"Hurts less, lasts longer"; a qualitative study on experiences of young people receiving high-dose subcutaneous injections of benzathine penicillin G to prevent rheumatic heart disease in New Zealand.

BACKGROUND: Four-weekly intramuscular (IM) benzathine penicillin G (BPG) injections to prevent acute rheumatic fever (ARF) progression have remained unchanged since 1955. A Phase-I trial in healthy volunteers demonstrated the safety and tolerability of high-dose subcutaneous infusions of BPG which resulted in a much longer effective penicillin exposure, and fewer injections. Here we describe the experiences of young people living with ARF participating in a Phase-II trial of SubCutaneous Injections of BPG (SCIP). METHODOLOGY: Participants (n = 20) attended a clinic in Wellington, New Zealand (NZ). After a physical examination, participants received 2% lignocaine followed by 13.8mL to 20.7mL of BPG (Bicillin-LA®; determined by weight), into the abdominal subcutaneous tissue. A Kaupapa Maori consistent methodology was used to explore experiences of SCIP, through semi-structured interviews and observations taken during/after the injection, and on days 28 and 70. All interviews were recorded, transcribed verbatim, and thematically analysed. PRINCIPAL FINDINGS: Low levels of pain were reported on needle insertion, during and following the injection. Some participants experienced discomfort and bruising on days one and two post dose; however, the pain was reported to be less severe than their usual IM BPG. Participants were 'relieved' to only need injections quarterly and the majority (95%) reported a preference for SCIP over IM BPG. CONCLUSIONS: Participants preferred SCIP over their usual regimen, reporting less pain and a preference for the longer time gap between treatments. Recommending SCIP as standard of care for most patients needing long-term prophylaxis has the potential to transform secondary prophylaxis of ARF/RHD in NZ and globally.

The American Heart Association's Call to Action for Reducing the Global Burden of Rheumatic Heart Disease: A Policy Statement From the American Heart Association.

Rheumatic heart disease (RHD) affects ≈40 million people and claims nearly 300 000 lives each year. The historic passing of a World Health Assembly resolution on RHD in 2018 now mandates a coordinated global response. The American Heart Association is committed to serving as a global champion and leader in RHD care and prevention. Here, we pledge support in 5 key areas: (1) professional healthcare worker education and training, (2) technical support for the implementation of evidence-based strategies for rheumatic fever/RHD prevention, (3) access to essential medications and technologies, (4) research, and (5) advocacy to increase global awareness, resources, and capacity for RHD control. In bolstering the efforts of the American Heart Association to combat RHD, we hope to inspire others to collaborate, communicate, and contribute.

Subcutaneous administration of benzathine benzylpenicillin G has favourable pharmacokinetic characteristics for the prevention of rheumatic heart disease compared with intramuscular injection: a randomized, crossover, population pharmacokinetic study in healthy adult volunteers.

BACKGROUND: Benzathine penicillin G has been used as monthly deep intramuscular (IM) injections since the 1950s for secondary prevention of acute rheumatic fever and rheumatic heart disease (RHD). Injection frequency and pain are major programmatic barriers for adherence, prompting calls for development of better long-acting penicillin preparations to prevent RHD. We hypothesized that subcutaneous (SC) administration of benzathine penicillin G could delay penicillin absorption when compared with IM injections. METHODS: To compare the pharmacokinetic profile and tolerability of benzathine penicillin G according to different routes of administration, 15 healthy males participated in a randomized crossover study to receive benzathine penicillin G by either SC or IM routes, with a 10 week washout period before the second dose by the alternative route. Ultrasound guidance confirmed injection location. Penicillin concentrations and pain scores were measured for 6 weeks following injections. RESULTS: SC administration was well tolerated with no significant differences in pain scores. Following SC injection, the principal absorption half-life (95% CI) was 20.1 (16.3-29.5) days and 89.6% (87.1%-92.0%) of the drug was directed via this pathway compared with 10.2 (8.6-12.5) days and 71.3% (64.9%-77.4%) following IM administration. Lower peak and higher trough penicillin concentrations resulted following SC injection. Simulations demonstrated that SC infusion of higher doses of benzathine penicillin G could provide therapeutic penicillin concentrations for 3 months. CONCLUSIONS: SC administration of benzathine penicillin G is safe and significantly delays penicillin absorption. High-dose benzathine penicillin G via the SC route would fulfil many product characteristics required for the next generation of longer-acting penicillins for use in RHD.

