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 <0.005). Compared with VSC− patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions ( P <0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. 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.
Imatinib is the mainstay of treatment of patients with chronic myeloid leukemia (CML) in Tanzania. Monitoring molecular response to therapy by real-time polymerase chain reaction at defined milestones is necessary for early detection of treatment failure. However, this assay is not routinely performed in Tanzania; therefore, the depth of molecular response among patients with CML is not known. A total of 158 patients with previously diagnosed CML who received imatinib treatment were recruited from January 2019 and followed up through October 2020 at Ocean Road Cancer Institute. Information was obtained at the time of diagnosis and follow-up. Blood samples were collected in EDTA tubes to measure the BCR/ABL ratio on the Gene Xpert system for molecular response determination. The median age of the 158 adult patients was 45 years (range, 18-86). By reference to established treatment milestones, only 37 (23.4%) achieved optimal molecular response. Signs of advanced-stage disease, in particular the need for red cell transfusions before diagnosis (adjusted odds ratio [AOR], 3.4; 95% CI, 1.32-9.17) and cytopenias (AOR, 2.26; 95% CI, 1.03-4.96) necessitating drug interruptions were statistically validated predictors of treatment failure on multivariate, multinomial logistic regression. Patient survival at the 22-month follow-up was lowest, with 78.6% (95% CI, 69.4-85.4) in the failure-to-respond category and highest in patients achieving optimal response 97.0% (95% CI, 80.9-99.6). In summary, the majority of patients with CML treated with imatinib in Tanzania do not obtain deep molecular response. This outcome can be attributed to late diagnosis, the development of cytopenias requiring multiple drug interruptions, and poor adherence to treatment.
Background The capacity for invasive tissue biopsies followed by histopathology diagnosis in sub-Saharan Africa is severely limited. Consequently, many cancer patients are diagnosed late and outcomes are poor. Here, we propose to evaluate circulating tumour (ct) DNA analysis (“liquid biopsy”), a less invasive and faster approach to diagnose endemic EBV-driven lymphomas (EBVL) in East Africa. Methods We will evaluate the clinical utility of an already validated ctDNA test prospectively in a head-to-head comparison against histopathology. The primary endpoint is the time from presentation to the specialist centre to a final diagnosis of EBV- Lymphoma. Secondary endpoints include the sensitivity and specificity of liquid biopsy and health economic benefits over histopathology. One hundred forty-six patients will be recruited over 18 months. Patients will be eligible if they are 3–30 years of age and have provided written consent or assent as per IRB guidelines. Tissue and venous blood samples will be processed as per established protocols. Clinical data will be captured securely and in real-time into a REDCap database. The time from presentation to diagnosis will be documented. The sensitivity and specificity of the methods can be estimated within 5% error margin with 95% confidence level using 73 cases and 73 controls. Health-economic assessment will include micro-costing of ctDNA test and histopathology. All results will be reviewed in a multidisciplinary tumour board. Discussion The study evaluates the clinical utility of ctDNA in improving the speed of diagnostic pathways for EBVL in sub-Saharan Africa. Our results would provide proof-of-principle that ctDNA can be used as a diagnostic tool in areas without access to regular pathology, that transfer of the tool is feasible, and that it leads to an earlier and faster diagnosis. The potential clinical and economic impact of this proposal is thus significant. If successful, this study will provide appropriate, and cost-effective diagnostic tools that will promote earlier diagnosis of EBVL and potentially other cancers in countries with restricted healthcare resources. Trial registration Pan African Clinical Trials Registry: PACTR202204822312651, registered on 14th-April-2022.
Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with blood transfusion an integral part in its management. Red cell exchange (RCE) transfusion is usually regarded as preferable to top-up transfusion, because it reduces the proportion of Hemoglobin (Hb) S while at the same time avoiding circulatory overload. Despite its obvious benefits, RCE is underutilized, particularly in low-resource settings which may be due to scarcity of blood products and of expertise in carrying out exchange transfusion. We report on a young woman with SCD with severe ACS who responded promptly and dramatically to a RCE of only 0.95 L (instead of the recommended 1.4 L) and had in the end an HbS level of 48% (instead of the recommended level below 30%). Limited RCE resulted in significant clinical improvement. We suggest that limited RCE may be of benefit than no RCE in SCD patients with ACS, particularly in settings where RCE is not available.
