Christa L. Fischer Walker

Global, regional, and national causes of child mortality in 2008: a systematic analysis

BACKGROUND Up-to-date information on the causes of child deaths is crucial to guide global efforts to improve child survival. We report new estimates for 2008 of the major causes of death in children younger than 5 years. METHODS We used multicause proportionate mortality models to estimate deaths in neonates aged 0-27 days and children aged 1-59 months, and selected single-cause disease models and analysis of vital registration data when available to estimate causes of child deaths. New data from China and India permitted national data to be used for these countries instead of predictions based on global statistical models, as was done previously. We estimated proportional causes of death for 193 countries, and by application of these proportions to the country-specific mortality rates in children younger than 5 years and birth rates, the numbers of deaths by cause were calculated for countries, regions, and the world. FINDINGS Of the estimated 8.795 million deaths in children younger than 5 years worldwide in 2008, infectious diseases caused 68% (5.970 million), with the largest percentages due to pneumonia (18%, 1.575 million, uncertainty range [UR] 1.046 million-1.874 million), diarrhoea (15%, 1.336 million, 0.822 million-2.004 million), and malaria (8%, 0.732 million, 0.601 million-0.851 million). 41% (3.575 million) of deaths occurred in neonates, and the most important single causes were preterm birth complications (12%, 1.033 million, UR 0.717 million-1.216 million), birth asphyxia (9%, 0.814 million, 0.563 million-0.997 million), sepsis (6%, 0.521 million, 0.356 million-0.735 million), and pneumonia (4%, 0.386 million, 0.264 million-0.545 million). 49% (4.294 million) of child deaths occurred in five countries: India, Nigeria, Democratic Republic of the Congo, Pakistan, and China. INTERPRETATION These country-specific estimates of the major causes of child deaths should help to focus national programmes and donor assistance. Achievement of Millennium Development Goal 4, to reduce child mortality by two-thirds, is only possible if the high numbers of deaths are addressed by maternal, newborn, and child health interventions. FUNDING WHO, UNICEF, and Bill & Melinda Gates Foundation.

Global burden of childhood pneumonia and diarrhoea

Summary Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010–11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.

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.

Diarrhea incidence in low- and middle-income countries in 1990 and 2010: a systematic review

BackgroundDiarrhea is recognized as a leading cause of morbidity and mortality among children under 5 years of age in low- and middle-income countries yet updated estimates of diarrhea incidence by age for these countries are greatly needed. We conducted a systematic literature review to identify cohort studies that sought to quantify diarrhea incidence among any age group of children 0-59 mo of age.MethodsWe used the Expectation-Maximization algorithm as a part of a two-stage regression model to handle diverse age data and overall incidence rate variation by study to generate country specific incidence rates for low- and middle-income countries for 1990 and 2010. We then calculated regional incidence rates and uncertainty ranges using the bootstrap method, and estimated the total number of episodes for children 0-59 mo of age in 1990 and 2010.ResultsWe estimate that incidence has declined from 3.4 episodes/child year in 1990 to 2.9 episodes/child year in 2010. As was the case previously, incidence rates are highest among infants 6-11 mo of age; 4.5 episodes/child year in 2010. Among these 139 countries there were nearly 1.9 billion episodes of childhood diarrhea in 1990 and nearly 1.7 billion episodes in 2010.ConclusionsAlthough our results indicate that diarrhea incidence rates may be declining slightly, the total burden on the health of each child due to multiple episodes per year is tremendous and additional funds are needed to improve both prevention and treatment practices in low- and middle-income countries.

