Browsing by Department "Medicine"

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    Antiplasmodial and cytotoxic activity of isolated sesquiterpene lactones from the acetone leaf extract of vernonia colorata
    (2009) Chukwujekwu, J. C.; Lategan, C. A.; Smith, P. J.; Van Heerden, F. R.; Van Staden, J.
    Vernonia colorata is used throughout Africa to treat various ailments. Its antiplasmodial activity has been widely reported. Using bioassay-guided fractionation, we isolated two antiplasmodial compounds — vernolide (IC50 = 1.87 μg/ml) and vernodalin (IC50 = 0.52 μg/ml) with selective indices of 1.02 and 2.79 for vernolide and vernodalin respectively. These compounds are non-specific towards parasites.
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    Developing, implementing, and monitoring tailored strategies for integrated knowledge translation in five sub-Saharan African countries
    (BioMed Central, 2023-09-04) Sell, Kerstin; Jessani, Nasreen S.; Mesfin, Firaol; Rehfuess, Eva A.; Rohwer, Anke; Delobelle, Peter; Balugaba, Bonny E.; Schmidt, Bey-Marrié; Kedir, Kiya; Mpando, Talitha; Niyibizi, Jean B.; Osuret, Jimmy; Bayiga-Zziwa, Esther; Kredo, Tamara; Mbeye, Nyanyiwe M.; Pfadenhauer, Lisa M.
    Background Integrated knowledge translation (IKT) through strategic, continuous engagement with decision-makers represents an approach to bridge research, policy and practice. The Collaboration for Evidence-based Healthcare and Public Health in Africa (CEBHA +), comprising research institutions in Ethiopia, Malawi, Rwanda, South Africa, Uganda and Germany, developed and implemented tailored IKT strategies as part of its multifaceted research on prevention and care of non-communicable diseases and road traffic injuries. The objective of this article is to describe the CEBHA + IKT approach and report on the development, implementation and monitoring of site-specific IKT strategies. Methods We draw on findings derived from the mixed method IKT evaluation (conducted in 2020–2021), and undertook document analyses and a reflective survey among IKT implementers. Quantitative data were analysed descriptively and qualitative data were analysed using content analysis. The authors used the TIDieR checklist to report results in a structured manner. Results Preliminary IKT evaluation data (33 interviews with researchers and stakeholders from policy and practice, and 31 survey responses), 49 documents, and eight responses to the reflective survey informed this article. In each of the five African CEBHA + countries, a site-specific IKT strategy guided IKT implementation, tailored to the respective national context, engagement aims, research tasks, and individuals involved. IKT implementers undertook a variety of IKT activities at varying levels of engagement that targeted a broad range of decision-makers and other stakeholders, particularly during project planning, data interpretation, and output dissemination. Throughout the project, the IKT teams continued to tailor IKT strategies informally and modified the IKT approach by responding to ad hoc engagements and involving non-governmental organisations, universities, and communities. Challenges to using systematic, formalised IKT strategies arose in particular with respect to the demand on time and resources, leading to the modification of monitoring processes. Conclusion Tailoring of the CEBHA + IKT approach led to the inclusion of some atypical IKT partners and to greater responsiveness to unexpected opportunities for decision-maker engagement. Benefits of using systematic IKT strategies included clarity on engagement aims, balancing of existing and new strategic partnerships, and an enhanced understanding of research context, including site-specific structures for evidence-informed decision-making.
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    Helicobacter pylori Infection: Antibiotic Resistance and Solutions for Effective Management in Africa
    (Multidisciplinary Digital Publishing Institute, 2023-05-26) Setshedi, Mashiko; Smith, Stella I.
