Association Between Early Sexual Debut and New HIV Infections Among Adolescents and Young Adults in 11 African Countries.

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

The impact of the COVID-19 pandemic and associated suppression measures on the burden of tuberculosis in India.

BACKGROUND: Tuberculosis (TB) is a major cause of death globally. India carries the highest share of the global TB burden. The COVID-19 pandemic has severely impacted diagnosis of TB in India, yet there is limited data on how TB case reporting has changed since the pandemic began and which factors determine differences in case notification. METHODS: We utilized publicly available data on TB case reporting through the Indian Central TB Division from January 2017 through April of 2021 (prior to the first COVID-19 related lockdown). Using a Poisson model, we estimated seasonal and yearly patterns in TB case notification in India from January 2017 through February 2020 and extended this estimate as the counterfactual expected TB cases notified from March 2020 through April 2021. We characterized the differences in case notification observed and those expected in the absence of the pandemic by State and Territory. We then performed a linear regression to examine the relationship between the logit ratio of reported TB to counterfactual cases and mask use, mobility, daily hospitalizations/100,000 population, and public/total TB case reporting. RESULTS: We found 1,320,203 expected cases of TB (95% uncertainty interval (UI) 1,309,612 to 1,330,693) were not reported during the period from March 2020 through April 2021. This represents a 63.3% difference (95% UI 62.8 to 63.8) in reporting. We found that mobility data and average hospital admissions per month per population were correlated with differences in TB case notification, compared to the counterfactual in the absence of the pandemic (p > 0.001). CONCLUSION: There was a large difference between reported TB cases in India and those expected in the absence of the pandemic. This information can help inform the Indian TB program as they consider interventions to accelerate case finding and notification once the pandemic related TB service disruptions improve. Mobility data and hospital admissions are surrogate measures that correlate with a greater difference in reported/expected TB cases and may correlate with a disruption in TB diagnostic services. However, further research is needed to clarify this association and identify other key contributors to gaps in TB case notifications in India.

Progress towards the 2020 milestones of the end TB strategy in Cambodia: estimates of age and sex specific TB incidence and mortality from the Global Burden of Disease Study 2019.

BACKGROUND: Cambodia was recently removed from the World Health Organization's (WHO's) top 30 high tuberculosis (TB) burden countries. However, Cambodia's TB burden remains substantial, and the country is on the WHO's new global TB watchlist. We aimed to examine the levels and trends in the fatal and non-fatal TB burden in Cambodia from 1990 to 2019, assessing progress towards the WHO End TB interim milestones, which aim to reduce TB incidence rate by 20% and TB deaths by 35% from 2015 to 2020. METHODS: We leveraged the Global Burden of Disease 2019 (GBD 2019) analytical framework to compute age- and sex-specific TB mortality and incidence by HIV status in Cambodia. We enumerated TB mortality utilizing a Bayesian hierarchical Cause of Death Ensemble modeling platform. We analyzed all available data sources, including prevalence surveys, population-based tuberculin surveys, and TB cause-specific mortality, to produce internally consistent estimates of incidence and mortality using a compartmental meta-regression tool (DisMod-MR 2.1). We further estimated the fraction of tuberculosis mortality among individuals without HIV coinfection attributable to the independent effects of alcohol use, smoking, and diabetes. RESULTS: In 2019, there were 6500 (95% uncertainty interval 4830-8680) deaths due to all-form TB and 50.0 (43.8-57.8) thousand all-form TB incident cases in Cambodia. The corresponding age-standardized rates were 53.3 (39.9-69.4) per 100,000 population for mortality and 330.5 (289.0-378.6) per 100,000 population for incidence. From 2015 to 2019, the number of all-form TB deaths decreased by 11.8% (2.3-21.1), while the age-standardized all-form TB incidence rate decreased by 11.1% (6.3-15.6). Among individuals without HIV coinfection in 2019, alcohol use accounted for 28.1% (18.2-37.9) of TB deaths, smoking accounted for 27.0% (20.2-33.3), and diabetes accounted for 12.5% (7.1-19.0). Removing the combined effects of these risk factors would reduce all-form TB deaths by 54.2% (44.2-62.2). DISCUSSION: Despite significant progress in reducing TB morbidity and mortality since 1990, Cambodia is not on track to achieve the 2020 WHO End TB interim milestones. Existing programs in Cambodia can benefit from liaising with risk factor control initiatives to accelerate progress toward eliminating TB in Cambodia.

Incidence of HIV in Sub-Saharan Africa, 2000-2015: The Interplay Between Social Determinants and Behavioral Risk Factors.

