Olatunji Adetokunboh

Global, regional, and national age-sex specific mortality for 264 causes of death, 1980-2016

The last 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. n nA global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. n nIncreasing levels of YLLs may reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems.Summary Background Monitoring levels and trends in premature mortality is crucial to understanding how societies can address prominent sources of early death. The Global Burden of Disease 2016 Study (GBD 2016) provides a comprehensive assessment of cause-specific mortality for 264 causes in 195 locations from 1980 to 2016. This assessment includes evaluation of the expected epidemiological transition with changes in development and where local patterns deviate from these trends. Methods We estimated cause-specific deaths and years of life lost (YLLs) by age, sex, geography, and year. YLLs were calculated from the sum of each death multiplied by the standard life expectancy at each age. We used the GBD cause of death database composed of: vital registration (VR) data corrected for under-registration and garbage coding; national and subnational verbal autopsy (VA) studies corrected for garbage coding; and other sources including surveys and surveillance systems for specific causes such as maternal mortality. To facilitate assessment of quality, we reported on the fraction of deaths assigned to GBD Level 1 or Level 2 causes that cannot be underlying causes of death (major garbage codes) by location and year. Based on completeness, garbage coding, cause list detail, and time periods covered, we provided an overall data quality rating for each location with scores ranging from 0 stars (worst) to 5 stars (best). We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to generate estimates for each location, year, age, and sex. We assessed observed and expected levels and trends of cause-specific deaths in relation to the Socio-demographic Index (SDI), a summary indicator derived from measures of average income per capita, educational attainment, and total fertility, with locations grouped into quintiles by SDI. Relative to GBD 2015, we expanded the GBD cause hierarchy by 18 causes of death for GBD 2016. Findings The quality of available data varied by location. Data quality in 25 countries rated in the highest category (5 stars), while 48, 30, 21, and 44 countries were rated at each of the succeeding data quality levels. Vital registration or verbal autopsy data were not available in 27 countries, resulting in the assignment of a zero value for data quality. Deaths from non-communicable diseases (NCDs) represented 72·3% (95% uncertainty interval [UI] 71·2–73·2) of deaths in 2016 with 19·3% (18·5–20·4) of deaths in that year occurring from communicable, maternal, neonatal, and nutritional (CMNN) diseases and a further 8·43% (8·00–8·67) from injuries. Although age-standardised rates of death from NCDs decreased globally between 2006 and 2016, total numbers of these deaths increased; both numbers and age-standardised rates of death from CMNN causes decreased in the decade 2006–16—age-standardised rates of deaths from injuries decreased but total numbers varied little. In 2016, the three leading global causes of death in children under-5 were lower respiratory infections, neonatal preterm birth complications, and neonatal encephalopathy due to birth asphyxia and trauma, combined resulting in 1·80 million deaths (95% UI 1·59 million to 1·89 million). Between 1990 and 2016, a profound shift toward deaths at older ages occurred with a 178% (95% UI 176–181) increase in deaths in ages 90–94 years and a 210% (208–212) increase in deaths older than age 95 years. The ten leading causes by rates of age-standardised YLL significantly decreased from 2006 to 2016 (median annualised rate of change was a decrease of 2·89%); the median annualised rate of change for all other causes was lower (a decrease of 1·59%) during the same interval. Globally, the five leading causes of total YLLs in 2016 were cardiovascular diseases; diarrhoea, lower respiratory infections, and other common infectious diseases; neoplasms; neonatal disorders; and HIV/AIDS and tuberculosis. At a finer level of disaggregation within cause groupings, the ten leading causes of total YLLs in 2016 were ischaemic heart disease, cerebrovascular disease, lower respiratory infections, diarrhoeal diseases, road injuries, malaria, neonatal preterm birth complications, HIV/AIDS, chronic obstructive pulmonary disease, and neonatal encephalopathy due to birth asphyxia and trauma. Ischaemic heart disease was the leading cause of total YLLs in 113 countries for men and 97 countries for women. Comparisons of observed levels of YLLs by countries, relative to the level of YLLs expected on the basis of SDI alone, highlighted distinct regional patterns including the greater than expected level of YLLs from malaria and from HIV/AIDS across sub-Saharan Africa; diabetes mellitus, especially in Oceania; interpersonal violence, notably within Latin America and the Caribbean; and cardiomyopathy and myocarditis, particularly in eastern and central Europe. The level of YLLs from ischaemic heart disease was less than expected in 117 of 195 locations. Other leading causes of YLLs for which YLLs were notably lower than expected included neonatal preterm birth complications in many locations in both south Asia and southeast Asia, and cerebrovascular disease in western Europe. Interpretation The past 37 years have featured declining rates of communicable, maternal, neonatal, and nutritional diseases across all quintiles of SDI, with faster than expected gains for many locations relative to their SDI. A global shift towards deaths at older ages suggests success in reducing many causes of early death. YLLs have increased globally for causes such as diabetes mellitus or some neoplasms, and in some locations for causes such as drug use disorders, and conflict and terrorism. Increasing levels of YLLs might reflect outcomes from conditions that required high levels of care but for which effective treatments remain elusive, potentially increasing costs to health systems. Funding Bill & Melinda Gates Foundation.

