@article{Bukini2025b,

title = {I know that one day I will be cured, and all will be well: Perspectives on acceptability of curative therapies for sickle cell disease in Tanzania.},

author = {Daima Bukini and Kassim Kassim and Collins Kanza and Aisha Rifai and Rahma Chanzi and Augostino Amando and Elianna Amin and Jonathan Spector and Julie Makani},

url = {http://medrxiv.org/lookup/doi/10.1101/2025.07.31.25332489},

doi = {10.1101/2025.07.31.25332489},

year  = {2025},

date = {2025-07-31},

urldate = {2025-07-31},

publisher = {Cold Spring Harbor Laboratory},

abstract = {While curative treatments for sickle cell disease (SCD) including hematopoietic stem cell

transplant and gene therapies are largely restricted to high-resource settings, recent

advancements have raised hopes that they will eventually become more accessible to patients in

Africa, where the disease is particularly prominent and contributes to substantial morbidity and

mortality. Understanding the factors that influence acceptability of curative therapies will

therefore be important in developing strategies for successful adoption and implementation. To

address this need, a qualitative study was conducted to gain insights into the perspectives of

patients and families in Tanzania regarding curative therapies for SCD, focusing on factors

affecting treatment acceptability. A total of 81 individuals participated through Focus Group

Discussions or In-Depth Interviews. The results indicated substantial interest in current and

prospective curative programs, with various factors influencing the attitudes of patients and

caregivers differently. Study findings suggested, caregivers decisions were likely to be

influenced by the burden of caregiving roles and the financial costs related to care for SCD.

Patients were likely to accept the therapies if provided with information on safety of the

therapies and requested for transparency of data from treated patients. In preparation for gene

therapy trials or transplants, tailored engagement strategies for patients younger than 18 years old

will be necessary as majority of SCD patients in Africa are children. Healthcare professionals

must be well-informed to address questions and concerns from patients families. Future efforts

should incorporate early involvement of patients and caregivers in Africa in programs related to

curative therapies for SCD.},

howpublished = {medRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bukini2025,

title = {Combining deliberative engagement with qualitative research to assess patient and caregiver perspectives on curative therapies for sickle cell disease in Africa},

author = {Daima Bukini and Jennifer Mashaka and Aisha Rifai and Collin Kanza and Kassim Kassim and Rahma Chanzi and Deogratius Maingu and Frederick Luoga and Winfrida Lema and Fatou Konteh and Mohammed Zahir and Elianna Amin and Jonathan Spector and Julie Makani},

url = {http://medrxiv.org/lookup/doi/10.1101/2025.07.30.25332426},

doi = {10.1101/2025.07.30.25332426},

year  = {2025},

date = {2025-07-30},

urldate = {2025-07-30},

publisher = {Cold Spring Harbor Laboratory},

abstract = {The vast majority of individuals impacted by sickle cell disease (SCD) live in Africa, where access to potentially curative therapies such as hematopoietic stem cell transplant and gene therapies have been severely limited until now. As part of a broad effort to help prepare scientific, healthcare, and patient communities in Tanzania for the introduction of advanced SCD therapies, we sought to understand perspectives relating to curative options for SCD held by patients and their families. To achieve this, innovative qualitative research methodology was required given the highly variable level of baseline knowledge among patient communities regarding curative treatments for SCD. We therefore adopted an approach of deliberative engagement followed by traditional qualitative methods that facilitated successful identification of participants, development of research tools, and, ultimately, elicitation of valuable insights that enabled in-depth analyses. Our experience demonstrates that, when exploring perspectives relating to complex medical procedures in this population, deliberative engagement substantially enhances the outputs of qualitative research.},

howpublished = {medRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39104574,

title = {Consensus-driven target product profiles for curative sickle cell disease gene therapies},

author = {Daima Bukini and Julie Makani and Joseph McCune and Dennis Lee and Cathy Bansbach and Serena De Vita and Dominic Kemps and Elianna Amin and Jonathan Spector and John Tisdale},