HIV incidence in sub-Saharan Africa declined substantially between 2000 and 2015. In this analysis, we consider the relative associations of nine structural and individual determinants with this decline. A linear mixed effects model of logged HIV incidence rates versus determinants was used. The data were from mathematical modelling as part of the 2019 Global Burden of Disease Study in 43 sub-Saharan African countries. We used forwards selection to determine a single final model of HIV incidence rate. The association of economic variables and HIV knowledge with incidence was found to be driven by education, while ART coverage had the largest impact on other determinants' coefficients. In the final model, education years per capita contributed the most to explaining variation in HIV incidence rates; a 1-year increase in mean education years was associated with a 0.39 (- 0.56; - 0.2, t = - 4.48 p < 0.01) % decline in incidence rate while a unit increase in ART coverage was associated with a 0.81 (- 1.34; - 0.28, t = - 3.01, p < 0.01) % decline in incidence rate.

Interferon-gamma release assay levels and risk of progression to active tuberculosis: a systematic review and dose-response meta-regression analysis.

BACKGROUND: Identifying and treating individuals with high risk of progression from latent tuberculosis infection to active tuberculosis (TB) disease is critical for eliminating the disease. We aimed to conduct a systematic review and meta-regression analysis to quantify the dose-response relationship between interferon-gamma release assay (IGRA) levels and the risk of progression to active TB. METHODS: We searched PubMed and Embase from 1 January 2001 to 10 May 2020 for longitudinal studies that reported the risk of progression from latent to active TB as a function of baseline IGRA values. We used a novel Bayesian meta-regression method to pool effect sizes from included studies and generate a continuous dose-response risk curve. Our modeling framework enabled us to incorporate random effects across studies, and include data with different IGRA ranges across studies. The quality of included studies were assessed using the Newcastle-Ottawa scale (NOS). RESULTS: We included 34 studies representing 581,956 person-years of follow-up with a total of 788 incident cases of TB in the meta-regression analysis. Higher levels of interferon-gamma were associated with increased risk of progression to active tuberculosis. In the dose-response curve, the risk increased sharply between interferon-gamma levels 0 and 5 IU/ml, after which the risk continued to increase moderately but at a slower pace until reaching about 15 IU/ml where the risk levels off. Compared to 0 IU/ml, the relative risk of progression to active TB among those with interferon-gamma levels of 0.35, 1, 5, 10, 15, and 20 IU/ml were: 1.64 (1.28-2.08), 2.90 (2.02-3.88), 11.38 (6.64-16.38), 19.00 (13.08-26.90), 21.82 (14.65-32.57), and 22.31 (15.43-33.00), respectively. The dose-response relationship remains consistent when limiting the analysis to studies that scored highest in the NOS. CONCLUSION: The current practice of dichotomizing IGRA test results simplifies the TB infection disease continuum. Evaluating IGRA test results over a continuous scale could enable the identification of individuals at greatest risk of progression to active TB.

Progress toward eliminating TB and HIV deaths in Brazil, 2001-2015: a spatial assessment.

BACKGROUND: Brazil has high burdens of tuberculosis (TB) and HIV, as previously estimated for the 26 states and the Federal District, as well as high levels of inequality in social and health indicators. We improved the geographic detail of burden estimation by modelling deaths due to TB and HIV and TB case fatality ratios for the more than 5400 municipalities in Brazil. METHODS: This ecological study used vital registration data from the national mortality information system and TB case notifications from the national communicable disease notification system from 2001 to 2015. Mortality due to TB and HIV was modelled separately by cause and sex using a Bayesian spatially explicit mixed effects regression model. TB incidence was modelled using the same approach. Results were calibrated to the Global Burden of Disease Study 2016. Case fatality ratios were calculated for TB. RESULTS: There was substantial inequality in TB and HIV mortality rates within the nation and within states. National-level TB mortality in people without HIV infection declined by nearly 50% during 2001 to 2015, but HIV mortality declined by just over 20% for males and 10% for females. TB and HIV mortality rates for municipalities in the 90th percentile nationally were more than three times rates in the 10th percentile, with nearly 70% of the worst-performing municipalities for male TB mortality and more than 75% for female mortality in 2001 also in the worst decile in 2015. The same municipality ranking metric for HIV was observed to be between 55% and 61%. Within states, the TB mortality rate ratios by sex for municipalities in the worst decile versus the best decile varied from 1.4 to 2.9, and HIV varied from 1.4 to 4.2. The World Health Organization target case fatality rate for TB of less than 10% was achieved in 9.6% of municipalities for males versus 38.4% for females in 2001 and improved to 38.4% and 56.6% of municipalities for males versus females, respectively, by 2014. CONCLUSIONS: Mortality rates in municipalities within the same state exhibited nearly as much relative variation as within the nation as a whole. Monitoring the mortality burden at this level of geographic detail is critical for guiding precision public health responses.

Global variation in bacterial strains that cause tuberculosis disease: a systematic review and meta-analysis.

