Questions/Answers

Tuberculosis (TB) and HIV remain a public health priority, and is now the leading cause of death from an infectious disease worldwide. In sub-Saharan Africa, TB incidence rates initially skyrocketed, driven principally by extremely high prevalence rates of HIV infection. South Africa is the country with the largest number of people living with HIV worldwide, and has experienced extremely high rates of TB incidence, prevalence and mortality. HIV contributes to 50% of deaths in South Africa with the highest mortality among those who are severely immunocompromised and not yet receiving ART. South Africa is facing a growing drug-resistant tuberculosis (TB) burden as nationally there remains a large gap between the number of patients diagnosed with (MDR-TB) and those who start treatment. Multidrug-resistant TB (MDR TB) and XDR TB are a growing concern. Despite an increase in diagnosis times, Patients encounter difficulties to access the treatment while new drugs are difficult to come by.

The multi-component research project goals and objectives are: • To ascertain the impact of operationally implementing intensified case finding for TB and HIV in household of TB patients • To reduce waiting time for MDR treatment initiation • To ensure patents with XDR TB receive optimal treatment • To search for safe, effective MDR TB drugs with shortened treatment duration • To describe the aetiology and spectrum of renal disease observed in adult hospitalized HIV-infected patients • To look at determining the time to known latent TB infection status (LTBI) • To screen for TB in pregnancy • To determine if the nicotine patch and nicotine gum effectively reduces smoking more than intensive counseling alone in rural HIV-infected patients attending an antiretroviral clinic • To assist nurses in decentralized clinics to either start IPT for those asymptomatic patients and refer symptomatic patients for evaluation of TB disease • To conduct HIV prevention program such as Medical Male Circumcision • To raise community awareness on TB, HIV, circumcisions and research • To empower government medical officers with research tools • To provide an opportunity for registrars to study for Master of Medicine Degree (MMED) • To provide employment opportunities and career advancement to the community

In attempt to improve the health care delivery system, we established partnerships with the following organizations : • The National Institute for Communicable Diseases (NICD) which is a major global player in infectious disease intelligence like influenza, pneumococcal and TB • The Council for Scientific and Industrial Research (CSIR) in which is one of the leading scientific and technology research, development and implementation organizations in Africa. CSIR undertakes directed research and development for socio-economic growth • The Aurum Institute, a research and health systems management organization that focuses on TB and HIV prevention, treatment and care We conduct the following research projects at hospital and clinic level to inform on policy making: • Renal Impairment in HIV infected patients receiving Tenofovir-Based Antiretroviral Therapy in a South African Hospital - to describe the aetiology and spectrum of renal disease observed in adult hospitalized HIV-infected patients • The Quantiferon gold in tube test (QGIT) study, a cluster randomized trial - to look at determining the time to known latent TB infection status (LTBI) • Screening for TB in Pregnancy, Supplement to: The Effect of Tuberculosis and Its Treatment on HIV-Infected Pregnant Women and Their Infants • Smoking Cessation is a Randomized Clinical Trial - to determine if the nicotine patch and nicotine gum effectively reduces smoking more than intensive counseling alone in rural HIV-infected patients attending an antiretroviral clinic • A cluster randomized trial of nurse-led, symptom-based screening of household child contacts of tuberculosis index cases - to assist nurses in decentralized clinics to either start IPT for those asymptomatic patients and refer symptomatic patients for evaluation of TB disease

The Perinatal HIV Research Unit (PHRU) and Klerksdorp/Tshepong Hospital Complex (KTHC) conduct clinical research to save humanity and provide scientific knowledge on TB and HIV as they are major public health issues. PHRU and KTHC are able to enhance the health care delivery system. We play an active role in identifying individuals with TB and HIV earlier and bringing them into care. The hospital MDR outpatient clinic traces Rifampicin resistant patients and help them access treatment early. Patients are identified and put onto treatment as soon as possible and thus prevent the spread of TB. We also conduct the Bedaquilline Programme - compassionate use for pre XDR patients, where the first pre-XDR patient was cured in North-West Province. The Klerksdorp Clinical Trials Units (KCTU) specializes in biomedical research units which, conducts TB drug sensitive and drug resistant (MDR/XDR) clinical trials of all phases. Our activities aim to achieve the 90-90-90 strategies. Voluntary Medical Male circumcision (VMMC) has been shown to be partially (at least 60%) effective at reducing the risk of HIV acquisition in heterosexual males. VMMC has been recommended by the World Health Organization (WHO) as part of the biomedical HIV prevention strategies for countries with high HIV prevalence. In response to this directive, We have performed over 30 000 circumcisions in Dr. Kenneth Kaunda District. The high volume VMMC sites have also provided an opportunity to conduct research studies on increased number of males seeking the service. These include PrePex Male Circumcision, HIV Incidence comparing the PrePex and surgical methods and Smoking Prevalence Studies.

