Establishment of screening procedures for genetic disorders and risk factors in the South African Caucasian population

Please read the abstract in the section 00front of this documentDissertation (MSc (Chemical Pathology))--University of Pretoria, 2005.Chemical Pathologyunrestricte

In Vitro Medicinal Properties of Novel Compounds from Croton steenkampianus

The effect of infectious diseases on the population in the developing countries is of utmost concern. Malaria, tuberculosis (TB) and human immunodeficiency virus (HIV) are the three major infectious disease threats. They account for approximately half of the mortality caused by infectious diseases, which is almost half of the mortality in the developing countries. With no vaccine likely in the foreseeable future, drugs remain the best means of controlling infectious diseases. In the industrialized nations at the present time, some 50% of all prescribed drugs are derived or synthesized from natural products (animals, marine species, plants and micro-organisms). It has been estimated that plants are the most important source of medicine for more than 80% of the world’s population. As previous work on the leaves of Croton steenkampianus gave promising results and revealed that it still contained bioactive compounds that could be isolated, it was chosen for further work. The bioassay guided fractionation of the ethanol crude extract using silica and Sephadex column chromatography resulted in the isolation of six compounds: three flavoniods (quercetin, tamarixetin and eriodictyol), one new indane (1) (2,6-dimethyl-1-oxo-4 indanecarboxylic acid) and two new diterpenes (steenkrotin A (2) and steenkrotin B (3)) with novel skeletons. The structure of the compounds was determined using NMR, IR, UV, MS and X-ray crystallography. Ethanol crude extract, quercetin, steenkrotin A, steenkrotin B and the indane were tested against four strains of Plasmodium falciparum (D6, D10, Dd2 and W2). Quercetin showed good antiplasmodial activity against the D10 and Dd2 strains. The antiplasmodial activity of steenkrotin A and crude extract were moderate. The antimalarial activity of steenkrotin A in particular is promising, as it showed more activity against resistant strains. The indane, and steekrotin B were not active against the strains of P. falciparum used (IC50 > 10 μg/m). The IC50 of the compounds improved when they were combined with chloroquine. However, the IC50 of chloroquine was still the lowest. The compounds showed moderate bioactivity against Bacillus cereus and Escherichia coli. The three new compounds (1, 2 and 3) tested against Mycobacterium (H37Rv) were not active (IC50 > 10 μg/ml). The indane (1) showed anti-HIV activity at 50 μg/ml against reverse transcriptase. The antioxidant activity of the compounds tested ranged from weak to excellent (>280.00 μg/ml for compound 1 and 2 to 0.05 μg/ml for quercetin). The cytotoxicity of the compounds and extract were determined against Vero cells lines. Their IC50 values ranged from 34.0 to 305.9 ìg/ml, which is higher and better than that of chloroquine. The IC50 values obtained are: chloroquine (25.0), quercetin (33.6), steenkrotin A (35.0), ethanol extract (45.0), tamarixetin (53.8), indane (248.2) and steenkrotin B (305.9).Thesis (PhD)--University of Pretoria, 2009.Plant Scienceunrestricte

Gender pay gap in salary bands among employees in the formal sector of South Africa

Orientation: The gender pay gap is a worldwide challenge that has persisted despite political will and interventions. Comparably qualified women performing similar work as men continue to earn less. There are conflicting views in the literature regarding the status of the gender pay gap. Research purpose: The purpose of the study was to determine status of the gender pay gap among employees in the same salary band and to establish whether men and women receive similar pay for similar work in the study population. Motivation for study: The status of the gender pay gap would establish the progress made towards closing the gap and guide necessary adjustments to interventions. Research approach/design and method: A quantitative analysis was conducted on the pay information of 217 902 employees collected in a survey from over 700 companies, across 10 job families and 6 industries. Main findings: Men’s pay was consistently higher than that of women in all salary bands except at the 75th and 95th percentile in sub-bands B-lower and B-upper and 25th percentile in sub-band E-upper. The gender pay gap ranged from 8% in band A to 27.1% in sub-band F-upper. The gaps observed in the salary bands were statistically significant (p < 0.0001) except in sub-band E-upper, F-lower and F-upper, indicating convergence towards similar pay for similar work at senior to top management levels. Women were under-represented in all salary bands with the lowest presence in band F, especially sub-band F-upper. Gender, race, job family and industry have a significant effect on income earned in the study sample. Practical/managerial implications: Government’s efforts seemed to have produced minimal results as women are represented in all job families, industries and salary bands. The pay of men and women in senior and top management levels was similar. However, more still needs to be done to achieve the 50% target representation of women in senior management and close the gap at all levels. Contribution/value-add: The number of women at management levels is still very low when compared to their male counterparts. However, the gender pay gap in senior to top management positions are converging towards similar pay for work of similar value

