Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease.

BACKGROUND: Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown. METHODS: We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years. RESULTS: Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P<0.001). Two participants in the prophylaxis group had serious adverse events that were attributable to receipt of prophylaxis, including one episode of a mild anaphylactic reaction (representing <0.1% of all administered doses of prophylaxis). CONCLUSIONS: Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended. (Funded by the Thrasher Research Fund and others; GOAL ClinicalTrials.gov number, NCT03346525.).

Realigning noncommunicable disease monitoring with health systems priorities in the Africa region.

The African region of the World Health Organization (WHO) recently adopted a strategy aimed at more comprehensive care for noncommunicable diseases (NCDs) in the region. The WHO's World Health Assembly has also newly approved several ambitious disease-specific targets that raise the expectations of chronic care and plans to revise and update the NCD-Global Action Plan. These actions provide a critically needed opportunity for reflection and course correction in the global health response to NCDs. In this paper, we highlight the status of the indicators that are currently used to monitor progress towards global goals for chronic care. We argue that weak health systems and lack of access to basic NCD medicines and technologies have prevented many countries from achieving the level of progress required by the NCD epidemic, and current targets do little to address this reality. We identify gaps in existing metrics and explore opportunities to realign the targets with the pressing priorities facing today's health systems.

The prevalence of hypertension and its distribution by sociodemographic factors in Central Mozambique: a cross sectional study.

BACKGROUND: Hypertension (HTN) is a major risk factor for cardiovascular diseases, and its prevalence has been rising in low- and middle-income countries. The current study describes HTN prevalence in central Mozambique, association between wealth and blood pressure (BP), and HTN monitoring and diagnosis practice among individuals with elevated BP. METHODS: The study used data from a cross-sectional, representative household survey conducted in Manica and Sofala provinces, Mozambique. There were 4101 respondents, aged ≥20 years. We measured average systolic and diastolic BP (SBP and DBP) from three measurements taken in the household setting. Elevated BP was defined as having either SBP ≥140 or DBP ≥90 mmHg. RESULTS: The mean age of the participants was 36.7 years old, 59.9% were women, and 72.5% were from rural areas. Adjusting for complex survey weights, 15.7% (95%CI: 14.0 to 17.4) of women and 16.1% (13.9 to 18.5) of men had elevated BP, and 7.5% (95% CI: 6.4 to 8.7) of the overall population had both SBP ≥140 and DBP ≥90 mmHg. Among participants with elevated BP, proportions of participants who had previous BP measurement and HTN diagnosis were both low (34.9% (95% CI: 30.0 to 40.1) and 12.2% (9.9 to 15.0) respectively). Prior BP measurement and HTN diagnosis were more commonly reported among hypertensive participants with secondary or higher education, from urban areas, and with highest relative wealth. In adjusted models, wealth was positively associated with higher SBP and DBP. CONCLUSIONS: The current study found evidence of positive association between wealth and BP. The prevalence of elevated BP was lower in Manica and Sofala provinces than the previously estimated national prevalence. Previous BP screening and HTN diagnosis were uncommon in our study population, especially among rural residents, individuals with lower education levels, and those with relatively less wealth. As the epidemiological transition advances in Mozambique, there is a need to develop and implement strategies to increase BP screening and deliver appropriate clinical services, as well as to encourage lifestyle changes among people at risk of developing hypertension in near future.

Endemic Cardiovascular Diseases of the Poorest Billion.

