Four-Weekly Benzathine Penicillin G Provides Inadequate Protection against Acute Rheumatic Fever in Some Children.

This study aimed to identify recurrent acute rheumatic fever (ARF) episodes which occurred despite adherence to prophylactic benzathine penicillin G (BPG). Data from Australia's Northern Territory were analyzed; ARF recurrences between 2012 and 2017 diagnosed while the person was prescribed BPG were identified. Days at risk (DAR)-median and interquartile range-preceding ARF onset were calculated. The timing of BPG doses was examined for individuals with no DAR. One hundred sixty-nine ARF recurrences were analyzed; median DAR in the previous 8 weeks before ARF onset was 29. Most recurrences occurred following > 7 DAR (87%). Eight recurrences (5%) occurred despite no DAR; all were aged less than 16 years at the time of their recurrence/s. Recurrent ARF most commonly occurs after delayed BPG doses, but in some cases, receiving every prescribed BPG dose on time did not prevent recurrent ARF. A method to identify high-risk individuals before recurrent ARF is needed.

Improving Delivery of Secondary Prophylaxis for Rheumatic Heart Disease in a High-Burden Setting: Outcome of a Stepped-Wedge, Community, Randomized Trial.

BACKGROUND: Health system strengthening is needed to improve delivery of secondary prophylaxis against rheumatic heart disease. METHODS AND RESULTS: We undertook a stepped-wedge, randomized trial in northern Australia. Five pairs of Indigenous community clinics entered the study at 3-month steps. Study phases comprised a 12 month baseline phase, 3 month transition phase, 12 month intensive phase and a 3- to 12-month maintenance phase. Clinics received a multicomponent intervention supporting activities to improve penicillin delivery, aligned with the chronic care model, with continuous quality-improvement feedback on adherence. The primary outcome was the proportion receiving ≥80% of scheduled penicillin injections. Secondary outcomes included "days at risk" of acute rheumatic fever recurrence related to late penicillin and acute rheumatic fever recurrence rates. Overall, 304 patients requiring prophylaxis were eligible. The proportion receiving ≥80% of scheduled injections during baseline was 141 of 304 (46%)-higher than anticipated. No effect attributable to the study was evident: in the intensive phase, 126 of 304 (41%) received ≥80% of scheduled injections (odds ratio compared with baseline: 0.78; 95% confidence interval, 0.54-1.11). There was modest improvement in the maintenance phase among high-adhering patients (43% received ≥90% of injections versus 30% [baseline] and 28% [intensive], P<0.001). Also, the proportion of days at risk in the whole cohort decreased in the maintenance phase (0.28 versus 0.32 [baseline] and 0.34 [intensive], P=0.001). Acute rheumatic fever recurrence rates did not differ between study sites during the intensive phase and the whole jurisdiction (3.0 versus 3.5 recurrences per 100 patient-years, P=0.65). CONCLUSIONS: This strategy did not improve adherence to rheumatic heart disease secondary prophylaxis within the study time frame. Longer term primary care strengthening strategies are needed. CLINICAL TRIAL REGISTRATION: URL: www.anzctr.org.au. Unique identifier: ACTRN12613000223730.

Qualitative Evaluation of a Complex Intervention to Improve Rheumatic Heart Disease Secondary Prophylaxis.

BACKGROUND: Rheumatic heart disease is a high-burden condition in Australian Aboriginal communities. We evaluated a stepped-wedge, community, randomized trial at 10 Aboriginal communities from 2013 to 2015. A multifaceted intervention was implemented using quality improvement and chronic care model approaches to improve delivery of penicillin prophylaxis for rheumatic heart disease. The trial did not improve penicillin adherence. This mixed-methods evaluation, designed a priori, aimed to determine the association between methodological approaches and outcomes. METHODS AND RESULTS: An evaluation framework was developed to measure the success of project implementation and of the underlying program theory. The program theory posited that penicillin delivery would be improved through activities implemented at clinics that addressed elements of the chronic care model. Qualitative data were derived from interviews with health-center staff, informants, and clients; participant observation; and project officer reports. Quantitative data comprised numbers and types of "action items," which were developed by participating clinic staff with project officers to improve delivery of penicillin injections. Interview data from 121 health-center staff, 22 informants, and 72 clients revealed barriers to achieving the trial's aims, including project-level factors (short trial duration), implementation factors (types of activities implemented), and contextual factors (high staff turnover and the complex sociocultural environment). Insufficient actions were implemented addressing "self-management support" and "community linkage" streams of the chronic care model. Increased momentum was evident in later stages of the study. CONCLUSIONS: The program theory underpinning the study was sound. The limited impact made by the study on adherence was attributable to complex implementation challenges.

Long-Term Outcomes From Acute Rheumatic Fever and Rheumatic Heart Disease: A Data-Linkage and Survival Analysis Approach.

