Emmanuela Eusebio Ambrose

Hepatobiliary complications are common in children with sickle cell anemia (SCA) due to chronic hemolysis and vaso-occlusion, but are often underdiagnosed in low-resource settings where imaging is limited. This hospital-based cross-sectional study, conducted from March to May 2023, assessed the prevalence and characteristics of hepatobiliary abnormalities using ultrasound among children younger than 18 years with SCA at a tertiary hospital in Tanzania. Demographic and clinical characteristics, laboratory findings, and abdominal ultrasonography were obtained. Logistic regression was used to identify factors associated with hepatobiliary abnormalities. A total of 194 children aged 2 to 16 years were enrolled, of whom 52% were male and 47.9% were receiving hydroxyurea. The overall prevalence of hepatobiliary abnormalities was 57.2%. The most common findings were hepatomegaly (41%), low portal vein peak systolic velocity (14%), and biliary calculi or sludge (9%). Children aged 6 to 10 years (aOR=0.1, 95% CI: 0.05-0.3; P P P =0.005). Hepatobiliary abnormalities are highly prevalent and often asymptomatic, highlighting the importance of early screening and routine monitoring.

Introduction: African children with sickle cell anemia (SCA) often have splenomegaly with recurrent cytopenias that complicate management, rather than the splenic atrophy typically observed in SCA. Methods: We analyzed the presence, persistence, and impact of splenomegaly in the Stroke Prevention with Hydroxyurea Enabled through Research and Education (SPHERE) trial (NCT03948867), an open-label trial of dose-escalated hydroxyurea to prevent stroke in Tanzanian children with SCA. Palpable splenomegaly was recorded at each visit. Annual ultrasound measurements were compared to age- and height-related references. Longitudinally, palpable splenomegaly was categorized as infrequent (present in 50% visits). Adverse events (AEs) and hydroxyurea dose-limiting toxicities (DLTs) were compared using incidence rate ratios (IRRs) among the three categories. Results: At enrollment, splenomegaly was identified in 48/196 (25%) by palpation and 78 (40%) by ultrasound. Across 221 patient-years of treatment in 53 children, splenomegaly was intermittent in 19% and persistent in 21%. At 12 months, children with persistent splenomegaly were compared to those with infrequent splenomegaly and had achieved similar hydroxyurea dose (23.1 vs. 27.6 mg/kg/day, p = 0.136), hemoglobin (9.0 vs. 9.1 g/dL, p = 0.877), and HbF (23.8 vs. 24.3%, p = 0.481), but experienced more vaso-occlusive AE (IRR = 3.8, p value 0.122), transfusions (IRR = 7.1, p value 0.014), and DLTs (IRR = 3.2, p value 0.073). Conclusion: Splenomegaly is common in Tanzanian children with SCA, often persistent, worsens clinical outcomes, and complicates hydroxyurea. Its cause remains unclear, and further investigation is urgently needed to clarify its etiology, improve its management, and ensure optimal hydroxyurea treatment.

Sickle cell disease (SCD) is a major individual and public health challenge in sub‐Saharan Africa, where over 5 million affected individuals live and where access to disease‐modifying treatment is limited. Despite established safety and efficacy of hydroxyurea, its use is limited across the region due to inconsistent healthcare infrastructure, high medication and laboratory costs, inadequate clinician training, and persistent disease stigma. Practical hydroxyurea dosing strategies, integration into national health plans, and a stronger supply chain are necessary to improve access to this life‐saving medication. Newly approved medications, such as L‐glutamine and crizanlizumab, may provide additional benefits to select patients, but are expensive and unavailable. The increased mortality observed in people on voxelotor in Africa highlights the need to ensure the safety of any new medication in varied settings through high‐quality research conducted on the continent. Overall, holistic strategies are needed to improve SCD care in Africa, such as universal screening with connection to comprehensive care that includes disease‐modifying treatment, community and healthcare worker education, centers of excellence, and capacity building. SCD management in Africa can be transformed by addressing systemic barriers and leveraging collaborative partnerships, leading to reduced mortality and alleviation of the individual and economic burdens of the disease. It is a moral and economic imperative to prioritize access to SCD treatment in Africa, the region with the greatest disease burden globally.

