Streptococcus Pyogenes and Acute Rheumatic Fever: How Strong are the Links in the Chain?
By: Scott H. Wirth, Andrea Z. Beaton and Andrew Steer
References
- Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2021 (GBD 2021) [Internet]. Seattle, Washington: Institute of Health Metrics and Evaluation (IHME); 2022. Available from:
https://vizhub.healthdata.org/gbd-results/ - Naseeb K, Khan MN, Aslam Soomro N, Hameed A, Chand G, Ram J, et al. Temporal trends and burden of rheumatic heart disease in South Asia: A comprehensive analysis of three decades from Global Burden of Disease Study. Global Heart. 2024;19(1):
53 . DOI: 10.5334/gh.1336 - Carapetis JR, Beaton A, Cunningham MW, Guilherme L, Karthikeyan G, Mayosi BM, et al. Acute rheumatic fever and rheumatic heart disease. Nature Reviews Disease Primers. 2016;2:
15084 . DOI: 10.1038/nrdp.2015.84 - Watkins D, Daskalakis A. The economic impact of rheumatic heart disease in developing countries. The Lancet Global Health. 2015;3(Special issue):
S37 . DOI: 10.1016/S2214-109X(15)70156-7 - Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 Study. Journal of the American College of Cardiology. 2020;76(25):2982–3021. DOI: 10.1016/j.jacc.2020.11.010
- Robertson KA, Mayosi BM. Rheumatic heart disease: Social and economic dimensions. South African Medical Journal. 2008;98(10):780–781.
- Zühlke LJ, Karthikeyan G. Primary prevention for rheumatic Fever: Progress, obstacles, and opportunities. Global Heart. 2013;8(3):221–226. DOI: 10.1016/j.gheart.2013.08.005
- Ndagire E, Ollberding N, Sarnacki R, Meghna M, Pulle J, Atala J, et al. Modelling study of the ability to diagnose acute rheumatic fever at different levels of the Ugandan healthcare system. BMJ Open. 2022;12(3):
e050478 . DOI: 10.1136/bmjopen-2021-050478 - Longenecker CT, Morris SR, Aliku TO, Beaton A, Costa MA, Kamya MR, et al. Rheumatic heart disease treatment cascade in Uganda. Circulation. Cardiovascular Quality and Outcomes. 2017;10(11):
e004037 . DOI: 10.1161/CIRCOUTCOMES.117.004037 - Opara CC, Du Y, Kawakatsu Y, Atala J, Beaton AZ, Kansiime R, et al. Household economic consequences of rheumatic heart disease in Uganda. Frontiers in Cardiovascular Medicine. 2021;8:
636280 . DOI: 10.3389/fcvm.2021.636280 - Walkinshaw DR, Wright MEE, Mullin AE, Excler JL, Kim JH, Steer AC. The Streptococcus pyogenes vaccine landscape. NPJ Vaccines. 2023;8(1):
16 . DOI: 10.1038/s41541-023-00609-x - Massell BF. Rheumatic fever and streptococcal infection: Unraveling the mysteries of a dread disease. Boston: Harvard University Press; 1997.
- Markowitz M, Kuttner A. Rheumatic fever: Diagnosis, management, and prevention. Philadelphia: W.B. Saunders Company; 1965.
- Taranta A, Markowitz M. Rheumatic fever: A guide to its recognition, prevention, and cure with special reference to developing countries. Boston: MTP Press Limited; 1981. DOI: 10.1007/978-94-015-7171-5
- Howick J, Chalmers I, Glasziou P, Greenhalgh T, Heneghan C, Liberati A, et al. OCEBM Levels of Evidence (Introductory Document) [Internet]. Oxford Centre For Evidence-Based Medicine. Available from:
https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence - Fedak KM, Bernal A, Capshaw ZA, Gross S. Applying the Bradford Hill criteria in the 21st century: How data integration has changed causal inference in molecular epidemiology. Emerging Themes in Epidemiology. 2015;12(1):
14 . DOI: 10.1186/s12982-015-0037-4 - Quinn RW. Did scarlet fever and rheumatic fever exist in Hippocrates’ time? Reviews of Infectious Diseases. 1991;13(6):1243–1244. DOI: 10.1093/clinids/13.6.1243 PubMed PMID: 1775859
- Pasero G, Marson P. Hippocrates and rheumatology. Clinical and Experimental Rheumatology. 2004;22(6):687–689.
- Hippocrates, Adams F. The genuine works of Hippocrates; translated from the Greek with a preliminary discourse and annotations [Internet]. Vol. 1. New York: William Wood and Company; 1886. Available from:
https://archive.org/details/genuineworksofhi00tran/page/n7/mode/2up - Celsus, Spencer WG. De medicina. Cambridge, MA: Harvard University Press; 1971.
