Hydroxyurea mobile directly observed therapy versus standard monitoring in patients with sickle cell anemia: a phase 2 randomized trial.

BACKGROUND: Sickle cell anemia (SCA) prevalence remains high in sub-Saharan Africa. Long-term treatment with hydroxyurea (HU) increases survival, however, poor adherence to treatment could limit effectiveness. Whilst HU treatment adherence is currently high, this might decrease over time. METHODS: We conducted a single-center, randomized, open-label, parallel group phase 2 controlled clinical trial to determine whether mobile Directly Observed Therapy (m-DOT) increases HU treatment adherence (NCT02844673). Eligible participants were adults with homozygous SCA. People on a chronic blood transfusion program, with hemoglobin (Hb) A levels greater than 20% of the total Hb, total Hb less than 4 g/dL, pregnant or HIV positive were excluded. After a 3-month pre-treatment period participants were randomized to either m-DOT or standard monitoring arm. All participants received smart mobile phones and were treated with HU (15 mg/kg) daily for three months. In the m-DOT arm, drug intake was video recorded on cell phone by the participant and the video sent to the study team. The primary objective was to evaluate the effect of m-DOT on adherence to HU treatment by medication possession ratio (MPR). RESULTS: Of the 86 participants randomized, 76 completed the trial (26.13 ± 6.97 years, 63.5 % female). Adherence was high (MPR > 95 %) in both groups, 29 (80.6 %) in m-DOT versus 37 (94.9 %) in the standard monitoring arm (P = 0.079). No HU treatment was withheld from participants due to safety concerns. CONCLUSIONS: m-DOT did not increase adherence to HU treatment. We recommend that further testing in larger trials with a longer follow up period be undertaken.

Sickle cell anemia (SCA) is an inherited blood disorder in which there is an abnormal protein inside red blood cells. This results in red blood cells becoming sickle shaped and more easily destroyed in the body. Long-term treatment with hydroxyurea can reduce the frequency of illness and hospitalization. However, often people do not manage to take their medication regularly when treatment is long-term. We therefore investigated whether people with SCA in sub-Saharan Africa are more likely to take hydroxyurea when they are remotely monitored than when they are not. Remote monitoring did not improve adherence. However, our study is small and was undertaken over a short time period when hydroxyurea had only recently become available to people with SCA. We propose further studies, to see if remote monitoring increases medication adherence in people with SCA in other scenarios.

Barriers and Enablers to Retention in HIV Care and Adherence to Antiretroviral Therapy: Evidence from Dar es Salaam, Tanzania.

Purpose: To explore the enabling factors, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among adults (18 years and above) living with HIV in Dar es Salaam, Tanzania. Methods: We conducted a descriptive qualitative study to better understand and explore enablers, barriers, and strategies to improve retention in HIV care and adherence to antiretroviral therapy (ART) among PLHIV in Dar es Salaam, Tanzania. Focus group discussions (FGD) were conducted with a semi-structured discussion guide between December 2021 and June 2022. A non-random purposive sampling technique was used to select PLHIV and people involved in provision of healthcare and socioeconomic support to PLHIV. Thematic analysis was used to identify and interpret the themes. Results: Three major themes with 10 sub-themes emerged. Participants indicated that family and partner support, peer-support group/adherence clubs, and healthcare provider counselling on medication adherence facilitated retention and adherence to ART. In contrast, stigma and discrimination, financial constraints, disease outbreaks such as the COVID-19 pandemic, myths and misconceptions about HIV, and side effects of antiretrovirals were mentioned as barriers. Strengthening community and patient education about HIV and ART through peer support groups and financial support for poor PLHIV were the proposed mitigation. Conclusion: Addressing the challenges to ART adherence may require a more holistic approach. We recommend the implementation of peer support groups and financial support through small microfinance groups as interventions to increase retention in HIV care and adherence to ART in the study area.

Towards genomic medicine: a tailored next-generation sequencing panel for hydroxyurea pharmacogenomics in Tanzania.

