A safe supply of blood and the knowledge, skill, and resources for the appropriate use of blood are essential for medical services. Many problems are faced in the development of transfusion services in low- or medium-income countries (LMICs). Unfortunately, in many countries, providing safe blood is made more difficult by a lack of blood donors and the high frequency of transfusion-transmissible infections. The problems are compounded by the frequent need for urgent life-saving transfusions. This article examines the problems in supply, safety, and use of blood and how they are being addressed in LMICs, predominantly focusing on sub-Saharan Africa.

Problems and Approaches for Blood Transfusion in the Developing Countries.

Malaria can be transmitted by blood transfusion from human to human and it is responsible for the majority of transfusion-transmitted infectious diseases worldwide. In sub-Saharan Africa, it had been estimated that almost a quarter of blood donations contain malaria parasites. Since rapid diagnostic tests and thick blood smear microscopy lack sensitivity for low density parasitaemia, particularly in asymptomatic adults, the most reliable method to assess the problem of transfusion-transmitted malaria are nucleic acid-based molecular approaches such as quantitative polymerase chain reaction. The study was undertaken to determine the prevalence of sub-microscopic malaria parasite infection among blood donors in Malabo, Equatorial Guinea. Between July and August 2017, a total of 200 individual blood samples from blood donors at the Malabo Blood Bank were collected and screened by rapid diagnostic tests and thick blood smear microscopy. Retrospectively, the same samples were analysed for the presence of undetected, low-density malaria parasites using quantitative polymerase chain reaction. In comparison to 6.5% (13/200) by rapid diagnostic test and 2.0% (4/200) by microscopy, the proportion of Plasmodium falciparum positive blood donations analysed by quantitative polymerase chain reaction was significantly higher (26%, 52/200). Densities of P. falciparum positive blood donations were ranging from 0.06 to 3707.0 parasites/µL with 79.6% below 100 parasites/µL and therefore not detectable by non-molecular malaria diagnostic tests. qPCR based species identification revealed that P. falciparum was the dominating species responsible for 88.1% (52/59) of positive blood donations, followed by Plasmodium malariae (15.3%, 9/59) and Plasmodium ovale (3.4%, 2/59). This study confirms that in malaria endemic settings, sub-patent malaria infections among blood donors are prevalent. In blood collected from healthy donors living in Malabo, P. falciparum, P. malariae and P. ovale parasites were identified. Currently widely used malaria diagnostic tools have missed more than 75% of P. falciparum containing blood donations, demonstrating the value of quantitative polymerase chain reaction to reliably detect low density P. falciparum infections. Since the availability of molecular diagnostic methods in malaria endemic countries is still limited, the blood recipients living in malaria endemic countries should be treated following WHO recommendations.

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Molecular monitoring of the diversity of human pathogenic malaria species in blood donations on Bioko Island, Equatorial Guinea.

Objective: To summarize prevalence data on the neurologic complications of sickle cell disease (SCD) in Africa. Methods: We searched EMBASE, PubMed, and African Index Medicus to identify all relevant articles published from inception to May 31, 2016. Each study was reviewed for methodologic quality. A random-effects model was used to estimate the prevalence of neurologic complications of SCD across studies. Results: Thirty-one studies were included. Methodologic quality was high or moderate in 90% of studies. Stroke, conditional and abnormal cerebral blood flow, seizures, and headache were the complications most frequently reported, with overall prevalence rates of 4.2%, 10.6%, 6.1%, 4.4%, and 18.9%, respectively. Some complications, like silent brain infarcts, peripheral neuropathies, neurocognitive deficits, or moyamoya disease, have been rarely or not studied at all in the African setting. Incidence data were scarce and of poor quality. Conclusions: The burden of neurologic complications of SCD is important in Africa and most likely underestimated. A better evaluation of this burden requires larger prospective studies using standard up-to-date screening methods. Accessibility to diagnostic tools such as neuroimaging, transcranial Doppler, EEG, and neuropsychological evaluation, as well as to preventive and therapeutic interventions and trained health care providers, should be improved in routine clinical practice.

https://n.neurology.org/content/neurology/89/14/1516.full.pdf

Neurologic complications of sickle cell disease in Africa: A systematic review and meta-analysis.

Red blood cell alloimmunization in transfused patients in sub-Saharan Africa: A systematic review and meta-analysis.

