Siana Nkya

• PhD
• Senior Lecturer at Muhimbili University of Health and Allied Sciences

Background Prevalence of sickle cell disease (SCD) across African countries ranges between 1–3% and contributes up to 7–16% of under-five mortality. In order to bridge the gap in management and cognate research, the SickleInAfrica consortium was established in 2017 to facilitate collaboration among African nations in order to establish regionally r...

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...

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...

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...

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 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...

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...

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...

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...

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...

Rare diseases (RDs) affect a small proportion of the population compared to infectious and non-communicable diseases. However, there are more than 10,000 known RDs affecting about 300 million people worldwide, with the majority being hereditary and affecting children. RDs receive limited attention, making diagnosis, management, and treatment challe...

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...

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...

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...

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...

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 Tan...

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...

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...

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...

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...

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...

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...

Hemoglobinopathies, including sickle cell disease (SCD) and thalassemia syndromes, represent the commonest monogenic diseases in the world. Although their pathogenicity is well established, the diverse clinical manifestations and the varying degree of severity are less understood and are thought to be governed, in part, by genetic modifiers. Despit...

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. This study aime...

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. 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 o...

Due to the insufficient human and infrastructure capacity to use novel genomics and bioinformatics technologies, Sub-Saharan Africa countries have not entirely ripped the benefits of these technologies in health and other sectors. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related res...

Due to the insufficient human and infrastructure capacity to use novel genomics and bioinformatics technologies, Sub-Saharan Africa countries have not entirely ripped the benefits of these technologies in health and other sectors. The main objective of this study was to map out the interest and capacity for conducting bioinformatics and related res...

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 Tan...

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 b...

Introducing newborn screening (NBS) services for sickle cell disease (SCD) in Africa has been proven to be one of the most cost-effective approach to reducing morbidity and mortality associated with this condition. In view of this evidence, efforts have been made by countries in Africa where SCD prevalence is high to pilot NBS programmes and to str...

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. However, African populations are grossly underrepresented in va...

Abstract 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 a...

ABSTRACT: Prevalence of Sickle Cell Disease is high in Africa, with significant public health effects to the affected countries. Many of the countries with the highest prevalence of the disease also have poor health care system, high burden of infectious diseases with many other competing healthcare priorities. Though, considerable efforts have bee...

Patients with sickle cell disease (SCD) with high fetal haemoglobin (HbF) tend to have a lower incidence of complications and longer survival due to inhibition of deoxyhaemoglobin S (HbS) polymerisation by HbF. HbF‐containing cells, namely F cells, are strongly influenced by genetic factors. We measured the percentage of F cells (Fcells%) in 222 pa...

Background: Low literacy of study participants in Sub - Saharan Africa has been associated with poor comprehension during the consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore...

Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common genetic variants which differ across populations and...

Background: Low literacy of study participants in Sub Saharan Africa has been associated with poor comprehension during consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore possibi...

Background: Monitoring of patient’s clinical attendance is one of the crucial means that is used to improve adherence to care and treatment among the Sickle Cell Disease (SCD) patients. Adherence to care has been shown to improve health outcomes in SCD patients. However, these benefits cannot be achieved when patients are lost to follow-up to care....

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 t...

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 t...

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 t...

Background The pathophysiology of sickle cell disease (SCD) is complex and involves nitric oxide depletion, increased inflammation/adhesion molecules and vaso-occlusion in addition to the chronic hemolytic anemia. This pathophysiology results in systemic clinical complications including recurrent episodes of severe pain, stroke, acute chest syndrom...

Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do...

Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do...

Background: Low literacy of study participants in Sub Saharan Africa has been associated with poor comprehension during consenting process in research participation. The concerns in comprehension are far greater when consenting to participate in genomic studies due to the complexity of the science involved. While efforts are made to explore possibi...

Affiliation 1Muhimbili University of Health and Allied Sciences, Dar es salaam, Tanzania. 2Department of Oncology, University of Oxford, Oxford UK. 3Dar es salaam University College of Education, Dar es salaam, Tanzania. ABSTRACT. Background; SCD constitutes to be a major public health problem in Tanzania. NBS for SCD identify infants with SCD at b...

Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do...

Background: Sickle cell disease (SCD) is a recognized cause of childhood mortality. Tanzania has the fifth highest incidence of SCD (with an estimated 11 000 SCD annual births) worldwide. Although newborn screening (NBS) for SCD and comprehensive healthcare have been shown to reduce under-5 mortality by up to 94% in high-income countries such as t...

Background Africa has the highest burden of Sickle cell disease (SCD) but there are few large, systematic studies providing reliable descriptions of the disease spectrum. Tanzania, with 11,000 SCD births annually, established the Muhimbili Sickle Cell program aiming to improve understanding of SCD in Africa. We report the profile of SCD seen in the...

