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.).

Does It Matter What Screener We Use? A Comparison of Ultra-brief PHQ-4 and E-mwTool-3 Screeners for Anxiety and Depression Among People With and Without HIV.

The burden of depression and anxiety disorders is high in sub-Saharan Africa, especially for people with HIV (PWH). The Patient Health Questionnaire-4 (PHQ-4) and Electronic Mental Wellness Tool-3 (E-mwTool-3) are ultra-brief screening tools for these disorders. We compared the performance of PHQ-4 and E-mwTool-3 for screening MINI-International Neuropsychiatric Interview diagnoses of depression and anxiety among a sample of individuals with and without HIV in two primary care clinics and one general hospital in Maputo City, Mozambique. Areas-under-the-curve (AUC) were calculated along with sensitivities and specificities at a range of cutoffs. For PWH, at a sum score cutoff of ≥ 1, sensitivities were strong: PHQ-4:Depression = 0.843; PHQ-4:Anxiety = 0.786; E-mwTool-3:Depression = 0.843; E-mwTool-3:Anxiety = 0.929. E-mwTool-3 performance was comparable to PHQ-4 among people with and without HIV.

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.

A Multi-Site Study of Mental Disorders in the Mozambican Health Care System.

In Mozambique, human and financial resources for public mental health services are extremely limited. Understanding the mental health needs of those seeking healthcare can inform efficient targeting of mental health services. We examined if the frequency of mental disorders in a health facility varied based on the level of specialization of such facility, from primary care without mental health specialists (PrCMH -), to those with mental health specialists (PrCMH +) and tertiary care (TerC), where both inpatient and outpatient mental health services are available. Participants were adults (convenience sample) seeking health or mental health services at six facilities (2 PrCMH + , 3 PrCMH -, and 1 TerC) in the cities of Maputo and Nampula in Mozambique. Mental disorders were assessed by the MINI International Neuropsychiatric Interview (MINI) 4.0.0. We compared the sociodemographic characteristics and MINI diagnoses across the three types of health facilities. Multiple logistic regression models determined the likelihood that a person seeking services at each type of facility would have any mental disorder, common mental disorders (CMD), severe mental disorders (SMD), substance use disorders (SUD), and moderate-to-high suicide risk, adjusting for sociodemographic factors. Of the 612 total participants, 52.6% (n = 322) were positive for at least one mental disorder: 37.1% were positive for CMD, 28.9% for SMD, 13.2% for SUD, and 10.5% had suicide risk. Presence of any mental disorder was highest in TerC (62.5%) and lowest in PrCMH - (48.4%). Adjusting for sociodemographic covariates, participants in PrCMH + were significantly more likely to have SMD (OR 1.85, 95%CI 1.10-3.11) and SUD (OR 2.79, 95%CI 1.31-5.94) than participants in PrCMH -; participants in TerC were more likely to have CMD (OR 1.70, 95%CI 1.01-2.87) and SUD (OR 2.57, 95%CI 1.14-5.79) than in PrCMH -. Suicide risk was the only condition that did not differ across facility types. As anticipated, people with mental disorders were more likely to be cared for at facilities with mental health specialists. However, our study detected in this convenience sample a remarkably high frequency of mental disorders across different types of facilities within the Mozambican healthcare system. These results, if confirmed in representative samples, suggest a need to increase mental health services at the primary care level.

Data-independent acquisition mass spectrometry in severe rheumatic heart disease (RHD) identifies a proteomic signature showing ongoing inflammation and effectively classifying RHD cases.

BACKGROUND: Rheumatic heart disease (RHD) remains a major source of morbidity and mortality in developing countries. A deeper insight into the pathogenetic mechanisms underlying RHD could provide opportunities for drug repurposing, guide recommendations for secondary penicillin prophylaxis, and/or inform development of near-patient diagnostics. METHODS: We performed quantitative proteomics using Sequential Windowed Acquisition of All Theoretical Fragment Ion Mass Spectrometry (SWATH-MS) to screen protein expression in 215 African patients with severe RHD, and 230 controls. We applied a machine learning (ML) approach to feature selection among the 366 proteins quantifiable in at least 40% of samples, using the Boruta wrapper algorithm. The case-control differences and contribution to Area Under the Receiver Operating Curve (AUC) for each of the 56 proteins identified by the Boruta algorithm were calculated by Logistic Regression adjusted for age, sex and BMI. Biological pathways and functions enriched for proteins were identified using ClueGo pathway analyses. RESULTS: Adiponectin, complement component C7 and fibulin-1, a component of heart valve matrix, were significantly higher in cases when compared with controls. Ficolin-3, a protein with calcium-independent lectin activity that activates the complement pathway, was lower in cases than controls. The top six biomarkers from the Boruta analyses conferred an AUC of 0.90 indicating excellent discriminatory capacity between RHD cases and controls. CONCLUSIONS: These results support the presence of an ongoing inflammatory response in RHD, at a time when severe valve disease has developed, and distant from previous episodes of acute rheumatic fever. This biomarker signature could have potential utility in recognizing different degrees of ongoing inflammation in RHD patients, which may, in turn, be related to prognostic severity.

Persisting burden and challenges of rheumatic heart disease.