Neurodevelopmental outcomes for high-risk neonates in a low-resource setting.

Worldwide, most neonates who survive prematurity and serious illness reside in low-resource settings where developmental outcome data and follow-up care are limited. This study aimed to assess in Fiji, a low-resource Pacific setting, prevalence and risk factors for moderate to severe neurodevelopmental impairment (NDI) in early childhood among high-risk neonates compared with controls. Retrospective cohort study comparing long-term outcomes for high-risk neonatal intensive care unit patients (n=149) compared with matched term, normal birth weight neonates (n=147) discharged from Colonial War Memorial Hospital between November 2008 and April 2010. NDI was defined as one or more of cerebral palsy, moderate to severe hearing or visual impairment, or global developmental delay using Bayley Scales of Infant and Toddler Development Third Edition (ie, score <70 in ≥1 of cognitive, language or motor domains). At median (IQR) age 36.1 (28.3, 38.0) months, prevalence of moderate to severe NDI % (95% CI, n) in high-risk and control groups was 12 (5 to 17, n=13) and 5 (2 to 12, n=5), respectively, an increased risk ratio (95% CI) of 2.7 (0.8 to 8.9). Median gestational age (weeks (median, IQR)) in the high-risk group was 37.5 (34-40) weeks. Among high-risk neonates, gestational age, birth weight, asphyxia, meningitis and/or respiratory distress were significantly associated with risk of NDI. Prevalence of NDI was high among this predominantly term high-risk neonatal cohort compared with controls. Results, including identified risk factors, inform efforts to strengthen quality of care and models of follow-up for high-risk neonates in this low-resource setting.

Secondary prevention for screening detected rheumatic heart disease: opportunities to improve adherence.

Background: Secondary prevention is an effective treatment for rheumatic heart disease (RHD), but ensuring high adherence to prophylaxis over many years is challenging and requires understanding of local factors. Methods: Participants were young people diagnosed with RHD through echocardiographic screening in Fiji. We used a structured interview to evaluate the following: health seeking behaviours; attitudes, practice, barriers and potential improvement strategies for adherence to antibiotic prophylaxis; and adolescent-friendly qualities of the health service. Results: One hundred and one participants were interviewed (median age, 17.2 years). Adherence was very low overall (adequate in 6%). Sore throat and fever with sore joints were experienced in the preceding year by 42% and 28%, respectively. Barriers to receiving treatment included taking alternate treatments and the perception that symptoms were benign and self-limiting. Reasons for missing prophylaxis injections included lack of awareness, feeling well, transport cost and access, and medication unavailability (>40% of participants each). The injection health service had many perceived strengths, but inclusion of adolescents in decision making, and quality of educational materials were deficiencies. Reminder strategies, particularly phone-based reminders, were considered helpful by 94%. Conclusions: We identified several factors influencing secondary prevention that may be used to develop interventions to improve adherence.

Clinical outcomes for young people with screening-detected and clinically-diagnosed rheumatic heart disease in Fiji.