To provide a focused review of sickle cell retinopathy in the light of recent advances in the pathogenesis, multimodal retinal imaging, management of the condition, and migration trends, which may lead to increased prevalence of the condition in the Western world. Non-systematic focused literature review. Sickle retinopathy results from aggregation of abnormal hemoglobin in the red blood cells in the retinal microcirculation, leading to reduced deformability of the red blood cells, stagnant blood flow in the retinal precapillary arterioles, thrombosis, and ischemia. This may be precipitated by hypoxia, acidosis, and hyperosmolarity. Sickle retinopathy may result in sight threatening complications, such as paracentral middle maculopathy or sequelae of proliferative retinopathy, such as vitreous hemorrhage and retinal detachment. New imaging modalities, such as wide-field imaging and optical coherence tomography angiography, have revealed the microstructural features of sickle retinopathy, enabling earlier diagnosis. The vascular growth factor ANGPTL-4 has recently been identified as a potential mediator of progression to proliferative retinopathy and may represent a possible therapeutic target. Laser therapy should be considered for proliferative retinopathy in order to prevent visual loss; however, the evidence is not very strong. With recent development of wide-field imaging, targeted laser to ischemic retina may prove to be beneficial. Exact control of intraoperative intraocular pressure, including valved trocar vitrectomy systems, may improve the outcomes of vitreoretinal surgery for complications, such as vitreous hemorrhage and retinal detachment. Stem cell transplantation and gene therapy are potentially curative treatments, which may prevent retinopathy. There is lack of evidence regarding the optimal management of sickle retinopathy. Further study is needed to determine if recent progress in the understanding of the pathophysiology and diagnosis of sickle retinopathy may translate into improved management and outcome.

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Sickle cell retinopathy. A focused review.

Red cell transfusion is one of the main treatments in sickle cell disease. However there are potential risks of blood transfusions. In order to propose strategies to improve blood safety in sickle cell disease in Mali, we conducted a prospective study of 133 patients with sickle cell anemia recruited at the sickle cell disease research and control center of Bamako, November 2010 to October 2011. The study aimed to determine the prevalence of human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections by serum screening and the frequency of red cell alloimmunization before and after blood transfusion. The diagnosis of sickle cell syndrome was made by HPLC, the detection of markers of viral infection was performed by ELISA, and the diagnosis of alloimmunization was conducted by the Indirect Coombs test. Prevalence of viral infections observed at the time of enrolment of patients in the study was 1%, 3% and 1% respectively for HIV, HBV and HCV. Three cases of seroconversion after blood transfusion were detected, including one for HIV, one for HBV and one another for HCV in sickle cell anemia patients. All these patients had received blood from occasional donors. The red cell alloimmunization was observed in 4.4% of patients. All antibodies belonged to Rh system only. Blood transfusion safety in sickle cell anemia patients in Mali should be improved by the introduction of at least the technique for detecting the viral genome in the panel of screening tests and a policy of transfusions of blood units only from regular blood donors.

Sécurité transfusionnelle et drépanocytose à Bamako, Mali. Séroprévalence des infections à VIH, VHB, VHC et allo-immunisation anti-Rh et Kell chez les drépanocytaires.

Resume Introduction La retinopathie est une complication chronique a risque fonctionnel important chez le drepanocytaire, dont l’incidence est mal connue en Afrique subsaharienne, faute de depistage. Ce travail decrit les resultats d’un depistage systematique de la retinopathie drepanocytaire dans un centre de suivi des drepanocytaires au Mali. Methodes Tous les drepanocytaires âges de 10 ans et plus, suivis au centre, ont ete depistes entre 2010 et 2012 par un examen du fond d’œil complete si besoin par une angiographie. Les caracteristiques des patients porteurs d’une retinopathie ont ete comparees a celles de drepanocytaires sans retinopathie recrutes durant la meme periode et selectionnes au hasard. Resultats La retinopathie avait une prevalence globale de 8,8 % chez les 1604 drepanocytaires âges de 10 ans et plus et concernait 91/731 (12,4 %) drepanocytaires SC, 38/734 (5,2 %) SS, 5/53 (9,4 %) Sβ 0  thalassemiques et 8/86 (9,3 %) Sβ +  thalassemiques. La forme proliferante de la retinopathie etait plus frequente chez les SC ( p 0 thalassemiques. Conclusion La retinopathie touche pres d’un patient drepanocytaire sur dix et sa prevalence est negativement associee au taux d’hemoglobine fœtale. L’efficience d’un depistage systematique de la retinopathie drepanocytaire doit etre etudiee en Afrique, ainsi que l’interet de la phlebotomie et de l’hydroxycarbamide en traitement preventif.

Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d’Afrique subsaharienne

Resume La vasculopathie drepanocytaire expose a un risque eleve d’accident vasculaire cerebral (AVC) pouvant entrainer le deces ou un handicap important. Le doppler transcrânien (DTC) permet d’identifier les drepanocytaires a risque de cette complication majeure de la maladie, afin de reduire par un traitement approprie, la morbidite et la mortalite qu’elle peut engendrer. De 2008 a 2013, nous avons effectue un depistage systematique de la vasculopathie cerebrale par DTC chez 572 drepanocytaires, âges de 1 a 17 ans et repartis entre 375 sujets SS, 144 SC, 26 S/β 0  et 27 S/β + thalassemiques. Apres exclusion de 30 cas de DTC incomplets et d’un cas de DTC pathologique observe dans un contexte de defaillance multiviscerale, nous avons constate un resultat pathologique ou limite chez 18 % des 541 enfants examines a l’etat basal. Les prevalences de DTC pathologique les plus elevees ont ete observees chez les homozygotes SS (8,1 %). Aucun cas de DTC anormal n’a ete observe chez les enfants S/β + thalassemiques. Les taux d’hemoglobine (Hb) etaient significativement plus bas en cas de resultat au DTC limite ou pathologique. Parmi 68 enfants dont les resultats etaient limites, 9 (13 %) ont presente des resultats pathologiques au bout d’un an de suivi. Dans ce groupe, une diminution ou une augmentation du taux d’Hb de base etait predictive d’un resultat limite ou pathologique au controle. Les enfants dont le resultat etait pathologique ont beneficie, autant que possible, de transfusions ou d’echanges transfusionnels mensuels. Un cas d’AVC transitoire sans signe neurologique, dans un contexte de deglobulisation massive par paludisme et un deces ont ete observes. Ces resultats soulignent la necessite de la pratique systematique du DTC au cours du suivi de l’enfant drepanocytaire et l’urgence de la mise en œuvre de programmes de transfusions chroniques adaptes aux contextes de difficultes d’acces a des transfusions regulieres et securisees.

Dépistage de la vasculopathie cérébrale drépanocytaire par doppler transcrânien au Mali

Dear Sir, Sickle cell disease (SCD) is a common worldwide inherited haematologic disorder. Blood transfusion therapy is an essential component in SCD management particularly during vaso-occlusive crisis, acute chest syndrome and cerebral vasculopathy prevention. According to De Montalembert, over 60% of homozygous (SS) SCD patients, 17% of heterozygote SC and 45% of S/Beta-thalassemia patients have been transfused at least once before they are 18 years old. Despite progresses achieved during the last decades in improving blood transfusion safety, it still represents a risk for the recipient, as it can result in transmission of various pathogens including Plasmodium falciparum (Pf ). Pf can withstand storage at 4 ∘C for at least 3 weeks as well as survive in asymptomatic individuals willing to donate blood. In non-endemic areas, prevention of post-transfusion malaria (PTM) is carried out by permanent or temporary exclusion of blood donors who stayed even briefly in endemic areas (Garraud et al., 2007). The health of blood donors is of paramount importance for both the donor and the recipient; hence, screening for Pf in malaria-endemic areas may increase the safety of blood transfusion. However, despite the risk of blood transmitted Pf infection in sub-Saharan Africa and in spite of the established World Health Organization recommendations (Kitchen and Chiodini, 2006), no systematic screening for Pf is presently conducted by transfusion centres and few studies have been carried out on the risk of transfusion-transmitted Pf . The potential use of Pf -infected blood units in malaria-endemic areas for SCD-affected patients raises an ethical issue which needs to be addressed by the scientific community. In a 2014 report from Brazil, only four cases of malaria transmission by transfusions were identified since 2002 (Lacerda et al., 2014). We report here our findings from a systematic screening for Pf in concentrated red blood cell (CRBC) units collected for transfusion during the management of SCD-affected individuals in Mali. The aim of this study was to evaluate the risk of transmission of Pf by blood transfusion in SCD patients living in malaria-endemic areas. From January to December of 2013 (covering low and high malaria transmission season in Mali), a cross-sectional study was

B. Fané

Papers

Sécurité transfusionnelle et drépanocytose à Bamako, Mali. Séroprévalence des infections à VIH, VHB, VHC et allo-immunisation anti-Rh et Kell chez les drépanocytaires.

Prévalence et facteurs de risque de la rétinopathie drépanocytaire dans un centre de suivi drépanocytaire d’Afrique subsaharienne

Dépistage de la vasculopathie cérébrale drépanocytaire par doppler transcrânien au Mali

Transmission of Plasmodium falciparum by red blood cell transfusions in the management of sickle cell disease patients in Mali.