Intramuscular versus Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease: Study protocol for a non-inferiority randomized trial (the GOALIE trial).

BACKGROUND: Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low- and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, sub-optimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This non-inferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. METHODS/DESIGN: The Intramuscular versus Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5-17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1004 participants will provide 90% power to demonstrate non-inferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Figure 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. DISCUSSION: The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05693545.

Outcomes of rheumatic fever in Uganda: a prospective cohort study.

BACKGROUND: Rheumatic heart disease is the largest contributor to cardiac-related mortality in children worldwide. Outcomes in endemic settings after its antecedent illness, acute rheumatic fever, are not well understood. We aimed to describe 3-5 year mortality, acute rheumatic fever recurrence, changes in carditis, and correlates of mortality after acute rheumatic fever. METHODS: We conducted a prospective cohort study of Ugandan patients aged 4-23 years who were diagnosed with definite acute rheumatic fever using the modified 2015 Jones criteria from July 1, 2017, to March 31, 2020, enrolled at three rheumatic heart disease registry sites in Uganda (in Mbarara, Mulago, or Lira), and followed up for at least 1 year after diagnosis. Patients with congenital heart disease were excluded. Patients underwent annual review, most recently in August, 2022. We calculated rates of mortality and acute rheumatic fever recurrence, tabulated changes in carditis, performed Kaplan-Meier survival analyses, and used Cox regression models to identify correlates of mortality. FINDINGS: Data were collected between Sept 1 and Sept 30, 2022. Of 182 patients diagnosed with definite acute rheumatic fever, 156 patients were included in the analysis. Of these 156 patients (77 [49%] male and 79 (51%) female; data on ethnicity not collected), 25 (16%) died, 21 (13%) had a cardiac-related death, and 17 (11%) had recurrent acute rheumatic fever over a median of 4·3 (IQR 3·0-4·8) years. 16 (24%) of the 25 deaths occurred within 1 year. Among 131 (84%) of 156 survivors, one had carditis progression by echo. Moderate-to-severe carditis (hazard ratio 12·7 [95% CI 3·9-40·9]) and prolonged PR interval (hazard ratio 4·4 [95% CI 1·7-11·2]) at acute rheumatic fever diagnosis were associated with increased cardiac-related mortality. INTERPRETATION: These are the first contemporary data from sub-Saharan Africa on medium-term acute rheumatic fever outcomes. Mortality rates exceeded those reported elsewhere. Most decedents already had chronic carditis at initial acute rheumatic fever diagnosis, suggesting previous undiagnosed episodes that had already compounded into rheumatic heart disease. Our data highlight the large burden of undetected acute rheumatic fever in these settings and the need for improved awareness of and diagnostics for acute rheumatic fever to allow earlier detection. FUNDING: Strauss Award at Cincinnati Children's Hospital, American Heart Association, and Wellcome Trust.

Silent Acute Rheumatic Fever Unmasked by Using Handheld Echocardiography for Febrile Children Presenting in a Rheumatic Heart Disease-Endemic Area.

OBJECTIVE: To understand the burden of acute rheumatic fever (ARF) among children living in low-income countries who present to the hospital with febrile illness and to determine the role of handheld echocardiography (HHE) in uncovering subclinical carditis as a major manifestation of ARF. STUDY DESIGN: This was a cross-sectional study carried at the Pediatric Hospital in Al Obeid, North Kordofan, Sudan, from September 2022 to January 2023 and including febrile children 3 through 18 years of age with or without clinical features of ARF and without another cause for their fever (not excluding malaria). History, examination, blood investigations, and HHE were done. ARF was diagnosed according to the Jones criteria. Clinical ARF was diagnosed if there was a major clinical Jones criterion and silent ARF if the only major Jones criteria was subclinical carditis. RESULTS: The study cohort included 400 children with a mean age of 9 years. Clinical ARF was diagnosed in 95 patients (95/400, 24%), most of whom presented with a joint major manifestation (88/95, 93%). Among the 281 children who did not present with a clinical manifestation of ARF, HHE revealed rheumatic heart disease (RHD) in 44 patients (44/281, 16%); 31 of them fulfilled criteria for silent ARF (31/281, 11%). HHE increased the detection of ARF by 24%. HHE revealed mild RHD in 41 of 66 (62%) and moderate or severe RHD in 25 of 66 (38%) patients. Both sensitivity and specificity of HHE compared with standard echocardiography were 88%. CONCLUSIONS: There is a significant burden of ARF among febrile children in Sudan. HHE increased the sensitivity of diagnosis, with 11% of children having subclinical carditis as their only major manifestation (ie, silent ARF). RHD-prevention policies need to prioritize decentralization of echocardiography to improve ARF detection.

