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Meta-Analysis
. 2024 Sep 23;9(9):CD015779.
doi: 10.1002/14651858.CD015779.

Long-term antibiotic prophylaxis for prevention of rheumatic fever recurrence and progression to rheumatic heart disease

Jonathan JH Bray  1 , Sophie Thompson  2 , Samuel Seitler  3 , Syed Ahsan Ali  4 , Janice Yiu  5 , Mahan Salehi  6 , Mahmood Ahmad  7 , Ferruccio Pelone  8   9 , Hyeriju Gashau  10 , Farhad Shokraneh  9   11   12   13 , Nida Ahmed  14 , Miryan Cassandra  15 , Eloi Marijon  16 , David S Celermajer  17 , Rui Providencia  14
Affiliations
Meta-Analysis

Long-term antibiotic prophylaxis for prevention of rheumatic fever recurrence and progression to rheumatic heart disease

Jonathan JH Bray et al. Cochrane Database Syst Rev. .

Abstract

Background: Rheumatic fever is a non-suppurative, inflammatory sequela of group A Streptococcus pharyngitis that can occur at two to four weeks after infection. Following an episode of rheumatic fever, there is a risk of developing rheumatic heart disease (RHD) later in life that carries significant risk of morbidity and mortality. RHD remains the largest global cause of cardiovascular disease in the young (age < 25 years). The historical literature provides inconclusive evidence that antibiotic prophylaxis is beneficial in reducing the risk of recurrence of rheumatic fever and development of RHD. Antibiotics are thought to work by reducing the carriage of group A Streptococcus and thus reducing the risk of infection. This review was commissioned by the World Health Organization (WHO) for an upcoming guideline.

Objectives: 1. To assess the effects of long-term antibiotics versus no antibiotics (control) for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD. 2. To assess the effects of long-term intramuscular penicillin versus long-term oral antibiotics for secondary prevention of rheumatic fever recurrence and associated sequelae in people with previous rheumatic fever or RHD.

Search methods: We systematically searched CENTRAL, MEDLINE, Embase, Conference Proceedings Citation Index-Science, clinical trial registers, ISRCTN.com and reference lists without restrictions on language or date up to 10 March 2024.

Selection criteria: We sought randomised controlled trials or quasi-randomised trials, described in any language, including participants with previous rheumatic fever and/or RHD of any age, based in community or hospital settings. Studies were included if they compared firstly antibiotic prophylaxis with no antibiotic prophylaxis, and, secondly, intramuscular penicillin prophylaxis versus oral antibiotic prophylaxis.

Data collection and analysis: We used standardised methodological, Cochrane-endorsed procedures and performed meta-analyses with risk ratios (RR) and Peto odds ratios (Peto OR). Our primary outcomes were recurrence of rheumatic fever, progression or severity of RHD and cardiac complications. Our secondary outcomes were obstetric complications (maternal and foetal events), mortality, treatment adherence, adverse events and acceptability to participants. We performed comprehensive assessments of risk of bias and certainty of evidence, applying the GRADE methodology.

Main results: We included 11 studies (seven RCTs and four quasi-randomised trials) including 3951 participants. The majority of the included studies were conducted in the USA, UK and Canada during the 1950s to 1960s. Most participants with previous rheumatic fever had been diagnosed using the modified Jones criteria (mJC) (four studies), were an average of 12.3 years of age and 50.6% male. We assessed the majority of the included studies to be at high risk of bias, predominantly relating to blinding and attrition bias. Comparison one: antibiotics versus no antibiotics Pooled meta-analysis of six RCTs provides moderate-certainty evidence that antibiotics overall (oral or intramuscular) probably reduce the risk of recurrence of rheumatic fever substantially (0.7% versus 1.7%, respectively) (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.22 to 0.69; 1721 participants). People with early or mild RHD likely have the greatest capacity to benefit from intramuscular antibiotic prophylaxis (8.1%) compared to no antibiotics (0.7%) (RR 0.09, 95% CI 0.03 to 0.29; 1 study, 818 participants; moderate-certainty evidence). Antibiotics may not affect mortality in people with late-stage RHD (RR 1.23, 95% CI 0.78 to 1.94; 1 study, 994 participants; low-certainty evidence). Antibiotics may not affect the risk of anaphylaxis (Peto odds ratio (OR) 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) or sciatic nerve injury (Peto OR 7.39, 95% CI 0.15 to 372; 1 study, 818 participants; low-certainty evidence) compared with no antibiotics, but probably have an increased risk of hypersensitivity reactions (RR 137, 8.51 to 2210; 2 studies, 894 participants; moderate-certainty evidence) and local reactions (RR 29, 1.74 to 485; 1 study, 818 participants; moderate-certainty evidence). Comparison two: intramuscular antibiotics versus oral antibiotics Pooled analysis of two RCTs showed that prophylactic intramuscular benzathine benzylpenicillin likely reduces recurrence of rheumatic fever substantially when compared to oral antibiotics (0.1% versus 1%, respectively) (RR 0.07, 95% CI 0.02 to 0.26; 395 participants; moderate-certainty evidence). Furthermore, it is unclear whether intramuscular benzyl penicillin is superior to oral antibiotics in reducing the risk of mortality in the context of RHD (Peto OR 0.22, 95% CI 0.01 to 4.12; 1 study, 431 participants; very low-certainty evidence). There were no data available on progression of latent RHD or adverse events including anaphylaxis, sciatic nerve injury, delayed hypersensitivity/allergic reactions and local reactions to injection.