BACKGROUND: Pharmacogenomics of hydroxyurea is an important aspect in the management of sickle cell disease (SCD), especially in the era of genomic medicine. Genetic variations in loci associated with HbF induction and drug metabolism are prime targets for hydroxyurea (HU) pharmacogenomics, as these can significantly impact the therapeutic efficacy and safety of HU in SCD patients. METHODS: This study involved designing of a custom panel targeting BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. These genes were selected based on their known roles in HbF induction and HU metabolism. The panel was designed using the Illumina Design Studio (Illumina, San Diego, CA, USA) and achieved a total coverage of 96% of all genomic targets over a span of 51.6 kilobases (kb). This custom panel was then sequenced using the Illumina MiSeq platform to ensure high coverage and accuracy. RESULTS: We are reporting a successfully designed Illumina (MiSeq) HU pharmacogenomics custom panel encompassing 51.6 kilobases. The designed panel achieved greater than 1000x amplicon coverage which is sufficient for genomic analysis. CONCLUSIONS: This study provides a valuable tool for research in HU pharmacogenomics, especially in Africa where SCD is highly prevalent, and personalized medicine approaches are crucial for improving patient outcomes. The custom-designed Illumina (MiSeq) panel, with its extensive coverage and high sequencing depth, provides a robust platform for studying genetic variations associated with HU response. This panel can contribute to the development of tailored therapeutic strategies, ultimately enhancing the management of SCD through more effective and safer use of hydroxyurea.

Trends in Utilization of Emergency Contraceptives in Tanzania: A Retrospective Longitudinal Study From 2018 to 2023.

Introduction Emergency contraceptives (ECs) are a critical method for preventing unwanted pregnancies following unprotected sexual intercourse. However, Tanzania is experiencing an alarming surge in the misuse of ECs among reproductive-aged females, particularly younger girls and women. Reports of their use as regular contraceptives are a rising concern. Deviations from their intended use in emergencies may not only increase the risk of contraceptive failure but also increase the risk of adverse health events. This study aims to delineate and evaluate the utilization patterns of ECs over six consecutive years using importation data obtained from the Tanzania Medicines and Medical Devices Authority (TMDA). Materials and methods We analyzed the EC data collected by TMDA over six consecutive years using a retrospective longitudinal design. Microsoft Power BI (Microsoft® Corp., Redmond, WA) was used to clean, organize, and aggregate the data. IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States) was used to analyze annual trend utilization using linear regression. Results We analyzed 114 importation consignments for ECs, identifying 95.6% (109 records) as oral ECs and 4.4% (five records) as intrauterine devices (IUDs) between 2018 and 2023. This data revealed a significant increase in the volume of EC imports, with its contribution increasing from 1.9% in 2018 to 60.1% in 2023. This highlights the marked increase in EC consumption in Tanzania. In 2023, the defined daily dose per 1000 inhabitants per year (DID) peaked at 3.917826, indicating an unprecedented increase of 4,983.06% compared to the lowest DID observed in 2019 at 0.0873552. The year 2023 alone accounted for 41.63% of the total DID (9.43) over the entire study period. In 2019 and 2020, there was a decrease in EC consumption, followed by a rapid increase from 2021 to 2023. The reduction in EC consumption from 2019 to 2020 was 36.9% compared to that between 2021 and 2022. Conclusions The significant rise in EC importation and utilization in Tanzania between 2018 and 2023, marked by fluctuating consumption trends and a notable surge, highlights the urgent need for targeted educational and policy intervention. This will guide the rational and informed use of ECs, ensuring access aligns with best practices for reproductive health.

Prevalence of Urinary Tract Infections and Antibiogram of Bacteria Isolated From Children With Sickle Cell Disease in Tanzania.