A Qualitative Study of Patients' Experiences, Enablers and Barriers of Rheumatic Heart Disease Care in Uganda.

Introduction: Rheumatic heart disease (RHD) remains a significant public health problem in countries with limited health resources. People living with RHD face numerous social challenges and have difficulty navigating ill-equipped health systems. This study sought to understand the impact of RHD on PLWRHD and their households and families in Uganda. Methods: In this qualitative study, we conducted in-depth interviews with 36 people living with RHD sampled purposively from Uganda's national RHD research registry, stratifying the sample by geography and severity of disease. Our interview guides and data analysis used a combination of inductive and deductive methods, with the latter informed by the socio-ecological model. We ran thematic content analysis to identify codes that were then collapsed into themes. Coding was done independently by three analysts, who compared their results and iteratively updated the codebook. Results: The inductive portion of our analysis, which focused on the patient experience, revealed a significant impact of RHD on work and school. Participants often lived in fear of the future, faced limited childbirth choices, experienced domestic conflict, and suffered stigmatization and low self-esteem. The deductive portion of our analysis focused on barriers and enablers to care. Major barriers included the high out-of-pocket cost of medicines and travel to health facilities, as well as poor access to RHD diagnostics and medications. Major enablers included family and social support, financial support within the community, and good relationships with health workers, though this varied considerably by location. Conclusion: Despite several personal and community factors that support resilience, PLWRHD in Uganda experience a range of negative physical, emotional, and social consequences from their condition. Greater investment is needed in primary healthcare systems to support decentralized, patient-centered care for RHD. Implementing evidence-based interventions that prevent RHD at district level could greatly reduce the scale of human suffering. There is need to increase investment in primary prevention and tackling social determinants, to reduce the incidence of RHD in communities where the condition remains endemic.

Positive impact of training rural health workers in identification and prevention of acute rheumatic fever in eastern Uganda.

BACKGROUND: Diagnosis of acute rheumatic fever (ARF) is mainly clinical. Delayed or missed diagnosis and failure to administer appropriate and timely treatment of ARF leads to rheumatic heart disease (RHD), which could necessitate expensive treatments such as open-heart surgery. Implementation of preventative guidelines depends on availability of trained healthcare workers. As part of the routine support supervision, the Uganda Heart Institute sent out a team to rural eastern Uganda to evaluate health workers' knowledge level regarding management of ARF. METHODS: Health workers from selected health facilities in Tororo district, eastern Uganda, were assessed for their knowledge on the clinical features and role of benzathine penicillin G (BPG) in the treatment and prevention of ARF recurrence. Using the RHD Action Needs assessment tool, we generated and administered a pre-test, then conducted training and re-administered a post-test. Eight months later, health workers were again assessed for knowledge retention and change in practices. Statistical analysis was done using Stata version 15. RESULTS: During the initial phase, 34 of the 109 (31%) health workers passed the pre-test, indicating familiarity with clinical features of ARF. The level of knowledge of BPG use in ARF was very poor in all the health units [25/109 (22.6%)] but improved after training to 80%, as shown by the chi-squared test ( χ2 = 0.000). However, retention of this knowledge waned after eight months and was not significantly different compared to pre-training (χ2 ≥ 0.2). CONCLUSIONS: A critical knowledge gap is evident among health workers, both in awareness and treatment of ARF, and calls for repetitive training as a priority strategy in prevention.

Cardiovascular diseases in Africa in the twenty-first century: Gaps and priorities going forward.

