Dr Phetole Walter Mahasha, PhD in Medical Immunology - South African Medical Research Council (SAMRC) - Project Manager/Senior Scientist

Dr Phetole Walter Mahasha

PhD in Medical Immunology

South African Medical Research Council (SAMRC)

Project Manager/Senior Scientist

Pretoria, Gauteng Province | South Africa

Main Specialties: Biochemical Genetics, Biology, Clinical & Laboratory Immunology, Epidemiology, Infectious Disease, Medical Genetics, Medical Microbiology, Public Health

Additional Specialties: Vaccinology, HIV and TB pathogenesis, Medical Immunology, Medical Biochemistry.

ORCID logohttps://orcid.org/0000-0002-5750-3595


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Dr Phetole Walter Mahasha, PhD in Medical Immunology - South African Medical Research Council (SAMRC) - Project Manager/Senior Scientist

Dr Phetole Walter Mahasha

PhD in Medical Immunology

Introduction

I am currently employed by the South African Medical Research Council (SAMRC), Grants, Innovation and Product Development Unit as a Project Manager/Senior Scientist. I am responsible for liaising with sponsors, project teams, regulatory bodies, universities to ensure proper conduct of the projects; meeting milestone targets as indicated in the awards; reporting writing to Directorate and funding bodies; development and maintenance of standard operating procedures; develop service level agreements and ensure smooth project delivery within the SAMRC Genomics Centre. Previously, I worked for the South Africa Centre as a Senior Scientist working on Vaccine Implementation Research responsible for preparing research findings for publication in leading academic journals in collaboration with other Unit staff and lead/coordinate ongoing projects on vaccine acceptance and uptake. I am a registered Professional Natural Scientist (registration number: 119189) holding a PhD in Medical Immunology and an M.Sc. degree in Medical Sciences (Medical Biochemistry). I have also completed training courses in ICH GCP, CITI, Good Clinical Practices and Protecting Human Research Participants, and Good Clinical Laboratory Practice (GCLP). I have over 8 years’ research experience on HIV/AIDS and over two years on TB. I was previously employed by EQUIP Innovation for Health (Right to Care) as a Senior Research Manager working in 17 countries across Africa, South East Asia, Eastern Europe and the Caribbean towards achieving the UNAIDS 90- 90-90 targets, the project is funded by USAID which include HIV Self-testing (HIV)-Co-PI, Multi-month Scripting and Dispensing (MMSD) and other projects include Pre-exposure prophylaxis (PreP) demo projects (Namibia), Hepatitis C Virus projects (HCV) (Ukraine and Myanmar) and Costing and cost-effectiveness assessments of various innovative interventions. I also was previously employed by the University of Limpopo as a Senior Lecturer in the Department of Pre-Clinical Sciences (Medical Biochemistry), lectured Medical and Nutritional Biochemistry.

I have completed an NIH FIC Postdoctoral Research Fellowship with the University of Venda (South Africa), HIV/AIDS & Global Health Research Programme, Department of Microbiology and the University of Virginia (USA), Center for Global Health where I worked as a Genetic Epidemiology/Statistical Genetics and Metabonomics Research Fellow conducting analytical and genetic epidemiological research with existing data sets. Primary analytical methods included statistical modelling of common genetic variant factors influencing a trait or clinical outcome and statistical modelling of rare genetic variant factors influencing a trait or clinical outcome including the use of burden or aggregate marker test. I worked under the mentorship of Drs. Richard Guerrant, Infectious Diseases and International Health and Josyf Mychaleckyj, Public Health Sciences Administration at UVA and Dr. Bessong at Univen collaboratively analyzing existing GWAS samples from Gambia and Sierra Leone with local South African children after obtaining and isolating salivary DNA and another Postdoctoral fellowship with the National Institute for Communicable Diseases, in the Cell Biology Laboratory within the Centre for HIV and STIs.

