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Tanzania is one of the countries with a high burden of sickle cell disease (SCD). Haemolytic anaemia is a clinical feature of SCD, and has been linked to major complications leading to morbidity and mortality. Treatment with hydroxyurea (HU) has shown to induce foetal haemoglobin (HbF) which in turn decreases haemolysis in patients. This study aimed to investigate the effects of HU on haemolysis in SCD patients attending Muhimbili National Hospital, Tanzania by comparing their haemolytic parameters before and after therapy. Patients meeting the criteria were initiated on HU therapy for 3 months. Two haemolytic biomarkers: unconjugated plasma bilirubin levels and absolute reticulocyte counts were measured from patients’ blood samples at baseline and after 3 months of HU therapy and compared. Both absolute reticulocyte counts and indirect plasma bilirubin levels significantly declined after HU therapy. Median (IQR) plasma unconjugated bilirubin levels dropped significantly from 20.3 (12.7–34.4) μmol/L to 14.5 (9.6–24.1) μmol/L (p < 0.001) and mean (SD) absolute reticulocyte counts dropped significantly from 0.29 (0.1) x 109/L to 0.17 (0.1) x 109/L (p < 0.001) after therapy, thus, a decline in both haemolytic biomarkers after treatment was observed. This study found a potential for use of HU therapy in managing SCD patients in our settings evidenced by improvements in their haemolytic parameters. Clinical trials with a lager sample size conducted for a longer time period would be beneficial in guiding towards the inclusion of HU in treatment protocols for the Tanzanian population. Keywords: Sickle cell disease; hydroxyurea; haemolysis; foetal haemoglobin

Research productivity and outcomes of junior researchers are usually correlated with the degree and quality of mentorship they receive. A bottom-up approach was followed to develop a research group at the Ocean Road Cancer Institute (ORCI), the major cancer center in Tanzania, to build upon the existing clinical and research resources and institutional global collaborations. The ORCI is a clinical center focused on radio- and chemo-therapy treatment of cancer patients from all over Tanzania. In addition, ORCI has a long-standing early detection program for educating women and screening them for cervical cancer. The ORCI physicians have been exposed to cancer research for the past 20 years through non-degree and degree training in the USA and Europe. In addition, US and European groups have been conducting collaborative research and training of oncologists and graduate students at ORCI. The exposure to research through the above-listed venues motivated the clinicians at ORCI to develop their own Research Club (RC) to learn about research methods, seek independent funding, and outline a research agenda for cancer research in Tanzania. However, it seems that mentorship is needed to help the RC members apply the lessons learned from didactic teaching. Mentorship is also needed to enable the RC members to utilize the enormous clinical and epidemiologic data generated by the institutional programs for prevention, treatment, and follow up of patients. This manuscript describes the inception of the program and its achievements, limitations, and suggested opportunities for improvement as a possible model for other LMICs.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers’ behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Background Monitoring patient’s clinical attendance is a crucial means of improving retention in care and treatment programmes. Sickle cell patients’ outcomes are improved by participation in comprehensive care programmes, but these benefits cannot be achieved when patients are lost from clinical care. In this study, patients are defined as loss to follow-up when they did not attend clinic for more than 9 months. Precise information on the retention rate and characteristics of those who are not following their clinic appointments is needed to enable the implementation of interventions that will be effective in increasing the retention to care. Method This was a retrospective study involving sickle cell patients registered in the Muhimbili Sickle Cohort in Tanzania. Descriptive and survival analysis techniques both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox’s proportional hazard model), were used. A p-value of 0.05 was considered significant to make an inference from the analysis. Results A total of 5476 patients were registered in the cohort from 2004 to 2016. Of these, 3350 (58.13%) were actively participating in clinics, while 2126 (41.87%) were inactive, of which 1927 (35.19%) were loss to follow-up. We used data from 2004 to 2014 because between 2015 and 2016, patients were referred to other government hospitals. From the survival analysis results, pediatric (HR: 14.29,95% CI: 11.0071–18.5768, p p p = 0.0039) or mean cell volume (HR: 4.28, (95% CI: 1.0260–1.0598, p Conclusion Loss to follow-up is evident in the cohort of patients in long term comprehensive care. It is, therefore, necessary to design interventions that improve patients’ retention. Suggested solutions include refresher training for health care workers and those responsible for patient follow-up on techniques for retaining patients and comprehensive transition programs to prepare patients who are moving from pediatric to adult clinics.