BACKGROUND: Echocardiographic screening is under consideration as a disease control strategy for rheumatic heart disease (RHD). However, clinical outcomes of young people with screening-detected RHD are unknown. We aimed to describe the outcomes for a cohort with screening-detected RHD, in comparison to patients with clinically-diagnosed RHD. METHODS: A retrospective cohort study included all young people with screening-detected RHD in the Central Division of Fiji in the primary cohort. Screen-negative and clinically-diagnosed comparison groups were matched 1:1 to the primary cohort. Data were collected on mortality, clinical complications and healthcare utilisation from the electronic and paper health records and existing databases. RESULTS: Seventy participants were included in each group. Demographic characteristics of the groups were similar (median age 11years, 69% female, median follow-up 7years). There were nine (12.9%) RHD-related deaths in the clinically-diagnosed group and one (1.4%) in the screening-detected group (Incident Rate Ratio: 9.6, 95% CI 1.3-420.6). Complications of RHD were observed in 39 (55.7%) clinically-diagnosed cases, four (20%) screening-detected cases and one (1.4%) screen-negative case. There were significant differences in the cumulative complication curves of the groups (p<0.001). Rates of admission and surgery were highest in the clinically-diagnosed group, and higher in the screening-detected than screen-negative group. CONCLUSIONS: Young people with screening-detected RHD have worse health outcomes than screen-negative cases in Fiji. The prognosis of clinically-diagnosed RHD remains poor, with very high mortality and complication rates. Further studies in other settings will inform RHD screening policy. Comprehensive control strategies are required for disease prevention.

Screening-detected rheumatic heart disease can progress to severe disease.

OBJECTIVES: Echocardiography is a sensitive test for rheumatic heart disease (RHD) screening; however the natural history of RHD detected on screening has not been established. We aimed to evaluate the progression of screening-detected RHD in Fiji. METHODS: All young people previously diagnosed with RHD through screening, with echocardiograms available for review, were eligible. All baseline echocardiograms were reported again. Participants underwent follow-up echocardiography. A paediatric cardiologist determined the diagnosis using the World Heart Federation criteria and assessed the severity of regurgitation and stenosis. RESULTS: Ninety-eight participants were recruited (mean age, 17 years; median duration of follow-up, 7.5 years). Two other children had died from severe RHD. Fourteen of 20 (70%) definite RHD cases persisted or progressed, including four (20%) requiring valve surgery. Four (20%) definite RHD cases improved to borderline RHD and two (10%) to normal. Four of 17 (24%) borderline cases progressed to definite RHD (moderate: 2; severe: 2) and two (12%) improved to normal. Four of the 55 cases reclassified as normal at baseline progressed to borderline RHD. Cases with a follow-up interval >5 years were more likely to improve (37% vs 6%, p=0.03). CONCLUSIONS: The natural history of screening-detected RHD is not benign. Most definite RHD cases persist and others may require surgery or succumb. Progression of borderline cases to severe RHD demonstrates the need for monitoring and individualised consideration of prophylaxis. Robust health system structures are needed for follow-up and delivery of secondary prophylaxis if RHD screening is to be scaled up.

Adherence to secondary antibiotic prophylaxis for patients with rheumatic heart disease diagnosed through screening in Fiji.

OBJECTIVES: Echocardiographic screening for rheumatic heart disease (RHD) can detect subclinical cases; however, adequate adherence to secondary antibiotic prophylaxis (SAP) is required to alter disease outcomes. We aimed to investigate the adherence to SAP among young people with RHD diagnosed through echocardiographic screening in Fiji and to investigate factors associated with adherence. METHODS: Patients diagnosed with RHD through echocardiographic screening in Fiji from 2006 to 2014 were included. Dates of benzathine penicillin G injections were collected from 76 health clinics nationally from December 2011 to December 2014. Adherence was measured using the proportion of days covered (PDC). Multivariate logistic regression analysis was used to identify characteristics associated with any adherence (≥1 injection received) and adequate adherence (PDC ≥0.80). RESULTS: Of 494 patients, 268 (54%) were female and the median age was 14 years. Overall, 203 (41%) had no injections recorded and just 33 (7%) had adequate adherence. Multivariate logistic regression showed increasing age (OR 0.93 per year, 95% CI 0.87-0.99) and time since diagnosis ≥1.5 years (OR 0.53, 95% CI 0.37-0.79) to be inversely associated with any adherence. Non-iTaukei ethnicity (OR 2.58, 95%CI 1.04-6.33) and urban residence (OR 3.36, 95% CI 1.54-7.36) were associated with adequate adherence, whereas time since diagnosis ≥1.5 years (OR 0.38, 95%CI 0.17-0.83) was inversely associated with adequate adherence. CONCLUSIONS: Adherence to SAP after screening in Fiji is currently inadequate for individual patient protection or population disease control. Secondary prevention should be strengthened before further screening can be justified.

