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Collen Masimirembwa

Collen Masimirembwa
University of the Witswatersrand · Sydney Brenner Institute for Molecualr Biosciences

PhD,DPhil

About

144
Publications
17,569
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4,205
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Publications

Publications (144)
Preprint
AIMS Doxorubicin-induced cardiotoxicity (DIC) is a significant cause of mortality in cancer care. This study was conducted to establish the frequency of DIC in Zimbabwean breast cancer patients on doxorubicin and to test the DIC predictive power of genetic biomarkers. METHODS A cohort of 50 Zimbabwean breast cancer patients treated with doxorubicin...
Article
Objective: Pharmacogenomics (PGx) is a clinically significant factor in the safe and efficacious use of medicines. While PGx knowledge is abundant for other populations, there are scarce PGx data on African populations and is little knowledge on drug-gene interactions for medicines used to treat diseases common in Africa. The aim of this study was...
Article
Full-text available
Pharmacogenomics is universally relevant for worldwide modern therapeutics and yet needs further development in resource-limited countries. While there is an abundance of genetic association studies in controlled medical settings, there is a paucity of studies with a naturalistic design in real-life clinical practice in patients with comorbidities...
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Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identifi...
Article
Full-text available
Adverse drug reactions (ADRs) are one of the major causes of morbidity and mortality worldwide. It is well-known that individual genetic make-up is one of the causative factors of ADRs. Approximately 14 million single nucleotide polymorphisms (SNPs) are distributed throughout the entire human genome and every patient has a distinct genetic make-up...
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In this study, we aimed to evaluate the utility of endogenous 1β-hydroxy-deoxycholic acid/total deoxycholic acid ratio (1β-OH-DCA/ToDCA) in spot urine as a surrogate marker of cytochrome P450 3A (CYP3A) activity in the assessment inhibition-based drug–drug interactions in healthy volunteers. This was accomplished through an open-label, three-treatm...
Article
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We conducted a clinical study to determine the effect of efavirenz and ritonavir on the pharmacokinetics of R- and S-PZQ in healthy male participants. This was toward evaluating the risk of drug-drug interactions, which may occur after PZQ administration to HIV patients on efavirenz or ritonavir containing regimens. A non-randomized, open-label, si...
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Introduction: Sub-Saharan Africa and other low- and middle-income countries (LMICs) have the highest rates of antimicrobial resistance (AMR) driven by high rates of antimicrobial utilization. This is a concern as AMR appreciably increases morbidity, mortality and costs. Pharmacogenetics (PGx) and precision medicine are emerging approaches to combat...
Article
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Racemic praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis. R‐Praziquantel (R‐PZQ) has been shown as the therapeutic form, whereas S‐PZQ is less efficacious and responsible for the bitter taste of the tablet. This study aimed at investigating the metabolism of R‐ and S‐PZQ as this could have implications on efficacy and s...
Preprint
Full-text available
Chloroquine/hydroxychloroquine have been proposed as potential treatments for COVID-19. These drugs have warning labels for use in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Analysis of whole-genome sequence data of 458 individuals from sub-Saharan Africa showed significant G6PD variation across the continent. We identifi...
Article
Full-text available
Introduction The contribution of high tuberculosis (TB) transmission pockets in propagating area-wide transmission has not been adequately described in Zimbabwe. This study aimed to describe the presence of hotspot transmission of TB cases in Harare city from 2011 to 2012 using geospatial techniques. Methods Anonymised TB patient data stored in an...
Article
Full-text available
Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have eno...
Article
Full-text available
Aim The study sought to determine the effect of ketoconazole (KTZ) on the pharmacokinetics of praziquantel (PZQ) and on the formation of its major hydroxylated metabolites, cis- and trans-4-OH-PZQ, and X-OH-PZQ in healthy subjects. Methods Two treatments were evaluated by single-dose PK studies; the reference treatment was a 20 mg/kg dose of prazi...
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The African Pharmacogenomics Consortium (APC) was formally launched on the 6th September 2018. This white paper outlines its vision, and objectives towards addressing challenges of conducting and applying pharmacogenomics in Africa and identifies opportunities for advancement of individualized drugs use on the continent. Africa, especially south of...