A chronic inflammatory state to a large extent explains sickle cell disease (SCD) pathophysiology. Nonetheless, the principal dysregulated factors affecting this major pathway and their mechanisms of action still have to be fully identified and elucidated. Integrating gene expression and genome-wide association study (GWAS) data analysis represents...

rSNPs located in the promoter region of NFE2 and altering MYC-binding sites’ affinity. (XLSX)

Preferred reporting items for systematic reviews and meta-analyses (PRISMA). Guidelines Checklist. (PDF)

Complete list of differentially-expressed genes obtained from the meta-analysis. (XLSX)

The rSNPs located in the promoter region and altering TF-binding sites’ affinity identified by the atSNP R package. (XLSX)

Evaluation of the functional impact of the coding variants in the affected candidate gene proteins using Sift software. (XLSX)

Gene set enrichment analyses of biological processes and metabolic pathways using multiple tools. (XLSX)

Key Points The 3 established HbF genetic loci can be summarized into 1 quantitative variable, g(HbF), in SCD and influence markers of SCD severity. g(HbF) provides a quantitative marker for the genetic component of HbF% variability, potentially useful in genetic and clinical studies in SCD.

Platelet activation and platelet-derived cytokines contribute to the vascular inflammation and increased thrombotic activity known to occur in patients with sickle cell anemia (SCA). CD40 ligand (CD40L), a platelet-associated pro-inflammatory molecule that promotes endothelial cell activation, is elevated in the circulation of SCA patients. We soug...

Fetal hemoglobin (HbF) is normally synthesized during intrauterine life and it starts to decline before birth being replaced by adult hemoglobin (HbA). However some individuals continue to synthesize HbF to adulthood and are relatively protected from severe sickle cell disease. The mechanism of HbF protection in SCD has not been entirely establishe...

Common genetic variants residing near upstream regulatory elements for MYB, the gene encoding transcription factor cMYB, promote the persistence of fetal hemoglobin (HbF) into adulthood. While they have no consequences in healthy individuals, high HbF levels have major clinical benefits in patients with sickle cell disease (SCD) or β thalassemia. H...

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants and microbiota occurs in Africa, yet genomic research outp...

Background: Haemoglobin variants, Sickle (HbS) and foetal (HbF) have been associated with malaria protection. This study explores epistatic interactions between HbS and HbF on malaria infection. Methods: The study was conducted between March 2004 and December 2013 within the sickle cell disease (SCD) programme at Muhimbili National Hospital, Tan...

Fetal hemoglobin (HbF) is a recognized modulator of sickle cell disease (SCD) severity. HbF levels are strongly influenced by genetic variants at three major genetic loci, Xmn1-HBG2, HMIP-2 and BCL11A, but the effect of these loci on the hematological phenotype in SCD, has so far not been investigated. In a cohort of individuals with SCD in Tanzani...

Background Fetal hemoglobin (HbF) is an important modulator of sickle cell disease (SCD). HbF has previously been shown to be affected by variants at three loci on chromosomes 2, 6 and 11, but it is likely that additional loci remain to be discovered. Methods and Findings We conducted a genome-wide association study (GWAS) in 1,213 SCA (HbSS/HbSβ0...

Figure S1 Detailed haplotype composition of the core of the “A/a” sublocus in individuals of European and African descent. Figure S2 Linkage disequilibrium plot for 21 variants across HMIP-2 in 2183 healthy Europeans. Figure S3 Linkage disequilibrium plot for 20 variants across HMIP-2 in 198 African British patients with sickle cell anemia. Table S...

HMIP-2 is a human quantitative trait locus affecting peripheral numbers, size and hemoglobin composition of red blood cells, with a marked effect on the persistence of the fetal form of hemoglobin, HbF, in adults. The locus consists of multiple common variants in an enhancer region for MYB (chr 6q23.3), which encodes the hematopoietic transcription...

Adhesion data for clinical P. falciparum isolates under static and flow adhesion assays. Numbers represent number of adherent parasites/mm2. (-) no data available. (0.14 MB DOC)

Binding signatures for clinical isolates under static conditions. Binding signatures of clinical isolates presented as % binding and coloured codes. K29, % adhesion to ICAM-1Kilifi, S22, % adhesion to ICAM-1S22/A and column 3, binding signature. Binding is calculated relative to ICAM-1Reference as reference standard. The numbers of isolates in SMA...

Genotype frequencies for ICAM-1, CD36, α-thalassaemia and HbS. Genotype frequencies for patients studied. HbS, haemoglobin S variant (sickle cell genotype). CD36, point mutation from T to G in the CD36 gene at nucleotide position 188 in exon 10. Numbers represent the number of children that fall into each genotype (wild-type, heterozygous and homoz...

Our understanding of the basis of severe disease in malaria is incomplete. It is clear that pathology is in part related to the pro-inflammatory nature of the host response but a number of other factors are also thought to be involved, including the interaction between infected erythrocytes and endothelium. This is a complex system involving severa...