Cell Anemia In Africa Research Articles

Sickle cell disease: time to act on the most neglected global health problem

Despite being the first monogenic disease described in scientific literature over a century ago, sickle cell disease remains an illness with high morbidity and early mortality, particularly in sub-Saharan Africa and other low-income and middle-income countries (LMICs) in historically malaria-endemic regions of the world. 1 Piel FB Steinberg MH Rees DC Sickle cell disease. N Engl J Med. 2017; 376: 1561-1573 Crossref PubMed Scopus (635) Google Scholar Sickle cell disease is a chronic and progressive condition associated with frequent painful, vaso-occlusive episodes, multiple end-organ complications, and detrimental effects on the psychosocial wellbeing of those affected, their families, and communities. Significant advances in the care of individuals with sickle cell disease over the past several decades, including newborn screening (NBS), penicillin prophylaxis, expanded immunisation programmes, and hydroxyurea therapy, have substantially reduced mortality among children and adolescents living in higher income countries. 2 Quinn CT Rogers ZR McCavit TL Buchanan GR Improved survival of children and adolescents with sickle cell disease. Blood. 2010; 115: 3447-3452 Crossref PubMed Scopus (619) Google Scholar , 3 Telfer P Coen P Chakravorty S et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. 2007; 92: 905-912 Crossref PubMed Scopus (237) Google Scholar Unfortunately, premature mortality from sickle cell disease during early childhood persists in LMICs, 4 Makani J Cox SE Soka D et al. Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania. PLoS One. 2011; 6e14699 Crossref PubMed Scopus (191) Google Scholar where a majority of the global sickle cell disease burden is found. The clinical framework in LMICs is decades behind that of higher income countries, with most affected infants dying in the first years of life due to scarce access to an early diagnosis and available prophylactic or disease-modifying interventions. Despite multiple statements and calls to action from WHO to recognise and address the global burden of sickle cell disease, 5 WHO Regional Committee for AfricaSickle-cell disease: a strategy for the WHO African Region. World Health Organization, Geneva2010 Google Scholar there remains a crucial paucity of data in individual countries or across the highest burdened regions of the world to accurately quantify this problem and drive resource allocation to improve the diagnosis, management, and awareness of sickle cell disease. Global, regional, and national prevalence and mortality burden of sickle cell disease, 2000–2021: a systematic analysis from the Global Burden of Disease Study 2021Our findings show a strikingly high contribution of sickle cell disease to all-cause mortality that is not apparent when each death is assigned to only a single cause. Sickle cell disease mortality burden is highest in children, especially in countries with the greatest under-5 mortality rates. Without comprehensive strategies to address morbidity and mortality associated with sickle cell disease, attainment of SDG 3.1, 3.2, and 3.4 is uncertain. Widespread data gaps and correspondingly high uncertainty in the estimates highlight the urgent need for routine and sustained surveillance efforts, further research to assess the contribution of conditions associated with sickle cell disease, and widespread deployment of evidence-based prevention and treatment for those with sickle cell disease. Full-Text PDF Open Access

DNA testing for sickle cell anemia in Africa: Implementation choices for the Democratic Republic of Congo.

BackgroundHemoglobin‐based tests form the reference diagnostic test for SCA. In limited resource countries, these tests face limitations including cost, low sensitivity due to recurrent transfusions in endemic malaria region, and interference from fetal hemoglobin in neonatal diagnostic. This study aimed at adapting DNA‐based SCA tests to limited resource countries and evaluating the economic benefit.Methods338 participants were recruited in the Democratic Republic of Congo, sorted in 3 cohorts based on venous blood, umbilical cord blood (UCB) and buccal swab sampling. RFLP was performed to identify mutated allele. The feasibility and technical validity of this RFLP was evaluated for specimens collected on DBS cards and on EDTA tubes. RFLP on DBS stored at room temperature was regularly repeated to assess sample conservation. Finally, the cost analysis was performed.ResultsDBS cards yielded identical results to extracted DNA. Repeated testing returned the same result after four years. The DBS‐based test performed on UCB or on buccal swab had a sensitivity and a precision of 100%. Cost comparison indicated that our approach costs half price of the widely used isoelectrofocussing of hemoglobin.ConclusionThe implemented DNA‐based test approach overcomes the limitations faced by hemoglobin‐based tests, while being more affordable. We propose to implement the RFLP test as a first line diagnostic test after transfusion and as second tiers for newborn screening. However, users should be aware that this test is unable to differentiate HbC from HbS or identify other point mutation of gene deletion of HBB gene.

