Field evaluation of the PIMA™ point-of-care CD4 machine in a mobile clinic, South Africa

Includes abstract.Includes bibliographical references.This aim of this thesis was to validate the PIMA™ in a mobile clinic in South Africa in 2010 and to review current literature regarding CD4 technology, with a focus on point-of-care technology in the HIV infected individual

Monitoring of non-communicable diseases such as hypertension in South Africa: Challenges for the post-2015 global development agenda

Background. Examining the non-communicable disease (NCD) profile for South Africa (SA) is crucial when developing health interventions that aim to reduce the burden of NCDs.Objective. To review NCD indicators in national data sources in order to describe the burden of NCDs in SA, using hypertension as an example.Methods. Age, gender, district of death and underlying cause of death data were obtained for 2008 and 2009 mortality unit records from Statistics SA and adjusted using STATA 11. Data for raised blood pressure were obtained from four national household surveys: the South African Demographic and Health Survey 1998, the Study on Global Ageing and Adult Health 2007, and the National Income Dynamics Study 2008 and 2010.Results. The proportion of years of life lost due to NCDs was highest in the metros and least-deprived districts, with all metros (especially Mangaung) showing high age-standardised mortality rates for ischaemic heart disease, cerebrovascular disease and hypertensive disease. The prevalence of hypertension has increased since 1998. National household surveys showed a measured hypertension prevalence of over 40% in adults aged ≥25 years in 2010. Treatment coverage was 35.7%. Only 36.4% of hypertensive cases (on treatment) were controlled.Conclusion. Further work is needed if NCD monitoring is to be enhanced. Priority targets for NCDs must be integrated into national health planning processes. Surveillance requires integration into national health information systems. Within primary healthcare, a larger focus on integrated chronic care is essential

High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing : a cross-sectional population based sero-survey in South Africa

CITATION: Kranzer, K. et al. 2011. High prevalence of self-reported undiagnosed HIV despite high coverage of HIV testing : a cross-sectional population based sero-survey in South Africa. PLoS ONE, 6(9): e25244, doi:10.1371/journal.pone.0025244.The original publication is available at http://journals.plos.org/plosoneObjectives To measure HIV prevalence and uptake of HIV counseling and testing (HCT) in a peri-urban South African community. To assess predictors for previous HIV testing and the association between the yield of previously undiagnosed HIV and time of last negative HIV test Methods A random sample of 10% of the adult population (≥15 years) were invited to attend a mobile HCT service. Study procedures included a questionnaire, HIV testing and CD4 counts. Predictors for previous testing were determined using a binominal model. Results 1,144 (88.0%) of 1,300 randomly selected individuals participated in the study. 71.0% (68.3–73.6) had previously had an HIV test and 37.5% (34.6–40.5) had tested in the past 12 months. Men, migrants and older (>35 years) and younger (<20 years) individuals were less likely to have had a previous HIV test. Overall HIV prevalence was 22.7 (20.3–25.3) with peak prevalence of 41.8% (35.8–47.8) in women aged 25.1–35 years and 37.5% (26.7–48.3) in men aged 25.1–45 years. Prevalence of previously undiagnosed HIV was 10.3% (8.5–12.1) overall and 4.5% (2.3–6.6), 8.0% (CI 3.9–12.0) and 20.0% (13.2–26.8) in individuals who had their most recent HIV test within 1, 1–2 and more than 2 years prior to the survey. Conclusion The high burden of undiagnosed HIV in individuals who had recently tested underscores the importance of frequent repeat testing at least annually. The high prevalence of previously undiagnosed HIV in individuals reporting a negative test in the 12 months preceding the survey indicates a very high incidence. Innovative prevention strategies are needed.http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025244Publisher's versio

Linkage to HIV, TB and Non-Communicable Disease Care from a Mobile Testing Unit in Cape Town, South Africa

Background: HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives: To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods: A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results: Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion: Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care

Correction:Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene–drug interaction between CYP2D6 and opioids (codeine, tramadol and oxycodone) (European Journal of Human Genetics, (2021), 10.1038/s41431-021-00920-y)

The Data statement was partly wrong and should have read as below. DATA AVAILABILITY All data and material are either included in the Supplementary information or publicly available (i.e., the published articles, PubMed). The guidelines and background information are available on the website of the Royal Dutch Pharmacists Association (KNMP) (Pharmacogenetic Recommendations. Available from: https://www.knmp.nl/). The guidelines and background information will be available on PharmGKB.org

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction of DPYD and fluoropyrimidines