Article
Full-text available
Studies in Caucasian and Asian populations consistently associated interindividual and interethnic variability in rosuvastatin pharmacokinetics to the polymorphisms SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A (rs2231142, p. Gln141Lys). To investigate the pharmacogenetics of rosuvastatin in African populations, we first screened 785...
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Objective: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing...
Article
Introduction: Treatment of HIV has reduced HIV/AIDS-related mortality. Sustaining >90% virologic suppression in sub-Saharan Africa requires decentralized care and prevention services to rural communities. In Zimbabwe, the number of people receiving ART has increased rapidly. However, access to treatment monitoring tools such as viral load and drug...
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Full-text available
Background Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV tes...
Data
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. (DOCX)
Data
BRTI-ZENITH Anonymous HIV Test Form ZP03. (PDF)
Data
Individual questionnaire: Prevalence survey ZP02. (PDF)
Data
Sampling strategy for census enumeration areas (CEAs). (DOCX)
Data
Factors associated with HIV among all participants (N = 5,486). (DOCX)
Data
Unweighted HIV prevalence and proportion with undiagnosed HIV. (DOCX)
Data
Biomedical Research and Training Institute–Zimbabwe Study for Enhancing Testing and Improving Treatment of HIV in Children (BRTI-ZENITH) Household Baseline Form ZP01. (PDF)
Data
BRTI-ZENITH Diagnostic HIV Test ZP04. (PDF)
Data
ZENITH Protocol v4.0, 1 June 2015. (DOC)
Data
Statistical analysis plan v1.2, 7 April 2016. (DOCX)
Article
Introduction: Although Roche COBAS Ampliprep/COBAS Taqman (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from Dried blood spots (DBS), viral load monitoring with this system is not practical due to non-specific extraction of both cell free and cell associated viral nucleic acids. A simplified DBS extractio...
Data
Supplemental Tables Tab 1: Frequency data for principal components analysis Tab 2: Frequencies of CYP450 allelic variants in different African populations Tab 3: Clinically relevant substrates of CYP450 enzymes Supplemental References.
Article
Full-text available
Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolizing enzymes may contribute to the high numbers of adverse drug reactions reported in Africa. We reviewed publications (1995–April 2016) reporting frequencies of known cytochrome P450 (CYP) variants in African populations...
Article
Full-text available
Background: As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence and treatment failure on high viral load. Self-reported data are susceptible to response bias and although biomarker data on drug presence and concentration can...
Article
Full-text available
The introduction of antiretroviral therapy (ART) led to huge reductions in human immunodeficiency virus (HIV)-related deaths, turning HIV-infection into a chronic condition. Attention is now turning to quality of life for patients on lifelong ART treatment, reflecting on the safety of antiretroviral drugs. In sub-Saharan Africa, efavirenz (EFV) for...
Article
Full-text available
The incidence of cardiovascular diseases (CVDs) in African populations residing in the African continent is on the rise fueled by both a steady increase in CVD risk factors and comorbidities such as human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), tuberculosis, and parasitic diseases such as bilharzia. Statins are recomm...
Article
What is known and objective: Imatinib mesylate is the first-line drug for the treatment of Philadelphia/bcr-abl positive chronic myeloid leukaemia (CML). It is known to be metabolized mostly by CYP3A4 and CYP3A5 isoforms while its efflux is mediated by the transporters ABCB1 and ABCG2. Genetic polymorphism of some of these enzymes and transporters...
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Full-text available
The growing need for biobanks in health research presents an opportunity for building capacity in developing countries. In Zimbabwe, there is limited knowledge and awareness about biobanking. As such we report the proceedings of a biobanking course, which included research scientists, healthcare professionals, and regulatory authorities as a start...
Article
Aims: Genetic variation in the transporters BCRP and OATP1B1 affects systemic exposure of rosuvastatin and hence contributes to statin induced myopathy. This study investigated the role of these transporters in the pharmacokinetics of rosuvastatin among individuals of African ancestry. Methods: A single site, open label, single oral dose pharmac...
Article
Over the years, under the North-South (N-S) Scientific and Technology transfer drive, many African scientists went for postgraduate training in developed countries such as Sweden, UK, USA, and France. This N-S initiative however did not achieve the technology transfer aspect resulting in the trained African scientists failing to continue with their...
