SummaryBackgroundWe have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.MethodsWe estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.FindingsWe estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6–50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7–3·8) hospital admissions, and 59 600 (48 000–74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2–1·7) hospital admissions, and 27 300 (UR 20 700–36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600–149 400). Incidence and mortality varied substantially from year to year in any given population.InterpretationGlobally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.FundingThe Bill & Melinda Gates Foundation.

Summary Background Pneumonia is the leading cause of death among children younger than 5 years. In this study, we estimated causes of pneumonia in young African and Asian children, using novel analytical methods applied to clinical and microbiological findings. Methods We did a multi-site, international case-control study in nine study sites in seven countries: Bangladesh, The Gambia, Kenya, Mali, South Africa, Thailand, and Zambia. All sites enrolled in the study for 24 months. Cases were children aged 1–59 months admitted to hospital with severe pneumonia. Controls were age-group-matched children randomly selected from communities surrounding study sites. Nasopharyngeal and oropharyngeal (NP-OP), urine, blood, induced sputum, lung aspirate, pleural fluid, and gastric aspirates were tested with cultures, multiplex PCR, or both. Primary analyses were restricted to cases without HIV infection and with abnormal chest x-rays and to controls without HIV infection. We applied a Bayesian, partial latent class analysis to estimate probabilities of aetiological agents at the individual and population level, incorporating case and control data. Findings Between Aug 15, 2011, and Jan 30, 2014, we enrolled 4232 cases and 5119 community controls. The primary analysis group was comprised of 1769 (41·8% of 4232) cases without HIV infection and with positive chest x-rays and 5102 (99·7% of 5119) community controls without HIV infection. Wheezing was present in 555 (31·7%) of 1752 cases (range by site 10·6–97·3%). 30-day case-fatality ratio was 6·4% (114 of 1769 cases). Blood cultures were positive in 56 (3·2%) of 1749 cases, and Streptococcus pneumoniae was the most common bacteria isolated (19 [33·9%] of 56). Almost all cases (98·9%) and controls (98·0%) had at least one pathogen detected by PCR in the NP-OP specimen. The detection of respiratory syncytial virus (RSV), parainfluenza virus, human metapneumovirus, influenza virus, S pneumoniae, Haemophilus influenzae type b (Hib), H influenzae non-type b, and Pneumocystis jirovecii in NP-OP specimens was associated with case status. The aetiology analysis estimated that viruses accounted for 61·4% (95% credible interval [CrI] 57·3–65·6) of causes, whereas bacteria accounted for 27·3% (23·3–31·6) and Mycobacterium tuberculosis for 5·9% (3·9–8·3). Viruses were less common (54·5%, 95% CrI 47·4–61·5 vs 68·0%, 62·7–72·7) and bacteria more common (33·7%, 27·2–40·8 vs 22·8%, 18·3–27·6) in very severe pneumonia cases than in severe cases. RSV had the greatest aetiological fraction (31·1%, 95% CrI 28·4–34·2) of all pathogens. Human rhinovirus, human metapneumovirus A or B, human parainfluenza virus, S pneumoniae, M tuberculosis , and H influenzae each accounted f...

BackgroundThere exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia.MethodsUsing an established database, a retrospective cohort study was conducted of children aged 0–15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records.ResultsAmong 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio [aOR] = 0.48 (95% confidence interval [CI] 0.23–0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05–2.58).ConclusionsDespite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment to improve outcome.

Pneumococcal colonization density >6.9 log10 copies/mL was strongly associated with MCPP and could be used to improve estimates of pneumococcal pneumonia prevalence in childhood pneumonia studies. Our findings do not support its use for individual diagnosis in a clinical setting.

Background.Lack of a gold standard for identifying bacterial and viral etiologies of pneumonia has limited evaluation of C-reactive protein (CRP) for identifying bacterial pneumonia. We evaluated the sensitivity and specificity of CRP for identifying bacterial vs respiratory syncytial virus (RSV) pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) multicenter case-control study.Methods.We measured serum CRP levels in cases with World Health Organization–defined severe or very severe pneumonia and a subset of community controls. We evaluated the sensitivity and specificity of elevated CRP for “confirmed” bacterial pneumonia (positive blood culture or positive lung aspirate or pleural fluid culture or polymerase chain reaction [PCR]) compared to “RSV pneumonia” (nasopharyngeal/oropharyngeal or induced sputum PCR-positive without confirmed/suspected bacterial pneumonia). Receiver operating characteristic (ROC) curves were constructed to assess the performance of elevated CRP in distinguishing these cases.Results.Among 601 human immunodeficiency virus (HIV)–negative tested controls, 3% had CRP ≥40 mg/L. Among 119 HIV-negative cases with confirmed bacterial pneumonia, 77% had CRP ≥40 mg/L compared with 17% of 556 RSV pneumonia cases. The ROC analysis produced an area under the curve of 0.87, indicating very good discrimination; a cut-point of 37.1 mg/L best discriminated confirmed bacterial pneumonia (sensitivity 77%) from RSV pneumonia (specificity 82%). CRP ≥100 mg/L substantially improved specificity over CRP ≥40 mg/L, though at a loss to sensitivity.Conclusions.Elevated CRP was positively associated with confirmed bacterial pneumonia and negatively associated with RSV pneumonia in PERCH. CRP may be useful for distinguishing bacterial from RSV-associated pneumonia, although its role in discriminating against other respiratory viral-associated pneumonia needs further study.

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SummaryIn the Pneumonia Etiology Research for Child Health study, abnormal chest radiographs (CXRs) in cases were associated with hypoxemia, crackles, tachypnea, and fever. Overall, 54% of CXRs were abnormal (site range, 35%–64%). Consolidation on CXR was associated with an increased risk of mortality.

Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain lifelong post CM sequelae, including seizures and neurocognitive deficits profoundly affecting their quality of life. As the Plasmodium parasite does not enter the brain, but resides inside erythrocytes and are confined to the lumen of the brain's vasculature, the neuropathogenesis leading to these neurologic sequelae is unclear and underinvestigated. Interestingly, postmortem CM pathology differs in brain regions, such as the appearance of haemorragic punctae in white versus gray matter. Various host and parasite factors contribute to the risk of CM, including exposure at a young age, parasite-and host-related genetics, parasite sequestration and the extent of host inflammatory responses. Thus far, several proposed adjunctive treatments have not been successful in the treatment of CM but are highly needed. The region-specific CM neuro-pathogenesis leading to neurologic sequelae is intriguing, but not sufficiently addressed in research. More attention to this may lead to the development of effective adjunctive treatments to address CM neurologic sequelae.