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% (β = 8·238; P < 0·001) and with HbF% (β = 2·490; P < 0·001) 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.

Haematopoietic stem cell transplantation (HSCT) is a much‐needed service in Tanzania, to provide curative therapy for sickle cell disease (SCD), aplastic anaemia and haematological malignancies. The experience of other countries with limited resources has demonstrated that it is possible to set up such a service within similar economic and healthcare settings. This article summarises the current progress that has been made towards setting up an HSCT service in Tanzania and highlights the areas that require more work and investment to make the service a reality.

Introducing newborn screening (NBS) services for sickle cell disease (SCD) in Africa has been proven to be one of the most cost-effective approach to reducing morbidity and mortality associated with this condition. In view of this evidence, efforts have been made by countries in Africa where SCD prevalence is high to pilot NBS programmes and to strengthen comprehensive care services for SCD. While it is important to reap the benefits of NBS for SCD in Africa in terms of overall quantitative measures, it is also important to understand how certain social and cultural conditions may disproportionately influence the outcomes of screening for some groups. The aim of this study was to analyse the role of gender norms before and after NBS for SCD in Tanzania, and to assess how they influence the quality of care of diagnosed children. Using qualitative methods, we did in-depth interviews with families of children with SCD identified through the NBS services and focus group sessions with nurses working in neonatal and postnatal sections of regional referral hospitals in Dar es Salaam. By analysing the experiences of both the families and nurses, we were able to provide evidence on, firstly, the gendered relations that undergird childcare and, secondly, how those relations influence the quality of care the child may potentially receive. The results emphasize the importance of studying the social implications of SCD in Africa, especially with regard to improving the quality of care for patients with SCD in the region. We propose simple interventions, including gender-conscious health education and genetic counselling, which can help to improve the community understanding of genetic diseases while also reducing gender-related inequalities related to SCD care in Africa.

Background: The pathophysiology of sickle cell disease (SCD) is complex and involves nitric oxide depletion, increased inflammation/adhesion molecules and vaso-occlusion in addition to the chronic hemolytic anemia. This pathophysiology results in systemic clinical complications including recurrent episodes of severe pain, stroke, acute chest syndrome (ACS) and an increased susceptibility to infection. SCD severity varies among individuals and fetal hemoglobin (HbF) is known as a major modulator of the disease. To date, hydroxyurea (HU) is a known intervention that acts by increasing HbF in individuals with SCD. The increase in HbF reduces the risk of ‘sickling’ events and improves clinical outcomes. This is the first study on the use of HU in individuals with SCA in Tanzania.Methods: A case-control study to determine the proportion, indications, clinical and laboratory outcomes of SCD patients with HU use was conducted at Muhimbili National Hospital in Dar Es Salaam, Tanzania.Results: Forty-two patients with Sickle cell anemia (SCA) on HU treatment and 32 patients with SCA not on HU treatment were enrolled. The proportion of HU use by individuals with SCA at Muhimbili National Hospital was 10 per 1000. The mean HbF % was 9.8 ± 2.4 vs 6.2 ±1.4 for controls (P

Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. Methods: We investigated rare and common genetic variants that influence HbF levels in 14 SCD patients to elucidate variants and pathways in SCD patients with extreme HbF levels (≥7.7% for high HbF) and (≤2.5% for low HbF) in Tanzania. We performed targeted next generation sequencing (Illumina_Miseq) covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1.Results: Results revealed a range of genetic variants, including bi-allelic and multi-allelic SNPs, frameshift insertions and deletions, some of which have functional importance. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified deletions with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. Conclusions: This study provides new insights in selecting essential variants and identifying potential biological pathways associated with extreme HbF levels in SCD using multiple genomic variants associated with HbF in SCD.

