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In South Sudan, three case-control studies found a positive association between Nodding Syn-drome (NS) and a Mansonella perstans infection. To investigate whether M. perstans could play the primary and sole causal role in the development of NS, we examined blood films of persons with and without epilepsy in rural villages affected by NS in Mahenge, Tanzania, to identify M. perstans infections. Study participants were also examined for onchocercal nodules and skin lesions and tested for the presence of anti-O. volvulus antibodies (Ov16 ELISA). One hundred and thirteen epilepsy cases and 132 controls were enrolled, with a mean age of 28.3 years (interquartile range 22 – 34 years); 125 (51%) were females. Of the persons with epilepsy, 43 (38.1%) met the probable NS criteria. M. perstans infection was absent in all participants, but Ov16 prevalence and oncho-cerciasis-associated skin manifestations were positively associated with epilepsy, including probable NS. Onchocercal nodules in the mothers of cases were also positively associated with epilepsy. In conclusion, in contrast with O. volvulus, M. perstans is likely not endemic in Mahenge and therefore cannot be a co-factor for NS in the area. Hence, this filaria cannot be the primary and sole causal factor in the development of NS.

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.

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

IntroductionThe paucity of data describing cardiovascular disease (CVD) in pregnancy in many parts of Africa including Tanzania has given rise to challenges in proper management by the healthcare providers. This study is set out to (1) determine the prevalence of a range of CVDs during pregnancy in women attending antenatal clinics in Tanzania and (2) determine the impact of these CVDs on maternal and fetal outcomes at delivery.Methods and analysisThis is a cross-sectional study with a prospective component to be conducted in two referral hospitals in Tanzania. Pregnant women aged ≥18 years diagnosed with a CVD during the antenatal period are being identified and extensively characterised by performing clinical assessment, modified WHO staging, electrocardiography, echocardiography and laboratory tests. Patients identified with CVDs (exposed) and a subset without (unexposed) will be followed up to determine maternal and fetal outcomes at delivery. A minimum sample of 1560 will be sufficient to estimate the prevalence of CVDs with a 95% CI of 2.75% to 5.25%.Ethics and disseminationThe study is being conducted in accordance with the Helsinki declaration on studies involving human subjects. Ethical approvals have been obtained from Muhimbili University (reference number DA.282/298/01.C/) and Bugando Medical Centre (reference number CREC/330/2019) Ethics Committees. Informed consent is sought from all potential participants before any interview or investigations are performed. Study findings will be disseminated to the scientific community through different methods. Results will also be communicated to policymakers and to the public, as appropriate.

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.

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.

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.

Background The distribution of human parvovirus B19 (HPV B19) infection is ubiquitous and occurs worldwide. The virus has high tropism to red blood cells progenitor's cells leading to temporary infection of bone marrow and transient arrest of erythropoiesis. People with frequent episodes of hemolytic anemia including sickle cell disease (SCD) and thalassemia are at increased risk of infection. This study aimed at assessing prevalence and factors associated with HPV B19 infections among hospitalized SCD patients. Methodology This was a cross-sectional hospital-based study among SCD patients hospitalized at Muhimbili National Hospital. HPV B19 was detected using RT-PCR. Hematological and Chemistry tests were done using Sysmex XT2000i and Chemistry analyzer respectively. Results A total of 329 SCD patients, median age 15 years (interquartile range 7-22 years) were tested for HPV B19. The prevalence of HPV B19 was 29%. In multivariate logistic regression model, HPV B19 infection was associated with pain (OR=4.28, 95%CI: 1.20-15.19; p=0.025), low neutrophil counts (OR=0.57, 95%CI: 0.35-0.92, p=0.022) and MCH (OR=0.92, 95%CI: 0.85-0.99; p=0.033). Individuals infected with HPV B19 had slightly higher prevalence of severe anaemia (30.4% vs. 20.3%, p=0.054) and HIV infection (6.0% vs. 2.1%, p=0.083) in the univariate analysis. Considering the effect of HPV B19 virus on spleen, aplastic anemia and platelet counts in SCD patients, our study did not find any association with these parameters (p=0.244; p= 0.205 and p=0.567 respectively). Conclusion The prevalence of HPV B19 among hospitalized SCD patients at MNH was high. SCD patients with HPV B19 were more likely to present with pain, low neutrophils levels, and MCH. HIV infection might be associated with a high risk of HPV infection in SCD patients; however, this requires further investigation.

BACKGROUND Sickle cell disease (SCD) is the most common inherited disorder worldwide, with the highest burden in sub-Saharan Africa. The natural history of SCD is characterized by periods of steady state interspersed by acute episodes. The acute anemic crises may be transient and are precipitated by treatable factors like infections, nutritional deficiencies, and sequestration. Anemia is almost always present, although it occurs at different levels of severity. OBJECTIVE This paper describes the protocol of a cross-sectional study to determine the prevalence of severe anemia and associated factors among sickle cell patients hospitalized at the Muhimbili National Hospital. METHODS This is an ongoing, descriptive, cross-sectional, hospital-based study among individuals with SCD, admitted to the Muhimbili National Hospital in Dares Salaam, Tanzania. A minimum sample size of 369 was calculated based on the previous prevalence of hospitalizations due to severe anemia (20%) in the same cohort. We are using a piloted standardized case report form to document clinical and laboratory parameters following informed consent. Data analysis will be performed using Stata software. Severe anemia is defined as Hb RESULTS Enrolment commenced in January 2015 and concluded in September 2016. Complete data analysis will begin in February 2018. The study results are expected to be published in May 2018. CONCLUSIONS This protocol paper will provide a useful and practical model for conducting cross-sectional studies in hospitalized patients that cover a wide ranging of clinical and laboratory variables.