BACKGROUND: The host, microbial, and environmental factors that contribute to variation in tuberculosis (TB) disease are incompletely understood. Accumulating evidence suggests that one driver of geographic variation in TB disease is the local ecology of mycobacterial genotypes or strains, and there is a need for a comprehensive and systematic synthesis of these data. The objectives of this study were to (1) map the global distribution of genotypes that cause TB disease and (2) examine whether any epidemiologically relevant clinical characteristics were associated with those genotypes. METHODS: We performed a systematic review of PubMed and Scopus to create a comprehensive dataset of human TB molecular epidemiology studies that used representative sampling techniques. The methods were developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We extracted and synthesized data from studies that reported prevalence of bacterial genotypes and from studies that reported clinical characteristics associated with those genotypes. RESULTS: The results of this study are twofold. First, we identified 206 studies for inclusion in the study, representing over 200,000 bacterial isolates collected over 27 years in 85 countries. We mapped the genotypes and found that, consistent with previously published maps, Euro-American lineage 4 and East Asian lineage 2 strains are widespread, and West African lineages 5 and 6 strains are geographically restricted. Second, 30 studies also reported transmission chains and 4 reported treatment failure associated with genotypes. We performed a meta-analysis and found substantial heterogeneity across studies. However, based on the data available, we found that lineage 2 strains may be associated with increased risk of transmission chains, while lineages 5 and 6 strains may be associated with reduced risk, compared with lineage 4 strains. CONCLUSIONS: This study provides the most comprehensive systematic analysis of the evidence for diversity in bacterial strains that cause TB disease. The results show both geographic and epidemiological differences between strains, which could inform our understanding of the global burden of TB. Our findings also highlight the challenges of collecting the clinical data required to inform TB diagnosis and treatment. We urge future national TB programs and research efforts to prioritize and reinforce clinical data collection in study designs and results dissemination.

The State of US Health, 1990-2016: Burden of Diseases, Injuries, and Risk Factors Among US States.

Introduction: Several studies have measured health outcomes in the United States, but none have provided a comprehensive assessment of patterns of health by state. Objective: To use the results of the Global Burden of Disease Study (GBD) to report trends in the burden of diseases, injuries, and risk factors at the state level from 1990 to 2016. Design and Setting: A systematic analysis of published studies and available data sources estimates the burden of disease by age, sex, geography, and year. Main Outcomes and Measures: Prevalence, incidence, mortality, life expectancy, healthy life expectancy (HALE), years of life lost (YLLs) due to premature mortality, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 333 causes and 84 risk factors with 95% uncertainty intervals (UIs) were computed. Results: Between 1990 and 2016, overall death rates in the United States declined from 745.2 (95% UI, 740.6 to 749.8) per 100 000 persons to 578.0 (95% UI, 569.4 to 587.1) per 100 000 persons. The probability of death among adults aged 20 to 55 years declined in 31 states and Washington, DC from 1990 to 2016. In 2016, Hawaii had the highest life expectancy at birth (81.3 years) and Mississippi had the lowest (74.7 years), a 6.6-year difference. Minnesota had the highest HALE at birth (70.3 years), and West Virginia had the lowest (63.8 years), a 6.5-year difference. The leading causes of DALYs in the United States for 1990 and 2016 were ischemic heart disease and lung cancer, while the third leading cause in 1990 was low back pain, and the third leading cause in 2016 was chronic obstructive pulmonary disease. Opioid use disorders moved from the 11th leading cause of DALYs in 1990 to the 7th leading cause in 2016, representing a 74.5% (95% UI, 42.8% to 93.9%) change. In 2016, each of the following 6 risks individually accounted for more than 5% of risk-attributable DALYs: tobacco consumption, high body mass index (BMI), poor diet, alcohol and drug use, high fasting plasma glucose, and high blood pressure. Across all US states, the top risk factors in terms of attributable DALYs were due to 1 of the 3 following causes: tobacco consumption (32 states), high BMI (10 states), or alcohol and drug use (8 states). Conclusions and Relevance: There are wide differences in the burden of disease at the state level. Specific diseases and risk factors, such as drug use disorders, high BMI, poor diet, high fasting plasma glucose level, and alcohol use disorders are increasing and warrant increased attention. These data can be used to inform national health priorities for research, clinical care, and policy.