The poorest billion people are distributed throughout the world, though most are concentrated in rural sub-Saharan Africa and South Asia. Cardiovascular disease (CVD) data can be sparse in low- and middle-income countries beyond urban centers. Despite this urban bias, CVD registries from the poorest countries have long revealed a predominance of nonatherosclerotic stroke, hypertensive heart disease, nonischemic and Chagas cardiomyopathies, rheumatic heart disease, and congenital heart anomalies, among others. Ischemic heart disease has been relatively uncommon. Here, we summarize what is known about the epidemiology of CVDs among the world's poorest people and evaluate the relevance of global targets for CVD control in this population. We assessed both primary data sources, and the 2013 Global Burden of Disease Study modeled estimates in the world's 16 poorest countries where 62% of the population are among the poorest billion. We found that ischemic heart disease accounted for only 12% of the combined CVD and congenital heart anomaly disability-adjusted life years (DALYs) in the poorest countries, compared with 51% of DALYs in high-income countries. We found that as little as 53% of the combined CVD and congenital heart anomaly burden (1629/3049 DALYs per 100 000) was attributed to behavioral or metabolic risk factors in the poorest countries (eg, in Niger, 82% of the population among the poorest billion) compared with 85% of the combined CVD and congenital heart anomaly burden (4439/5199 DALYs) in high-income countries. Further, of the combined CVD and congenital heart anomaly burden, 34% was accrued in people under age 30 years in the poorest countries, while only 3% is accrued under age 30 years in high-income countries. We conclude although the current global targets for noncommunicable disease and CVD control will help diminish premature CVD death in the poorest populations, they are not sufficient. Specifically, the current framework (1) excludes deaths of people <30 years of age and deaths attributable to congenital heart anomalies, and (2) emphasizes interventions to prevent and treat conditions attributed to behavioral and metabolic risks factors. We recommend a complementary strategy for the poorest populations that targets premature death at younger ages, addresses environmental and infectious risks, and introduces broader integrated health system interventions, including cardiac surgery for congenital and rheumatic heart disease.

Hypertension among people living with human immunodeficiency virus in sub-Saharan Africa: a systematic review and meta-analysis.

We performed a systematic review and meta-analysis of hypertension in people living with human immunodeficiency virus (HIV) in sub-Saharan Africa (SSA). We searched the PubMed, Google Scholar, African Index Medicus, and Embase databases to identify studies published from January 1, 2010, to December 31, 2021. We used a random-effects model to estimate the pooled prevalence of hypertension and mean SBP/DBP level on a sex-specific basis. We included 48 studies reporting data on a pooled sample of 193,843 people living with HIV (PLW-HIV) in SSA. The pooled mean SBP/DBP level was 120 (95% CI 113-128)/77 (95%CI 72-82) mmHg, while the overall pooled prevalence of hypertension was 21.9% (95% CI 19.9-23.9%). Further meta-regression analyses suggested that the prevalence of hypertension was 1.33 times greater in males, 1.23 times greater in individuals receiving antiretroviral therapy (ART) and 1.45 times greater in those individuals with a CD4-count ≥ 200. This meta-analysis of the contemporary pattern of BP levels among PLW-HIV in SSA, suggests that around one in five of such individuals also have hypertension. Given the further context of greater access to ART and subsequently greater longevity, study findings support calls to integrate cardiovascular management into routine HIV care.

Projected burden and distribution of elevated blood pressure levels and its consequence among adolescents in sub-Saharan Africa.

Background: There is minimal data on the number of adolescents in sub-Saharan Africa (SSA) with elevated blood pressure (BP) at increased risk of future cardiovascular events. Combining country-specific population data with data derived from two previously conducted meta-analyses (one African-specific, one based on international cohorts), we sought to address this knowledge deficit. Methods: We used meta-analysis data from 37 926 adolescents participating in 36 contemporary SSA studies to generate sex-specific proportions of adolescents aged 10-14 and 15-19 years with elevated BP. The estimates were applied to the 2021 World Bank population data for each country in SSA. We then applied the rate of cardiovascular events attributable to elevated BP levels, derived from a meta-analysis of 17 observational, longitudinal cohort studies comprising 4.5 million young adults (non-African), to determine the excess number of cardiovascular events linked to hypertension among those aged 15-19 years transitioning to adulthood. Results: The estimated prevalence of elevated BP among male and female adolescents aged 10-14 years living in SSA was 7.2% (95% confidence interval (CI) = 4.9-9.9) and 6.9% (95% CI = 4.7-9.5), respectively, which increased to 13.0% (95% CI = 10.6-15.6) and 12.5% (95% CI = 10.4-15.3) among male and female adolescents aged 15-19 years, respectively. Consequently, we estimate that 13.6/138.0 million (95% CI = 10.4-17.3) male and 12.9/135.7 million (95% CI = 9.83-16.3) female adolescents living in SSA have elevated BP. Among the estimated 16.1 million adolescents aged 15-19 years with elevated BP approaching adulthood, the projected excess in cardiovascular events attributable to hypertension (vs normotension) is 201 000 (95% CI = 115 000-322 000) to 503 000 (95% CI = 286 000-805 000) over the next 10-25 years. Conclusions: Based on the best available data, we estimate that 26.5 million adolescents living in SSA have elevated BP. If left undetected and untreated among those approaching adulthood (those aged 15-19 years), they will experience >0.5 million excess cardiovascular events associated with persistently elevated BP within the next 25 years. Registration: PROSPERO: CRD42022297948.

