OVERVIEW
OBJECTIVES
FUNCTIONS
CURRENT PROJECTS
LEADERSHIP & TEAM
OVERVIEW
The Centre for Tuberculosis (CTB) was established in 2012. It was formerly known as the National TB Reference laboratory which was incorporated into the CTB with broader functions. In line with the mandate of the NICD, the CTB conducts laboratory-based public health surveillance of TB in South Africa. It continues to serve as a National TB reference laboratory (NTBRL) and was endorsed by the World Health Organization (WHO) as a supranational reference laboratory in 2016. The WHO Prequalification Unit designated the Centre for Tuberculosis, as the first tuberculosis laboratory for performance evaluation effective April 20, 2023 in connection with WHO prequalification of in vitro diagnostics. In addition, CTB contributes to the development of National and Global TB policies and guidelines.
OBJECTIVES
The objectives of CTB are:
- To conduct laboratory-based public health surveillance for drug sensitive TB, drug resistant TB and new drugs for the treatment of TB;
- To provide specialized reference mycobacteriological services to South Africa and the African continent;
- Apply innovative techniques such as next generation tools to improve the diagnosis and treatment of TB and drug resistant TB;
- To initiate applied public health research aimed at providing enhanced intelligence on the drivers and protective factors that underlie the TB epidemic in South Africa; and
- To advise and work closely with the Department of Health on strategic planning of the national TB program and formulate guidelines and policies for the diagnosis and treatment of TB in South Africa.
- Training laboratorians and healthcare workers in relevant laboratory and epidemiologic skills to build local and regional capacity.
FUNCTIONS
The first-ever South African National TB Prevalence survey was a collaboration between the MRC, HSRC, NICD and NDoH. The survey aimed to establish the true burden of pulmonary TB disease in South Africa and was conducted according to the international recommendations of the WHO Global Task Force on TB Impact Measurement. The Centre for TB (NICD) was tasked with providing the laboratory services for the survey. Cases of presumptive TB were detected through an initial screening for TB symptoms and chest X-ray (CXR) of all eligible individuals, and a subsequent bacteriological examination of two sputum samples per individual. All sputum samples were processed for Xpert MTB/RIF Ultra and liquid TB culture. This was one of the first TB prevalence surveys to use the Xpert MTB/RIF Ultra for TB case detection. Findings from the survey were used to develop an algorithm for the management of patients with Xpert ‘Trace’ result. See section ‘’Advancing Diagnostics, Epidemiology and Treatment’’ for the algorithm.
TB Prevalence survey report (Feb 2021)
The CTB conducts and supports other countries to undertake population based survey and research to enhance our understanding of the disease burden and factors impacting on efforts aimed at controlling and eliminating TB and DR-TB. These are aimed at informing policy and practice.
Public Health Surveillance plays a critical role in informing and directing health responses and is a key activity of the CTB. Time series analysis is an important tool applied to monitor success or failure. Additional geospatial analysis is applied to define the epidemic and guide responses.
Microbiologically confirmed tuberculosis 2004-15 South Africa
The incidence of tuberculosis (TB) in South Africa is especially high. Critical to the control and management of TB is universal testing of all individuals with indicator symptoms. This approach has been severely impacted by the COVID-19 pandemic, primarily because of lockdown restrictions. Data and modelled projections described in this report show how the implementation of Level 5 restrictions resulted in a sudden and dramatic decrease in laboratory investigations for TB across all of South Africa’s provinces.
To read the report, please click on the below link
SPECIAL PUBLIC HEALTH SURVEILLANCE BULLETIN (ISSUE 4: 16 Sept 2020)
The centre serves not only as the NTBRL for South Africa, but also as the supranational reference laboratory in Africa. The services provided address complex clinical cases as well as programmatic support and quality assurance to laboratories locally and globally.
Treatment of drug resistant TB has evolved over the last couple of years with new and re-purposed drugs being included in the treatment regimens. The CTB performs drug susceptibility testing for the following new drugs: Bedaquiline, Clofazimine, Linezolid and Pretomanid and monitors resistance to these agents. Early detection ensures that correct treatment is instituted earlier aiding in the control of drug resistant TB.
Innovations are the key to success and the CTB has prioritised this aspect. This advancement is aimed at developing and evaluating novel approaches to improving diagnostic and treatment landscape for TB and DR-TB. The use of next generation technologies has expanded the horizon in addressing challenges with TB control and has been well established at the centre. Several new cutting-edge diagnostic technologies have been evaluated, which include targeted next-generation sequencing (tNGS) technologies for predicting drug resistance. Based on these evaluations and WHO recommendations, national implementation of tNGS is planned for 2025. Other core themes pursued by CTB are understanding transmission dynamics and latency.