Introduction Individuals with sickle cell disease (SCD) are particularly vulnerable to urinary tract infections (UTIs) due to immunological deficits and renal abnormalities associated with the disorder. These infections can exacerbate underlying health issues and lead to severe complications if not managed promptly and effectively. Due to the heightened risk and potential consequences of UTIs in this population, this study aimed to determine their prevalence and explore the resistance patterns of causative pathogens among children attending the SCD Clinic at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. Focusing on this demographic group, we sought to provide targeted insights to inform better clinical protocols and intervention strategies in regions heavily affected by SCD. Materials and methods This prospective cross-sectional study was conducted at the MNH, Dar es Salaam, Tanzania, with an enrollment over two months from 19th March to 21st May 2015. We diagnosed UTIs in children with SCD using dipstick and culture methods. Antibiotic susceptibility was assessed using the Kirby-Bauer disc diffusion method, evaluating resistance patterns to antibiotics such as ampicillin, cloxacillin, erythromycin, chloramphenicol, ceftriaxone, and trimethoprim-sulfamethoxazole. The diagnostic accuracy of the dipstick and culture methods was validated to ensure reliability in detecting UTIs. Statistical analysis was conducted using Statistical Product and Service Solutions (SPSS) software (Released 2019; IBM Corp., Armonk, New York, United States). Results Among the 250 children, 56 (22.4%) were UTI-positive according to the culture method and 62 (24.8%) were UTI-positive according to the dipstick test. Girls were more likely to be UTI-positive than boys (29.1% and 13.6%, respectively; p-value = 0.011). Escherichia coli was the most common uropathogen, followed by Klebsiella, Staphylococcus, Proteus, and Pseudomonas (44.2%, 26.9%, 21.2%, 3.8%, and 1.9%, respectively). All isolates were resistant to ampiclox. Resistance rates to ampicillin, erythromycin, cotrimoxazole, chloramphenicol, and ceftriaxone were 94.2%, 76.9%, 59.6%, 46.2%, and 21.2%, respectively. Conclusion This study indicated that dipsticks diagnosed more UTIs. The prevalence was higher in girls than in boys. Escherichia coli was the most commonly isolated antibiotic-resistant organism. High resistance levels were observed against the combination of ampicillin and cloxacillin. However, the isolates were less resistant to ceftriaxone. These results call for increased surveillance of resistant uropathogens in the pediatric population with SCD.

Utilization Trends of Phosphodiesterase Type-5 Inhibitors for Erectile Dysfunction Between 2019 and 2023 in Tanzania.

Introduction Erectile dysfunction (ED) profoundly affects millions of people globally, including interfering with mental health and quality of life. Phosphodiesterase type-5 inhibitors (PDE5Is) such as sildenafil are pivotal in ED treatment. This study aimed to examine the utilization patterns of PDE5Is in Tanzania. Materials and methods In this retrospective longitudinal study, data on sildenafil and other similar PDE5Is imported between 2019 and 2023 were sourced from the Tanzania Medicines and Medical Devices Authority (TMDA). Pre-processing and visualization were performed using Microsoft Power BI Desktop, and further analysis was performed using IBM SPSS Statistics for Windows, Version 26 (Released 2019; IBM Corp., Armonk, New York, United States). Utilization trends were ascertained through curve fitting, Holt's linear trend model, and autoregressive integrated moving average (ARIMA) models. The defined daily doses (DDDS) per 1000 inhabitants (DID) were calculated using the World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) Classification System and the DDD methodology endorsed by the WHO Collaborating Centre for Drug Statistics Methodology. Results Between 2019 and 2023, there was a pronounced increase in the importation of approximately 587 consignments of PDE5Is. Employing the Holt model (R-square = 0.843), a substantial increase from 0.220910 DID in 2019 to 0.534272 DID by 2025 was observed and anticipated. The period witnessed sildenafil dominating 75.5% of the total use, with Erecto being the most consumed brand (37.6% of total DID). Notably, 2022 had the highest surge (27.2% of the total), albeit a slight decline was observed in 2023 (20.5%). This trend was supported by a linear regression model (R-square = 0.889). Conclusion We found increasing annual trends of PDE5Is of utilization. This requires critical oversight and effective policies to ensure appropriate use and risk minimization.

Childhood vaccination trends during 2019 to 2022 in Tanzania and the impact of the COVID-19 pandemic.