- Sydenham T, Pechey J. The whole works of that excellent practical physician Dr. Thomas Sydenham wherein not only the history and cures of acute diseases are treated of, after a new and accurate method; but also the shortest and safest way of curing most chronical diseases [Internet]. London: M. Wellington; 1767 [cited 2024 Nov 19]. Available from:
https://wellcomecollection.org/works/adn6hmuj - Tulchinsky TH. John Snow, cholera, the Broad Street pump; Waterborne diseases then and now. Case Studies in Public Health. 2018;77–99. DOI: 10.1016/B978-0-12-804571-8.00017-2
- Trousseau A. Lectures on clinical medicine. Philadelphia, PA: Lindsay & Blakiston; 1873.
- Fowler JK. On the association of affections of the throat with acute rheumatism. The Lancet. 1880;116(2989):933–934. DOI: 10.1016/S0140-6736(02)32274-8
- Longstaff GB. On some statistical indications of a relationship between scarlatina, puerperal fever, and certain other diseases. Transactions of the Epidemiological Society of London. 1880;4:421–430.
- Haig-Brown C. Tonsillitis in adolescents. London: Baillière, Tindall and Cox; 1886.
- Osler W. The Gulstonian lectures, on malignant endocarditis. The British Medical Journal. 1885;1(1262):467–470. DOI: 10.1136/bmj.1.1262.467
- Ullmann A. Pasteur–Koch: Distinctive ways of thinking about infectious diseases. Microbe. 2007;2(8):383–387.
- Mantle A. Infectious sore-throat, in which rheumatism played a prominent part. British Medical Journal. 1885;2(1299):960–961. DOI: 10.1136/bmj.2.1299.960
- Poynton F. The etiology of rheumatic fever. The Lancet. 1900;156(4022). DOI: 10.1016/S0140-6736(01)86866-5
- Beaton R, Ainley Walker E. The etiology of acute rheumatism and allied conditions. British Medical Journal. 1903;1:237–239. DOI: 10.1136/bmj.1.2196.237
- Cole R. Experimental streptococcus arthritis in relation to the etiology of acute articular rheumatism. Journal of Infectious Diseases. 1904;1:714–737. DOI: 10.1093/infdis/1.4.714
- Beattie J. The “Micrococcus Rheumaticus”: Its cultural and other characteristics. British Medical Journal. 1904;2:1510–1511. DOI: 10.1136/bmj.2.2292.1510
- Meyer F. Zur Bakteriologie des acuten Gelenkrheumatismus. Zeitschrift fur Klinische Medizin. 1902;45:311–338.
- Philipp C. Zur Aetiologie des acuten Gelenkrheumatismus. Deutsches Archiv fur Klinische Medizin. 1903;76:150–173.
- Emerson H. Le Rhumatisme Articulaire aigu Maladie Contagieuse. Etude epidemiologie et pathogenigal. American Journal of Public Health. 1927;17(4):
388 . DOI: 10.2105/AJPH.17.4.388-a - Raven MO. Rheumatic carditis: Some principles governing its prevention and early treatment. The Lancet. 1932;1:1227–1233. DOI: 10.1016/S0140-6736(01)29351-9
- Andrewes CH, Derick CL, Swift HF. A study of hemolytic streptococci in acute rheumatic fever, with an analysis of the antigenic relationships existing among certain strains. Journal of Experimental Medicine. 1926;43(1):13–29. DOI: 10.1084/jem.43.1.13
- Schlesinger B. The relationship of throat infection to acute rheumatism in childhood. Archives of Disease in Childhood. 1930;5(30):411–430. DOI: 10.1136/adc.5.30.411
- Hiller RI, Graef I. An epidemic of rheumatism at a cardiac camp. American Heart Journal. 1928;3(3):271–278. DOI: 10.1016/S0002-8703(28)90325-7
- Atwater RM. Studies in the epidemiology of acute rheumatic fever and related diseases in the united states, based on mortality statistics*. American Journal of Epidemiology. 1927;7(3):343–369. DOI: 10.1093/oxfordjournals.aje.a120418
- Glover JA. Milroy lecture on the incidence of rheumatic heart disease. The Lancet. 1930 Apr 5;215(5562):733–738. DOI: 10.1016/S0140-6736(00)88247-1
- Collis WRF. Acute rheumatism and haemolytic streptococci. The Lancet. 1931;217(5625):1341–1345. DOI: 10.1016/S0140-6736(00)46851-0
- Coburn A, Pauli R. Studies on the relationship of streptococcus hemolyticus to the rheumatic process. I. Observations on the ecology of hemolytic streptococcus in relation to the epidemiology of rheumatic fever. The Journal of Experimental Medicine. 1932;56(5):609–632. DOI: 10.1084/jem.56.5.609
- Coburn A. Observations on the mechanism of rheumatic fever. The Lancet. 1936; Originally published as Volume 2, Issue 5905228(5905): 1025–1030. DOI: 10.1016/S0140-6736(00)48235-8
- Merschel M. How the war against rheumatic heart disease was – and wasn’t – won. American Heart Association News [Internet]. 2024 Aug 23 [cited 2024 Nov 21]. Available from:
https://www.heart.org/en/news/2024/08/23/how-the-war-against-rheumatic-heart-disease-was-and-wasnt-won - Thomas CB, France R, Reichsman F. The prophylactic use of sulfanilamide. The Journal of the American Medical Association. 1941;116(7):552–560. DOI: 10.1001/jama.1941.02820070001001
- Thomas CB. The prophylactic treatment of rheumatic fever by sulfanilamide. The Bulletin of the New York Academy of Medicine. 1942;18(8).
