Strengthening global partnerships for sustainable sickle cell disease care: insights from SickleInAfrica at the 77th United Nations General Assembly and the US-Africa Leaders' Summit.

Background: Addressing sickle cell disease (SCD) is crucial for achieving health-related Sustainable Development Goals, particularly in Africa. The region is significantly affected, with 78.7% of patients with SCD residing in sub-Saharan Africa and over 515 000 newborns diagnosed annually.

FLT1 and other candidate fetal haemoglobin modifying loci in sickle cell disease in African ancestries.

Known fetal haemoglobin (HbF)-modulating loci explain 10-24% variation of HbF level in Africans with Sickle Cell Disease (SCD), compared to 50% among Europeans. Here, we report fourteen candidate loci from a genome-wide association study (GWAS) of HbF level in patients with SCD from Cameroon, Tanzania, and the United States of America. We present results of cell-based experiments for FLT1 candidate, demonstrating expression in early haematopoiesis and a possible involvement in hypoxia associated HbF induction.

Harnessing genomics and translational research to improve health in Africa: a report of the 13 African Society of Human Genetics meeting in Dar es Salaam, Tanzania.

The thirteenth conference of the African Society of Human Genetics with the theme "harnessing genomics and translational research to improve health in Africa" was held in Dar es Salaam, Tanzania, in August 2021, using a hybrid in-person and virtual model for participation in the wake of COVID-19 pandemic. During the meeting, African research across various human genetics disciplines was presented, including talks on the genetics of infectious and non-communicable diseases, population genetics, and translational research. The meeting also featured presentations on pharmacogenomics, genetics of developmental disorders, cancer genetics and genetics of rare diseases.

Acceptability, barriers and facilitators of using dried blood spots-point-of-care testing for sickle cell disease in Africa: an implementation science protocol for a multinational qualitative study.

Background: Sickle cell disease (SCD) is a prevalent inherited blood disorder. Globally, approximately 515 000 babies are born with SCD annually, with 75% of these births occurring in Africa. Integrating newborn screening (NBS) for SCD into primary healthcare structures, such as immunisation programmes, holds significant promise, with dried blood spots (DBS)-point-of-care technologies (POCT) like HaemoTypeSC offering cost-effective screening solutions.

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.

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/HbSβ0), followed by a replication and meta-analysis exercise in four independent SCD cohorts (3,582 patients).

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.

Implementation of a gene therapy education initiative by the ASGCT and Muhimbili University of Health and Allied Sciences.

There has been rapid growth in gene therapy development with an expanding list of approved clinical products. Several therapies are particularly relevant to patients in low- and middle-income countries. Moreover, investing in research and manufacturing presents an opportunity for economic development.

Genomics of fetal haemoglobin: a targeted approach for reticulocyte transcriptome study.

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.

The rate and pattern of fetal hemoglobin decline adjusted to sickle cell status of newborns in Dar es Salaam, Tanzania: A prospective cohort study.

Foetal haemoglobin (%) and foetal cell (%) according to sickle cell status.

Building research capacity for sickle cell disease in Africa: Lessons and challenges from establishing a birth cohort in Tanzania.

Sickle Cell Disease (SCD) is a known public health burden in sub-Saharan Africa (SSA). The manifestation of SCD starts in early childhood and if not well-managed may lead to early death (before the age of 5 years). Understanding the underlying mechanisms that influence early SCD manifestation is of great importance for early disease and intervention management which will in turn, reduce both morbidity and mortality rates in children.

Rare diseases in Tanzania: a National Call for Action to address policy and urgent needs of individuals with rare diseases.

A rare disease is generally defined as a condition which affects about 1 among 2000 people and currently, there are approximately 5000-8000 rare diseases (RDs) affecting over 400 million people world-wide. Although RDs may arise from different causes such as infections and environmental factors, about 80% are caused by genetic abnormalities. In Tanzania, there are no reports of the types of RDs, their incidence, distribution and numbers of individuals affected.

Potential of point of care tests for newborn screening for sickle cell disease: Evaluation of HemotypeSC™ and sickle SCAN® in Tanzania.

Background: Sickle cell disease (SCD) is an important cause of <5 mortality. In Tanzania, it is estimated up to 11 000 children are born with SCD annually, making this the fifth country with the highest SCD annual births worldwide. The biggest challenge of expanding the service of newborn screening for SCD as the national health intervention in Tanzania is due to the high cost of the currently used assays and lack of rapid screening methods.

Enablers and barriers to newborn screening for sickle cell disease in Africa: results from a qualitative study involving programmes in six countries.

Objectives: Given the fundamental role of newborn bloodspot screening (NBS) to enable prompt diagnosis and optimal clinical management of individuals with sickle cell disease (SCD), we sought to systematically assess enablers and barriers to implementation of NBS programmes for SCD in Africa using established qualitative research methods.

Setting: Childbirth centres and NBS laboratories from six countries in East, West and Southern Africa.

Participants: Eight programme leaders involved with establishing and operating NBS programmes for SCD in Angola, Democratic Republic of Congo, Ghana, Liberia, Nigeria and Tanzania.

Using DNA testing for the precise, definite, and low-cost diagnosis of sickle cell disease and other Haemoglobinopathies: findings from Tanzania.

Background: Sickle cell disease (SCD) is an important cause of under-five mortality. Tanzania is the 5th country in the world with the highest births prevalence of SCD individuals. Significant advances in the neonatal diagnosis of SCD using rapid point-of-care testing have been made.

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

Tanzania is one of the countries with a high burden of sickle cell disease (SCD). Haemolytic anaemia is a clinical feature of SCD, and has been linked to major complications leading to morbidity and mortality. Treatment with hydroxyurea (HU) has shown to induce foetal haemoglobin (HbF) which in turn decreases haemolysis in patients.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use.

Perspectives on Building Sustainable Newborn Screening Programs for Sickle Cell Disease: Experience from Tanzania.

The prevalence of sickle cell disease is high in Africa, with significant public health effects on the affected countries. Many of the countries with the highest prevalence of the disease also have poor health care systems and a high burden of infectious diseases with many other competing health care priorities. Although considerable efforts have been made to implement newborn screening for sickle cell disease programs in Africa, coverage is still low.

Inauguration of the Tanzania Society of Human Genetics: Biomedical Research in Tanzania with Emphasis on Human Genetics and Genomics.

Human genetics research and applications are rapidly growing areas in health innovations and services. African populations are reported to be highly diverse and carry the greatest number of variants per genome. Exploring these variants is key to realize the genomic medicine initiative.

Patterns and patient factors associated with loss to follow-up in the Muhimbili sickle cell cohort, Tanzania.

Background: Monitoring patient's clinical attendance is a crucial means of improving retention in care and treatment programmes. Sickle cell patients' outcomes are improved by participation in comprehensive care programmes, but these benefits cannot be achieved when patients are lost from clinical care. In this study, patients are defined as loss to follow-up when they did not attend clinic for more than 9 months.