Authors' conclusions: This review provides evidence that antibiotic prophylaxis likely reduces the risk of recurrence of rheumatic fever compared to no antibiotics, and that intramuscular benzathine benzylpenicillin is probably superior to oral antibiotics (approximately 10 times better). Moreover, intramuscular benzathine benzylpenicillin likely reduces the risk of progression of latent RHD. Evidence is scarce, but antibiotics compared with no antibiotics may not affect the risk of anaphylaxis or sciatic nerve injury, but probably carry an increased risk of hypersensitivity reactions and local reactions. Antibiotics may not affect all-cause mortality in late-stage RHD compared to no antibiotics. There is no evidence available to comment on the effect of intramuscular penicillin over oral antibiotics for progression of latent RHD and adverse events, and little evidence for all-cause mortality. It is important to interpret these findings in the context of major limitations, including the following: the vast majority of the included studies were conducted more than 50 years ago, many before contemporary echocardiographic studies; methodology was often at high risk of bias; outdated treatments were used; only one study was in latent RHD; and there are concerns regarding generalisability to low socioeconomic regions. This underlines the need for ongoing research to understand who benefits most from prophylaxis.

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Conflict of interest statement

JJHB works as an Internal Medicine Trainee at Oxford University Hospitals Trust. He has no conflicts of interest.

ST works as an Internal Medicine Trainee at University Hospitals Birmingham NHS Foundation Trust. She has no conflicts of interest.

SS works as an Internal Medicine Trainee at Royal Free London NHS foundation Trust. He has no conflicts of interest.

SAA works as an Internal Medicine Trainee at Health Education England West Midlands. He has no conflicts of interest.

JY works as an Academic Foundation Doctor at Guy's and St Thomas' NHS Foundation Trust. She has no conflicts of interest.

MS works as a Radiology Registrar at Sheffield Teaching Hospitals. He has no conflicts of interest.

MA works as a Cardiology Consultant at Barts Heart Centre. He has no conflicts of interest.

FP works as a health professional at UCL, University of London. He has no conflicts of interest.

HG works as an Internal Medicine Trainee at The University Hospital Monklands. He has no conflicts of interest.

FS is the Director at Systematic Review Consultants LTD, Evidence Synthesis Manager at the University of Oxford and Senior Research Associate at the University of Bristol. He holds an honorary assistant professorship from the University of Nottingham and an honorary lectureship from University College London. He was an Information Specialist for Cochrane Schizophrenia, Cochrane Neuromuscular, Cochrane Gut, Cochrane Heart and Cochrane Developmental, Psychosocial and Learning Problems. FS was not involved in the editorial process for the review. He has no conflicts of interest.

NA works as a Cardiology Registrar at Barts Heart Centre. She has no conflicts of interest.

MC is a Consultant Cardiologist at São Tomé and Príncipe Hospital. She has no conflicts of interest.

EM is a Professor of Cardiology at Paris City University and works as a health professional for APHP and INSERM. He declares grants from Abbott Fund, Boston Scientific Corporation, Medtronic USA Inc and Zoll Medical Corporation (personal payments). He has published opinions on the topic for INSERM.

DC is the Head of the Discipline of Cardiology and Cardiology Consultant at The University of Sydney. He reports conducting studies eligible for inclusion in the review; these are academic papers only, none of which had any external funding. DC was not involved in decisions regarding the eligibility of these studies, extracting data, assessing risk of bias or grading the certainty of the evidence. These tasks were performed by at least two independent review authors (JJHB, SAA, MS, ST, MA, JY). He has no conflicts of interest.

RP is a Professor of Cardiology at University College of London and works as a Cardiology Consultant ‐ Cardiac Electrophysiologist at St Bartholomew's Hospital London, UK. He is the former Co‐ordinating Editor of Cochrane Heart and was not involved in the editorial process for this review. RP declares a grant from the World Health Organization for writing eight systematic reviews for the new Rheumatic Heart Disease and Acute Rheumatic Fever guideline, paid to UCL; however, as Principal Investigator for the project, with responsibility for budget decisions, RP did have access to the funds.