In 2015, the United Nations set important targets to reduce premature cardiovascular disease (CVD) deaths by 33% by 2030. Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide. There is currently an epidemiological transition on the continent, where NCDs is projected to outpace communicable diseases within the current decade. Unchecked increases in CVD risk factors have contributed to the growing burden of three major CVDs-hypertension, cardiomyopathies, and atherosclerotic diseases- leading to devastating rates of stroke and heart failure. The highest age standardized disability-adjusted life years (DALYs) due to hypertensive heart disease (HHD) were recorded in Africa. The contributory causes of heart failure are changing-whilst HHD and cardiomyopathies still dominate, ischemic heart disease is rapidly becoming a significant contributor, whilst rheumatic heart disease (RHD) has shown a gradual decline. In a continent where health systems are traditionally geared toward addressing communicable diseases, several gaps exist to adequately meet the growing demand imposed by CVDs. Among these, high-quality research to inform interventions, underfunded health systems with high out-of-pocket costs, limited accessibility and affordability of essential medicines, CVD preventive services, and skill shortages. Overall, the African continent progress toward a third reduction in premature mortality come 2030 is lagging behind. More can be done in the arena of effective policy implementation for risk factor reduction and CVD prevention, increasing health financing and focusing on strengthening primary health care services for prevention and treatment of CVDs, whilst ensuring availability and affordability of quality medicines. Further, investing in systematic country data collection and research outputs will improve the accuracy of the burden of disease data and inform policy adoption on interventions. This review summarizes the current CVD burden, important gaps in cardiovascular medicine in Africa, and further highlights priority areas where efforts could be intensified in the next decade with potential to improve the current rate of progress toward achieving a 33% reduction in CVD mortality.

Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system.

OBJECTIVE: To determine the ability to accurately diagnose acute rheumatic fever (ARF) given the resources available at three levels of the Ugandan healthcare system. METHODS: Using data obtained from a large epidemiological database on ARF conducted in three districts of Uganda, we selected variables that might positively or negatively predict rheumatic fever based on diagnostic capacity at three levels/tiers of the Ugandan healthcare system. Variables were put into three statistical models that were built sequentially. Multiple logistic regression was used to estimate ORs and 95% CI of predictors of ARF. Performance of the models was determined using Akaike information criterion, adjusted R2, concordance C statistic, Brier score and adequacy index. RESULTS: A model with clinical predictor variables available at a lower-level health centre (tier 1) predicted ARF with an optimism corrected area under the curve (AUC) (c-statistic) of 0.69. Adding tests available at the district level (tier 2, ECG, complete blood count and malaria testing) increased the AUC to 0.76. A model that additionally included diagnostic tests available at the national referral hospital (tier 3, echocardiography, anti-streptolysin O titres, erythrocyte sedimentation rate/C-reactive protein) had the best performance with an AUC of 0.91. CONCLUSIONS: Reducing the burden of rheumatic heart disease in low and middle-income countries requires overcoming challenges of ARF diagnosis. Ensuring that possible cases can be evaluated using electrocardiography and relatively simple blood tests will improve diagnostic accuracy somewhat, but access to echocardiography and tests to confirm recent streptococcal infection will have the greatest impact.

Community Perspectives on Primary Prevention of Rheumatic Heart Disease in Uganda.

Background: Untreated streptococcal pharyngitis is a precursor to rheumatic heart disease (RHD) and remains a significant public health issue in many countries. Understanding local determinants of treatment-seeking behaviors can help tailor RHD prevention programs. Objective: We sought to elicit perceptions of pharyngitis and related healthcare use in a range of communities in Uganda. Methods: We conducted six focus group discussions (FGD) in three districts that were representative of the country's socioeconomic and cultural heterogenetity. Participants were recruited from six villages (two per district), and FGDs were audio recorded, transcribed and translated into English. Deductive and inductive analysis of the transcripts was done via open axial and sequential coding, which informed development of clusters, themes and subthemes. We extracted quotations from the transcripts to illustrate these themes. Results: We identified nine key themes in three major domains: knowledge and perception of pharyngits, treatment practices, and barriers to uptake of formal public-sector healthcare services. Community awareness and understanding of the consequences of pharyngitis were low. Stated barriers to care were usually systemic in nature and included low overall confidence in the healthcare system and substantial costs associated with transportation and medications. Conclusion: The FGDs identified several approaches to shape community perceptions of pharyngitis and improve utilization of interventions to prevent RHD. In Uganda, information-education-communication interventions probably need to be combined with structural interventions that make formal public-sector healthcare more accessible to at-risk populations.