Community-Based Interventions to Improve and Sustain Antiretroviral Therapy Adherence, Retention in HIV Care and Clinical Outcomes in Low- and Middle-Income Countries for Achieving the UNAIDS 90-90-90 Targets

Little is known about the effect of community versus health facility-based interventions to improve and sustain antiretroviral therapy (ART) adherence, virologic suppression, and retention in care among HIV-infected individuals in low- and middle-income countries (LMICs). We systematically searched four electronic databases for all available randomized controlled trials (RCTs) and comparative cohort studies in LMICs comparing community versus health facility-based interventions. Relative risks (RRs) for pre-defined adherence, treatment engagement (linkage and retention in care), and relevant clinical outcomes were pooled using random effect models. Eleven cohort studies and eleven RCTs (Nu2009=u200997,657) were included. Meta-analysis of the included RCTs comparing community- versus health facility-based interventions found comparable outcomes in terms of ART adherence (RRu2009=u20091.02, 95xa0% CI 0.99 to 1.04), virologic suppression (RRu2009=u20091.00, 95xa0% CI 0.98 to 1.03), and all-cause mortality (RRu2009=u20090.93, 95xa0% CI 0.73 to 1.18). The result of pooled analysis from the RCTs (RRu2009=u20091.03, 95xa0% CI 1.01 to 1.06) and cohort studies (RRu2009=u20091.09, 95xa0% CI 1.03 to 1.15) found that participants assigned to community-based interventions had statistically significantly higher rates of treatment engagement. Two studies found community-based ART delivery model either cost-saving or cost-effective. Community- versus facility-based models of ART delivery resulted in at least comparable outcomes for clinically stable HIV-infected patients on treatment in LMICs and are likely to be cost-effective.

Eliminating mother-to-child transmission of the human immunodeficiency virus in sub-Saharan Africa: The journey so far and what remains to be done

This review was carried out to provide a comprehensive overview of efforts toward elimination of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) with respect to progress, challenges, and recommendations in 21 sub-Saharan African priority countries. We reviewed literature published from 2011 to April 2015 using 3 databases; PubMed, Scopus, and Web of Science, as well as the 2014 Global Plan Progress Report. A total of 39 studies were included. Between 2009 and 2013, there was a 43% reduction in new HIV infections, the final MTCT rate was reduced from 28% to 18%, and antiretroviral therapy (ART) coverage increased from 11% to 24%. Challenges included poor adherence to antiretroviral therapy, poor linkage between mother-child pairs and post-natal healthcare services low early infant diagnosis coverage, low pediatric ART coverage, and high unmet needs for contraceptive services. Future recommendations include identification of key barriers, health system strengthening, strengthening community involvement, and international collaboration. There has been significant progress toward eliminating MTCT of HIV, but more effort is still needed.

Children who have received no routine polio vaccines in Nigeria: Who are they and where do they live?

ABSTRACT Nigeria has made remarkable progress against polio, but 2 wild polio virus cases were reported in August 2016; putting an end to 2 y without reported cases. We examined the extent of geographical disparities in childhren not vaccinated against polio and examined individual- and community-level predictors of non-vaccination in Nigeria. We applied multilevel logistic regression models to the recent Nigeria Demographic and Health Survey. The percentage of children not routinely vaccinated against polio in Nigeria varied greatly and clustered geographically, mainly in north-eastern states, with a great risk of spread of transmission within these states and potential exportation to neighboring states and countries. Only about one-third had received all recommended 4 routine oral polio vaccine doses. Non-vaccinated children tended to have a mother who had no formal education and who was currently not working, live in poorer households and were from neighborhoods with higher maternal illiteracy rates.

