Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers
Background The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa. Methods A 3‐year targeted sickle cell screening project in Uganda was des...
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| Veröffentlicht in: | Pediatric blood & cancer 2019-08, Vol.66 (8), p.e27807-n/a |
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| creator | Kiyaga, Charles Hernandez, Arielle G. Ssewanyana, Isaac Schaefer, Beverly A. McElhinney, Kathryn E. Ndeezi, Grace Howard, Thad A. Ndugwa, Christopher M. Ware, Russell E. Aceng, Jane R. |
| description | Background
The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa.
Methods
A 3‐year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high‐burden districts, (2) document the prevalence among HIV‐exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co‐inheritance of known genetic modifiers of sickle cell disease.
Results
A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid‐Northern districts, in both HIV‐exposed and nonexposed children. Based on crude birth‐rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40‐0.64, P |
| doi_str_mv | 10.1002/pbc.27807 |
| format | Article |
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The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa.
Methods
A 3‐year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high‐burden districts, (2) document the prevalence among HIV‐exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co‐inheritance of known genetic modifiers of sickle cell disease.
Results
A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid‐Northern districts, in both HIV‐exposed and nonexposed children. Based on crude birth‐rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40‐0.64, P < .0001). Alpha‐thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution.
Conclusions
High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district‐level comprehensive care programs.</description><identifier>ISSN: 1545-5009</identifier><identifier>EISSN: 1545-5017</identifier><identifier>DOI: 10.1002/pbc.27807</identifier><identifier>PMID: 31094093</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>alpha-Thalassemia - complications ; alpha-Thalassemia - diagnosis ; alpha-Thalassemia - epidemiology ; alpha-Thalassemia - genetics ; Anemia, Sickle Cell - complications ; Anemia, Sickle Cell - diagnosis ; Anemia, Sickle Cell - epidemiology ; Anemia, Sickle Cell - genetics ; Child, Preschool ; Children ; Comorbidity ; Exposure ; Female ; Follow-Up Studies ; Genes, Modifier ; Glucosephosphate dehydrogenase ; Glucosephosphate Dehydrogenase Deficiency - complications ; Glucosephosphate Dehydrogenase Deficiency - diagnosis ; Glucosephosphate Dehydrogenase Deficiency - epidemiology ; Glucosephosphate Dehydrogenase Deficiency - genetics ; Hematology ; Heredity ; HIV ; HIV - genetics ; HIV - isolation & purification ; HIV Infections - complications ; HIV Infections - diagnosis ; HIV Infections - epidemiology ; HIV Infections - genetics ; Human immunodeficiency virus ; Humans ; Infant ; Infant, Newborn ; Infants ; Male ; Mass Screening - methods ; newborn screening ; Oncology ; Pediatrics ; Phenotypes ; Prevalence ; Prognosis ; Prospective Studies ; sickle cell anemia ; Sickle cell disease ; Thalassemia ; Uganda</subject><ispartof>Pediatric blood & cancer, 2019-08, Vol.66 (8), p.e27807-n/a</ispartof><rights>2019 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3537-7535a094cb4b3a9a1f04ec208c354352f7971d5588cf804c558a259593a2ddc63</citedby><cites>FETCH-LOGICAL-c3537-7535a094cb4b3a9a1f04ec208c354352f7971d5588cf804c558a259593a2ddc63</cites><orcidid>0000-0001-9582-0594 ; 0000-0002-3079-4695</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpbc.27807$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpbc.27807$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31094093$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kiyaga, Charles</creatorcontrib><creatorcontrib>Hernandez, Arielle G.</creatorcontrib><creatorcontrib>Ssewanyana, Isaac</creatorcontrib><creatorcontrib>Schaefer, Beverly A.</creatorcontrib><creatorcontrib>McElhinney, Kathryn E.</creatorcontrib><creatorcontrib>Ndeezi, Grace</creatorcontrib><creatorcontrib>Howard, Thad A.</creatorcontrib><creatorcontrib>Ndugwa, Christopher M.</creatorcontrib><creatorcontrib>Ware, Russell E.</creatorcontrib><creatorcontrib>Aceng, Jane R.</creatorcontrib><title>Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers</title><title>Pediatric blood & cancer</title><addtitle>Pediatr Blood Cancer</addtitle><description>Background
The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa.
Methods
A 3‐year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high‐burden districts, (2) document the prevalence among HIV‐exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co‐inheritance of known genetic modifiers of sickle cell disease.
Results
A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid‐Northern districts, in both HIV‐exposed and nonexposed children. Based on crude birth‐rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40‐0.64, P < .0001). Alpha‐thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution.