This multi component public health intervention is conducted in Dr. Kenneth Kaunda District which has an estimated population is 716 272. The PHRU is a research wing liked to the KTHC as a tertiary hospital. The district also has 3 District Hospitals; 9 Community Health Centres; 27 Primary Health Care (PHC) Clinics; 6 satellite and 2 mobile clinics. PHC Nurse Workload (clients per nurse per day) was 24.5, and PHC Doctor Workload was 13.2 in 2015. The annual TB incidence is 696/100,000. TB Successful Treatment is 60%, and Provincial HIV Prevalence is 13%. Matlosana Sub-District has 16 health care facilities situated in 4 local areas/townships; Jouberton, Khuma, Kanana and Tigane and surrounding small towns. Various research projects have been conducted at these health facilities to improve the health care delivery system and inform policy making. The community is the vital component of the project and bears witness to the activities and its impact in improving the health care delivery system. All initiatives and strategies are aimed at improving the public health problems currently encountered

Through the multi-component research project helped address the service delivery challenges: • The Mass ACF study scaled up Active Case Finding for TB and HIV contacts in Matlosana. The strategy highly recommended WHO and was also adopted by the South African National Department of Health (NDoH) • The MDR outpatient clinic reduced the waiting time from more than 2 weeks to less than 5 days. Rifampicin resistant patients are traced and have access to early treatment. Patients are therefore identified and put onto treatment as soon as possible and thus prevent the spread of TB • Hospital medical officers were introduced and familiarized to research. Five registrars were able to study Master of Medicine Degree • Various clinical trials are conducted to search for safe, effective MDR TB drugs with shortened treatment duration • Over 30 000 medical male circumcisions have been performed. The circumcision sites also provides an opportunity to HIV Testing and counselling • We are actively involved in community engagement activities to raise awareness on TB, HIV, circumcisions and research. We also established a 20 member community advisory board (CAB) • We employed 161 research employees of various categories to form part of the health research team. In addition to that, the employees have an opportunity to career development and advancement through formal and informal trainings

We ensured successful implementation of intensified active case finding for TB and HIV in household of TB patients. Patients with HIV and TB were diagnosed early and initiated on treatment early. This best practice is highly recommended by WHO and also adopted by NDoH. The MDR outpatient clinic reduced treatment initiation waiting time from more than 2 weeks to less than 5 days. Through the Bedaquilline programme we ensure patients with XDR TB receive optimal treatment. We conduct clinical trials to search for safe, effective MDR TB drugs with shortened treatment duration. We have performed about 30 000 circumcisions since inception of the VMMC high volume sites in 2012. We are actively involved in community engagement activities to raise awareness on TB, HIV, circumcisions and research. We also established a 20 member community advisory board (CAB). Hospital medical officers were introduced and familiarized to research. Five registrars were able to study Master of Medicine Degree. We currently conduct 20 projects, have 12 upcoming projects and employed 161 people of various health care categories.

The Perinatal HIV Research Unit (PHRU) is a large and complex clinical research organization focusing on TB and HIV treatment and prevention. PHRU in Chris Hani Baragwanath Hospital in Gauteng Province was established 21 years ago. Through expansion and interest in TB, the PHRU Matlosana site in Klerksdorp/Tshepong Hospital Complex (KTHC) was established in 2007 in Matlosana Municipality, a sub-district of the Dr Kenneth Kaunda (KK) health district in North West Province, starting with only 2 employees conducting TB mortality study. This site developed and evolved significantly throughout the years. A major highlight was the Clinical Trials Unit established in 2012 at KTHC Multi-Drug Resistant Tuberculosis (MDR-TB) Unit. The unit commenced with two clinical trials. Due to support from the hospital, commitment and hard work of the research team, the unit developed and currently conducts several clinical trials, other TB diagnostic and biomarkers studies

The initial 2 clinical trials were completed successfully and we received international recognition and we are approached by different funders with an attempt to collaborate and conduct more research studies. We currently employ 161 employees of various health professions. There is an on-site data management centre, three clinical facilities with consulting rooms, offices, counselling room, specimen processing room, pharmacy, a–80oC freezer and a cooled centrifuge. We have access to hospital facilities for radiological investigations and research specimens are couriered to one of three laboratories in Johannesburg daily. In 2012, PHRU received funding to start the Voluntary Medical Male Circumcision (VMMC) program. The high volume VMMC sites were established in Klerksdorp/ Tshepong Hospital and Potchefstroom Hospital in 2012. The overall PHRU Matlosana developed significantly.