Focused cardiac ultrasound screening for rheumatic heart disease by briefly trained health workers: a study of diagnostic accuracy.

BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) can identify individuals with subclinical disease who could benefit from antibiotic prophylaxis. However, most settings have inadequate resources to implement conventional echocardiography and require a feasible, accurate screening method. We aimed to investigate the accuracy of screening by non-expert operators using focused cardiac ultrasound (FoCUS). METHODS: In this prospective study of diagnostic accuracy, we recruited schoolchildren aged 5 to 15 years in Fiji to undergo two blinded tests. The index test was a FoCUS assessment of mitral and aortic regurgitation, performed by nurses after an 8-week training programme. The reference standard was the diagnosis of RHD by a paediatric cardiologist, based on a standard echocardiogram performed by a skilled echocardiographer. The primary outcome was the accuracy of the index test with use of the most sensitive criteria (any regurgitation). FINDINGS: We included 2004 children in the study. The index tests were done between September, 2012, and September, 2013, by seven nurses in eight schools in Fiji. The diagnostic accuracy of the screening test (area under receiver operator characteristic curve) was 0·89 (95% CI 0·83-0·94). When the primary cut-off point (any regurgitation) was used for analysis, sensitivity was 84·2% (72·1-92·5) and specificity was 85·6% (83·9-87·1). The sensitivity of individual nurses ranged from 66·7% to 100% and specificity 74·0% to 93·7%. INTERPRETATION: Screening by briefly trained nurses using FoCUS was accurate for the diagnosis of RHD. Refinements to training and screening test methods should be studied in a range of settings, and in parallel with investigations of the long-term clinical and cost-effectiveness of screening for RHD. FUNDING: Cure Kids, New Zealand; the Fiji Water Foundation provided funding for portable ultrasound equipment; see acknowledgments for further details of funders.

Screening for rheumatic heart disease: quality and agreement of focused cardiac ultrasound by briefly trained health workers.

BACKGROUND: Echocardiographic screening for rheumatic heart disease (RHD) has the potential to detect subclinical cases for secondary prevention, but is constrained by inadequate human resources in most settings. Training non-expert health workers to perform focused cardiac ultrasound (FoCUS) may enable screening at a population-level. We aimed to evaluate the quality and agreement of FoCUS for valvular regurgitation by briefly trained health workers. METHODS: Seven nurses participated in an eight week training program in Fiji. Nurses performed FoCUS on 2018 children aged five to 15 years, and assessed any valvular regurgitation. An experienced pediatric cardiologist assessed the quality of ultrasound images and measured any recorded regurgitation. The assessment of the presence of regurgitation and measurement of the longest jet by the nurse and cardiologist was compared, using the Bland-Altman method. RESULTS: The quality of FoCUS overall was adequate for diagnosis in 96.6%. There was substantial agreement between the cardiologist and the nurses overall on the presence of mitral regurgitation (κ = 0.75) and aortic regurgitation (κ = 0.61) seen in two views. Measurements of mitral regurgitation by nurses and the cardiologist were similar (mean bias 0.01 cm; 95% limits of agreement -0.64 to 0.66 cm). CONCLUSIONS: After brief training, health workers with no prior experience in echocardiography can obtain adequate quality images and make a reliable assessment on the presence and extent of valvular regurgitation. Further evaluation of the imaging performance and accuracy of screening by non-expert operators is warranted, as a potential population-level screening strategy in high prevalence settings.