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References

References to studies included in this review

Beaton 2022 {published data only}
    1. Beaton A, Okello E, Rwebembera J, Grobler A, Engelman D, Alepere J, et al. Secondary antibiotic prophylaxis for latent rheumatic heart disease. New England Journal of Medicine 2022;386(3):230-40. - PubMed
    1. Nascimento BR, Nunes MCP, da Silva JLP, Steer A, Engelman D, Okello E, Rwebembera J, Zuhlke L, Mirabel M, Nakitto M, Sarnacki R, Ribeiro ALP, Sable CA, Beaton AZ, (Gwoko Adunu pa Lutino) trial investigators. Outcomes of latent rheumatic heart disease: External validation of a simplified score in patients with and without secondary prophylaxis. International Journal of Cardiology 2024;399:131662. - PubMed
Brick 1950 {published data only}
    1. Brick M, McKinley H, Gourley M, Roy TE, Keith JD. Oral penicillin prophylaxis in rheumatic fever patients. Canadian Medical Association Journal 1950 ;63(3):255-8. - PMC - PubMed
Cope 1960 {published data only}
    1. Cope S, Sanderson G, Hill CAS, Chamberlain EN. Prophylactic use of oral penicillin in rheumatic fever, chorea, and carditis. BMJ 1960;1(5177):913-7. - PMC - PubMed
Evans 1950 {published data only}
    1. Evans JA. Oral penicillin in the prophylaxis of streptococcal infection and rheumatic relapse. Proceedings of the Royal Society of Medicine 1950;43(3):206-8. - PMC - PubMed
Feinstein 1959 {published data only}
    1. Feinstein AR, Wood HF, Epstein JA, Taranta A, Simpson R, Tursky E. A controlled study of three methods of prophylaxis against streptococcal infection in a population of rheumatic children. II. Results of the first three years of the study, including methods for evaluating the maintenance of oral prophylaxis. New England Journal of Medicine 1959;260(14):697-702. - PubMed
    1. Feinstein AR, Wood HF, Spagnuolo M, Taranta A, Tursky E, Kleinberg E. Oral prophylaxis of recurrent rheumatic fever. Sulfadiazine vs a double daily dose of penicillin. Journal of the American Medical Association 1964;188(6):489-92. - PubMed
Feinstein 1966 {published data only}
    1. Feinstein AR, Spagnuolo M, Levitt M, Jonas S, Tursky E. Discontinuation of antistreptococcal prophylaxis - a double-blind study in rheumatic patients free of heart disease. Journal of the American Medical Association 1966 ;197(12):949-52. - PubMed
Feinstein 1968 {published data only}
    1. Feinstein AR, Spagnuolo M, Jonas S, Kloth H, Tursky E, Levitt M. Therapeutic-continuous oral penicillin vs monthly injections. Journal of the American Medical Association 1968 ;206(3):565-68. - PubMed
    1. Feinstein AR, Spaguolo M, Jonas S, Tursky E, Stern EK, Levitt M. Prophylaxis of recurrent rheumatic fever. Ineffectiveness of intermittent 'therapeutic' oral penicillin. Journal of the American Medical Association 1965;191(6):451-4. - PubMed
Gale 1952 {published data only}
    1. Gale AH, Gillespie WA, Perry CB. Oral penicillin in the prophylaxis of streptococcal infection in rheumatic children. Lancet 1952;2(6724):61-3. - PubMed
Markowitz 1957 {published data only}
    1. Markowitz M, Ferencz C, Bonet A. A comparison of oral and intramuscular benzathine penicillin G for the prevention of streptococcal infections and recurrences of rheumatic fever. Pediatrics 1957;19(2):201-7. - PubMed
Padmavati 1973 {published data only}
    1. Padmavati S, Sharma KB, Jayaram O. Epidemiology and prophylaxis of rheumatic fever in Delhi - a five year follow-up. Singapore Medical Journal 1973;14(3):457-61. - PubMed
Wood 1964 {published data only}
    1. Stollerman GH, Rusoff JH, Hirschfeld I. Prophylaxis against group A streptococci in rheumatic fever. The use of single monthly injections of benzathine penicillin G. New England Journal of Medicine 1955;252:787-92. - PubMed
    1. Wood HF, Simpson R, Feinstein AR, Taranta A, Tursky E, Stollerman G. Rheumatic fever in children and adolescents. A long-term epidemiological study of subsequent prophylaxis, streptococcal infections, and clinical sequelae. I. Description of the investigative techniques and of the population studied. Annals of Internal Medicine 1964 ;60(Suppl 5):6-17. - PubMed

