Laura M. Lamberti

Breastfeeding and the risk for diarrhea morbidity and mortality

BackgroundLack of exclusive breastfeeding among infants 0-5 months of age and no breastfeeding among children 6-23 months of age are associated with increased diarrhea morbidity and mortality in developing countries. We estimate the protective effects conferred by varying levels of breastfeeding exposure against diarrhea incidence, diarrhea prevalence, diarrhea mortality, all-cause mortality, and hospitalization for diarrhea illness.MethodsWe systematically reviewed all literature published from 1980 to 2009 assessing levels of suboptimal breastfeeding as a risk factor for selected diarrhea morbidity and mortality outcomes. We conducted random effects meta-analyses to generate pooled relative risks by outcome and age category.ResultsWe found a large body of evidence for the protective effects of breastfeeding against diarrhea incidence, prevalence, hospitalizations, diarrhea mortality, and all-cause mortality. The results of random effects meta-analyses of eighteen included studies indicated varying degrees of protection across levels of breastfeeding exposure with the greatest protection conferred by exclusive breastfeeding among infants 0-5 months of age and by any breastfeeding among infants and young children 6-23 months of age. Specifically, not breastfeeding resulted in an excess risk of diarrhea mortality in comparison to exclusive breastfeeding among infants 0-5 months of age (RR: 10.52) and to any breastfeeding among children aged 6-23 months (RR: 2.18).ConclusionsOur findings support the current WHO recommendation for exclusive breastfeeding during the first 6 months of life as a key child survival intervention. Our findings also highlight the importance of breastfeeding to protect against diarrhea-specific morbidity and mortality throughout the first 2 years of life.

Breastfeeding for reducing the risk of pneumonia morbidity and mortality in children under two: a systematic literature review and meta-analysis

BackgroundSuboptimal breastfeeding practices among infants and young children <24 months of age are associated with elevated risk of pneumonia morbidity and mortality. We conducted a systematic review and meta-analysis to quantify the protective effects of breastfeeding exposure against pneumonia incidence, prevalence, hospitalizations and mortality.MethodsWe conducted a systematic literature review of studies assessing the risk of selected pneumonia morbidity and mortality outcomes by varying levels of breastfeeding exposure among infants and young children <24 months of age. We used random effects meta-analyses to generate pooled effect estimates by outcome, age and exposure level.ResultsSuboptimal breastfeeding elevated the risk of pneumonia morbidity and mortality outcomes across age groups. In particular, pneumonia mortality was higher among not breastfed compared to exclusively breastfed infants 0-5 months of age (RR: 14.97; 95% CI: 0.67-332.74) and among not breastfed compared to breastfed infants and young children 6-23 months of age (RR: 1.92; 95% CI: 0.79-4.68).ConclusionsOur results highlight the importance of breastfeeding during the first 23 months of life as a key intervention for reducing pneumonia morbidity and mortality.

Systematic review of diarrhea duration and severity in children and adults in low- and middle-income countries

BackgroundDiarrhea is a leading cause of morbidity and mortality globally; yet the overall burden of diarrhea in terms of duration and severity has not been quantified. As improvements in treatment lead to decreases in diarrhea mortality, it is important to understand the substantial impact of diarrhea morbidity on disability among children and adults worldwide.MethodsWe conducted a systematic review to generate estimates of duration and severity outcomes for individuals 0-59 mos, 5-15 yrs, and ≥ 16 yrs, and for 3 severity indexes: mild, moderate, and severe.ResultsWe estimate that among children under-five, 64.8% of diarrheal episodes are mild, 34.7% are moderate, and 0.5% are severe. On average, mild episodes last 4.3 days, and severe episodes last 8.4 days and cause dehydration in 84.6% of cases. We estimate that among older children and adults, 95% of episodes are mild; 4.95% are moderate; and 0.05% are severe. Among individuals ≥ 16 yrs, severe episodes typically last 2.6 days and cause dehydration in 92.8% of cases.ConclusionsModerate and severe episodes constitute a substantial portion of the total envelope of diarrhea among children under-five (35.2%; about 588 million episodes). Among older children and adults, moderate and severe episodes account for a much smaller proportion of the total envelope of diarrhea (5%), but the absolute number of such episodes is noteworthy (about 21.5 million episodes among individuals ≥ 16 yrs). Hence, the global burden of diarrhea consists of significant morbidity, extending beyond episodes progressing to death.