The COVID-19 pandemic has significantly disrupted healthcare systems at all levels globally, notably affecting routine healthcare services, such as childhood vaccination. This study examined the impact of these disruptions on routine childhood vaccination programmes in Tanzania. We conducted a longitudinal study over four years in five Tanzanian regions: Mwanza, Dar es Salaam, Mtwara, Arusha, and Dodoma. This study analyzed the trends in the use of six essential vaccines: Bacille Calmette-Guérin (BCG), bivalent Oral Polio Vaccine (bOPV), Diphtheria Tetanus Pertussis, Hepatitis-B and Hib (DTP-HepB-Hib), measles-rubella (MR), Pneumococcal Conjugate Vaccine (PCV), and Rota vaccines. We evaluated annual and monthly vaccination trends using time-series and regression analyses. Predictive modeling was performed using an autoregressive integrated moving average (ARIMA) model. A total of 32,602,734 vaccination events were recorded across the regions from 2019 to 2022. Despite declining vaccination rates in 2020, there was a notable rebound in 2021, indicating the resilience of Tanzania's immunization program. The analysis also highlighted regional differences in vaccination rates when standardized per 1000 people. Seasonal fluctuations were observed in monthly vaccination rates, with BCG showing the most stable trend. Predictive modeling of BCG indicated stable and increasing vaccination coverage by 2023. These findings underscore the robustness of Tanzania's childhood immunization infrastructure in overcoming the challenges posed by the COVID-19 pandemic, as indicated by the strong recovery of vaccination rates post-2020. We provide valuable insights into the dynamics of vaccination during a global health crisis and highlight the importance of sustained immunization efforts to maintain public health.

Antibiotic utilization patterns in Tanzania: a retrospective longitudinal study comparing pre- and intra-COVID-19 pandemic era using Tanzania Medicines and Medical Devices Authority data.

Background: Antimicrobial resistance (AMR) is a growing public health concern globally, and misuse of antibiotics is a major contributor. Objective: This study investigated antibiotic utilization patterns before and during the COVID-19 pandemic in Tanzania using data from the Tanzania Medicines and Medical Devices Authority (TMDA). Methods: This retrospective longitudinal study analysed secondary data. The study compared antibiotics consumption in defined daily doses per 1000 inhabitants per day (DID) in two distinct eras: 2018-2019 as the pre-COVID-19 era and 2020-2021 as the intra-COVID-19 era. A sample t-test was conducted using Statistical Package for the Social Sciences. Results: The study analysed 10 614 records and found an overall increase in antibiotics consumption from 2018 to 2021. We found that the consumption was 61.24 DID in the intra-COVID-19 era and 50.32 DID in the pre-COVID-19 era. Levofloxacin had the highest percentage increase in use, with a 700% increase in DID during the intra-COVID-19 era. Azithromycin had a 163.79% increase, while cefotaxime had a 600% increase. By contrast, some antibiotics exhibited a decrease in usage during the intra-COVID-19 era, such as nalidixic acid, which had a 100% decrease, and cefpodoxime, which had a 66.67% decrease. Conclusions: Increased antibiotic consumption during the COVID-19 pandemic highlights the importance of implementing effective antimicrobial stewardship strategies to prevent AMR, especially during pandemics.

The genetic dissection of fetal haemoglobin persistence in sickle cell disease in Nigeria.

The clinical severity of sickle cell disease (SCD) is strongly influenced by the level of fetal haemoglobin (HbF) persistent in each patient. Three major HbF loci (BCL11A, HBS1L-MYB, and Xmn1-HBG2) have been reported, but a considerable hidden heritability remains. We conducted a genome-wide association study for HbF levels in 1006 Nigerian patients with SCD (HbSS/HbSß0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients). To dissect association signals at the major loci, we performed stepwise conditional and haplotype association analyses and included public functional annotation datasets. Association signals were detected for BCL11A (lead SNP rs6706648, ß = -0.39, P = 4.96 × 10-34) and HBS1L-MYB (lead SNP rs61028892, ß = 0.73, P = 1.18 × 10-9), whereas the variant allele for Xmn1-HBG2 was found to be very rare. In addition, we detected three putative new trait-associated regions. Genetically, dissecting the two major loci BCL11A and HBS1L-MYB, we defined trait-increasing haplotypes (P < 0.0001) containing so far unidentified causal variants. At BCL11A, in addition to a haplotype harbouring the putative functional variant rs1427407-'T', we identified a second haplotype, tagged by the rs7565301-'A' allele, where a yet-to-be-discovered causal DNA variant may reside. Similarly, at HBS1L-MYB, one HbF-increasing haplotype contains the likely functional small indel rs66650371, and a second tagged by rs61028892-'C' is likely to harbour a presently unknown functional allele. Together, variants at BCL11A and HBS1L-MYB SNPs explained 24.1% of the trait variance. Our findings provide a path for further investigation of the causes of variable fetal haemoglobin persistence in sickle cell disease.

