HIV and Hepatitis Research Unit (HHRU)
HIV and Hepatitis Research Unit (HHRU)
Head of Unit: Prof SG Selabe
Contact: gloria.selabe@smu.ac.za
Tel: 012 521 4117/4227
The HIV and Hepatitis Research Unit (HHRU) was established in the early 1980s as the Viral Hepatitis Research Laboratory. The focus of the research undertaken by this unit was initially on the epidemiology of viral hepatitis, caused by various unrelated viruses (hepatitis A virus [HAV], hepatitis B virus [HBV], hepatitis C virus [HCV] and hepatitis E virus [HEV]). In the late 1980s, the focus turned to measuring plasma-derived vaccine immunogenicity and efficacy against HBV infections, with the work being done by this unit informing the South African National Department of Health’s (SANDoH) decision to include vaccination against HBV in the country’s EPI-SA in April 1995. Post-introduction, the unit focused on testing effectiveness of the vaccine, and conducted the clinical trial that resulted in the introduction of a safer recombinant vaccine against HBV in 2005. In addition, post-introduction research on the identification and molecular characterisation of medically relevant HBV variants, such as vaccine-escape mutants, diagnostic-escape mutants, and treatment-escape mutants, became a major focus area. Other focus areas at that time were on new hepatitis agents such as GBV-C / hepatitis G virus, as well as HBV and HIV co-infection studies. Currently, the HHRU is still actively involved in HBV prevention and control studies, as well as studies on HIV co-infection with HBV and /or HCV. The current research projects / activities of the HHRU include, but are not limited to:
(a) HBV infection in HIV infected and uninfected individuals.
Principal Investigator: Prof SG Selabe
Contact: gloria.selabe@smu.ac.za/gloria.selabe@nhls.ac.za
HBV is the causative agent of hepatitis B (HB), a liver disease with severe outcomes in chronically infected patients, including liver cirrhosis and hepatocellular carcinoma. HBV is highly endemic in South Africa, thus the SANDoH introduced the HB vaccine into EPI-SA in April 1995. While studies conducted by this unit and other South African scientists have shown that the introduction of the HB vaccine has dramatically decreased HBV prevalence in vaccinated populations, our studies have also found high rates of occult HBV (O-HBV) in HIV-positive South Africans. Furthermore, O-HBV has been detected in pregnant women, and babies born to HBsAg-positive and negative women. However, we have limited data on O-HBV infection and their associated mutations in patients on highly active anti-retroviral treatment (HAART), and in HIV-positive and HIV-negative pregnant women and its impact on HBV transmission to their children. Thus this research project provides valuable data that can be used to improve future diagnostic sensitivity for O-HBV infection, limit secondary transmission of HBV, provide critical information on treatment options for O-HBV, and improve our understanding of HBV pathogenesis.
(b) Institutional policies and training in HBV prevention and control, and the infectivity and immunity of healthcare workers (HCWs)
Principal Investigator: Prof RJ Burnett
Contact: rose.burnett@smu.ac.za
This project also falls under the South African Vaccination and Immunisation Centre (SAVIC) umbrella, being a public health project with a laboratory science component conducted within the HHRU. HBV is a highly infectious blood-borne virus, thus unvaccinated HCWs who are exposed to patients’ blood and body fluids are at high risk of being infected. The research conducted by this unit on HCWs working in Gauteng and Mpumalanga provinces, has shown that among South African HCWs (i) the uptake of HB vaccination is sub-optimal; (ii) a large proportion are not protected against HBV infection; (iii) there is a high rate of active infection; and (iv) there is a high rate of O-HBV infection. This unit was the first to report high HBV infection rates in South African HCWs, and is currently undertaking studies to investigate the factors associated with the HBV status of HCWs, as well as to investigate the molecular characteristics of HBV infections in HCWs
(c) Genetic characterisation of HCV infections in patients with and without HIV infection
Principal Investigator: Prof SG Selabe
Contact: gloria.selabe@smu.ac.za/gloria.selabe@nhls.ac.za
Chronic HCV infection is another important cause of hepatocellular carcinoma in sub-Saharan Africa. Although highly effective antiviral treatments are available, there is currently no vaccine against HCV. Furthermore, HCV diversity poses challenges for antiviral therapy, vaccine design and diagnosis. Previously, HCV treatment employed a combination of ribavirin and interferon, which had varying levels of efficacy against different HCV genotypes. Recently, new direct acting antivirals (DAAs) offer the promise of better outcomes with far fewer side effects. However, the emergence of naturally occurring mutations have been observed with the use of DAAs. The presence of drug resistance mutations can affect treatment outcomes, thus an understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. This research project is particularly interested in the molecular characterisation of HCV, with a focus on drug resistance mutations, as well as in HIV-co-infected patients before, during and after cancer therapy.