References to studies excluded from this review

Belay 2022 {published data only}
    1. Belay W, Dessie A, Ahmed H, Gedlu E, Mariyo A, Shehibo A, et al. Secondary prevention of rheumatic heart disease in Ethiopia: a multicenter study. BMC Cardiovascular Disorders 2022;22(1):26. [DOI: 10.1186/s12872-022-02473-4.] - DOI - PMC - PubMed
Breese 1958 {published data only}
    1. Breese BB, Disney FA. Failure of penicillin and sulfonamide to prevent betahemolytic streptococcal infections; sibling prophylaxis of streptococcal infection. American Journal of Diseases of Children 1958;95(4):359-63. [DOI: 10.1001/archpedi.1958.02060050361003] - DOI - PubMed
Bywaters 1958 {published data only}
    1. Bywaters EG, Thomas GT. Prevention of rheumatic fever recurrences. British Medical Journal 1958;2(5092):350-2. - PMC - PubMed
Chamovitz 1954 {published data only}
    1. Chamovitz R, Catanzaro FJ, Stetson CA, Rammelkamp CH Jr. Prevention of rheumatic fever by treatment of previous streptococcal infections. I. Evaluation of benzathine penicillin G. New England Journal of Medicine 1954;251(12):466-71. - PubMed
Frank 1965 {published data only}
    1. Frank PF, Stollerman GH, Miller LF. Protection of a military population from rheumatic fever: routine administration of benzathine penicillin G to healthy individuals. JAMA 1965;193(10):775-83. [DOI: 10.1001/jama.1965.03090100021005] - DOI - PubMed
Hand 2019 {published data only}
    1. Hand RM, Salman S, Newall N, Vine J, Page-Sharp M, Bowen AC, et al. A population pharmacokinetic study of benzathine benzylpenicillin G administration in children and adolescents with rheumatic heart disease: new insights for improved secondary prophylaxis strategies. Journal of Antimicrobial Chemotherapy 2019;74(7):1984–91. [PMID: ] - PMC - PubMed
Hassell 1974 {published data only}
    1. Hassell TA, Stuart KL. Rheumatic fever prophylaxis: a three year study. British Medical Journal 1974;2(5909):39-40. [DOI: 10.1136/bmj.2.5909.39] [PMCID: PMC1610170] [PMID: ] - DOI - PMC - PubMed
Herdy 1996 {published data only}
    1. Herdy GV, Souza DC, Barros PB, Pinto CA. Secondary prophylaxis in rheumatic fever. Oral antibiotic therapy versus benzathine penicillin [Profilaxia secundaria na febre reumatica. Antibioticoterapia oral versus penicilina benzatina]. Arquivos Brasileiros de Cardiologia 1996;67(5):331-3. [PMID: ] - PubMed
Kassem 1992 {published data only}
    1. Kassem AS, Madkour AA, Massoud BZ, Zaher SR. Benzathine penicillin G for rheumatic fever prophylaxis: 2-weekly versus 4-weekly regimens. Indian Journal of Pediatrics 1992;59(6):741-8. [DOI: 10.1007/BF02859412] - DOI - PubMed
Kassem 1996 {published data only}
    1. Kassem AS, Zaher SR, Abou Shleib H, el-Kholy AG, Madkour AA, Kaplan EL. Rheumatic fever prophylaxis using benzathine penicillin G (BPG): two- week versus four-week regimens: comparison of two brands of BPG. Pediatrics 1996;97(6 Pt 2):992-5. [PMID: ] - PubMed
Kohn 1950 {published data only}
    1. Kohn KH, Milzer A, Maclean H. Oral penicillin prophylaxis of recurrence of rheumatic fever. Journal of the American Medical Association 1950;142(1):20-5. - PubMed
Lalchandani 2016 {published data only}
    1. Lalchandani AD. Azithromycin (ARMOR) must replace benzathine penicillin for treatment and prophylaxis of rheumatic fever. In: 8th Global Cardiologists & Echocardiography Annual Meeting; 2016 Jul 18-20; Berlin, Germany. 2016.
Lue 1996 {published data only}
    1. Lue HC, Wu MH, Wang JK, Wu FF, Wu YN. Three- versus four-week administration of benzathine penicillin G: effects on incidence of streptococcal infections and recurrences of rheumatic fever. Pediatrics 1996;97(6 Pt 2):984-8. - PubMed
Roberts 1953 {published data only}
    1. Roberts E. Use of sulfonamides and penicillin to prevent recurrence of rheumatic fever; a twelve-year study. American Journal of Diseases of Children 1953;85(6):643-7. [DOI: 10.1001/archpedi.1953.02050070660002] - DOI - PubMed
Schreier 1958 {published data only}
    1. Schreier, A, Hockett, VE, Seal, JR. Mass prophylaxis of epidemic streptococcal infections with benzathine penicillin G. I. Experience at a naval training center during the winter of 1955–56. New England Journal of Medicine 1958;258(25):1231-8. [DOI: 10.1056/NEJM195806192582501] - DOI - PubMed
Spinetto 2011 {published data only}
    1. Spinetto H, Lennon D, Horsburgh M. Rheumatic fever recurrence prevention: a nurse-led programme of 28-day penicillin in an area of high endemnicity. Journal of Paediatric Child Health 2011;47(4):228-34. - PubMed
Sprenger 2016 {published data only}
    1. Sprenger K, Annamalai M, Lobenstein J, Hoosen EGM. Amoxicillin for the secondary prevention of rheumatic fever in children not allergic to penicillin. South African Medical Journal 2016;106(4):317. [DOI: 10.7196/samj.2016v106i4.10711] - DOI
Stollerman 1955 {published data only}
    1. Stollerman GH, Rusoff JH, Hirschfeld I. Prophylaxis against group A streptococci in rheumatic fever; the use of single monthly injections of benzathine penicillin G. New England Journal of Medicine 1955;252(19):787-92. - PubMed
Thomas 1988 {published data only}
    1. Thomas RJ, Conwill DE, Morton DE, Brooks TJ, Holmes CK, Mahaffey WB. Penicillin prophylaxis for streptococcal infections in United States Navy and Marine Corps recruit camps, 1951-1985. Reviews of Infectious Diseases 1988;10(1):125-30. [DOI: 10.1093/clinids/10.1.125] - DOI - PubMed
Tompkins 1972 {published data only}
    1. Tompkins DG, Boxerbaum B, Liebman J. Long-term prognosis of rheumatic fever patients receiving regular intramuscular benzathine penicillin. Circulation 1972;45(3):543-51. - PubMed

References to ongoing studies

NCT05693545 {unpublished data only}
    1. NCT05693545. GOALIE: intramuscular vs enteral penicillin prophylaxis to prevent progression of latent RHD trial [Intramuscular vs enteral penicillin prophylaxis to prevent progression of latent rheumatic heart disease: a non-inferiority randomized trial]. clinicaltrials.gov/study/NCT05693545 (first received 23 January 2023).