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

Improved Biorepository to Support Sickle Cell Disease Genomics and Clinical Research: A Practical Approach to Link Patient Data and Biospecimens from Muhimbili Sickle Cell Program, Tanzania.

In Africa, sickle cell disease phenotypes' genetic contributors remain understudied due to the dearth of databases that pair biospecimens with demographic and clinical details. The absence of biorepositories in these settings can exacerbate this issue. This article documents the physical verification process of biospecimens in the biorepository, connecting them to patient clinical and demographic data and aiding in the planning of future genomic and clinical research studies' experience from the Muhimbili Sickle Cell Program in Dar es Salaam, Tanzania. The biospecimen database was updated with the current biospecimen position following the physical verification and then mapping this information to its demographic and clinical data using demographic identifiers. The biorepository stored 74,079 biospecimens in three -80°C freezers, including 63,345 from 5159 patients enrolled in the cohort between 2004 and 2016. Patients were identified by a control (first visit), entry (when confirmed sickle cell homozygous), admission (when hospitalized), and follow-up numbers (subsequent visits). Of 63,345 biospecimens, follow-ups were 46,915 (74.06%), control 8067 (12.74%), admission 5517 (8.71%), and entry 2846 (4.49%). Of these registered patients, females were 2521 (48.87%) and males were 2638 (51.13%). The age distribution was 1-59 years, with those older than 18 years being 577 (11.18%) and children 4582 (88.82%) of registered patients. The notable findings during the process include a lack of automated biospecimen checks, laboratory information management system, and tubes with volume calibration; this caused the verification process to be tedious and manual. Biospecimens not linked to clinical and demographic data, date format inconsistencies, and lack of regular updating of a database on exhausted biospecimens and updates when biospecimens are moved between positions within freezers were other findings that were found. A well-organized biorepository plays a crucial role in answering future research questions. Enforcing standard operating procedures and quality control will ensure that laboratory users adhere to the best biospecimen management procedures.

Prevalence of urinary tract infection and antimicrobial resistance patterns of uropathogens with biofilm forming capacity among outpatients in morogoro, Tanzania: a cross-sectional study.

INTRODUCTION: Urinary tract infection (UTI) is the second most common infectious disease affecting more than 150 million people globally annually. Uropathogenic E. coli (UPEC), the predominant cause of UTI, can occur as a biofilm associated with antimicrobial resistance (AMR). There is a data gap on global AMR patterns from low-income settings, including Tanzania. Data on antimicrobial susceptibility patterns in relation to biofilm formation will help in the proper selection of antibiotics and the fight against AMR. METHODS: This analytical cross-sectional study was conducted among consecutively selected outpatients (n = 344) from January to May 2022 at Morogoro Regional Referal Hospital. Mid-stream urine samples were collected aseptically from symptomatic patients. A significant UTI was defined when more than 105 colonies/ml of urine were recorded. Kirby Bauer's disc diffusion method was used for antibiotics susceptibility patterns and a Congo Red Agar method was used to determine biofilm formation. Two-sided χ2 test or Fisher's exact test, Cohen's kappa coefficient and logistic regression were used for data analysis. A p-value < 0.05 was considered statistically significant. RESULTS: The prevalence of UTIs was 41% (141/344) and elders (>=60 years) had five times higher odds of having UTI as compared to adolescents (p < 0.001). E. coli was the most predominant bacteria (47%; 66/141), which displayed moderate susceptibility against ciprofloxacin (59.1%) and nitrofurantoin (57.6%). A total of 72 (51%) of all isolated bacteria were multi-drug resistant. All isolated bacteria demonstrated high resistance (> 85%) against ampicillin and co-trimoxazole. In this study, 51.5% (34/66) were biofilm-forming E. coli and demonstrated relatively higher antibiotic resistance as compared to non-biofilm forming bacteria (p < 0.05). CONCLUSION: We report high antibiotic resistance against commonly used antibiotics. Slightly more than half of the isolated bacteria were biofilm forming E. coli. A need to strengthen stewardship programs is urgently advocated.

Impact of differentiated service delivery models on retention in HIV care and viral suppression among people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis of randomised controlled trials.

Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client-centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub-Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08-1.11, I2 : 0%, p: <0.96) and 1.01 (95% CI: 1.00-1.02, I2 : 0%, p: <0.85) for RC and VS, respectively. The RR between ACs and SoC was 1.01 (95% CI: 0.96-1.07, I2 : 84%, p: <0.01) and 1.02 (95% CI: 0.98-1.07, I2 : 77%, p: <0.01) for RC and VS, respectively. DSD models, including ACs, show comparable effectiveness to SoC in maintaining care and achieving viral suppression for stable PLHIV. To maximise adoption, an implementation science approach is crucial for designing effective strategies and overcoming challenges.

Genetic regulation of fetal hemoglobin across global populations.

Human genetic variation has enabled the identification of several key regulators of fetal-to-adult hemoglobin switching, including BCL11A, resulting in therapeutic advances. However, despite the progress made, limited further insights have been obtained to provide a fuller accounting of how genetic variation contributes to the global mechanisms of fetal hemoglobin (HbF) gene regulation. Here, we have conducted a multi-ancestry genome-wide association study of 28,279 individuals from several cohorts spanning 5 continents to define the architecture of human genetic variation impacting HbF. We have identified a total of 178 conditionally independent genome-wide significant or suggestive variants across 14 genomic windows. Importantly, these new data enable us to better define the mechanisms by which HbF switching occurs in vivo. We conduct targeted perturbations to define BACH2 as a new genetically-nominated regulator of hemoglobin switching. We define putative causal variants and underlying mechanisms at the well-studied BCL11A and HBS1L-MYB loci, illuminating the complex variant-driven regulation present at these loci. We additionally show how rare large-effect deletions in the HBB locus can interact with polygenic variation to influence HbF levels. Our study paves the way for the next generation of therapies to more effectively induce HbF in sickle cell disease and ß-thalassemia.

Infrastructure for bioinformatics applications in Tanzania: Lessons from the Sickle Cell Programme.

Sickle cell disease (SCD) is a common genetic disorder in Africa. Some ongoing work in SCD research includes the analysis and comparisons of variation in phenotypic presentations and disease outcomes with the genotypic signatures. This has contributed to the observed growth of molecular and genetic data in SCD. However, while the "omics" data continues to pile, the capacity to interpret and turn the genetic findings into clinical practice is still underdeveloped, especially in the developing region. Building bioinformatics infrastructure and capacity in the region is key to bridging the gap. This paper seeks to illustrate how the Sickle Cell Programme (SCP) at the Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania, modeled the integration of infrastructure for bioinformatics and clinical research while running day-to-day clinical care for SCD in Tanzania.

Comparison of knowledge, attitude, practice and predictors of self-medication with antibiotics among medical and non-medical students in Tanzania.

Introduction: Self-medication with antibiotics (SMA) is a widespread problem in developing nations, including Tanzania. Methods: This study compared knowledge, attitudes, practices, and factors influencing antibiotic SMA among medical and non-medical students. Results: The prevalence of SMA among medical students was 49.1% and 59.2% among non-medical students, respectively. The mean knowledge score of medical students (6.4) was significantly higher (p-value <0.001) than that of non-medical students (5.6). The main factors influencing SMA practices were the availability of antibiotics without a prescription, easy access to pharmacies, and a lack of knowledge about the risks of SMA. This experience was pivotal in influencing medical students to take antibiotics, with a substantial proportion of 67.5% as opposed to 59.4% of non-medical students. Medical students were 1.6 times more likely to self-medicate with antibiotics than non-medical students (Adjusted Odds Ratio (AOR): 1.6; 95% Confidence Interval (CI): 1.2-2.3, p-value = 0.004). Age was also associated with self-medication, with an AOR of 1.1 (95% CI: 1.04-1.2, p-value = 0.006) per year increase in age. Additionally, attitude was associated with self-medication, with an AOR of 1.05 (95% CI: 1.04-1.1, p-value = 0.001) per unit increase in attitude score. Discussion: No significant associations were found between sex, marital status, having children, year of study, knowledge score, and self-medication with antibiotics. This study emphasizes the importance of educational interventions and public awareness campaigns to promote antimicrobial stewardship, appropriate antibiotic use, and preventing pharmacies from dispensing antibiotics without a prescription.