- Kuttner AG, Reyersbach G. The prevention of streptococcal upper respiratory infections and rheumatic recurrences in rheu- matic children by the prophylactic use of sulfanilamide. Journal of Clinical Investigation. 1942;22(1):77–85. DOI: 10.1172/JCI101371
- Dodge KG, Baldwin JS, Weber MW. The prophylactic use of sulfanilamide in children with inactive rheumatic fever. The Journal of Pediatrics. 1944;24(5):483–501. DOI: 10.1016/S0022-3476(44)80026-9
- Holbrook WP. The Army Air Forces Rheumatic Fever Control Program. JAMA. 1944;126(2):84–87. DOI: 10.1001/jama.1944.02850370022005
- Kuttner AG. Sulfonamide prophylaxis for the prevention of rheumatic recurrences. The Journal of Pediatrics. 1945;26(3):216–219. DOI: 10.1016/S0022-3476(45)80097-5
- Kilbourne ED, Loge JP. The comparative effects of continuous and intermittent penicillin therapy on the formation of antistreptolysin in hemolytic streptococcal pharyngitis 1. Journal of Clinical Investigation. 1948;27(4):418–424. DOI: 10.1172/JCI101985
- Massell BF, Dow JW, Jones TD. Orally administered penicillin in patients with rheumatic fever. Journal of the American Medical Association. 1948;138(14):1030–1036. DOI: 10.1001/jama.1948.02900140022005
- Ottolini MG, Burnett MW. History of U.S. Military contributions to the study of respiratory infections. Military Medicine. 2005;170(4S):66–70. DOI: 10.7205/MILMED.170.4S.66
- Denny FW, Houser HB.
Section 4: Commission on streptococcal and staphylococcal Disease . In Woodward TE (Ed.) Armed Forces Epidemiological Board: The histories of the commissions [Internet]. Washington, DC: Borden Institute, Office of the Surgeon General, Department of the Army; 2006. pp. 259–359 [cited 2024 Nov 21]. Available from:https://achh.army.mil/history/book-historiesofcomsn-section4 - Gordis Leon. Effectiveness of comprehensive-care programs in preventing rheumatic fever. New England Journal of Medicine. 1973;289(7):331–335. DOI: 10.1056/NEJM197308162890701
- Nordet P, Lopez R, Sarmiento L, Nordet P, Dueñas A. Prevention and control of rheumatic fever and rheumatic heart disease: The Cuban experience (1986–1996–2002). Cardiovascular Journal of Africa. 2008;19(3):135–140.
- Bach JF, Chalons S, Mosser A, Forier E, Elana G, Jouanelle J, et al. 10-year educational programme aimed at rheumatic fever in two French Caribbean islands. The Lancet. 1996;347(9002):644–648. DOI: 10.1016/S0140-6736(96)91202-7
- Coulehan J, Grant S, Reisinger K, Killian P, Rogers KD, Kaltenbach C. Acute rheumatic fever and rheumatic heart disease on the Navajo reservation, 1962–77. Public Health Reports (1974). 1980;95(1).