Background: Sickle cell disease (SCD) is an important cause of <5 mortality. In Tanzania, it is estimated up to 11 000 children are born with SCD annually, making this the fifth country with the highest SCD annual births worldwide. The biggest challenge of expanding the service of newborn screening for SCD as the national health intervention in Tanzania is due to the high cost of the currently used assays and lack of rapid screening methods. Therefore, in this study, we assessed the diagnostic accuracy of point-of-care tests for SCD diagnosis in newborns.Aim: To evaluate the sensitivity and specificity of HemotypeSC™ and sickle SCAN ® in diagnosing SCD in newborns.Methods: Diagnostic accuracy of HemotypeSC™ and sickle SCAN ® were evaluated in comparison to isoelectric focusing as a confirmatory method.Results: A total of 706 newborns were enrolled in the study. The sensitivity and specificity of HemotypeSC in detecting Hb SS, Hb AS and Hb AA phonotypes was 100%. The sensitivity and specificity of sickle SCAN ® in detecting Hb SS, Hb AS and Hb AA phenotypes were 100%, 97% and 100% respectively. Conclusion:Both POC tests displayed high accuracy in detecting SCD, we believe the introduction of either of these tests in health facilities will help in the early detection and management of SCD. In addition, the margin of cost per test is relatively affordable (1.
Burkitt lymphoma (BL) has a cure rate of around 95% when treated with chemo-immunotherapy that is standard of care in high-income countries (Minard-Colin et al., 2020, New England Journal of Medicine 382, 2207–2219), but currently, more than 50% of children and young adults with endemic BL (Epstein Barr virus driven BL) in sub-Saharan Africa (SSA) do not survive. Treatment for BL is largely free of charge, but there is limited access to reliable diagnostic services leading to significant delays and misdiagnoses. Innovations in histopathology such as whole slide imaging and the use of novel diagnostic approaches, in particular using circulating cell-free viral and/or lymphoma DNA (liquid biopsy), could increase access to timely and reliable diagnosis and improve outcomes in SSA.
Introduction. Anaemia is a common problem in sub-Saharan Africa. While most literature has focused on children, women of childbearing age, and pregnant women, data for the elderly population are relatively scarce. Anaemia exhorts negative consequences to functional ability of elderly patients, both physically and cognitively. The purpose of this study was to determine the prevalence of anaemia, severity, and micronutrient deficiency status in the elderly hospitalized patients in Tanzania. Methods. A total of 156 hospitalized adults aged 60 years and above were enrolled in this study. A structured questionnaire was used to capture sociodemographic and clinical characteristics. Blood samples were collected, and a complete blood count, serum cobalamin, serum ferritin, and serum folate levels were measured to assess anaemia and micronutrient deficiency status in all participants who had anaemia. Results. The prevalence of anaemia was 79.5% (124/156) with severe anaemia in 33.9% (42/124) of participants, moderate anaemia in 42.7% (53/124) of participants, and 23.4% (29/124) of all participants had mild anaemia. Micronutrient deficiency was found in 14.5% (18/124) of all participants with anaemia. Combined deficiency (either iron and vitamin B12 deficiency or iron and folate deficiency) was the most common micronutrient deficiency anaemia with a frequency of 33.3% (6/18), followed by isolated iron and folate deficiencies at equal frequency of 27.8% (5/18) and vitamin B12 deficiency at 11.1% (2/18). Conclusion. The prevalence of anaemia in the hospitalized elderly population is high warranting public health attention and mostly present in moderate and severe forms. Micro-nutrient deficiency anaemia is common in this age group and is mostly due to combined micronutrient deficiency.
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