SickleInAfrica

Makani, Julie; Sangeda, Raphael Zozimus; Nnodu, Obiageli; Nembaware, Victoria; Osei‐Akoto, Alex; Paintsil, Vivian; Balandya, Emmanuel; Kent, Jill; Luzzatto, Lucio; Ofori-Acquah, Solomon Fiifi; Olopade, Olofunmi I; Pallangyo, Kisali; Minja, Irene Kida; Jonas, Mario; Mazandu, Gaston K.; Mulder, Nicola; Ohene‐Frempong, Kwaku; Wonkam, Ambroise

doi:10.1016/s2352-3026(20)30006-5

Cited by 30 publications

(31 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We acknowledge the limitations of our present study in terms of sample size; however, this does not detract from the positive associations we have observed, but it may mean that some other associations may have been missed. A future larger study may benefit from the multi‐country consortium created by SickleInAfrica and H3Africa 40–42 . It will be important to investigate further age and gender effects, particularly because the latter may be different in the pre‐ and post‐pubertal age groups.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

F cell numbers are associated with an X‐linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Patients with sickle cell disease (SCD) with high fetal haemoglobin (HbF) tend to have a lower incidence of complications and longer survival due to inhibition of deoxyhaemoglobin S (HbS) polymerisation by HbF. HbF-containing cells, namely F cells, are strongly influenced by genetic factors. We measured the percentage of F cells (Fcells%) in 222 patients with SCD to evaluate the association of (i) Fcells% with genetic HbF-modifier variants and (ii) Fcells% with haematological parameters. There was a different distribution of Fcells% in females compared to males. The association of the B-cell lymphoma/leukaemia 11A (BCL11A) locus with Fcells% (b = 8Á238; P < 0Á001) and with HbF% (b = 2Á490; P < 0Á001) was significant. All red cell parameters except for Hb and mean corpuscular Hb concentration levels in males and females were significantly different. The Fcells% was positively associated with mean cell Hb, mean cell volume and reticulocytes. To explain the significant gender difference in Fcells%, we tested for associations with single nucleotide polymorphisms on the X chromosomal region Xp22.2, where a genetic determinant of HbF had been previously hypothesised. We found in males a significant association with a SNP in FERM and PDZ domain-containing protein 4 (FRMPD4) and adjacent to male-specific lethal complex subunit 3 (MSL3). Thus, we have identified an X-linked locus that could account for a significant fraction of the Fcells% variation in patients with SCD.

show abstract

Section: Discussionmentioning

confidence: 99%

“…A future larger study may benefit from the multi-country consortium created by SickleInAfrica and H3Africa. [40][41][42] It will be important to investigate further age and gender effects, particularly because the latter may be different in the pre-and post-pubertal age groups.…”

Section: Discussionmentioning

confidence: 99%

F cell numbers are associated with an X‐linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…We then analysed what actually happens in Africa: again based on the literature, drawing also from our personal experience. In Tanzania the burden of SCD is high, and a programme aiming to combine clinical care, research, training and advocacy has been running for over 15 years (Makani et al, 2018) and it has become within the continent a hub of wider cooperation named SickleinAfrica (Makani et al, 2020). For both diseases the pathophysiology is complex; but in SCD the primary problem is clearly sickling, whereas other features are important consequences, particularly a chronic inflammatory state; in PNH the primary abnormality is in the deficiency of the GPI-linked surface proteins CD55 and CD59, that make both red cells and platelets exquisitely sensitive to activated complement (C) (although it is not yet certain whether the marked thrombophilic tendency is a direct consequence of the platelet abnormality or an indirect consequence of intravascular haemolysis).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Treating Rare Diseases in Africa: The Drugs Exist but the Need Is Unmet

Luzzatto

Makani

2022

Front. Pharmacol.

Self Cite

View full text Add to dashboard Cite

Rare diseases (RD) pose serious challenges in terms of both diagnosis and treatment. Legislation was passed in the US (1983) and in EU (2000) aimed to reverse the previous neglect of RD, by providing incentives for development of “orphan drugs” (OD) for their management. Here we analyse the current situation in Africa with respect to (1) sickle cell disease (SCD), that qualifies as rare in the US and in EU, but is not at all rare in African countries (frequencies up to 1–2%); (2) paroxysmal nocturnal haemoglobinuria (PNH), that is ultra-rare in Africa as everywhere else (estimated <10 per million). SCD can be cured by bone marrow transplantation and recently by gene therapy, but very few African patients have access to these expensive procedures; on the other hand, the disease-ameliorating agent hydroxyurea is not expensive, but still the majority of patients in Africa are not receiving it. For PNH, currently most patients In high income countries are treated with a highly effective OD that costs about $400,000 per year per patient: this is not available in Africa. Thus, the impact of OD legislation has been practically nil in this continent. As members of the medical profession and of the human family, we must aim to remove barriers that are essentially financial: especially since countries with rich economies share a history of having exploited African countries. We call on the Global Fund to supply hydroxyurea for all SCD patients; and we call on companies who produce ODs to donate, for every patient who receives an expensive OD in a high income country, enough of the same drug, at a symbolic price, to treat one patient in Africa.

show abstract

“…The working group is made up of members of the H3AbioNet (Mulder et al, 2017 ), the Sickle Pan Africa Network (SPAN), and internationally recognized ontology experts. This working group currently operates under the auspice of the SickleInAfrica consortium (Makani et al, 2020 ). The SickleInAfrica consortium is made up of SPAN and two National Institutes of Health (United States)-funded projects: The Sickle Pan-African Consortium Network (SPARCo) and the Sickle Africa Data Coordinating Center (SADaCC) (Makani et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications

Nembaware

Mazandu

Hotchkiss

et al. 2020

OMICS: A Journal of Integrative Biology

Self Cite

View full text Add to dashboard Cite

Sickle cell disease (SCD) is one of the most common blood disorders impacting planetary health. Over 300,000 newborns are diagnosed with SCD each year globally, with an increasing trend. The sickle cell disease ontology (SCDO) is the most comprehensive multidisciplinary SCD knowledge portal. The SCDO was collaboratively developed by the SCDO working group, which includes experts in SCD and data standards from across the globe. This expert review presents highlights and lessons learned from the fourth SCDO workshop that marked the beginning of applications toward planetary health impact, and with an eye to empower and cultivate multisite SCD collaborative research. The workshop was organized by the Sickle Africa Data Coordinating Center (SADaCC) and attended by 44 participants from 14 countries, with 2 participants connecting remotely. Notably, from the standpoint of democratizing and innovating scientific meeting design, an SCD patient advocate also presented at the workshop, giving a broader real-life perspective on patients' aspirations, needs,

show abstract

SickleInAfrica

Cited by 30 publications

References 0 publications

F cell numbers are associated with an X‐linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease

F cell numbers are associated with an X‐linked genetic polymorphism and correlate with haematological parameters in patients with sickle cell disease

Treating Rare Diseases in Africa: The Drugs Exist but the Need Is Unmet

The Sickle Cell Disease Ontology: Enabling Collaborative Research and Co-Designing of New Planetary Health Applications

Contact Info

Product

Resources

About