- Chun LT, Reddy V, Rhoads G. Occurrence and prevention of rheumatic fever among ethnic groups of Hawaii. American Journal of Diseases of Children. 1984;138(5). DOI: 10.1001/archpedi.1984.02140430052013
- Brant LJ, Bender TR, Bross DS. Evaluation of an Alaskan streptococcal control program: Importance of the program’s intensity and duration. Preventive Medicine. 1986;15(6):632–642. DOI: 10.1016/0091-7435(86)90068-X
- Arguedas A, Mohs E. Prevention of rheumatic fever in Costa Rica. The Journal of Pediatrics. 1992;121(4):569–572. DOI: 10.1016/S0022-3476(05)81146-1
- Jack SJ, Williamson DA, Galloway Y, Pierse N, Zhang J, Oliver J, et al. Primary prevention of rheumatic fever in the 21st century: Evaluation of a national programme. International Journal of Epidemiology. 2018;47(5):1585–1593. DOI: 10.1093/ije/dyy150
- Lennon D, Anderson P, Kerdemilidis M, Farrell E, Crengle Mahi S, Percival T, et al. First presentation acute rheumatic fever is preventable in a community setting: A school-based Intervention. Pediatric Infectious Disease Journal. 2017;36(12):1113–1118. DOI: 10.1097/INF.0000000000001581
- Walsh L, Innes-Smith S, Wright J, Michniewicz T, Tozer M, Humby J, et al. School-based streptococcal a sore-throat treatment programs and acute rheumatic fever amongst indigenous Māori: A retrospective cohort study. Pediatric Infectious Disease Journal. 2020;39(11):995–1001. DOI: 10.1097/INF.0000000000002770
- Lennon D, Stewart J, Farrell E, Palmer A, Mason H. School-based prevention of acute rheumatic fever: A group randomized trial in New Zealand. Pediatric Infectious Disease Journal. 2009;28(9):787–794. DOI: 10.1097/INF.0b013e3181a282be
- Sheldon W. On acute rheumatism following tonsillitis. The Lancet. 1931;217(5625). DOI: 10.1016/S0140-6736(00)46850-9
- Grossman BJ, Stamler J. Potential preventability of first attacks of acute rheumatic fever in children. JAMA. 1963;183(12). DOI: 10.1001/jama.1963.03700120043006
- Gordis L, Lilienfeld A, Rodriguez R. An evaluation of the Maryland Rheumatic Fever Registry. Public Health Reports (1896–1970). 1969;84(4):
333 . DOI: 10.2307/4593555 - Schottmuller HV. Munchener Medizinische Wochenschrift. 1930;50:
849 . - Bradley WH. Discussion on some problems concerning the prevention and treatment of acute rheumatic infection. Proceedings of the Royal Society of Medicine. 1932;25(12):1631–1642. DOI: 10.1177/003591573202501104
- Rammelkamp CH, Stolzer BL. The latent period before the onset of acute rheumatic fever. Yale Journal of Biology and Medicine. 1961;34(3–4):386–398.
- Gewitz MH, Baltimore RS, Tani LY, Sable CA, Shulman ST, Carapetis J, et al. Revision of the Jones criteria for the diagnosis of acute rheumatic fever in the era of Doppler echocardiography a scientific statement from the American Heart Association. Circulation. 2015;131(20):1806–1818. DOI: 10.1161/CIR.0000000000000205
- Todd EW, Camb MD, Durh DPH. Antihæmolysin titres in hæmolytic streptococcal infections and their significance in rheumatic fever. British Journal of Experimental Pathology. 1932;13(3):248–259.
- Mote JR, Jones TD. Studies of hemolytic streptococcal antibodies in control groups, rheumatic fever, and rheumatoid arthritis1: III. The magnitude of antistreptolysin “O”, antifibrinolysin, and precipitating-antibody responses; the persistence of the antibodies, and variations in antistreptolysin “O” curves in scarlet fever, hemolytic streptococcal infections, and rheumatic fever. The Journal of Immunology. 1941;41(1):87–118. DOI: 10.4049/jimmunol.41.1.87
- Rejholec V, Wagner V. Response by antibodies to tissue antigens in the course of rheumatic fever. Annals of the Rheumatic Diseases. 1956;15(4):364–372. DOI: 10.1136/ard.15.4.364
- Stollerman GH, Lewis AJ, Schultz I, Taranta A. Relationship of immune response to group A streptococci to the course of acute, chronic and recurrent rheumatic fever. The American Journal of Medicine. 1956;20(2):163–169. DOI: 10.1016/0002-9343(56)90185-1
- Ayoub EM, Wannamaker LW. Evaluation of the streptococcal desoxyribo-nuclease b and diphosphopyridine nucleotidase antibody tests in acute rheumatic fever and acute glomerulonephritis. Pediatrics. 1962;29(4):527–538. DOI: 10.1542/peds.29.4.527
- Ayoub EM, Wannamaker LW. Streptococcal antibody titers in Sydenham’s chorea. Pediatrics. 1966;38(6):946–956. DOI: 10.1542/peds.38.6.946
- Schmidt WC, Moore DJ. The determination of antibody to group a streptococcal polysaccharide in human sera by hemagglutination. Journal of Experimental Medicine. 1965;121(5):793–806. DOI: 10.1084/jem.121.5.793
- Wannamaker LW, Ayoub EM. Antibody titers in acute rheumatic fever. Circulation. 1960;21:598–614. DOI: 10.1161/01.CIR.21.4.598
- Rammelkamp CH, Wannamaker LW, Denny FW. The epidemiology and prevention of rheumatic fever. Bulletin of the New York Academy of Medicine. 1952;28(5):321–334.
