Samantha M. Colquhoun

Screening for rheumatic heart disease: current approaches and controversies.

Rheumatic heart disease (RHD) is a leading cause of cardiac disease among children in developing nations, and in indigenous populations of some industrialized countries. In endemic areas, RHD has long been a target of screening programmes that, historically, have relied on cardiac auscultation. The evolution of portable echocardiographic equipment has changed the face of screening for RHD over the past 5 years, with greatly improved sensitivity. However, concerns have been raised about the specificity of echocardiography, and the interpretation of minor abnormalities poses new challenges. The natural history of RHD in children with subclinical abnormalities detected by echocardiographic screening remains unknown, and long-term follow-up studies are needed to evaluate the significance of detecting these changes at an early stage. For a disease to be deemed suitable for screening from a public health perspective, it needs to fulfil a number of criteria. RHD meets some, but not all, of these criteria. If screening programmes are to identify additional cases of RHD, parallel improvements in the systems that deliver secondary prophylaxis are essential.

Global, Regional, and National Burden of Rheumatic Heart Disease, 1990-2015.

BACKGROUND Rheumatic heart disease remains an important preventable cause of cardiovascular death and disability, particularly in low‐income and middle‐income countries. We estimated global, regional, and national trends in the prevalence of and mortality due to rheumatic heart disease as part of the 2015 Global Burden of Disease study. METHODS We systematically reviewed data on fatal and nonfatal rheumatic heart disease for the period from 1990 through 2015. Two Global Burden of Disease analytic tools, the Cause of Death Ensemble model and DisMod‐MR 2.1, were used to produce estimates of mortality and prevalence, including estimates of uncertainty. RESULTS We estimated that there were 319,400 (95% uncertainty interval, 297,300 to 337,300) deaths due to rheumatic heart disease in 2015. Global age‐standardized mortality due to rheumatic heart disease decreased by 47.8% (95% uncertainty interval, 44.7 to 50.9) from 1990 to 2015, but large differences were observed across regions. In 2015, the highest age‐standardized mortality due to and prevalence of rheumatic heart disease were observed in Oceania, South Asia, and central sub‐Saharan Africa. We estimated that in 2015 there were 33.4 million (95% uncertainty interval, 29.7 million to 43.1 million) cases of rheumatic heart disease and 10.5 million (95% uncertainty interval, 9.6 million to 11.5 million) disability‐adjusted life‐years due to rheumatic heart disease globally. CONCLUSIONS We estimated the global disease prevalence of and mortality due to rheumatic heart disease over a 25‐year period. The health‐related burden of rheumatic heart disease has declined worldwide, but high rates of disease persist in some of the poorest regions in the world. (Funded by the Bill and Melinda Gates Foundation and the Medtronic Foundation.)

Validation of an Integrated Management of Childhood Illness algorithm for managing common skin conditions in Fiji.

OBJECTIVE To assess the sensitivity of an Integrated Management of Childhood Illness (IMCI) algorithm to detect common skin conditions in children in Fiji. METHODS We collected data from the assessments of children aged between 2 months and 5 years who presented to one of two health clinics. Every child was assessed by a nurse trained in the use of the IMCI algorithm and also an expert paediatrician. We used a kappa statistic to measure agreement between the nurse/algorithm assessment method and the paediatricians diagnosis. FINDINGS High sensitivity for identifying skin problems (sensitivity: 98.7%; 95% confidence interval, CI: 95.5-99.9) was found for the algorithm applied by IMCI-trained nurses, who were able to identify the one child with a severe skin infection and all three children with periorbital cellulitis. Sensitivity was high for the classification of abscess/cellulitis (sensitivity: 95%; 95% CI: 75.1-99.9) and infected scabies (sensitivity: 89.1%; 95% CI: 77.8-95.9), but lower for identification of impetigo, fungal infection and, in particular, non-infected scabies. CONCLUSION The IMCI skin algorithm is a robust tool that should be incorporated into the IMCI after some modifications relating to scabies and impetigo. Its use by primary health-care workers will reduce the burden of skin diseases in children in Fiji through improved case identification and management. The algorithm should be considered in other countries where skin diseases in children are a priority, particularly in the Pacific region.

Safety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy.

Fijian infants aged 6 weeks were stratified by ethnicity and randomized to receive 0, 1, 2, or 3 PCV-7 doses with or without the 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months. Strong booster effects for all 7 PCV-7 serotypes were elicited, and for 4/7 serotypes these responses were highest in the single PCV-7 group. There were fourfold rises in GMC for all non-PCV-7 serotypes. By 17 months the PPV-23 group still had significantly higher GMC (each p<0.001) for all serotypes. The PPV-23 was well tolerated and induced excellent responses for all serotypes which were greatest in the single PCV-7 group.