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.).

Household Economic Consequences of Rheumatic Heart Disease in Uganda.

Background: Rheumatic heart disease (RHD) has declined dramatically in wealthier countries in the past three decades, but it remains endemic in many lower-resourced regions and can have significant costs to households. The objective of this study was to quantify the economic burden of RHD among Ugandans affected by RHD. Methods: This was a cross-sectional cost-of-illness study that randomly sampled 87 participants and their households from the Uganda National RHD registry between December 2018 and February 2020. Using a standardized survey instrument, we asked participants and household members about outpatient and inpatient RHD costs and financial coping mechanisms incurred over the past 12 months. We used descriptive statistics to analyze levels and distributions of costs and the frequency of coping strategies. Multivariate Poisson regression models were used to assess relationships between socioeconomic characteristics and utilization of financial coping mechanisms. Results: Most participants were young or women, demonstrating a wide variation in socioeconomic status. Outpatient and inpatient costs were primarily driven by transportation, medications, and laboratory tests, with overall RHD direct and indirect costs of $78 per person-year. Between 20 and 35 percent of households experienced catastrophic healthcare expenditure, with participants in the Northern and Western Regions 5-10 times more likely to experience such hardship and utilize financial coping mechanisms than counterparts in the Central Region, a wealthier area. Increases in total RHD costs were positively correlated with increasing use of coping behaviors. Conclusion: Ugandan households affected by RHD, particularly in lower-income areas, incur out-of-pocket costs that are very high relative to income, exacerbating the poverty trap. Universal health coverage policy reforms in Uganda should include mechanisms to reduce or eliminate out-of-pocket expenditures for RHD and other chronic diseases.

Incidence of acute rheumatic fever in northern and western Uganda: a prospective, population-based study.

BACKGROUND: Acute rheumatic fever is infrequently diagnosed in sub-Saharan African countries despite the high prevalence of rheumatic heart disease. We aimed to determine the incidence of acute rheumatic fever in northern and western Uganda. METHODS: For our prospective epidemiological study, we established acute rheumatic fever clinics at two regional hospitals in the north (Lira district) and west (Mbarara district) of Uganda and instituted a comprehensive acute rheumatic fever health messaging campaign. Communities and health-care workers were encouraged to refer children aged 3-17 years, with suspected acute rheumatic fever, for a definitive diagnosis using the Jones Criteria. Children were referred if they presented with any of the following: (1) history of fever within the past 48 h in combination with any joint complaint, (2) suspicion of acute rheumatic carditis, or (3) suspicion of chorea. We excluded children with a confirmed alternative diagnosis. We estimated incidence rates among children aged 5-14 years and characterised clinical features of definite and possible acute rheumatic fever cases. FINDINGS: Data were collected between Jan 17, 2018, and Dec 30, 2018, in Lira district and between June 5, 2019, and Feb 28, 2020, in Mbarara district. Of 1075 children referred for evaluation, 410 (38%) met the inclusion criteria; of these, 90 (22%) had definite acute rheumatic fever, 82 (20·0%) had possible acute rheumatic fever, and 24 (6%) had rheumatic heart disease without evidence of acute rheumatic fever. Additionally, 108 (26%) children had confirmed alternative diagnoses and 106 (26%) had an unknown alternative diagnosis. We estimated the incidence of definite acute rheumatic fever among children aged 5-14 years as 25 cases (95% CI 13·7-30·3) per 100 000 person-years in Lira district (north) and 13 cases (7·1-21·0) per 100 000 person-years in Mbarara district (west). INTERPRETATION: To the best of our knowledge, this is the first population-based study to estimate the incidence of acute rheumatic fever in sub-Saharan Africa. Given the known rheumatic heart disease burden, it is likely that only a proportion of children with acute rheumatic fever were diagnosed. These data dispel the long-held hypothesis that the condition does not exist in sub-Saharan Africa and compel investment in improving prevention, recognition, and diagnosis of acute rheumatic fever. FUNDING: American Heart Association Children's Strategically Focused Research Network Grant, THRiVE-2, General Electric, and Cincinnati Children's Heart Institute Research Core.