- Myers WK, Keefer CS. Antistreptolysin content of the blood serum in rheumatic fever and rheumatoid arthritis. Journal of Clinical Investigation. 1934;13(1):155–167. DOI: 10.1172/JCI100575
- Thomas S, Bennett J, Jack S, Oliver J, Purdie G, Upton A, et al. Descriptive analysis of group A streptococcus in skin swabs and acute rheumatic fever, Auckland, New Zealand, 2010–2016. The Lancet Regional Health. Western Pacific. 2021;8:
100101 . DOI: 10.1016/j.lanwpc.2021.100101 - Baker MG, Gurney J, Oliver J, Moreland NJ, Williamson DA, Pierse N, et al. Risk factors for acute rheumatic fever: Literature review and protocol for a case-control study in New Zealand. International Journal of Environmental Research and Public Health. 2019;16(22). DOI: 10.3390/ijerph16224515
- Malcolm J, Snell L, Grimwade K, Innes-Smith S, Bennett M, Lowe L, et al. Rheumatic fever trends in the context of skin infection and group A streptococcal sore throat programmes in the Bay of Plenty: An observational study, 2000–2022. The New Zealand Medical Journal. 2025;138(1609):15–44. DOI: 10.26635/6965.6532
- Baker MG, Gurney J, Moreland NJ, Bennett J, Oliver J, Williamson DA, et al. Risk factors for acute rheumatic fever: A case-control study. The Lancet Regional Health. Western Pacific. 2022;26. DOI: 10.1016/j.lanwpc.2022.100508
- O’Sullivan L, Moreland NJ, Webb RH, Upton A, Wilson NJ. Acute rheumatic fever after group A streptococcus pyoderma and group G streptococcus pharyngitis. Pediatric Infectious Disease Journal. 2017;36(7):692–694. DOI: 10.1097/INF.0000000000001558
- Mikkelsen CS, Gelvan A, Ibrahim A, Ladefoged K. A case of rheumatic fever with acute post-streptococcal glomerulonephritis and nephrotic syndrome caused by a cutaneous infection with beta-hemolytic streptococci. Dermatology Reports. 2010;1(1):
e4 . DOI: 10.4081/dr.2009.e4 - Amic-Desvaud Q, Maillard O, Iacobelli S, Bardin T, Ducrot YM. Pos1189 rheumatic fever and cutaneous streptococcal infection: A case-control study in the Loyalty Islands, New Caledonia. Annals of the Rheumatic Diseases. 2022;81:
922 . DOI: 10.1136/annrheumdis-2022-eular.4436 - Baker MG, Bennett J, Percival T, Leversha A, Gurney J, Moreland NJ. New evidence supports a greater focus on streptococcal skin infections to prevent rheumatic fever. Medical Journal of Australia. 2025;223(3):114–116. DOI: 10.5694/mja2.52708
- Wannamaker LW, Rammelkamp CH, Denny FW, Brink WR, Houser HB, Hahn EO, et al. Prophylaxis of acute rheumatic fever by treatment of the preceding streptococcal infection with various amounts of depot penicillin. American Journal of Medicine. 1951;673–695. DOI: 10.1016/0002-9343(51)90336-1
- Houser HB, Eckhardt GC, Hahn EO, Denny FW, Wannamaker LW, Rammelkamp CH. Effect of aureomycin treatment of streptococcal sore throat, on the streptococcal carrier state, the immunologic response of the host, and the incidence of acute rheumatic fever. Pediatrics. 1953;12(6):593–606. DOI: 10.1542/peds.12.6.593
- Kulik E, Stuart B, Willcox M. Predictors of rheumatic fever in sore throat patients: A systematic review and meta-analysis. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2021;116(4):286–297. DOI: 10.1093/trstmh/trab156
- Denny FW, Wannamaker LW, Hahn EO. Comparative effects of penicillin, aureomycin and terramycin on streptococcal tonsillitis and pharyngitis. Pediatrics. 1953;11(1):7–13. DOI: 10.1542/peds.11.1.7
- Brink WR, Rammelkamp CH, Denny FW, Wannamaker LW. Effect of penicillin and aureomycin on the natural course of streptococcal tonsillitis and pharyngitis. The American Journal of Medicine. 1951;10(3):300–308. DOI: 10.1016/0002-9343(51)90274-4
- Catanzaro FJ, Brock LL, Chamovitz R, Perry WD, Siegel AC, Stetson CA, et al. Effect of oxytetracycline therapy of streptococcal sore throat on the incidence of acute rheumatic fever. Annals of Internal Medicine. 1955;42(2):
345 . DOI: 10.7326/0003-4819-42-2-345 - Denny FW, Wannamaker LW, Brink WR, Rammelkamp CH, Custer EA. Prevention of rheumatic fever; treatment of the preceding streptococcic infection. Journal of the American Medical Association. 1950;143(2):151–153. DOI: 10.1001/jama.1950.02910370001001
- Catanzaro FJ, Stetson CA, Morris AJ, Chamovitz R, Rammelkamp CH, Stolzer BL, et al. The role of the streptococcus in the pathogenesis of rheumatic fever. The American Journal of Medicine. 1954;17(6):749–756. DOI: 10.1016/0002-9343(54)90219-3
