TB Epidemiology and Intervention Research Unit

Current projects

Administration and Management
Principal Investigator: K Weyer
Project Leader: K Weyer

Objectives: To provide research direction, administrative and management support to baseline and externally funded projects, to secure external contracts and grants and to provide financial monitoring of projects.

Status: Ongoing and productive. Direction and support were provided to 18 research projects (2 baseline, 16 contract/grant). National research activities are coordinated through the SA TB Operational Research Group (consisting of provincial TB Managers and designated researchers) and the DOTSPlus Group of SA (consisting of provincial TB Managers and MDR-TB Hospital Managers). Formal research collaborations were established with several local and international agencies, resulting in contract/grant income to the value of R9.1 million.

WHO Supranational Reference Laboratory
Principal Investigator: J Brand
Project Leader: K Weyer

Objectives: To function as the WHO Supranational Reference Laboratory (SRL) for Africa, with specific responsibilities aimed at strengthening of TB laboratory capacity, development and implementation of quality assurance and proficiency testing programmes, consultancies and reference activities, training of laboratory technologists, bacteriological support to MRC TB research projects, maintenance of the TB laboratories in Pretoria to biosafety level II and III standards, and health monitoring of staff involved in TB research.

Status: Ongoing and productive. Proficiency testing programmes for TB microscopy and culture are maintained in 10 African countries with technical support from the National Health Laboratory Service (NHLS) in SA.

Proficiency testing programmes for TB drug susceptibility testing are maintained in four African countries where WHO-supported drug resistance surveillance is being conducted. NHLS and KwaZulu-Natal laboratories joined the network in 2004.

A two-week training course on TB drug susceptibility testing is formally recognised by WHO and offered to African attendees. Trainees from Tanzania and Malawi attended this course during 2004.

Bacteriological support (microscopy, culture, drug susceptibility testing) was provided to project 2236 (completed, 3 000 specimens investigated) and project 2204 (ongoing, 7 000 specimens investigated).

Six-monthly testing and validation of biosafety cabinets and fume cupboards in the Pretoria TB laboratories were conducted. Precision equipment (microscopes, balances, autoclaves, pH meters, incubators) were serviced and calibrated.

TB screening and health monitoring were provided for internal and external staff members involved in baseline and contract research.

WHO consultancies were conducted for Tanzania, Malawi and Nigeria.

Budget 2003-2004: R80 000

DOTSPlus for MDR-TB patients in SA
Principal Investigator: M van der Walt
Project Leader: K Weyer

Objectives: To evaluate the effectiveness of standardised management of MDR-TB patients in SA, to determine the cost-effectiveness and cost-benefit of DOTSPlus in SA, and to develop an effective model for MDR-TB management as a public health strategy in SA.

Status: Ongoing and productive.

A user-friendly relational computer database was implemented at the nine provincial MDR-TB treatment centres, facilitating data capture, patient management, calculation of outcome indicators and preparation of management reports. Data generated by this system were used internationally to develop a standard set of core variables and outcome definitions for MDR-TB, to be used in international WHO DOTS-Plus pilot projects. Added functionalities to the system included surveillance reporting, automatic calculation of treatment outcomes based on patient-specific bacteriology and treatment data, and data on adherence to anti-retroviral treatment, for MDR-TB patients on both standardised and individualised treatment.

A patient pamphlet containing essential information on MDR-TB was developed. The pocketsize pamphlet is made of durable material and given to patients at the onset of treatment.

DOTS-Plus policy guidelines were updated to allow for highly active anti-retroviral therapy for HIV-positive MDR-TB patients. New policy directives around legal dilemmas in the management of MDR-TB were developed. These Guidelines were implemented as national policy by the Department of Health in 2004.

Ethical and legal dilemmas around MDR-TB management in SA
Principal Investigator: M van der Walt
Project Leader: K Weyer

Objectives: To develop national policy around ethical and legal dilemmas encountered in the management of MDR-TB patients, aggravated by conflicting health legislation.

Status: Ongoing and productive. A case series of typical problems was reviewed by constitutional Court experts, highlighting conflicts between the Constitution and the new Health Act. A policy brief and policy guidelines were prepared to assist the Department of Health with legislative reform.

TB drug resistance in TB-HIV pilot sites in SA
Principal Investigator: J Lancaster
Project Leader: K Weyer

Objectives: To monitor drug resistance levels in two TB-HIV pilot sites in SA where isoniazid is given as TB preventive therapy to HIV-positive individuals as part of a comprehensive package of TB, HIV/AIDS and STI care provided by the Department of Health.

Status: Completed. Findings indicate high levels (>20%) of culture-positivity among persons eligible for isoniazid preventive therapy (IPT), indicating the need for bacteriological culture as a screening tool. Low levels of isoniazid resistance (<10%) were found, which will serve as baseline for roll-out of the national policy on IPT for HIV-positive individuals.

Effectiveness of MDR-TB treatment prior to SA DOTSPlus implementation
Principal Investigators: M van der Walt (MRC), M Pooe (MRC), T Holtz (CDC), A Findlay (CDC)
Project leader: K Weyer

Objective: To evaluate MDR-TB treatment effectiveness prior to DOTSPlus implementation in SA.

Status: Ongoing and productive. Data collection was completed in the Eastern Cape (167 patients), Western Cape (728 patients) and Gauteng (115 patients). Data from the Western Cape (individualised treatment) indicated that 47% of patients had a successful treatment outcome, 32% defaulted, 18% died and 3% failed. Eastern Cape (standardised treatment) data showed 46% successful treatment, 35% default, 15% death and 4% failure. Two-year post-treatment follow-up indicated high mortality (>30%) and high loss to follow-up (>30%) in both groups.