International audience; The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.

Raphael Z. Sangeda's presentation at the ISCB Student Council Symposium-Africa 2015, Dar es Salaam, Tanzania

BACKGROUND: Common genetic variants residing near upstream regulatory elements for MYB, the gene encoding transcription factor cMYB, promote the persistence of fetal hemoglobin (HbF) into adulthood. While they have no consequences in healthy individuals, high HbF levels have major clinical benefits in patients with sickle cell disease (SCD) or β thalassemia. Here, we present our detailed investigation of HBS1L-MYB intergenic polymorphism block 2 (HMIP-2), the central component of the complex quantitative-trait locus upstream of MYB, in 1,022 individuals with SCD in Tanzania. METHODS: We have looked at 1022 individuals with HbSS or HbS/β(0) in Tanzania. In order to achieve a detailed analysis of HMIP-2, we performed targeted genotyping for a total of 10 SNPs and extracted additional 528 SNPs information from a genome wide scan involving the same population. Using MACH, we utilized the existing YRI data from 1000 genomes to impute 54 SNPs situated within HIMP-2. RESULTS: Seven HbF-increasing, low-frequency variants (β > 0.3, p

BACKGROUND: Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection. METHODS: The study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tanzania. SCD status was categorized into HbAA, HbAS and HbSS using hemoglobin electrophoresis and High Performance Liquid Chromatography (HPLC). HbF levels were determined by HPLC. Malaria was diagnosed using rapid diagnostic test and/or blood film. Logistic regression and generalized estimating equations models were used to evaluate associations between SCD status, HbF and malaria. FINDINGS: 2,049 individuals with age range 0-70 years, HbAA 311(15.2%), HbAS 241(11.8%) and HbSS 1,497(73.1%) were analysed. At enrolment, malaria prevalence was significantly higher in HbAA 13.2% compared to HbAS 1.24% and HbSS 1.34% (p

Fetal hemoglobin (HbF) is a recognized modulator of sickle cell disease (SCD) severity. HbF levels are strongly influenced by genetic variants at three major genetic loci, Xmn1‐HBG2, HMIP‐2, and BCL11A, but the effect of these loci on the hematological phenotype in SCD, has so far not been investigated. In a cohort of individuals with SCD in Tanzania (HbSS and HbS/β° thalassemia, n = 726, aged 5 or older), HbF levels were positively correlated with hemoglobin, red blood cell (RBC) indices, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH), and negatively with white blood cell (WBC) and platelet counts (all P < 0.0001). We subsequently assessed the contribution of the three HbF modifier loci and detected diverse effects, including a reduction in anemia, leukocytosis, and thrombocytosis associated with certain HbF‐promoting alleles. The presence of the ‘T’ allele at Xmn1‐HBG2 led to a significant increase in hemoglobin (P = 9.8 × 10−3) but no changes in cellular hemoglobin content. Xmn1‐HBG2 ‘T’ also has a weak effect decreasing WBC (P = 0.06) and platelet (P = 0.06) counts. The BCL11A variant (rs11886868‐‘C’) increases hemoglobin (P = 2 × 10−3) and one of the HBS1L‐MYB variants decreases WBC values selectively (P = 2.3 × 10−4). The distinct pattern of effects of each variant suggests that both, disease alleviation through increased HbF production, and ‘pleiotropic’ effects on blood cells, are involved, affecting a variety of pathways. Am. J. Hematol. 90:E1–E4, 2015. © 2014 Wiley Periodicals, Inc.

In January 2007, Tanzania replaced sulfadoxine-pyrimethamine (SP) with artemether-lumefantrine for treatment of uncomplicated malaria. This study examined the impact of widespread SP use on molecular markers of Plasmodium falciparum drug resistance in blood samples from persons living in two villages in Korogwe District, Tanzania, from 2003 through 2007. The prevalence of the P. falciparum dihydropteroate synthase (Pfdhps) gene 581G mutation increased from 12% in 2003 to 56% in 2007 (P0.001), resulting in an increase in the triple mutant Pfdhps haplotype SGEGA from 8% to 32% (P0.001). In contrast, the chloroquine-sensitive P. falciparum chloroquine resistance transporter (Pfcrt) CVMNK haplotype increased from 6% to 30% (P0.001). The dramatic increase of the triple Pfdhps mutant SGEGA haplotype may endanger the continued use of SP for intermittent presumptive treatment of pregnant women (IPTp). Further studies are needed to determine the importance of Pfdhps SGEGA haplotype parasites on the efficacy of SP for IPTp.

The prevalence of human red blood cell (RBC) polymorphisms is high in areas of intense Plasmodium falciparum transmission, and individuals carrying these genetic traits are believed to be partially protected against severe malaria. However, it remains uncertain how RBC polymorphisms affect the susceptibility to uncomplicated malaria. We compared the risk of suffering from febrile, uncomplicated malaria between individuals carrying three common RBC polymorphisms (sickle cell trait, alpha(+)-thalassemia, and glucose-6-phosphate-dehydrogenase deficiency) and controls. The study was performed in an area of intense malaria transmission where 202 individuals 0-19 years of age were monitored clinically for a period of 6 months. RBC polymorphisms were assessed with molecular methods, and plasma antibodies to P. falciparum variant surface antigens (anti-VSA IgG) and glutamate-rich protein (anti-GLURP IgG) were measured with flow cytometry and ELISA assays, respectively. Regression analyses showed that alpha(+)-thalassemia was associated with a reduced risk of uncomplicated malaria episodes and that this advantageous effect seemed to be more predominant in children older than 5 years of age, but was independent of levels of antibodies to VSA and GLURP.