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.; We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).; Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8-75·9 million [7·2%, 6·0-8·3]), 45·1 million (29·0-62·8 million [5·6%, 4·0-7·2]), 36·3 million (25·3-50·9 million [4·5%, 3·8-5·3]), 34·7 million (23·0-49·6 million [4·3%, 3·5-5·2]), and 34·1 million (23·5-46·0 million [4·2%, 3·2-5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3-3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0-11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimers disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100u2008000, 95% UI 6862-11943) and highest rate (Yemen, 14u2008774 YLDs per 100u2008000, 11u2008018-19u2008228).; The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response.; Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.Summary Background As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016. Methods We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between incidence, prevalence, remission, and cause of death rates for each condition. For some causes, we used alternative modelling strategies if incidence or prevalence needed to be derived from other data. YLDs were estimated as the product of prevalence and a disability weight for all mutually exclusive sequelae, corrected for comorbidity and aggregated to cause level. We updated the Socio-demographic Index (SDI), a summary indicator of income per capita, years of schooling, and total fertility rate. GBD 2016 complies with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, low back pain, migraine, age-related and other hearing loss, iron-deficiency anaemia, and major depressive disorder were the five leading causes of YLDs in 2016, contributing 57·6 million (95% uncertainty interval [UI] 40·8–75·9 million [7·2%, 6·0–8·3]), 45·1 million (29·0–62·8 million [5·6%, 4·0–7·2]), 36·3 million (25·3–50·9 million [4·5%, 3·8–5·3]), 34·7 million (23·0–49·6 million [4·3%, 3·5–5·2]), and 34·1 million (23·5–46·0 million [4·2%, 3·2–5·3]) of total YLDs, respectively. Age-standardised rates of YLDs for all causes combined decreased between 1990 and 2016 by 2·7% (95% UI 2·3–3·1). Despite mostly stagnant age-standardised rates, the absolute number of YLDs from non-communicable diseases has been growing rapidly across all SDI quintiles, partly because of population growth, but also the ageing of populations. The largest absolute increases in total numbers of YLDs globally were between the ages of 40 and 69 years. Age-standardised YLD rates for all conditions combined were 10·4% (95% UI 9·0–11·8) higher in women than in men. Iron-deficiency anaemia, migraine, Alzheimers disease and other dementias, major depressive disorder, anxiety, and all musculoskeletal disorders apart from gout were the main conditions contributing to higher YLD rates in women. Men had higher age-standardised rates of substance use disorders, diabetes, cardiovascular diseases, cancers, and all injuries apart from sexual violence. Globally, we noted much less geographical variation in disability than has been documented for premature mortality. In 2016, there was a less than two times difference in age-standardised YLD rates for all causes between the location with the lowest rate (China, 9201 YLDs per 100u2008000, 95% UI 6862–11943) and highest rate (Yemen, 14u2008774 YLDs per 100u2008000, 11u2008018–19u2008228). Interpretation The decrease in death rates since 1990 for most causes has not been matched by a similar decline in age-standardised YLD rates. For many large causes, YLD rates have either been stagnant or have increased for some causes, such as diabetes. As populations are ageing, and the prevalence of disabling disease generally increases steeply with age, health systems will face increasing demand for services that are generally costlier than the interventions that have led to declines in mortality in childhood or for the major causes of mortality in adults. Up-to-date information about the trends of disease and how this varies between countries is essential to plan for an adequate health-system response. Funding Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.

Antiretroviral Treatment and Resistance Patterns in HIV-Infected Children.

Paediatric HIV-infected patients have higher risk of developing resistance to antiretroviral drugs, and from public health perspective, drug resistance remains a limiting factor for effective management of HIV infection in children. We reviewed the current evidences available on the antiretroviral treatment and resistance patterns in HIV-infected children. Prevalence of HIV drug resistance varied among the three main classes of antiretroviral drugs, namely nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors in both treatment naïve and treatment-experienced children in different countries. Most of the patients with extensive triple-class drug-resistant mutations were found to be considerably exposed to the three main classes of antiretroviral agents. Identification of genetic factors linked with susceptibility to perinatal transmission of HIV may be key in understanding the development of resistance due to waning antiviral effectiveness. Children who were less likely to achieve viral re-suppression were more likely to have resistance mutations. Newer drugs such as etravirine can be used as alternatives in case of resistance to efavirenz while newly developed diagnostic method such as next-generation sequencing is a platform for improving quality of detections especially minor variant drug resistance mutations.

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

BackgroundAbacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseasesMethodsWe searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool.ResultsWe included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48xa0weeks between abacavir- and stavudine-containing regimens (2 trials; nu2009=u2009326: RR 1.28; 95 % CI 0.67–2.42) with significant heterogeneity (Pu2009=u20090.02; I2u2009=u200981xa0%). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; nu2009=u200969: RR 1.96; 95 % CI 1.11–3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, nu2009=u20092165: RR 0.79, 95 % CI 0.67–0.92) and efavirenz sub-groups (1 study, nu2009=u20093204: RR 0.79, 95 % CI 0.67–0.92) respectively. The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events, while that of cohort studies was low for all three these outcomes.ConclusionsAvailable evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy.