Scaling-up and scaling-out the Systems Analysis and Improvement Approach to optimize the hypertension diagnosis and care cascade for HIV infected individuals (SCALE SAIA-HTN): a stepped-wedge cluster randomized trial.

BACKGROUND: Undiagnosed and untreated hypertension is a main driver of cardiovascular disease and disproportionately affects persons living with HIV (PLHIV) in low- and middle-income countries. Across sub-Saharan Africa, guideline application to screen and manage hypertension among PLHIV is inconsistent due to poor service readiness, low health worker motivation, and limited integration of hypertension screening and management within HIV care services. In Mozambique, where the adult HIV prevalence is over 13%, an estimated 39% of adults have hypertension. As the only scaled chronic care service in the county, the HIV treatment platform presents an opportunity to standardize and scale hypertension care services. Low-cost, multi-component systems-level strategies such as the Systems Analysis and Improvement Approach (SAIA) have been found effective at integrating hypertension and HIV services to improve the effectiveness of hypertension care delivery for PLHIV, reduce drop-offs in care, and improve service quality. To build off lessons learned from a recently completed cluster randomized trial (SAIA-HTN) and establish a robust evidence base on the effectiveness of SAIA at scale, we evaluated a scaled-delivery model of SAIA (SCALE SAIA-HTN) using existing district health management structures to facilitate SAIA across six districts of Maputo Province, Mozambique. METHODS: This study employs a stepped-wedge design with randomization at the district level. The SAIA strategy will be "scaled up" with delivery by district health supervisors (rather than research staff) and will be "scaled out" via expansion to Southern Mozambique, to 18 facilities across six districts in Maputo Province. SCALE SAIA-HTN will be introduced over three, 9-month waves of intensive intervention, where technical support will be provided to facilities and district managers by study team members from the Mozambican National Institute of Health. Our evaluation of SCALE SAIA-HTN will be guided by the RE-AIM framework and will seek to estimate the budget impact from the payer's perspective. DISCUSSION: SAIA packages user-friendly systems engineering tools to support decision-making by frontline health workers and to identify low-cost, contextually relevant improvement strategies. By integrating SAIA delivery into routine management structures, this pragmatic trial will determine an effective strategy for national scale-up and inform program planning. TRIAL REGISTRATION: ClinicalTrials.gov NCT05002322 (registered 02/15/2023).

Elevated blood pressure among adolescents in sub-Saharan Africa: a systematic review and meta-analysis.

BACKGROUND: More people from sub-Saharan Africa aged between 20 years and 60 years are affected by end-organ damage due to underlying hypertension than people in high-income countries. However, there is a paucity of data on the pattern of elevated blood pressure among adolescents aged 10-19 years in sub-Saharan Africa. We aimed to provide pooled estimates of high blood pressure prevalence and mean levels in adolescents aged 10-19 years across sub-Saharan Africa. METHODS: In this systematic review and meta-analysis, we searched PubMed, Google Scholar, African Index Medicus, and Embase to identify studies published from Jan 1, 2010, to Dec 31, 2021. To be included, primary studies had to be observational studies of adolescents aged 10-19 years residing in sub-Saharan African countries reporting the pooled prevalence of elevated blood pressure or with enough data to compute these estimates. We excluded studies on non-systemic hypertension, in African people not living in sub-Saharan Africa, with participant selection based on the presence of hypertension, and with adult cohorts in which we could not disaggregate data for adolescents. We independently extracted relevant data from individual studies using a standard data extraction form. We used a random-effects model to estimate the pooled prevalence of elevated blood pressure and mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels overall and on a sex-specific basis. This study is registered with PROSPERO (CRD42022297948). FINDINGS: We identified 2559 studies, and assessed 81 full-text studies for eligibility, of which 36 studies comprising 37 926 participants aged 10-19 years from ten (20%) of 49 sub-Saharan African countries were eligible. A pooled sample of 29 696 adolescents informed meta-analyses of elevated blood pressure and 27 155 adolescents informed meta-analyses of mean blood pressure. Sex data were available from 26 818 adolescents (14 369 [53·6%] were female and 12 449 [46·4%] were male) for the prevalence of elevated blood pressure and 23 777 adolescents (12 864 [54·1%] were female and 10 913 [45·9%] were male) for mean blood pressure. Study quality was high, with no low-quality studies. The reported prevalence of elevated blood pressure ranged from 4 (0·2%) of 1727 to 1755 (25·1%) of 6980 (pooled prevalence 9·9%, 95% CI 7·3-12·5; I?=99·2%, pheterogeneity<0·0001). Mean SBP was 111 mm Hg (95% CI 108-114) and mean DBP was 68 mm Hg (66-70). 13·4% (95% CI 12·9-13·9; pheterogeneity<0·0001) of male participants had elevated blood pressure compared with 11·9% (11·3-12·4; pheterogeneity<0·0001) of female participants (odds ratio 1·04, 95% CI 0·81-1·34; pheterogeneity<0·0001). INTERPRETATION: To our knowledge, this systematic review and meta-analysis is the first systematic synthesis of blood pressure data specifically derived from adolescents in sub-Saharan Africa. Although many low-income countries were not represented in our study, our findings suggest that approximately one in ten adolescents have elevated blood pressure across sub-Saharan Africa. Accordingly, there is an urgent need to improve preventive heart-health programmes in the region. FUNDING: None.