I graduated with a PhD in Medical Immunology with the University of Pretoria (South Africa) at a graduation ceremony held on the 5th of September 2014, with a research project titled: “Compartmentalization, Adaptive Evolution and Therapeutic Response of HIV-1 in the Gastrointestinal Tract (GIT) of African patients infected with Subtype C: Implications for the Enhancement of Therapeutic Efficacy”. I completed a B.Sc. degree with the University of the North (now University of Limpopo), where I majored in Microbiology and Biochemistry. During my Honours work at the same institution, I completed a project on cancer research titled, “Determination of the influence of lithium chloride (LiCl) on pro- and anti-apoptotic proteins in PK cells (15)”. These studies solidified my desire to pursue a career in health research, and highlighted the need to focus on transitional research that is of critical importance to South Africa and the developing world. As a result of a growing interest in HIV-1/AIDS and AIDS-related infections including tuberculosis and malnutrition and enteric diseases, I seized the opportunity to continue my scientific training in TB research with Dr. Gey van Pittius and Professor Rob Warren at the University of Stellenbosch (South Africa), where I successfully co-designed and completed a research project entitled, “Trafficking of the Mycobacterium tuberculosis PE and PPE proteins”. I graduated for my M.Sc. in Medical Sciences at a graduation ceremony held at the University of Stellenbosch in December 2007.

These research projects provided me with a range of different skills that are necessary for the development of a successful career in health research, including laboratory-based experience in tissue and cell culture, DNA isolation, immunohistochemistry, SDS-PAGE, Western blotting, PCR, site-directed mutagenesis, cloning, and gene knockout techniques, the use of statistical genomics/genetic epidemiology techniques and tools. Teaching experience has ranged from assisting undergraduate students with their practicals (as a lab demonstrator) to the marking of their scripts and the supervision of undergraduate research activities. I also facilitated lectures on HIV and TB pathology and pathogenesis and on how to write a scientific abstract, paper/manuscript and dissertation/thesis. I also learned a lot working in the field, managing a project for collecting saliva samples to determine the impact of malnutrition and enteric diseases on child growth and development.

Through out my studies and research career over the years financial support was provided by the NIH Forgaty International Center, South African National Research Foundation, South African Medical Research Council, Poliomyelitis Research Foundation, Department of Immunology University of Pretoria, University of Pretoria Postgraduate Scholarship, University of Stellenbosch Postgraduate Bursary, DST/NRF Centre of Excellence in Biomedical Tuberculosis Research and US/MRC Centre for Molecular and Cellular Biology Bursary. I have published more than 8 articles/papers published in reputable journals and have been serving as an editorial board member of repute in international journals.

My Research Interest is in Vaccine Implementation Research, Infectious Diseases, HIV/AIDS Research, Tuberculosis (TB) Research, Malnutrition and Enteric Pathogens Research, Clinical Research and Clinical Trials and Public Health research.

Primary Affiliation: South African Medical Research Council (SAMRC) - Pretoria, Gauteng Province , South Africa

Specialties:

Additional Specialties:

Research Interests:


View Dr Phetole Walter Mahasha’s Resume / CV

Education

Sep 2014
University of Pretoria
PhD
PhD in Medical Immunology
Dec 2007
University of Stellenbosch
M.Sc.
M.Sc in Medical Biochemistry
Oct 2004
University of Limpopo
B.Sc. Honours
Honours in Biochemistry
Apr 2003
University of Limpopo
B.Sc.
B.Sc. in Life Sciences

Experience

Jul 2019
South African Medical Research Council
Project Manager/Senior Scientist
Precision Medicine and South African Medical Research Council Genomics Centre
Jul 2018
South African Medical Research Council
Senior Scientist
Cochrane South Africa centre, Vaccinologist
Jan 2017
EQUIP - Right to Care
Senior Research Manager
USAID/PEPFAR funded programme working towards the UNAIDS 90-90-90 targets
Feb 2016
University of Limpopo
Senior Lecturer
Taught Medical and Nutritional Biochemistry
Sep 2014
University of Virginia/University of Venda
Postdoctoral Research Fellow
Global Research Fellow
May 2014
National Institute of Communicable Diseases
Postdoctoral Research Fellow
HIV functional cure project
Aug 2013
South African Medical Research Council
Project Manager/Science Writer
HIV Prevention Research Unit_ working on Microbicide gels/ring to prevent HIV
Feb 2008
South African Medical Research Council/University of Pretoria
PhD Research Intern
Research on HIV pathogenesis
Jul 2007
University of Pretoria
Research Assistant
Research on HIV pathogenesis
Feb 2006
South African Medical Research Council/University of Stellenbosch
M.Sc. Research Intern
Research on TB pathogenesis
Feb 2003
University of Limpopo
Laboratory Assistant
Biochemistry

Publications

15Publications

870Reads

129Profile Views

437PubMed Central Citations

Contextualized strategies to increase childhood and adolescent vaccination coverage in South Africa: a mixed-methods study