Does Childhood Diarrhea Influence Cognition Beyond the Diarrhea-Stunting Pathway?

Background Diarrhea is a leading cause of morbidity among children under 5 years of age in low- and middle-income countries yet the additional effects and sequelae, such as cognitive impairment associated with diarrhea, have not been quantified. Methods We quantified the association between diarrhea prevalence and cognitive outcomes while controlling for linear growth in 4 study populations. Cognition was assessed using different methods across sites and was expressed in standardized units. We built linear regression models for each study with standardized cognitive score as the outcome and diarrhea prevalence as the main predictor variable. We then conducted meta-analyses of the regression coefficients to generate pooled estimates of the association between diarrhea prevalence and cognition whilst controlling for anthropometric status and other covariates. Results Diarrhea was not a significant predictor of cognitive score in any site in the regression models or in the meta-analyses (Coefficient = 0.07; 95% CI: −0.1, 0.2). The length for age Z- score was negatively related to cognition in all sites (0.18; 95% CI: 0.14, 0.21), with coefficients remarkably similar across sites (Coefficient Range: 0.168–0.186). Conclusions We did not demonstrate an association between diarrhea and cognition with stunting included in the model. The links between diarrhea, stunting, and cognition provide additional rationale for accelerating interventions to reduce diarrhea.

Estimating Diarrheal Illness and Deaths Attributable to Shigellae and Enterotoxigenic Escherichia coli among Older Children, Adolescents, and Adults in South Asia and Africa

Introduction While Shigellae and strains of enterotoxigenic Escherichia coli (ETEC) are important causes of diarrhea-associated morbidity and mortality among infants and young children (<5 years of age), their health impact in older age groups is unclear. We sought to quantify the overall burden of shigellosis and ETEC diarrhea among older children, adolescents, and adults in Africa and South Asia, the two regions with the highest levels of diarrhea-related morbidity and mortality worldwide. Methods We employed two distinct methodological approaches to estimate the burden of diarrhea due to Shigellae and ETEC among persons ≥5 years of age in the WHO regions of South Asia (SEAR) and Africa (AFR). Under method 1, we conducted a systematic review to identify the median proportion of total deaths due to diarrhea and then applied this figure to the number of all-cause deaths that occurred in 2010 among this age group. To estimate the total number of diarrhea deaths attributable to Shigellae and ETEC, we subsequently applied previously published estimates of the median percentage of diarrhea hospitalizations due to Shigellae and ETEC to the estimated number of diarrhea deaths. For method 2, we applied previously published incidence rates to 2010 population figures and estimated the total number of episodes due to Shigellae and ETEC using published estimates of the average proportion of pathogen-positive outpatients from studies of >4 pathogens. We then estimated the number of pathogen-specific deaths by determining the number of hospitalized patients and applying the case-fatality rate. Results By method 1, there were 19,451 deaths due to Shigellae and 42,973 due to ETEC in AFR, and 20,691 due to Shigellae and 45,713 due to ETEC in SEAR in 2010. By method 2, there were 15.0 million ETEC episodes and 30.4 million episodes due to Shigellae in AFR, and 28.7 million episodes due to ETEC and 58.1 million episodes due to Shigellae in SEAR in 2010. We were unable to identify published case-fatality rates for ETEC and thus could only estimate Shigellae-related deaths using method 2, by which there were 5,308 and 10,158 Shigellae-related deaths in AFR and SEAR in 2010, respectively. Discussion Methods 1 and 2 underscore the importance of Shigellae and ETEC as major causes of morbidity and mortality among older children, adolescents, and adults in AFR and SEAR. Understanding the epidemiology of these pathogens is imperative for the development and use of future vaccines and other preventative interventions.