Establishment of a cardiac telehealth program to support cardiovascular diagnosis and care in a remote, resource-poor setting in Uganda.

INTRODUCTION: To address workforce shortages and expand access to care, we developed a telemedicine program incorporating existing infrastructure for delivery of cardiovascular care in Gulu, Northern Uganda. Our study had three objectives: 1) assess feasibility and clinical impact 2) evaluate patient/parent satisfaction and 3) estimate costs. METHODS: All cardiology clinic visits during a two-year study period were included. All patients received an electrocardiogram and echocardiogram performed by a local nurse in Gulu which were stored and transmitted to the Uganda Heart Institute in the capital of Kampala for remote consultation by a cardiologist. Results were relayed to patients/families following cardiologist interpretation. The following telemedicine process was utilized: 1) clinical intake by nurse in Gulu; 2) ECG and echocardiography acquisition in Gulu; 3) echocardiography transmission to the Uganda Heart Institute in Kampala, Uganda; 4) remote telemedicine consultation by cardiologists in Kampala; and 5) communication of results to patients/families in Gulu. Clinical care and technical aspects were tracked. Diagnoses and recommendations were analyzed by age groups (0-5 years, 6-21 years, 22-50 years and > 50 years). A mixed methods approach involving interviews and surveys was used to assess patient satisfaction. Healthcare sector costs of telemedicine-based cardiovascular care were estimated using time-driven activity-based costing. RESULTS: Normal studies made up 47%, 55%, 76% and 45% of 1,324 patients in the four age groups from youngest to oldest. Valvular heart disease (predominantly rheumatic heart disease) was the most common diagnosis in the older three age groups. Medications were prescribed to 31%, 31%, 24%, and 48% of patients in the four age groups. The median time for consultation was 7 days. A thematic analysis of focus group transcripts displayed an overall acceptance and appreciation for telemedicine, citing cost- and time-saving benefits. The cost of telemedicine was $29.48/visit. CONCLUSIONS: Our data show that transmission and interpretation of echocardiograms from a remote clinic in northern Uganda is feasible, serves a population with a high burden of heart disease, has a significant impact on patient care, is favorably received by patients, and can be delivered at low cost. Further study is needed to better assess the impact relative to existing standards of care and cost effectiveness.

Examining the Ugandan health system's readiness to deliver rheumatic heart disease-related services.

BACKGROUND: In 2018, the World Health Assembly mandated Member States to take action on rheumatic heart disease (RHD), which persists in countries with weak health systems. We conducted an assessment of the current state of RHD-related healthcare in Uganda. METHODOLOGY/PRINCIPAL FINDINGS: This was a mixed-methods, deductive simultaneous design study conducted in four districts of Uganda. Using census sampling, we surveyed health facilities in each district using an RHD survey instrument that was modeled after the WHO SARA tool. We interviewed health workers with experience managing RHD, purposively sampling to ensure a range of qualification and geographic variation. Our final sample included 402 facilities and 36 health workers. We found major gaps in knowledge of clinical guidelines and availability of diagnostic tests. Antibiotics used in RHD prevention were widely available, but cardiovascular medications were scarce. Higher levels of service readiness were found among facilities in the western region (Mbarara district) and private facilities. Level III health centers were the most prepared for delivering secondary prevention. Health worker interviews revealed that limited awareness of RHD at the district level, lack of diagnostic tests and case management registries, and absence of clearly articulated RHD policies and budget prioritization were the main barriers to providing RHD-related healthcare. CONCLUSIONS/SIGNIFICANCE: Uganda's readiness to implement the World Health Assembly RHD Resolution is low. The forthcoming national RHD strategy must focus on decentralizing RHD diagnosis and prevention to the district level, emphasizing specialized training of the primary healthcare workforce and strengthening supply chains of diagnostics and essential medicines.

Active Case Finding for Rheumatic Fever in an Endemic Country.