Global burden of diseases, injuries, and risk factors for young people's health during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: Young people's health has emerged as a neglected yet pressing issue in global development. Changing patterns of young people's health have the potential to undermine future population health as well as global economic development unless timely and effective strategies are put into place. We report the past, present, and anticipated burden of disease in young people aged 10-24 years from 1990 to 2013 using data on mortality, disability, injuries, and health risk factors. METHODS: The Global Burden of Disease Study 2013 (GBD 2013) includes annual assessments for 188 countries from 1990 to 2013, covering 306 diseases and injuries, 1233 sequelae, and 79 risk factors. We used the comparative risk assessment approach to assess how much of the burden of disease reported in a given year can be attributed to past exposure to a risk. We estimated attributable burden by comparing observed health outcomes with those that would have been observed if an alternative or counterfactual level of exposure had occurred in the past. We applied the same method to previous years to allow comparisons from 1990 to 2013. We cross-tabulated the quantiles of disability-adjusted life-years (DALYs) by quintiles of DALYs annual increase from 1990 to 2013 to show rates of DALYs increase by burden. We used the GBD 2013 hierarchy of causes that organises 306 diseases and injuries into four levels of classification. Level one distinguishes three broad categories: first, communicable, maternal, neonatal, and nutritional disorders; second, non-communicable diseases; and third, injuries. Level two has 21 mutually exclusive and collectively exhaustive categories, level three has 163 categories, and level four has 254 categories. FINDINGS: The leading causes of death in 2013 for young people aged 10-14 years were HIV/AIDS, road injuries, and drowning (25·2%), whereas transport injuries were the leading cause of death for ages 15-19 years (14·2%) and 20-24 years (15·6%). Maternal disorders were the highest cause of death for young women aged 20-24 years (17·1%) and the fourth highest for girls aged 15-19 years (11·5%) in 2013. Unsafe sex as a risk factor for DALYs increased from the 13th rank to the second for both sexes aged 15-19 years from 1990 to 2013. Alcohol misuse was the highest risk factor for DALYs (7·0% overall, 10·5% for males, and 2·7% for females) for young people aged 20-24 years, whereas drug use accounted for 2·7% (3·3% for males and 2·0% for females). The contribution of risk factors varied between and within countries. For example, for ages 20-24 years, drug use was highest in Qatar and accounted for 4·9% of DALYs, followed by 4·8% in the United Arab Emirates, whereas alcohol use was highest in Russia and accounted for 21·4%, followed by 21·0% in Belarus. Alcohol accounted for 9·0% (ranging from 4·2% in Hong Kong to 11·3% in Shandong) in China and 11·6% (ranging from 10·1% in Aguascalientes to 14·9% in Chihuahua) of DALYs in Mexico for young people aged 20-24 years. Alcohol and drug use in those aged 10-24 years had an annual rate of change of >1·0% from 1990 to 2013 and accounted for more than 3·1% of DALYs. INTERPRETATION: Our findings call for increased efforts to improve health and reduce the burden of disease and risks for diseases in later life in young people. Moreover, because of the large variations between countries in risks and burden, a global approach to improve health during this important period of life will fail unless the particularities of each country are taken into account. Finally, our results call for a strategy to overcome the financial and technical barriers to adequately capture young people's health risk factors and their determinants in health information systems. FUNDING: Bill & Melinda Gates Foundation.

Mortality from tetanus between 1990 and 2015: findings from the global burden of disease study 2015.

BACKGROUND: Although preventable, tetanus still claims tens of thousands of deaths each year. The patterns and distribution of mortality from tetanus have not been well characterized. We identified the global, regional, and national levels and trends of mortality from neonatal and non-neonatal tetanus based on the results from the Global Burden of Disease Study 2015. METHODS: Data from vital registration, verbal autopsy studies and mortality surveillance data covering 12,534 site-years from 1980 to 2014 were used. Mortality from tetanus was estimated using the Cause of Death Ensemble modeling strategy. RESULTS: There were 56,743 (95% uncertainty interval (UI): 48,199 to 80,042) deaths due to tetanus in 2015; 19,937 (UI: 17,021 to 23,467) deaths occurred in neonates; and 36,806 (UI: 29,452 to 61,481) deaths occurred in older children and adults. Of the 19,937 neonatal tetanus deaths, 45% of deaths occurred in South Asia, and 44% in Sub-Saharan Africa. Of the 36,806 deaths after the neonatal period, 47% of deaths occurred in South Asia, 36% in sub-Saharan Africa, and 12% in Southeast Asia. Between 1990 and 2015, the global mortality rate due to neonatal tetanus dropped by 90% and that due to non-neonatal tetanus dropped by 81%. However, tetanus mortality rates were still high in a number of countries in 2015. The highest rates of neonatal tetanus mortality (more than 1,000 deaths per 100,000 population) were observed in Somalia, South Sudan, Afghanistan, and Kenya. The highest rates of mortality from tetanus after the neonatal period (more than 5 deaths per 100,000 population) were observed in Somalia, South Sudan, and Kenya. CONCLUSIONS: Though there have been tremendous strides globally in reducing the burden of tetanus, tens of thousands of unnecessary deaths from tetanus could be prevented each year by an already available inexpensive and effective vaccine. Availability of more high quality data could help narrow the uncertainty of tetanus mortality estimates.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.