doi = {10.1016/j.omtm.2024.101287},

issn = {2329-0501},

year  = {2024},

date = {2024-09-01},

urldate = {2024-09-01},

journal = {Mol Ther Methods Clin Dev},

volume = {32},

number = {3},

pages = {101287},

abstract = {Therapeutic innovation to address sickle cell disease (SCD) is at a historical apex, characterized by a drug discovery, development, and commercialization landscape that includes potentially curative gene therapies. Given the wide geographic distribution of SCD, with a major presence in Africa, it is imperative that new medicines are designed to meet the specific needs of persons with SCD everywhere. Target product profiles (TPPs) detail the desired attributes of new medicines and serve as a guide for drug developers. To support research efforts for curative treatments for SCD, we mobilized a large multi-disciplinary expert group to generate consensus-driven TPPs for  and  SCD gene therapies, utilizing a modified Delphi methodology supplemented with virtual workshops. The main findings are TPPs that describe 20 minimal and optimal criteria for novel gene therapy products in categories of scope (3 criteria), performance/safety (11 criteria), manufacturing (4 criteria), and administration (2 criteria). TPPs for  and  products differed in some performance/safety criteria and all criteria pertaining to manufacturing and administration. These outputs will ideally support development of durable treatments that are safe, efficacious, and practical for persons with SCD in global settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Athman2024,

title = {Depression Prevalence and Associated Factors Among Adolescents with Sickle Cell Anemia in Dar es Salaam, Tanzania: A Cross-Sectional Study},

author = {Linda Paul Athman and Agnes Jonathan and Fatima Mussa and Honesta kipasika and Isihaka Mahawi and Florence Urio and Mwashungi Ally and Ritha Mutagonda and Lulu Chirande and Julie Makani and Emmanuel Balandya},

url = {https://www.researchsquare.com/article/rs-4693535/v1},

doi = {10.21203/rs.3.rs-4693535/v1},

year  = {2024},

date = {2024-08-10},

urldate = {2024-08-10},

publisher = {Springer Science and Business Media LLC},

abstract = {Background: Depression commonly arises among adolescents who have experienced long-standing psychosocial difficulties especially those facing chronic illnesses like Sickle Cell Anemia (SCA).  SCA is a global health concern, and Tanzania is one of the countries with a high incidence, estimated at 8,000 to 11,000 births per year. This study aims to assess the magnitude and factors associated with depression among adolescents with SCA.

Methodology: A cross-sectional analytical study conducted on adolescents aged 11-19 years attending sickle cell clinics in referral hospitals in Dar-es-salaam Tanzania, from October 2023-March 2024. A validated Patient Health Questionnaire (PHQ-9) tool was used to screen for depression. Univarite and multivariate regression model was used to determine factors associated with clinical depression.A P value of less than 0.05 was considered statistically significant.

Results: Among 326 adolescents enrolled, the majority (64.7%) were 10-14 years of age. A total of 216 (54 %) had depression; when categorized into severity, 167 (38.7 %) had mild, 48 (14.7 %) had moderate and 1 (0.3%) had severe depression. Clinical depression, encompassing moderate to severe depression, was prevalent in 49 (15%) adolescents. Painful episodes were significantly associated with depression (aOR = 2.49) (95% CI: 1.17 - 5.29, p = 0.01).

Conclusion: Depression is common among adolescents with SCA in our setting. Painful episodes experienced by these adolescents were significantly associated with depression. This study highlights the need for screening adolescents with SCA for depression and integration of mental health services in sickle cell clinics.},

howpublished = {Research Square},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid39089806b,

title = {Update on SickleInAfrica: a collaborative and multidimensional approach to conduct research and improve health},

author = {Siana Nkya and Upendo Masamu and Patience Kuona and Sarah Kiguli and Aldiouma Guindo and Fred Stephen Sarfo and Obiageli Nnodu and Ambroise Wonkam and Emmanuel Balandya and Julie Makani and },

doi = {10.1016/S2352-3026(24)00219-9},

issn = {2352-3026},

year  = {2024},

date = {2024-08-01},

journal = {Lancet Haematol},

volume = {11},

number = {8},

pages = {e565--e566},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Masamu2024,

