Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

Andrea Beaton; Emmy Okello; Joselyn Rwebembera; Anneke Grobler; Daniel Engelman; Juliet Alepere; Lesley Canales; Jonathan Carapetis; Alyssa DeWyer; Peter Lwabi; Mariana Mirabel; Ana O. Mocumbi; Meghna Murali; Miriam Nakitto; Emma Ndagire; Maria C. P. Nunes; Isaac O. Omara; Rachel Sarnacki; Amy Scheel; Nigel Wilson; Meghan Zimmerman; Liesl Zuhlke; Ganesan Karthikeyan; Craig A. Sable; Andrew C. Steer

doi:10.1056/NEJMoa2102074

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

Andrea Beaton, Emmy Okello, Joselyn Rwebembera, Anneke Grobler, Daniel Engelman, Juliet Alepere, Lesley Canales, Jonathan Carapetis, Alyssa DeWyer, Peter Lwabi, Mariana Mirabel, Ana O. Mocumbi, Meghna Murali, Miriam Nakitto, Emma Ndagire, Maria C. P. Nunes, Isaac O. Omara, Rachel Sarnacki, Amy Scheel, Nigel WilsonMeghan Zimmerman, Liesl Zuhlke, Ganesan Karthikeyan, Craig A. Sable, Andrew C. Steer

UWA Centre for Child Health Research (affiliated with the Telethon Kids Institute)

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

BACKGROUND

Rheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.

METHODS

We conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.

RESULTS

Among 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; P

CONCLUSIONS

Among children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended.

Original language	English
Pages (from-to)	230-240
Number of pages	11
Journal	New England Journal of Medicine
Volume	386
Issue number	3
DOIs	https://doi.org/10.1056/NEJMoa2102074
Publication status	Published - 20 Jan 2022

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Beaton, A., Okello, E., Rwebembera, J., Grobler, A., Engelman, D., Alepere, J., Canales, L., Carapetis, J., DeWyer, A., Lwabi, P., Mirabel, M., Mocumbi, A. O., Murali, M., Nakitto, M., Ndagire, E., Nunes, M. C. P., Omara, I. O., Sarnacki, R., Scheel, A., ... Steer, A. C. (2022). Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease. New England Journal of Medicine, 386(3), 230-240. https://doi.org/10.1056/NEJMoa2102074

@article{f920ea61bcde4eb59f2d0355cdbd2c24,

title = "Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease",

abstract = "BACKGROUNDRheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.METHODSWe conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.RESULTSAmong 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; PCONCLUSIONSAmong children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended.",

keywords = "SCIENTIFIC STATEMENT, CLINICAL-OUTCOMES, FOLLOW-UP, FEVER, PREVENTION, PREVALENCE, PENICILLIN, DIAGNOSIS, CHILDREN, ECHOCARDIOGRAPHY",

author = "Andrea Beaton and Emmy Okello and Joselyn Rwebembera and Anneke Grobler and Daniel Engelman and Juliet Alepere and Lesley Canales and Jonathan Carapetis and Alyssa DeWyer and Peter Lwabi and Mariana Mirabel and Mocumbi, {Ana O.} and Meghna Murali and Miriam Nakitto and Emma Ndagire and Nunes, {Maria C. P.} and Omara, {Isaac O.} and Rachel Sarnacki and Amy Scheel and Nigel Wilson and Meghan Zimmerman and Liesl Zuhlke and Ganesan Karthikeyan and Sable, {Craig A.} and Steer, {Andrew C.}",

year = "2022",

month = jan,

day = "20",

doi = "10.1056/NEJMoa2102074",

language = "English",

volume = "386",

pages = "230--240",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "MASSACHUSETTS MEDICAL SOC",

number = "3",

}

Beaton, A, Okello, E, Rwebembera, J, Grobler, A, Engelman, D, Alepere, J, Canales, L, Carapetis, J, DeWyer, A, Lwabi, P, Mirabel, M, Mocumbi, AO, Murali, M, Nakitto, M, Ndagire, E, Nunes, MCP, Omara, IO, Sarnacki, R, Scheel, A, Wilson, N, Zimmerman, M, Zuhlke, L, Karthikeyan, G, Sable, CA & Steer, AC 2022, 'Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease', New England Journal of Medicine, vol. 386, no. 3, pp. 230-240. https://doi.org/10.1056/NEJMoa2102074