Evaluation of the association between long-lasting insecticidal nets mass distribution campaigns and child malaria in Nigeria.

BACKGROUND: Nigeria carries the greatest malaria burden among countries in the world. As part of the National Malaria Control Strategic Plan, free long-lasting insecticidal nets (LLINs) were distributed in 14 states of Nigeria through mass campaigns led by different organizations (the World Bank, UNICEF, or the Global Fund) between May 2009 and August 2010. The objective of this study was to evaluate the association between LLIN distribution campaigns and child malaria in Nigeria. METHODS: Data were from the Nigeria Malaria Indicator Survey which was carried out from October to December 2010 on a nationally representative sample of households. Participants were women aged 15-49 years and their children aged less than five years (N = 4082). The main outcome measure was the presence or absence of malaria parasites in blood samples of children (6-59 months). RESULTS: Compared with children living in communities with no campaigns, those in the campaign areas were less likely to test positive for malaria after adjusting for geographic locations, community- and individual-level characteristics including child-level use of insecticide-treated nets (ITNs). The protective effects were statistically significant for the World Bank Booster Project areas (OR = 0.18, 95% CI = 0.04-0.73) but did not reach statistical significance for other campaign areas. Results also showed that community-level wealth (OR = 0.51, 95% CI = 0.34-0.76), community-level maternal knowledge regarding malaria prevention (OR = 0.70, 95% CI = 0.50-0.97), and child-level use of ITNs (OR = 0.79, 95% CI = 0.63-0.99) were negatively associated with child malaria. CONCLUSIONS: The observed protective effects on child malaria of these campaigns (statistically significant in the World Bank Booster Project areas and non-significant in the other areas) need to be corroborated by future effectiveness studies. Results also show that improving community-level maternal knowledge through appropriate channels might be helpful in preventing child malaria in Nigeria.

Global-, Regional-, and National-Level Impacts of the COVID-19 Pandemic on Tuberculosis Diagnoses, 2020-2021.

Evaluating cross-country variability on the impact of the COVID-19 pandemic on tuberculosis (TB) may provide urgent inputs to control programs as countries recover from the pandemic. We compared expected TB notifications, modeled using trends in annual TB notifications from 2013-2019, with observed TB notifications to compute the observed to expected (OE) ratios for 170 countries. We applied the least absolute shrinkage and selection operator (LASSO) method to identify the covariates, out of 27 pandemic- and tuberculosis-relevant variables, that had the strongest explanatory power for log OE ratios. The COVID-19 pandemic was associated with a 1.55 million (95% CI: 1.26-1.85, 21.0% [17.5-24.6%]) decrease in TB diagnoses in 2020 and a 1.28 million (0.90-1.76, 16.6% [12.1-21.2%]) decrease in 2021 at a global level. India, Indonesia, the Philippines, and China contributed the most to the global declines for both years, while sub-Saharan Africa achieved pre-pandemic levels by 2021 (OE ratio = 1.02 [0.99-1.05]). Age-stratified analyses revealed that the ≥ 65-year-old age group experienced greater relative declines in TB diagnoses compared with the under 65-year-old age group in 2020 (RR = 0.88 [0.81-0.96]) and 2021 (RR = 0.88 [0.79-0.98]) globally. Covariates found to be associated with all-age OE ratios in 2020 were age-standardized smoking prevalence in 2019 (ß = 0.973 [0.957-990]), school closures (ß = 0.988 [0.977-0.998]), stay-at-home orders (ß = 0.993 [0.985-1.00]), SARS-CoV-2 infection rate (ß = 0.991 [0.987-0.996]), and proportion of population ≥65 years (ß = 0.971 [0.944-0.999]). Further research is needed to clarify the extent to which the observed declines in TB diagnoses were attributable to disruptions in health services, decreases in TB transmission, and COVID-19 mortality among TB patients.

Meningococcal A conjugate vaccine coverage in the meningitis belt of Africa from 2010 to 2021: a modelling study.

