Rheumatic fever (RF) and rheumatic heart disease (RHD) are major public health problems among children and young adults in developing countries; though RF/RHD has declined in developed countries. Acute rheumatic fever (ARF) is an illness caused by an immunological reaction to infection with the bacterium group A streptococcus (GAS). RF affects connective tissues, and may result in rheumatic heart disease which may progress to heart failure, atrial fibrillation, and embolic stroke.
RF and RHD are nonsuppurative complications of Group A streptococcal pharyngitis (sore throat) due to a delayed immune response. Group A streptococcal infection is endemic throughout the world, but epidemics are common, particularly among schoolchildren, in residential facilities for the elderly, and in other unique populations such as military personnel. ARF, considered as a classical disease of poverty, commonly appears in children between the ages of 5 and 15 years in developing countries. It occurs 1–3 weeks after an untreated GAS pharyngitis and is an inflammatory disease, with marked tendency to recur.
The consequences of RF and RHD include continuing damage to the heart, increasing disability, repeated hospitalization, and premature death.
World Health Organization (WHO) in 2005 estimated that there are about 15.6 million cases of RHD world-wide. A vast majority of cases are in developing countries. About 2, 82,000 new cases of RHD and over 4, 70,000 new cases of RF occur every year, and 2, 33,000 people die due to RHD each year.
In India population based study indicates prevalence of RHD to be about 2/1000 population, however survey conducted in school children in the age group of 5-16 years by ICMR gives overall prevalence of 6/1000(range 1.8 to 11/1000).
Rheumatic fever is endemic in India and remains one of the major causes of cardiovascular disease, accounting for nearly 25-45% of the acquired heart disease.
The burden of ARF in industrialized countries declined dramatically during the 20th century, due to improved living conditions and increased hygiene standards, along with better access to appropriate health services and increased access to penicillin-based medications. In many developing countries, lack of awareness of these measures, coupled with shortages of money and resources, are important barriers to the control of the disease.
Early treatment of streptococcal sore throat can prevent the development of rheumatic fever. Regular long term penicillin treatment can prevent rheumatic fever becoming rheumatic heart disease, and can halt disease progression in people whose heart valves are already damaged by the disease. RF/RHD is a neglected public health problem in India. If treated, 75% of people with rheumatic fever recover completely. RHD is one of the preventable chronic disorders of heart.
Acute rheumatic fever (ARF) is preceded by sore throat. Sore throats are caused by a variety of bacteria and viruses and commonly affect all age groups; however, important symptoms and signs of Streptococcus sore throat are-
Signs of common cold, conjunctivitis, running nose, hoarseness of voice are not by themselves suggestive of this infection. Special tests such as culture of the throat are needed for laboratory confirmation. If group A Streptococcal pharyngitis is not treated then some children can get affected by Rheumatic fever (RF).
In RF typically, the child may complain of fever, accompanied by following symptoms-
Arthritis- Pain and swelling of joints is the common symptom of the ARF, occurring in up to 75% of patients in the first attack of RF. Larger joints such as knees, ankles, elbows and wrists on both sides of body are usually affected. There is sequential involvement of joints, with each completing a cycle of inflammation and resolution. There is excruciating pain on touch. Symptoms of arthritis pass within four to six weeks without causing any permanent damage.
Carditis (inflammation of heart) occurs in an estimated 30-60% of people with rheumatic fever. Symptoms may be seen in the form of shortness of breath, persistent cough, rapid heartbeat (tachycardia), chest pain, and feeling of tiredness all the time.
Subcutaneous nodules- Round, firm, freely movable, painless nodules varying in size from 0.5–2.0cm are found over bony prominences or extensor tendons.
Rheumatic chorea- About 1 in four children with rheumatic fever can develop involuntary and uncontrolled jerking and twitching of the body, mostly hands and feet, difficulty in performing task requiring fine hand movements such as writing, problem with balance, unusual emotional outbursts, such as crying or laughing for no apparent reason. These symptoms pass within few months.