To address the global burden of sickle cell disease and the need for novel therapies, the American Society of Hematology partnered with the US Food and Drug Administration to engage the work of 7 panels of clinicians, investigators, and patients to develop consensus recommendations for clinical trial end points. The panels conducted their work through literature reviews, assessment of available evidence, and expert judgment focusing on end points related to patient-reported outcome, pain (non–patient-reported outcomes), the brain, end-organ considerations, biomarkers, measurement of cure, and low-resource settings. This article presents the findings and recommendations of the end-organ considerations, measurement of cure, and low-resource settings panels as well as relevant findings and recommendations from the biomarkers panel.

Factors contributing to low use of HU among SCD patients exist in high-income countries. The latter leaves a drift of literature on factors for low utilization of HU in developing countries. This study aimed to explore the factors influencing the use of HU in the management of SCD in Tanzania. A qualitative study was employed to interview purposively selected participants for this study. The in-depth interviews were conducted with 11 parents of children with SCD, four medical doctors working at sickle cell clinics, and two representatives of the national health insurance fund (NHIF). Interviews were audio-recorded, transcribed, and thematically analysed. Barriers identified were misconception of parents on SCD, financial constraints, regulatory restrictions, worries and fears of medical doctors on the acceptability of HU, shortages of laboratory equipment and consumables, and limited availability of HU. Adequate knowledge of the parents and medical doctors on SCD and HU and opportunities for HU accessibility were the facilitators identified. The utilization of HU by the individual with SCD is affected by several factors, from individual to policy level. Nevertheless, parents of children with SCD and medical doctors working in sickle cell clinics demonstrated good knowledge of the diseases and HU.

On March 2–3, 2011—ahead of the first UN High-Level Meeting on NCDs—a conference hosted in Boston (MA, USA) focused on the NCDs of the world's poorest billion, whose poverty was embodied in young average age, low energy intake, and subsistence through physical labour.30 Participants at the Boston event argued that global thinking about NCDs had been too focused on a theory of epidemiological transition, which projected epidemics of chronic disease associated with development.31 This theory created a blind spot regarding the existence and pattern of non-infectious conditions before declines in infectious mortality (pre-transitional NCDIs). The poorest populations were still experiencing NCDIs as part of a nexus of hunger, toxic environments, infectious diseases, and lack of health care. The NCDIs that emerged under these circumstances were both more severe and more varied than could be captured by frameworks developed for other populations. In April, 2011, the WHO African Regional Office held a consultation of health ministers in Congo (Brazzaville).32 The Brazzaville Declaration on NCDs called for an expanded NCDI agenda addressing haemoglobinopathies (sickle cell disease), mental disorders, and violence and injury.32 Other prominent African health experts called for a 5 × 5 strategy inclusive of neuropsychiatric disorders and infectious risks.33, 34 In July, 2013, at a meeting in Rwanda, a group of NCD unit leaders from ten African ministries of health called for a complementary strategy for NCDIs.35 This NCDI equity agenda focused on policies and integrated health-sector interventions to eliminate deaths among the poorest children and young adults (aged

ObjectivesTo provide lay information about genetics and sickle cell disease (SCD) and to identify and address ethical issues concerning the Sickle Cell Disease Genomics of Africa Network covering autonomy and research decision-making, risk of SCD complications and organ damage, returning of genomic findings, biorepository, data sharing, and healthcare provision for patients with SCD.DesignFocus groups using qualitative methods.SettingSix cities in Ghana, Nigeria and Tanzania within communities and secondary care.ParticipantsPatients, parents/caregivers, healthcare professionals, community leaders and government healthcare representatives.ResultsResults from 112 participants revealed similar sensitivities and aspirations around genomic research, an inclination towards autonomous decision-making for research, concerns about biobanking, anonymity in data sharing, and a preference for receiving individual genomic results. Furthermore, inadequate healthcare for patients with SCD was emphasised.ConclusionsOur findings revealed the eagerness of patients and parents/caregivers to participate in genomics research in Africa, with advice from community leaders and reassurance from health professionals and policy-makers, despite their apprehensions regarding healthcare systems.