BACKGROUND: We investigated adverse outcomes for people with acute rheumatic fever (ARF) and rheumatic heart disease (RHD) and the effect of comorbidities and demographic factors on these outcomes. METHODS: Using linked data (RHD register, hospital, and mortality data) for residents of the Northern Territory of Australia, we calculated ARF recurrence rates, rates of progression from ARF to RHD to severe RHD, RHD complication rates (heart failure, endocarditis, stroke, and atrial fibrillation), and mortality rates for 572 individuals diagnosed with ARF and 1248 with RHD in 1997 to 2013 (94.9% Indigenous). RESULTS: ARF recurrence was highest (incidence, 3.7 per 100 person-years) in the first year after the initial ARF episode, but low-level risk persisted for >10 years. Progression to RHD was also highest (incidence, 35.9) in the first year, almost 10 times higher than ARF recurrence. The median age at RHD diagnosis in Indigenous people was young, especially among males (17 years). The development of complications was highest in the first year after RHD diagnosis: heart failure incidence rate per 100 person-years, 9.09; atrial fibrillation, 4.70; endocarditis, 1.00; and stroke, 0.58. Mortality was higher among Indigenous than non-Indigenous RHD patients (hazard ratio, 6.55; 95% confidence interval, 2.45-17.51), of which 28% was explained by comorbid renal failure and hazardous alcohol use. RHD complications and mortality rates were higher for urban than for remote residents. CONCLUSIONS: This study provides important new prognostic information for ARF/RHD. The residual Indigenous survival disparity in RHD patients, which persisted after accounting for comorbidities, suggests that other factors contribute to mortality, warranting further research.

Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial.

BACKGROUND: Rheumatic heart disease (RHD), caused by acute rheumatic fever (ARF), is a major health problem in Australian Aboriginal communities. Progress in controlling RHD requires improvements in the delivery of secondary prophylaxis, which comprises regular, long-term injections of penicillin for people with ARF/RHD. METHODS/DESIGN: This trial aims to improve uptake of secondary prophylaxis among Aboriginal people with ARF/RHD to reduce progression or worsening of RHD. This is a stepped-wedge, randomised trial in consenting communities in Australia's Northern Territory. Pairs of randomly-chosen clinics from among those consenting enter the study at 3-monthly steps. The intervention to which clinics are randomised comprises a multi-faceted systems-based package, in which clinics are supported to develop and implement strategies to improve penicillin delivery, aligned with elements of the Chronic Care Model. Continuous quality improvement processes will be used, including 3-monthly feedback to clinic staff of adherence rates of their ARF/RHD clients. The primary outcome is the proportion of people with ARF/RHD receiving ≥ 80% of scheduled penicillin injections over a minimum 12-month period. The sample size of 300 ARF/RHD clients across five community clusters will power the study to detect a 20% increase in the proportion of individuals achieving this target, from a worrying low baseline of 20%, to 40 %. Secondary outcomes pertaining to other measures of adherence will be assessed. Within the randomised trial design, a mixed-methods evaluation will be embedded to evaluate the efficiency, effectiveness, impact and relevance, sustainability, process and fidelity, and performance of the intervention. The evaluation will establish any causal link between outcomes and the intervention. The planned study duration is from 2013 to 2016. DISCUSSION: Continuous quality improvement has a strong track record in Australia's Northern Territory, and its use has resulted in modest benefits in a pilot, non-randomised ARF/RHD study. If successful, this new intervention using the Chronic Care Model as a scaffold and evaluated using a well-developed theory-based framework, will provide a practical and transferable approach to ARF/RHD control. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613000223730. Date registered: 25 February 2013.

Controlling acute rheumatic fever and rheumatic heart disease in developing countries: are we getting closer?

PURPOSE OF REVIEW: To describe new developments (2013-2014) in acute rheumatic fever (ARF) and rheumatic heart disease (RHD) relevant to developing countries. RECENT FINDINGS: Improved opportunities for the primary prevention of ARF now exist, because of point-of-care antigen tests for Streptococcus pyogenes, and clinical decision rules which inform management of pharyngitis without requiring culture results. There is optimism that a vaccine, providing protection against many ARF-causing S. pyogenes strains, may be available in coming years. Collaborative approaches to RHD control, including World Heart Federation initiatives and the development of registers, offer promise for better control of this disease. New data on RHD-associated costs provide persuasive arguments for better government-level investment in primary and secondary prevention. There is expanding knowledge of potential biomarkers and immunological profiles which characterize ARF/RHD, and genetic mutations conferring ARF/RHD risk, but as yet no new diagnostic testing strategy is ready for clinical application. SUMMARY: Reduction in the disease burden and national costs of ARF and RHD are major priorities. New initiatives in the primary and secondary prevention of ARF/RHD, novel developments in pathogenesis and biomarker research and steady progress in vaccine development, are all causes for optimism for improving control of ARF/RHD, which affect the poorest of the poor.