Effect of maternal HIV status on vaccination coverage among sub-Saharan African children : a socio-ecological analysis

ABSTRACT We investigated the relationship between maternal HIV status and uptake of the full series of three doses of diphtheria-tetanus-pertussis containing vaccines (DTP3) in sub-Saharan African children. We used data obtained from demographic and health surveys conducted in sub-Saharan Africa. We conducted meta-analysis and calculated pooled odds ratios (OR) for the association between maternal HIV status and DTP3 vaccination status for each country. A total of 4,187 out of 5,537 children of women living with HIV received DTP3 (75.6%), compared to 71,290 of 113,513 (62.8%) children of HIV negative women. National DTP3 coverage among children of HIV-positive women varied between 24% and 96% while among children of HIV negative women it was between 26% and 92%. Overall pooled result showed no significant difference in DTP3 coverage between the two groups (OR = 1.05; 95% confidence interval 0.91 – 1.22), with statistically significant heterogeneity (Chi2 = 91.63, P = 0.000, I2 = 71.6%). There was no significant association between DTP3 coverage and maternal HIV status in sub-Saharan Africa. However, DTP3 coverage for both HIV-exposed and non-exposed children were below the required target. Meta-regression revealed no significant association between DTP3 coverage and country characteristics (e.g. HIV prevalence among women, antiretroviral therapy coverage, gross domestic product per capita, human development index, adult literacy rate and sub-region). Improved prevention of mother-to-child transmission services might have contributed to some extent to the higher DTP3 vaccination coverage among the HIV-exposed children. There is also need to address barriers impeding uptake of vaccination among HIV-exposed and non-exposed children.

Morbidity benefit conferred by childhood immunisation in relation to maternal HIV status: a meta-analysis of demographic and health surveys

ABSTRACT The study determined the prevalence of acute respiratory infections and diarrhoea among sub-Saharan African children. It also examined if there was any significant morbidity benefit conferred by three doses of diphtheria-tetanus-pertussis containing vaccines (DTP3) with respect to maternal HIV status. Data were obtained from the Demographic and Health Survey (DHS) program, United Nations Development Programs, World Bank and Joint United Nations Programme on HIV/AIDS. Pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated for the countries. Test of heterogeneity, sensitivity analyses and meta-regression were also conducted. The prevalence of acute respiratory infections and diarrhoea were similar between the children that were vaccinated and those who were not vaccinated with DTP3. The pooled result shows that children who did not receive DTP3 were more likely to have symptoms of acute respiratory infections than children who had DTP3 (OR 1.09, 95% CI 1.02 to 1.17); with low heterogeneity across the countries. The combined result for diarrhoea shows that children who did not receive DTP3 were less likely to have episodes of diarrhoea than children who received DTP3 (OR 0.83, 95% CI 0.74 to 0.92); with substantial heterogeneity across the countries. There was no difference between the estimates of DTP3 vaccinated and unvaccinated children of HIV seropositive mothers with respect to symptoms of acute respiratory infections or episodes of diarrhoea. Tackling various causes and risk factors for respiratory tract infections and diarrhoeal diseases should be a priority for various stakeholders in sub-Saharan Africa.

Antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children and adolescents: a systematic review protocol

BackgroundAbacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseases.MethodsWe plan to do a systematic review to evaluate the antiviral efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV-infected children aged between 3xa0months and 18xa0years, compared with other NRTIs. We will search Scopus, Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science databases for eligible studies regardless of language or publication status. We will check the reference lists of included studies, search relevant conference proceedings, email the authors of included studies and also look for unpublished and ongoing trials in prospective clinical trial registries. Two authors will independently screen search outputs, select studies, extract data and assess the risk of bias in included studies. All disagreements will be resolved by discussion and consensus. Where data allow, we will conduct meta-analysis for similar types of participants, study designs, interventions, and outcome measures. If the results are statistically homogeneous, we will use the fixed-effect model; otherwise, we will use the random-effects model and explore the reasons for heterogeneity using subgroup analyses. Heterogeneity will be assessed with the Chi-squared test and quantified with the I-squared statistic.DiscussionThe findings will be useful to policy makers and programme managers to inform treatment and management of HIV in children and adolescents and to point out research gaps for future research.Trial registrationThis review is registered with PROSPERO, registration number CRD42014009157.