Increased memory phenotypes of CD4+ and CD8+ T cells in children with sickle cell anaemia in Tanzania

Background: Infection is an important cause of morbidity in children with sickle cell anaemia (SCA). However, little is currently known regarding the spectrum of adaptive immune derangement in SCA, especially of populations in Sub-Saharan Africa. In this study, we investigated the phenotype and activation status of T and B lymphocytes among children with SCA in Tanzania.Methods: We compared 30 children with SCA aged 1–6 years in steady-state with 10 age-matched controls. We assessed white blood cell count, T and B lymphocyte phenotype and activation status using an automated haematology analyser and multiparameter Flow Cytometry.Results: In children with SCA, the absolute lymphocyte, monocyte and granulocyte counts were all increased. There was also an increase in proportion of central/transitional memory (42.4% vs. 33.3%, p = 0.0100), effector memory (7.8% vs. 5.4%, p = 0.0086) and terminally differentiated (2.3% vs. 1.3%, p = 0.0355) CD4+ T cells as well as effector memory CD8+ T cells (21.3% vs. 11.5%, p = 0.0060) in children with SCA. In contrast, there was no difference in naïve, classical memory, atypical memory and IgM memory B-cells between the two groups. The level of activation of both T and B cells were comparable between children with and without SCA. Furthermore, we observed a significant inverse correlation between frequency of the effector memory CD8+ T cells and haematocrit (Spearman rho = -0.3859, p = 0.0352). Conclusions: Children with SCA in Tanzania show an absolute increase in all leukocyte types, including lymphocytes, with skewing of both CD4+ and CD8+ T cells towards the memory phenotypes. These findings provide insights on the development of adaptive immunity which may have implications on vaccine responsiveness, allo-immunisation, auto-immune diseases and transplant immunology in children with SCA

Effects of Hydroxyurea Treatment on Haemolysis in Patients with Sickle Cell Disease at Muhimbili National Hospital, Tanzania

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 &nbsp

National Non-Communicable Diseases Conferences- A Platform to Inform Policies and Practices in Tanzania

Background: Non-communicable diseases (NCDs) arise from diverse risk factors with differences in the contexts and variabilities in regions and countries. Addressing such a complex challenge requires local evidence. Tanzania has been convening stakeholders every year to disseminate and discuss scientific evidence, policies, and implementation gaps, to inform policy makers in NCDs responses. This paper documents these dissemination efforts and how they have influenced NCDs response and landscape in Tanzania and the region. Methods: Desk review was conducted through available MOH and conference organizers’ documents. It had both quantitative and qualitative data. The review included reports of the four NCDs conferences, conference organization, and conduct processes. In addition, themes of the conferences, submitted abstracts, and presentations were reviewed. Narrative synthesis was conducted to address the objectives. Recommendations emanated from the conference and policy uptake were reviewed and discussed to determine the impact of the dissemination. Findings: Since 2019, four theme-specific conferences were organized. This report includes evidence from four conferences. The conferences convened researchers and scientists from research and training institutions, implementers, government agencies, and legislators in Tanzania and other countries within and outside Africa. Four hundred and thirty-five abstracts were presented covering 14 sub-themes on health system improvements, financing, governance, prevention intervention, and the role of innovation and technology. The conferences have had a positive effect on governments’ response to NCDs, including health care financing, NCDs research agenda, and universal health coverage. Conclusion: The National NCDs conferences have provided suitable platforms where stakeholders can share, discuss, and recommend vital strategies for addressing the burden of NCDs through informing policies and practices. Ensuring the engagement of the right stakeholders, as well as the uptake and utilization of the recommendations from these platforms, remains crucial for addressing the observed epidemiological transition in Tanzania and other countries with similar contexts

Training in the art and science of facilitation to scale research mentor training in low and middle income countries

