The public health importance of HIV and sexually transmitted infections within Africa
Sexually transmitted infections (STIs), including those caused by the human immunodeficiency virus (HIV) types 1 and 2, remain a major public health problem in Africa. Published estimates of the Joint United Nations Programme on HIV/AIDS show that South Africa has the highest burden of HIV infections with recent estimates of 7.7 million people living with HIV.
The Centre for HIV and STIs (CHIVSTI) has a strong track record in the research disciplines of HIV virology, HIV immunology, HIV/STI epidemiology, HIV/STI diagnostics and HIV-STI interactions.
CHIVSTI addresses the challenges of HIV and STI diseases through various programmes:
- Surveillance of disease burden and antimicrobial resistance;
- Measurement of endpoint infections and detection;
- Broadly neutralising antibodies as part of prophylactic HIV vaccine and antibody-mediated protection clinical trials;
- Exploring an HIV “cure” strategy; and
- Development and implementation of reference diagnostics and implementation science.
CHIVSTI consists of four sections:
- HIV Virology;
- Cell Biology;
- HIV Molecular and Serology;
- Sexually Transmitted Infections section.
The centre provides a suitable academic environment for successful supervision of undergraduate and postgraduate students and fellows. The centre has well-established links and collaborations with various key national and international organisations in the field of HIV and STIs.
The objectives of CHIVSTI are:
- To serve as a resource of knowledge and expertise in HIV and other regionally relevant STIs to the South African Government, SADC countries and the African continent at large, in order to assist in the planning of policies and programmes related to the control and effective management of HIV and STIs; and
- To perform world-class surveillance, research and teach/train future scientists.
The Section is a globally accredited laboratory responsible for performing validated end-point antibody for the HIV Vaccine Trials Network (HVTN), including passive and active vaccination regimens. A major research focus of the Section is to understand how broadly neutralizing antibodies to HIV develop (including virology, immunology and immunogenetics), as such antibodies are crucial for the development of an effective HIV vaccine.
Since the emergence of SARS-CoV-2 the laboratory has studied the humoral response to this virus, with a particular focus on variants of concern and their impact on neutralization by vaccinee and convalescent sera, which has contributed to understanding the immune response to emerging variants and the implications for the design of second generation adapted COVID-19 vaccines. The section also isolates HIV and SARS-CoV-2 specific antibodies of interest from both infected and vaccinated individuals. A major focus is training and the Section hosts many students and post-doctoral fellows.
A major focus of this research group is the study of natural resistance models which include maternal-infant HIV-1 transmission for understanding protective immunity to HIV-1, and long term nonprogressors and elite controllers to understand natural attenuation of disease progression. A more recent focus of research efforts is in the field of paediatric HIV cure. This encompasses studies of the viral reservoir and host biomarkers in the context of very early antiretroviral treatment of infants as part of the LEOPARD clinical trial being conducted in Johannesburg, and detailed exploration of the recent case of the HIV-infected South African child in long-term remission. This case offers a unique opportunity to find clues as to what might make long-term remission possible for more individuals, and could help inform the search for the more challenging goal of a complete cure for HIV.
The section focuses on the implementation of HIV surveillance for prevalence, incidence and drug surveillance including the Annual Antenatal HIV survey. South Africa has the world’s largest antiretroviral treatment programme with 4.3 million PLHIV on treatment. Monitoring of HIV drug resistance is thus a key part of the sections activities. Paediatric HIV surveillance and monitoring provides critical dashboards for monitoring and key weekly action reports to reduce missed opportunities for diagnosis and treatment. The section takes advantage of the “Big Data” opportunities. Linking patient-level CD4 and viral load test result data from the NHLS corporate data warehouse and data from the health information system enabled a new analysis of immune recovery. The section supports the monitoring of HIV rapid test quality through a post-market programme. The section has a well-developed sero-molecular diagnostic section in support of its activities including the evaluation of diagnostic technologies and introducing cutting edge and relevant technologies including point of care testing. The section provides the endpoint diagnostic HIV infection results for the major HIV prevention vaccine trials in South Africa and the African region. The section provides technical expert support in various areas and staff are part of national and international expert committees.
The STI Reference section is responsible for providing intelligence on the aetiology of major STI syndromes, as well as antimicrobial resistance data related to gonococcal infections. Findings are communicated annually to the national and relevant provincial health departments in South Africa as well as to those working in public health and directly with STI patients. The STI Reference section undertakes teaching and training activities, assisting with training of medical scientists, doctors, nurses and other healthcare staff. The STI section undertakes operational research relevant to public health and to that end, it has established several international links with STI researchers overseas.