title = {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},

author = {Upendo Masamu and Raphael Z. Sangeda and Josephine Mgaya and Siana Nkya and Beatrice Octavian and Frank R. Mtiiye and Joyce Nduguru and Agnes Jonathan and Daniel Kandonga and Irene K. Minja and Paschal Rugajo and Emmanuel Balandya and Julie Makani},

doi = {10.1089/bio.2023.0060},

issn = {1947-5543},

year  = {2024},

date = {2024-06-01},

journal = {Biopreservation and Biobanking},

volume = {22},

number = {3},

pages = {248--256},

publisher = {Mary Ann Liebert Inc},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nkya2024c,

title = {Exploring Pharmacogenetic Factors Influencing Hydroxyurea Response in Tanzanian Sickle Cell Disease Patients: A Genomic Medicine Approach},

author = {Siana Nkya and Collin Nzunda and Emmanuel Saukiwa and Frida Kaywanga and Eliud Buchard and David Solomon and Heavenlight Christopher and Doreen Ngowi and Julieth Johansen and Florence Urio and Josephine Mgaya and Christina Kindole and Mbonea Yonazi and Salman Karim and Mohamed Zahir Alimohamed and Raphael Z. Sangeda and Clara Chamba and Collet Dandara and Enrico Novelli and Emile R. Chimusa and Julie Makani},

url = {http://biorxiv.org/lookup/doi/10.1101/2024.05.23.595488},

doi = {10.1101/2024.05.23.595488},

year  = {2024},

date = {2024-05-27},

urldate = {2024-05-27},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Sickle cell disease (SCD) continues to pose a significant public health challenge, particularly in sub-Saharan Africa. Despite its discovery over a century ago, the progress in developing and accessing effective interventions has been notably restricted. Currently, hydroxyurea stands as the primary drug in widespread use, and has been associated with elevated levels of fetal hemoglobin (HbF) and enhanced clinical outcomes. Notably, a substantial proportion, up to 30%, of patients do not exhibit a positive response to hydroxyurea treatment. There is compelling evidence suggesting that genetic factors play a crucial role in influencing the effectiveness of hydroxyurea. In this study, we present findings on the investigation of genetic variants influencing hydroxyurea response in 13 genetic loci associated with HbF synthesis and hydroxyurea drug metabolism focusing on MYB, HBB, HBG1, HBG2, BCL11A, KLF10, HAO2, NOS1, ARG2, SAR1A, CYP2C9, CYP2E1. We report remarkable genetic associations with CYP2C9, CYP2E1, KLF10, BCL11A, ARG2, HBG1, SAR1A, MYB, and NOS1 loci with hydroxyurea response. We also highlight associated pathway’s enrichment and gene-gene interactions analysis in the context of hydroxyurea treatment response.},

howpublished = {bioRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ally2024b,

title = {Caregivers’ Perceived Threat of Sickle Cell Disease Complications and Hydroxyurea Use Among Health Insured Children with Sickle Cell Disease in Dar es Salaam, Tanzania: an Analytical Cross-Sectional Study},

author = {Mwashungi Ally and Deodatus Kakoko and Calvin Swai and Emmy Metta and Mbonea Yonaz and Julie Makani and Elia Mmbaga and Melkizedeck Leshabari and Kåre Moen and Tone Kristen Omsland and Emmanuel Balandya},

url = {https://www.researchsquare.com/article/rs-4350150/v1},

doi = {10.21203/rs.3.rs-4350150/v1},

year  = {2024},

date = {2024-05-08},

urldate = {2024-05-08},

publisher = {Springer Science and Business Media LLC},

abstract = {Background

Tanzania is among the five countries with the highest prevalence of sickle cell disease (SCD) globally. Although hydroxyurea (HU) is available, only a quarter of persons with SCD are reported to use it in Tanzania. Perceived disease threat is associated with medication usage in patients with chronic diseases. We assessed the factors associated with caregivers’ perceived threat of SCD complications and its relationship with HU use among health-insured children with SCD attending clinics in Dar-es-Salaam.