BMJ Open 2020;10:e028476. doi: 10.1136/bmjopen-2018-028476

BMJ Open

Introduction Despite the unparalleled success of immunisation in the control of vaccine preventable diseases, immunisation coverage in South Africa remains suboptimal. While many evidence-based interventions have successfully improved vaccination coverage in other countries, they are not necessarily appropriate to the immunisation needs, barriers and facilitators of South Africa. The aim of this research is to investigate barriers and facilitators to optimal vaccination uptake, and develop contextualised strategies and implementation plans to increase childhood and adolescent vaccination coverage in South Africa. Methods The study will employ a mixed-methods research design. It will be conducted over three iterative phases and use the Adopt, Contextualise or Adapt (ACA) model as an overarching conceptual framework. Phase 1 will identify, and develop a sampling frame of, immunisation stakeholders involved in the design, planning and implementation of childhood and human papillomavirus immunisation programmes in South Africa. Phase 2 will identify the main barriers and facilitators to, and solutions for, increasing vaccination coverage. This phase will comprise exploratory qualitative research with stakeholders and a review of existing systematic reviews on interventions for improving vaccination coverage. Using the findings from Phase 2 and the ACA model, Phase 3 will develop a set of proposed interventions and implementation action plans for improving immunisation coverage in South Africa. These plans will be discussed, revised and finalised through a series of participatory stakeholder workshops and an online questionnaire, conducted as part of Phase 3. Ethics Ethical approval was obtained from the South African Medical Research Council (EC018-11/2018). No risks to participants are expected. Various steps will be taken to ensure the anonymity and confidentiality of participants.Dissemination The study findings will be shared at stakeholder workshops, the website of Cochrane South Africa and academic publications and conferences.

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June 2020

Impact Factor 2.420

Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017.

The Lancet. 2020 May 6; in press

The Lancet

Background

Across low-income and middle-income countries (LMICs), one in ten deaths in children younger than 5 years is attributable to diarrhoea. The substantial between-country variation in both diarrhoea incidence and mortality is attributable to interventions that protect children, prevent infection, and treat disease. Identifying subnational regions with the highest burden and mapping associated risk factors can aid in reducing preventable childhood diarrhoea.

Methods

We used Bayesian model-based geostatistics and a geolocated dataset comprising 15 072 746 children younger than 5 years from 466 surveys in 94 LMICs, in combination with findings of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, to estimate posterior distributions of diarrhoea prevalence, incidence, and mortality from 2000 to 2017. From these data, we estimated the burden of diarrhoea at varying subnational levels (termed units) by spatially aggregating draws, and we investigated the drivers of subnational patterns by creating aggregated risk factor estimates.

Findings

The greatest declines in diarrhoeal mortality were seen in south and southeast Asia and South America, where 54·0% (95% uncertainty interval [UI] 38·1–65·8), 17·4% (7·7–28·4), and 59·5% (34·2–86·9) of units, respectively, recorded decreases in deaths from diarrhoea greater than 10%. Although children in much of Africa remain at high risk of death due to diarrhoea, regions with the most deaths were outside Africa, with the highest mortality units located in Pakistan. Indonesia showed the greatest within-country geographical inequality; some regions had mortality rates nearly four times the average country rate. Reductions in mortality were correlated to improvements in water, sanitation, and hygiene (WASH) or reductions in child growth failure (CGF). Similarly, most high-risk areas had poor WASH, high CGF, or low oral rehydration therapy coverage.

Interpretation

By co-analysing geospatial trends in diarrhoeal burden and its key risk factors, we could assess candidate drivers of subnational death reduction. Further, by doing a counterfactual analysis of the remaining disease burden using key risk factors, we identified potential intervention strategies for vulnerable populations. In view of the demands for limited resources in LMICs, accurately quantifying the burden of diarrhoea and its drivers is important for precision public health.

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May 2020

Impact Factor 59.102

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017. https://doi.org/10.1038/s41591-020-0807-6

Nat. Med. 2020 April 20; 26:750–759

Nature Medicine

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of

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May 2020

Impact Factor 30.641

Effectiveness of the female condom in preventing HIV and sexually transmitted infections: a systematic review and meta-analysis.

BMC Public Health 2020 Mar 12;20(1):319. Epub 2020 Mar 12.

Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.