MDR-TB transmission dynamics and infection control strategies
Principal Investigators: K Weyer (MRC), E Nardell ( Harvard University), P Jensen (CDC)
Project leader: K Weyer

Objective: To establish a unique airborne infection research (AIR) facility for studying MDR-TB transmission dynamics in vivo through human and animal (guinea pig) models, with the aim to develop affordable infection control strategies for low-resourced countries.

Status: Ongoing and productive. The project proposal was cleared by human and animal ethics committees at MRC, CDC and Harvard University. A detailed engineering plan was completed by the consulting engineer, outlining the design intent (requirements, criteria, constraints), operational parameters (architectural requirements, air quantity and velocity tolerances, temperature and humidity requirements), animal exposure chambers and husbandry, and solution specifications (architectural work, animal exposure chambers, heating, ventilation and air conditioning systems, UVGI fixtures). A biosafety-level II TB laboratory was established on site. Renovation and construction of the AIR facility is currently underway and patient intake is scheduled for January 2005.

Telemedicine in DOTSPlus pilot sites in SA
Principal Investigator: M Cheche-Kachienga
Project Leader: K Weyer

Objectives: To establish and pilot test telemedicine capacity in DOTSPlus sites in order to investigate suitable communication technologies for MDR-TB management in remote rural areas in SA.

Status: Developmental. Pilot telemedicine workstations were established at two primary and one tertiary care facilities in a remote rural district in Mpumalanga. Electronic protocols for decentralised management of MDR-TB were developed.

Risk factors for default from MDR-TB treatment in SA
Principal Investigators: T Holtz (CDC), J Lancaster (MRC)
Project Leader: K Weyer

Objective: To determine patient and health-service related risk factors for default from MDR-TB treatment in SA.

Status: Completed. Preliminary data analysis showed high loss (35% not found) and high death rates (23%) among defaulters. Univariate analysis indicated dissatisfaction with health care staff attitude as the major determinant of treatment default (odds ratio 9.6, 95% CI 2.7 – 36.6), while gender, age, employment status, use of traditional healers, knowledge about TB and living conditions were not found to be associated with default from MDR-TB treatment.

Paediatric MDR-TB database
Principal Investigator: L Nelson (CDC)
Project Leader: K Weyer

Objective: To provide SA data to a multi-country CDC database on paediatric MDR-TB and the outcome of treatment in these children.

Status: Completed. 63 cases meeting the study inclusion criteria were identified from SA. 46% of SA paediatric MDR-TB cases had a close adult contact, 63% were new MDR-TB cases and 25% had concomitant HIV infection. Treatment with second-line drugs indicated high toxicity, with more than 30% of children experiencing drug adverse effects.

TB Control Programme operational research capacity development
Principal Investigator: K Weyer (MRC), T Holtz (CDC)
Project Leader: K Weyer

Objective: To develop essential epidemiological skills for operational research capacity in tuberculosis control programmes in Southern Africa.

Status: Ongoing and productive. Eight operational research projects are currently being conducted throughout SA by individuals associated with provincial and national tuberculosis control programmes. Site visits by the joint MRC-CDC monitoring team were conducted regularly to provide support. Two projects ( Free State and KwaZulu-Natal) are close to completion.

Prevalence and annual risk of TB infection in Gugulethu, Cape Town
Principal Investigators: S Tsiouris ( Columbia University), J Lancaster (MRC)
Project Leader: K Weyer

Objective: To determine the prevalence and annual risk of TB infection in Gugulethu, Cape Town, in order to establish baseline epidemiological data for anticipated TB vaccine trials.

Status: Completed. 3 000 learners in Grades 1 and 5 in primary schools in Gugulethu were tuberculin tested to establish the prevalence and annual risk of TB infection. Data analysis is currently underway. Project information will provide baseline data on the epidemiology of TB in the area, against which future interventions (particularly new TB vaccines) will be evaluated.

Risk factors for default from TB treatment in SA
Principal Investigators: A Miranda (CDC), M Pooe (MRC)
Project Leader: K Weyer

Objective: To determine patient and health-service related risk factors for default from TB treatment in SA.

Status: Ongoing and productive. Approval from the individual provinces was obtained and the protocol cleared by Ethics Committees at the MRC and CDC. Field interviewers were appointed and trained. Preparation of study sites was completed, including sampling and logistics. Patient interviews started in June 2004.

Electronic TB Register roll-out
Principal Investigator: W Coggin (Department of Health)
Project Leader: K Weyer

Objective: Expansion of the Department of Health Electronic TB Register to all provinces in SA.

Status: Completed. Pilot testing of the new Electronic TB Register was completed in four provinces and the software adapted for SA purposes. Rollout to the other provinces was completed in 2004. Purchase and distribution of hardware to all provinces was completed.

Due to staff constraints only one new activity is anticipated for 2005/06. This activity will form part of the international PEPFAR Initiative by USAID to improve access to HIV care, and will focus on tuberculosis patients.

Project title: Improving access to HIV care for tuberculosis patients in SA through a best-practices approach
Principal Investigator: N Naidoo
Project Leader: K Weyer

Objectives: To improve access to HIV care for tuberculosis patients in SA

Status: Developmental. The study protocol and standard operating procedures are currently being developed in consultation with stakeholders. Logistics are being established and pilot testing of the various research instruments are being conducted.