Methods

We conducted a cross-sectional hospital-based study from May to August 2023. We enrolled 374 caregivers of health-insured children with SCD from 4 public SCD clinics. The modified original and revised Champion’s Health Belief Model Scales were used to derive scores for the main outcomes (perceived susceptibility, severity, and threat of SCD; highest possible score, corresponding to the largest perceived threat = 765). Mann-Whitney and Kruskal Wallis tests were used for comparisons of the outcomes across sociodemographic characteristics. Regression analysis of factors associated with perceived SCD threat, and Poisson regression for analysis of association between perceived threat and HU usage were conducted.



Results

The median scores (InterQuartale Range) for perceived susceptibility, severity, and threat of SCD complications were 13 (7, 14), 39 (26, 44), and 559 (175, 598), respectively. Sixty-one percent of caregivers had high SCD perceived threat. The caregivers of under-five children had 141 lower median SCD threat scores compared to those of children aged 13–17 years, p-value < 0.001. Participants from Regional Referral Hospitals had lower median threat scores compared to participants attending Muhimbili National Hospital (MNH), 177 for Amana, 325 Temeke, 585 MNH Mloganzila, and 557 MNH Upanga, p-value < 0.001. Children of caregivers with high perceived SCD threat were 3.4 times more likely to use HU compared to those with low SCD threat perception (Incidence Rate Ratio 3.4, 95% CI: 2.7–4.5, p-value < 0.001).



Conclusion

Perceived threat of SCD predicts the likelihood of SCD patients using HU in Dar-es-Salaam, Tanzania. We recommend health education to caregivers aiming to improve their SCD threat perception and thus improve the use of HU among children with SCD in similar settings.},

howpublished = {Research Square},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sangeda2024,

title = {Prevalence of Urinary Tract Infections and Antibiogram of Bacteria Isolated From Children With Sickle Cell Disease in Tanzania},

author = {Raphael Z Sangeda and Joseph Yohana and Agnes Jonathan and Vicky P Manyanga and Deogratius Soka and Julie Makani},

doi = {10.7759/cureus.58786},

issn = {2168-8184},

year  = {2024},

date = {2024-04-22},

publisher = {Springer Science and Business Media LLC},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nkya2023,

title = {Towards Genomic Medicine: A Tailored Next-Generation Sequencing Panel for Hydroxyurea Pharmacogenomics in Tanzania},

author = {Siana Nkya and Collin Nzunda and Emmanuel Saukiwa and Frida Kaywanga and Eliud Buchard and David Solomon and Heavenlight Christopher and Doreen Ngowi and Julieth Johansen and Florence Urio and Josephine Mgaya and Salman Karim and Mohamed Zahir Alimohamed and Raphael Z. Sangeda and Clara Chamba and Emile R. Chimusa and Enrico Novelli and Julie Makani},

url = {https://www.researchsquare.com/article/rs-3235315/v1},

doi = {10.21203/rs.3.rs-3235315/v1},

year  = {2023},

date = {2023-08-25},

urldate = {2023-08-25},

publisher = {Springer Science and Business Media LLC},

abstract = {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. This study investigated genetic variations in BCL11A, ARG2, HBB, HBG1, WAC, HBG2, HAO2, MYB, SAR1A, KLF10, CYP2C9, CYP2E1 and NOS1 as potential HU pharmacogenomics targets. 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). 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 which is sufficient for genomic analysis. Therefore, this study provides a valuable tool for research in HU pharmacogenomics, especially in Africa.},

howpublished = {Research Square},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nkya2023b,

title = {Genomics of fetal haemoglobin: a targeted approach for reticulocyte transcriptome study},

author = {Siana Nkya and Frida Kaywanga and Collin Nzunda and Salmaan Karim and David Solomon and Emmanuel Saukiwa and Heavenlight Christopher and Doreen Ngowi and Julieth Johansen and Florence Urio and Josephine Mgaya and Clara Chamba and Fadya Hashim and Emmanuela Ambroise and Solomon Ofori Acquah and Julie Makani},

