Background Respiratory syncytial virus (RSV) is a leading cause of pediatric death, with >99% of mortality occurring in low- and lower middle-income countries. At least half of RSV-related deaths are estimated to occur in the community, but clinical characteristics of this group of children remain poorly characterized. Methods The RSV Global Online Mortality Database (RSV GOLD), a global registry of under-5 children who have died with RSV-related illness, describes clinical characteristics of children dying of RSV through global data sharing. RSV GOLD acts as a collaborative platform for global deaths, including community mortality studies described in this supplement. We aimed to compare the age distribution of infant deaths <6 months occurring in the community with in-hospital. Results We studied 829 RSV-related deaths <1 year of age from 38 developing countries, including 166 community deaths from 12 countries. There were 629 deaths that occurred <6 months, of which 156 (25%) occurred in the community. Among infants who died before 6 months of age, median age at death in the community (1.5 months; IQR: 0.8−3.3) was lower than in-hospital (2.4 months; IQR: 1.5−4.0; P < .0001). The proportion of neonatal deaths was higher in the community (29%, 46/156) than in-hospital (12%, 57/473, P < 0.0001). Conclusions We observed that children in the community die at a younger age. We expect that maternal vaccination or immunoprophylaxis against RSV will have a larger impact on RSV-related mortality in the community than in-hospital. This case series of RSV-related community deaths, made possible through global data sharing, allowed us to assess the potential impact of future RSV vaccines.

Introduction Adolescents with perinatally acquired HIV ( PHIV ) are at risk of chronic disease due to long‐standing immune suppression, HIV disease and antiretroviral therapy ( ART ) exposure. However, there are few data on multisystem disease in this population. We investigated the overlapping burden of neurocognitive, cardiovascular, respiratory and/or renal impairment among PHIV positive ( PHIV +) adolescents. Methods In this cross‐sectional analysis, participants aged 9 to 14 years on ART for >6 months were recruited from seven sites across Cape Town from July 2013 through March 2015, together with age‐matched HIV‐negative ( HIV‐ ) adolescents. Impairment at enrolment was assessed across neurocognitive functioning (using the youth‐International HIV Dementia Scale); cardiac function (echocardiogram abnormality); respiratory function (abnormal spirometry) and renal function (abnormal glomerular filtration rate). Results and Discussion Overall, 384 PHIV + and 95 HIV‐ adolescents were included (mean age, 11.9 years; 49% female). Median age of ART initiation was 4.2 years ( IQR : 1.7 to 7.6) and median CD 4 count was 709 ( IQR : 556 to 944) with 302 (79%) of PHIV + adolescents virologically suppressed. Abacavir and Zidovudine were the most commonly used nucleoside reverse transcriptase inhibitors ( NRTI s) with 60% of adolescents on non‐nucleoside reverse transcriptase inhibitors ( NNRTI ) and 38% on a protease inhibitor ( PI ). Among PHIV + adolescents, 167 (43.5%) had single system impairment only, 110 (28.6%) had two systems involved, and 39 (10.2%) had three or four systems involved. PHIV + participants had more 2‐system and 3‐system impairment than HIV‐ , 110 (28.6%) versus 17 (17.9%), p = 0.03 and 39 (10.2%) versus 3 (4.3%), p = 0.03. PHIV + participants who had failed a year of school (73.8% vs. 46.4%, p = 0.00) and with a viral load >1000 copies/mL at enrolment (16.8% vs. 8.1%, p = 0.03) were more likely to have dual or multisystem impairment. Of those with cardiac impairment, 86.7% had an additional system impaired. Similarly, in those with neurocognitive impairment, almost 60% had additional systems impaired and of t...

Background. Tuberculosis (TB) notification in South Africa has increased six-fold over the past two decades, mainly because of the HIV epidemic. Objectives. To describe the sociodemographic and outcome characteristics of TB patients, and to identify risk factors associated with TB treatment outcomes stratified by HIV status. Methods. A cross-sectional study was used to analyse data from the Cape Town Metro East geographical service area (GSA) electronic TB register (ETR.Net), including adult patients aged ≥15 years who initiated TB treatment between 1 July 2011 and 30 June 2012. Results. TB case notification in the GSA was 922 per 100 000 population. Of the 12 672 TB patients registered, 50.5% were co-infected with HIV. The death rate in co-infected patients was 5.4% v. 2.8% in HIV-negative patients, the rate of treatment success 66.6% v. 73.5%, and the rate of unfavourable treatment outcome 28.1% v. 23.7%. The Khayelitsha subdistrict had the highest proportion of TB burden (37.0%) and co-infection (47.6%). Fourteen percent of patients had extrapulmonary TB, 65.9% of whom were co-infected with HIV. In the multivariate analysis, HIV infection (relative risk (RR) 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The Eastern (RR 0.9) and Northern (RR 0.7) subdistricts were less likely to have unfavourable outcomes compared with Khayelitsha. In the stratified analysis, retreatment and smear not done were significant risk factors for an unfavourable treatment outcome in both co-infected and HIV-negative patients. Conclusions. The burdens of both TB and co-infection were high in this community, although HIV prevalence varied. Mortality was higher and treatment completion lower in co-infected patients than in those who were HIV-negative. Co-infection, previous TB treatment and smear not done were significant risk factors for an unfavourable outcome in all patients.