Background: As of the end of 2021, twenty-four countries in the African meningitis belt have rolled out mass campaigns of MenAfriVac®, a meningococcal A conjugate vaccine (MACV) first introduced in 2010. Twelve have completed introduction of MACV into routine immunisation (RI) schedules. Although select post-campaign coverage data are published, no study currently comprehensively estimates MACV coverage from both routine and campaign sources in the meningitis belt across age, country, and time. Methods: In this modelling study, we assembled campaign data from the twenty-four countries that had introduced any immunisation activity during or before the year 2021 (Benin, Burkina Faso, Burundi, Cameroon, Central African Republic, Chad, Côte d'Ivoire, Democratic Republic of the Congo, Ethiopia, Eritrea, the Gambia, Ghana, Guinea, Guinea Bissau, Kenya, Mali, Mauritania, Niger, Nigeria, Senegal, South Sudan, Sudan, Togo and Uganda) via WHO reports and RI data via systematic review. Next, we modelled RI coverage using Spatiotemporal Gaussian Process Regression. Then, we synthesized these estimates with campaign data into a cohort model, tracking coverage for each age cohort from age 1 to 29 years over time for each country. Findings: Coverage in high-risk locations amongst children aged 1-4 in 2021 was estimated to be highest in Togo with 96.0% (95% uncertainty interval [UI] 92.0-99.0), followed by Niger with 87.2% (95% UI 85.3-89.0) and Burkina Faso, with 86.4% (95% UI 85.1-87.6). These countries had high coverage values driven by an initial successful mass immunisation campaign, followed by a catch-up campaign, followed by introduction of RI. Due to the influence of older mass vaccination campaigns, coverage proportions skewed higher in the 1-29 age group than the 1-4 group, with a median coverage of 82.9% in 2021 in the broader age group compared to 45.6% in the narrower age group. Interpretation: These estimates highlight where gaps in immunisation remain and emphasise the need for broader efforts to strengthen RI systems. This methodological framework can be applied to estimate coverage for any vaccine that has been delivered in both routine and supplemental immunisation activities. Funding: Bill and Melinda Gates Foundation.

Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis.

BACKGROUND: Rotavirus caused an estimated 151,714 deaths from diarrhea among children under 5 in 2019. To reduce mortality, countries are considering adding rotavirus vaccination to their routine immunization program. Cost-effectiveness analyses (CEAs) to inform these decisions are not available in every setting, and where they are, results are sensitive to modeling assumptions, especially about vaccine efficacy. We used advances in meta-regression methods and estimates of vaccine efficacy by location to estimate incremental cost-effectiveness ratios (ICERs) for rotavirus vaccination in 195 countries. METHODS: Beginning with Tufts University CEA and Global Health CEA registries we used 515 ICERs from 68 articles published through 2017, extracted 938 additional one-way sensitivity analyses, and excluded 33 ICERs for a sample of 1,418. We used a five-stage, mixed-effects, Bayesian metaregression framework to predict ICERs, and logistic regression model to predict the probability that the vaccine was cost-saving. For both models, covariates were vaccine characteristics including efficacy, study methods, and country-specific rotavirus disability-adjusted life-years (DALYs) and gross domestic product (GDP) per capita. All results are reported in 2017 United States dollars. RESULTS: Vaccine efficacy, vaccine cost, GDP per capita and rotavirus DALYs were important drivers of variability in ICERs. Globally, the median ICER was $2,289 (95% uncertainty interval (UI): $147-$38,993) and ranged from $85 per DALY averted (95% UI: $13-$302) in Central African Republic to $70,599 per DALY averted (95% UI: $11,030-$263,858) in the United States. Among countries eligible for support from Gavi, The Vaccine Alliance, the mean ICER was $255 per DALY averted (95% UI: $39-$918), and among countries eligible for the PAHO revolving fund, the mean ICER was $2,464 per DALY averted (95% UI: $382-$3,118). CONCLUSION: Our findings incorporate recent evidence that vaccine efficacy differs across locations, and support expansion of rotavirus vaccination programs, particularly in countries eligible for support from Gavi, The Vaccine Alliance.

Time trends in tuberculosis mortality across the BRICS: an age-period-cohort analysis for the GBD 2019.