Advancing biomedical research in low and middle income countries (LMICs) to expand the capacity for LMICs to integrate biomedical research into their health care systems and education has been the focus of many programs in global health over the past two decades. Central to the success of these programs is effective research mentoring, characterized by academic, career and psychosocial support through culturally appropriate practices. Research mentoring is a learned skill, developed through training, mutual discussions, practice and feedback. The majority of extant training programs are designed and delivered by US partners, so the next stage in building capacity is to train facilitators within the LMIC partner institutions to contextualize and advance mentoring specifically within their cultural and institutional norms by co-developing, delivering and evaluating semi-annual research mentoring training. To this end, we describe the development, delivery and outcome evaluation of a 5-week course in the art and skill of facilitation. Care was taken to explicitly distinguish between concepts of “teaching” and “facilitation,” since “teaching” is closely connected to a transmission or banking model of education, which is characterized by “top-down,” hierarchical relationship. The course discussed power and positionality, themes that resonate with partners in Nigeria and Tanzania. These themes provided unique entry into deeper conversations core to advancing mentoring practice away from the traditional dyadic power structure that remains from colonization. Evaluation findings indicate significant advances in awareness of differences between teaching and facilitating, increased confidence in facilitation skills, especially in the area of structured planning and organization, as well as improved communication and interpersonal skills. All respondents felt that students in Nigeria and Tanzania would respond well to the facilitation approach conveyed during the course and they found value in participating in the course as a cohort

Non-communicable Diseases Week: Best Practices in Addressing the NCDs Burden from Tanzania

Background: Five million people die every year from non-communicable diseases (NCDs) globally. In Tanzania, more than two-thirds of deaths are NCD-related. The country is investing in preventive and advocacy activities as well as interventions to reduce the burden. Of particular interest, the Ministry of Health (MoH) commemorates NCDs’ week using a multisectoral and multi-stakeholders’ approach. This paper highlights activities conducted during NCDs week with the aim of sharing lessons for other countries with similar context and burdens. Methods: A thorough review of official reports and the national strategic plans for NCDs was done including the 2020 and 2021 National NCDs’ week reports, the National Strategic Plan for NCDs 2015–2020, and the National NCDs agenda. Findings: NCDs week is commemorated annually throughout the country involving the five key activities. First, community awareness and participation are encouraged through media engagement and community-based preventive and advocacy activities. Second, physical activities and sports festivals are implemented with a focus on developing and renovating infrastructures for sports and recreation. Third, health education is provided in schools to promote healthy behaviors for secondary school adolescents in transition to adulthood. Fourth, health service provision and exhibitions are conducted involving screening for hypertension, diabetes, obesity, alcohol use, and physical activities. The targeted screening of NCDs identified 10% of individuals with at least one NCD in 2020. In 2021, a third of all screened individuals were newly diagnosed with hypertension, and 3% were found to have raised blood glucose levels. Fifth, the national NCDs scientific conferences conducted within the NCDs week provide an avenue for stakeholders to discuss scientific evidence related to NCDs and recommend strategies to mitigate NCDs burden. Conclusion: The initiation of NCDs week has been a cornerstone in advocating for NCDs control and prevention in the country. It has created awareness on NCDs, encourage healthy lifestyles and regular screening for NCDs. The multi-stakeholder and multi-sectoral approaches have made the implementation of the mentioned activities feasible and impactful. This has set an example for the united efforts toward NCD control and prevention at national, regional, and global platforms while considering contextual factors during adoption and implementation

Newborn Screening for Sickle Cell Disease in Tanzania: The Past, Present and Future

Sickle Cell Disease (SCD) is an inherited disorder of the Haemoglobin molecule of the red blood cells that is associated with serious complications and reduced life expectancy. Over 75% of people with SCD live in Sub-Saharan Africa (SSA), and this proportion are projected to increase to 85% by the year 2050. In Tanzania, approximately 11,000 babies are born with SCD each year, ranking 5th in the world. The high prevalence of SCD in SSA is compounded by the disproportionately higher mortality compared to that observed in the high-income countries. In Tanzania, SCD is a major contributor to under-five mortality and is estimated to account for 7% of all-cause mortality in this age group. Newborn screening (NBS) is the practice of testing babies right after delivery to ascertain whether they have diseases that are potentially lethal if not treated early. Where routinely practiced, NBS has significantly reduced morbidity and mortality associated with such diseases. The Sickle Cell Programme at Muhimbili University of Health and Allied Sciences (MUHAS) in Dar-es-salaam and Bugando Medical Center in Mwanza have both conducted pilot NBS for SCD, showing that the intervention is generally feasible and acceptable in Tanzania. The successful introduction and expansion of NBS in Tanzania will require careful planning and advocacy at community to national level