Echocardiographic screening in a resource poor setting: Borderline rheumatic heart disease could be a normal variant

OBJECTIVE To estimate the echocardiography confirmed prevalence of rheumatic heart disease (RHD) in school children in Fiji. DESIGN Cross-sectional observational study. SETTING Ten primary schools in Fiji. PATIENTS School children aged 5-14 years. INTERVENTIONS Each child had an echocardiogram performed by an echocardiographic technician subsequently read by a paediatric cardiologist not involved with field screening, and auscultation performed by a paediatrician. MAIN OUTCOME MEASURES Echocardiographic criteria for RHD diagnosis were based on those previously published by the National Institutes of Health (NIH) and World Health Organization (WHO), and data were also analyzed using the new World Heart Federation (WHF) criteria. Prevalence figures were calculated with binomial 95% confidence intervals. RESULTS Using the modified NIH/WHO criteria the prevalence of definite RHD prevalence was 7.2 cases per 1000 (95% CI 3.7-12.5), and the prevalence of probable RHD 28.2 cases per 1000 (95% CI 20.8-37.3). By applying the WHF criteria the prevalence of definite and borderline RHD was 8.4 cases per 1000 (95% CI 4.6-14.1) and 10.8 cases per 1000 (95% CI 6.4-17.0) respectively. Definite RHD was more common in females (OR 5.1, 95% CI 1.1-48.3) and in children who attended school in a rural location (OR 2.3, 95% CI 0.6-13.50). Auscultation was poorly sensitive compared to echocardiography (30%). CONCLUSION There is a high burden of undiagnosed RHD in Fiji. Auscultation is poorly sensitive when compared to echocardiography in the detection of asymptomatic RHD. The results of this study highlight the importance of the use of highly sensitive and specific diagnostic criteria for echocardiography diagnosis of RHD.

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.

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.

Underdiagnosis of acute rheumatic fever in primary care settings in a developing country

Objectives  To determine the incidence rate, characterize the clinical features and assess the diagnostic evaluation of children presenting with features of acute rheumatic fever (ARF) at two clinics in a region of Fiji where rheumatic heart disease is known to be endemic.

Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania

The indigenous populations of the South Pacific experience a high burden of rheumatic heart disease (RHD). Here we report a genome-wide association study (GWAS) of RHD susceptibility in 2,852 individuals recruited in eight Oceanian countries. Stratifying by ancestry, we analysed genotyped and imputed variants in Melanesians (607 cases and 1,229 controls) before follow-up of suggestive loci in three further ancestral groups: Polynesians, South Asians and Mixed or other populations (totalling 399 cases and 617 controls). We identify a novel susceptibility signal in the immunoglobulin heavy chain (IGH) locus centring on a haplotype of nonsynonymous variants in the IGHV4-61 gene segment corresponding to the IGHV4-61*02 allele. We show each copy of IGHV4-61*02 is associated with a 1.4-fold increase in the risk of RHD (odds ratio 1.43, 95% confidence intervals 1.27–1.61, P=4.1 × 10−9). These findings provide new insight into the role of germline variation in the IGH locus in disease susceptibility.

Rheumatic Heart Disease-Attributable Mortality at Ages 5–69 Years in Fiji: A Five-Year, National, Population-Based Record-Linkage Cohort Study

Background Rheumatic heart disease (RHD) is considered a major public health problem in developing countries, although scarce data are available to substantiate this. Here we quantify mortality from RHD in Fiji during 2008–2012 in people aged 5–69 years. Methods and Findings Using 1,773,999 records derived from multiple sources of routine clinical and administrative data, we used probabilistic record-linkage to define a cohort of 2,619 persons diagnosed with RHD, observed for all-cause mortality over 11,538 person-years. Using relative survival methods, we estimated there were 378 RHD-attributable deaths, almost half of which occurred before age 40 years. Using census data as the denominator, we calculated there were 9.9 deaths (95% CI 9.8–10.0) and 331 years of life-lost (YLL, 95% CI 330.4–331.5) due to RHD per 100,000 person-years, standardised to the portion of the WHO World Standard Population aged 0–69 years. Valuing life using Fiji’s per-capita gross domestic product, we estimated these deaths cost United States Dollar