Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case
Identifieur interne : 003829 ( Ncbi/Merge ); précédent : 003828; suivant : 003830Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case
Auteurs : Twalib Aliku [Ouganda] ; Craig Sable [États-Unis] ; Amy Scheel [États-Unis] ; Alison Tompsett [États-Unis] ; Peter Lwabi [Ouganda] ; Emmy Okello [Ouganda] ; Robert Mccarter [États-Unis] ; Marshall Summar [États-Unis] ; Andrea Beaton [États-Unis]Source :
- PLoS Neglected Tropical Diseases [ 1935-2727 ] ; 2016.
Abstract
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.
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%).
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.
Url:
DOI: 10.1371/journal.pntd.0004727
PubMed: 27294545
PubMed Central: 4905680
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<front><div type="abstract" xml:lang="en"><sec id="sec001"><title>Background</title>
<p>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.</p>
</sec>
<sec id="sec002"><title>Methodology/Principal Findings</title>
<p>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%).</p>
</sec>
<sec id="sec003"><title>Conclusions/Significance</title>
<p>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.</p>
</sec>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS Negl Trop Dis</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosntds</journal-id>
<journal-title-group><journal-title>PLoS Neglected Tropical Diseases</journal-title>
</journal-title-group>
<issn pub-type="ppub">1935-2727</issn>
<issn pub-type="epub">1935-2735</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">27294545</article-id>
<article-id pub-id-type="pmc">4905680</article-id>
<article-id pub-id-type="doi">10.1371/journal.pntd.0004727</article-id>
<article-id pub-id-type="publisher-id">PNTD-D-16-00039</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Cardiovascular Medicine</subject>
<subj-group><subject>Cardiovascular Diseases</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Social Sciences</subject>
<subj-group><subject>Sociology</subject>
<subj-group><subject>Human Families</subject>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Diagnostic Medicine</subject>
<subj-group><subject>Diagnostic Radiology</subject>
<subj-group><subject>Ultrasound Imaging</subject>
<subj-group><subject>Echocardiography</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Research and Analysis Methods</subject>
<subj-group><subject>Imaging Techniques</subject>
<subj-group><subject>Diagnostic Radiology</subject>
<subj-group><subject>Ultrasound Imaging</subject>
<subj-group><subject>Echocardiography</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Radiology and Imaging</subject>
<subj-group><subject>Diagnostic Radiology</subject>
<subj-group><subject>Ultrasound Imaging</subject>
<subj-group><subject>Echocardiography</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and health sciences</subject>
<subj-group><subject>Infectious diseases</subject>
<subj-group><subject>Bacterial diseases</subject>
<subj-group><subject>Group A streptococcal infection</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Biology and Life Sciences</subject>
<subj-group><subject>Genetics</subject>
<subj-group><subject>Genetics of Disease</subject>
<subj-group><subject>Genetic Predisposition</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>People and Places</subject>
<subj-group><subject>Geographical Locations</subject>
<subj-group><subject>Africa</subject>
<subj-group><subject>Uganda</subject>
</subj-group>
</subj-group>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Medicine and Health Sciences</subject>
<subj-group><subject>Public and Occupational Health</subject>
</subj-group>
</subj-group>
<subj-group subj-group-type="Discipline-v3"><subject>Social Sciences</subject>
<subj-group><subject>Sociology</subject>
<subj-group><subject>Education</subject>
<subj-group><subject>Schools</subject>
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</subj-group>
</article-categories>
<title-group><article-title>Targeted Echocardiographic Screening for Latent Rheumatic Heart Disease in Northern Uganda: Evaluating Familial Risk Following Identification of an Index Case</article-title>
<alt-title alt-title-type="running-head">Familial Risk of Latent Rheumatic Heart Disease</alt-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Aliku</surname>
<given-names>Twalib</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sable</surname>
<given-names>Craig</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Scheel</surname>
<given-names>Amy</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tompsett</surname>
<given-names>Alison</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lwabi</surname>
<given-names>Peter</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Okello</surname>
<given-names>Emmy</given-names>
</name>
<xref ref-type="aff" rid="aff003"><sup>3</sup>
</xref>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McCarter</surname>
<given-names>Robert</given-names>
</name>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Summar</surname>
<given-names>Marshall</given-names>
</name>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Beaton</surname>
<given-names>Andrea</given-names>
</name>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor001">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>School of Medicine, Gulu University, Gulu, Uganda</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>Division of Cardiology, Children’s National Health System, Washington, District of Columbia, United States of America</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Uganda Heart Institute, Kampala, Uganda</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<addr-line>School of Medicine, Makerere University, Kampala, Uganda</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<addr-line>Division of Biostatistics and Informatics, Children’s National Health System, Washington, District of Columbia, United States of America</addr-line>
