Sickle cell anemia in sub-Saharan Africa: advancing the clinical paradigm through partnerships and research

McGann, Patrick T.; Hernandez, Arielle G.; Ware, Russell E.

doi:10.1182/blood-2016-09-702324

Cited by 77 publications

(73 citation statements)

References 76 publications

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“…Soon after the US3 study documented a large burden of sickle cell trait and disease, the Uganda Ministry of Health made plans to act on these results . Maintaining the strong research partnership principles already established among government, industry, and academia, additional research goals were developed, with subsequent screening and testing plans that could address each of those goals.…”

Section: Discussionmentioning

confidence: 99%

“…About two‐thirds of the samples were EID samples that confirmed a high prevalence (Table ), but the remaining one‐third were collected from non‐HIV exposed infants and toddlers, and also documented a large sickle burden. Based on crude birth‐rate data, an estimated 236 905 trait births and 16 695 disease births will have occurred in 2018 . These data represent the most accurate sickle cell trait and disease estimates ever reported for an entire country within sub‐Saharan Africa.…”

Section: Discussionmentioning

confidence: 99%

“…Based on crude birth-rate data, an estimated 236 905 trait births and 16 695 disease births will have occurred in 2018. 10 The fourth research goal was to estimate the frequency of known genetic modifiers of sickle cell disease, specifically -thalassemia trait, G6PD deficiency, and the -globin haplotype. Despite having a single monogenic molecular origin, sickle cell disease is known to be highly variable in its phenotypic expression, and numerous genetic polymorphisms have been proposed with varying levels of accuracy and validation.…”

Section: Discussionmentioning

confidence: 99%

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Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers

Kiyaga

Hernandez

Ssewanyana

et al. 2019

Pediatric Blood & Cancer

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers

Kiyaga

Hernandez

Ssewanyana

et al. 2019

Pediatric Blood & Cancer

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“…[10][11][12] Although these are potential therapies for patients in the United States, neither will be available for several decades for millions of patients in sub-Saharan Africa and elsewhere. 13 Therefore, what is needed to treat the vast majority of patients is an affordable drug that can be taken orally. The development of hydroxyurea has been a major advance in the treatment of sickle cell disease, but it is only partially effective in preventing vaso-occlusive crises.…”

Section: Introductionmentioning

confidence: 99%

Treating sickle cell disease by targeting HbS polymerization

Eaton

Bunn

2017

Blood

204

224

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Although the root cause of sickle cell disease is the polymerization of hemoglobin S (HbS) to form fibers that make red cells less flexible, most drugs currently being assessed in clinical trials are targeting the downstream sequelae of this primary event. Less attention has been devoted to investigation of the multiple ways in which fiber formation can be inhibited. In this article, we describe the molecular rationale for 5 distinct approaches to inhibiting polymerization and also discuss progress with the few antipolymerization drugs currently in clinical trials.

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“…4,5 This limits the use of hydroxyurea in parts of Africa where frequent blood monitoring is not feasible. 7 In the United States and United Kingdom, the complexity and need for frequent monitoring of the recommended "maximum tolerated dose" regimen cause primary care providers to hesitate to prescribe hydroxyurea 8 and create barriers to compliance. 9 In the original MSH study, pain crises in SCA adults decreased during the first 12 weeks of hydroxyurea 15 mg/kg/day before dose escalation and before maximal increase in F-cells.…”

mentioning

confidence: 99%

“Maximum tolerated dose” vs “fixed low‐dose” hydroxyurea for treatment of adults with sickle cell anemia

et al. 2019

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Despite evidence that hydroxyurea is effective for sickle cell anemia (SCA), implementation of the "maximum tolerated dose" regimen in adults is poor. 1 We recently reported a study of "fixed low-dose" hydroxyurea (500 mg/day) for adults with SCA in Ibadan, Nigeria. 2 Here we compare the outcomes of "fixed low-dose" hydroxyurea in Nigeria with "maximum tolerated dose" hydroxyurea in the United States and Canada as reported in the Multicenter Study of Hydroxyurea (MSH). 3,4 The MSH was the seminal trial conducted in the 1990s that led to FDA approval of hydroxyurea for SCA. Responses to "fixed low-dose" and "maximum tolerated dose" hydroxyurea appear to be similar. We propose that these two regimens be compared in a prospective trial in adults with SCA. Hydroxyurea for SCA increases hemoglobin F and reduces pain crises, acute chest syndrome and blood transfusions. 5 The agent is initiated at 15 mg/kg/day in adults followed by dose escalations up to 35 mg/kg/day if tolerated-the "maximum tolerated dose" approach of

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Sickle cell anemia in sub-Saharan Africa: advancing the clinical paradigm through partnerships and research

Cited by 77 publications

References 76 publications

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers

Sickle cell screening in Uganda: High burden, human immunodeficiency virus comorbidity, and genetic modifiers

Treating sickle cell disease by targeting HbS polymerization

“Maximum tolerated dose” vs “fixed low‐dose” hydroxyurea for treatment of adults with sickle cell anemia

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