Capacity Building for Primary Stroke Prevention Teams in Children Living With Sickle Cell Anemia in Africa

BackgroundNigeria has the highest proportion of children with sickle cell anemia (SCA) globally; an estimated 150,000 infants with SCA are born annually. Primary stroke prevention in children with SCA must include Nigeria. We describe capacity-building strategies in conjunction with two National Institutes of Health–funded primary stroke prevention trials (a feasibility trial and phase III randomized controlled trial) with initial hydroxyurea treatment for children with SCA and abnormal transcranial Doppler (TCD) velocities in Nigeria. We anticipated challenges to conducting clinical trials in a low-resource setting with a local team that had not previously been involved in clinical research and sought a sustainable strategy for primary stroke prevention. MethodsThis is a descriptive, prospective study of challenges, solutions, and research teams in two trials that enrolled a total of 679 children with SCA. ResultsAs part of the capacity-building component of the trials, over eight years, 23 research personnel (physicians, nurses, research coordinators, a statistician, and a pharmacist) completed a one-month research governance and ethics training program at Vanderbilt University Medical Center, USA. A lead research coordinator for each site completed the Society of Clinical Research Professionals certification. TCD machines were donated; radiologists and nonradiologists were trained and certified to perform TCD. A scalable E-prescription was implemented to track hydroxyurea treatment. We worked with regional government officials to support ongoing TCD-based screening and funding for hydroxyurea for children with SCA at a high risk of stroke. ConclusionsOur trials and capacity building demonstrate a sustainable strategy to initiate and maintain pediatric SCA primary stroke prevention programs in Africa.

Transfusion and sickle cell anemia in Africa.

Sickle cell anemia (SCA) is the commonest life-threatening genetic disorder in tropical regions, particularly in sub-Saharan Africa. It has been estimated that between 50-90% of SCA children will die in Africa before the age of 5, corresponding to a number of 150,000-300,000 annual SCA child deaths, which represents 5-10% of total child mortality. Transfusion support remains an essential component in the management of patients with SCA and has made a significant contribution to improving patient morbidity and mortality. In Africa where the majority of patients with SCA reside, many blood transfusion challenges remains, including shortage of blood supplies, risks related to infectious and immunologic potential side effects and limitation on the diagnosis and management of post-transfusion iron overload. The proportion of transfused SCA patients varies from different studies, between 30% and 90%. This variation can be related to environmental factors, disease genetic factors and other factors including the low availability of blood, difficulties in accessing to health care and inadequacies of the transfusion system. Because blood transfusion therapy is an integral component of the management of SCA, improved efforts and strategies to overcome these challenges and optimize blood transfusion practices are needed in African countries.

World Health Organization's Growth Reference Overestimates the Prevalence of Severe Malnutrition in Children with Sickle Cell Anemia in Africa.

Anthropometric indices are widely used to assess the health and nutritional status of children. We tested the hypothesis that the 2007 World Health Organization (WHO) reference for assessment of malnutrition in children with sickle cell anemia (SCA) overestimates the prevalence of severe malnutrition when compared to a previously constructed SCA-specific reference. We applied the WHO and SCA-specific references to children with SCA aged 5–12 years living in northern Nigeria (Primary Prevention of Stroke in Children with SCA in sub-Saharan Africa (SPRING) trial) to determine the difference in prevalence of severe malnutrition defined as body mass index (BMI) Z-score <−3 and whether severe malnutrition was associated with lower mean hemoglobin levels or abnormal transcranial Doppler measurements (>200 cm/s). A total of 799 children were included in the final analysis (median age 8.2 years (interquartile range (IQR) 6.4–10.4)). The application of the WHO reference resulted in lower mean BMI than the SCA-specific reference (−2.3 versus −1.2; p < 0.001, respectively). The use of the WHO reference when compared to the SCA-specific reference population also resulted in a higher prevalence of severe malnutrition (28.6% vs. 6.4%; p < 0.001). The WHO reference significantly overestimates the prevalence of severe malnutrition in children with SCA when compared to an SCA-specific reference. Regardless of the reference population, severe malnutrition was not associated with lower mean hemoglobin levels or abnormal transcranial Doppler (TCD) measurements.