Xpert mtb rif ultra_guidance on clinical management of trace_19 december 2019
Standardisation of phenotypic drug susceptibility testing across nhls tb culture laboratories
CTB provides advisory, technical and epidemiological support and training, both locally and regionally, assisting with training of among others medical technologists, medical scientists, epidemiologists, public health and microbiology registrars. The centre has a strong focus on supervising and mentoring postgraduate students (MMed, MSc and PhD), and also contributes to lectures and course facilitation at The University of Pretoria and The University of the Witwatersrand.
FUNCTIONS
NICD Investigators: Farzana Ismail, Shaheed V Omar, Halima Said, Lavania Joseph, Ayanda Shabalala, Carrol Tshabane
Collaborator: Centre for Disease Control, South Africa / USA
This research activity aims to assess Whole Genome Sequencing (WGS) as the primary phylogenetic investigation tool for longitudinal surveillance of transmission in selected regions with relatively high burdens of MDR-TB, improving the detection of high-risk cluster transmissions with outbreak potential and demonstrate the effective use of WGS to improve surveillance by comprehensive detection of drug resistance to guide National policy. Furthermore, the study aims to validate the diagnostic performance of targeted next-generation sequencing (tNGS) assays in predicting drug resistance to first-line, second-line and new anti-TB drugs and diagnostic performance among smear positive and negative samples. The primary findings of the proportion of BDQ resistance prompted investigation of national data, provided a basis of the national BDQ testing and prompted the implementation of targeted next generation sequencing for rapid detection of BDQ resistance
NICD Investigators: Shaheed Vally Omar, Lavania Joseph, Farzana Ismail
Collaborators: TB Control & Management (National Department of Health)
Targeted next generation sequencing (tNGS) assays can be applied directly to clinical specimens without the need for a pure cultured isolate and incorporates targeted amplification of genes associated with M. tuberculosis identification, typing and resistance, as well as a cloud-based automated pipeline for resistance prediction. This study aims to evaluate the diagnostic accuracy of tNGS compared to the current standard of care for patient management to predict drug resistance at a centralized laboratory. The study is the first step in a longer-term vision for the role of tNGS in the fight against DR-TB with important public health impact by changing the management of patients with DR-TB.
NICD Investigators: Shaheed Vally Omar; Lavania Joseph, Farzana Ismail
Collaborators: Columbia University, Emory University, Albert Einstein College of Medicine
Bedaquiline (BDQ) and pretomanid (Pa) are medications from the first novel TB drug classes created since 1968. Combined with a repurposed medication, linezolid (LZD), these new drugs have provided substantial improvements in survival and cure rates. The emergence of widespread BDQ, Pa or LZD resistance could undermine these drugs’ potential. In the study, we will examine the emergence of BDQ, Pa, and LZD resistance in South Africa as treatment with these new drugs is expanded to all drug-resistant TB cases. Samples will be processed for MICs to each of the three drugs and whole genome sequencing.
NICD Investigators: Shaheed V Omar, Harry Moultrie, Lavania Joseph, Halima Said, Farzana Ismail, Thabisile Gwala
Collaborators: PanGens Consortium
The main purpose of this project is to increase Africa’s capacity in genomic epidemiology and to conduct genomic epidemiology of drug-resistant tuberculosis and malaria across 12 African countries. The capacity building strategy will include engagement of Post-docs, conducting of on-site workshops and development of free training virtual materials. The initiative will expand south-south research collaborations, train the next generation of African scientists with cutting-edge techniques, and develop advances in disease surveillance, contributing to the African Union Agenda. The Pan-Africa Network For Genomic Surveillance Of Poverty Related Disease And Emerging Pathogens is part of the EDCTP3 Programme and supported by the European Union. The project was initiated in this reporting period. DR-TB isolates from across the country are being collected and stored for processing since inception of the study. To date over 1000 isolates eligible for this study have been stored in the repository. Currently, routine staff are supporting the activity and once reagents are received, laboratory processing will be initiated to complete the activity. During this period, two staff members participated in the Biobanking and Data Management training held at the MRC in The Gambia in October 20-25, 2024.
NICD Investigators: Shaheed Vally Omar, Thabisile Gwala, Lavania Joseph, Dumisani Ngcamu and Mamello Motsei
Collaborators: Foundation for Innovative New Diagnostics (FIND), Geneva, Switzerland
FIND, the global alliance for diagnostics, and Unitaid recently signed a new US$15.9 million grant to accelerate the introduction of new TB diagnostics, to address access barriers and improve case detection at primary healthcare and community levels. The Drive Diagnostics for Tuberculosis (DriveDx4TB) project is harnessing the power of collaboration to increase TB testing options in primary care clinics and community settings. By working with local communities, as well as manufacturers, in-country partners and the global health organization Unitaid, DriveDx4TB aims to accelerate the development and implementation of next-generation TB diagnostics. During this financial year, three technologies were assessed which include a Point-of-Care TB-NAAT, a near-patient TB-NAAT as well as a Urine LAM assay.