    Helicobacter pylori. pylori infection is ubiquitous worldwide, with prevalence rates of greater than 70% in Africa. Symptomatic patients present with foregut gastrointestinal symptoms which can be readily diagnosed with standardized non-invasive or invasive tests. The biggest challenge, however, is in the management of this condition with rising antimicrobial resistance rates to most of the antibiotics recommended for therapy. This is a problem worldwide, but more specifically in Africa, where the socio-economic and political climate is such that eradication of this organism seems impossible. Furthermore, the recommended antimicrobial susceptibility testing for drug resistance is not widely available in Africa due to the lack of infrastructural as well as human resources. With the widespread unregulated use of antibiotics in some parts of Africa, the figures of antimicrobial resistance are likely to soar. In the face of these significant challenges, this ‘perspectives’ article aims to address the issue of antimicrobial resistance in Africa, by providing achievable and targeted goals to curb the spread of infection and rising antimicrobial resistance.
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    Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function
    (BioMed Central, 2023-08-29) Kintu, Christopher; Soremekun, Opeyemi; Machipisa, Tafadzwa; Mayanja, Richard; Kalyesubula, Robert; Bagaya, Bernard S.; Jjingo, Daudi; Chikowore, Tinashe; Fatumo, Segun
    Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia. We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations. We identified one novel variant, rs77408001 which is an intronic variant mapped to the ELN gene. We validated three previously reported loci at GATM-SPATA5L1, SLC15A5 and AGPAT3. Fine-mapping analysis identified variants rs77121243 and rs201602445 as having a 99.9% posterior probability of being causal. Our results warrant designing bigger studies within individuals of African ancestry to gain new insights into the pathogenesis of Chronic Kidney Disease (CKD), and identify genomic variants unique to this ancestry that may influence renal function and disease.
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    Symptoms of posttraumatic stress partially mediate the relationship between gender-based violence and alcohol misuse among South African women
    (BioMed Central, 2023-06-22) Nguyen, Kim A.; Myers, Bronwyn; Abrahams, Naeemah; Jewkes, Rachel; Mhlongo, Shibe; Seedat, Soraya; Lombard, Carl; Garcia-Moreno, Claudia; Chirwa, Esnat; Kengne, Andre P.; Peer, Nasheeta
    Abstract Background The association of traumatic experiences with problematic alcohol use has been described, but data on possible mediation effects of mental distress are sparse. We examined whether mental ill-health mediated the association between trauma exposure across the lifespan and alcohol use. Method We analysed cross-sectional data from a sample of rape-exposed and non-rape-exposed women, living in KwaZulu-Natal, with self-reported data on alcohol misuse (AUDIT-C cut-off ≥ 3) and exposure to childhood maltreatment (CM), intimate partner violence (IPV), non-partner sexual violence (NPSV), other traumatic events, and mental ill-health. Logistic regression and multiple mediation models were used to test the mediation effects of symptoms of depression and PTSS on the association between abuse/trauma and alcohol misuse. Results Of 1615 women, 31% (n = 498) reported alcohol misuse. Exposure to any CM (adjusted odds ratio (aOR): 1.59, 95% confidence interval (CI): 1.27–1.99), as well as to sexual, physical and emotional CM, were independently associated with alcohol misuse. Lifetime exposure to any IPV (aOR:2.01, 95%CI:1.59–2.54), as well as to physical, emotional and economic IPV, NPSV (aOR: 1.75, 95%CI: 1.32–2.33), and other trauma (aOR:2.08, 95%CI:1.62–2.66), was associated with alcohol misuse. Exposure to an increasing number of abuse types, and other traumatic events, was independently associated with alcohol misuse. PTSS partially mediated the associations of CM, IPV, NPSV and other trauma exposures with alcohol misuse (ps ≤ 0.04 for indirect effects), but depression symptoms did not. Conclusions These findings highlight the need for trauma-informed interventions to address alcohol misuse that are tailored to the needs of women who have experienced violence.
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    Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa
    (BioMed Central, 2023-09-14) Singh, Y.; Castillo-Mancilla, J.; Madimabe, R.; Jennings, L.; Ferraris, C. M.; Robbins, R. N.; Anderson, P. L.; Remien, R. H.; Orrell, C.
