Effectiveness of Systematic Echocardiographic Screening for Rheumatic Heart Disease in Nepalese Schoolchildren: A Cluster Randomized Clinical Trial

Abstract

Importance: Echocardiographic screening allows for early detection of subclinical stages of rheumatic heart disease among children in endemic regions.

Objective: To investigate the effectiveness of systematic echocardiographic screening in combination with secondary antibiotic prophylaxis on the prevalence of rheumatic heart disease.

Design, setting, and participants: This cluster randomized clinical trial included students 9 to 16 years of age attending public and private schools in urban and rural areas of the Sunsari district in Nepal that had been randomly selected on November 17, 2012. Echocardiographic follow-up was performed between January 7, 2016, and January 3, 2019.

Interventions: In the experimental group, children underwent systematic echocardiographic screening followed by secondary antibiotic prophylaxis in case they had echocardiographic evidence of latent rheumatic heart disease. In the control group, children underwent no echocardiographic screening.

Main outcomes and measures: Prevalence of the composite of definite or borderline rheumatic heart disease according to the World Heart Federation criteria in experimental and control schools as assessed 4 years after intervention.

Results: A total of 35 schools were randomized to the experimental group (n = 19) or the control group (n = 16). After a median of 4.3 years (interquartile range [IQR], 4.0-4.5 years), 17 of 19 schools in the experimental group (2648 children; median age at follow-up, 12.1 years; IQR, 10.3-12.5 years; 1308 [49.4%] male) and 15 of 16 schools in the control group (1325 children; median age at follow-up, 10.6 years; IQR, 10.0-12.5 years; 682 [51.5%] male) underwent echocardiographic follow-up. The prevalence of definite or borderline rheumatic heart disease was 10.8 per 1000 children (95% CI, 4.7-24.7) in the control group and 3.8 per 1000 children (95% CI, 1.5-9.8) in the experimental group (odds ratio, 0.34; 95% CI, 0.11-1.07; P = .06). The prevalence in the experimental group at baseline had been 12.9 per 1000 children (95% CI, 9.2-18.1). In the experimental group, the odds ratio of definite or borderline rheumatic heart disease at follow-up vs baseline was 0.29 (95% CI, 0.13-0.65; P = .008).

Conclusions and relevance: School-based echocardiographic screening in combination with secondary antibiotic prophylaxis in children with evidence of latent rheumatic heart disease may be an effective strategy to reduce the prevalence of definite or borderline rheumatic heart disease in endemic regions.

Trial registration: ClinicalTrials.gov Identifier: NCT01550068.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Jüni reported receiving grants from Canadian Institutes of Health Research (this is a grant to the institution under the Canada Research Chairs Program), AstraZeneca, Biotronik, Biosensors International, Eli Lilly, The Medicines Company, and Appili Therapeutics outside the submitted work; honoraria from Amgen, Ava, and Fresenius; serves as unpaid member of the steering group of trials funded by AstraZeneca, Biotronik, Biosensors International, St. Jude Medical, and The Medicines Company; and has participated in advisory boards and/or consulting with Amgen, Ava, and Fresenius. Dr Pilgrim reported receiving grants from Biotronik, Boston Scientific, and Edwards Lifesciences; personal fees from Biotronik, Boston Scientific, and HighLife SAS; and nonfinancial support from Medtronic outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Study Flowchart According to the CONSORT Statement

Figure 2.. Prevalence of Definite and Borderline Rheumatic Heart Disease in Experimental Schools and Control Schools

Error bars indicate 95% CIs.

Figure 3.. Stratified Analyses of Definite or Borderline Rheumatic Heart Disease (RHD) Across Major Subgroups

All subgroup analyses were post hoc. Odds ratios (ORs) (95% CIs) are estimated using the Mantel-Cox method with 2-sided P values from the log-rank test. P values for interactions were obtained with approximate χ2 tests for unequal ORs in the subgroups.

Figure 4.. Longitudinal Data of Children in the Experimental Group With Definite Rheumatic Heart Disease (RHD) Who Underwent Follow-up

Orange lines indicate children in the eligible age range who underwent follow-up in the setting of the auxiliary cross-sectional examination; blue lines, children in the eligible age range who no longer attended (the same) school.