Hydroxyurea Treatment for Sickle Cell Anemia in Africa

Hydroxyurea Treatment for Sickle Cell Anemia in Africa

Extremely High Carrier Frequency of the GJB2 Splice Site IVS1+1G&gt;A Mutation in Eastern Siberia is Comparable to the Carrier Frequency of the Sickle Cell Anemia in Africa

C l i n M e d International Library Citation: Barashkov NA (2014) Extremely High Carrier Frequency of the GJB2 Splice Site IVS1+1G>A Mutation in Eastern Siberia is Comparable to the Carrier Frequency of the Sickle Cell Anemia in Africa. J Genet Genome Res 1:001 Received: July 24, 2014: Accepted: August 02, 2014: Published: August 06, 2014 Copyright: © 2014 Barashkov NA. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Barashkov, et al., J Genet Genome Res 2014, 1:1 ISSN: 2378-3648

Building partnerships to target sickle cell anemia in Africa

Building partnerships to target sickle cell anemia in Africa

Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease

Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke,making primary stroke prevention a reality. A cross-sectional study of145 Nigerian children aged ≥3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 ±27.0 cm/sec and122 ±22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C cases. Cerebral flow velocities showed a negative correlation with age and hematocrit. Compared with African-American children, Nigerian children with Hb SS disease have a considerably higher prevalence of CR velocities.

Mortality in Sickle Cell Anemia in Africa: A Prospective Cohort Study in Tanzania

BackgroundThe World Health Organization has declared Sickle Cell Anemia (SCA) a public health priority. There are 300,000 births/year, over 75% in Africa, with estimates suggesting that 6 million Africans will be living with SCA if average survival reaches half the African norm. Countries such as United States of America and United Kingdom have reduced SCA mortality from 3 to 0.13 per 100 person years of observation (PYO), with interventions such as newborn screening, prevention of infections and comprehensive care, but implementation of interventions in African countries has been hindered by lack of locally appropriate information. The objective of this study was to determine the incidence and factors associated with death from SCA in Dar-es-Salaam.Methods and FindingsA hospital-based cohort study was conducted, with prospective surveillance of 1,725 SCA patients recruited from 2004 to 2009, with 209 (12%) lost to follow up, while 86 died. The mortality rate was 1.9 (95%CI 1.5, 2.9) per 100 PYO, highest under 5-years old [7.3 (4.8–11.0)], adjusting for dates of birth and study enrollment. Independent risk factors, at enrollment to the cohort, predicting death were low hemoglobin (<5 g/dL) [3.8 (1.8–8.2); p = 0.001] and high total bilirubin (≥102 µmol/L) [1.7 (1.0–2.9); p = 0.044] as determined by logistic regression.ConclusionsMortality in SCA in Africa is high, with the most vulnerable period being under 5-years old. This is most likely an underestimate, as this was a hospital cohort and may not have captured SCA individuals with severe disease who died in early childhood, those with mild disease who are undiagnosed or do not utilize services at health facilities. Prompt and effective treatment for anemia in SCA is recommended as it is likely to improve survival. Further research is required to determine the etiology, pathophysiology and the most appropriate strategies for management of anemia in SCA.

