Julie Makani

• MD, PhD, FRCP, FTAAS
• Professor (Associate) at Muhimbili University of Health and Allied Sciences

Introduction Sickle cell disease (SCD) is most prevalent in Sub‐Saharan Africa (SSA), where incomplete patient profiles and limited management strategies hinder research and healthcare standards. Methods We describe the first large‐scale and multinational assessment of 13,403 SCD patients enrolled from 2017–2021 across 31 facilities in Ghana, Nige...

In sub-Saharan Africa, sickle cell disease (SCD) remains a significant public health challenge. Despite the discovery of SCD over a century ago, progress in developing and accessing effective treatments has been limited. Hydroxyurea is the primary drug used for managing SCD and associated with improving clinical outcomes. However, up to 30% of pati...

Globally, sickle cell disease (SCD) is the most common inherited haemoglobinopathy. The highest burden of SCD is encountered in low‐ and middle‐income countries (LMICs), most of which lack the resources to contend with the disease. There is a marked divide between care for individuals with SCD in high‐income countries (HICs) versus LMICs, whereby t...

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. Historically, African health systems have struggled to provi...

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 r...

Despite progress in healthcare services for individuals living with sickle cell disease (SCD) in Africa, substantial gaps remain in advanced treatments for SCD. To help address this burden, Tanzania has established one of the largest single-centre SCD programmes in the world and developed an advanced therapy programme for SCD focused on patient eng...

Background Depression commonly arises among adolescents who have experienced long-standing psychosocial difficulties, especially those facing chronic illnesses such as sickle cell anemia (SCA). SCA is a global health concern, and Tanzania is one of the countries with a high incidence, estimated at 8,000–11,000 births per year. This study aims to as...

Purpose Tanzania is the fifth country with the highest sickle cell disease (SCD) prevalence globally. Although hydroxyurea (HU) is available, only 25% 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 caregiv...

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 sp...

Background : Prevalence of Sickle Cell Disease (SCD) across African countries ranges between 1–3% and contributes up to 7-16% of under-five mortality. Nigeria, Ghana and Tanzania are among the top ten countries globally, with over 11,000 babies born with SCD annually. In order to bridge the gap in management and cognate research, the SickleInAfrica...

Background Anaemia in sickle cell disease (SCD) is a significant cause of morbidity and mortality, but few studies have reported on the burden and outcome of very severe anaemia. This study described the epidemiology of very severe anaemia by determining the prevalence and incidence, investigating associated clinical and laboratory factors, and ass...

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...

Background Sub-Saharan Africa bears the highest burden of sickle cell disease (SCD) globally with Nigeria, Democratic Republic of Congo, Tanzania, Uganda being the most affected countries. Uganda reports approximately 20,000 SCD births annually, constituting 6.67% of reported global SCD births. Despite this, there is a paucity of comprehensive data...

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...

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 as...

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 me...

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 wi...

Gene therapies are designed to address the root cause of disease. As scientific understanding of disease prevention, diagnosis, and treatment improves in tandem with technological innovation, gene therapies have the potential to become safe and effective treatment options for a wide range of genetic and nongenetic diseases. However, as the medical...

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 asso...

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 heigh...

Purpose This comparative study sets out to report dental caries status among individuals with Sickle Cell Disease (HbSS) against those with sickle cell trait (HbSA) and those without the disease (HbAA) as controls. The study further assessed the impact of penicillin chemoprophylaxis and hydroxyurea use on dental caries among Sickle Cell Disease par...

Sickle cell disease (SCD) is a single gene blood disorder characterised by frequent episodes of pain, chronic anaemic, acute chest syndrome, severe disease complications and lifelong debilitating multi-system organ damage. Genetic testing and screening programs for SCD and the sickle cell trait (SCT) are valuable for early diagnosis and management...

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 patient...

Introduction The Package of Essential Noncommunicable Disease Interventions—Plus (PEN-Plus) is a strategy decentralising care for severe non-communicable diseases (NCDs) including type 1 diabetes, rheumatic heart disease and sickle cell disease, to increase access to care. In the PEN-Plus model, mid-level clinicians in intermediary facilities in lo...