Despite advances in the field of pharmacogenetics (PGx), clinical acceptance has remained limited. The Dutch Pharmacogenetics Working Group (DPWG) aims to facilitate PGx implementation by developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy. This guideline describes the starting dose optimization of three anti-cancer drugs (fluoropyrimidines: 5-fluorouracil, capecitabine and tegafur) to decrease the risk of severe, potentially fatal, toxicity (such as diarrhoea, hand-foot syndrome, mucositis or myelosuppression). Dihydropyrimidine dehydrogenase (DPD, encoded by the DPYD gene) enzyme deficiency increases risk of fluoropyrimidine-induced toxicity. The DPYD-gene activity score, determined by four DPYD variants, predicts DPD activity and can be used to optimize an individual's starting dose. The gene activity score ranges from 0 (no DPD activity) to 2 (normal DPD activity). In case it is not possible to calculate the gene activity score based on DPYD genotype, we recommend to determine the DPD activity and adjust the initial dose based on available data. For patients initiating 5-fluorouracil or capecitabine: subjects with a gene activity score of 0 are recommended to avoid systemic and cutaneous 5-fluorouracil or capecitabine; subjects with a gene activity score of 1 or 1.5 are recommended to initiate therapy with 50% the standard dose of 5-fluorouracil or capecitabine. For subjects initiating tegafur: subjects with a gene activity score of 0, 1 or 1.5 are recommended to avoid tegafur. Subjects with a gene activity score of 2 (reference) should receive a standard dose. Based on the DPWG clinical implication score, DPYD genotyping is considered "essential", therefore directing DPYD testing prior to initiating fluoropyrimidines

Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia

OBJECTIVE : To evaluate the safety of combination antiretroviral therapy (ART) in conception and pregnancy in different health systems. DESIGN : A pilot ART registry to measure the prevalence of birth defects and adverse pregnancy outcomes in South Africa and Zambia. METHODS : HIV-infected pregnant women on ART prior to conception were enrolled until delivery, and their infants were followed until 1 year old. RESULTS : Between October 2010 and April 2011, 600 women were enrolled. The median CD4þ cell count at study enrollment was lower in South Africa than Zambia (320 vs. 430 cells/ml; P<0.01). The most common antiretroviral drugs at the time of conception included stavudine, lamivudine, and nevirapine. There were 16 abortions (2.7%), 1 ectopic pregnancy (0.2%), 12 (2.0%) stillbirths, and 571 (95.2%) live infants. Deliveries were more often preterm (29.7 vs. 18.4%; P¼0.01) and the infants had lower birth weights (2900 vs. 2995 g; P¼0.11) in Zambia compared to South Africa. Thirty-six infants had birth defects: 13 major and 23 minor. There were more major anomalies detected in South Africa and more minor ones in Zambia. No neonatal deaths were attributed to congenital birth defects. CONCLUSIONS : An Africa-specific, multi-site antiretroviral drug safety registry for pregnant women is feasible. Different prevalence for preterm delivery, delivery mode, and birth defect types between women on preconception ART in South Africa and Zambia highlight the potential impact of health systems on pregnancy outcomes. As countries establish ART drug safety registries, documenting health facility limitations may be as essential as the specific ART details.President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) under the terms of Cooperative Agreements U62/CCU123541, 3U2GGH000175–01W1, and 3U2GPS001421.http://www.lww.com/product/?0269-9370hb201

Pregnancy outcomes and birth defects from an antiretroviral drug safety study of women in South Africa and Zambia

To evaluate the safety of combination antiretroviral therapy (ART) in conception and pregnancy in different health systems

Mobile HIV Screening in Cape Town, South Africa: Clinical Impact, Cost and Cost-Effectiveness

Background: Mobile HIV screening may facilitate early HIV diagnosis. Our objective was to examine the cost-effectiveness of adding a mobile screening unit to current medical facility-based HIV testing in Cape Town, South Africa. Methods and Findings: We used the Cost Effectiveness of Preventing AIDS Complications International (CEPAC-I) computer simulation model to evaluate two HIV screening strategies in Cape Town: 1) medical facility-based testing (the current standard of care) and 2) addition of a mobile HIV-testing unit intervention in the same community. Baseline input parameters were derived from a Cape Town-based mobile unit that tested 18,870 individuals over 2 years: prevalence of previously undiagnosed HIV (6.6%), mean CD4 count at diagnosis (males 423/µL, females 516/µL), CD4 count-dependent linkage to care rates (males 31%–58%, females 49%–58%), mobile unit intervention cost (includes acquisition, operation and HIV test costs, $29.30 per negative result and$31.30 per positive result). We conducted extensive sensitivity analyses to evaluate input uncertainty. Model outcomes included site of HIV diagnosis, life expectancy, medical costs, and the incremental cost-effectiveness ratio (ICER) of the intervention compared to medical facility-based testing. We considered the intervention to be “very cost-effective” when the ICER was less than South Africa's annual per capita Gross Domestic Product (GDP) ($8,200 in 2012). We projected that, with medical facility-based testing, the discounted (undiscounted) HIV-infected population life expectancy was 132.2 (197.7) months; this increased to 140.7 (211.7) months with the addition of the mobile unit. The ICER for the mobile unit was$2,400/year of life saved (YLS). Results were most sensitive to the previously undiagnosed HIV prevalence, linkage to care rates, and frequency of HIV testing at medical facilities. Conclusion: The addition of mobile HIV screening to current testing programs can improve survival and be very cost-effective in South Africa and other resource-limited settings, and should be a priority