BackgroundSickle cell disease (SCD) is a recognized cause of childhood mortality. Tanzania has the fifth highest incidence of SCD (with an estimated 11 000 SCD annual births) worldwide. Although newborn screening (NBS) for SCD and comprehensive healthcare have been shown to reduce under-5 mortality by up to 94% in high-income countries such as the USA, no country in Africa has maintained NBS for SCD as a national health program. The aims of this program were to establish and evaluate NBS-SCD as a health intervention in Tanzania and to determine the birth prevalence of SCD.MethodsMuhimbili University of Health and Allied Sciences conducted NBS for SCD from January 2015 to November 2016. Dried blood spot samples were collected and tested for SCD using isoelectric focusing.ResultsScreening was conducted on 3981 newborns. Thirty-one (0.8%) babies had SCD, 505 (12.6%) had sickle cell trait and 26 (0.7%) had other hemoglobinopathies. Twenty-eight (90.3%) of the 31 newborns with SCD were enrolled for comprehensive healthcare.ConclusionsThis is the first report on NBS as a health program for SCD in Tanzania. The SCD birth prevalence of 8 per 1000 births is of public health significance. It is therefore important to conduct NBS for SCD with enrollment into a comprehensive care program.

Background: Malaria morbidity and mortality, almost entirely from Plasmodium falciparum, are still rampant in Africa: therefore, it is important to study the biology of the parasite and the parasite-host cell interactions. In vitro cultivation of Plasmodium falciparum is most useful for this purpose, as well as for investigating drug resistance and possible new therapies. Here we report that the Trager & Jensen continuous culture of P. falciparum can be established in a laboratory in Tanzania with minimal facilities and with modest expenditure. Methodology: This was an in-vitro set up of continuous culture of Plasmodium falciparum study, carried out in 2016-2020 at Muhimbili university of health and allied sciences, Dar-es salaam. Parasite samples were obtained from patients with acute malaria, frozen parasites, and live cultures. Data was collected and analyzed using GraphPad Prism version 8. Results: We have successfully achieved exponential growth of existing strains that are used worldwide, as well as of parasites in clinical samples from patients with acute malaria. In the aim to optimize growth we have compared human serum and bovine serum albumin as components of the culture media. Additionally, culture synchronization has been achieved using sorbitol. Conclusion: This experimental system is now available to our institution and to researchers aiming at investigating drug sensitivity and mechanisms of protection against Plasmodium falciparum that accrue from various genes expressed in red cells.

BackgroundEven though the genomics technologies have grown to a large extent, Sub Saharan Africa countries have not entirely reaped the benefits due to the lack of enough capacity to use these technologies. The lack of documentation on existing bioinformatics capacity in these countries hinders the guidance on leveraging the resources and in the identification of areas for improvement. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related research in Tanzania. Our findings identify critical areas for skills and infrastructure development for bioinformatics research. The study is a cross-sectional, explorative, descriptive study, among Tanzanian researchers in public and private academic and research institutionsResultsOut of 84 respondents, 50 (59.5%) were males. More than half of these 44 (52.4%) were in the age between 26-32 years. The majority 41 (48.8%) were master's degree holders with at least one publication related to bioinformatics. Eighty (95.2%) were willing to join the bioinformatics network and initiative in Tanzania. The major challenge faced by 22 (26.2%) of respondents was the lack of training and skills. The most used resources for bioinformatics analyses were the BLAST, PubMed and GenBank. Most performed analyses include sequence alignment and phylogenetic, which was reported by 57 (67.9%) and 42 (50%) of respondents, respectively. The most frequently used statistical software packages were SPSS and R. A quarter of the respondents were conversant with computer programming.ConclusionEarly career and young scientists were the largest group of responders engaged in bioinformatics research and activities across surveyed institutions in Tanzania. The use of bioinformatics tools for analysis is still low, including basic analysis tools such as BLAST, GenBank, sequence alignment software, Swiss-prot and TrEMBL. There is also poor access to resources and tools for bioinformatics analyses. As a way to address the skills and resources gaps, we recommend various modes of training and capacity building of relevant bioinformatics skills and provision of infrastructure so as to improve bioinformatics capacity in Tanzania.