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http://dx.doi.org/10.1186/s12889-020-8384-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7068875PMC
March 2020
2.264 Impact Factor

Systematic review protocol on Bacillus Calmette-Guerin (BCG) revaccination and protection against tuberculosis.

BMJ Open 2019 10 15;9(10):e027033. Epub 2019 Oct 15.

Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.

Introduction: Tuberculosis (TB) is a disease caused by (M.TB) and other species of the Mycobacterium tuberculosis complex. Globally, TB is ranked as the ninth leading cause of death and the leading cause of death from a single infectious agent. The bacille Calmette-Guerin (BCG) vaccine has been used globally since 1921 for the prevention of TB in humans, and was derived from an attenuated strain of . Evidence from previous randomised trials show that the efficacy of primary BCG vaccination against pulmonary TB ranged from no protection to very high protection. In addition, some studies suggest a benefit of BCG revaccination. For example, a recent trial conducted in South Africa showed that BCG revaccination of adolescents could reduce the risk of TB infection by half. However, we are not aware of any recent systematic reviews of the effects of BCG revaccination. Thus, the need for this systematic review of the effects of BCG revaccination on protection against TB infection and disease.

Method And Analysis: We will search PubMed, the Cochrane Central Register of Controlled Trials, EMBASE, WHO International Clinical Trials Registry Platform and reference lists of relevant publications for potentially eligible studies. We will screen search outputs, select eligible studies, extract data and assess risk of bias in duplicate. Discrepancies will be resolved by discussion and consensus or arbitration. We will use the Grading of Recommendations Assessment, Development and Evaluation method to assess the certainty of the evidence. The planned systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) in August 2018.

Ethics And Dissemination: Publicly available data will be used, hence no formal ethical approval will be required for this review. The findings of the review will be disseminated through conference presentations and publication in an open-access peer-reviewed journal.

Prospero Registration Number: CRD42018105916.

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http://dx.doi.org/10.1136/bmjopen-2018-027033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6797475PMC
October 2019
3 Reads
2.376 Impact Factor

HIV ENTEROPATHY_ SYSTEMATIC EVALUATION OF THE GUT BY DOUBLE BALLOON ENTEROSCOPY AND FLOW CYTOMETRY.

SAMJ. 2008 Aug 98(8); pp. 638 - 638

South African Medical Journal

IntroductionHuman immunodeficiency virus infection in humans may be associated with protracted diarrhoea and weight loss. This has been termed slim disease. HIV-associated enteropathy defines a specific clinical entity where no secondary cause such as opportunistic infections or drug-induced diarrhoea can be shown. Recent developments in double balloon enteroscopy techniques have allowed endoscopic evaluation of the distal gut.Materials and methodsDouble balloon enteroscopy was performed in 26 treatment naïve HIV patients after informed consent was obtained. Biopsies were taken of the duodenum, jejunum, ileum and R and L colon at baseline. Patients were then placed on HAART therapy and duodenal biopsies were taken at 3 months. At 6 months biopsies were taken of the duodenum and L colon. Patients were followed up monthly at the HIV clinic where serum was taken for viral load and other parameters. The bowel biopsies were processed for the following: T-lymphocyte and macrophage isolation by flow cytometry, histology, electron microscopy, tissue viral load.ResultsThe mean CD4+ count was 77.65 x 10^6/l at baseline. Double balloon enteroscopy was successful in 26/26 (100%) of the patients. The mean endoscopy time was 154 minutes +/- 36 min. Flow cytometry showed the mean CD4+% from duodenum, jejunum, ileum and R colon to be 3.5, 3.7, 12.5 and 6.9 respectively. At 3 months and 6 months the peripheral CD4+ count increased to 155.6 x 10^6/l and 240 x 10^6/l. At 3 months and 6 months CD4+ count in the duodenum increased by 5.0% and 4.2% respectively. There was a decrease in naïve CD4+ and CD8+ T-cells and an increase in CD4+ and CD8+ effector cells, central memory and effector memory T-cells in the duodenum at 3 and 6 months. The mean percentage weight gain after 6 months follow-up was 8.12%. Clinical improvement correlated strongly with a decrease in CD8+ cells in the duodenum.ConclusionsHIV enteropathy is associated with low CD4+ T-cells in all gut compartments. Peripheral blood CD4+ cells promptly increased on HAART therapy, while the gut CD4+ cell count remained low. Improvement in diarrhoea and weight gain occurred in all patients and correlated with a decrease in CD8+ T-cells. The gut was repopulated by effector and memory T-cells. The naive T-cell populations remained low.

