Browsing by Author "Thein, Swee L"

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    Fetal Hemoglobin is Associatedwith Peripheral Oxygen Saturation in Sickle Cell Disease in Tanzania
    (EBioMedicine, 2017) Nkya, Siana; Mgaya, Josephine; Urio, Florence; Makubi, Abel; Thein, Swee L; Menzel, Stephan; Cox, Sharon E.; Newton, Charles R; Kirkham, Fenella J; Mmbando, Bruno P; Makani, Julie
    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 laboratorymeasureswere available in a Tanzanian cohort of 1175 SCD individuals aged ≥ 5 years and the associationwith 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.
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    g(HbF): a genetic model of fetal hemoglobin in sickle cell disease.
    (Blood advances., 2018) Gardner, Kate; Fulford, Tony; Silver, Nicholas; Rooks, Helen; Angelis, Nikolaos; Allman, Marlene; Nkya, Siana; Makani, Julie; Howard, Jo; Kesse-Adu, Rachel; Rees, David C; Stuart-Smith, Sara; Yeghen, Tullie; Awogbade, Moji; Sangeda, Raphael; Mgaya, Josephine; Patel, Hamel; Newhouse, Stephen; Menzel, Stephan; Thein, Swee L
    Fetal hemoglobin (HbF) is a strong modifier of sickle cell disease (SCD) severity and isassociated with 3 common genetic loci. Quantifying the genetic effects of the 3 loci wouldspecifically address the benefits of HbF increases in patients. Here, we have applied statisticalmethods using the most representative variants:rs1427407andrs6545816inBCL11A,rs66650371(3-bp deletion) andrs9376090inHMIP-2A,rs9494142andrs9494145inHMIP-2B,andrs7482144(Xmn1-HBG2in theb-globin locus) to createg(HbF), a genetic quantitativevariable for HbF in SCD. Only patients aged$5 years with complete genotype and HbFdata were studied. Five hundred eighty-one patients with hemoglobin SS (HbSS) or HbSb0thalassemia formed the“discovery”cohort. Multiple linear regression modeling rational-ized the 7 variants down to 4 markers (rs6545816,rs1427407,rs66650371, andrs7482144)eachindependentlycontributing HbF-boosting alleles, together accounting for 21.8% of HbFvariability (r2) in the HbSS or HbSb0patients. The model was replicated with consistentr2in 2 different cohorts: 27.5% in HbSC patients (N5186) and 23% in 994 Tanzanian HbSSpatients.g(HbF), our 4-variant model, provides a robust approach to account for the geneticcomponent of HbF in SCD and is of potential utility in sickle genetic and clinical studies
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    A ten year review of the sickle cell program in Muhimbili National Hospital, Tanzania
    (BMC Hematology, 2018) Makani, Julie; Tluway, Furahini; Makubi, Abel; Soka, Deogratius; Nkya, Siana; Sangeda, Raphael; Mgaya, Josephine; Rwezaula, Stella; Kirkham, Fenella J; Kindole, Christina; Osati, Elisha; Meda, Elineema; Snow, Robert W; Newton, Charles R; Roberts, David; Aboud, Muhsin; Thein, Swee L; Cox, Sharon E.; Luzzatto, Lucio; Mmbando, Bruno P
    Background:Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studiesproviding reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established theMuhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seenin the first 10 years at Muhimbili National Hospital (MNH).Methods:Individuals seen at MNH known or suspected to have SCD were enrolled at clinic and laboratory testingfor SCD, haematological and biochemical analyses done. Ethnicity was self-reported. Clinical and laboratory featuresof SCD were documented. Comparison was made with non-SCD population as well as within 3 different agegroups (< 5, 5–17 and≥18 years) within the SCD population.Results:From 2004 to 2013, 6397 individuals, 3751 (58.6%) SCD patients, were enrolled, the majority (47.4%) in agegroup 5–17 years. There was variation in the geographical distribution of SCD. Individuals with SCD compared tonon-SCD, had significantly lower blood pressure and peripheral oxygen saturation (SpO2). SCD patients had higherprevalence of severe anemia, jaundice and desaturation (SpO2< 95%) as well as higher levels of reticulocytes, whiteblood cells, platelets and fetal hemoglobin. The main causes of hospitalization for SCD within a 12-month periodpreceding enrolment were pain (adults), and fever and severe anemia (children). When clinical and laboratoryfeatures were compared in SCD within 3 age groups, there was a progressive decrease in the prevalence of splenicenlargement and an increase in prevalence of jaundice. Furthermore, there were significant differences withmonotonic trends across age groups in SpO2, hematological and biochemical parameters.Conclusion:This report confirms that the wide spectrum of clinical expression of SCD observed elsewhere is alsopresent in Tanzania, with non-uniform geographical distribution across the country. Age-specific analysis is consistentwith different disease-patterns across the lifespan.