Data
This data is an accompaniment to the journal article 'Might ART Adherence Estimates Be Improved by Combining Biomarker and Self-Report Data?' (Rhead et al. 2016) Abstract: As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence an...
Data
This data is an accompaniment to the journal article 'Might ART Adherence Estimates Be Improved by Combining Biomarker and Self-Report Data?' (Rhead et al. 2016) Abstract: As we endeavour to examine rates of viral suppression in PLHIV, reliable data on ART adherence are needed to distinguish between the respective contributions of poor adherence an...
Article
Full-text available
Objective: To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country. Methods: A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years) and adolescents (10-19 years) attending a pu...
Data
Immunologic and clinical outcomes on ART, overall and by age at cross-sectional evaluation. (DOC)
Data
Demographic and baseline clinical characteristics of children and adolescents receiving HIV care in a public HIV program in Zimbabwe, by age at ART initiation. (DOC)
Data
Demographic and baseline clinical characteristics of children and adolescents with virologic failure, by resistance testing status. (DOC)
Article
Full-text available
1. Chemotherapy remains the effective way of controlling malaria infections. Many of the treatments have been rendered ineffective as a result of drug resistance by plasmodia species as well as toxicity. Molecular hybridisation is one of the techniques used in the synthesis of new-generation antimalarial techniques. In this paper, we explore some p...
Article
A novel class of benzoheterocyclic analogues of amodiaquine designed to avoid toxic reactive metabolite formation was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant) and NF54 (sensitive) strains of the malaria parasite Plasmodium falciparum. Structure-activity relationship studies led to the identification of...
Article
Full-text available
Efavirenz (EFV) therapeutic response and toxicity are associated with high inter-individual variability attributed to variation in its pharmacokinetics. Plasma concentrations below 1 μg/ml may result in virologic failure and above 4 μg/ml, may result in central nervous system adverse effects. This study used population pharmacokinetics modeling to...
Article
The safety and efficacy of herbal medicines remain major issues of concern especially in the developing world where the use is high. The World Health Organisation estimates up to 80% of the population in Africa relies on herbal medicines for treatment of many diseases. Minimum safety evaluations need to be done for both the herbal and conventional...
Chapter
In this chapter we discuss the implications of African populations’ great diversity for pharmacogenomics and stratified medicine—including those in Africa and those in the African diaspora. Overwhelming evidence indicates that Homo sapiens developed in Central-Eastern Africa about 200,000 years ago. Various migrations occurred from Africa to Europe...
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Abstract Interest in genomics research in African populations is experiencing exponential growth. This enthusiasm stems in part from the recognition that the genomic diversity of African populations is a window of opportunity for innovations in postgenomics medicine, ecology, and evolutionary biology. The recently launched H3Africa initiative, for...
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NIPRD-AH1 is being developed from freeze-dried aqueous extract of Andrographis paniculata at the National Institute for Pharmaceutical Research and Development (NIPRD), Abuja Nigeria as immune-stimulant for HIV infected patients. The aim of this study was to evaluate the effect of NIPRD-AH1 on human cytochrome P450 3A4 (CYP3A4) drug metabolising en...
Article
Introduction: There are more than 500 000 HIV-infected people on antiretroviral treatment (ART) in Zimbabwe with very limited laboratory monitoring. To ensure effective treatment and prevent transmission of drug resistance, affordable treatment monitoring is needed to guide individual treatment. Methods: 125 whole blood samples from patients on...
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Full-text available
Background and objective: Drug resistance by Plasmodium falciparum remains a challenge in malaria chemotherapy. This paper will focus on physicochemical and drug metabolism characterization of a series of 4-aminoquinoline-3-hydroxypyridin-4-one hybrid shown to have antimalarial activity against chloroquine-resistant P. falciparum. The aim is to id...
Poster
Full-text available
Labdane diterpenes containing a mono-substituted furan ring have been isolated from Southern African medicinal plants of the genus Leonotis. Extracts from plants of this genus are used as traditional remedies for headaches, epilepsy, hypertension and chest infections. Furan rings in xenobiotics are regarded as structural alerts amenable to undesira...