Background: Tuberculosis is the leading cause of death from a single infectious agent among the HIV-negative population and ranks first among the HIV-positive population. However, few studies have assessed tuberculosis trends in Brazil, Russia, India, China and South Africa (BRICS) or with an emphasis on HIV status. This study assesses the time trends of tuberculosis mortality across the BRICS with an emphasis on HIV status from 1990 to 2019. Methods: We obtained tuberculosis data from the Global Burden of Disease 2019 study (GBD 2019). We calculated the relative proportion of tuberculosis to all communicable, maternal, neonatal, and nutritional diseases by HIV status across the BRICS. We used age-period-cohort modelling to estimate cohort and period effects in tuberculosis from 1990 to 2019, and calculated net drift (overall annual percentage change), local drift (annual percentage change in each age group), longitudinal age curves (expected longitudinal age-specific rate), and period (cohort) relative risks. Findings: There were 549,522 tuberculosis deaths across the BRICS in 2019, accounting for 39.3% of global deaths. Among HIV-negative populations, the age-standardised mortality rate (ASMR) of tuberculosis in BRICS remained far higher than that of high-income Asia Pacific countries, especially in India (36.1 per 100 000 in 2019, 95% UI [30.7, 42.6]) and South Africa (40.1 per 100 000 in 2019, 95% UI [36.8, 43.7]). China had the fastest ASMR reduction across the BRICS, while India maintained the largest tuberculosis death numbers with an annual decrease much slower than China's (-4.1 vs -8.0%). Among HIV-positive populations, the ASMR in BRICS surged from 0.24 per 100 000 in 1990 to 5.63 per 100 000 in 2005, and then dropped quickly to 1.70 per 100 000 in 2019. Brazil was the first country to reverse the upward trend of HIV/AIDS-tuberculosis (HIV-TB) mortality in 1995, and achieved the most significant reduction (-3.32% per year). The HIV-TB mortality in South Africa has realised much progress since 2006, but still has the heaviest HIV-TB burden across the BRICS (ASMR: 70.0 per 100 000 in 2019). We also found unfavourable trends among HIV-negative middle-aged (35-55) adults of India, men over 50 in the HIV-negative population and whole HIV-positive population of South Africa, and women aged 45-55 years of Russia. China had little progress in its HIV-positive population with worsening period risks from 2010 to 2019, and higher risks in the younger cohorts born after 1980. Interpretation: BRICS' actions on controlling tuberculosis achieved positive results, but the overall improvements were less than those in high-income Asia Pacific countries. BRICS and other high-burden countries should strengthen specified public health approaches and policies targeted at different priority groups in each country. Funding: National Natural Science Foundation of China (82073573; 72074009), Peking University Global Health and Infectious Diseases Group.

Aetiology and incidence of diarrhoea requiring hospitalisation in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network.

INTRODUCTION: Diarrhoea remains a leading cause of child morbidity and mortality. Systematically collected and analysed data on the aetiology of hospitalised diarrhoea in low-income and middle-income countries are needed to prioritise interventions. METHODS: We established the Global Pediatric Diarrhea Surveillance network, in which children under 5 years hospitalised with diarrhoea were enrolled at 33 sentinel surveillance hospitals in 28 low-income and middle-income countries. Randomly selected stool specimens were tested by quantitative PCR for 16 causes of diarrhoea. We estimated pathogen-specific attributable burdens of diarrhoeal hospitalisations and deaths. We incorporated country-level incidence to estimate the number of pathogen-specific deaths on a global scale. RESULTS: During 2017-2018, 29 502 diarrhoea hospitalisations were enrolled, of which 5465 were randomly selected and tested. Rotavirus was the leading cause of diarrhoea requiring hospitalisation (attributable fraction (AF) 33.3%; 95% CI 27.7 to 40.3), followed by Shigella (9.7%; 95% CI 7.7 to 11.6), norovirus (6.5%; 95% CI 5.4 to 7.6) and adenovirus 40/41 (5.5%; 95% CI 4.4 to 6.7). Rotavirus was the leading cause of hospitalised diarrhoea in all regions except the Americas, where the leading aetiologies were Shigella (19.2%; 95% CI 11.4 to 28.1) and norovirus (22.2%; 95% CI 17.5 to 27.9) in Central and South America, respectively. The proportion of hospitalisations attributable to rotavirus was approximately 50% lower in sites that had introduced rotavirus vaccine (AF 20.8%; 95% CI 18.0 to 24.1) compared with sites that had not (42.1%; 95% CI 33.2 to 53.4). Globally, we estimated 208 009 annual rotavirus-attributable deaths (95% CI 169 561 to 259 216), 62 853 Shigella-attributable deaths (95% CI 48 656 to 78 805), 36 922 adenovirus 40/41-attributable deaths (95% CI 28 469 to 46 672) and 35 914 norovirus-attributable deaths (95% CI 27 258 to 46 516). CONCLUSIONS: Despite the substantial impact of rotavirus vaccine introduction, rotavirus remained the leading cause of paediatric diarrhoea hospitalisations. Improving the efficacy and coverage of rotavirus vaccination and prioritising interventions against Shigella, norovirus and adenovirus could further reduce diarrhoea morbidity and mortality.

Socioeconomic and geographic patterning of under- and overnutrition among women in Bangladesh.