TY - JOUR

T1 - Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

AU - Beaton, Andrea

AU - Okello, Emmy

AU - Rwebembera, Joselyn

AU - Grobler, Anneke

AU - Engelman, Daniel

AU - Alepere, Juliet

AU - Canales, Lesley

AU - Carapetis, Jonathan

AU - DeWyer, Alyssa

AU - Lwabi, Peter

AU - Mirabel, Mariana

AU - Mocumbi, Ana O.

AU - Murali, Meghna

AU - Nakitto, Miriam

AU - Ndagire, Emma

AU - Nunes, Maria C. P.

AU - Omara, Isaac O.

AU - Sarnacki, Rachel

AU - Scheel, Amy

AU - Wilson, Nigel

AU - Zimmerman, Meghan

AU - Zuhlke, Liesl

AU - Karthikeyan, Ganesan

AU - Sable, Craig A.

AU - Steer, Andrew C.

PY - 2022/1/20

Y1 - 2022/1/20

N2 - BACKGROUNDRheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.METHODSWe conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.RESULTSAmong 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; PCONCLUSIONSAmong children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended.

AB - BACKGROUNDRheumatic heart disease affects more than 40.5 million people worldwide and results in 306,000 deaths annually. Echocardiographic screening detects rheumatic heart disease at an early, latent stage. Whether secondary antibiotic prophylaxis is effective in preventing progression of latent rheumatic heart disease is unknown.METHODSWe conducted a randomized, controlled trial of secondary antibiotic prophylaxis in Ugandan children and adolescents 5 to 17 years of age with latent rheumatic heart disease. Participants were randomly assigned to receive either injections of penicillin G benzathine (also known as benzathine benzylpenicillin) every 4 weeks for 2 years or no prophylaxis. All the participants underwent echocardiography at baseline and at 2 years after randomization. Changes from baseline were adjudicated by a panel whose members were unaware of the trial-group assignments. The primary outcome was echocardiographic progression of latent rheumatic heart disease at 2 years.RESULTSAmong 102,200 children and adolescents who had screening echocardiograms, 3327 were initially assessed as having latent rheumatic heart disease, and 926 of the 3327 subsequently received a definitive diagnosis on the basis of confirmatory echocardiography and were determined to be eligible for the trial. Consent or assent for participation was provided for 916 persons, and all underwent randomization; 818 participants were included in the modified intention-to-treat analysis, and 799 (97.7%) completed the trial. A total of 3 participants (0.8%) in the prophylaxis group had echocardiographic progression at 2 years, as compared with 33 (8.2%) in the control group (risk difference, -7.5 percentage points; 95% confidence interval, -10.2 to -4.7; PCONCLUSIONSAmong children and adolescents 5 to 17 years of age with latent rheumatic heart disease, secondary antibiotic prophylaxis reduced the risk of disease progression at 2 years. Further research is needed before the implementation of population-level screening can be recommended.

KW - SCIENTIFIC STATEMENT

KW - CLINICAL-OUTCOMES

KW - FOLLOW-UP

KW - FEVER

KW - PREVENTION

KW - PREVALENCE

KW - PENICILLIN

KW - DIAGNOSIS

KW - CHILDREN

KW - ECHOCARDIOGRAPHY

U2 - 10.1056/NEJMoa2102074

DO - 10.1056/NEJMoa2102074

M3 - Article

C2 - 34767321

VL - 386

SP - 230

EP - 240

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 3

ER -

Secondary Antibiotic Prophylaxis for Latent Rheumatic Heart Disease

Abstract

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