Oral Zinc Supplementation for the Treatment of Acute Diarrhea in Children: A Systematic Review and Meta-Analysis

Evidence supporting the impact of therapeutic zinc supplementation on the duration and severity of diarrhea among children under five is largely derived from studies conducted in South Asia. China experiences a substantial portion of the global burden of diarrhea, but the impact of zinc treatment among children under five has not been well documented by previously published systematic reviews on the topic. We therefore conducted a systematic literature review, which included an exhaustive search of the Chinese literature, in an effort to update previously published estimates of the effect of therapeutic zinc. We conducted systematic literature searches in various databases, including the China National Knowledge Infrastructure (CNKI), and abstracted relevant data from studies meeting our inclusion and exclusion criteria. We used STATA 12.0 to pool select outcomes and to generate estimates of percentage difference and relative risk comparing outcomes between zinc and control groups. We identified 89 Chinese and 15 non-Chinese studies for the review, including studies in 10 countries from all WHO geographic regions, and analyzed a total of 18,822 diarrhea cases (9469 zinc and 9353 control). None of the included Chinese studies had previously been included in published pooled effect estimates. Chinese and non-Chinese studies reported the effect of therapeutic zinc supplementation on decreased episode duration, stool output, stool frequency, hospitalization duration and proportion of episodes lasting beyond three and seven days. Pooling Chinese and non-Chinese studies yielded an overall 26% (95% CI: 20%−32%) reduction in the estimated relative risk of diarrhea lasting beyond three days among zinc-treated children. Studies conducted in and outside China report reductions in morbidity as a result of oral therapeutic zinc supplementation for acute diarrhea among children under five years of age. The WHO recommendation for zinc treatment of diarrhea episodes should be supported in all low- and middle-income countries.

A Systematic Review of the Effect of Rotavirus Vaccination on Diarrhea Outcomes Among Children Younger Than 5 Years.

Background: Rotavirus is the leading cause of vaccine-preventable diarrhea among children under 5 globally. Rotavirus vaccination has been shown to prevent severe rotavirus infections with varying efficacy and effectiveness by region. Methods: We sought to generate updated region-specific estimates of rotavirus vaccine efficacy and effectiveness. We systematically reviewed published vaccine efficacy and effectiveness studies to assess the region-specific effect of rotavirus vaccination on select diarrheal morbidity and mortality outcomes in children under 5 years of age. We employed meta-analytic methods to generate pooled effect sizes by Millennium Development Goal region. Results: Rotavirus vaccination was both efficacious and effective in preventing rotavirus diarrhea, severe rotavirus diarrhea and rotavirus hospitalizations among children under 5 across all regions represented by the 48 included studies. Efficacy against severe rotavirus diarrhea ranged from 90.6% [95% confidence interval (CI): 82.3–95.0] in the developed region to 88.4% (95% CI: 67.1–95.9) in Eastern/Southeastern Asia, 79.6% (95% CI: 71.3–85.5) in Latin America and the Caribbean, 50.0% (95% CI: 34.4–61.9) in Southern Asia and 46.1% (95% CI: 29.1–59.1) in sub-Saharan Africa. Region-specific effectiveness followed a similar pattern. There was also evidence of vaccine efficacy against severe diarrhea and diarrheal hospitalizations. Conclusion: Our findings confirm the protective efficacy and effectiveness of rotavirus vaccination against rotavirus diarrheal outcomes among children under 5 globally.

