Understanding patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, Uganda, a qualitative study.

BACKGROUND: In 2016, Uganda added Hydroxyurea (HU) to the list of essential drugs to treat sickle cell disease SCD. However, Hydroxyurea utilization has been low for several countries in sub-Saharan Africa. This study examined patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease in Mulago and Kiruddu hospitals, in Uganda. METHODS: To understand the patient-related barriers to hydroxyurea use among adolescent and adult patients with sickle cell disease, we conducted a parallel convergent mixed methods study at outpatient departments of two national referral hospitals in Uganda from October 2022 to January 2023. The cross-sectional mixed-methods study employed both quantitative and qualitative methods. We collected survey data from a systematic sample of 259 participants and conducted individual interviews with a purposive sample of 40 participants (20 adolescents or their caregivers and 20 adult patients with SCD) and interviewed them individually on their knowledge, perceptions, barriers, and facilitators of HU utilization. Descriptive data were analyzed using Stata 16, whereas qualitative data were analyzed thematically using an inductive approach supported by NVivo 12 software. We triangulated data to determine the concordance of qualitative and quantitative data. RESULTS: The study enrolled 40 participants for qualitative interviews and 259 patients for quantitative, with an average age of 16, over half being female, 46% having secondary education, and 96% unmarried. The prevalence of HU use was 78%. The study identified three themes as follows: Patient barriers at the individual including Inadequate knowledge about HU, Persistent pain, Poor adherence to HU, Poor communication with health care workers, and Psychosocial and emotional challenges. At the facility level, long queues and poor quality of care, drug-related side effects that affect HU, and drug stock-outs were reported. Myths, rumors, and misconceptions about HU, and gender-related barriers were reported to affect HU utilization at a community level. Facilitators for the use of HU and recommendations for improvement. Facilitators included perceived benefits, long duration on HU, information sharing by healthcare workers, availability of complementary drugs, confirmation of diagnosis, and availability of medication at public health facilities or private pharmacies. Patients suggested continuous adherence support, encouragement from healthcare workers, sensitization about benefits and risks, a peer-to-peer approach, and financial support for adolescents and women to start businesses to resolve financial problems. CONCLUSION: Implementing the use of HU has been challenging in Uganda and needs improvement. Facilitators to hydroxyurea use have been highlighted, though Patient-identified barriers at individual, facility, and community levels that need to be resolved. The experiences and insights shared by our participants provide invaluable guidance for increasing the uptake of HU. Further studies are needed to establish validated instruments to assess patients' pain communication and adherence to the HU regimen.

Survival of children with endemic Burkitt lymphoma in a prospective clinical care project in Uganda.

PURPOSE: "Endemic" Burkitt lymphoma (BL) is a common childhood cancer in Africa. Social and treatment factors may contribute to poor survival. With the aim of improving BL outcomes in Uganda, we undertook a comprehensive project (BL Project) that provided diagnostic support, access to standard chemotherapy, nutritional evaluations, and case management. We evaluated survival of children with BL in the context of the project. PATIENTS AND METHODS: Patients followed by the BL Project who consented to research were enrolled in this study. Children with a pathology diagnosis consistent with BL were eligible. Data were collected prospectively. First-line chemotherapy generally consisted of six cycles of cyclophosphamide, vincristine, low-dose methotrexate (COM). We used Kaplan-Meier and Cox regression analyses to evaluate factors associated with overall survival (OS). RESULTS: Between July 2012 and June 2017, 341 patients with suspected BL presented to the BL Project. One hundred eighty patients with a pathology-based diagnosis were included in this study. The median age was seven years (interquartile range, 5-9), 74% lived ≥100 km from the Uganda Cancer Institute, 61% had late-stage disease, 84% had ECOG performance status < 3, 63% reported B-symptoms, and 22% showed neurologic symptoms. Fewer than 10% abandoned therapy. The four-year OS rate was 44% (95% CI, 36%-53%). In a multivariate model, ECOG status was significantly associated with mortality. CONCLUSION: The BL Project reduced effects of lacking supportive care and oncology resources, and allowed patients from Uganda to receive curative intent therapy with minimal loss to follow-up. Nonetheless, OS remains unacceptably low. Improved therapeutic approaches to endemic BL are urgently needed in Africa.

The signature of a T-cell response to KSHV persists across space and time in individuals with epidemic and endemic KS from Uganda.

Inadequate T-cell control of Kaposi sarcoma-associated herpesvirus (KSHV) infection predisposes to development of Kaposi sarcoma (KS), but little is known about the T-cell response to KSHV. Postulating that KS tumors contain abundant KSHV-specific T-cells, we performed transcriptional profiling and T-cell receptor (TCR) repertoire analysis of tumor biopsies from 144 Ugandan adults with KS. We show that CD8+ T-cells and M2-polarized macrophages dominate the tumor micro-environment (TME). The TCR repertoire of KS tumor infiltrating lymphocytes (TIL) is shared across non-contiguous tumors and persists across time. Clusters of T-cells with predicted shared specificity for uncharacterized antigens, potentially encoded by KSHV, comprise ~25% of KS TIL, and are shared across tumors from different time points and individuals. Single-cell RNA-sequencing of blood identifies a non-proliferating effector memory phenotype and captured the TCRs in 14,698 putative KSHV-specific T-cells. These results suggest that a polyspecific KSHV-specific T-cell response inhibited by M2 macrophages exists within the KS TME, and provide a foundation for studies to define its specificity at a large scale.

One-Year Survival and Prognosticators of Adults With Acute Leukemia at the Uganda Cancer Institute.

PURPOSE: Acute leukemias are associated with substantial morbidity and mortality, particularly in the adult population. Despite an increasing burden of acute leukemia in developing countries, there are limited data on clinical outcomes and prognostic factors in this setting. In this study, we aimed to describe the clinical characteristics, survival, and prognostic factors of adults with acute leukemia at the Uganda Cancer Institute (UCI). METHODS: A retrospective cohort study was conducted between January 2009 and December 2018, reviewing data of patients 18 years or older with a cytopathologic diagnosis of acute leukemia at UCI. Data were extracted on clinical and laboratory characteristics, response to treatment, and survival. Cox-proportional hazards regression and survival analysis were performed to determine survival rates and associated factors. P < .05 was considered statistically significant. RESULTS: In total, 233 participants were enrolled. Most (59.2%. n = 138) participants were male, with a median age of 32 years (IQR, 23-48 years), and 136 (58.4%) had AML. Overall, the 1-year survival was 16.5%, with a median survival time of 47 (IQR, 21-219) days. Predictors of mortality were being a female (adjusted hazard ratio [aHR], 2.8; 95% CI, 1.2 to 6.7; P = .022) and overweight (aHR, 4.2; 95% CI, 1.3 to 13.4; P = .015). Among the patients who had AML, the predictors were poor Eastern Cooperative Oncology Group (ECOG; aHR, 3.1; 95% CI, 1.6 to 6.2; P = .001) and HIV (aHR, 6.0; 95% CI, 1.7 to 20.5; P = .004). Among the patients who had ALL, the predictors were poor ECOG (aHR, 2.3; 95% CI, 1.3 to 4.1; P = .006). CONCLUSION: Patients with acute leukemia in Uganda have poor overall survival. Prospective studies are recommended to better understand causes of early mortality.