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October 2019

Impact Factor 1.325

10 Reads

A systematic review of immunogenicity, clinical efficacy and safety of human papillomavirus vaccines in people living with the human immunodeficiency virus.

Hum Vaccin Immunother 2020 20;16(2):426-435. Epub 2019 Sep 20.

Cochrane South Africa, South African Medical Research Council, Cape Town, South Africa.

The human papillomavirus (HPV) is the most prevalent sexually transmitted infection worldwide. People living with the human immunodeficiency virus (HIV) are at high risk of HPV infection. This systematic review evaluates the immunogenicity, clinical efficacy, and safety of prophylactic HPV vaccines in people living with HIV. We registered the protocol for this review in the International Prospective Register of Systematic Reviews (CRD42018109898) and prepared the review following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Five randomized trials with 1042 participants are included in this review. One trial with 120 participants compared the bivalent HPV vaccine to placebo, three trials with 830 participants compared the quadrivalent vaccine to placebo, and another trial with 92 participants compared the quadrivalent to the bivalent vaccine. There was low to moderate certainty evidence suggesting that seroconversion was higher among participants in the vaccine arms compared to the placebo arms for both vaccines. In one study with very low certainty evidence, participants who received the bivalent vaccine had higher anti-HPV-18 geometric mean titres (GMTs) compared to those who received the quadrivalent vaccine, despite little difference in anti-HPV-16 GMTs between the two vaccines. There were no differences in incident and persistent HPV infections in both groups. None of the studies reported data on the incidence of precancerous lesions, or cancer. There were no reports of serious adverse events following vaccination in any of the trials. None of the included studies assessed the effects of HPV vaccines in adolescents living with HIV. Very limited evidence suggests lower immunogenicity of HPV vaccines in HIV positive compared to HIV negative people. Finally, the long-term effect of the HPV vaccine in the incidence of cervical precancerous lesions and cervical cancer need to be monitored. There is an urgent need for more high-quality randomized controlled trials that can address these gaps.

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http://dx.doi.org/10.1080/21645515.2019.1656481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062428PMC
September 2019
8 Reads
2.932 Impact Factor

A global review of seasonal influenza vaccine introduction: analysis of the WHO/UNICEF Joint Reporting Form.

Expert Rev Vaccines 2019 08 18;18(8):859-865. Epub 2019 Jul 18.

a Cochrane South Africa, South African Medical Research Council , Cape Town , South Africa.

Background: Influenza is a highly contagious disease that affects the upper and lower respiratory tract caused by several subtypes of influenza viruses. While vaccination remains the mainstay strategy to protect populations against influenza, there is a global shortage and inequitable access to influenza vaccines. Although influenza vaccine production capacity increased from 500 million doses in 2006 to 1.5 billion doses in 2013, little is known about the global distribution of these vaccines albeit its introduction. We assessed the global status of influenza vaccine introduction.

Research design and methods: We analyzed data from the World Health Organization (WHO) Joint Reporting Form, a publicly available source of immunization data from 194 countries of all six WHO regions. We used 2017 data, available as of July 2018.

Results: By December 2017, 117 of 194 (60%) WHO Member States had introduced the seasonal influenza vaccine. European and American regions accounted for 70% (82/117) of the total number of countries that had introduced influenza vaccine. The other four regions account for only 30%. Ninety-four percent (50/53) of countries in the European region and 91% (32/35) in the American region had introduced influenza vaccine. In the Eastern Mediterranean and Western Pacific regions, 67% (14/21) and 52% (14/27), respectively, had introduced the vaccine. Yet only 27% (3/11) and 9% (4/47) in the Southeast Asian and African regions, respectively, had introduced the vaccine. Among countries (n = 117) that had introduced the vaccine, children (56%), older adults (87%), and risk groups (99%) were prioritized and given the vaccines.

Conclusions: Introduction of influenza vaccine in the African and Southeast Asian regions remains suboptimal. This critically underscores the need for financing mechanisms and having countries in the regions that are lagging behind to prioritize seasonal influenza vaccine.

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http://dx.doi.org/10.1080/14760584.2019.1640119DOI Listing
August 2019
6 Reads
4.531 Impact Factor

Global, regional, and national incidence, prevalence, and mortality of HIV from 1980 to 2017 with forecasts to 2030, for 195 countries and 2 territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2017 Study.

