Acute rheumatic fever is a major cause of heart disease in large parts of the world, but it remains unknown why only a small fraction of those who are infected with rheumatogenic group A streptococci develop an abnormal immune response that leads to acute rheumatic fever. An understanding of the mechanisms underlying host susceptibility can provide important insights into pathogenesis that in turn can inform new treatments. Extensive searches for susceptibility factors have been undertaken, including human leukocyte antigens, B-cell alloantigens, and cytokine genes. Although significant associations have been found between genetic factors and acute rheumatic fever, study results often conflict with each other. This review explores current understanding about host susceptibility to acute rheumatic fever and provides an overall perspective to the number of studies that have recently addressed this subject.

/pdf/some-of-the-people-some-of-the-time-susceptibility-to-acute-3gkkgws8qz.pdf

Some of the People, Some of the Time Susceptibility to Acute Rheumatic Fever

Summary


Objectives To establish the incidence of post-streptococcal glomerulonephritis (PSGN) and acute rheumatic fever, the prevalence of rheumatic heart disease (RHD), and to estimate morbidity and mortality caused by these diseases globally.



Methods  Systematic literature review and review of World Health Organisation (WHO) vital registration data (VRD).



Results  Incidence and prevalence of rheumatic fever and RHD show very significant global variation. The greatest burden was found in sub-Saharan Africa, the lowest in North America. The highest mortality rates from these two diseases were reported in the indigenous populations of Australia (23.8 per 100 000). Among countries with VRD, the highest mortality was found in Mauritius (4.32 per 100 000). A few studies reported mortality from PSGN and these reported low mortality rates (mean 0.028 per 100 000 in developing countries).



Conclusion  Lack of data from key parts of the world limits our ability to make precise statements of disease burden. Further research and surveillance is required to generate more primary data to inform future estimates.




Objectifs:  Etablir l’incidence de la glomerulonephrite post-streptococcique et du rhumatisme articulaire aigu, la prevalence de la cardiopathie rhumatismale et estimer la morbidite et la mortalite causees globalement par ces maladies.



Methodes:  Revue systematique de la litterature et examen des donnees du registre vital de l’OMS.



Resultats:  L’incidence et la prevalence du rhumatisme articulaire aigu et des cardiopathies rhumatismales montrent une tres importante variation globale. La plus lourde charge est retrouvee en Afrique sub-saharienne et la plus basse en Amerique du Nord. Les taux de mortalite les plus eleves de ces deux maladies ont ete signales dans les populations autochtones d’Australie (23,8 pour 100.000).



Parmi les pays disposant de donnees de registre vital, la mortalite la plus elevee a ete retrouvee en ile Maurice (4,32 pour 100.000). Peu d’etudes ont signale la mortalite due a la glomerulonephrite post-streptococcique et celles-ci ont signale des taux faibles de mortalite (moyenne 0,028 pour 100.000 dans les pays en developpement).



Conclusion:  Le manque de donnees sur les regions cles du monde limite notre capacitea faire des declarations precises sur la charge de la maladie. Des recherches supplementaires et de surveillance sont necessaires pour generer davantage de donnees primaires afin d’informer les estimations futures.





Objetivos:  Establecer la incidencia de la glomerulonefritis postestreptococica y de la fiebre reumatica aguda, la prevalencia de cardiopatias reumaticas, y estimar la morbilidad y mortalidad causada por estas enfermedades a nivel global.



Metodos:  Revision sistematica de la literatura y revision de los datos de registros vitales de la OMS.



Resultados:  La incidencia y prevalencia de la fiebre reumatica y de las cardiopatias reumaticas muestran una variabilidad global muy significativa. La mayor carga se encontro en Africa sub-Sahariana, y la menor en America del Norte. La mayor tasa de mortalidad por estas dos enfermedades se reporto entre las poblaciones indigenas de Australia (23.8 por 100,000). La mortalidad mas alta en paises con datos de registros vitales era la de Mauricio (4.32 por 100,000). Pocos estudios reportaban mortalidad por glomerulonefritis postestreptococica y estos reportaban unas bajas tasas de mortalidad (media 0.028 por 100,000 en paises en vias de desarrollo).



Conclusion:  La falta de datos de algunos lugares clave a nivel mundial limita nuestra habilidad para sacar conclusiones precisas sobre la carga de enfermedad. Se requiere de mas estudios y de vigilancia que generen mas datos primarios con los cuales realizar estimaciones futuras.

/pdf/systematic-review-estimation-of-global-burden-of-non-2lbr9ijijq.pdf

Systematic Review: Estimation of global burden of non-suppurative sequelae of upper respiratory tract infection: rheumatic fever and post-streptococcal glomerulonephritis

IMPORTANCE

Although rheumatic heart disease has been nearly eradicated in high-income countries, 3 in 4 children grow up in parts of the world where it is still endemic.

OBJECTIVES

To determine the prevalence of clinically silent and manifest rheumatic heart disease as a function of age, sex, and socioeconomic status and to estimate age-specific incidence.

