BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

BACKGROUND: The vast majority of deaths in the Kilifi study area are not recorded through official systems of vital registration. As a result, few data are available regarding causes of death in this population. OBJECTIVE: To describe the causes of death (CODs) among residents of all ages within the Kilifi Health and Demographic Surveillance System (KHDSS) on the coast of Kenya. DESIGN: Verbal autopsies (VAs) were conducted using the 2007 World Health Organization (WHO) standard VA questionnaires, and VA data further transformed to align with the 2012 WHO VA instrument. CODs were then determined using the InterVA-4 computer-based probabilistic model. RESULTS: Five thousand one hundred and eighty seven deaths were recorded between January 2008 and December 2011. VA interviews were completed for 4,460 (86%) deaths. Neonatal pneumonia and birth asphyxia were the main CODs in neonates; pneumonia and malaria were the main CODs among infants and children aged 1-4, respectively, while HIV/AIDS was the main COD for adult women of reproductive age. Road traffic accidents were more commonly observed among men than women. Stroke and neoplasms were common CODs among the elderly over the age of 65. CONCLUSIONS: We have established the main CODs among people of all ages within the area served by the KHDSS on the coast of Kenya using the 2007 WHO VA questionnaire coded using InterVA-4. We hope that our data will allow local health planners to estimate the burden of various diseases and to allocate their limited resources more appropriately.

BACKGROUND: Stroke is the second leading cause of death globally. Computerized tomography is used to distinguish between ischemic and hemorrhagic subtypes, but it is expensive and unavailable in low and middle income countries. Clinical stroke scores are proposed to differentiate between stroke subtypes but their reliability is unknown. MATERIALS AND METHODS: We searched online databases for studies written in English and identified articles using predefined criteria. We considered studies in which the Siriraj, Guy's Hospital, Besson and Greek stroke scores were compared to computerized tomography as the reference standard. We calculated the pooled sensitivity and specificity of the clinical stroke scores using a bivariate mixed effects binomial regression model. RESULTS: In meta-analysis, sensitivity and specificity for the Siriraj stroke score, were 0.69 (95% CI 0.62-0.75) and 0.83 (95% CI 0.75-0.88) for ischemic stroke and 0.65 (95% CI 0.56-0.73) and 0.88 (95% CI 0.83-0.91) for hemorrhagic stroke. For the Guy's hospital stroke score overall sensitivity and specificity were 0.70 (95% CI 0.53-0.83) and 0.79 (95% CI 0.68-0.87) for ischemic stroke and 0.54 (95% CI 0.42-0.66) and 0.89 (95% CI 0.83-0.94) for hemorrhagic stroke. CONCLUSIONS: Clinical stroke scores are not accurate enough for use in clinical or epidemiological settings. Computerized tomography is recommended for differentiating stroke subtypes. Larger studies using different patient populations are required for validation of clinical stroke scores.

OBJECTIVE: To determine the extent and pattern of treatment failure (TF) among children hospitalised with community-acquired pneumonia at a large tertiary hospital in Kenya. METHODS: We followed up children aged 2-59 months with WHO-defined severe pneumonia (SP) and very severe pneumonia (VSP) for up to 5 days for TF using two definitions: (i) documentation of pre-defined clinical signs resulting in change of treatment (ii) primary clinician's decision to change treatment with or without documentation of the same pre-defined clinical signs. RESULTS: We enrolled 385 children. The risk of TF varied between 1.8% (95% CI 0.4-5.1) and 12.4% (95% CI 7.9-18.4) for SP and 21.4% (95% CI 15.9-27) and 39.3% (95% CI 32.5-46.4) for VSP depending on the definition applied. Higher rates were associated with early changes in therapy by clinician in the absence of an obvious clinical rationale. Non-adherence to treatment guidelines was observed for 70/169 (41.4%) and 67/201 (33.3%) of children with SP and VSP, respectively. Among children with SP, adherence to treatment guidelines was associated with the presence of wheeze on initial assessment (P = 0.02), while clinician non-adherence to guideline-recommended treatments for VSP tended to occur in children with altered consciousness (P < 0.001). Using propensity score matching to account for imbalance in the distribution of baseline clinical characteristics among children with VSP revealed no difference in TF between those treated with the guideline-recommended regimen vs. more costly broad-spectrum alternatives [risk difference 0.37 (95% CI -0.84 to 0.51)]. CONCLUSION: Before revising current pneumonia case management guidelines, standardised definitions of TF and appropriate studies of treatment effectiveness of alternative regimens are required.