Background: Fetal hemoglobin (HbF) is found at a measurable amount in red blood cells (RBCs) called F cells. High fetal hemoglobin (HbF) levels are linked with milder forms of sickle cell disease (SCD). However, some patients with high HbF levels still have severe symptoms. This variability has been associated with HbF per F cell (HbF/F cell) concentration; thus, it is hypothesized that high HbF/F cell (≥ 10 pg) is crucial in determining SCD disease severity rather than the overall HbF and F cell levels. This study assessed the utility of these three HbF parameters as predictors of SCD clinical events in Tanzania. Methods: A retrospective cohort study was conducted at Muhimbili University of Health and Allied Sciences, involving 92 SCD individuals aged ≥ 6 years, not on hydroxyurea, between September 2022 and February 2023. Data was collected from the Sickle Pan-African Research Consortium (SPARCO)-Tanzania registry. HbF/F cell was calculated as: HbF/F cell = (HbF% × MCH pg)/F cell%. STATA version 15 was used to analyze the association between HbF parameters and clinical events measured by ordinal logistic regression. A p-value < 0.05 was considered statistically significant. Results: Of the 92 SCD participants, the median age was 16 (IQR: 10– 21) years, 53 (57.6%) were below 18 years, and males were 48 (52.2%). Eighty-two patients (89.1%) had HbF/F cells below 10pg. Males had significantly higher HbF/F cell levels with a median of 6.4 (IQR: 4.3– 9.5) pg compared to females 5.3 (IQR: 3.5– 6.5) pg (p-value = 0.004). Although, we did not observe a statistically significant association between HbF/F cell with clinical parameters, increased HbF and F cell percentages correlated with reduced odds of multiple blood transfusions by 11% (p-value = 0.016) and 3% (p-value = 0.020), respectively. Conclusion: In this cohort, HbF and F cell levels remain important predictors of disease severity, as higher levels predicted reduced requirement for multiple blood transfusions in SCD patients, while HbF/F cells did not correlate with SCD clinical events.

Purpose: This study aimed to determine the prevalence of alpha+ thalassemia and its hematological indices in a newborn population in Mwanza city, North-western Tanzania. Patients and Methods: A cross-sectional study screened 803 newborns for alpha+ thalassemia that extracted DNA from dried blood spots using the Qiagen Mini Kit then analysed by multiplex PCR. Demographic data, anemia-related clinical information, and CBC parameters were collected at birth. Prevalence was determined by the proportion of newborns with the alpha+ thalassemia deletion. Fisher’s Exact test assessed differences in demographic and clinical variables, while Student’s t-tests and ANOVA evaluated hematological parameters. A P-value < 0.05 was considered statistically significant. Results: Alpha thalassemia was detected in 49.6% (398/803) of neonates, with 38.6% heterozygous and 11.0% homozygous deletions. Significant differences in erythrocyte indices were observed across groups. Hemoglobin (Hb) levels were lower in heterozygous (_α/αα) and homozygous (_α/_α) newborns (16.42± 3.62 g/dl and 16.04± 3.37 g/dl, respectively) compared to the αα/αα group (17.03± 3.35 g/dl, p < 0.05). Mean Corpuscular Volume (MCV) was reduced in heterozygous (_α/αα) and homozygous (_α/_α) groups (99.23± 9.12 μm³ and 94.75± 9.88 μm³, respectively) compared to αα/αα (102.41± 9.56 μm³, p < 0.0001). Mean Corpuscular Hemoglobin (MCH) followed a similar pattern, being lowest in the homozygous group (p ≤ 0.0001). Red Cell Distribution Width (RDW) was higher in homozygous (_α/_α) newborns (10.03± 1.22) compared to heterozygous (_α/αα) (9.57± 0.79, p < 0.001). Leucocyte counts were significantly higher in heterozygous (_α/αα) newborns (13.91± 12.14) compared to homozygous (_α/_α) (12.60± 7.91) and αα/αα groups (11.26± 9.76, p = 0.001). Conclusion: Alpha+ thalassemia is highly prevalent in North-western Tanzania and significantly affects blood indices. Neonatal screening is an effective tool for identifying affected children, especially in settings with high prevalence of a trait and low awareness of genetic inheritance.

Hydroxyurea is effective in reducing the severity of Sickle cell anemia (SCA) symptoms, yet adherence remains challenging, particularly in resource-limited settings. Bugando Medical Centre, a major healthcare provider, faces undocumented adherence issues among its pediatric SCA patients. This study aims to evaluate the adherence rate to hydroxyurea therapy among caregivers of children with SCA at Bugando Medical Centre and identify factors contributing to non-adherence. This analytical cross-sectional study involved 172 participants. Data were analyzed using Stata version 15 and modified Poisson regression determined the association between exposures and adherence to hydroxyurea treatment. More than half (68.6%) of the children were aged between 1 and 10 years, with a median age of 8 years (IQR: 5–12). Good adherence to hydroxyurea was observed in 23.8% of participants, while 76.2% showed moderate to poor adherence. Children aged 1–10 years were twice as likely to have good adherence compared to those aged 11–17 years (aPR = 2.98, 95% CI = 1.18, 7.47). Children of caregivers with secondary education had a 41% higher chance of good adherence (aPR = 1.41, 95% CI = 1.19, 2.87) compared to those with primary education. Additionally, children of caregivers with college/university education had a 92% higher chance of good adherence (aPR = 1.92, 95% CI = 1.09, 4.63) compared to those with primary education. Participants with good knowledge of hydroxyurea had a 55% higher chance of good adherence (aPR = 1.55, 95% CI = 1.10, 4.78) compared to those with poor knowledge. Factors such as the child’s age and caregiver’s educational level are associated with good adherence to hydroxyurea treatment. Despite these associations, overall adherence rates are low, highlighting the need for targeted interventions to enhance knowledge and awareness about the importance of adherence to hydroxyurea treatment.