Prevalence of drug-resistant tuberculosis and imputed burden in South Africa : a national and sub-national cross-sectional survey

BACKGROUND : Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001–02 estimates. METHODS : A cross-sectional survey was done between June 15, 2012–June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model. FINDINGS : 101 422 participants were tested in 2012–14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5–2·7) among new tuberculosis cases and 4·6% (3·2–6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9–2·9) and 5·1% (3·7–7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5–5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0–3·6; p=0·01). Comparing the current survey with the previous (2001–02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25·9–63·6) and 59·1% (49·0–69·1), respectively. The prevalence of XDR tuberculosis was 4·9% (95% CI 1·0–8·8). Nationally, the estimated numbers of cases of rifampicin-resistant tuberculosis, MDR tuberculosis, and isoniazid mono-resistant tuberculosis for 2014 were 13 551, 8249, and 17 970, respectively. INTERPRETATION : The overall prevalence of MDR tuberculosis in South Africa in 2012–14 was similar to that in 2001–02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management.President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of 1U19GH000571.http://www.thelancet.com/infection2019-07-01hj2018Medical Microbiolog

High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients

Background High mortality rates among asymptomatic cryptococcal antigen (CrAg)–positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Methods Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts <100/µL at 17 clinics and 3 hospitals in Johannesburg from September 2012 until September 2015, and at 2 hospitals until June 2016. Cerebrospinal fluid samples from 90 of 254 asymptomatic patients (35%) and 78 of 173 (45%) with headache only were analyzed for cryptococcal meningitis, considered present if Cryptococcus was identified by means of India ink microscopy, culture, or CrAg test. CrAg titers were determined with stored blood samples from 62 of these patients. The associations between blood CrAg titer, concurrent cryptococcal meningitis, and mortality rate were assessed. Results Cryptococcal meningitis was confirmed in 34% (95% confidence interval, 25%–43%; 31 of 90) of asymptomatic CrAg-positive patients and 90% (81%–96%; 70 of 78) with headache only. Blood CrAg titer was significantly associated with concurrent cryptococcal meningitis in asymptomatic patients (P 160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3–143.1; P < .001). Conclusions About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis

Gender pay gap in salary bands among employees in the formal sector of South Africa

ORIENTATION : The gender pay gap is a worldwide challenge that has persisted despite political will and interventions. Comparably qualified women performing similar work as men continue to earn less. There are conflicting views in the literature regarding the status of the gender pay gap. RESEARCH PURPOSE : The purpose of the study was to determine status of the gender pay gap among employees in the same salary band and to establish whether men and women receive similar pay for similar work in the study population. MOTIVATION FOR STUDY: The status of the gender pay gap would establish the progress made towards closing the gap and guide necessary adjustments to interventions. RESEARCH APPROACH/DESIGN AND METHOD : A quantitative analysis was conducted on the pay information of 217 902 employees collected in a survey from over 700 companies, across 10 job families and 6 industries. MAIN FINDINGS : Men’s pay was consistently higher than that of women in all salary bands except at the 75th and 95th percentile in sub-bands B-lower and B-upper and 25th percentile in sub-band E-upper. The gender pay gap ranged from 8% in band A to 27.1% in sub-band F-upper. The gaps observed in the salary bands were statistically significant (p < 0.0001) except in sub-band E-upper, F-lower and F-upper, indicating convergence towards similar pay for similar work at senior to top management levels. Women were under-represented in all salary bands with the lowest presence in band F, especially sub-band F-upper. Gender, race, job family and industry have a significant effect on income earned in the study sample. PRACTICAL/MANAGERIAL IMPLICATIONS : Government’s efforts seemed to have produced minimal results as women are represented in all job families, industries and salary bands. The pay of men and women in senior and top management levels was similar. However, more still needs to be done to achieve the 50% target representation of women in senior management and close the gap at all levels. CONTRIBUTION/VALUE-ADD : The number of women at management levels is still very low when compared to their male counterparts. However, the gender pay gap in senior to top management positions are converging towards similar pay for work of similar value.http://www.sajhrm.co.zaam2019Gordon Institute of Business Science (GIBS