Skin rash- About one in ten children of rheumatic fever skin rash develops known as erythema marginatum. The rash is painless, non-itchy and subsides usually within few weeks or months.
Less common symptoms of ARF include high temperature, abdominal pain, bleeding nose.
Rheumatic fever is caused by the immune system overreacting to the presence of group A streptococcus bacteria. During infection the immune system fights the infection by producing antibodies to proteins on the surface of the bacteria. In certain strains of group A streptococcal bacteria, the proteins on the bacteria appear similar to proteins in the human cells and the immune system begins to attack human cells with similar proteins such as heart, joints, skin.
RF and RHD are epidemiologically associated with Streptococcus pyogenes pharyngitis. Streptococci are a large group of gram-positive, nonmotile, non–spore-forming cocci about 0.5-1.2 µm in size.
Streptococcus pyogenes causes a wide variety of diseases in humans. It is one of the most common causes of acute bacterial pharyngitis that leads to RF/RHD. Impetigo, a common skin infection, is also caused by S. pyogenes and is associated with acute glomerulonephritis (AGN). In rare cases, S. pyogenes causes invasive diseases such as cellulitis, bacteremia, necrotizing fasciitis, and toxic shock syndrome (TSS).
The risk of an attack of acute rheumatic fever (ARF) following GAS pharyngitis has been reported to be 0.3% under endemic conditions to 3% during epidemic conditions. During the winter and spring seasons in temperate climates, up to 20% of the school-aged children may be GAS carriers. The commonest age group involved is 5-15 years with no sex predisposition.
RF is linked to overcrowding in poor housing conditions (due to increased GAS infection). It declines sharply when the standard of living improves.
There is currently no single test to diagnose acute rheumatic fever (ARF). Diagnosis is based on clinical assessment and the identification of a number of signs and symptoms that are associated with the illness. Signs and symptoms of ARF are divided into two categories: major and minor.
Major signs and symptoms are strongly associated with ARF and include carditis (swelling of the heart), arthritis (pain, redness and swelling of one or more joints), Sydenham’s chorea (strange movements of the body and face), erythema marginatum (painless skin pigmentation), and subcutaneous nodules (small lumps under the skin).
Minor signs and symptoms are used to help support the diagnosis. These include fever, arthralgia (generalised joint aches), blood tests that suggest general illness (elevated ESR), and changes seen on electrocardiogram (Increased P-R interval).
Jones criteria for the diagnosis of rheumatic fever-The Jones criteria were introduced in 1944 as a set of clinical guidelines for the diagnosis of rheumatic fever (RF). According to revised Jones criteria, the diagnosis of RF can be made when two of the major criteria or one major criterion plus two minor criteria, are present along with evidence of Streptococcal infection (Streptococcal serum antibody tests).
Rheumatic heart disease (RHD) is most accurately diagnosed using ultrasound. Ultrasound of the heart is referred to as echocardiography.
Management of Acute rheumatic fever (ARF) is based on treating infection and relieving symptoms. This includes:
Following ARF diagnosis regular secondary prevention in the form of prophylaxis with antibiotic is started to prevent recurrent ARF and heart damage. The regular intramuscular injection of repository penicillin (benzathine benzylpenicillin) is given every three to four weeks interval.
For patients for whom the regular and repeated injections of benzathine benzylpenicillin are not given, daily oral phenoxymethylpenicillin may be used. An oral sulfonamide is recommended for secondary prophylaxis to patients known to be allergic to penicillin. For individuals who cannot take either penicillin or sulfadiazine, erythromycin may be used. The duration of secondary prophylaxis is managed by the physician for each patient individually.
Chronic rheumatic heart disease- The main complication of rheumatic fever is rheumatic heart disease. It's estimated that around one in three people with a history of rheumatic fever will go on to develop rheumatic heart disease. More often valvular lesions as mitral regurgitation, mitral stenosis, aortic regurgitation and aortic stenosis develop as long-lasting heart dysfunction. It can take many years for the symptoms to develop after a previous episode of rheumatic fever. Mild rheumatic heart disease can usually be treated with medication while replacement of the heart valves may be advised in severe cases.