(d) Hepatitis E virus epidemiology
Principal Investigator: Dr OE Simani
Contact: Omphile.simani@smu.ac.za
The earliest documented outbreak of HEV infection likely occurred in 1950 in Tunisia, and since the early 1980s when HEV diagnostic assays became available, an estimated half of the African countries including, north, south, east and central Africa have reported on hepatitis E infection. These results suggest that HEV infection is not new in Africa and may imply that it is a continent-wide public health problem. Since there is paucity in surveillance data for HEV infection, it is difficult to estimate the disease burden of disease in Africa. As a few outbreaks are likely identified and reported, there is a possibility that outbreaks in Africa are even more common that what the reports imply. A study in South Africa Cape town region found a prevalence of 27.9% which is very high compared to previous reports in the same country (2% to 10%). To address the question of HEV burden of disease and acute infection control, routine HEV sero-prevalence and genotype distribution surveillance is necessary. Therefore, the broad aim of this study is to determine the epidemiology and molecular characteristics of hepatitis E virus strains isolated from five South African Provinces, from human, animal and environmental samples.
(e) HPV and STI Research
Principal Investigator: Dr RL Lebelo
Contact: ramokone.lebelo@smu.ac.za/ramokone.lebelo@nhls.ac.za
In 2017, the most common bacterial STIs reported in South Africa were gonorrhoea with 2.3 million cases, followed by chlamydia with 1.9 million cases. In 2020, WHO reported that 37.7 million people were HIV positive with an incidence of 1.5 million and over 680 000 HIV-related deaths; of most of the infections were from Africa (25.4 million). South Africa has the highest incidence of HIV at an estimated 8.2 million in the world. In 2022 the WHO estimated that over 3.7 billion people <50 years of age have HSV-1 and 491 million people aged 15-49 are infected with HSV-2 worldwide. The human papillomavirus (HPV) is one of the most common sexually transmitted infections (STIs) worldwide. The virus is associated with development of cervical cancer, although not a sufficient cause of the disease alone. Co-infection with other STIs play a huge role in the acquisition of HPV, persistence of HPV infections, and eventually development of cervical cancer. Cervical cancer is a serious public health burden worldwide and the fourth most common cause of female mortality worldwide with 604 000 annual cases and 342,000 deaths estimated in 2021. In South Africa, the incidence and mortality rates are among the highest in sub-Saharan Africa. With 10 702 new cases and 5 870 associated deaths estimated in 2021. Although HPV is associated with over 99% of cervical cancer cases, the virus is also associated with other cancers and benign lesions. For cervical cancer, there are prevention and control measures in place such as (i) cervical cancer screening programs; (ii) HPV vaccination and (iii) treatment for cervical abnormal lesions. Almost all developed countries have now introduced HPV vaccination programs however the picture is different for developing countries especially African countries. Some of these countries have yet to introduce the HPV vaccine into their national immunisation programme. Furthermore, cervical cancer screening programmes in Africa have either collapsed or are non-existent. Due to lack of expertise, capacity and financial contrast, there is the lack of baseline epidemiological data on the circulating HPV types causing cervical cancer and other cancers in most African countries. Therefore, in 2014 a network of HPV researchers was formed to address some of these challenges. The network was formalised through funding from the Flemish Interuniversity Research Council (VLIR)-UOS North-South-South Cooperation Programme, with a HPV and STI reference laboratory being established in the HHRU in 2015. This laboratory serves as a training and teaching centre for clinicians and scientists within SMU, South Africa and Africa, providing (i) testing platform through collaboration or (ii) provision of services, (iii) training and teaching through supervision and mentoring, and finally (iv) providing expertise and assistance with laboratory set up.
As a unit, we conduct research in vaccine preventable diseases (VPDs), vaccinology and cancer-causing viruses’ particularly HPV. The focus of our research is on (i) the epidemiology of HPV infection and HPV-related diseases, (ii) cervical cancer screening tests and methods, (iii) genetic diversity of HPV and (iv) factors associated with HPV acquisition, development of HPV-related diseases and HPV co-infections with other STIs. Our recent research focused on finding better screening tests, methods, biomarkers, and devices that can be used to improve cervical cancer screening programs and thereby increase screening coverage and uptake in South Africa.
(f) Infectious neurological diseases
Principal Investigator: Dr KM Mothapo
Contact: khutso.mothapo@smu.ac.za
South Africa has the largest HIV epidemic in the world, with 6.3 million people living with HIV in 2013. Apart from systemic complications related to HIV infection such as weakened immune system that leave HIV infected patients highly susceptible to opportunistic infections, cancer development, wasting syndrome and HIV-associated nephropathy, HIV is also associated with neurological complications, termed HIV-associated neurocognitive disorders (HAND). HAND can cause significant morbidity and mortality, and affects 12% to 56 % of people living with HIV. Since the introduction of combined antiretroviral therapy (cART), HIV-related mortality has reduced significantly, and life expectancy has dramatically improved. In addition, the severity of HAND declined significantly, since HIV dementia is less commonly diagnosed in the post cART era, with mild neurocognitive impairments being more commonly seen. Although there have been great improvements after the introduction of cART, such as reduced mortality and reduced severity of HAND, African countries still experience a high prevalence of HAND. This might be due to misdiagnosed central nervous system (CNS) opportunistic infections that often remain undiagnosed, including amongst others CNS infections caused by Treponema pallidum, Toxoplasma gondii, Cryptoccocus neoformans, Mycobacterium tuberculosis, Epstein-Barr virus, John Cunningham virus and cytomegalovirus. Therefore, determining the actual cause of neurological complications in HIV infected patients is critical especially in a country highly endemic for HIV, like South Africa. This research project seeks to identify and characterise infectious neurological diseases and is currently investigating potential biomarkers for the diagnosis of HAND.