Estimating the Fraction of Severe Malaria among Malaria-Positive Children: Analysis of Household Surveys in 19 Malaria-Endemic Countries in Africa.

To date, the only robust estimates of severe malaria cases include children who present to the formal healthcare system. It is a challenge to use these data because of varying age ranges of reporting, different diagnosis techniques, surveillance methods, and healthcare utilization. This analysis examined data from 37 Demographic and Health Surveys and Malaria Indicator Surveys across 19 countries in sub-Saharan Africa collected between 2011 and 2018. The outcome of interest is a proxy indicator for severe malaria, defined as a proportion of children aged 6-59 months with at least one self-reported symptom of severe illness including loss of consciousness, rapid breathing, seizures, or severe anemia (hemoglobin < 5 g/dL) among those who were positive for malaria. The study includes a weighted descriptive, country-level analysis and a multilevel mixed-effects logistic regression model to assess the determinants of severe malaria. Among children positive for malaria across all surveys, 4.5% (95% CI: 4.1-4.8) had at least one sign or symptom of severe malaria, which was significantly associated with age, residence, wealth, and year of survey fieldwork at a P-value less than 0.05. This analysis presents a novel and an alternative approach of estimating the fraction of severe malaria cases among malaria-positive children younger than 5 years in malaria-endemic countries. Estimating severe malaria cases through population-based surveys allows countries to estimate severe malaria across time and to compare with other countries. Having a population-level estimate of severe malaria cases helps further our understanding of the burden and epidemiology of severe malaria.

Mortality in the First 3 Months on Antiretroviral Therapy Among HIV-Positive Adults in Low- and Middle-income Countries: A Meta-analysis.

Previous meta-analyses reported mortality estimates of 12-month post-antiretroviral therapy (ART) initiation; however, 40%-60% of deaths occur in the first 3 months on ART, a more sensitive measure of averted deaths through early ART initiation. To determine whether early mortality is dropping as treatment thresholds have increased, we reviewed studies of 3 months on ART initiation in low- to middle-income countries. Studies of 3-month mortality from January 2003 to April 2016 were searched in 5 databases. Articles were included that reported 3-month mortality from a low- to middle-income country; nontrial setting and participants were ≥15. We assessed overall mortality and stratified by year using random effects models. Among 58 included studies, although not significant, pooled estimates show a decline in mortality when comparing studies whose enrollment of patients ended before 2010 (7.0%; 95% CI: 6.0 to 8.0) with the studies during or after 2010 (4.0%; 95% CI: 3.0 to 5.0). To continue to reduce early HIV-related mortality at the population level, intensified efforts to increase demand for ART through active testing and facilitated referral should be a priority. Continued financial investments by multinational partners and the implementation of creative interventions to mitigate multidimensional complex barriers of accessing care and treatment for HIV are needed.

A meta-analysis assessing all-cause mortality in HIV-exposed uninfected compared with HIV-unexposed uninfected infants and children.

OBJECTIVE: Conduct a meta-analysis examining differential all-cause mortality rates between HIV-exposed uninfected (HEU) infants and children as compared with their HIV-unexposed uninfected (HUU) counterparts. DESIGN: Meta-analysis summarizing the difference in mortality between HEU and HUU infants and children. Reviewed studies comparing children in the two groups for all-cause mortality, in any setting, from 1994 to 2016 from six databases. METHODS: Meta-analyses were done estimating overall mortality comparing the two groups, stratified by duration of follow-up time from birth (0-12, 12-24 and >24 months) and by year enrollment ended in each study: less than 2002 compared with at least 2002, when single-dose nevirapine for prevention of mother-to-child transmission (PMTCT) commenced in low-income and middle-income countries. RESULTS: Included 22 studies, for a total of 29 212 study participants [n = 8840 (30.3%) HEU; n = 20 372 (37.7%) HUU]. Random effects models showed HEU had a more than 70% increased risk of mortality vs. HUU. Stratifying by age showed that HEU vs. HUU had a significant 60-70% increased risk of death at every age strata. There was a significant 70% increase in the risk of mortality between groups before the implementation of PMTCT, which remained after 2002 [risk ratio: 1.46; 95% confidence interval (CI): 1.14-1.87], when the availability of PMTCT services was widespread, suggesting that prenatal antiretroviral therapy, and healthier mothers, does not fully eliminate this increased risk in mortality. CONCLUSION: We show a consistent increase risk of mortality for HEU vs. HUU infants and children. Longitudinal research is needed to elucidate underlying mechanisms, such as maternal and infant health status and breast feeding practices, which may help explain these differences in mortality.

Systematic Differences between Cochrane and Non-Cochrane Meta-Analyses on the Same Topic: A Matched Pair Analysis.

BACKGROUND: Meta-analyses conducted via the Cochrane Collaboration adhere to strict methodological and reporting standards aiming to minimize bias, maximize transparency/reproducibility, and improve the accuracy of summarized data. Whether this results in differences in the results reported by meta-analyses on the same topic conducted outside the Cochrane Collaboration is an open question. METHODS: We conducted a matched-pair analysis with individual meta-analyses as the unit of analysis, comparing Cochrane and non-Cochrane reviews. Using meta-analyses from the cardiovascular literature, we identified pairs that matched on intervention and outcome. The pairs were contrasted in terms of how frequently results disagreed between the Cochrane and non-Cochrane reviews, whether effect sizes and statistical precision differed systematically, and how these differences related to the frequency of secondary citations of those reviews. RESULTS: Our search yielded 40 matched pairs of reviews. The two sets were similar in terms of which was first to publication, how many studies were included, and average sample sizes. The paired reviews included a total of 344 individual clinical trials: 111 (32.3%) studies were included only in a Cochrane review, 104 (30.2%) only in a non-Cochrane review, and 129 (37.5%) in both. Stated another way, 62.5% of studies were only included in one or the other meta-analytic literature. Overall, 37.5% of pairs had discrepant results. The most common involved shifts in the width of 95% confidence intervals that would yield a different statistical interpretation of the significance of results (7 pairs). Additionally, 20% differed in the direction of the summary effect size (5 pairs) or reported greater than a 2-fold difference in its magnitude (3 pairs). Non-Cochrane reviews reported significantly higher effect sizes (P< 0.001) and lower precision (P<0.001) than matched Cochrane reviews. Reviews reporting an effect size at least 2-fold greater than their matched pair were cited more frequently. CONCLUSION: Though results between topic-matched Cochrane and non-Cochrane reviews were quite similar, discrepant results were frequent, and the overlap of included studies was surprisingly low. Non-Cochrane reviews report larger effect sizes with lower precision than Cochrane reviews, indicating systematic differences, likely reflective of methodology, between the two types of reviews that could generate different interpretations of the interventions under question.