</aff>
<aff id="aff006"><label>6</label>
<addr-line>Division of Genetics and Metabolism, Children’s National Health System, Washington, District of Columbia, United States of America</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Vinetz</surname>
<given-names>Joseph M.</given-names>
</name>
<role>Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>University of California San Diego School of Medicine, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="conflict" id="coi001"><p>The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: TA CS AS PL EO MS AB. Performed the experiments: TA AS AT AB. Analyzed the data: TA CS RM AB. Wrote the paper: TA CS AS AT PL EO MS RM AB.</p>
</fn>
<corresp id="cor001">* E-mail: <email>abeaton@childrensnational.org</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>13</day>
<month>6</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="collection"><month>6</month>
<year>2016</year>
</pub-date>
<volume>10</volume>
<issue>6</issue>
<elocation-id>e0004727</elocation-id>
<history><date date-type="received"><day>11</day>
<month>1</month>
<year>2016</year>
</date>
<date date-type="accepted"><day>2</day>
<month>5</month>
<year>2016</year>
</date>
</history>
<permissions><copyright-statement>© 2016 Aliku et al</copyright-statement>
<copyright-year>2016</copyright-year>
<copyright-holder>Aliku et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License</ext-link>
, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:href="pntd.0004727.pdf"></self-uri>
<abstract><sec id="sec001"><title>Background</title>
<p>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.</p>
</sec>
<sec id="sec002"><title>Methodology/Principal Findings</title>
<p>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%).</p>
</sec>
<sec id="sec003"><title>Conclusions/Significance</title>
<p>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.</p>
</sec>
</abstract>
<abstract abstract-type="summary"><title>Author Summary</title>
<p>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.</p>
</abstract>
<funding-group><award-group id="award001"><funding-source><institution>Gift of Life International/Rotary International</institution>
</funding-source>
<principal-award-recipient><name><surname>Aliku</surname>
<given-names>Twalib</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award002"><funding-source><institution>Children's Research Institute</institution>
</funding-source>
<award-id>UL1TR000075 and KL2TR000076 from the NIH National Center for Advancing Translational Sciences</award-id>
<principal-award-recipient><name><surname>Beaton</surname>
<given-names>Andrea</given-names>
</name>
</principal-award-recipient>
</award-group>
<award-group id="award003"><funding-source><institution-wrap><institution-id institution-id-type="funder-id">http://dx.doi.org/10.13039/100004313</institution-id>
<institution>General Electric</institution>
</institution-wrap>
</funding-source>
<principal-award-recipient><name><surname>Beaton</surname>
<given-names>Andrea</given-names>
</name>
</principal-award-recipient>
</award-group>
<funding-statement>This project was supported by Award Nos. UL1TR000075 and KL2TR000076 from the NIH National Center for Advancing Translational Sciences (AB). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Center for Advancing Translational Sciences or the National Institutes of Health. This study was also funded in part by grants from Rotary International/Gift of Life International (AB,CS) and General Electric who provided the echocardiography equipment used in this study (AB, CS). The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement>
</funding-group>
<counts><fig-count count="2"></fig-count>
<table-count count="4"></table-count>
<page-count count="11"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
<affiliations><list><country><li>Ouganda</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="Ouganda"><noRegion><name sortKey="Aliku, Twalib" sort="Aliku, Twalib" uniqKey="Aliku T" first="Twalib" last="Aliku">Twalib Aliku</name>
</noRegion>
<name sortKey="Lwabi, Peter" sort="Lwabi, Peter" uniqKey="Lwabi P" first="Peter" last="Lwabi">Peter Lwabi</name>
<name sortKey="Okello, Emmy" sort="Okello, Emmy" uniqKey="Okello E" first="Emmy" last="Okello">Emmy Okello</name>
<name sortKey="Okello, Emmy" sort="Okello, Emmy" uniqKey="Okello E" first="Emmy" last="Okello">Emmy Okello</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Sable, Craig" sort="Sable, Craig" uniqKey="Sable C" first="Craig" last="Sable">Craig Sable</name>
</noRegion>
<name sortKey="Beaton, Andrea" sort="Beaton, Andrea" uniqKey="Beaton A" first="Andrea" last="Beaton">Andrea Beaton</name>
<name sortKey="Mccarter, Robert" sort="Mccarter, Robert" uniqKey="Mccarter R" first="Robert" last="Mccarter">Robert Mccarter</name>
<name sortKey="Scheel, Amy" sort="Scheel, Amy" uniqKey="Scheel A" first="Amy" last="Scheel">Amy Scheel</name>
<name sortKey="Summar, Marshall" sort="Summar, Marshall" uniqKey="Summar M" first="Marshall" last="Summar">Marshall Summar</name>
<name sortKey="Tompsett, Alison" sort="Tompsett, Alison" uniqKey="Tompsett A" first="Alison" last="Tompsett">Alison Tompsett</name>
</country>
</tree>
</affiliations>
</record>
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