Teaching focused echocardiography for rheumatic heart disease screening.

Screening for rheumatic heart disease (RHD) requires workers skilled in echocardiography, which typically involves prolonged, specialized training. Task shifting echocardiographic screening to nonexpert health workers may be a solution in settings with limited human resources. An 8-week training program was designed to train health workers without any prior experience in focused echocardiography for RHD screening. Seven health workers participated. At the completion of training, the health workers performed unsupervised echocardiography on 16 volunteer children with known RHD status. A pediatric cardiologist assessed image quality. Participants provided qualitative feedback. The quality of echocardiograms were high at completion of training (55 of 56 were adequate for diagnosis) and all cases of RHD were identified. Feedback was strongly positive. Training health workers to perform focused echocardiography for RHD screening is feasible. After systematic testing for accuracy, this training program could be adapted in other settings seeking to expand echocardiographic capabilities.

Closing the gaps in child health in the Pacific: an achievable goal in the next 20 years.

It is not inconceivable that by 2035 the substantial gaps in child health across the Pacific can close significantly. Currently, Australia and New Zealand have child mortality rates of 5 and 6 per 1000 live births, respectively, while Pacific island developing nations have under 5 mortality rates ranging from 13 to 16 (Vanuatu, Fiji and Tonga) to 47 and 58 per 1000 live births (Kiribati and Papua New Guinea, respectively). However, these Pacific child mortality rates are falling, by an average of 1.4% per year since 1990, and more rapidly (1.9% per year) since 2000. Based on progress elsewhere, there is a need to (i) define the specific things needed to close the gaps in child health; (ii) be far more ambitious and hopeful than ever before; and (iii) form a new regional compact based on solidarity and interdependence.

Pilot study of nurse-led rheumatic heart disease echocardiography screening in Fiji--a novel approach in a resource-poor setting.

We designed a pilot study of a training module for nurses to perform rheumatic heart disease echocardiography screening in a resource-poor setting. The aim was to determine whether nurses given brief, focused, basic training in echocardiography could follow an algorithm to potentially identify cases of rheumatic heart disease requiring clinical referral, by undertaking basic two-dimensional and colour Doppler scans. Training consisted of a week-long workshop, followed by 2 weeks of supervised field experience. The nurses' skills were tested on a blinded cohort of 50 children, and the results were compared for sensitivity and specificity against echocardiography undertaken by an expert, using standardised echocardiography definitions for definite and probable rheumatic heart disease. Analysis of the two nurses' results revealed that when a mitral regurgitant jet length of 1.5 cm was used as the trigger for rheumatic heart disease identification, they had a sensitivity of 100% and 83%, respectively, and a specificity of 67.4% and 79%, respectively. This pilot supports the principle that nurses, given brief focused training and supervised field experience, can follow an algorithm to undertake rheumatic heart disease echocardiography in a developing country setting to facilitate clinical referral with reasonable accuracy. These results warrant further research, with a view to developing a module to guide rheumatic heart disease echocardiographic screening by nurses within the existing public health infrastructure in high-prevalence, resource-poor regions.

Rheumatic heart disease and its control in the Pacific.

Rheumatic fever and rheumatic heart disease continue to be a huge public-health burden on many Pacific Island countries. Prevalence reported in some nations are some of the highest seen globally, yet many countries in the region do not have national disease registers. Despite the will of many Pacific Island countries, there are a number of barriers to the implementation and sustainability of effective coordinated prevention programs, including limited funding and competing health priorities. In promising recent developments, a number of countries in the region have been able to develop or strengthen national rheumatic heart disease registers. These registers allow for more effective delivery of secondary prophylaxis, the mainstay of disease control in the Pacific. Primary prevention of rheumatic fever and screening for rheumatic heart disease are important adjunctive strategies. Recent advances in screening methods, focusing on portable echocardiography, may allow for the early detection of rheumatic heart disease in the community.