The STI Section undertakes human papillomavirus (HPV)-related surveillance and research. HPV is the cause of almost all cervical cancer, which is the commonest female cancer in South African women aged 15-44 years. Surveillance for HPV infection and genotype prevalence in unvaccinated adolescent girls and young women is important to establish a baseline for monitoring the impact and effectiveness of HPV vaccination of young girls. Additionally, the centre aims to conduct research on primary cervical cancer screening, and the performance and operational characteristics of rapid tests that may be utilised effectively in a screening algorithm.
Defining immunity to SARS-CoV-2 in key South African populations will provide much-needed insights into immune correlates of recovery and of protection. Such immune data will also enable the rapid development of locally relevant antibody-based interventions, key to mitigating the mid- to long-term public health impact of this pandemic in South Africa.
The HIV Virology Section has re-purposed existing HIV platforms to define the kinetics, durability, and targets of SARS-CoV-2 neutralising and non-neutralising B cell responses, in order to isolate monoclonal antibodies for therapeutic utility. The team will determine the titers, kinetics, durability of neutralising antibodies and Fc effector functions to SARS-CoV-2 in longitudinal samples from individuals with mild disease and severe disease, and with or without HIV infection.
They will also adapt their HIV epitope mapping approaches to map the targets of neutralising antibodies and isolate monoclonal antibodies from individuals with potent neutralisation activity and/or Fc activity. They will incorporate into assays SARS-CoV-2 spike protein sequences obtained from local viral surveillance efforts to tailor immune correlates and monoclonal antibodies to be locally useful.
Collaborators: Key aspects of the work are led by Drs Simone Richardson, Thandeka Moyo and Nono Mkhize, working very closely with Dr Jinal Bhiman of NICD CRDM and Prof Carolyn Williamson of UCT.
For collaborative studies please contact:
Prof Penny Moore – email@example.com
In 2020 South Africa, like any other country, has had to manage the new public health threat, namely COVID-19 with all the available measures, including the non-pharmaceutical interventions. Critical to the future management of this health problem if the virus was to become endemic is to have as much detailed information on the epidemic. It was observed early on in the outbreak that there was a spectrum of how transmission occurs. Thus, it was not only individuals who presented with symptoms but also those who were infected and transmitted before developing symptoms.
Critical is the transmission of the virus by those who were infected but who never developed symptoms, i.e. were asymptomatic, as well as those who develop systems much later, i.e. were presymptomatic. The proportion of asymptomatic and presymptomatic infections varies depending on study and range from 20% to 40% and even higher (70%). Factors that can influence the way the virus is transmitted include spatial geography, population density, demographics, adherence to non-pharmaceutical interventions, immune or genetic factors. Essential information on how many South Africans acquired the infection is needed. Seroprevalence studies, i.e. how many people have produced antibodies against the new virus is how this information is collected.
The critical epidemiological questions include (1) what number of South Africans were infected with the virus, (2) the age distribution of the those infected and (3) the number of persons who had asymptomatic infections at the time of testing. Community acceptance and involvement will be essential factors for the success of the study. Two cross-sectional studies 6-8 weeks apart will be conducted across South Africa. The studies intend to enrol under 20,000 people from 6300 households. The numbers of participants in the study (sample size) will provide an accurate estimate of the numbers of South Africans who have been infected by the virus. A questionnaire will collect information on the risk factors for infection and questions on symptoms that are COVID-19 related. Also, a blood sample will be collected to measure antibodies to the virus. Various statistical analyses will be performed to answer the questions that the survey sets out to answer. Following data analysis feedback will be provided.
Since the beginning of 2020, the majority of countries in the world have been facing the global public health pandemic of coronavirus disease (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To date, very little is known internationally and nationally about the magnitude and determinants of the epidemic, as prevalence is estimated mainly from confirmed cases based on polymerase chain reaction (PCR) testing for patients who have mild to severe symptoms. The proportion of asymptomatic and presymptomatic cases in the general population is unknown and marks an important goal of the present study. More specifically, the proposed study has two primary objectives:
- To determine the extent of SARS CoV-2 virus infection in the general population with age-specific infection cumulative incidence, as determined by seropositivity; and
- To determine the proportion of asymptomatic or subclinical COVID-19 infections.