Conclusions
High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district‐level comprehensive care programs.</description><subject>alpha-Thalassemia - complications</subject><subject>alpha-Thalassemia - diagnosis</subject><subject>alpha-Thalassemia - epidemiology</subject><subject>alpha-Thalassemia - genetics</subject><subject>Anemia, Sickle Cell - complications</subject><subject>Anemia, Sickle Cell - diagnosis</subject><subject>Anemia, Sickle Cell - epidemiology</subject><subject>Anemia, Sickle Cell - genetics</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Comorbidity</subject><subject>Exposure</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Genes, Modifier</subject><subject>Glucosephosphate dehydrogenase</subject><subject>Glucosephosphate Dehydrogenase Deficiency - complications</subject><subject>Glucosephosphate Dehydrogenase Deficiency - diagnosis</subject><subject>Glucosephosphate Dehydrogenase Deficiency - epidemiology</subject><subject>Glucosephosphate Dehydrogenase Deficiency - genetics</subject><subject>Hematology</subject><subject>Heredity</subject><subject>HIV</subject><subject>HIV - genetics</subject><subject>HIV - isolation & purification</subject><subject>HIV Infections - complications</subject><subject>HIV Infections - diagnosis</subject><subject>HIV Infections - epidemiology</subject><subject>HIV Infections - genetics</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Male</subject><subject>Mass Screening - methods</subject><subject>newborn screening</subject><subject>Oncology</subject><subject>Pediatrics</subject><subject>Phenotypes</subject><subject>Prevalence</subject><subject>Prognosis</subject><subject>Prospective Studies</subject><subject>sickle cell anemia</subject><subject>Sickle cell disease</subject><subject>Thalassemia</subject><subject>Uganda</subject><issn>1545-5009</issn><issn>1545-5017</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10U1PGzEQBmALUUGa9tA_UFniAhIJ_ozX3GjUFqRIILWcV157NjisvcHOFuXf1zQpByROHsmPX814EPpCyZQSwi7WjZ0yVRF1gEZUCjmRhKrD15roY_Qx51WhMyKrI3TMKdGCaD5C4Ze3jx1gC12Hs00A0ccl9hHfL0105hJf--UDbobkIJ7jhyGYiH0IQ-wdtN56iHaL__g0ZGz70KfGO7_ZnuPyGC8hwsZbHHrnWw8pf0IfWtNl-Lw_x-j-x_ff8-vJ4vbnzfxqMbFccjVRkktTOrSNaLjRhrZEgGWkKteCS9YqraiTsqpsWxFhS2WY1FJzw5yzMz5Gp7vcdeqfBsibOvj8MqKJ0A-5ZowzwiupdaEnb-iqH1Is3RUlBFVMUVHU2U7Z1OecoK3XyQeTtjUl9csO6rKD-t8Oiv26TxyaAO5V_v_0Ai524Nl3sH0_qb77Nt9F_gX2AY9V</recordid><startdate>201908</startdate><enddate>201908</enddate><creator>Kiyaga, Charles</creator><creator>Hernandez, Arielle G.</creator><creator>Ssewanyana, Isaac</creator><creator>Schaefer, Beverly A.</creator><creator>McElhinney, Kathryn E.</creator><creator>Ndeezi, Grace</creator><creator>Howard, Thad A.</creator><creator>Ndugwa, Christopher M.</creator><creator>Ware, Russell E.</creator><creator>Aceng, Jane R.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9582-0594</orcidid><orcidid>https://orcid.org/0000-0002-3079-4695</orcidid></search><sort><creationdate>201908</creationdate><title>Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers</title><author>Kiyaga, Charles ; Hernandez, Arielle G. ; Ssewanyana, Isaac ; Schaefer, Beverly A. ; McElhinney, Kathryn E. ; Ndeezi, Grace ; Howard, Thad A. ; Ndugwa, Christopher M. ; Ware, Russell E. ; Aceng, Jane R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3537-7535a094cb4b3a9a1f04ec208c354352f7971d5588cf804c558a259593a2ddc63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>alpha-Thalassemia - complications</topic><topic>alpha-Thalassemia - diagnosis</topic><topic>alpha-Thalassemia - epidemiology</topic><topic>alpha-Thalassemia - genetics</topic><topic>Anemia, Sickle Cell - complications</topic><topic>Anemia, Sickle Cell - diagnosis</topic><topic>Anemia, Sickle Cell - epidemiology</topic><topic>Anemia, Sickle Cell - genetics</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Comorbidity</topic><topic>Exposure</topic><topic>Female</topic><topic>Follow-Up Studies</topic><topic>Genes, Modifier</topic><topic>Glucosephosphate dehydrogenase</topic><topic>Glucosephosphate Dehydrogenase Deficiency - complications</topic><topic>Glucosephosphate Dehydrogenase Deficiency - diagnosis</topic><topic>Glucosephosphate Dehydrogenase Deficiency - epidemiology</topic><topic>Glucosephosphate Dehydrogenase Deficiency - genetics</topic><topic>Hematology</topic><topic>Heredity</topic><topic>HIV</topic><topic>HIV - genetics</topic><topic>HIV - isolation & purification</topic><topic>HIV Infections - complications</topic><topic>HIV Infections - diagnosis</topic><topic>HIV Infections - epidemiology</topic><topic>HIV Infections - genetics</topic><topic>Human immunodeficiency virus</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Male</topic><topic>Mass Screening - methods</topic><topic>newborn screening</topic><topic>Oncology</topic><topic>Pediatrics</topic><topic>Phenotypes</topic><topic>Prevalence</topic><topic>Prognosis</topic><topic>Prospective Studies</topic><topic>sickle cell anemia</topic><topic>Sickle cell disease</topic><topic>Thalassemia</topic><topic>Uganda</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kiyaga, Charles</creatorcontrib><creatorcontrib>Hernandez, Arielle G.