url = {https://www.researchsquare.com/article/rs-3061395/v1},

doi = {10.21203/rs.3.rs-3061395/v1},

year  = {2023},

date = {2023-06-30},

urldate = {2023-06-30},

publisher = {Research Square Platform LLC},

abstract = {Background: Fetal haemoglobin (HbF) remains a major sickle cell disease modifier. The mechanism of HbF synthesis has been studied for several decades with the intention of increasing interventions for sickle cell disease (SCD), including drugs. However, the complex mechanism of HbF synthesis is influenced by multiple genetic factors interacting with environmental factors. In order to capture useful genetic information, especially with limited resources, one has to carefully design the study. This includes choosing the relevant participants, the correct phenotyping, the choice of samples, and the right genomic assays. This paper describes the approach undertaken as part of preparations for a reticulocyte transcriptome study intended to discover genes associated with HbF decline in newborns in Tanzania.



Results: Of the 152 newborns enrolled in the larger study, 40 babies were selected for the reticulocyte transcriptome study based on their HbF levels at birth and later stage of life. Of these, 30 individuals were included under the category of high HbF levels ranging from 72.6-90% and the remaining 10 under the category of low HbF levels ranging from 5.9 - 10.3%. The reticulocyte enrichment recovery purity ranged from 85% - 97%. The total RNA concentrations obtained were >250 ng total RNA, with the average purity of 1.9 (A 260/280) respectively. The total concentration obtained was sufficient for the transcriptome and other downstream assays.



Conclusion: We have documented important steps and factors to consider in identifying the relevant participants and required laboratory sample processes prior to the final stage, which involves total reticulocyte RNA sequencing.},

howpublished = {Research Square},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kandonga2023,

title = {Development of the sickle Pan-African research consortium registry in Tanzania: opportunity to harness data science for sickle cell disease},

author = {Daniel Kandonga and Raphael Zozimus Sangeda and Upendo Masamu and Eliah Kazumali and Agnes Jonathan and Michael Msangawale and Winfrida Kaihula and Julieth Rwegalulila and Jesca Ondego and Hilda J. Tutuba and Joyce Ndunguru and Emmanuela E. Ambrose and Benson R. Kidenya and Mbonea Yonazi and Irene Kyomugisha and Wilson Mupfururirwa and Mario Jonas and Victoria Nembaware and Gaston Kuzamunu Mazandu and Andre Pascal Kengne and Ambroise Wonkam and Julie Makani and Emmanuel Balandya},

doi = {10.3389/frhem.2023.1040720},

issn = {2813-3935},

year  = {2023},

date = {2023-04-11},

urldate = {2023-04-11},

journal = {Front. Hematol.},

volume = {2},

publisher = {Frontiers Media SA},

abstract = {Background: Sickle cell disease (SCD) is a severe hereditary form of anemia that contributes between 50% and 80% of under-five mortality in Africa. Eleven thousand babies are born with SCD annually in Tanzania, ranking 4th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to health research in SCD in Africa.



Objective: This paper describes the Sickle Pan African Consortium (SPARCO) database in Tanzania, from the development, design of the study instruments, data collection, analysis of data and management of data quality issues.



Methods: The SPARCO registry used existing Muhimbili Sickle Cell Cohort (MSC) study case report forms (CRF) and later harmonized data elements from the SickleInAfrica consortium to develop Research Electronic Data Capture (REDCap) instruments. Patients were enrolled through various strategies, including mass screening following media sensitization and health education events during World Sickle Cell Day each June and the SCD awareness month in September. Additional patients were identified through active surveillance of previously participating patients in the MSC.



Results: Three thousand eight hundred patients were enrolled between October 2017 and May 2021. Of these, 1,946 (51.21%) were males and 1,864 (48.79%) were females. The hemoglobin phenotype distribution was 3,762 (99%) HbSS, 3 (0.08%) HbSC and 35 (0.92%) HbSβ +thalassemia. Hemoglobin levels, admission history, blood transfusion and painful events were recorded from December 2017 to May 2021.