Sickle cell disease (SCD) is associated with high rates of undernutrition and stunting. Undernutrition in combination with chronic haemolysis may lead to deficiencies in micronutrients necessary for erythropoiesis. Here we examined selected levels of ferritin, vitamins B2, B6, B9 and B12, and vitamin C that were measured in blood samples from 820 S...

Gene therapy (GT) provides a potentially curative treatment option for patients with sickle cell disease (SCD); however, the occurrence of myeloid malignancies in GT clinical trials has prompted concern, with several postulated mechanisms. Here, we used whole-genome sequencing to track hematopoietic stem cells (HSCs) from six patients with SCD at p...

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, co...

Purpose Sickle cell disease (SCD) is an inherited blood disorder characterized by unpredictable episodes of acute pain and numerous health complications. Individuals with SCD often face stigma from the public, including perceptions that they are lazy or weak tending to exaggerate their pain crisis, which can profoundly impact their quality of life...

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,...

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

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 wit...

Background: 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. Aim: Building on the power of a large and genetically diverse patient po...

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 4 th after Nigeria, the Democratic Republic of Congo and India. The absence of well-described SCD cohorts is a major barrier to heal...

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 conti...

Purpose To assess clinical and haematological outcomes of Hydroxyurea accessed via various access means and uncover the barriers to its utilization in children with Sickle cell anaemia (SCA), North-western Tanzania. Patients and Methods A retrospective study was conducted between October 2020 and April 2021 at Bugando Medical Centre (BMC) through...

Introduction: Sickle Cell Disease (SCD) causes significant morbidity and mortality particularly in sub-Saharan Africa (SSA) where it contributes to early childhood deaths. There is need to standardize treatment guidelines to help improve overall SCD patient health outcomes. We set out to review existing guidelines on SCD and to set minimum standard...

Background Globally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions. The purpose of this study was to assess the efficacy of maternal health education and matern...

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 biospecim...

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...

Brain injury is a common complication of sickle cell anaemia (SCA). White matter (WM) and cortical and subcortical grey matter (GM), structures may have reduced volume in patients with SCA. This study focuses on whether silent cerebral infarction (SCI), vasculopathy or anaemia affects WM and regional GM volumes in children living in Africa. Childre...

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...

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...

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 interventio...

Background: Globally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions. The purpose of this study was to assess the predictors of the effectiveness of health educa...

Objectives HemoTypeSCTM is one of the immunoassay methods currently used for the early diagnosis of Sickle Cell Disease (SCD) in newborns. Earlier diagnosis remains the key strategy for early preventive care needs and parents’ education about the child's future well-being throughout his life. Before considering these children as sick and aligning t...

The African Society of Human Genetics (AfSHG) was formed to provide a forum for human genetics and genomics scientists in Africa to interact, network, and collaborate. This is critical to facilitate development of solutions to the public health burden of many rare and common diseases across the continent. AfSHG fully supports the Black Lives Matter...

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...

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 Ta...

Skills development, the building of human capacity, is key to any sustainable capacity building effort, however, such undertakings require adaptable and tailored strategies. The Sickle Pan-African Research Consortium (SPARCo) is building capacity in sickle cell disease (SCD) management and research in sub-Saharan Africa, including a multi-national...

Tanzania is among the top five countries with a high burden of sickle cell disease (SCD) in the world. Even though the effects of SCD on quality of life have been documented in other countries including Nigeria and the United States of America, few are known from Tanzania. Therefore, this study focused on evaluating the effects of SCD on the qualit...

Hydroxyurea (HU) alone has the potential to prevent one out of every three deaths due to sickle cell disease (SCD) and almost all forms of disabilities caused by SCD. However, in Tanzania, only one out of every six registered SCD patients in the SPARCO-Tanzania Sickle Cell Cohort use HU. We conducted studies to understand factors influencing utiliz...