The secondary objectives of the study are:
- To determine risk factors for COVID-19 virus infection
- To estimate the prevalence of SARS-CoV-2 antibodies in age and sex sub-groups
- To assess antibody levels quantitatively and neutralising antibody concentrations for future comparisons with correlates of protection for herd immunity estimations
- To assess cytotoxic T-cell responses in a sub-group of participants who have and do not have antibody responses, in order to identify what proportion of individuals may have been infected with SARS-CoV-2 but do not have detectable antibodies
The proposed study will use two waves of cross-sectional population-based household seroprevalence surveys. The study will be implemented in all nine provinces in South Africa. The survey will target all the locality types (urban areas, rural formal and rural informal areas) within the selected geographic area (Small Area Layer, SAL).
A random sample of 6,390 households from 426 SALs will realise an estimated eligible sample of 19,170 respondents, based on the assumption of an average of three people per household. Considering the assumed response rate, it is estimated that 13,419 sero-tests will be completed nationally.
Overall, two survey waves are planned that will be initiated at the beginning of September 2020, and that will be repeated in mid-November 2020.
Each survey wave will be conducted for over 6-8 weeks and will consist of two distinct phases. In Phase 1, 18 junior researchers from the HSRC will undertake preliminary community entry visits and engage with community gatekeepers before the arrival of the data collection teams. During Phase 2, fieldworker teams, each consisting of a driver, a supervisor and six field workers, will be deployed into the selected SALs across all the nine provinces in the country. The fieldworkers will all be qualified phlebotomists who will conduct short interviews using tablets and also collect blood through venesection for serology testing.
The interviews will be based on a short questionnaire adapted from the World Health Organization (WHO) COVID-19 study questionnaire and will be used for obtaining information at the individual level on socio-demographic characteristics and various key risk factors for COVID-19 virus infection. Information includes the history of COVID-19 infection, history of exposure to contacts, co-morbidities, and behavioural prevention practices such as hand washing and social distancing. Heads of households will be asked to complete an initial questionnaire that will be used for household enumeration. The data collected with the tablets will be sent to the central server at the HSRC’s main office in Pretoria for management and storage.
Blood collected will be couriered under cold-chain conditions and within 24 hours, to the National Institute of Communicable Disease (NICD) for serology testing.
The prevalence of infection, taking into account the survey weights, stratification and clustering will be calculated and descriptive statistics used to illustrate the prevalence of COVID-19 antibodies (IgM and IgG) among the study population, differentiating between the population which exhibited symptoms and those who were asymptomatic. The risk factors associated with being exposed to the COVID-19 virus, and those who are not infected will be determined through multiple regression analysis. Furthermore, we shall also measure both T-cell responses to specific viral antigens and neutralising antibodies in a sub-study to better understand the immune responses and for future comparisons with correlates of protection for herd immunity estimations.
Intended feedback on the study
The study was requested by the COVID-19 Ministerial Advisory Committee (MAC) to inform both the modelling of the disease and other decisions that will be taken by the government of South Africa to mitigate the impact of the epidemic on the country. Results will be reported to the Minister of Health, the COVID-19 MAC, and the National Department of Health. It will also be published in peer-reviewed journals and presented to both national and international conferences.
Principal investigators (PIs): Leickness Simbayi, Sizulu Moyo (Human Sciences Research Council)
Co-PIs: Khangelani Zuma, Nompumelelo Zungu, Edmore Marinda, Sean Jooste (Human Sciences Research Council), Adrian Puren (National Institute of Communicable Diseases), Lynn Morris (National Institute of Communicable Diseases)
LEADERSHIP AND TEAM
Prof Adrian Puren was trained and held a lectureship at the University of the Witwatersrand, before taking on various positions at the NICD. Adrian was appointed as Deputy Director and Head of Virology in 1999 and Head of the Centre for HIV and STIs in 2017. As head of virology, he focused on developing and implementing a range of viral diagnostic platforms in support of the NICD’s EPI surveillance programmes and diagnostic support. Adrian’s main interest is in the development of HIV surveillance programmes with a particular focus on HIV incidence and the use of “big data” to inform surveillance, monitoring and evaluation. Prof Puren heads the regional and national endpoint diagnostics laboratory for HVTN-supported vaccine and antibody-mediated preventions trials.
He serves as the quality assurance technical manager for the NICD and in this capacity, he has provided support to the National Department of Health’s implementation and quality assurance of HIV rapid testing. Prof Puren serves on various expert bodies and the most recent is the South African Lancet Commission on High Quality Health in the era of Sustainable Development Goals.
Dr Ahmad Haeri Mazanderani