Conclusion: The Tanzania SPARCO registry will improve healthcare for SCD in Africa through the facilitation of collaborative data-driven research for SCD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mwita2023,

title = {Infrastructure for bioinformatics applications in Tanzania: Lessons from the Sickle Cell Programme},

author = {Liberata A. Mwita and William F. Mawalla and Frank R. Mtiiye and Daniel Kandonga and Jill Kent and Julie Makani and Raphael Z. Sangeda},

editor = {Patricia M. Palagi},

doi = {10.1371/journal.pcbi.1010848},

issn = {1553-7358},

year  = {2023},

date = {2023-02-23},

urldate = {2023-02-23},

journal = {PLoS Comput Biol},

volume = {19},

number = {2},

publisher = {Public Library of Science (PLoS)},

abstract = {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.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Masamu2023,

title = {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},

author = {Upendo Masamu and Raphael Z Sangeda and Josephine Mgaya and Siana Nkya and Beatrice Octavian and Frank R Mtiiye and Joyce Nduguru and Agnes Jonathan and Daniel Kandonga and Irene K Minja and Paschal Rugajo and Emmanuel Balandya and Julie Makani},

url = {http://medrxiv.org/lookup/doi/10.1101/2023.01.06.23284272},

doi = {10.1101/2023.01.06.23284272},

year  = {2023},

date = {2023-01-09},

urldate = {2023-01-09},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Genetic modifiers underlying various sickle cell disease phenotypic expressions are largely unexplored in Africa due to lack of databases linking biospecimens with demographic and clinical data. The problem may be compounded by a complete lack of biorepositories in these settings. This article aims to document the physical verification of biospecimens stored in the biorepository and link them to patient clinical and demographic information to facilitate plans for genomic and related clinical research studies. We reviewed and updated the existing biorepository infrastructure at Muhimbili Sickle Cell Programme in Dar es Salaam, Tanzania. The database of archived biospecimens was updated with the location information of respective biospecimens following the physical verification of biospecimens and then mapping the patient demographic and clinical data with the biospecimen data using sickle cell patients’ demographic identifiers. Three freezers maintained at -80°C store a total of 74,079 biospecimens, of which 63,345 were from 5,159 patients registered in the Muhimbili Sickle Cohort from 2004 to 2016. Out of stored biospecimens, follow-ups were 46,915 (74.06%), control 8,067 (12.74%), admission 5,517 (8.71%) and entry 2,846 (4.49%). Of these registered patients, females were 2,521 (48.87%) and males were 2,638 (51.13%). The age distribution was 1 to 59 years, with those above 18 years being 577 (11.18%) and children 4,582 (88.82%) of registered patients. The notable findings during the process include a lack of automated biospecimen checks, laboratory information management system and standardization of equipment used, biospecimens not linked to clinical and demographic data, date format inconsistencies, lack of regular updating of a database on exhausted biospecimens and updates when biospecimens are moved between positions within freezers. Well-organized biorepository plays a crucial role in answering future research questions. Enforcing strict standard operating procedures and quality control standards will ensure that laboratory scientists and other users adhere to the best biospecimen management procedures.},

howpublished = {medRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bukini2022,

title = {The contribution of social and family networks in supporting care of children with sickle cell disease in Tanzania},

author = {Daima Bukini and Irene Msirikale and Collins Kanza and Jesca Odengo and Deogratius Maingu and Upendo Masamu and Karim Manji and Julie Makani and Columba Mbekenga},

url = {http://medrxiv.org/lookup/doi/10.1101/2022.11.01.22281740},

doi = {10.1101/2022.11.01.22281740},

year  = {2022},

date = {2022-11-02},

urldate = {2022-11-02},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Background The care of children with Sickle cell disease (SCD) in Africa has been the work of mothers or women within communities. Previous studies have indicated that mothers in these families are supported by other women within the family or even from outside family structures. Such support has allowed significant sharing of responsibilities in both domestic and care giving roles for children with sickle cell disease. However, there is limited recognition of this informal support and its importance as a key element in health care provision.



Objective In this paper, we aim to demonstrate how these support networks have been used by mothers in shouldering their caregiving roles. We also propose how the networks can be integrated into the health care system to improve quality of care of the children with SCD.