Additional references

Abrams 2020
    1. Abrams J, Watkins DA, Abdullahi LH, Zühlke LJ, Engel ME. Integrating the prevention and control of rheumatic heart disease into country health systems: a systematic review and meta-analysis. Global Heart 2020;15(1):62. [DOI: 10.5334/gh.874] - DOI - PMC - PubMed
Ambari 2024
    1. Ambari AM, Radi B, Dwiputra B, Arityanti D, Rikl T, Inggriani MP, et al. Adherence to penicillin treatment is essential for effective secondary prevention of rheumatic heart disease: a systematic review and meta-analysis. Annals of Medicine & Surgery 2024;84:4. - PMC - PubMed
Beaton 2012
    1. Beaton A, Okello E, Lwabi P, Mondo C, McCarter R, Sable C. Echocardiography screening for rheumatic heart disease in Ugandan schoolchildren. Circulation 2012;125(25):3127-32. [DOI: 10.1161/CIRCULATIONAHA.112.092312] - DOI - PubMed
Beaton 2017
    1. Beaton A, Aliku T, Dewyer A, Jacobs M, Jiang J, Longenecker CT, et al. Latent rheumatic heart disease: identifying the children at highest risk of unfavorable outcome. Circulation 2017;136(23):2233-44. [DOI: 10.1161/CIRCULATIONAHA.117.029936] - DOI - PMC - PubMed
Beaton 2019
    1. Beaton A, Okello E, Engelman D, Grobler A, Scheel A, DeWyer A, et al. Determining the impact of Benzathine penicillin G prophylaxis in children with latent rheumatic heart disease (GOAL trial): study protocol for a randomized controlled trial. American Heart Journal 2019;215:95-105. [DOI: 10.1016/j.ahj.2019.06.001] - DOI - PubMed
Campbell 2020
    1. Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ 2020;368:l6890. - PMC - PubMed
Carapetis 2016
    1. 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. - PMC - PubMed
Cilliers 2006
    1. Cilliers AM. Rheumatic fever and its management. British Medical Journal 2006;333(7579):1153-6. - PMC - PubMed
Cnattingius 2020
    1. Cnattingius S, Johansson S, Razaz N. Apgar score and risk of neonatal death among preterm infants. New England Journal of Medicine 2020;383(1):49–57. [DOI: 10.1056/NEJMoa1915075] - DOI - PubMed
Cupido 2021
    1. Cupido B, Zühlke L, Osman A, Dyk D, Sliwa K. Managing rheumatic heart disease in pregnancy: a practical evidence-based multidisciplinary approach. Canadian Journal of Cardiology 2021;37(12):2045–55. [DOI: 10.1016/j.cjca.2021.09.01] - DOI - PubMed
de Dassel 2019
    1. Dassel JL, Malik H, Ralph AP, Hardie K, Remenyi B, Francis JR. Four-weekly Benzathine Penicillin G provides inadequate protection against acute rheumatic fever in some children. American Journal of Tropical Medicine and Hygeine 2019;100(5):1118-20. [DOI: 10.4269/ajtmh.18-0907] - DOI - PMC - PubMed
Deeks 2011
    1. Deeks JJ, Higgins JPT, Altman DG. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JP, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Deeks 2022
    1. Deeks JJ, Higgins JP, Altman DG, editor(s). Chapter 10: Analysing data and undertaking meta-analyses. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane, 2022. Available from www.training.cochrane.org/handbook.
Dixit 2023
    1. Dixit J, Prinja S, Jyani G, Bahuguna P, Gupta A, Vijayvergiya R, et al. Evaluating efficiency and equity of prevention and control strategies for rheumatic fever and rheumatic heart disease in India: an extended cost-effectiveness analysis. Lancet Global Health 2023;11(3):e445-55. [DOI: 10.1016/S2214-109X(22)00552-6] - DOI - PubMed
Fønhus 2020
    1. Fønhus MS, Dalsbø TK. Secondary prophylaxis with penicillin for rheumatic fever or established rheumatic heart disease - a rapid review. www.fhi.no/globalassets/dokumenterfiler/global-helse/evidence/secondary-....
Gerber 2009
    1. Gerber MA, Baltimore RS, Eaton CB, Gewitz M, Rowley AH, Shulman ST, et al. Prevention of rheumatic fever and diagnosis and treatment of acute Streptococcal pharyngitis: a scientific statement from the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation 2009 ;119(11):1541-51. [DOI: 10.1161/CIRCULATIONAHA.109.191959] - DOI - PubMed
Gewitz 2015
    1. 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):1806–18. [DOI: 10.1161/CIR.0000000000000205] - DOI - PubMed
Ghamari 2022
    1. Ghamari SH, Abbasi-Kangevari M, Saeedi Moghaddam S, Aminorroaya A, Rezaei N, Shobeiri P, et al. Rheumatic heart disease is a neglected disease relative to its burden worldwide: findings from global burden of disease 2019. Journal of the American Heart Association 2022;11(13):e025284. [DOI: 10.1161/JAHA.122.025284] [PMCID: PMC9333364] [PMID: ] - DOI - PMC - PubMed
Google Translate [Computer program]
    1. Google Translate. Google, accessed 29 March 2024. Available at translate.google.co.uk/.
GRADEpro GDT [Computer program]