Establishing a database for sickle cell disease patient mapping and survival tracking: The sickle pan-african research consortium Nigeria example.

Background: The Sickle Pan-African Research Consortium (SPARCO) and Sickle Africa Data Coordinating Center (SADaCC) were set up with funding from the US National Institute of Health (NIH) for physicians, scientists, patients, support groups, and statisticians to collaborate to reduce the high disease burden and alleviate the impact of Sickle Cell Disease (SCD) in Africa. For 5 years, SPARCO and SADaCC have been collecting basic clinical and demographic data from Nigeria, Tanzania, and Ghana. The resulting database will support analyses to estimate significant clinical events and provide directions for targeting interventions and assessing their impacts. Method: The Nigerian study sited at Centre of Excellence for Sickle Cell Disease Research and Training (CESRTA), University of Abuja, adopted REDCap for online database management. The case report form (CRF) was adapted from 1,400 data elements adopted by SPARCO sites. It captures 215 data elements of interest across sub-sites, i.e., demographic, social, diagnostic, clinical, laboratory, imaging, and others. These were harmonized using the SADaCC data dictionary. REDCap was installed on University of Abuja cloud server at https://www.redcap.uniabuja.edu.ng. Data collected at the sites are sent to CESRTA for collation, cleaning and uploading to the database. Results: 7,767 people living with sickle cell disease were enrolled at 25 health institutions across the six zones in Nigeria with 5,295 having had at least one follow-up visit with their clinical data updated. They range from 44 to 1,180 from 3 centers from South East, 4 from South, 5 from South West, 8 from North Central, 4 in North West and 3 in the North East. North West has registered 1,383 patients, representing 17.8%; North East, 359 (4.6%); North Central, 2,947 (37.9%); South West, 1,609 (20.7%); South, 442 (5.7%) and South East, 1,027 patients (13.2%). Conclusion: The database is being used to support studies including analysis of clinical phenotypes of SCD in Nigeria, and evaluation of Hydroxyurea use in SCD. Reports undergoing review in journals have relied on the ease of data access in REDCap. The database is regularly updated by batch and individual record uploads while we are utilizing REDCap's in-built functions to generate simple statistic.

Nasopharyngeal Carriage and Antibiogram of Pneumococcal and Other Bacterial Pathogens from Children with Sickle Cell Disease in Tanzania.

Background: Bacterial infections contribute significantly to morbidity and mortality in sickle cell disease (SCD) patients, particularly children under five years of age. In Tanzania, prophylaxis against pneumococcal infection among children with SCD advocates the use of both oral penicillin V (PV) and pneumococcal vaccines (PNV). Therefore, this study aimed to investigate nasopharyngeal carriage and antibiogram of Streptococcal pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) in children with SCD in Tanzania. Methods: This cross-sectional study was undertaken at the two Sickle Pan-African Research Consortium (SPARCO) study sites in Dar es salaam, Tanzania. The study was conducted for six months and enrolled children with SCD between the ages of 6 to 59-months. A semi-structured questionnaire was used to collect patient data. Nasopharyngeal swabs were collected from all participants and cultured for Streptococcal pneumoniae and other bacterial isolates. Antimicrobial susceptibility tests of the isolates were done using the disc diffusion method. Results: Out of 204 participants, the overall prevalence of bacterial carriage was 53.4%, with S. aureus (23.5%), coagulase-negative Staphylococci (CoNS) (23%) and S. pneumoniae (7.8%) being commonly isolated. In antibiotic susceptibility testing, S. aureus isolates were most resistant to penicillin (81.8%), whereas 81.3% of S. pneumoniae isolates were resistant to co-trimoxazole. The least antimicrobial resistance was observed for chloramphenicol for both S. aureus and S. pneumoniae isolates (6.3% versus 0%). The proportion of multi-drug resistance (MDR) was 66.7% for S. aureus isolates and 25% for S. pneumoniae isolates. Conclusion: There are substantially high nasopharyngeal carriage pathogenic bacteria in children with SCD in Dar es Salaam, Tanzania. The presence of MDR strains to the commonly used antibiotics suggests the need to reconsider optimizing antimicrobial prophylaxis in children with SCD and advocacy on pneumococcal vaccines.