- McFarland RB, Colvin VG, Seal JR. Mass prophylaxis of epidemic streptococcal infections with benzathine penicillin G. II. Experience at a naval training center during the winter of 1956–57. The New England Journal of Medicine. 1958;258(26):
1277 . DOI: 10.1056/NEJM195806262582601 - Chamovitz R, Catanzaro FJ, Stetson CA, Rammelkamp CH. Prevention of rheumatic fever by treatment of previous streptococcal infections. I. Evaluation of benzathine penicillin G. The New England Journal of Medicine. 1954;251(12):466–471. DOI: 10.1056/NEJM195409162511203
- Catanzaro FJ, Rammelkamp CH, Chamovitz R. Prevention of rheumatic fever by treatment of streptococcal infections. The New England Journal of Medicine. 1958;259(2):51–57. DOI: 10.1056/NEJM195807102590201
- Siegel A, Johnson E, Stollerman G. Controlled studies of streptococcal pharyngitis in a pediatric population — Factors related to attack rate of rheumatic fever. The New England Journal of Medicine. 1961;265(12):
559 . DOI: 10.1056/NEJM196109212651201 - Breese BB. Treatment of beta hemolytic streptococcic infections in the home: Relative value of available methods. JAMA. 1953;152(1):
10 . DOI: 10.1001/jama.1953.03690010016003 - Robertson KA, Volmink JA, Mayosi BM. Antibiotics for the primary prevention of acute rheumatic fever: A meta-analysis. BMC Cardiovascular Disorders. 2005;5(1):
11 . DOI: 10.1186/1471-2261-5-11 - Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat. Cochrane Database of Systematic Reviews. 2013:
CD000023 . DOI: 10.1002/14651858.CD000023.pub4 - Kerdemelidis M, Lennon DR, Arroll B, Peat B, Jarman J. The primary prevention of rheumatic fever. Journal of Paediatrics and Child Health. 2010;46(9):534–548. DOI: 10.1111/j.1440-1754.2010.01854.x
- Ralph AP, Noonan S, Wade V, Currie BJ. The 2020 Australian guideline for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. Medical Journal of Australia. 2021;214(5):220–227. DOI: 10.5694/mja2.50851
- Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database of Systematic Reviews. 2002;2002(3):
CD002227 . DOI: 10.1002/14651858.CD002227 - de Dassel JL, de Klerk N, Carapetis JR, Ralph AP. How many doses make a difference? An analysis of secondary prevention of rheumatic fever and rheumatic heart disease. Journal of the American Heart Association. 2018;7(24):
e010223 . DOI: 10.1161/JAHA.118.010223 - McGlacken-Byrne SM, Parry HM, Currie PF, Wilson NJ. Failure of oral penicillin as secondary prophylaxis for rheumatic heart disease: A lesson from a low-prevalence rheumatic fever region. BMJ Case Reports. 2015;2015. DOI: 10.1136/bcr-2015-212861
- Beaton A, Okello E, Rwebembera J, Grobler A, Engelman D, Alepere J, et al. Secondary antibiotic prophylaxis for latent rheumatic heart disease. The New England Journal of Medicine. 2022;386(3):230–240. DOI: 10.1056/NEJMoa2102074
- Kado J, Salman S, Hla TK, Enkel S, Henderson R, Hand RM, et al. Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: A phase 1 open-label population pharmacokinetic study. Antimicrobial Agents and Chemotherapy. 2023;67(12):
e0096223 . DOI: 10.1128/aac.00962-23 - Kazahura PT, Mushi TL, Pallangyo P, Janabi M, Kisenge R, Albaghdadi M, et al. Prevalence and risk factors for subclinical rheumatic heart disease among primary school children in Dar es Salaam, Tanzania: A community based cross-sectional study. BMC Cardiovascular Disorders. 2021;21(1):
610 . DOI: 10.1186/s12872-021-02377-9 - Sharma N, Toor D. Impact of socio-economic factors on increased risk and progression of rheumatic heart disease in developing nations. Current Infectious Disease Reports. 2019;21(6):
21 . DOI: 10.1007/s11908-019-0677-6 - Bennett J, Moreland NJ, Zhang J, Crane J, Sika-Paotonu D, Carapetis J, et al. Risk factors for group A streptococcal pharyngitis and skin infections: A case control study. The Lancet Regional Health. Western Pacific. 2022;26:
100507 . DOI: 10.1016/j.lanwpc.2022.100507 - Coffey PM, Ralph AP, Krause VL. The role of social determinants of health in the risk and prevention of group A streptococcal infection, acute rheumatic fever and rheumatic heart disease: A systematic review. PLOS Neglected Tropical Diseases. 2018;12(6):
e0006577 . DOI: 10.1371/journal.pntd.0006577 - Schlesinger B, Signy AG. Precipitin reactions in the blood of rheumatic patients following acute throat infections. QJM. 1933;2(2):255–266. DOI: 10.1093/oxfordjournals.qjmed.a066911
- Stetson CA. Streptococcal infections. New York, NY: Columbia University Press; 1954.