Methods We conducted interviews with families of children who are diagnosed with sickle cell disease through newborn screening program in Tanzania between 2015 and 2019. In total, 15 families were included through focus group discussions (FGDs), dyadic interviews, and individual interviews. Also, a survey was conducted involving 100 families of children with SCD aged between 0 and 17 years to assess the different networks of care that exists within families and communities. Thematic analysis was used for the qualitative data while data from the survey was presented in proportions as pie charts.



Results The results from the FGDs and IDIs demonstrated three ways in which the networks of care were supportive to mothers (1) Facilitating sickle cell disease diagnosis to children who were undiagnosed (2) Caring for the sick child (children) after diagnosis and (3) Support at home in caring for other children who are not sick and helping with domestic work responsibilities. Survey results indicated that the highest proportion of the respondents listed mothers of the children as the primary care giver (88%), followed by grandmothers (10%) and close family members (2%). Extended family members (20%) were recognized as the largest network of care in the absence of the primary caregiver outside the parents, followed by siblings, defined as elder brothers and sisters (18%) and grandparents (16%).



Conclusion The findings from this study confirm that there is an important network supporting care of children with SCD in communities supporting parents. Enabling these support networks to be more formally integrated into the health care system will ensure those members of the community providing care are equipped with knowledge on sickle cell disease and having positive impact on the quality of care of the children born with SCD in sub-Saharan Africa.},

howpublished = {medRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36360565,

title = {Barriers and Facilitators of Availability of Hydroxyurea for Sickle Cell Disease in Tanzania; A Qualitative Study of Pharmaceutical Manufacturers, Importers, and Regulators},

author = {Hamu J Mlyuka and Manase Kilonzi and Ritah F Mutagonda and Lulu Chirande and Wigilya P Mikomangwa and David T Myemba and Godfrey Sambayi and Dorkasi L Mwakawanga and Joyce Ndunguru and Agnes Jonathan and Julie Makani and Paschal Ruggajo and Irene K Minja and Emmanuel Balandya and Appolinary A R Kamuhabwa},

doi = {10.3390/healthcare10112223},

issn = {2227-9032},

year  = {2022},

date = {2022-11-01},

journal = {Healthcare (Basel)},

volume = {10},

number = {11},

abstract = {Despite three decades of proven safety and effectiveness of hydroxyurea in modifying sickle cell disease (SCD), its accessibility is limited in Sub-Saharan Africa, which shares 75% of the world's SCD burden. Therefore, it is time to explore the barriers and facilitators for manufacturing and importation of hydroxyurea for SCD in Tanzania. This was qualitative research that employed a case study approach. Purposive sampling followed by an in-depth interview (IDI) using a semi-structured questionnaire aspired by data saturation enabled us to gather data from 10 participants. The study participants were people with more than three years of experience in pharmaceuticals importation, manufacturing, and regulation. The audio-recorded data were verbatim transcribed and analyzed using thematic analysis. Two themes were generated. The first comprised barriers for importation and manufacturing of hydroxyurea with sub-themes such as inadequate awareness of SCD and hydroxyurea, limited market, and investment viability. The second comprised opportunities for importation and manufacturing of hydroxyurea with sub-themes such as awareness of activities performed by medicines regulatory authority and basic knowledge on SCD and hydroxyurea. Inadequate understanding of SCD, hydroxyurea, and orphan drug regulation are major issues that aggravate the concern for limited market and investment viability. Existing opportunities are a starting point towards increasing the availability of hydroxyurea.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bukini2022b,

title = {Communicating sickle cell trait results after newborn screening: Approaches and implications to families},

author = {Daima Bukini and Irene Msirikale and Emanuela Marco and Michael Msangawale and Lulu Chirande and Columba Mbekenga and Karim Manji and Julie Makani},

url = {http://medrxiv.org/lookup/doi/10.1101/2022.10.30.22281739},

doi = {10.1101/2022.10.30.22281739},

year  = {2022},

date = {2022-11-01},

urldate = {2022-11-01},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Introduction Tanzania is amongst the countries in Africa with one of the highest prevalence of individuals with Sickle Cell Trait (SCT). Identifying individuals with SCT is important as they may potentially have children with Sickle Cell Disease (SCD). Interventions such as Newborn Screening (NBS) for SCD can identify individuals carrying the gene very early on to explore strategies for primary prevention.