HIV status and survival of patients with pulmonary hypertension due to left heart disease: the Pan African Pulmonary Hypertension Cohort.

In sub-Saharan Africa, little is known about pulmonary hypertension in left heart disease (PH-LHD). We used multivariate logistic and cox-hazard proportional regression models to examine factors associated with increased right ventricular systolic pressure (RVSP) and the effect of real-world HIV status scenarios on 6-month survival rate in the Pan African Pulmonary Hypertension Cohort (PAPUCO) study, a prospective cohort from four African countries. Exposure to biomass fuel smoke (aOR, 95%CI 3.07, 1.02-9.28), moderate to severe NYHA/FC III/IV (aOR, 95%CI 4.18, 1.01-17.38), and unknown HIV status (aOR, 95%CI 2.73, 0.96-7.73) predicted moderate to severe RVSP at the time of presentation. Six months later, HIV infection, moderate-to-severe NYHA/FC, and alcohol consumption were associated with decreased survival probabilities. Upon adjusting for HIV infection, it was observed that an incremental rise in RVSP (1 mmHg) and inter-ventricular septal thickness (1 mm) resulted in an 8% (aHR, 95%CI 1.08, 1.02-1.13) and 20% (aHR, 95%CI 1.2, 1.00-1.43) increase in the probability of mortality due to PH-LHD. In contrast, the risk of death from PH-LHD was reduced by 23% for each additional unit of BMI. (aHR, 95%CI 0.77, 0.59-1.00). In conclusion, the present study offers insights into the determinants that are notably linked to unfavorable survival outcomes in patients with pulmonary hypertension due to left heart disease. Certain factors identified in this study are readily evaluable and amenable to modification, even in settings with limited resources.

Rationale, Design, and the Baseline Characteristics of the RHDGen (The Genetics of Rheumatic Heart Disease) Network Study†.

BACKGROUND: The genetics of rheumatic heart disease (RHDGen) Network was developed to assist the discovery and validation of genetic variations and biomarkers of risk for rheumatic heart disease (RHD) in continental Africans, as a part of the global fight to control and eradicate rheumatic fever/RHD. Thus, we describe the rationale and design of the RHDGen study, comprising participants from 8 African countries. METHODS: RHDGen screened potential participants using echocardiography, thereafter enrolling RHD cases and ethnically-matched controls for whom case characteristics were documented. Biological samples were collected for conducting genetic analyses, including a discovery case-control genome-wide association study (GWAS) and a replication trio family study. Additional biological samples were also collected, and processed, for the measurement of biomarker analytes and the biomarker analyses are underway. RESULTS: Participants were enrolled into RHDGen between December 2012 and March 2018. For GWAS, 2548 RHD cases and 2261 controls (3301 women [69%]; mean age [SD], 37 [16.3] years) were available. RHD cases were predominantly Black (66%), Admixed (24%), and other ethnicities (10%). Among RHD cases, 34% were asymptomatic, 26% had prior valve surgery, and 23% had atrial fibrillation. The trio family replication arm included 116 RHD trio probands and 232 parents. CONCLUSIONS: RHDGen presents a rare opportunity to identify relevant patterns of genetic factors and biomarkers in Africans that may be associated with differential RHD risk. Furthermore, the RHDGen Network provides a platform for further work on fully elucidating the causes and mechanisms associated with RHD susceptibility and development.