Atrial fibrillation-In some cases, rheumatic heart disease can lead to atrial fibrillation a heart condition that causes an irregular and often abnormally fast heart rate and can lead to increased risk of stroke. Treatment may involve medication to control the heart rate or rhythm, and medication to prevent a stroke.
Heart failure- In more severe cases of RHD, the heart damaged so much that it can’t pump enough blood to the body.
Pregnancy and RHD- RHD is the commonest heart disease associated with pregnancy. It is found in about 1% of pregnant women which leads to significant maternal and fetal morbidity and mortality. RHD is considered as one of the major indirect causes of maternal mortality in developing nations. Physiological changes occurring in the cardiovascular system during pregnancy has a negative impact on the health of pregnant women suffering from RHD.
Prevention and control of diseases caused by S. pyogenes can be achieved by education of parents, teachers and health care providers regarding the source, transmission, clinical course, treatment, and complications of S. pyogenes infections.
Parents can also be educated regarding importance of primordial, primary, secondary and tertiary prevention.
Primordial Prevention- A consolidated effort is necessary to improve the socio-economic condition of the poorer strata in society, particularly to ensure proper housing to reduce overcrowding and malnutrition. Health education programme should generate awareness regarding maintenance of both personal and environmental hygiene and about all the factors that predispose to GAS infection.
Primary Prevention is the treatment of acute streptococcal pharyngitis in order to prevent the initial attack of rheumatic fever. In general, once the diagnosis has been made, antibiotic therapy is indicated, thus preventing initial attack of ARF. The most appropriate antibiotic treatment for prevention of RF and RHD is Benzathine Penicillin G injection. The infection can usually be eradicated by a single intramuscular injection of Benzathine Penicillin G or by ten days treatment with oral penicillin. For patients allergic to penicillin, erythromycin is an acceptable alternative.
Efforts to ensure primary prevention of RF should be focused on education of general community regarding proper treatment for sore throat. Health personnel also need to be trained regarding early diagnosis and effective treatment of streptococcal pharyngitis. However, due to inadequate laboratory resources, diagnosis of GAS is usually not feasible in developing countries. It is difficult to distinguish GAS sore throat from viral sore throats on clinical basis.
Till date, no effective vaccine is currently available against streptococcal diseases though a number of candidate vaccines are in development phase.
Secondary Prevention- According to WHO, for all individuals who have had an initial attack of rheumatic fever, whether or not they have rheumatic heart disease, continuous administration of an antibiotic is mandatory to prevent infection of the upper respiratory tract by group A streptococci. Secondary prevention strategy has shown to reduce recurrences, morbidity and mortality.
WHO recommends the regular intramuscular injection of repository penicillin (benzathine benzylpenicillin) every three to four weeks as a secondary prophylaxis. For patients for whom the regular and repeated injections of benzathine benzylpenicillin are not given, daily oral phenoxymethylpenicillin may be used. An oral sulfonamide is recommended for secondary prophylaxis to patients known to be allergic to penicillin (It is not effective for treating established group A streptococcal infection). For individuals who cannot take either penicillin or sulfadiazine, erythromycin may be used.
Duration of secondary prophylaxis-The duration of secondary prophylaxis depends on the several factors that affect the likelihood of recurrences of rheumatic fever such as the time since the most recent attack, the age of the patient and the risk posed by the environment. The duration of secondary prophylaxis should be adapted to the individual patient but some general principles are-
Tertiary Prevention is directed towards prevention of disability and premature death by surgical or medical management of heart failure and valve surgery, i.e., balloon mitral valvuloplasty or surgical mitral commissurotomy or valve replacement. The high cost of prosthetic valves, inadequate and limited facilities for operative procedures are barriers in provision of valve surgery to RHD patients in developing countries.
Jai Vigyan Mission Mode Project on community control of Rheumatic fever/Rheumatic heart disease in India was conducted by Indian Council of Medical Research (ICMR), New Delhi from 2000-2010.The project report published in 2015 is a guide to experts/institutions involved with prevention and control of disease*.