Aim This study aims to document experiences and perspectives of families who have received SCT results for their children through the NBS Program. We were interested to learn their perspectives on the communication approaches used and implications of the results to families. Our overall goal is to evaluate what approaches works best to support comprehension, understanding of genetic testing, concepts of inheritability and general understanding of SCD. We further aim to explore key issues considered by families as most important to inform not only methods, but also most locally relevant content to guide genetic counselling sessions.



Methods In total 29 families provided with SCT results participated in six (6) Focus Group Discussions. Families were recruited through NBS program implemented between June to September 2021. Analysis of the data was done through thematic content analysis.



Results Findings were categorized into two main categories; (1) Key issues to consider when communicating sickle cell trait results to families. The following themes were identified under this category; (1a) Language used to explain the results (1b) Methods used to provide the results (1c) Who was provided with the results (1d) Families comprehension of the results and (1e) What influences families’ understanding of the results (2) What are the implications of the results to families. The following themes were identified under this category; (2a) How results influenced future reproductive choices (2b) How will the information be kept within families (2c) Age a child will start to be informed about the results (2d) How results influence gender blames within families.



Conclusion Understanding how to ensure genetic results have been properly communicated is core in developing a genetic counselling program. In places where the programs are not well established, there is a need to explore contexts specific approaches to inform ethically relevant communication models that incorporated families and patient perspectives. This study un-packed the different aspects to consider when developing proper communication models and further highlighted issues to explore with families after receiving the results, with the hope that this information will help to inform genetic counselling sessions in places with high SCD burden.},

howpublished = {medRxiv},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35617818,

title = {The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children},

author = {Sri Riyati Sugiarto and George M Bwire and Brioni R Moore and Madhu Page-Sharp and Laurens Manning and Kevin T Batty and Omary M S Minzi and Billy Ngasala and Timothy M E Davis and Julie Makani and Sam Salman},

doi = {10.1016/j.ijpddr.2022.05.002},

issn = {2211-3207},

year  = {2022},

date = {2022-08-01},

journal = {Int J Parasitol Drugs Drug Resist},

volume = {19},

pages = {31--39},

abstract = {Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5-10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days. Sparse venous and mixed-capillary dried blood spot (DBS) samples were taken over 42 days. Plasma and DBS ARM and LUM, and their active metabolites dihydroartemisinin (DHA) and desbutyl-lumefantrine (DBL), were assayed using validated liquid chromatography-mass spectrometry. Multi-compartmental pharmacokinetic models were developed using a population approach. Plasma but not DBS concentrations of ARM/DHA were assessable. The majority (85%) of the 15 measurable values were within 95% prediction intervals from a published population pharmacokinetic ARM/DHA model in Papua New Guinean children of similar age without SCD/SCT who had uncomplicated malaria, and there was no clear sickle genotype clustering. Plasma (n = 38) and corrected DBS (n = 222) LUM concentrations were analysed using a two-compartment model. The median [inter-quartile range] LUM AUC was 607,296 [426,480-860,773] μg.h/L, within the range in published studies involving different populations, age-groups and malaria status. DBS and plasma DBL concentrations correlated poorly and were not modelled. These data support use of the conventional ARM-LUM treatment regimen for uncomplicated malaria in children with SCT/SCD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35595849,

title = {From Mendel to a Mendelian disorder: towards a cure for sickle cell disease},

author = {Julie Makani and Siana Nkya and Francis Collins and Lucio Luzzatto},

doi = {10.1038/s41576-022-00498-1},

issn = {1471-0064},

year  = {2022},

date = {2022-07-01},

journal = {Nat Rev Genet},

volume = {23},

number = {7},

pages = {389--390},

keywords = {},

pubstate = {published},

tppubtype = {article}

}