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Full-text available
Imidazolium trans-[tetrachloridodimethylsulfoxideimidazoleruthenate(iii)], NAMI-A, is a promising antimetastatic prodrug with high specificity for metastatic cancer cells. Limited activity of NAMI-A against primary tumor suggests that its use in combination with other anticancer drug(s) might present a more desirable therapeutic outcome. The mechan...
Poster
Gedunin is a tetranortriterpenoid limonoid natural product isolated from the Neem tree (Azadirachta indica) and other plant species of the Meliaceae family. This compound has been reported to exhibit antimalarial, insecticidal and anticancer activity and may thus represent a potentially new chemotype for drug development. However, gedunin possesses...
Article
Introduction: Africa harbors a disproportionate burden of disease when taking into account the triple challenge caused by HIV/AIDS, tuberculosis (TB) and malaria, against a backdrop of an increasing burden of noncommunicable diseases. More than 80% of therapeutic drugs used in the management of these diseases/conditions are metabolized by CYP enzy...
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Full-text available
Objectives: The objectives were to determine the pharmacokinetics (PK) of artemisone and artemisone formulated in the Pheroid® drug delivery system in primates and to establish whether the formulation affects the in vitro metabolism of artemisone in human and monkey liver and intestinal microsomes. Methods: For the PK study, a single oral dose of a...
Article
The purpose of this study was to evaluate the potential risk of common herbal medicines used by HIV-infected patients in Africa for herb-drug interactions (HDI). High throughput screening assays consisting of recombinant Cytochrome P450 enzymes (CYPs) and fluorescent probes, and parallel artificial membrane permeability assays (PAMPA) were used. Th...
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Full-text available
NIPRISAN(®) is a phytomedicine developed from herbal products used in folkloric practice for the management of sickle cell disease (SCD). The effect of NIPRISAN(®) was tested on human cytochrome P4503A4 drug metabolising enzyme to generate clinically significant data for its safe and efficacious use. Inhibitory activity on CYP3A4 was measured with...
Article
A study was conducted in an HIV/AIDS Zimbabwean cohort to assess possible associations of pharmacogenetic variants with common adverse drug reactions (ADRs) during anti-retroviral treatment (ART) and/or tuberculosis (TB) treatment. Genotype and allele frequencies for CYP2B6 G516T, CYP2B6 T983C, CYP2A6*17, ABCB1 rs10276036 C>T, NAT2*5 and NAT2*14 we...
Article
We characterised over 20 antiparasitic drugs with respect to the enzymes responsible for their metabolism. We showed that CYP2C8 is responsible for the metabolism of amodiaquine (ADQ) to desethylamodiaquine and identified a novel reactive metabolite catalysed by extrahepatic CYP1A1 and CYPIB1 which is giving us insights into possible ways of synthe...
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Full-text available
The modern human appeared in Africa around 200,000 years ago with subsequent later migrations to populate Europe, Asia, and North America.1 As humans adapted to various diets, diseases, climates, and so on, inherited traits emerged that gave rise to distinct population groups with physical and physiological differences, including the response to xe...
Article
Introduction: The use of many anti-retroviral drugs has been associated with a myriad of adverse drug reactions (ADRs) which could limit successful treatment outcome with respect to patient compliance and quality of life. An additional consideration is the high incidence of HIV infection with tuberculosis (TB) in Southern Africa, including Zimbabwe...
Article
Full-text available
Artemisinin-based combination therapy (ACT) is the recommended treatment of uncomplicated P.falciparum malaria by the World Health Organisation (WHO). Some artemisinin compounds and anti-retroviral drugs have been shown to be metabolized by CYP2B6. In the African clinical settings, the likelihood of co-administration of ACTs and antiretroviral drug...
Article
Full-text available
Objective: To evaluate the effect of NIPRD-AM1 on CYP3A4 in order to generate clinically significant data for its safe and efficacious use. Materials and Methods: NIPRD-AM1 is a phytomedicine developed from aqueous root extracts of Nauclea latifolia Smith (Rubiaceae) for the treatment of uncomplicated malaria. The effect of NIPRD-AM1 on CYP3A4 was...