Background Despite the high burden of rheumatic heart disease in sub-Saharan Africa, diagnosis with acute rheumatic fever (ARF) is exceedingly rare. Here, we report the results of the first prospective epidemiologic survey to diagnose and characterize ARF at the community level in Africa. Methods and Results A cross-sectional study was conducted in Lira, Uganda, to inform the design of a broader epidemiologic survey. Key messages were distributed in the community, and children aged 3 to 17 years were included if they had either (1) fever and joint pain, (2) suspicion of carditis, or (3) suspicion of chorea, with ARF diagnoses made by the 2015 Jones Criteria. Over 6 months, 201 children met criteria for participation, with a median age of 11 years (interquartile range, 6.5) and 103 (51%) female. At final diagnosis, 51 children (25%) had definite ARF, 11 (6%) had possible ARF, 2 (1%) had rheumatic heart disease without evidence of ARF, 78 (39%) had a known alternative diagnosis (10 influenza, 62 malaria, 2 sickle cell crises, 2 typhoid fever, 2 congenital heart disease), and 59 (30%) had an unknown alternative diagnosis. Conclusions ARF persists within rheumatic heart disease-endemic communities in Africa, despite the low rates reported in the literature. Early data collection has enabled refinement of our study design to best capture the incidence of ARF and to answer important questions on community sensitization, healthcare worker and teacher education, and simplified diagnostics for low-resource areas. This study also generated data to support further exploration of the relationship between malaria and ARF diagnosis in rheumatic heart disease/malaria-endemic countries.

Cross-sectional study of population-specific streptococcal antibody titres in Uganda.

OBJECTIVE: Despite substantial variation of streptococcal antibody titres among global populations, there is no data on normal values in sub-Saharan Africa. The objective of this study was to establish normal values for antistreptolysin O (ASO) and antideoxyribonuclease B (ADB) antibodies in Uganda. DESIGN: This was an observational cross-sectional study. SETTING: This study was conducted at Mulago National Referral Hospital, which is located in the capital city, Kampala, and includes the Uganda Heart Institute. PATIENTS: Participants (aged 0-50 years) were recruited. Of 428 participants, 22 were excluded from analysis, and 183 (44.4%) of the remaining were children aged 5-15 years. MAIN OUTCOME MEASURES: ASO was measured in-country by nephelometric technique. ADB samples were sent to Australia (PathWest) for analysis by enzyme inhibition assay: 80% upper limit values were established. RESULTS: The median ASO titre in this age group was 220 IU/mL, with the 80th percentile value of 389 IU/mL. The median ADB titre in this age group was 375 IU/mL, with the 80th percentile value of 568 IU/mL. CONCLUSIONS: The estimated Ugandan paediatric population standardised 80% upper-limit-of-normal ASO and ADB titres is higher than many global populations. Appropriateness of using population-specific antibody cutoffs is yet to be determined and has important implications for the sensitivity and specificity of rheumatic fever diagnosis.

Decreased Prevalence of Rheumatic Heart Disease Confirmed Among HIV-positive Youth.

BACKGROUND: There is geographical overlap between areas endemic for rheumatic heart disease (RHD) and those endemic for HIV. A recent pilot study demonstrated that children living with HIV might be at less risk for RHD development; however, the sample size was too small to make definitive conclusions. Our objective was to determine the prevalence of RHD among HIV-positive children in Uganda. METHODS: We conducted a prospective, cross-sectional study of HIV-positive children (5-15 years of age) receiving care at the Baylor Uganda HIV Clinic, Kampala, Uganda. A focused echocardiogram and chart review was performed. A sample size of 988 children was needed to provide 80% power to detect a difference in population prevalence between HIV-positive children and the general population, 2.97% [95% confidence interval (CI): 2.70-3.24%], based on previous reports. RESULTS: Screening echocardiography of 993 HIV-positive children found 15 individuals (1.5%; 95% CI: 0.88%-2.54%) with RHD. Of these 15, 2 were classified as definite RHD and 13 as borderline RHD. The majority of children had isolated mitral valve disease (93%). Children found to have RHD were older than those without RHD, 12 versus 10 years of age (P = 0.004). When separated based on geographic location, the prevalence of RHD among HIV-positive children from Kampala was 1.28% (95% CI: 0.63%-2.51%) compared with 2.1% (95% CI: 0.89%-4.89%) in those from outside Kampala. CONCLUSIONS: Children living with HIV have a lower prevalence of RHD than the general pediatric population. Further studies are needed to explore this protective association.