Background and Purpose— Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods— Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results— Compared with SCI− patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb ( P P Conclusions— SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.

Background: Monitoring of patient’s clinical attendance is one of the crucial means that is used to improve adherence to care and treatment among the Sickle Cell Disease (SCD) patients. Adherence to care has been shown to improve health outcomes in SCD patients. However, these benefits cannot be achieved when patients are lost to follow-up to care. Method : We analyzed data on loss to follow up to determine the patterns among sickle cell patients registered at Muhimbili Sickle Cell Cohort (MSC), in Dar es Salaam, Tanzania. Data was aggregated and analysed using R software and Microsoft Excel Spreadsheet. Survival analysis techniques, both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox’s proportional hazard model), were used. A p-value of 0.05 was considered significant to make a strong inference of the analysis. Results: 5476 SCD patients were registered at MSC from 2004 to 2016, 3350 (58.13%) were actively participating in clinics while, 2126 (41.87%) were inactive, out of which 35.19% were lost to follow-up. From the survival analysis results, patients who were between 5 to 17 years were more likely to be lost to follow-up than the rest with a hazard ratio of 2.65 times more than those who were above 18 years. Patients with mean cell volume above 77.73 fL and white blood cell above 15.73(10ˆ3/uL) were more likely to be loss to follow-up than those below average. Conclusion: Loss to follow-up is evident in a cohort of patients in long term comprehensive care follow-up. It is, therefore, necessary to design interventions that minimize its impacts. Suggested solutions might include training of the health care workers, more emphasis on newborn screening and advocacy to patients regarding the effect of loss to follow-up.

Background Patients with sickle cell disease (SCD), an inherited haemoglobinopathy, have increased risk of malaria, at least in part due to impaired splenic function. Infection with Plasmodium falciparum in SCD patients can trigger painful vaso-occlusive crisis, increase the severity of anaemia, and contribute to early childhood mortality. Case presentation A 17 year-old Tanzanian male with known SCD was admitted to Muhimbili National Hospital, a tertiary referral centre in Dar-es-Salaam, following an attack of malaria. From 2004 to 2007 the patient had lived in USA, and from 2010 to 2016 in France where, on account of hypersplenism and episodes of splenic sequestrations, in 2014 the spleen was removed. After appropriate clinical and laboratory assessment the patient was re-started on hydroxyurea; and anti-malarial-prophylaxis with proguanil was instituted. The patient has remained well and malaria-free for the following 15 months. Conclusion SCD patients are highly vulnerable to malaria infection, and impaired splenic function is a feature of SCD patients, even in those who still anatomically have a spleen. This patient had a surgical splenectomy and, in addition, had probably lost some of the acquired malaria-immunity by having lived for several years in malaria-free areas. This patient is a compelling reminder that long-term anti-malarial prophylaxis should be offered to all patients with SCD who live in malaria-endemic areas.

Sickle cell disease is one of the most common, life-threatening, non-communicable diseases in the world and a major public health problem. Following the implementation of simple preventive and therapeutic modalities, infant mortality has almost been abolished in high-income countries, but only a small amount of progress has been made in improving survival in adulthood. Progressive end-organ damage, partly related to a systemic vasculopathy, is increasingly recognised. With the availability of a variety of novel disease-modifying drugs, gene addition and gene editing strategies, matched sibling donor haematopoietic stem cell transplantation (HSCT) in children (offering an overall survival rate of 95% and an event-free survival rate of 92%), and encouraging outcomes after alternative donor HSCT, the new challenge is to risk stratify patients, revise transplantation indications, and define the best therapeutic approach for each patient. The ultimate challenge will be to enable these advances in low-income and middle-income countries, where disease prevalence is highest and where innovative strategies are most needed.