An external evaluation of the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program in Gujarat and Uttar Pradesh, India

Background To address inadequate coverage of oral rehydration salts (ORS) and zinc supplements for the treatment of diarrhea among children under–five, the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program was carried out from 2011–2013 in Gujarat and from 2011–2014 in Uttar Pradesh (UP), India. The program focused on improving the diarrhea treatment practices of public and private sector providers. Methods We conducted cross–sectional household surveys in program districts at baseline and endline and constructed state–specific logistic regression models with generalized estimating equations to assess changes in ORS and zinc treatment during the program period. Results Between baseline and endline, zinc coverage increased from 2.5% to 22.4% in Gujarat and from 3.1% to 7.0% in UP; ORS coverage increased from 15.3% to 39.6% in Gujarat but did not change in UP. In comparison to baseline, children with diarrhea in the two–weeks preceding the endline survey had higher odds of receiving zinc treatment in both Gujarat (odds ratio, OR = 11.2; 95% confidence interval (CI) 6.4–19.3) and UP (OR = 2.4; 95% CI 1.4–3.9), but the odds of receiving ORS only increased in Gujarat (OR = 3.6; 95% CI 2.7–4.8; UP OR = 0.9; 95% CI 0.7–1.2). Seeking care outside the home, especially from a public sector source, was associated with higher odds of receiving ORS and zinc. Conclusions During the duration of the DAZT program, there were modest improvements in the treatment of diarrhea among young children. Future programs should build upon and accelerate this trend with continued investment in public and private sector provider training and supply chain sustainability, in addition to targeted caregiver demand generation activities.

The Influence of Episode Severity on Caregiver Recall, Care-seeking, and Treatment of Diarrhea among Children 2-59 Months of Age in Bihar, Gujarat, and Uttar Pradesh, India

Increased diarrheal episode severity has been linked to better 2-week recall and improved care-seeking and treatment among caregivers of children under five. Using cross-sectional data from three Indian states, we sought to assess the relationship between episode severity and the recall, care-seeking, and treatment of childhood diarrhea. Recall error was higher for episodes with onset 8–14 days (31.2%) versus 1–7 days (4.8%) before the survey, and logistic regression analysis showed a trend toward increased severity of less recent compared with more recent episodes. This finding indicates that data collection with 2-week recall underestimates diarrhea prevalence while overestimating the proportion of severe episodes. There was a strong correlation between care-seeking and dehydration, fever, vomiting, and increased stool frequency and duration. Treatment with oral rehydration salts was associated with dehydration, vomiting, and higher stool frequency, and trends were established between therapeutic zinc supplementation and increased duration and stool frequency. However, state and care-seeking sector were stronger determinants of treatment than episode severity, illustrating the need to address disparities in treatment quality across regions and delivery channels. Our findings are of importance to researchers and diarrhea management program evaluators aiming to produce accurate estimates of diarrheal outcomes and program impact in low- and middle-income countries.

Zinc Deficiency in Childhood and Pregnancy: Evidence for Intervention Effects and Program Responses

Zinc is a key micronutrient of particular importance during childhood and pregnancy. Zinc deficiency has been linked to increased infection and stunting among children and is a risk factor for adverse pregnancy outcomes and preterm delivery. Targeted interventions have the potential to alleviate the adverse effects of zinc deficiency via therapeutic and preventive supplementation, fortification and biofortification, but implementation is challenging. A growing number of low- and middle- income countries have introduced national policies for zinc treatment of diarrhea among children under 5 years in response to mounting evidence of reduced episode duration and severity as well as reduced incidence in the ensuing months, but coverage remains low in the absence of effective scale-up efforts. Implementation of preventive zinc supplementation in young children has also been slow, despite evidence linking routine daily supplementation and treatment regimens with reductions in stunting and the incidence of diarrhea and pneumonia. Acceptance of other zinc interventions, including traditional fortification, fortification with micronutrient powders and biofortification, is hindered by unclear evidence on efficacy. Additional research is therefore warranted to ascertain the efficacy of delivering zinc through fortified and biofortified foods and in combination with other micronutrients in supplements or powders. Operations research is also necessary to establish best practices for scale-up of therapeutic zinc supplementation for diarrhea.