Is the FINDRISC Tool Useful in Screening Type 2 Diabetes and Metabolic Syndrome in an African Setting? Experience among Young Adults in Urban Tanzania

Background: Simple and less costly screening tools are needed to combat the rising non-communicable diseases epidemic. This study aimed to evaluate the utility of The Finnish Diabetes Risk Score (FINDRISC) as a screening tool for prediabetes, T2D, and metabolic syndrome (MetS) in a population of young adults in urban Mwanza, Tanzania. Methods: A cross-sectional community-based study was conducted among participants aged 18–35 years. The FINDRISC questionnaire was used to collect data and compute the FINDRISC scores for each participant. Socio-demographic, anthropometric, blood glucose, and lipid profiles data were collected accordingly. Results: A total of 259 participants were recruited into the study. The median age was 21 years (IQR 19–27), and more than half 60.2% (156) were females. In total, 32.8% (85) of the participants had at least a slightly elevated risk of developing T2D in 10 years’ time. Compared to the Oral Glucose Tolerance Test (OGTT), FINDRISC had a sensitivity and specificity of 39.1% and 69.2%, respectively (aROC = 0.5). The FINDRISC score significantly correlated with MetS (p = 0.001). Conclusion: In this study, FINDRISC has shown low sensitivity and specificity in the screening of pre-diabetes/T2D. However, it has potential utility in the screening of MetS in a young-adult population

Clinical application of circulating cell-free lymphoma DNA for fast and precise diagnosis of Burkitt lymphoma: Precision medicine for sub-Saharan Africa

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

Healthcare Workers’ knowledge and resource availability for care of Sickle Cell Disease in Dar es Salaam, Tanzania

Background: Sickle cell disease (SCD) is a global public health priority due to its high morbidity and mortality. In Tanzania, SCD accounts for 7% of under-five mortality. Cost-effective interventions such as early diagnosis and linkage to care have been shown to prevent 70% of deaths but require knowledge among healthcare workers and availability of resources at health facilities. In Tanzania, data on these critical determinants are currently lacking. Objective: To assess healthcare workers’ knowledge and resource availability for care of SCD at health facilities in Dar es Salaam, Tanzania. Methodology: A facility-based cross-sectional study was conducted between December 2020 and February 2021 among 490 nurses and clinicians at Regional Referral Hospitals (Temeke, Amana, and Mwananyamala) and Muhimbili National Hospital in Dar es Salaam, Tanzania. Data were collected using a pre-tested structured questionnaire consisting of 13 knowledge questions (scored good knowledge if correct response in \u3e7) and an inventory check list to record available resources. Pearson’s χ2 was used to determine the association between level of knowledge and demographic factors. Multivariate logistic regression was used to ascertain the strength of associations. A two-tailed p-value \u3c0.05 was considered to be statistically significant. Results: Of the 490 participants (median age 28 years [IQR = 26–35]), only 25.1% had good knowledge on SCD. The odds of good knowledge was 82% lower in nurses than clinicians (AOR = 0.177; 95% CI: 0.090, 0.349; p \u3c 0.001); 95% lower in diploma than Master’s degree holders (AOR = 0.049; 95% CI: 0.008, 0.300; p = 0.001) and 4.6 times higher in those with 5–9 years than ≥10 years of experience (AOR = 4.564; 95% CI: 1.341, 15.525; p = 0.015). The regional-level hospitals lacked diagnostic tests and hydroxyurea therapy. Conclusion: There was general lack of knowledge on SCD among healthcare workers and limited availability of critical resources for the diagnosis and care of SCD, especially at regional-level hospitals. Efforts are needed for their improvement to enhance care to patients, thus reducing the morbidity and mortality due to SCD in Tanzania