Distribution and clonality of drug-resistant tuberculosis in South Africa

BACKGROUND: Studies have shown that drug-resistant tuberculosis (DR-TB) in South Africa (SA) is clonal and is caused mostly by transmission. Identifying transmission chains is important in controlling DR-TB. This study reports on the sentinel molecular surveillance data of Rifampicin-Resistant (RR) TB in SA, aiming to describe the RR-TB strain population and the estimated transmission of RR-TB cases. METHOD: RR-TB isolates collected between 2014 and 2018 from eight provinces were genotyped using combination of spoligotyping and 24-loci mycobacterial interspersed repetitive-units-variable-number tandem repeats (MIRU-VNTR) typing. RESULTS: Of the 3007 isolates genotyped, 301 clusters were identified. Cluster size ranged between 2 and 270 cases. Most of the clusters (247/301; 82.0%) were small in size (< 5 cases), 12.0% (37/301) were medium sized (5–10 cases), 3.3% (10/301) were large (11–25 cases) and 2.3% (7/301) were very large with 26–270 cases. The Beijing genotype was responsible for majority of RR-TB cases in Western and Eastern Cape, while the East-African-Indian-Somalian (EAI1_SOM) genotype accounted for a third of RR-TB cases in Mpumalanga. The overall proportion of RR-TB cases estimated to be due to transmission was 42%, with the highest transmission-rate in Western Cape (64%) and the lowest in Northern Cape (9%). CONCLUSION: Large clusters contribute to the burden of RR-TB in specific geographic areas such as Western Cape, Eastern Cape and Mpumalanga, highlighting the need for community-wide interventions. Most of the clusters identified in the study were small, suggesting close contact transmission events, emphasizing the importance of contact investigations and infection control as the primary interventions in SA.The President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC), CTB and NICD.http://www.biomedcentral.com/bmcmicrobiolpm2021Medical Microbiolog

An overview of the quality assurance programme for HIV rapid testing in South Africa: Outcome of a 2-year phased implementation of quality assurance program

Objective This is the first large-scale assessment of the implementation of HIV Rapid Test Quality Improvement Initiative in South Africa. Methods We used a quasi-experimental one group post-test only design. The intervention implemented starting April 2014 comprised health-care worker training on quality assurance (QA) of HIV rapid testing and enrolment of the facilities in proficiency testing (PT), targeting 2,077 healthcare facilities in 32 high HIV burden districts. Following the intervention, two consecutive rounds of site assessments were undertaken. The first, conducted after a median of 7.5 months following the training, included 1,915 facilities that participated in the QA training, while the second, conducted after a median of one-year following the first-round assessment included 517 (27.0%) of the 1,915 facilities. In both assessments, the Stepwise-Process-for-Improving-the-quality-of-HIV-Rapid-Testing (SPI-RT) checklist was used to score facilities’ performance in 7 domains: training, physical facility, safety, pre-testing, testing, post-testing and external quality assessment. Facilities’ level of readiness for national certification was assessed. Result Between 2016 and 2017, there were four PT cycles. PT participation increased from 32.4% (620/1,915) in 2016 to 91.5% (1,753/1,915) in 2017. In each PT cycle, PT results were returned by 76%–87% of facilities and a satisfactory result (\u3e80%) was achieved by ≥95% of facilities. In the SPI-RT assessment, in round-one, 22.3% of facilities were close to or eligible for national certification—this significantly increased to 38.8% in round-two (P-value\u3c0.001). The median SPI-RT score for the domains HIV pre-testing (83.3%) and post-testing (72.2%) remained the same between the two rounds. The median score for the testing domain increased by 5.6% (to 77.8%). Conclusion Facilities performance on the domains that are critical for accuracy of diagnosis (i.e. pretesting, testing and post-testing) remained largely unchanged. This study provided several recommendations to improve QA implementation in South Africa, including the need to improve routine use of internal quality control for corrective actions

High Cryptococcal Antigen Titers in Blood Are Predictive of Subclinical Cryptococcal Meningitis Among Human Immunodeficiency Virus-Infected Patients.

Background: High mortality rates among asymptomatic cryptococcal antigen (CrAg)-positive patients identified through CrAg screening, despite preemptive fluconazole treatment, may be due to undiagnosed cryptococcal meningitis. Methods: Symptoms were reviewed in CrAg-positive patients identified by screening 19233 individuals with human immunodeficiency virus infection and CD4 cell counts 160 (sensitivity, 88.2%; specificity, 82.1%); the odds ratio for concurrent cryptococcal meningitis was 34.5 (95% confidence interval, 8.3-143.1; P < .001). Conclusions: About a third of asymptomatic CrAg-positive patients have concurrent cryptococcal meningitis. More effective clinical assessment strategies and antifungal regimens are required for CrAg-positive patients, including investigation for cryptococcal meningitis irrespective of symptoms. Where it is not possible to perform lumbar punctures in all CrAg-positive patients, blood CrAg titers should be used to target those most at risk of cryptococcal meningitis