- Eltohami EA, Hajar HA, Folger GM, Eltohami EA. Acute rheumatic fever in an Arabian Gulf country effect of climate, advantageous socioeconomic conditions, and access to medical care. Angiology. 1997;48(6):481–489. DOI: 10.1177/000331979704800602
- Lorenz N, Ho TKC, McGregor R, Davies MR, Williamson DA, Gurney JK, et al. Serological profiling of group A streptococcus infections in acute rheumatic fever. Clinical Infectious Diseases. 2021;73(12):2322–2325. DOI: 10.1093/cid/ciab180
- Martins TB, Hoffman JL, Augustine NH, Phansalkar AR, Fischetti VA, Zabriskie JB, et al. Comprehensive analysis of antibody responses to streptococcal and tissue antigens in patients with acute rheumatic fever. International Immunology. 2008;20(3):445–452. DOI: 10.1093/intimm/dxn004
- Raynes JM, Frost HRC, Williamson DA, Young PG, Baker EN, Steemson JD, et al. Serological evidence of immune priming by group A streptococci in patients with acute rheumatic fever. Frontiers in Microbiology. 2016;7:
1119 . DOI: 10.3389/fmicb.2016.01119 - Whitcombe AL, McGregor R, Bennett J, Gurney JK, Williamson DA, Baker MG, et al. Increased breadth of group A streptococcus antibody responses in children with acute rheumatic fever compared to precursor pharyngitis and skin infections. Journal of Infectious Diseases. 2022;226(1):167–176. DOI: 10.1093/infdis/jiac043
- Salie MT, Rampersadh K, Muhamed B, Engel KC, Zühlke LJ, Dale JB, et al. Utility of human immune responses to GAS antigens as a diagnostic indicator for ARF: A systematic review. Frontiers in Cardiovascular Medicine. 2021;8:
691646 . DOI: 10.3389/fcvm.2021.691646 - Fischetti VA. Surface proteins on gram-positive bacteria. Microbiology Spectrum. 2024;7(4):1–15. DOI: 10.1128/microbiolspec.GPP3-0012-2018
- Cunningham MW. Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection. International Reviews of Immunology. 2014;33(4):314–329. DOI: 10.3109/08830185.2014.917411
- Tandon R, Sharma M, Chandrashekhar Y, Kotb M, Yacoub MH, Narula J. Revisiting the pathogenesis of rheumatic fever and carditis. Nature Reviews. Cardiology. 2013;10(3):171–177. DOI: 10.1038/nrcardio.2012.197
- Guilherme L, Kalil J, Cunningham M. Molecular mimicry in the autoimmune pathogenesis of rheumatic heart disease. Autoimmunity. 2006;39(1):31–39. DOI: 10.1080/08916930500484674
- Sharma N, Toor D. Interleukin-10: Role in increasing susceptibility and pathogenesis of rheumatic fever/rheumatic heart disease. Cytokine. 2017;90:169–176. DOI: 10.1016/j.cyto.2016.11.010
- Fae KC, da Silva DD, Oshiro SE, Tanaka AC, Pomerantzeff PM, Douay C, et al. Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease. Journal of Immunology. 2006;176(9):5662–5670. DOI: 10.4049/jimmunol.176.9.5662
- Chung AW, Ho TK, Hanson-Manful P, Tritscheller S, Raynes JM, Whitcombe AL, et al. Systems immunology reveals a linked IgG3–C4 response in patients with acute rheumatic fever. Immunology & Cell Biology. 2020;98(1):12–21. DOI: 10.1111/imcb.12298
- Sikder S, Williams NL, Sorenson AE, Alim MA, Vidgen ME, Moreland NJ, et al. Group G streptococcus induces an autoimmune carditis mediated by interleukin 17A and interferon γ in the Lewis Rat Model of rheumatic heart disease. Journal of Infectious Diseases. 2018;218(2):324–335. DOI: 10.1093/infdis/jix637
- Parks T, Mirabel MM, Kado J, Auckland K, Nowak J, Rautanen A, et al. Association between a common immunoglobulin heavy chain allele and rheumatic heart disease risk in Oceania. Nature Communications. 2017;8:
14946 . DOI: 10.1038/ncomms14946 - Bright PD, Mayosi BM, Martin WJ. An immunological perspective on rheumatic heart disease pathogenesis: more questions than answers. Heart. 2016;102(19):1527–1532. DOI: 10.1136/heartjnl-2015-309188
- Quinn RW. Epidemiology of group A streptococcal infections--their changing frequency and severity. The Yale Journal of Biology and Medicine. 1982;55(3–4):265–270.