Yes

Due to the greater impact the project had on the health care delivery system, the project is replicated in other provinces in South Africa. Limpopo Province in Capricorn, Waterberg and Vembhe districts and Free State Province in Botshabelo are conducting the Home Active Case Finding. Gauteng Province is conducting clinical trials, TB biomarkers and diagnostic studies, and also engages in Voluntary Medical Male Circumcision Programme. Free State, Bloemfontein is conducting the Voluntary Medical Male Circumcision Programme.

This multi-component research project started 10 years ago with only 2 employees conducting a small observational study. The project was well sustained as the site now currently employs 161 employees conducting multiple Tb & HIV projects to improve the health care delivery system. we received international recognition and we are approached by different funders with an attempt to collaborate and conduct more research studies

Sustainability of this multi-component initiative depends on availability sponsors and funders. Project activities require revenue to sustain its existence. This calls for various stakeholders to invest and sponsor projects aiming at addressing public health issues. Unfortunately due to economic changes and limitations, the funding for VMMC program ended in September 2017, but our exit strategy ensured that there is skills transfer and capacitation of DoH to continue with the program. Through commitment, hard-work and dedication we strive to attract more sponsors to develop an interest in collaborating with us in doing health implementation projects.

Yes

The PHRU and KTHC highly upholds Good Clinical Principles (GCP) which makes emphasis on restoration and promotion of health and not to inflict harm or cause death. We therefore have internal monitoring and evaluation processes to track and report the progress of projects. Monitoring and evaluation processes are continuous and occur at different time points. In addition to these internal processes, the PHRU is also monitored by external funders, donors and regulatory bodies to monitor compliance to protocol.

We ensured successful implementation of intensified active case finding for TB and HIV in household of TB patients. Patients with HIV and TB were diagnosed early and initiated on treatment early. This best practice is highly recommended by WHO and also adopted by NDoH. The MDR outpatient clinic reduced treatment initiation waiting time from more than 2 weeks to less than 5 days. Through the Bedaquilline programme we ensure patients with XDR TB receive optimal treatment, where the first pre-XDR patient was cured in the province. We conduct clinical trials to search for safe, effective MDR TB drugs with shortened treatment duration. We have performed about 30 000 circumcisions since inception of the VMMC high volume sites in 2012. We are actively involved in community engagement activities to raise awareness on TB, HIV, circumcisions and research. We also established a 20 member community advisory board (CAB). Hospital medical officers were introduced and familiarized to research. Five registrars were able to study Master of Medicine Degree. We currently conduct 20 projects, have 12 upcoming projects and employed 161 people of various health care categories.

• Number of household contacts screened for TB, hypertension and diabetes • Number of patients tested for TB and HIV • Number of patients diagnosed with TB and HIV • Number of patients started on treatment (TB, HIV, hypertension and diabetes) • Prevalence and incidence of TB and HIV • TB treatment completion rate • TB treatment success rate • ART adherence rate • Number of participants enrolled into research studies • Participant decline rate • Participant retention rate • Participant lost to follow-up rate • Serious Adverse Events (SAE) rate

Key stakeholders from the South African Department of Health are responsible for setting the research agenda and collaborating with researchers to implement research projects and utilize the findings in addressing public health priority issues. Engagement activities were held with management from the North-West Province, Dr Kenneth Kaunda District, Matlosana Sub-District and Klerksdorp/Tshepong Hospital Complex to obtain management buy-in and approval multi-component research project. The PHRU also engaged the sixteen health care facilities in Matlosana Sub-District because the facilities are the primary recipient of TB and HIV patients. The nurses from health care facilities were trained on TB and HIV management of patients. Governmental departments in South Africa are often linked to provide services to citizens and such departments linked to the Department of Health are the Department of Social Development and Department of Education. Similarly, local Non-Governmental Organizations (NGO’s) also function in collaboration to serve the community. The two governmental departments and local NGO’s were engaged through activities of the PHRU Community Advisory Board (CAB) to inform them about the multi-component research project and collaborate with them to address these major public health issues.

Stakeholder engagement and support has often been difficult to obtain from key people directly involved in policy formulation and decision making. We have learned that patience, ongoing communication and continuous feedback play an important role to obtain their buy-in. Community members still lack knowledge about research, its importance and how it impacts our daily lives. The great achievement was establishment of the community advisory board (CAB) as these are people from the same community and understand the culture and dynamics involved.