NT‐proBNP as a marker of cardiopulmonary status in sickle cell anaemia in Africa

N-terminal (NT) pro-brain natriuretic peptide (proBNP) > or =160 ng/l has a 78% positive predictive value for pulmonary hypertension and is associated with increased mortality in US sickle cell disease patients, but the importance in sickle cell disease patients in Africa is not known. In a cross-sectional study at Ahmadu Bello University Teaching Hospital, Shika-Zaria, Nigeria, we studied 133 hydroxycarbamide-naïve Nigerian sickle cell anaemia patients aged 18-52 years at steady-state and 65 healthy controls. Twenty-six percent of patients versus 5% of controls had NT-proBNP > or =160 ng/l (P = 0.0006). By logistic regression among the patients, human immunodeficiency virus seropositivity, higher serum ferritin and lower haemoglobin or higher lactate dehydrogenase independently predicted elevated NT-proBNP. After adjustment for haemoglobin concentration, elevated NT-proBNP concentration was associated with an estimated 7.8-fold increase in the odds of severe functional impairment, defined as an inability to walk more than 300 m in 6 min (95% confidence interval 1.5-32.6; P = 0.005). Similarly, elevated tricuspid regurgitation velocity was associated with an estimated 5.6-fold increase in the odds of functional impairment (95% confidence interval 1.5-21.0; P = 0.011). In conclusion, NT-proBNP elevation is common and is associated with markers of anaemia, inflammation and iron status and with severe functional impairment among sickle cell anaemia patients in Nigeria.

Dietary nitriloside and sickle cell anemia in Africa

Dietary nitriloside and sickle cell anemia in Africa

Inhibition of DNA synthesis in Ehrlich ascites cells by actinomycin D. I. Delayed inhibition by low doses.

* This investigation was supported in part by USPHS fellowship 1-F3-AM 7959-02, by USPHS grants AM-07752-02 and AM 09381-01, all from the National Institute of Arthritis and Diseases, and in part by the Medical Research and Development Command, Office of the Surgeon General, Department of the Army, under contract IA-49-193-MD 2413 with the University of Chicago. t Recipient of USPHS Career Development Award l-K3-AM-7959-01. I Beet, E. A., Sickle cell disease in the Balovale District of Northern Rhodesia, E. African Med. J., 23, 75 (1946). 2 Brain, P., Sickle cell anaemia in Africa, Brit. Med. J., 2, 880 (1952). 3 Mackey, J. P., and F. Vivarelli, Sickle-cell anaemia, Brit. Med. J., 1, 276 (1954). 4 Allison, A. C., Protection afforded by sickle cell trait against subtertian malarial infection, Brit. Med. J., 1, 290 (1954). 5 Motulsky, A. G., Metabolic polymorphisms and the role of infectious diseases in human evolution, Human Biol., 32, 28 (1960). 6 Siniscalco, M., L. Bernini, B. Latte, and A. G. Motulsky, Favism and thalassemia in Sardinia and their relationship to malaria, Nature, 190, 1179 (1961). 7 Allison, A. C., and D. F. Clyde, Malaria in African children with deficient glucose-6-phosphate dehydrogenase in Brit. Med. J., 1, 1346 (1961). 8 Neel, J. V., The geography of hemoglobinopathies, in Proceedings of the Conference on Genetic Polymorphisms and Geographic Variations in Disease, ed. B. S. Blumberg (New York: Grune & Stratton, 1961), pp. 102-122. 9 Brewer, G. J., unpublished observations. 10 Neel, J. V., Discussion, in Methodology in Human Genetics, ed. W. J. Burdette (San Francisco: Holden-Day, Inc., 1962), pp. 198-199. 1 Powell, R. D., and G. J. Brewer, Glucose-6-phosphate dehydrogenase deficiency and falciparum malaria, Am. J. Trop. Med. Hyg., 14, 358 (1965). 12 Kornberg, A., Reversible enzymatic synthesis of diphosphopyridine nucleotide and inorganic pyrophosphate, J. Biol. Chem., 182, 779 (1950). 1 Brewer, G. J., and R. D. Powell, The adenosine triphosphate content of G-6-PD deficient and normal erythrocytes, including studies of a G-6-1D deficient man with elevated erythrocytic ATP, to be published, 14 Gross, R. T., E. A. R. Schroeder, and S. A. Brounstein, Energy metabolism in the erythrocytes of premature infants compared to full term newborn infants and adults, Blood, 21, 755 (1963). 15 Beutler, E., R. J. Dern, and C. L. Flanagan, Effect of the sickling trait on resistance to malaria, Brit. Med. J., 1, 1163 (1955). 16 Allison4 has reported evidence suggesting a decreased susceptibility to malaria infections in partially immune individuals with sickle cell trait contrasted with partially immune control individuals.