- Kaplan MH, Bolande R, Rakita L, Blair J. Presence of bound immunoglobulins and complement in the myocardium in acute rheumatic fever. Association with cardiac failure. New England Journal of Medicine. 1964;271:637–645. DOI: 10.1056/NEJM196409242711301
- Jasti AK, Selmi C, Sarmiento-Monroy JC, Vega DA, Anaya JM, Gershwin ME. Guillain-Barré syndrome: Causes, immunopathogenic mechanisms and treatment. Expert Review of Clinical Immunology. 2016;12(11):1175–1189. DOI: 10.1080/1744666X.2016.1193006
- Schmitt SK. Reactive arthritis. Infectious Disease Clinics in North America. 2017;31(2):265–277. DOI: 10.1016/j.idc.2017.01.002
- Munif MR, Hart RA, Rafeek RAM, Mallawaarachchi AC, Anderson L, McMillan DJ, et al. Mechanisms that potentially contribute to the development of post-streptococcal glomerulonephritis. Pathogens and Disease. 2024;82:
ftae024 . DOI: 10.1093/femspd/ftae024 - Berrios X, Quesney F, Morales A, Blazquez J, Lagomarsino E, Bisno AL. Acute rheumatic fever and poststreptococcal glomerulonephritis in an open population: Comparative studies of epidemiology and bacteriology. The Journal of Laboratory and Clinical Medicine. 1986;108(6).
- Potter EV, Svartman M, Mohammed I, Cox R, Poon-King T, Earle DP. Tropical acute rheumatic fever and associates treptococcal infections compared with concurrent acute glomerulonephritis. The Journal of Pediatrics. 1978;92(2):325–333. DOI: 10.1016/S0022-3476(78)80036-5
- Bisno AL, Pearce IA, Wall HP, Moody MD, Stollerman GH. Contrasting epidemiology of acute rheumatic fever and acute glomerulonephritis. New England Journal of Medicine. 1970;283(11):561–565. DOI: 10.1056/NEJM197009102831103
- Cecil R, Nicholls E, Stainsby W. Bacteriology of the blood and joints in rheumatic fever. The Journal of Experimental Medicine. 1929;50(5):617–642. DOI: 10.1084/jem.50.5.617
- Veasy LG, Tani LY, Hill HR. Persistence of acute rheumatic fever in the intermountain area of the United States. The Journal of Pediatrics. 1994;124(1):9–16. DOI: 10.1016/S0022-3476(94)70247-0
- Bland EF, Jones TD. Clinical observations on the events preceding the appearance of rheumatic fever 12. Journal of Clinical Investigation. 1935;14(5):633–648. DOI: 10.1172/JCI100712
- Jones TD. The diagnosis of rheumatic fever. JAMA. 1944;126(8):481–484. DOI: 10.1001/jama.1944.02850430015005
- Rantz LA, Boisvert PJ, Spink WW. Etiology and pathogenesis of rheumatic fever. Archives of Internal Medicine. 1945;76(131). DOI: 10.1001/archinte.1945.00210330002001
DOI: https://doi.org/10.5334/gh.1564 | Journal eISSN: 2211-8179
Language: English
Page range: 48 - 48
Submitted on: Mar 9, 2026
Accepted on: May 28, 2026
Published on: Jun 19, 2026
Published by: Ubiquity Press
In partnership with: Paradigm Publishing Services
Keywords:
© 2026 Scott H. Wirth, Andrea Z. Beaton, Andrew Steer, published by Ubiquity Press
This work is licensed under the Creative Commons Attribution 4.0 License.