To investigate the prevalence of and risk factors for insulin resistance (IR) in a cohort of youth living with perinatally acquired HIV (YLPHIV) receiving antiretroviral treatment (ART). A cross-sectional analysis of IR in YLPHIV and age-matched HIV-uninfected youth enrolled in the Cape Town Adolescent Antiretroviral Cohort. South African youth ages 9-14 years, with perinatally acquired HIV who were on ART for >6 months and age-matched HIV-uninfected adolescents, were eligible. The homeostatic model assessment of insulin resistance (HOMA-IR), calculated from fasting insulin and glucose measurements at enrollment, was used to assess IR. Multiple linear regression was used to examine adjusted associations between HOMA and HIV-related and traditional cardiovascular risk factors. Of 448 adolescents, 385 (85.9%) were YLPHIV; median age was 12.1 years [interquartile range (IQR): 10.8-13.5], and 50.4% were female. Median duration on ART was 7.5 (IQR: 4.5-9.2) years. The prevalence of IR in YLPHIV was 18%. Among YLPHIV, waist circumference (ß = 0.01, p = .01), hypertriglyceridemia (ß = 0.07, p = .01), CD4 count >500 cells/mm (ß = 0.08, p = .02), or prior use of abacavir (ß = 0.06, p = .04) were associated with increased HOMA, after adjusting for age, sex, body mass index, and Tanner stage. In a South African cohort of YLPHIV on ART, IR was not significantly different from uninfected adolescents. YLPHIV with traditional cardiovascular risk factors or abacavir exposure may be at higher risk for IR.

Introduction Antiretroviral therapy (ART) has reduced morbidity and mortality in sub‐Saharan Africa, but the burden of coexistent cardiopulmonary disease in perinatally HIV‐positive adolescents on antiretroviral therapy (ART) has not been well described. The aim of this study was to investigate the prevalence and associations of cardiopulmonary dysfunction in adolescents with perinatally acquired HIV on ART. Methods For this cross‐sectional analysis, 515 perinatally HIV‐positive adolescents ages 9 to 14 years on ART for at least six months, and a comparator group of 110 age‐matched HIV‐uninfected adolescents were tested between August 2013 and April 2015 using echocardiography, six‐minute walk test (6MWT) and spirometry. Those with either abnormal spirometry or abnormal 6MWT and any right or left systolic or diastolic dysfunction or abnormal mean pulmonary arterial pressure were considered as having impaired cardiopulmonary function. Logistic regression was used to investigate determinants of impaired cardiopulmonary function. Results Overall, 474 adolescents with perinatally acquired HIV (mean [SD] age, 12 [1.6] years; median [IQR] ART duration, 7 [4.6 to 9.3] years; median [IQR] CD4 count, 712 [571 to 959] cell/mm3) and 109 HIV‐uninfected adolescents mean (SD) age 11.8 (1.8) years, had successful cardiac and lung function testing. Impaired cardiopulmonary function was detected in 13% of adolescents with perinatally acquired HIV and 8% of HIV‐uninfected adolescents, p = 0.136. Among adolescents with perinatally acquired HIV, those with low tricuspid annular plane systolic excursion (TAPSE) had significantly lower mean FEV1, 1.5 L versus 1.6 L, p = 0.011. Height (OR 0.7, 95%CI 0.5 to 0.9), body mass index (OR 0.7, 95%CI 0.5 to 0.9) and past pulmonary tuberculosis (OR 2.3, 95%CI 1.2 to 4.4) were significantly associated with a low cardiopulmonary function. Conclusions Despite being on ART, cardiopulmonary dysfunction occurs in an appreciable proportion of perinatally HIV‐infected adolescents but no significant difference to uninfected controls. This finding requires further exploration. Factors associated with dysfunction may be amenable to public health interventions to reduce cardiopulmonary disease in this population.

Background The current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death. Methods and findings We examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings. Conclusions Including conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

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Proteinuria and microalbuminuria appear to be uncommon in this population. Follow up of those with microalbuminuria may inform long-term outcomes and management of this growing population of HIV+ youth.