BACKGROUND: Estimates of the burden of disease in adults in sub-Saharan Africa largely rely on models of sparse data. We aimed to measure the burden of disease in adults living in a rural area of coastal Kenya with use of linked clinical and demographic surveillance data. METHODS: We used data from 18,712 adults admitted to Kilifi District Hospital (Kilifi, Kenya) between Jan 1, 2007, and Dec 31, 2012, linked to 790,635 person-years of observation within the Kilifi Health and Demographic Surveillance System, to establish the rates and major causes of admission to hospital. These data were also used to model disease-specific disability-adjusted life-years lost in the population. We used geographical mapping software to calculate admission rates stratified by distance from the hospital. FINDINGS: The main causes of admission to hospital in women living within 5 km of the hospital were infectious and parasitic diseases (303 per 100,000 person-years of observation), pregnancy-related disorders (239 per 100,000 person-years of observation), and circulatory illnesses (105 per 100,000 person-years of observation). Leading causes of hospital admission in men living within 5 km of the hospital were infectious and parasitic diseases (169 per 100,000 person-years of observation), injuries (135 per 100,000 person-years of observation), and digestive system disorders (112 per 100,000 person-years of observation). HIV-related diseases were the leading cause of disability-adjusted life-years lost (2050 per 100,000 person-years of observation), followed by non-communicable diseases (741 per 100,000 person-years of observation). For every 5 km increase in distance from the hospital, all-cause admission rates decreased by 11% (95% CI 7-14) in men and 20% (17-23) in women. The magnitude of this decline was highest for endocrine disorders in women (35%; 95% CI 22-46) and neoplasms in men (30%; 9-45). INTERPRETATION: Adults in rural Kenya face a combined burden of infectious diseases, pregnancy-related disorders, cardiovascular illnesses, and injuries. Disease burden estimates based on hospital data are affected by distance from the hospital, and the amount of underestimation of disease burden differs by both disease and sex. FUNDING: The Wellcome Trust, GAVI Alliance.

BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a family of variant surface antigens (VSA) that mediate the adhesion of parasite infected erythrocytes to capillary endothelial cells within host tissues. Opinion is divided over the role of PfEMP1 in the widespread endothelial activation associated with severe malaria. In a previous study we found evidence for differential associations between defined VSA subsets and specific syndromes of severe malaria: group A-like PfEMP1 expression and the "rosetting" phenotype were associated with impaired consciousness and respiratory distress, respectively. This study explores the involvement of widespread endothelial activation in these associations. METHODS: We used plasma angiopoietin-2 as a marker of widespread endothelial activation. Using logistic regression analysis, we explored the relationships between plasma angiopoietin-2 levels, parasite VSA expression and the two syndromes of severe malaria, impaired consciousness and respiratory distress. RESULTS: Plasma angiopoietin-2 was associated with both syndromes. The rosetting phenotype did not show an independent association with respiratory distress when adjusted for angiopoietin-2, consistent with a single pathogenic mechanism involving widespread endothelial activation. In contrast, group A-like PfEMP1 expression and angiopoietin-2 maintained independent associations with impaired consciousness when adjusted for each other. CONCLUSION: The results are consistent with multiple pathogenic mechanisms leading to severe malaria and heterogeneity in the pathophysiology of impaired consciousness. The observed association between group A-like PfEMP1 and impaired consciousness does not appear to involve widespread endothelial activation.

BACKGROUND: Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a family of variant surface antigens (VSA) that mediate the adhesion of parasite infected erythrocytes to capillary endothelial cells within host tissues. Opinion is divided over the role of PfEMP1 in the widespread endothelial activation associated with severe malaria. In a previous study we found evidence for differential associations between defined VSA subsets and specific syndromes of severe malaria: group A-like PfEMP1 expression and the "rosetting" phenotype were associated with impaired consciousness and respiratory distress, respectively. This study explores the involvement of widespread endothelial activation in these associations. METHODS: We used plasma angiopoietin-2 as a marker of widespread endothelial activation. Using logistic regression analysis, we explored the relationships between plasma angiopoietin-2 levels, parasite VSA expression and the two syndromes of severe malaria, impaired consciousness and respiratory distress. RESULTS: Plasma angiopoietin-2 was associated with both syndromes. The rosetting phenotype did not show an independent association with respiratory distress when adjusted for angiopoietin-2, consistent with a single pathogenic mechanism involving widespread endothelial activation. In contrast, group A-like PfEMP1 expression and angiopoietin-2 maintained independent associations with impaired consciousness when adjusted for each other. CONCLUSION: The results are consistent with multiple pathogenic mechanisms leading to severe malaria and heterogeneity in the pathophysiology of impaired consciousness. The observed association between group A-like PfEMP1 and impaired consciousness does not appear to involve widespread endothelial activation.

BACKGROUND: Nearly 40% of Global Fund money goes toward procurement. However, no analyses have been published to show how costs vary across regions and time, despite the availability of procurement data collected through the Global Fund's price and quality reporting system. METHODOLOGY: We analyzed data for the 3 most widely procured commodities for the prevention, diagnosis, and treatment of HIV. These were male condoms, HIV rapid tests, and the antiretroviral (ARV) combination of lamivudine/nevirapine/zidovudine. The compared costs, first across time (2005-2012), then across regions, and finally, between individual procurement reported through the price and quality reporting and pooled procurement reported through the Global Fund's voluntary pooled procurement system. All costs were adjusted for inflation and reported in US dollars. KEY FINDINGS: There were 2337 entries from 578 grants in 125 countries. The procurement cost for the ARV dropped substantially over the period, whereas those for condoms and HIV tests remained relatively stable. None of the commodity prices increased. Regional variations were pronounced for HIV tests, but minimal for condoms and the ARV. The unit cost for the 3-table ARV combination, for instance, varied between US$0.15 and US$0.23 in South Asia and the Eastern Europe/Central Asia regions, respectively, compared with a range of $0.23 (South Asia)-$1.50 (Eastern Europe/Central Asia) for a single diagnostic test. Pooled procurement lowered costs for condoms but not the other commodities. CONCLUSIONS: We showed how global procurement costs vary by region and time. Such analyses should be done more often to identify and correct market insufficiencies.