</creatorcontrib><creatorcontrib>Ssewanyana, Isaac</creatorcontrib><creatorcontrib>Schaefer, Beverly A.</creatorcontrib><creatorcontrib>McElhinney, Kathryn E.</creatorcontrib><creatorcontrib>Ndeezi, Grace</creatorcontrib><creatorcontrib>Howard, Thad A.</creatorcontrib><creatorcontrib>Ndugwa, Christopher M.</creatorcontrib><creatorcontrib>Ware, Russell E.</creatorcontrib><creatorcontrib>Aceng, Jane R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Pediatric blood & cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kiyaga, Charles</au><au>Hernandez, Arielle G.</au><au>Ssewanyana, Isaac</au><au>Schaefer, Beverly A.</au><au>McElhinney, Kathryn E.</au><au>Ndeezi, Grace</au><au>Howard, Thad A.</au><au>Ndugwa, Christopher M.</au><au>Ware, Russell E.</au><au>Aceng, Jane R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers</atitle><jtitle>Pediatric blood & cancer</jtitle><addtitle>Pediatr Blood Cancer</addtitle><date>2019-08</date><risdate>2019</risdate><volume>66</volume><issue>8</issue><spage>e27807</spage><epage>n/a</epage><pages>e27807-n/a</pages><issn>1545-5009</issn><eissn>1545-5017</eissn><abstract>Background
The Uganda Sickle Surveillance Study provided evidence for a large sickle burden among HIV‐exposed infants in Uganda. To date, however, no large scale screening program has been developed for Central or East Africa.
Methods
A 3‐year targeted sickle cell screening project in Uganda was designed by the Ministry of Health to (1) determine sickle cell trait and disease prevalence within high‐burden districts, (2) document the prevalence among HIV‐exposed and nonexposed children, (3) confirm previously suggested HIV comorbidity, and (4) estimate the co‐inheritance of known genetic modifiers of sickle cell disease.
Results
A total of 163 334 dried blood spot samples collected between April 2015 and March 2018 were analyzed, including 112 352 samples within the HIV Early Infant Diagnosis program. A high burden with >1% sickle cell disease was found within targeted East Central and Mid‐Northern districts, in both HIV‐exposed and nonexposed children. Based on crude birth‐rate data, 236 905 sickle cell trait births and 16 695 sickle cell disease births will occur annually in Uganda. Compared to sickle cell disease without HIV, the odds ratio of having sickle cell disease plus HIV was 0.50 (95% confidence interval = 0.40‐0.64, P < .0001). Alpha‐thalassemia trait and G6PD deficiency were common with sickle cell disease, but with different geospatial distribution.
Conclusions
High sickle cell burden and potential HIV comorbidity are confirmed in Uganda. Genetic modifiers are common and likely influence laboratory and clinical phenotypes. These prospective data document that targeted sickle cell screening is feasible and effective in Uganda, and support development of district‐level comprehensive care programs.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31094093</pmid><doi>10.1002/pbc.27807</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0001-9582-0594</orcidid><orcidid>https://orcid.org/0000-0002-3079-4695</orcidid></addata></record> |
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| ispartof | Pediatric blood & cancer, 2019-08, Vol.66 (8), p.e27807-n/a |
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| subjects | alpha-Thalassemia - complications alpha-Thalassemia - diagnosis alpha-Thalassemia - epidemiology alpha-Thalassemia - genetics Anemia, Sickle Cell - complications Anemia, Sickle Cell - diagnosis Anemia, Sickle Cell - epidemiology Anemia, Sickle Cell - genetics Child, Preschool Children Comorbidity Exposure Female Follow-Up Studies Genes, Modifier Glucosephosphate dehydrogenase Glucosephosphate Dehydrogenase Deficiency - complications Glucosephosphate Dehydrogenase Deficiency - diagnosis Glucosephosphate Dehydrogenase Deficiency - epidemiology Glucosephosphate Dehydrogenase Deficiency - genetics Hematology Heredity HIV HIV - genetics HIV - isolation & purification HIV Infections - complications HIV Infections - diagnosis HIV Infections - epidemiology HIV Infections - genetics Human immunodeficiency virus Humans Infant Infant, Newborn Infants Male Mass Screening - methods newborn screening Oncology Pediatrics Phenotypes Prevalence Prognosis Prospective Studies sickle cell anemia Sickle cell disease Thalassemia Uganda |
| title | Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers |
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