The Lancet HIV 2019 Aug 14. pii: S2352-3018(19)30196-1.

The Lancet HIV

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact.  

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August 2019

Impact Factor 14.753

16 Reads

Access to HIV care and treatment for migrants between Lesotho and South Africa: a mixed methods study.

BMC Public Health 2018 05 29;18(1):668. Epub 2018 May 29.

EQUIP - Innovation for Health, 1006 Lenchen Avenue North, Centurion, South Africa.

Background: HIV treatment and care for migrants is affected by their mobility and interaction with HIV treatment programs and health care systems in different countries. To assess healthcare needs, preferences and accessibility barriers of HIV-infected migrant populations in high HIV burden, borderland districts of Lesotho.

Methods: We selected 15 health facilities accessed by high patient volumes in three districts of Maseru, Leribe and Mafeteng. We used a mixed methods approach by administering a survey questionnaire to consenting HIV infected individuals on anti-retroviral therapy (ART) and utilizing a purposive sampling procedure to recruit health care providers for qualitative in-depth interviews across facilities.

Results: Out of 524 HIV-infected migrants enrolled in the study, 315 (60.1%) were from urban and 209 (39.9%) from rural sites. Of these, 344 (65.6%) were women, 375 (71.6%) were aged between 26 and 45 years and 240 (45.8%) were domestic workers. A total of 486 (92.7%) preferred to collect their medications primarily in Lesotho compared to South Africa. From 506 who responded to the question on preferred dispensing intervals, 63.1% (n =?319) preferred 5-6 month ARV refills, 30.2% (n =?153) chose 3-4 month refills and only 6.7% (n =?34) opted for the standard-of-care 1-2 month refills. A total of 126 (24.4%) defaulted on their treatment and the primary reason for defaulting was failure to get to Lesotho to collect medication (59.5%, 75/126). Treatment default rates were higher in urban than rural areas (28.3% versus 18.4%, p =?0.011). Service providers indicated a lack of transfer letters as the major drawback in facilitating care and treatment for migrants, followed by discrimination based on nationality or language. Service providers indicated that most patients preferred all treatment services to be rendered in Lesotho, as they perceive the treatment provided in South Africa to be different often less strong or with more serious side effects.

Conclusion: Existing healthcare systems in both South Africa and Lesotho experience challenges in providing proper care and treatment for HIV infected migrants. A need for a differentiated model of ART delivery to HIV infected migrants that allows for multi-month scripting and dispensing is warranted.

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http://dx.doi.org/10.1186/s12889-018-5594-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975397PMC
May 2018
306 Reads
1 Citation
2.567 Impact Factor

HIV drug resistance levels in adults failing first-line antiretroviral therapy in an urban and a rural setting in South Africa.

HIV Med 2017 02 28;18(2):104-114. Epub 2016 Jun 28.

Africa Centre Population Health, University of KwaZulu-Natal, South Africa.

OBJECTIVES:

Urban and rural HIV treatment programmes face different challenges in the long-term management of patients. There are few studies comparing drug resistance profiles in patients accessing treatment through these programmes. The aim of this study was to perform such a comparison.

METHODS:

HIV drug resistance data and associated treatment and monitoring information for adult patients failing first-line therapy in an urban and a rural programme were collected. Data were curated and managed in SATuRN RegaDB before statistical analysis using Microsoft Excel 2013 and stata Ver14, in which clinical parameters, resistance profiles and predicted treatment responses were compared.

RESULTS:

Data for 595 patients were analysed: 492 patients from a rural setting and 103 patients from an urban setting. The urban group had lower CD4 counts at treatment initiation than the rural group (98 vs. 126 cells/?L, respectively; P = 0.05), had more viral load measurements performed per year (median 3 vs. 1.4, respectively; P < 0.01) and were more likely to have no drug resistance mutations detected (35.9% vs. 11.2%, respectively; P < 0.01). Patients in the rural group were more likely to have been on first-line treatment for a longer period, to have failed for longer, and to have thymidine analogue mutations. Notwithstanding these differences, the two groups had comparable predicted responses to the standard second-line regimen, based on the genotypic susceptibility score. Mutations accumulated in a sigmoidal fashion over failure duration.

CONCLUSIONS:

The frequency and patterns of drug resistance, as well the intensity of virological monitoring, in adults with first-line therapy failure differed between the urban and rural sites. Despite these differences, based on the genotypic susceptibility scores, the majority of patients across the two sites would be expected to respond well to the standard second-line regimen.

