WHO guideline on the prevention and diagnosis of rheumatic fever and rheumatic heart disease

Background:
Rheumatic heart disease (RHD) is a serious yet preventable public health problem in low- and middle-income countries and in marginalized communities in middle- and high-income countries, including Indigenous populations. RHD is characterized by chronic structural and/or functional changes in the heart, most commonly in the valves, caused by one or more episodes of rheumatic fever (RF). RF is an autoimmune inflammatory reaction to throat infections (pharyngitis) or possibly to superficial skin and skin structure infections (SSSIs) caused by Streptococcus pyogenes, a group A beta-haemolytic Streptococcus (GAS) bacterium. The first episode of RF is commonly seen in children aged 5 to 14 years. Recurrent episodes are most common within 1 year of the first episode but can occur throughout the life course. RHD most commonly starts in childhood with a diagnostic peak in young adults1 aged 20 to 39 years. RHD can lead to death or lifelong disability, however, effective early intervention can prevent premature morbidity and mortality.

RHD affected an estimated 55 million people globally and caused 360,000 deaths in 2021 (1). In the twentieth century, the incidence of RF and the prevalence of RHD declined substantially in Europe and North America, and in other high-income settings. However, the gains have not been equitably distributed globally and many regions including sub-Saharan Africa, the Middle East, Central and South Asia, tropical Latin America and the South Pacific continue to have endemic RF and RHD. The prevalence of RHD is estimated to peak between the ages of 20 and 29 years, declines steadily until around 50 years when it then remains relatively stable (2). There is a higher prevalence of RHD among women across nearly all world regions (2).

The prevention of RF/RHD is essential for addressing the significant health, social and economic burdens of RHD. There are four levels of prevention: 1) reducing GAS infections through improvements in housing, living conditions and sanitation (primordial prevention); 2) treatment of GAS throat infections and possibly GAS skin infections (primary prevention of RF); 3) prevention of recurrence of RF through antibiotic prophylaxis (secondary prevention of RHD onset and progression); and 4) treatment of the complications of RHD with medications including anticoagulants, and cardiac interventions including surgery (tertiary prevention).

Scope and target audience:
In this guideline, the World Health Organization (WHO) provides evidence-informed recommendations for selected topics relating to RF and RHD. It is not intended to encompass all aspects of the prevention, detection and clinical care of the disease in affected populations and subpopulations. Readers are encouraged to identify high-quality, evidence-informed national and local guidance to complement this guideline.

This guideline encompasses the following:

1- primary prevention of RF and RHD, specifically the identification and treatment of suspected GAS pharyngitis and GAS skin infections;
2- secondary prevention of recurrent RF and of RHD, specifically the use of long-term antibiotic prophylaxis, interventions to increase adherence to antibiotic prophylaxis regimes, and screening for early RHD; and
3- management of RF, specifically the treatment of RF with anti-inflammatory drugs.

This guideline is intended for use by a wide range of audiences, including national and local policy-makers and their expert advisers, as well as technical and programme staff at organizations involved in the prevention of RF and RHD, and the identification and care of people with RF or RHD. The guideline may also be used by health workers and their professional societies, and by researchers who are interested in addressing gaps in the evidence.

The audience for this guideline is a global one, across diverse settings with varied perspectives and resources. The content is relevant to all Member States, and in particular countries and regions where populations are at moderate/high risk of RF/RHD.

Methods:
These recommendations are based on the most current, high-quality scientific evidence and were formulated following processes and using methods meeting the highest international standards for guideline development, as outlined in the WHO handbook for guideline development (2nd edition, 2014) (3). The main steps for the development of WHO guidelines include: 1) establishment of the general scope of the guideline and development of the key questions and a detailed workplan; 2) identification of contributors to the guideline process including the Guideline Development Group (GDG; a diverse panel of technical experts and other stakeholders); 3) assessment of declarations of interest and management of any conflicts of interest of all contributors; 4) conduct of systematic reviews of the evidence to address the key questions; 5) assessment of the certainty (quality) of the body of evidence for critical and important outcomes; 6) formulation of recommendations by the GDG; 7) drafting of the guideline document for review and approval by the GDG followed by targeted peer review; 8) review and approval by WHO’s quality assurance body; and 9) publication and dissemination.

Updating:
The WHO Secretariat for this guideline will continue to follow advances in the research on the prevention, diagnosis and management of RF and RHD, particularly for questions for which the certainty (quality) of evidence was found to be low or very low. If new evidence emerges or other important considerations arise that may impact the current recommendations, the WHO Department of Maternal, Newborn, Child and Adolescent Health and Ageing (MCA) in Geneva, Switzerland, will coordinate an update of this guideline.

Unless new evidence necessitates an earlier review, at 5 years from publication of this guideline, the MCA Department, along with its internal partners, will conduct systematic reviews of the relevant evidence and appraise the need for updating or revalidating the current guideline. WHO will seek stakeholder input on the scope of the updated guideline, as new interventions and considerations emerge.

Guiding principles:
RF and RHD are associated with poverty, residential overcrowding, insufficient access to clean water and sanitation, and barriers to accessing primary health care. The GDG therefore formulated the following guiding principles, which underpin all of the recommendations in this guideline, as well as their adoption, adaptation and implementation in Member States:

Programme managers and health workers should work with local authorities and community leaders to ensure adequate living conditions including access to clean water, adequate sanitation and living spaces, housing, and appropriate ventilation in homes and residences.
Policy-makers and programme managers should ensure equitable access to screening and treatment services for people with suspected or confirmed GAS infections and RF/RHD. This applies particularly to vulnerable populations living in areas with moderate/high risk of RF/RHD. All people must have access to high-quality services for the prevention, diagnosis and treatment of RF/RHD, as recommended in this guideline.