Cohort Study: Theoretical and Analytic Framework

Individuals in the developing world live in conditions of intense exposure to enteric pathogens due to suboptimal water and sanitation. These environmental conditions lead to alterations in intestinal structure, function, and local and systemic immune activation that are collectively referred to as environmental enteropathy (EE). This condition, although poorly defined, is likely to be exacerbated by undernutrition as well as being responsible for permanent growth deficits acquired in early childhood, vaccine failure, and loss of human potential. This article addresses the underlying theoretical and analytical frameworks informing the methodology proposed by the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study to define and quantify the burden of disease caused by EE within a multisite cohort. Additionally, we will discuss efforts to improve, standardize, and harmonize laboratory practices within the MAL-ED Network. These efforts will address current limitations in the understanding of EE and its burden on children in the developing world.

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.

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.

Epidemiology and Impact of Campylobacter Infection in Children in 8 Low-Resource Settings: Results From the MAL-ED Study

In a multisite birth cohort study, we document a high burden of Campylobacter infection using enzyme immunoassay, demonstrate an association between Campylobacter and linear growth shortfalls and both increased intestinal permeability and intestinal and systemic inflammation, and identify potential interventions.

Quantitative review of antibody response to inactivated seasonal influenza vaccines.

Please cite this paper as: Seidman et al. (2012) Quantitative review of antibody response to inactivated seasonal influenza vaccines. Influenza and Other Respiratory Viruses 6(1), 52–62.

Determinants and impact of Giardia infection in the first 2 years of life in the MAL-ED birth cohort

Summary In a multisite birth-cohort study, Giardia spp were detected by enzyme immunoassay at least once in two-thirds of the children. Early persistent infection with Giardia, independent of diarrhea, was associated with deficits in both weight and length at 2 years of age.

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.

The MAL-ED Cohort Study: Methods and Lessons Learned When Assessing Early Child Development and Caregiving Mediators in Infants and Young Children in 8 Low- and Middle-Income Countries

More epidemiological data are needed on risk and protective factors for child development. In The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study, we assessed child development in a harmonious manner across 8 sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa, and Tanzania. From birth to 24 months, development and language acquisition were assessed via the Bayley Scales of Infant and Toddler Development and a modified MacArthur Communicative Development Inventory. Other measures were infant temperament, the childs environment, maternal psychological adjustment, and maternal reasoning abilities. We developed standard operating procedures and used multiple techniques to ensure appropriate adaptation and quality assurance across the sites. Test adaptation required significant time and human resources but is essential for data quality; funders should support this step in future studies. At the end of this study, we will have a portfolio of culturally adapted instruments for child development studies with examination of psychometric properties of each tool used.

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.