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http://dx.doi.org/10.1111/hiv.12400DOI Listing
February 2017
113 Reads
9 Citations
3.988 Impact Factor

CD14(+) macrophages that accumulate in the colon of African AIDS patients express pro-inflammatory cytokines and are responsive to lipopolysaccharide.

BMC Infect Dis 2015 Oct 17;15:430. Epub 2015 Oct 17.

MRC Unit for Inflammation and Immunity, Department of Immunology and the Tshwane Academic Division of the National Health Laboratory Service, University of Pretoria, Pretoria, South Africa.

Background: Intestinal macrophages are key regulators of inflammatory responses to the gut microbiome and play a central role in maintaining tissue homeostasis and epithelial integrity. However, little is known about the role of these cells in HIV infection, a disease fuelled by intestinal inflammation, a loss of epithelial barrier function and increased microbial translocation (MT).

Methods: Phenotypic and functional characterization of intestinal macrophages was performed for 23 African AIDS patients with chronic diarrhea and/or weight loss and 11 HIV-negative Africans with and without inflammatory bowel disease (IBD). AIDS patients were treated with cotrimoxazole for the prevention of opportunistic infections (OIs). Macrophage phenotype was assessed by flow cytometry and immuno-histochemistry (IHC); production of proinflammatory mediators by IHC and Qiagen PCR Arrays; in vitro secretion of cytokines by the Bio-Plex Suspension Array System. Statistical analyses were performed using Spearman's correlation and Wilcoxon matched-pair tests. Results between groups were analyzed using the Kruskal-Wallis with Dunn's post-test and the Mann-Whitney U tests.

Results: None of the study participants had evidence of enteric co-infections as assessed by stool analysis and histology. Compared to healthy HIV-negative controls, the colon of AIDS patients was highly inflamed with increased infiltration of inflammatory cells and increased mRNA expression of proinflammatory cytokine (tumour necrosis factor (TNF)-?, interleukin (IL)-1?, IFN-?, and IL-18), chemokines (chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C) motif ligand (CXCL)10) and transcription factors (TNF receptor-associated factor (TRAF)6 and T-box (TXB)21). IHC revealed significant co-localization of TNF-? and IL-1? with CD68(+) cells. As in IBD, HIV was associated with a marked increase in macrophages expressing innate response receptors including CD14, the co-receptor for lipopolysaccharide (LPS). The frequency of CD14(+) macrophages correlated positively with plasma LPS, a marker of MT. Total unfractionated mucosal mononuclear cells (MMC) isolated from the colon of AIDS patients, but not MMC depleted of CD14(+) cells, secreted increased levels of proinflammatory cytokines ex vivo in response to LPS.

Conclusions: Intestinal macrophages, in the absence of overt OIs, play an important role in driving persistent inflammation in HIV patients with late-stage disease and diarrhea. These results suggest intensified treatment strategies that target inflammatory processes in intestinal macrophages may be highly beneficial in restoring the epithelial barrier and limiting MT in HIV-infected patients.

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http://dx.doi.org/10.1186/s12879-015-1176-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4609115PMC
October 2015
66 Reads
14 Citations
2.620 Impact Factor

Impaired CD4+ T-cell restoration in the small versus large intestine of HIV-1-positive South Africans receiving combination antiretroviral therapy.

J Infect Dis 2013 Oct 6;208(7):1113-22. Epub 2013 Jun 6.

Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston MA 02215, USA.

Background: Human immunodeficiency virus type 1 (HIV-1) infection is associated with a massive depletion of intestinal CD4(+) T cells that is only partially reversed by combination antiretroviral therapy (cART). Here, we assessed the ability of nucleoside reverse-transcriptase inhibitor/nonnucleoside reverse-transcriptase inhibitor treatment to restore the CD4(+) T-cell populations in the intestine of South African patients with AIDS.

Methods: Thirty-eight patients with advanced HIV-1 infection who had chronic diarrhea (duration, >4 weeks) and/or unintentional weight loss (>10% decrease from baseline) of uncertain etiology were enrolled. Blood specimens were collected monthly, and gastrointestinal tract biopsy specimens were collected before cART initiation (from the duodenum, jejunum, ileum, and colon), 3 months after cART initiation (from the duodenum), and 6 months after cART initiation (from the duodenum and colon). CD4(+), CD8(+), and CD38(+)CD8(+) T cells were quantified by flow cytometry and immunohistochemistry analyses, and the HIV-1 RNA load was determined by the Nuclisens assay.