DESIGN, SETTING, AND PARTICIPANTS

In this school-based cross-sectional study with cluster sampling, 26 schools in the Sunsari district in Eastern Nepal with 5467 eligible children 5 to 15 years of age were randomly selected from 595 registered schools. After exclusion of 289 children, 5178 children were enrolled in the present study from December 12, 2012, through September 12, 2014. Data analysis was performed from October 1, 2014, to April 15, 2015.

EXPOSURES

Demographic and socioeconomic characteristics were acquired in a standardized interview by means of a questionnaire customized to the age of the children. A focused medical history was followed by a brief physical examination. Cardiac auscultation and transthoracic echocardiography were performed by 2 independent physicians.

MAIN OUTCOMES AND MEASURES

Rheumatic heart disease according to the World Heart Federation criteria.

RESULTS

The median age of the 5178 children enrolled in the study was 10 years (interquartile range, 8-13 years), and 2503 (48.3%) were female. The prevalence of borderline or definite rheumatic heart disease was 10.2 (95% CI, 7.5-13.0) per 1000 children and increased with advancing age from 5.5 (95% CI, 3.5-7.5) per 1000 children 5 years of age to 16.0 (95% CI, 14.9-17.0) in children 15 years of age, whereas the mean incidence remained stable at 1.1 per 1000 children per year. Children with rheumatic heart disease were older than children without rheumatic heart disease (median age [interquartile range], 11 [9-14] years vs 10 [8-13] years; P = .03), more commonly female (34 [64.2%] vs 2469 [48.2%]; P = .02), and more frequently went to governmental schools (40 [75.5%] vs 2792 [54.5%]; P = .002). Silent disease (n = 44) was 5 times more common than manifest disease (n = 9).

CONCLUSIONS AND RELEVANCE

Rheumatic heart disease affects 1 in 100 schoolchildren in Eastern Nepal, is primarily clinically silent, and may be more common among girls. The overall prevalence and the ratio of manifest to subclinical disease increase with advancing age, whereas the incidence remains stable at 1.1 per 1000 children per year. Early detection of silent disease may help prevent progression to severe valvular damage.

/pdf/prevalence-of-subclinical-rheumatic-heart-disease-in-eastern-wbcgqsdprl.pdf

Prevalence of Subclinical Rheumatic Heart Disease in Eastern Nepal: A School-Based Cross-sectional Study

This thesis is submitted to Newcastle University for the degree of Doctor of Philosophy by Published Work. It includes a series of published papers as well as new unpublished work. Chapter 1 provides an introduction to epidemiology, particularly in relation to the description and analysis of malformations and birth defects. Chapter 2 gives a brief introduction to the complex topic of cardiovascular malformations, in particular the problems of definitions and terminology and the importance of diagnostic hierarchy of multiple malformations. Chapter 3 describes the paediatric cardiology database and the preliminary studies which produced the first five published papers. Chapter 4 presents 10 important papers on aspects of the epidemiology of cardiovascular malformations – which together form the main part of this thesis. Chapter 5 presents a systematic review of published studies of the prevalence of congenital cardiovascular malformations which investigates whether there is any evidence of a real difference between populations. It finds wide variation in the reported prevalence at live birth of all congenital cardiovascular malformations (2-30 per 1000 live births) and of individual malformations and concludes that differences are almost certainly explained by various types of ascertainment bias. Specific malformations predicted to show least susceptibility to ascertainment bias show least variation in reported prevalence. The review makes recommendations for consistent methodology for future reports to allow proper comparison between different populations. Chapter 6 looks forward to consider the directions in which research might go in the future, looking in particular at outcome research and its use in performance analysis, and at future investigations into the aetiology of malformations.

The epidemiology of cardiovascular malformations

Microbiological diagnosis of streptococcal pharyngitis: lacunae and their implications

Background: Rheumatic heart disease remains a major public health problem in developing countries with its very high prevalence. Rheumatic and congenital heart disease are significant causes of morbidity and mortality among Nepalese schoolchildren. The aim of our study was to determine the prevalence of rheumatic and congenital heart disease among schoolchildren of the Kathmandu valley in Nepal. Methods and Results: The study included 9420 students, of whom 4466 were male and 4954 were female, with ages ranging from 5 to 18 years. A clinical survey was conducted by the examining team in selected schools, and involved answering standard questionnaires. A total of 83 children were suspected of having heart disease. Out of these 83 children, 23 were confirmed to have heart disease; 11 had rheumatic heart disease, and 12 congenital heart disease, giving a prevalence of 1.2/1000 and 1.3/1000, respectively. The commonest cardiac lesions were mitral regurgitation in the rheumatic heart disease group, and atrial septal defect in the congenital heart disease group. A higher prevalence of congenital heart disease was detected in females. Conclusions: The prevalence of rheumatic heart disease and congenital heart disease among schoolchildren of Kathmandu is 1.2/1000 and 1.3/1000, respectively, with mitral regurgitation and atrial septal defect being the commonest lesions.

Prevalence of rheumatic and congenital heart disease in schoolchildren of Kathmandu valley in Nepal.

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Prevalence of rheumatic and congenital heart disease in schoolchildren of Kathmandu valley in Nepal.