Intracardiac masses in young Africans: case reports and a brief review of the literature.

Intracardiac masses in the young occur in some conditions that are prevalent in Africa. Although usually non-malignant, they may present with refractory heart failure and other complications that can be fatal. In the majority of cases, the aetiologic differentiation can be achieved by careful history, physical examination, basic laboratory tests, and transthoracic echocardiography. We report three cases in young Africans and discuss the aetiology, clinical presentation, diagnosis, management, and outcome of selected conditions in resource-limited settings.

Long-Term Follow-up of Human Immunodeficiency Virus-Associated Pulmonary Hypertension: Clinical Features and Survival Outcomes of the Pan Africa Pulmonary Hypertension Cohort (PAPUCO).

Background: Data characterizing risk factors and long-term outcome studies on human immunodeficiency virus (HIV)-associated pulmonary hypertension (PH) in Africa are lacking. Methods: The Pan African Pulmonary Hypertension Cohort, a multinational registry of 254 consecutive patients diagnosed with PH (97% of African descent) from 9 centers in 4 African countries was implemented. We compared baseline characteristics and 3-year survival of an HIV-infected cohort newly diagnosed with PH (PH/HIV+) to an HIV-uninfected cohort with PH (PH/HIV-). Results: One hundred thirty-four participants with PH completed follow up (47 PH/HIV+ and 87 PH/HIV-; age median, 36 versus 44 years; P = .0004). Cardiovascular risk factors and comorbidities were similar except for previous tuberculosis (62% versus 18%, P < .0001). Six-minute walk distance (6MWD) <300 meters was common in PH/HIV- (P = .0030), but PH/HIV+ had higher heart (P = .0160) and respiratory (P = .0374) rates. Thirty-six percent of PH/HIV+ and 15% of PH/HIV- presented with pulmonary arterial hypertension (PAH) (P = .0084), whereas 36% of PH/HIV+ and 72% of PH/HIV- exhibited PH due to left heart disease (PHLHD) (P = .0009). Pulmonary hypertension due to lung diseases and hypoxia (PHLD) was frequent in PH/HIV+ (36% versus 15%) but did not reach statistical significance. Human immunodeficiency virus-associated PAH tended to have a poorer survival rate compared with PHLHD/PHLD in HIV-infected patients. Conclusions: The PH/HIV + patients were younger and commonly had previous tuberculosis compared to PH/HIV- patients. Despite a better 6MWD at presentation, they had more signs and symptoms of early onset heart failure and a worse survival rate. Early echocardiography assessment should be performed in HIV-infected patients with history of tuberculosis who present with signs and symptoms of heart failure or posttuberculosis lung disease.

Cardiopulmonary disease as sequelae of long-term COVID-19: Current perspectives and challenges.

COVID-19 infection primarily targets the lungs, which in severe cases progresses to cytokine storm, acute respiratory distress syndrome, multiorgan dysfunction, and shock. Survivors are now presenting evidence of cardiopulmonary sequelae such as persistent right ventricular dysfunction, chronic thrombosis, lung fibrosis, and pulmonary hypertension. This review will summarize the current knowledge on long-term cardiopulmonary sequelae of COVID-19 and provide a framework for approaching the diagnosis and management of these entities. We will also identify research priorities to address areas of uncertainty and improve the quality of care provided to these patients.

Early presentation of endomyocardial fibrosis in a 22-month-old child: a case report.

We present an unusual, biopsy-proven case of endomyocardial fibrosis in a 22-month-old male child, which progressed rapidly resulting in death. The patient was born to a father originating from Mozambique, where the disease is endemic but who had not himself travelled there, suggesting a genetic link. Other remarkable features were the presence of a right ventricular diverticulum, and a positive Mycoplasma pneumoniae immunoglobulin M enzyme-linked immunosorbent assay test.