Epidemiology and etiology of childhood pneumonia in 2010: estimates of incidence, severe morbidity, mortality, underlying risk factors and causative pathogens for 192 countries

Background The recent series of reviews conducted within the Global Action Plan for Pneumonia and Diarrhoea (GAPPD) addressed epidemiology of the two deadly diseases at the global and regional level; it also estimated the effectiveness of interventions, barriers to achieving high coverage and the main implications for health policy. The aim of this paper is to provide the estimates of childhood pneumonia at the country level. This should allow national policy–makers and stakeholders to implement proposed policies in the World Health Organization (WHO) and UNICEF member countries. Methods We conducted a series of systematic reviews to update previous estimates of the global, regional and national burden of childhood pneumonia incidence, severe morbidity, mortality, risk factors and specific contributions of the most common pathogens: Streptococcus pneumoniae (SP), Haemophilus influenzae type B (Hib), respiratory syncytial virus (RSV) and influenza virus (flu). We distributed the global and regional–level estimates of the number of cases, severe cases and deaths from childhood pneumonia in 2010–2011 by specific countries using an epidemiological model. The model was based on the prevalence of the five main risk factors for childhood pneumonia within countries (malnutrition, low birth weight, non–exclusive breastfeeding in the first four months, solid fuel use and crowding) and risk effect sizes estimated using meta–analysis. Findings The incidence of community–acquired childhood pneumonia in low– and middle–income countries (LMIC) in the year 2010, using World Health Organizations definition, was about 0.22 (interquartile range (IQR) 0.11–0.51) episodes per child–year (e/cy), with 11.5% (IQR 8.0–33.0%) of cases progressing to severe episodes. This is a reduction of nearly 25% over the past decade, which is consistent with observed reductions in the prevalence of risk factors for pneumonia throughout LMIC. At the level of pneumonia incidence, RSV is the most common pathogen, present in about 29% of all episodes, followed by influenza (17%). The contribution of different pathogens varies by pneumonia severity strata, with viral etiologies becoming relatively less important and most deaths in 2010 caused by the main bacterial agents – SP (33%) and Hib (16%), accounting for vaccine use against these two pathogens. Conclusions In comparison to 2000, the primary epidemiological evidence contributing to the models of childhood pneumonia burden has improved only slightly; all estimates have wide uncertainty bounds. Still, there is evidence of a decreasing trend for all measures of the burden over the period 2000–2010. The estimates of pneumonia incidence, severe morbidity, mortality and etiology, although each derived from different and independent data, are internally consistent – lending credibility to the new set of estimates. Pneumonia continues to be the leading cause of both morbidity and mortality for young children beyond the neonatal period and requires ongoing strategies and progress to reduce the burden further.

Typhoid fever and paratyphoid fever: Systematic review to estimate global morbidity and mortality for 2010

Background Typhoid and paratyphoid fever remain important causes of morbidity worldwide. Accurate disease burden estimates are needed to guide policy decisions and prevention and control strategies. Methods We conducted a systematic literature review of the PubMed and Scopus databases using pre-defined criteria to identify population-based studies with typhoid fever incidence data published between 1980 and 2009. We also abstracted data from annual reports of notifiable diseases in countries with advanced surveillance systems. Typhoid and paratyphoid fever input data were grouped into regions and regional incidence and mortality rates were estimated. Incidence data were extrapolated across regions for those lacking data. Age-specific incidence rates were derived for regions where age-specific data were available. Crude and adjusted estimates of the global typhoid fever burden were calculated. Results Twenty-five studies were identified, all of which contained incidence data on typhoid fever and 12 on paratyphoid fever. Five advanced surveillance systems contributed data on typhoid fever; 2 on paratyphoid fever. Regional typhoid fever incidence rates ranged from <0.1/100 000 cases/y in Central and Eastern Europe and Central Asia to 724.6/100 000 cases/y in Sub-Saharan Africa. Regional paratyphoid incidence rates ranged from 0.8/100 000 cases/y in North Africa/Middle East to 77.4/100 000 cases/y in Sub-Saharan Africa and South Asia. The estimated total number of typhoid fever episodes in 2010 was 13.5 million (interquartile range 9.1–17.8 million). The adjusted estimate accounting for the low sensitivity of blood cultures for isolation of the bacteria was 26.9 million (interquartile range 18.3–35.7 million) episodes. These findings are comparable to the most recent analysis of global typhoid fever morbidity, which reported crude and adjusted estimates of 10.8 million and 21.7 million typhoid fever episodes globally in 2000. Conclusion Typhoid fever remains a significant health burden, especially in low- and middle-income countries. Despite the availability of more recent data on both enteric fevers, additional research is needed in many regions, particularly Africa, Latin America and other developing countries.