    Background Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US. We explored the relationship of TFV-DP concentrations with antiretroviral drug resistance at the time of treatment failure in SA. Methods Adult PWH from health clinics in Cape Town, South Africa on efavirenz-based first-line ART containing tenofovir disoproxil fumarate (TDF) with an undetectable (< 50 copies/mL) HIV-1 viral load (VL) were prospectively enrolled in an observational cohort for 12 months. Monthly study visits included blood collection for HIV-1 VL and DBS for TFV-DP. The first confirmed viral breakthrough (VB) > 400 copies/mL triggered HIV-1 genotyping at the subsequent visit. An electronic adherence (EA) device monitored ART adherence in real-time, estimated as a percent for the 30-days prior to VB. Wilcoxon rank sum test was used to compare median [IQR] TFV-DP by genotype outcome. Results Of 250 individuals, (n = 195, 78% women), 21 experienced VB, with a median of 5 [4;7] months on study, and a median EA of 33.3 [13.3;53.3]%. Demographic characteristics between those with and without VB were similar. Median VL at VB was 4.0 [3.2;4.5] log copies/mL. TFV-DP concentrations trended down towards the VB visit. Median TFV-DP concentrations were significantly higher in those HIV-1 genotype did not amplify due to being virally suppressed at the subsequent visit (n = 10; 380 [227–661] fmol/punch, p = 0.035; EA 45 [24.9; 59.2]%); than in those who were successfully genotyped with evidence of drug resistance (n = 5, 241 [150–247] fmol/punch, EA 20 [6.7;36.7]%) and in individuals who did not have resistance (n = 3, 39.9 [16.6; 93.9] fmol/punch; EA 33.3 [16–38]%). Three genotype collections were not done. Only non-nucleoside reverse transcriptase inhibitor-associated mutations were identified on resistance testing. (K103N, E138K, Y118H). Conclusion TFV-DP in DBS showed a step-wise inverse relationship with VB and drug resistance, with evidence of low cumulative ART adherence in PWH who developed antiretroviral resistance. Monitoring TFV-DP concentrations could be a valuable tool for predicting future VB and future resistance.
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    Towards Evidence-Based Implementation of Pharmacogenomics in Southern Africa: Comorbidities and Polypharmacy Profiles across Diseases
    (Multidisciplinary Digital Publishing Institute, 2023-07-26) Soko, Nyarai Desiree; Muyambo, Sarudzai; Dandara, Michelle T. L.; Kampira, Elizabeth; Blom, Dirk; Jones, Erika S. W.; Rayner, Brian; Shamley, Delva; Sinxadi, Phumla; Dandara, Collet
    Pharmacogenomics may improve patient care by guiding drug selection and dosing; however, this requires prior knowledge of the pharmacogenomics of drugs commonly used in a specific setting. The aim of this study was to identify a preliminary set of pharmacogenetic variants important in Southern Africa. We describe comorbidities in 3997 patients from Malawi, South Africa, and Zimbabwe. These patient cohorts were included in pharmacogenomic studies of anticoagulation, dyslipidemia, hypertension, HIV and breast cancer. The 20 topmost prescribed drugs in this population were identified. Using the literature, a list of pharmacogenes vital in the response to the top 20 drugs was constructed leading to drug–gene pairs potentially informative in translation of pharmacogenomics. The most reported morbidity was hypertension (58.4%), making antihypertensives the most prescribed drugs, particularly amlodipine. Dyslipidemia occurred in 31.5% of the participants, and statins were the most frequently prescribed as cholesterol-lowering drugs. HIV was reported in 20.3% of the study participants, with lamivudine/stavudine/efavirenz being the most prescribed antiretroviral combination. Based on these data, pharmacogenes of immediate interest in Southern African populations include ABCB1, CYP2B6, CYP2C9, CYP2C19, CYP2D6 CYP3A4, CYP3A5, SLC22A1, SLCO1B1 and UGT1A1. Variants in these genes are a good starting point for pharmacogenomic translation programs in Southern Africa.