In Bangladesh, the prevalence of overweight among adults is increasing while underweight continues to be common. However, little is known about the pattern of underweight and overweight within Bangladesh and at the neighborhood level. The objective of this study was to assess the socioeconomic and geographic patterning of underweight and overweight in the population and determine if the burdens of these nutritional disorders coexist within neighborhoods in Bangladesh. A nationally representative sample of 10,589 ever-married women aged 15-49 y from 361 neighborhoods in Bangladesh was drawn from the 2004 Bangladesh Demographic and Health Survey. BMI (in kg/m(2)) was used to model nutritional status in a multinomial regression model with women classified as underweight (<18.5 kg/m(2)), overweight (≥25 kg/m(2)), or normal (18.5-24.9 kg/m(2)). Indicators of socioeconomic status and geography included household wealth, neighborhood wealth, and place of residence. Household wealth was related negatively to underweight (OR = 0.35 [95% credible interval (int) = 0.28-0.43] for the richest one-fifth vs. the poorest one-fifth) and positively to overweight [OR = 4.36 (95% int = 2.94-6.57) for the richest one-fifth vs. the poorest one-fifth] in a graded fashion. Neighborhood wealth was positively associated with overweight [OR = 1.75 (95% int = 1.25-2.44) for the top one-third vs. the lowest one-third] and negatively associated with underweight [OR = 0.81 (95% int = 0.69-0.96) for the top one-third vs. the lowest one-third]. Residence in rural neighborhoods was significantly associated with decreased levels of overweight [OR = 0.71 (95% int = 0.58-0.91)]. We observed an inverse relationship between the random effects associated with underweight and overweight at the neighborhood level (r = -0.66; P = 0.008). In conclusion, our results suggest burdens of underweight and overweight in Bangladesh are strongly related to individual socioeconomic position but geographically distinct. Neighborhoods where women were at a higher risk of being underweight were more likely to be those where women were at a lower risk of being overweight.

Meta-analysis of randomized trials on first line and adjunctive levetiracetam.

CONTEXT: New evidence suggests that levetiracetam may be as effective as traditional agents, with better safety profile. OBJECTIVE: To synthesize evidence regarding efficacy and tolerability of levetiracetam as first line, adjunctive or prophylactic antiepileptic agent. Study Selection & Data Extraction: Eligible studies were randomized controlled trials (RCTs) of levetiracetam used in adults with epilepsy. MEDLINE, EMBASE, CENTRAL, CINHAL, PAPERSFIRST, PROCEEDINGSFIRST, PROQUEST and conference proceedings identified studies (to September 30, 2010). Two investigators independently selected, appraised studies, collected and analyzed data. RESULTS: Of ten eligible randomized trials, eight investigated adjunctive levetiracetam for refractory seizures, one as monotherapy for newly diagnosed seizures, one as monotherapy for prophylaxis. Eight RCTs of adjunctive levetiracetam were of moderate quality (GRADE criteria), with two showing lack of allocation concealment. Meta-analyses showed adjunctive levetiracetam was more effective than placebo in achieving at least 50% reduction of seizure frequency, when added to baseline antiepileptic regimen (pooled RR 2.15 [1.65,2.82], I2 = 45%, p value (heterogeneity) = 0.08, p value (overall effect) < 0.01). Likelihood of serious adverse events necessitating withdrawal from study was not significantly different between levetiracetam and control (pooled RR 1.37 [0.88,2.13], I2 = 0%, p value (heterogeneity) = 0.84, p value (overall effect) = 0.17). Subgroup analyses suggested similar effects across different dosages. Sensitivity analysis of studies with adequate concealment showed similar effects. CONCLUSIONS: Levetiracetam is an effective adjunctive agent for refractory epilepsy. More studies are needed to establish whether it is effective as monotherapy for newly diagnosed seizures, and for prophylaxis in traumatic brain injury.

Predictors of surgical outcomes following anterior transposition of ulnar nerve for cubital tunnel syndrome: a systematic review.

PURPOSE: Although cubital tunnel syndrome is the second most common nerve entrapment neuropathy, few studies explore potential predictor(s) of surgical outcomes. The purpose of this systematic review was to determine which factors affect the postoperative outcome for patients who undertake anterior transposition of the ulnar nerve. METHODS: We included all studies reporting predictor(s) of clinical, electrophysiological study, or functional outcome after any anterior transposition of the ulnar nerve. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and CINAHL from 1980 to April 2011 and reference lists of articles. Two reviewers performed study selection, assessment of methodological quality, and data extraction independently of each other. RESULTS: We assessed 26 studies including 2 randomized controlled trials, 10 cohort studies, and 14 case series. Overall, the methodological quality of the studies ranged from low to moderate. Six aspects of prognosis were sufficiently studied for a narrative evidence synthesis on age, duration of symptom, severity of operative status, preoperative electrodiagnostic testing results, type of surgery, and work compensation status. Evidence was conflicting across studies in terms of both the direction and intensity of the impact of these 6 potential predictors on surgical outcomes. CONCLUSIONS: Because of conflicting results, we were unable to conclude which predictor(s) affect surgical outcomes after anterior transposition of the ulnar nerve. Surgeons who are aware of only a limited number of prognostic studies and their limited scope of evidence may not appreciate the extent of the inconsistency about whether factors commonly viewed as prognostic actually have a noteworthy impact on outcomes achieved. Such factors may be identified in the future with higher-quality studies, because limitations in the current research undoubtedly contribute to the controversies observed.