NICD Investigators: Shaheed V Omar & Farzana Ismail
Collaborator: TB Alliance
Pretomanid is a new nitroimidazooxazine antimycobacterial drug. One of the United States (US) Food and Drug Administration (FDA) post-marketing requirements (PMRs) specifies that a 5-year resistance surveillance study should be conducted after the introduction of pretomanid to the market to monitor changes in Mycobacterium tuberculosis complex susceptibility to pretomanid. The primary goal is to conduct a study over a 5-year period to determine pretomanid minimum inhibitory concentrations (MICs) of a sample of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis complex (MTBC) isolates. The CTB has successfully submitted year four data. Testing of year five samples is in progress.
NICD Investigators: Shaheed Vally Omar, Dumisani Ngcamu, Mamello Motsei & Lavania Joseph
Collaborator: The European Committee on Antimicrobial Susceptibility Testing
The purpose of the calibration portion of this study is: to propose quality control (QC) ranges/targets and epidemiological cut-offs (ECOFFs) for the European Committee on Antimicrobial Susceptibility Testing (EUCAST) Middlebrook 7H9 broth (7H9) microdilution (BMD) reference method and to calibrate surrogate methods. Testing has been completed and the results shared with the EUCAST Subcommittee on Antimycobacterial Susceptibility Testing (EUCAST-AMST) for review and recommendation.
NICD Investigators: Shaheed Vally Omar & Lavania Joseph
Collaborator: Janssen Pharmaceuticals
Bedaquiline (BDQ) is a key component in the shortened regimen for drug-resistant tuberculosis. This study aims to investigate the changes in prevalence of BDQ resistance following the increased uptake of the drug in the high burden districts in South Africa.
A total of 2315 people with MDR/RR-TB who had an isolate submitted to the NICD from a sample collected between 1 January 2019 to 31 December 2021 were included in the analysis. This included patients from 7 districts (5 provinces) including those with the highest burden of DR-TB and for representation districts from provinces with a lower burden. Of these, 4 of the provinces account for 77% of the DR-TB burden nationally and the districts included account for ~50% of the national burden.
Comprehensive resistance profiling of these samples was performed which included both phenotypic and genotypic diagnostic methods. In addition, whole genome sequencing (WGS) was performed on these isolates to provide genomic insights into resistance determinants for BDQ, full genotypic characterization of the isolate as well as strain relatedness. Post WGS samples harbouring mutations in any of the genes associated with resistance were then subjected to minimum inhibitory concentration (MIC) testing to determine the association with mutations and MIC. The dataset was then further merged with the electronic drug resistance register (EDRweb) to determine patient outcomes using probabilistic linkages (due to the lack of use of a unique identifier in the South Africa within and between data systems). The findings suggest that transmission of BDQ resistance is occurring within these districts (supported by genomic analysis) and patients with BDQ resistance had a significantly lower clinical success rate when compared to those without BDQ resistance.
LEADERSHIP AND TEAM
Dr Shaheed Vally Omar is a Medical Scientist with specialisation in Microbiology. He obtained an MSc in Medical Microbiology from the University of Limpopo and a PhD from the University of Pretoria. He currently leads the research programme at the Centre for Tuberculosis. He is a Joint Lecturer at the Faculty of Health Sciences, University of Witwatersrand and Extra-ordinary Lecturer at the Faculty of Health Sciences, University of Pretoria.
He has been instrumental in the establishment and implementation of molecular-based applications at the Centre, which shaped capacity to perform molecular typing and Next-Generation Sequencing. His current research focus includes; evaluation of new technologies for detection and drug resistance prediction of Mycobacterium tuberculosis, establishment of breakpoints and critical concentrations for diagnostic laboratory phenotypic drug susceptibility testing of new and repurposed TB drugs, drug-resistance surveillance and latent tuberculosis. Findings from the research programme have been used to guide both local and international policy.
He serves on the Expert Panel and Technical Expert Group advising in his area of expertise for the Foundation for New Innovative Diagnostics and the World Health Organization.
Read more
Administrator
Ria de Villiers
Tel: +27 11 885 5309/5317
Email: riad@nicd.ac.za
Pathologist: NTBRL/SRLN
Farzana Ismail
Email: farzanai@nicd.ac.za
Laboratory Manager: NTBRL/SRLN
Cecilia de Abreu
Email: ceciliad@nicd.ac.za
Scientific Lead
Shaheed Vally Omar
Email:shaheedvo@nicd.ac.za
Scientist: Molecular Epidemiology
Halima Said
Email: halimas@nicd.ac.za
Scientist: Whole Genome Sequencing
Lavania Joseph
Email: lavaniaj@nicd.ac.za