Results: CD4(+) T-cell and HIV-1 RNA levels were significantly lower, whereas CD8(+) T-cell levels, including activated CD38(+)CD8(+) T cell levels, were higher in the duodenum and jejunum, compared with the colon. After 6 months of cART, a significant but incomplete recovery of CD4(+) T cells was detected in the colon and peripheral blood but not in the duodenum. Failed restoration of the CD4(+) T-cell count in the duodenum was associated with nonspecific enteritis and CD8(+) T-cell activation.

Conclusions: Strategies that target inflammation and immune activation in the small intestine may be required to expedite CD4(+) T-cell recovery and improve therapeutic outcomes.

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http://dx.doi.org/10.1093/infdis/jit249DOI Listing
October 2013
138 Reads
15 Citations
5.997 Impact Factor

Persistent microbial translocation and immune activation in HIV-1-infected South Africans receiving combination antiretroviral therapy.

J Infect Dis 2010 Sep;202(5):723-33

MRC Unit for Inflammation and Immunity, Department of Immunology, Faculty of Health Sciences, University of Pretoria and the Tshwane Academic Division of the National Health Laboratory Service, Pretoria, South Africa.

Background: Microbial translocation contributes to immune activation and disease progression during chronic human immunodeficiency virus type 1 (HIV-1) infection. However, its role in the African AIDS epidemic remains controversial. Here, we investigated the relationship between markers of monocyte activation, plasma lipopolysaccharide (LPS), and HIV-1 RNA in South Africans prioritized to receive combination antiretroviral therapy (cART).

Methods: Ten HIV-1-negative African controls and 80 HIV-1-infected patients with CD4 T cell counts <200 cells/microL were sampled prior to (n=60) or during (n=20) receipt of effective cART. Viral load was measured by Nuclisens; LPS by the Limulus amoebocyte lysate assay; monocyte and T cell subsets by flow cytometry; and soluble CD14, cytokines, and chemokines by enzyme-linked immunosorbent assay and customized Bio-Plex plates.

Results: Three distinct sets of markers were identified. CCL2, CXCL10, and CD14(+)CD16(+) monocyte levels were positively correlated with HIV-1 viremia. This finding, together with cART-induced normalization of these markers, suggests that their upregulation was driven by HIV-1. Plasma interleukin-6 was associated with the presence of opportunistic coinfections. Soluble CD14 and tumor necrosis factor were linked to plasma LPS levels and, as observed for LPS, remained elevated in patients receiving effective cART.

Conclusions: Microbial translocation is a major force driving chronic inflammation in HIV-infected Africans receiving cART. Prevention of monocyte activation may be especially effective at enhancing therapeutic outcomes.

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http://dx.doi.org/10.1086/655229DOI Listing
September 2010
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185 Citations
5.997 Impact Factor

PPE and PE_PGRS proteins of Mycobacterium marinum are transported via the type VII secretion system ESX-5.

Mol Microbiol 2009 Aug 7;73(3):329-40. Epub 2009 Jul 7.

Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam, the Netherlands.

ESX-5 is one of the five type VII secretion systems found in mycobacteria. These secretion systems are also known as ESAT-6-like secretion systems. Here, we have determined the secretome of ESX-5 by a proteomic approach in two different strains of Mycobacterium marinum. Comparison of the secretion profile of wild-type strains and their ESX-5 mutants showed that a number of PE_PGRS and PPE-MPTR proteins are dependent on ESX-5 for transport. The PE and PPE protein families are unique to mycobacteria, are highly expanded in several pathogenic species, such as Mycobacterium tuberculosis and M. marinum, and certain family members are cell surface antigens associated with virulence. Using a monoclonal antibody directed against the PGRS domain we showed that nearly all PE_PGRS proteins that are recognized by this antibody are missing in the supernatant of ESX-5 mutants. In addition to PE_PGRS and PPE proteins, the ESX-5 secretion system is responsible for the secretion of a ESAT-6-like proteins. Together, these data show that ESX-5 is probably a major secretion pathway for mycobacteria and that this system is responsible for the secretion of recently evolved PE_PGRS and PPE proteins.

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http://dx.doi.org/10.1111/j.1365-2958.2009.06783.xDOI Listing
August 2009
178 Reads
213 Citations
4.419 Impact Factor

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