    1. GRADEpro GDT: GRADEpro Guideline Development Tool. Version accessed 10 December 2022. Hamilton (ON): McMaster University and Evidence Prime, 2024. Available at gradepro.org.
Higgins 2011a
    1. Higgins JPT, Green S, Altman DG, Sterne JAC (editors). Chapter 8: Assessing risk of bias in included studies. In: Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011] Available from www.handbook.cochrane.org edition. The Cochrane Collaboration, 2011.
Higgins 2011b
    1. Higgins JP, Deeks JJ, Altman DG, editor(s). Chatper 16: 16.9.5 Validity of methods of meta-analysis for rare events. Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Higgins 2022
    1. Higgins JP, Li T, Deeks JJ, editor(s). Chapter 6: Choosing effect measures and computing estimates of effect. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.2 (updated February 2022). Cochrane, 2022. Available from training.cochrane.org/handbook.
Higgins 2023a
    1. Higgins JP, Savović J, Page MJ, Elbers RG, Sterne JAC. Chapter 8: Assessing risk of bias in a randomized trial. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (updated August 2023). Cochrane, 2023. Available from www.training.cochrane.org/handbook.
Higgins 2023b
    1. Higgins JPT, Eldridge S, Li T. Chapter 23: Including variants on randomized trials. Available from www.training.cochrane.org/handbook.
Horton 2021
    1. Horton A, Gentles T, Remenyi B. Chapter 5 - clinical evaluation and diagnosis of rheumatic heart disease. In: Dougherty S, Carapetis J, Zühlke L, Wilson N, editors(s). Acute Rheumatic Fever and Rheumatic Heart Disease. Clayton, Australia: Elsevier, 2021:69-106. [DOI: 10.1016/B978-0-323-63982-8.00005-2] - DOI
Jaiteh 2021
    1. Jaiteh LES, Drammeh L, Anderson ST, Mendy J, Ceesay S, D'Alessandro U, et al. Rheumatic heart disease in The Gambia: clinical and valvular aspects at presentation and evolution under penicillin prophylaxis. BMC Cardiovascular Disorders 2021;21(1):503. [DOI: 10.1186/s12872-021-02308-8] - DOI - PMC - PubMed
Katzenellenbogen 2020
    1. Katzenellenbogen JM, Bond-Smith D, Ralph AP, Wilmot M, Marsh J, Bailie R, et al. Priorities for improved management of acute rheumatic fever and rheumatic heart disease: analysis of cross-sectional continuous quality improvement data in Aboriginal primary healthcare centres in Australia. Australian Health Review 2020;44(2):212-21. [DOI: 10.1071/AH19132] - DOI - PubMed
Kaya 2014
    1. Kaya A, Erkoçoğlu M, Senkon OG, Ekici FK, Toyran M, Çetin Iİ, et al. Confirmed penicillin allergy among patients receiving benzathine penicillin prophylaxis for acute rheumatic fever. Allergologia et Immunopathologia 2014;42(4):289-92. [DOI: 10.1016/j.aller.2012.12.007] - DOI - PubMed
Kevat 2017
    1. Kevat PM, Reeves BM, Ruben AR, Gunnarsson R. Adherence to secondary prophylaxis for acute rheumatic fever and rheumatic heart disease: a systematic review. Current Cardiology Reviews 2017;13(2):155–66. [DOI: 10.2174/1573403X13666170116120828] - DOI - PMC - PubMed
Klein 2018
    1. Klein EY, Van Boeckel TP, Martinez EM, Pant S, Gandra S, Levin SA, et al. Global increase and geographic convergence in antibiotic consumption between 2000 and 2015. Proceedings of the National Academy of Sciences 2018;115(15):E3463-70. [DOI: 10.1073/pnas.1717295115] - DOI - PMC - PubMed
Lefebvre 2022
    1. Lefebvre C, Glanville J, Briscoe S, Featherstone R, Littlewood A, Marshall C et al. Chapter 4: Searching for and selecting studies. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.3 (updated February 2022). Cochrane 2022. Available from www.training.cochrane.org/handbook.
Liberati 2009
    1. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta‐analyses of studies that evaluate health care interventions: explanation and elaboration. BMJ 2009;339:b2700. [DOI: 10.1136/bmj.b2700] - DOI - PMC - PubMed
Manji 2013
    1. Manji RA, Witt J, Tappia PS, Jung Y, Menkis AH, Ramjiawan B. Cost-effectiveness analysis of rheumatic heart disease prevention strategies. Expert Review of Pharmacoeconomics and Outcomes Research 2013;13:715-24. - PubMed
Manyemba 2002
    1. Manyemba J, Mayosi BM. Penicillin for secondary prevention of rheumatic fever. Cochrane Database of Systematic Reviews 2002, Issue 3. Art. No: CD002227. [DOI: 10.1002/14651858.CD002227] - DOI - PMC - PubMed
Marijon 2007
    1. Marijon E, Ou P, Celermajer DS, Ferreira B, Mocumbi AO, Jani D, et al. Prevalence of rheumatic heart disease detected by echocardiographic screening. New England Journal of Medicine 2007;357(5):470-76. [DOI: 10.1056/NEJMoa065085] - DOI - PubMed
Marijon 2021
    1. Marijon E, Mocumbi A, Narayanan K, Jouven X, Celermajer DS. Persistent burden and challenges of rheumatic heart disease. European Heart Journal 2021;42(34):3338-48. [DOI: 10.1093/eurheartj/ehab407] - DOI - PubMed