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 characterise the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thir...

In celebrating the bicentenary of Gregor Mendel’s birth, we reflect on progress and future directions in the application of genetics and genomics to delivering a cure for sickle cell disease, a classic Mendelian disorder that affects 5 million people globally, most of whom are in Africa. To mark the bicentenary of Gregor Mendel’s birth, the authors...

We report the case of a young female adult in her early 20s, who had COVID-19 infection for 8 weeks and COVID-19 vaccination 4 weeks prior to presentation with an extensive rash associated with erythema multiforme, resembling varicella zoster on initial presentation. After initial acyclovir therapy with no improvement, systemic corticosteroid treat...

Background: Sickle cell disease (SCD) is the single most important genetic cause of childhood mortality globally. Newborn screening (NBS) is the recommended intervention aimed at early identification of babies with SCD and their linkage to care. To ensure success of NBS, pregnant women need to have the required knowledge on SCD and therefore motiva...

Through studies in mice and in humans, Stuart Orkin showed that GATA-1 is a master transcriptional regulator of hematopoiesis. He has highlighted the role of BCL11A in the fetal-adult hemoglobin switch. The Gairdner Foundation Award recognizes Orkin’s contribution to the development of gene therapy of sickle cell disease.

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 C...

Sickle cell disease (SCD) is the most common clinically significant hemoglobinopathy, characterized by painful episodes, anemia, high risk of infection, and other acute and chronic complications. In Africa, where the disease is most prevalent, large longitudinal data on patients and their outcomes are lacking. This article describes the experiences...

Background: Sickle cell disease (SCD) is a global public health priority due to its high morbidity and mortality. In Tanzania, SCD accounts for 7% of under-five mortality. Cost-effective interventions such as early diagnosis and linkage to care have been shown to prevent 70% of deaths but require knowledge among healthcare workers and availability...

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and the evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania, to establish laboratory reference ranges among children and adults with SCD at steady state. Patients were group...

Background Developmental difficulties in many cognitive domains are common in children with sickle cell anaemia (SCA). Children with stroke are most affected but delayed or atypical cognitive function has been reported in children with SCA and silent infarcts (SCI), vasculopathy, and normal brain MRI. However, very few studies of cognition have bee...

Rare diseases (RD) pose serious challenges in terms of both diagnosis and treatment. Legislation was passed in the US (1983) and in EU (2000) aimed to reverse the previous neglect of RD, by providing incentives for development of “orphan drugs” (OD) for their management. Here we analyse the current situation in Africa with respect to (1) sickle cel...

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and evaluation of interventions. This study was conducted at Muhimbili National Hospital (MNH) in Dar es Salaam, to establish laboratory reference ranges in SCD at steady-state. Patients were grouped into five age groups with respects to t...

Purpose To determine oxygen saturation in the pulp of primary teeth in children with sickle cell disease (SCD) and sickle cell trait (SCT) for establishing the usefulness of pulse oximetry in screening and monitoring of SCD or therapy. Materials and Methods A cross-sectional study among 30–60 months children with sickle cell disease (SCD) and sick...

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. However genetic confirmation is still required for positive cases,...

Hematological and biochemical reference values in sickle cell disease (SCD) are crucial for patient management and evaluation of interventions. This study was conducted at Mu-himbili National Hospital (MNH) in Dar es Salaam, to establish laboratory reference ranges in SCD at steady-state. Patients were grouped into five age groups with respects to...

Introduction The paucity of data describing cardiovascular disease (CVD) in pregnancy in many parts of Africa including Tanzania has given rise to challenges in proper management by the healthcare providers. This study is set out to (1) determine the prevalence of a range of CVDs during pregnancy in women attending antenatal clinics in Tanzania and...

Factors contributing to low use of HU among SCD patients exist in high-income countries. The latter leaves a drift of literature on factors for low utilization of HU in developing countries. This study aimed to explore the factors influencing the use of HU in the management of SCD in Tanzania. A qualitative study was employed to interview purposive...