Earlier antiretroviral initiation is independently associated with better arterial stiffness in children living with perinatally acquired HIV with sustained viral suppression in Mozambique.

BACKGROUND: Cardiovascular disease is a major driver of morbidity and mortality in adults living with HIV. The drivers of cardiovascular disease in children living with perinatally acquired HIV (PHIV) with sustained HIV viral suppression are unclear. OBJECTIVES: We explored the contribution of HIV-specific risk factors to arterial stiffness independently of traditional risk factors (metabolic syndrome [MetS]) in prepubertal children with PHIV with sustained viral suppression in a low-income country in Africa. METHOD: For this cross-sectional analysis, arterial stiffness was assessed by pulse wave velocity z-score (PWVz), measured using a Vicorder device. Metabolic syndrome components were measured. We retrospectively collected the antiretroviral therapy (ART) exposures, HIV stage, CD4 count and HIV viral load. A multivariate linear regression model was constructed for MetS components, retaining age and gender as obligatory variables. We then added HIV-related metrics to assess whether these had an independent or additive effect. RESULTS: We studied 77 virally suppressed children with PHIV without evidence of cardiovascular disease (from medical history and physical examination). In the initial model, the PWVz was independently associated with each MetS component. The PWVz was higher in participants with proportionally greater visceral fat (waist/height ratio), elevated lipids (triglyceride/high-density lipoprotein ratio) and insulin resistance (log homeostatic model assessment [HOMA]). The addition of age at ART initiation increased the model R 2 value from 0.36 to 0.43. In the resulting model, younger age at ART initiation was independently associated with a better PWVz (P < 0.001). CONCLUSION: Earlier ART initiation was independently associated with lower large artery stiffness. This effect was independent of the effect of elevated lipids, visceral fat and insulin resistance.

An investment case for the prevention and management of rheumatic heart disease in the African Union 2021-30: a modelling study.

BACKGROUND: Despite declines in deaths from rheumatic heart disease (RHD) in Africa over the past 30 years, it remains a major cause of cardiovascular morbidity and mortality on the continent. We present an investment case for interventions to prevent and manage RHD in the African Union (AU). METHODS: We created a cohort state-transition model to estimate key outcomes in the disease process, including cases of pharyngitis from group A streptococcus, episodes of acute rheumatic fever (ARF), cases of RHD, heart failure, and deaths. With this model, we estimated the impact of scaling up interventions using estimates of effect sizes from published studies. We estimated the cost to scale up coverage of interventions and summarised the benefits by monetising health gains estimated in the model using a full income approach. Costs and benefits were compared using the benefit-cost ratio and the net benefits with discounted costs and benefits. FINDINGS: Operationally achievable levels of scale-up of interventions along the disease spectrum, including primary prevention, secondary prevention, platforms for management of heart failure, and heart valve surgery could avert 74 000 (UI 50 000-104 000) deaths from RHD and ARF from 2021 to 2030 in the AU, reaching a 30·7% (21·6-39·0) reduction in the age-standardised death rate from RHD in 2030, compared with no increase in coverage of interventions. The estimated benefit-cost ratio for plausible scale-up of secondary prevention and secondary and tertiary care interventions was 4·7 (2·9-6·3) with a net benefit of $2·8 billion (1·6-3·9; 2019 US$) through 2030. The estimated benefit-cost ratio for primary prevention scale-up was low to 2030 (0·2, <0·1-0·4), increasing with delayed benefits accrued to 2090. The benefit-cost dynamics of primary prevention were sensitive to the costs of different delivery approaches, uncertain epidemiological parameters regarding group A streptococcal pharyngitis and ARF, assumptions about long-term demographic and economic trends, and discounting. INTERPRETATION: Increased coverage of interventions to control and manage RHD could accelerate progress towards eradication in AU member states. Gaps in local epidemiological data and particular components of the disease process create uncertainty around the level of benefits. In the short term, costs of secondary prevention and secondary and tertiary care for RHD are lower than for primary prevention, and benefits accrue earlier. FUNDING: World Heart Federation, Leona M and Harry B Helmsley Charitable Trust, and American Heart Association.

Burden of disease among the world's poorest billion people: An expert-informed secondary analysis of Global Burden of Disease estimates.