McKenzie 2023
    1. McKenzie JE, Brennan SE, Ryan RE, Thomson HJ, Johnston RV, Thomas J. Chapter 3: Defining the criteria for including studies and how they will be grouped for the synthesis. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (updated August 2023). Cochrane, 2023. Available from training.cochrane.org/handbook.
MECIR 2023
    1. Higgins JPT, Lasserson T, Thomas J, Flemyng E, Churchill R. Methodological Expectations of Cochrane Intervention Reviews. Cochrane: London, Version August 2023. https://community.cochrane.org/mecir-manual.
Minozzi 2022
    1. Minozzi S, Dwan K, Borrelli F, Filippini G. Reliability of the revised Cochrane risk-of-bias tool for randomised trials (RoB2) improved with the use of implementation instruction. Journal of Clinical Epidemiology 2022;141:99-105. [DOI: 10.1016/j.jclinepi.2021.09.021] - DOI - PubMed
Negi 2021
    1. Negi PC, Mahajan K, Kondal D, Asotra S, Sondhi S, Rao S, et al. Long term outcomes in patients with RF/RHD: eight-year follow-up of HP-RF/RHD (Himachal Pradesh Rheumatic Fever/Rheumatic Heart Disease) registry in a Northern Indian state. International Journal of Cardiology 2021;343:149-55. [DOI: 10.1016/j.ijcard.2021.09.014] - DOI - PubMed
Oliver 2021
    1. Oliver J, Bennett J, Thomas S, Zhang J, Pierse N, Moreland NJ, et al. Preceding group A streptococcus skin and throat infections are individually associated with acute rheumatic fever: evidence from New Zealand. BMJ Global Health 2021;6(12):e007038. [DOI: 10.1136/bmjgh-2021-007038] - DOI - PMC - PubMed
Ouzzani 2016
    1. Ouzzani M, Hammady H, Fedorowi Z, Elmagarmid A. Rayyan — a web and mobile app for systematic reviews. Systematic Reviews 2016;5:210. [DOI: 10.1186/s13643-016-0384-4] - DOI - PMC - PubMed
Pelone 2024
    1. Pelone F, Kwok B, Ahmed S, Kilic Y, Ali SA, Ahmed N, et al. Local anaesthetic to reduce injection pain in patients who are prescribed intramuscular benzathine penicillin G: a systematic review and meta-analysis. eClinicalMedicine 2024;76:102817. - PMC - PubMed
Ralph 2016
    1. Ralph AP, Read C, Johnston V, Dassel JL, Bycroft K, Mitchell A, et al. Improving delivery of secondary prophylaxis for rheumatic heart disease in remote Indigenous communities: study protocol for a stepped-wedge randomised trial. Trials 2016;17:51. [DOI: 10.1186/s13063-016-1166-y] - DOI - PMC - PubMed
Ralph 2021
    1. 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):220-7. [DOI: 10.5694/mja2.50851] - DOI - PubMed
Reeves 2011
    1. Reeves BM, Kado J, Brook M. High prevalence of rheumatic heart disease in Fiji detected by echocardiography screening. Journal of Paediatric Child Health 2011;47:473-8. - PubMed
Reeves 2023
    1. Reeves BC, Deeks JJ, Higgins JPT, Shea B, Tugwell P, Wells GA. Chapter 24: Including non-randomized studies on intervention effects. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (updated August 2023). Cochrane, 2023. Available from training.cochrane.org/handbook.
Reményi 2012
    1. Reményi B, Wilson N, Steer A, Ferreira B, Kado J, Kumar K, et al. World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease - an evidence-based guideline. Nature Reviews Cardiology 2012 ;9(5):297-309. [DOI: 10.1038/nrcardio.2012.7] - DOI - PMC - PubMed
RevMan 2022 [Computer program]
    1. Review Manager Web (RevMan Web). Version 4.12.0. The Cochrane Collaboration, 2022. Available at revman.cochrane.org.
Roberts 2013
    1. Roberts KV, Brown AD, Maguire GP, Atkinson DN, Carapetis JR. Utility of auscultatory screening for detecting rheumatic heart disease in high-risk children in Australia's Northern Territory. Medical Journal of Australia 2013;199(3):196-9. [DOI: 10.5694/mja13.10520] - DOI - PubMed
Rwebembera 2023
    1. Rwebembera J, Marangou J, Mwita JC, Mocumbi AO, Mota C, Okello E, et al. 2023 World Heart Federation guidelines for the echocardiographic diagnosis of rheumatic heart disease. Nature Reviews Cardiology 2023;21:250-63. - PubMed
Rémond 2016
    1. Rémond MG, Coyle ME, Mills JE, Maguire GP. Approaches to improving adherence to secondary prophylaxis for rheumatic fever and rheumatic heart disease: a literature review with a global perspective. Cardiology in Review 2016;24(2):94-8. [DOI: 10.1097/CRD.0000000000000065] - DOI - PubMed
Sackett 1996
    1. Sackett DL, Deeks JJ, Altman DG. Down with odds ratios! Evidence-Based Medicine 1996;1(6):164–66. [URL: ebm.bmj.com/content/ebmed/1/6/164.full.pdf]
Schünemann 2011
    1. Schünemann HJ, Oxman AD, Higgins JH, Vist GE, Glasziou P, Guyatt GH. Chapter 11: 11.5.6.4 Illustrative comparative risks 2: corresponding risk (with experimental intervention). In: Higgins JH, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from training.cochrane.org/handbook/archive/v5.1/.