Sickle cell anemia neurologic complications The collaboration aims at exploring the relationship between the cerebral vasculature and neurologic complications in Tanzanian children with sickle cell anemia (SCA). Cerebral vasculopathy in internal carotid, middle, anterior cerebral, and posterior

Background Sickle cell anaemia (SCA) is prevalent in sub-Saharan Africa, with high risk of complications requiring emergency care. There is limited information about presentation of patients with SCA to hospitals for emergency care. We describe the clinical presentation, resource utilization, and outcomes of SCA patients presenting to the emergency department (ED) at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. Methods This was a prospective cohort study of consecutive patients with SCA presenting to ED between December 2014 and July 2015. Informed consent was obtained from all patients or patients’ proxies prior to being enrolled in the study. A standardized case report form was used to record study information, including demographics, relevant clinical characteristics and overall patients outcomes. Categorical variables were compared with chi-square test or Fisher’s exact test; continuous variables were compared with two-sample t-test or Mann-Whitney U-test. Results We enrolled 752 (2.7%) people with SCA from 28,322 patients who presented to the MNH-ED. The median age was 14 years (Interquartile range [IQR]: 6–23 years), and 395 (52.8%) were female. Pain 614 (81.6%), fever 289 (38.4%) were the most frequent presenting complaint. Patients with fever, hypoxia, altered mental status and bradycardia had statistically significant relative risk of mortality of 10.4, 153, 50 and 12.1 (p

Background: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia.Methods: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin.Results: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170Conclusions: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.

Sickle cell disease (SCD) is an inherited hemoglobinopathy leading to several serious organ complications and early death. It is mostly found in equatorial countries like Tanzania. Extradural hematoma (EDH) is a rare, but serious complication to SCD and may have debilitating consequences. Hitherto, there is no report of EDH in SCD where neuroimaging has been available before, during, and after such an event. Here, we describe a young female SCD patient who developed EDH that required surgical evacuation. She had made full recovery after three months. Neuroimaging performed two years prior to this event was unremarkable except for multiple small cerebral infarcts. On admission, neuroimaging revealed a subgaleal hematoma, possibly indicating disruption of the skull cortex due to increased hematopoiesis. Three months after evacuation of the hematoma, neuroimaging showed evidence of brain atrophy and the previously reported cerebral infarcts and multifocal bone infarction, but no vasculopathy. Possibly, disruption of the skull cortex with subsequent bleeding caused the EDH. As the differential diagnoses of neurological complications in SCD are many and some complications are reversible, neuroimaging should be performed without delay.

In April 2017, a workshop sponsored by the National Heart, Lung, and Blood Institute, Division of Blood Diseases and Resources, and the Center for Translation Research and Implementation Science was held to discuss blood availability and transfusion safety in low- and middle-income countries (LMICs). The purpose of the workshop was to identify research opportunities for implementation science (IS) to improve the availability of safe blood and blood components and transfusion practices in LMICs. IS describes the late stages of the translational research spectrum and studies optimal and sustainable strategies to deliver proven-effective interventions. Regional working groups were formed to focus on opportunities and challenges in East Africa, Central/West Africa, Middle East and North Africa, Latin America and the Caribbean, Southeast Asia, Western Pacific Asia, Eastern Europe, and Central Asia. The need for an "adequate supply of safe blood" emerged as the major overriding theme. Among the regional working groups, common cross-cutting themes were evident. The majority of research questions, priorities, and strategies fell into the categories of blood availability, blood transfusion safety, appropriate use of blood, quality systems, health economics and budgeting, and training and education in IS. The workshop also brought into focus inadequate country-level data that can be used as the basis for IS initiatives. A mixed approach of needs assessment and targeted interventions with sufficient evidence base to move toward sustainment is an appropriate next step for blood availability and transfusion safety research in LMICs.

Higher levels of fetal hemoglobin (HbF) ameliorate the clinical course of sickle cell disease. Hydroxyurea, an inhibitor of the enzyme ribonucleoside diphosphate reductase, increases HbF synthesis ...