BACKGROUND: The health of populations living in extreme poverty has been a long-standing focus of global development efforts, and continues to be a priority during the Sustainable Development Goal era. However, there has not been a systematic attempt to quantify the magnitude and causes of the burden in this specific population for almost two decades. We estimated disease rates by cause for the world's poorest billion and compared these rates to those in high-income populations. METHODS: We defined the population in extreme poverty using a multidimensional poverty index. We used national-level disease burden estimates from the 2017 Global Burden of Disease Study and adjusted these to account for within-country variation in rates. To adjust for within-country variation, we looked to the relationship between rates of extreme poverty and disease rates across countries. In our main modeling approach, we used these relationships when there was consistency with expert opinion from a survey we conducted of disease experts regarding the associations between household poverty and the incidence and fatality of conditions. Otherwise, no within-country variation was assumed. We compared results across multiple approaches for estimating the burden in the poorest billion, including aggregating national-level burden from the countries with the highest poverty rates. We examined the composition of the estimated disease burden among the poorest billion and made comparisons with estimates for high-income countries. RESULTS: The composition of disease burden among the poorest billion, as measured by disability-adjusted life years (DALYs), was 65% communicable, maternal, neonatal, and nutritional (CMNN) diseases, 29% non-communicable diseases (NCDs), and 6% injuries. Age-standardized DALY rates from NCDs were 44% higher in the poorest billion (23,583 DALYs per 100,000) compared to high-income regions (16,344 DALYs per 100,000). Age-standardized DALY rates were 2,147% higher for CMNN conditions (32,334 DALYs per 100,000) and 86% higher for injuries (4,182 DALYs per 100,000) in the poorest billion, compared to high-income regions. CONCLUSION: The disease burden among the poorest people globally compared to that in high income countries is highly influenced by demographics as well as large disparities in burden from many conditions. The comparisons show that the largest disparities remain in communicable, maternal, neonatal, and nutritional diseases, though NCDs and injuries are an important part of the "unfinished agenda" of poor health among those living in extreme poverty.

Association of Novel Locus With Rheumatic Heart Disease in Black African Individuals: Findings From the RHDGen Study.

Importance: Rheumatic heart disease (RHD), a sequela of rheumatic fever characterized by permanent heart valve damage, is the leading cause of cardiac surgery in Africa. However, its pathophysiologic characteristics and genetics are poorly understood. Understanding genetic susceptibility may aid in prevention, control, and interventions to eliminate RHD. Objective: To identify common genetic loci associated with RHD susceptibility in Black African individuals. Design, Setting, and Participants: This multicenter case-control genome-wide association study (GWAS), the Genetics of Rheumatic Heart Disease, examined more than 7 million genotyped and imputed single-nucleotide variations. The 4809 GWAS participants and 116 independent trio families were enrolled from 8 African countries between December 31, 2012, and March 31, 2018. All GWAS participants and trio probands were screened by use of echocardiography. Data analyses took place from May 15, 2017, until March 14, 2021. Main Outcomes and Measures: Genetic associations with RHD. Results: This study included 4809 African participants (2548 RHD cases and 2261 controls; 3301 women [69%]; mean [SD] age, 36.5 [16.3] years). The GWAS identified a single RHD risk locus, 11q24.1 (rs1219406 [odds ratio, 1.65; 95% CI, 1.48-1.82; P = 4.36 × 10-8]), which reached genome-wide significance in Black African individuals. Our meta-analysis of Black (n = 3179) and admixed (n = 1055) African individuals revealed several suggestive loci. The study also replicated a previously reported association in Pacific Islander individuals (rs11846409) at the immunoglobulin heavy chain locus, in the meta-analysis of Black and admixed African individuals (odds ratio, 1.16; 95% CI, 1.06-1.27; P = 1.19 × 10-3). The HLA (rs9272622) associations reported in Aboriginal Australian individuals could not be replicated. In support of the known polygenic architecture for RHD, overtransmission of a polygenic risk score from unaffected parents to affected probands was observed (polygenic transmission disequilibrium testing mean [SE], 0.27 [0.16] SDs; P = .04996), and the chip-based heritability was estimated to be high at 0.49 (SE = 0.12; P = 3.28 × 10-5) in Black African individuals. Conclusions and Relevance: This study revealed a novel candidate susceptibility locus exclusive to Black African individuals and an important heritable component to RHD susceptibility in African individuals.