Schünemann 2013
    1. Schünemann H, Brożek J, Guyatt G, Oxman A, editor(s). Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach (updated October 2013). GRADE Working Group, 2013. Available from gdt.guidelinedevelopment.org/app/handbook/handbook.html.
Schünemann 2023
    1. Schünemann HJ, Higgins JP, Vist GE, Glasziou P, Akl EA, Skoetz N, et al. Chapter 14: Completing ‘Summary of findings’ tables and grading the certainty of the evidence. In: Higgins JP, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA, editor(s). Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (updated August 2023). Cochrane, 2023. Available from www.training.cochrane.org/handbook.
Seckeler 2011
    1. Seckeler MD, Hoke TR. The worldwide epidemiology of acute rheumatic fever and rheumatic heart disease. Clinical Epidemiology 2011;3:67-84. [DOI: 10.2147/CLEP.S12977] - DOI - PMC - PubMed
Shimanda 2024
    1. Shimanda PP, Shumba TW, Brunström M, Iipinge SN, Söderberg S, Lindholm L, Norström F. Preventive interventions to reduce the burden of rheumatic heart disease in populations at risk: a systematic review. Journal of the American Heart Association 2024;13(5):e032442. - PMC - PubMed
Siegel 1961
    1. Siegel AC, Johnson EE, Stollerman GH. Controlled studies of streptococcal pharyngitis in a pediatric population — factors related to the attack rate of rheumatic fever. New England Journal of Medicine 1961;265:559-66.
Sinclair 1994
    1. Sinclair JC, Bracken MB. Clinically useful measures of effect in binary analyses of randomized trials. Journal of Clinical Epidemiology 1994;47(8):881-9. [DOI: 10.1016/0895-4356(94)90191-0] - DOI - PubMed
Spinetto 2011
    1. Spinetto H, Lennon D, Horsburgh M. Rheumatic fever recurrence prevention: a nurse-led programme of 28-day penicillin in an area of high endemnicity. Journal of Paediatric Child Health 2011;47(4):228-34. - PubMed
Stata [Computer program]
    1. Stata. Version 17. College Station, TX, USA: StataCorp LLC, 2021. Available at www.stata.com.
Torres 2021
    1. Torres RPA, Torres RFA, Crombrugghe G, Moraes da Silva SP, Cordeiro SLV, Bosi KA, et al. Improvement of rheumatic valvular heart disease in patients undergoing prolonged antibiotic prophylaxis. Frontiers in Cardiovascular Medicine 2021;8:676098. [DOI: 10.3389/fcvm.2021.676098] - DOI - PMC - PubMed
Ubels 2020
    1. Ubels J, Sable C, Beaton AZ, Nunes MCP, Oliveira KKB, Rabelo LC, et al, PROVAR+ (Programa de Rastreament O da VAlvopatia Reumática e Outras Doenças Cardiovasculares) investigators. Cost-effectiveness of rheumatic heart disease echocardiographic screening in Brazil: data from the PROVAR+ study: cost-effectiveness of RHD screening in Brazil. Global Heart 2020;15:18. - PMC - PubMed
Watkins 2017
    1. Watkins DA, Johnson CO, Colquhoun SM, Karthikeyan G, Beaton A, Bukhman G, et al. Global, regional, and national burden of rheumatic heart disease, 1990-2015. New England Journal of Medicine 2017;377(8):713-22. [DOI: 10.1056/NEJMoa1603693] - DOI - PubMed
WHO Expert Consultation 2001
    1. WHO Expert Consultation 2001. WHO technical report series: Rheumatic fever and rheumatic heart disease. WHO Technical Report Serie 2001. [WEBPAGE: https://iris.who.int/bitstream/handle/10665/42898/WHO_TRS_923.pdf]
Yip 2022
    1. Yip DW, Gerriets V. Penicillin. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022. [PMID: ] - PubMed
Zühlke 2013
    1. Zühlke LJ, Karthikeyan G. Primary prevention for rheumatic fever: progress, obstacles, and opportunities. Global Heart 2013;8(3):221-6. [DOI: 10.1016/j.gheart.2013.08.005] - DOI - PubMed
Zühlke 2015
    1. Zühlke L, Engel ME, Karthikeyan G, Rangarajan S, Mackie P, Cupido B, et al. Characteristics, complications, and gaps in evidence-based interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY study). European Heart Journal 2015;36(18):1115-22a. [DOI: 10.1093/eurheartj/ehu449] - DOI - PMC - PubMed
Çiftel 2015
    1. Çiftel M, Süleyman A, Ertuğ H. Penicillin therapy in children with acute rheumatic fever: side effects, malpractice and anaphylactic reactions. Journal of Current Pediatrics 2015;13:31-9. [DOI: 10.4274/jcp.46330] - DOI

References to other published versions of this review

Pelone 2022
    1. Pelone F, Mahmood A, Shokraneh F, Ahmed N, Mokhtar H, Cassandra M, et al. Long-term antibiotic treatment for secondary prevention of rheumatic fever recurrence and progression to rheumatic heart disease. www.crd.york.ac.uk/prospero/display_record.php?RecordID=342422 (first posted 11 July 2022).

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