Summary Anaemia and iron deficiency (ID) are common and of prognostic importance in heart failure (HF). In both conditions the epidemiology, diagnosis and therapies have been extensively studied in high-income countries but are still largely unexplored in sub-Saharan Africa (SSA). The lack of adequate and robust epidemiological data in SSA makes it difficult to recognise the significance of anaemia and ID in HF. From a clinical perspective, less attention is paid by clinicians to screening for anaemia in HF, and as far as interventions are concerned, there are no clinical trials in SSA that provide guidance on the appropriate interventional approach. Therefore studies are needed to provide more insight into the burden and peculiarities of and intervention for anaemia and ID in HF in SSA, where the pathophysiology might be different from that in high-income countries. There is increasing appreciation that targeting ID may serve as a useful additional treatment strategy for patients with chronic HF in high-income countries. However, there is limited information on the diagnosis of and therapy for ID in HF in SSA, where infections and malnutrition are more likely to influence the situation. This article reviews the present epidemiological gap in knowledge about anaemia and ID in HF, as well as the diagnostic and therapeutic challenges in SSA.

Fetal hemoglobin (HbF) and peripheral hemoglobin oxygen saturation (SpO2) both predict clinical severity in sickle cell disease (SCD), while reticulocytosis is associated with vasculopathy, but there are few data on mechanisms. HbF, SpO2 and routine clinical and laboratory measures were available in a Tanzanian cohort of 1175 SCD individuals aged ≥ 5 years and the association with SpO2 (as response variable transformed to a Poisson distribution) was assessed by negative binomial model with age and sex as covariates. Increase in HbF was associated with increased SpO2 (rate ratio, RR = 1.19; 95% confidence intervals [CI] 1.04, 1.37 per natural log unit of HbF; p = 0.0004). In univariable analysis, SpO2 was inversely associated with age, reticulocyte count, and log (total bilirubin) and directly with pulse, SBP, hemoglobin, and log(HbF). In multivariable regression log(HbF) (RR 1.191; 95%CI 1.04, 1.37; p = 0.013), pulse (RR 1.01; 95%CI 1.00, 1.01; p = 0.026), SBP (RR 1.008; 95%CI 1.00, 1.02; p = 0.014), and hemoglobin (1.120; 95%CI 1.05, 1.19; p = 0.001) were positively and independently associated with SpO2 while reticulocyte count (RR 0.985; 95%CI 0.97, 0.99; p = 0.019) was independently inversely associated with SpO2. In SCD, improving SpO2, in part through cardiovascular compensation and associated with reduced reticulocytosis, may be a mechanism by which HbF reduces disease severity., Highlights • Fetal hemoglobin may moderate sickle cell disease through increased oxygen saturation. • Low oxygen saturation is associated with reticulocytosis which might moderate cerebral vasculopathy and stroke risk. • Higher pulse rate and systolic blood pressure in those with higher SpO2 suggests cardiovascular compensation for low SpO2. Fetal hemoglobin (HbF) is normally synthesized during intrauterine life and it starts to decline before birth being replaced by adult hemoglobin (HbA). However some individuals continue to synthesize HbF to adulthood and are relatively protected from severe sickle cell disease. The mechanism of HbF protection in SCD has not been entirely established. This study reports a positive association between HbF and oxygen saturation (SpO2). Higher SpO2 is associated with decreased reticulocytes but increased pulse rate and systolic blood pressure, suggesting SpO2 is maintained in part through cardiovascular compensation. Increasing HbF may reduce disease severity partly through increasing SpO2.

Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity and mortality around the world. While decades of research have led to improved survival for SCD patients in wealthy countries, survival remains dismal in low- and middle-income countries. Much of the early mortality associated with SCD is attributed to increased risk of infections due to early loss of splenic function. In the West, bacterial infections with encapsulated organisms are a primary concern. In sub-Saharan Africa, where the majority of infants with SCD are born, the same is true. However malaria presents an additional threat to survival. The search for factors that define variability in sickle cell phenotypes should include environmental modifiers, such as malaria. Further exploration of this relationship could lead to novel strategies to reduce morbidity and mortality attributable to infections. In this review, we explore the interactions between SCD, malaria and the spleen to better understand how splenomegaly and splenic (dys)function may co-exist in patients with SCD living in malaria-endemic areas.