The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality

Background Most diarrhoeal deaths can be prevented through the prevention and treatment of dehydration. Oral rehydration solution (ORS) and recommended home fluids (RHFs) have been recommended since 1970s and 1980s to prevent and treat diarrhoeal dehydration. We sought to estimate the effects of these interventions on diarrhoea mortality in children aged <5 years. Methods We conducted a systematic review to identify studies evaluating the efficacy and effectiveness of ORS and RHFs and abstracted study characteristics and outcome measures into standardized tables. We categorized the evidence by intervention and outcome, conducted meta-analyses for all outcomes with two or more data points and graded the quality of the evidence supporting each outcome. The CHERG Rules for Evidence Review were used to estimate the effectiveness of ORS and RHFs against diarrhoea mortality. Results We identified 205 papers for abstraction, of which 157 were included in the meta-analyses of ORS outcomes and 12 were included in the meta-analyses of RHF outcomes. We estimated that ORS may prevent 93% of diarrhoea deaths. Conclusions ORS is effective against diarrhoea mortality in home, community and facility settings; however, there is insufficient evidence to estimate the effectiveness of RHFs against diarrhoea mortality.

Zinc for the treatment of diarrhoea: effect on diarrhoea morbidity, mortality and incidence of future episodes

Background Zinc supplementation for the treatment of diarrhoea has been shown to decrease the duration and severity of the diarrhoeal episode, diarrhoea hospitalization rates and, in some studies, all-cause mortality. Using multiple outcome measures, we sought to estimate the effect of zinc for the treatment of diarrhoea on diarrhoea mortality and subsequent pneumonia mortality. Methods We conducted a systematic review of efficacy and effectiveness studies. We used a standardized abstraction and grading format and performed meta-analyses for all outcomes with ≥2 data points. The estimated effect on diarrhoea mortality was determined by applying the standard Child Health Epidemiology Reference Group rules for multiple outcomes. Results We identified 13 studies for abstraction. Zinc supplementation decreased the proportion of diarrhoeal episodes which lasted beyond 7 days, risk of hospitalization, all-cause mortality and diarrhoea mortality. Using diarrhoea hospitalizations as the closest and most conservative possible proxy for diarrhoea mortality, zinc for the treatment of diarrhoea is estimated to decrease diarrhoea mortality by 23%. Conclusion Zinc is an effective therapy for diarrhoea and will decrease diarrhoea morbidity and mortality when introduced and scaled-up in low-income countries.

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.

Etiology of Diarrhea in Older Children, Adolescents and Adults: A Systematic Review

Background Diarrhea is an important cause of morbidity and mortality in all regions of the world and among all ages, yet little is known about the fraction of diarrhea episodes and deaths due to each pathogen. Methodology/Principal Findings We conducted a systematic literature review to identify all papers reporting the proportion of diarrhea episodes with positive laboratory tests for at least one pathogen in inpatient, outpatient and community settings that met our inclusion and exclusion criteria. We identified a total of 25,701 papers with possible etiology data and after final screening included 22 papers that met all inclusion and exclusion criteria. Enterotoxigenic Escherichia coli and V. cholerae O1/O139 were the leading causes of hospitalizations. In outpatient settings, Salmonella spp., Shigella spp., and E. histolytica were the most frequently isolated pathogens. Conclusions/Significance This is the first systematic review which has considered the relative importance of multiple diarrhea pathogens. The few studies identified suggest that there is a great need for additional prospective studies around the world in these age groups to better understand the burden of disease and the variation by region.