Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case

Background Echocardiographic screening for detection of latent RHD has shown potential as a strategy to decrease the burden of disease. However, further research is needed to determine optimal implementation strategies. RHD results from a complex interplay between environment and host susceptibility. Family members share both and relatives of children with latent RHD may represent a high-risk group. The objective of this study was to use echocardiographic family screening to determine the relative risk of RHD among first-degree relatives of children with latent RHD compared to the risk in first-degree relatives of healthy peers. Methodology/Principal Findings Previous school-based screening data were used to identify RHD positive children and RHD negative peers. All first-degree relatives ≥ 5 years were invited for echocardiography screening (2012 World Heart Federation Criteria). Sixty RHD positive cases (30 borderline/30 definite RHD) and 67 RHD negative cases were recruited. A total of 455/667 (68%) family members were screened. Definite RHD was more common in childhood siblings of RHD positive compared to RHD negative (p = 0.05). Children with any RHD were 4.5 times as likely to have a sibling with definite RHD, a risk that increased to 5.6 times when considering only cases with definite RHD. Mothers of RHD positive and RHD negative cases had an unexpectedly high rate of latent RHD (9.3%). Conclusions/Significance Siblings of RHD positive cases with RHD are more likely to have definite RHD and the relative risk is highest if the index case has definite RHD. Future screening programs should consider implementation of sibling screening following detection of an RHD positive child. Larger screening studies of adults are needed, as data on prevalence of latent RHD outside of childhood are sparse. Future studies should prioritize implementation research to answer questions of how RHD screening can best be integrated into existing healthcare structures, ensuring practical and sustainable screening programs.
Author Summary Rheumatic heart disease (RHD) affects at least 33 million people, most of who live in low-resource environments. RHD is a cumulative process and there exists a latent period between early valve damage and presentation with symptoms. Echocardiographic screening (ultrasound of the heart) has proven highly sensitive for latent RHD detection, but implementation research is needed to effectively develop sustainable public health strategies. Critical to this research is determining whom to screen. As family members have both a shared environment and shared genetic susceptibility, they may represent a high-risk group that could be targeted once a case of RHD is identified. We conducted an echocardiographic family screening study to determine the risk of RHD in families with and without an RHD positive child and found that siblings of children with latent RHD are more likely to have latent RHD themselves. Our data suggest that siblings may represent a particularly high-risk group that could be targeted for echocardiographic screening. Future studies are needed to answer questions of how RHD screening can best be integrated into existing healthcare structures, ensuring practical and sustainable RHD screening programs.