Rheumatic heart disease (RHD) is the result of episodes of acute rheumatic fever with valvular (and other cardiac) damage caused by an abnormal immune response to group A streptococcal infections, usually during childhood and adolescence. As a result of improved living conditions and the introduction of penicillin, RHD was almost eradicated in the developed world by the 1980s. However, being a disease of poverty, its burden remains disproportionately high in the developing world, despite being a fundamentally preventable disease. Rheumatic heart disease generates relatively little attention from the medical and science communities, in contrast to other common infectious problems (such as malaria, HIV, tuberculosis), despite the major cardiovascular morbidity/mortality burden imposed by RHD. This relative neglect and paucity of funding have probably contributed to limited fundamental medical advances in this field for over 50 years. Given the importance of prevention before the onset of major valvular damage, the main challenges for RHD prevention are improving social circumstances, early diagnosis, and effective delivery of antibiotic prophylaxis. Early identification through ultrasound of silent, subclinical rheumatic valve lesions could provide an opportunity for early intervention. Simple echocardiographic diagnostic criteria and appropriately trained personnel can be valuable aids in large-scale public health efforts. In addition, a better understanding of the immunogenic determinants of the disease may provide potential routes to vaccine development and other novel therapies.

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.

Assessment of care provision for hypertension at the emergency Department of an Urban Hospital in Mozambique.

BACKGROUND: Management of hypertension in Mozambique is poor, and rates of control are amongst the lowest in the world. Health system related factors contribute at least partially to this situation, particularly in settings where there is scarcity of resources to address the double burden of infectious and non-communicable diseases. This study aimed to assess the management of hypertension in an emergency department (ED). METHODS: During a pragmatic and prospective 30-day snapshot study (with 24 h surveillance) and random profiling of one-in-five presentations to the ED of Hospital Geral de Mavalane, Maputo, we assessed patient's flow and care, as well as health facility's infrastructure and resources through direct observation. Reports from pharmacy and laboratory stocks were used to assess availability of diagnostics and medicines needed for hypertension management. RESULTS: The 1911 hypertensive patients included in the study had several stops during their journey inside the health facility and followed a non-standardized care flow. No clinical protocols or algorithms for risk stratification of hypertension were available. Stock-outs of basic diagnostic tools for risk stratification and medicines were registered. The availability of medicines was 28% on average. CONCLUSIONS: Critical gaps in health facility readiness to address arterial hypertension seen in ED were uncovered, including lack of clinical protocols, insufficient availability of diagnostics and essential medicines, as well as low affordability of the families to guaranty continuum of care. Innovative financing mechanisms are needed to support the health system to address hypertension.

Endomyocardial Fibrosis: an Update After 70 Years.

PURPOSE OF REVIEW: This review aims at highlighting the need to better understand the pathogenesis and natural history of endomyocardial fibrosis when set against its changing endemicity and disease burden, improvements in diagnosis, and new options for clinical management. RECENT FINDINGS: Progress in imaging diagnostic techniques and availability of new targets for drug and surgical treatment of heart failure are contributing to earlier diagnosis and may lead to improvement in patient survival. Endomyocardial fibrosis was first described in Uganda by Davies more than 70 years ago (1948). Despite its poor prognosis, the etiology of this neglected tropical restrictive cardiomyopathy still remains enigmatic nowadays. Our review reflects on the journey of scientific discovery and construction of the current guiding concepts on this mysterious and fascinating condition, bringing to light the contemporary knowledge acquired over these years. Here we describe novel tools for diagnosis, give an overview of the improvement in clinical management, and finally, suggest research themes that can help improve patient outcomes focusing (whenever possible) on novel players coming into action.

Impact of Socioeconomic Status, Ethnicity, and Urbanization on Risk Factor Profiles of Cardiovascular Disease in Africa.

Africa is a continent characterized by marked ethnic, sociodemographic, and economic diversity, with profound changes in many regions over the past 2 decades. This diversity has an impact on cardiovascular disease presentation and outcomes. Within Africa and within the individual countries, one can find regions having predominantly communicable diseases such as rheumatic heart disease, tuberculous pericarditis, or cardiomyopathy and others having a marked increase in noncommunicable disease such as hypertension and hypertensive heart disease. Ischemic heart disease remains rare in most countries. Difficulties in the planning and implementation of effective health care in most African countries are compounded by a paucity of studies and a low rate of investment in research and data acquisition. The fiduciary responsibilities of companies working in Africa should include the effective and efficient use of natural resources to promote the overall health of populations.

Tropical Endomyocardial Fibrosis: Natural History, Challenges, and Perspectives.

Tropical endomyocardial fibrosis (EMF) is a neglected disease of poverty that afflicts rural populations in tropical low-income countries, with some certain high-prevalence areas. Tropical EMF is characterized by the deposition of fibrous tissue in the endomyocardium, leading to restrictive physiology. Since the first descriptions in Uganda in 1948, high-frequency areas for EMF have included Africa, Asia, and South America. Although there is no clear consensus on a unified hypothesis, it seems likely that dietary, environmental, and infectious factors may combine in a susceptible individual to give rise to an inflammatory process leading to endomyocardial damage and scar formation. The natural history of EMF includes an active phase with recurrent flare-ups of inflammation evolving to a chronic phase leading to restrictive heart failure. In the chronic phase, biventricular involvement is the most common presentation, followed by isolated right-sided heart disease. Marked ascites out of proportion to peripheral edema usually develops as a typical feature of EMF. EMF carries a very poor prognosis. In addition to medical management of heart failure, early open heart surgery (endocardectomy and valve repair/replacement) appears to improve outcomes to some extent; however, surgery is technically challenging and not available in most endemic areas. Increased awareness among health workers and policy makers is the need of the hour for the unhindered development of efficient preventive and therapeutic strategies.

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.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.