Technical assistance and support by TB Supranational Reference Laboratory (SRL) in Milan to the EXPAND-TB project funded by UNITAID and to drug resistance surveillance (DRS) activities in countries.
Lack of laboratory capacity is the main bottleneck also for surveillance of resistance to anti- TB drugs (DRS) which is a cornerstone of any effective TB control programme. Surveillance is needed to measure the frequency of drug resistance as a reflection of the effectiveness of prevention and control activities; to accurately forecast the need for patient treatments and plan accordingly; to assess epidemiological trends; and to design new standardized regimens for the treatment of TB and DR-TB. In particular, assessing baseline levels of resistance to fluoroquinolones and pyrazinamide, in addition to rifampicin and isoniazid, is of paramount importance for all countries that are planning to introduce new shorter regimens for the treatment of TB.
Establishing, equipping, financing, and ensuring sustainability of appropriate laboratory networks are challenging, complex and expensive. The establishment of well maintained TB laboratories with appropriate bio-safety measures and equipment for quality assured testing presents the greatest challenges for both initial financing and sustainability. Hence, innovative approaches to expanding TB laboratory services are needed to address different tiers of laboratories with different levels of laboratory testing with good referral mechanisms to higher level laboratories while still addressing the epidemiological disease burden in each country setting. TB Supranational Reference Laboratories (SRLs) play a critical role in strengthening national laboratory networks as a well as surveillance systems to monitor drug resistance.
In 2009, UNITAID approved funding for a project to accelerate access to diagnostics for patients at risk of multidrug-resistant tuberculosis in 27 countries. The EXPAND-TB (Expanding Access to New Diagnostics for TB) Project is a collaboration between the World Health Organization (WHO), the Global Laboratory Initiative (GLI), the Foundation for Innovative New Diagnostics (FIND) and the Stop TB Partnership Global Drug Facility (GDF). The overall goal of the five-year Project is to narrow the huge diagnostic gap in MDR-TB control by expanding and accelerating access to new and rapid diagnostic technologies within appropriate laboratory services at country level, accompanied by the necessary know-how for technology transfer, and ensuring these new technologies are properly integrated within TB control programmes. EXPAND-TB has full ownership by the Ministries of Health of the recipient countries and works on a model of best-practices, learning-by-doing, and optimising resources for laboratory strengthening at country level. EXPAND-TB will be successful only with support of all existing partners inside and outside of each country it strives to serve and assist. Building partnerships around its operations and support is the project’s key feature.
b. Global Project on anti-tuberculosis drug resistance surveillance (DRS)
The Global Project on Anti-Tuberculosis Drug Resistance Surveillance is a collaborative surveillance project coordinated at WHO, and in operation since 1994. The project was begun in an effort to gather comparable data on the prevalence and patterns of anti-TB drug resistance worldwide through use of a standardized surveillance methodology. The objectives of the Global Project are to estimate the magnitude of drug resistance globally, determine trends and provide data to inform WHO policy decisions. Core principles of the Global Project are to ensure accurate and representative sampling of the populations under study, allow for the differentiation of new and previously treated cases and ensure that laboratory results are quality assured.
Since 1994 drug resistance data have been collected from 135 countries worldwide (70% of WHO’s 194 Member States) and are published regularly on WHO Reports. Expanding surveillance of drug resistance to fluoroquinolones and pyrazinamide, in addition to rifampicin and isoniazid, is being recognized of critical importance for all countries that are planning to introduce new shorter regimens for the treatment of TB.Recent developments in molecular biology have opened the door to a new generation of drug resistance testing technologies that are easier to implement on a large scale and provide quicker results. These technologies are now being implemented in several countries for the rapid identification of patients with multidrug-resistant tuberculosis in need of second-line treatment. Effective surveillance systems in countries receiving EXPAND-TB support could make a big difference to capture and make proper use of the data generated using these new technologies. The information produced could greatly assist national health authorities in the identification of the most effective measures to address the epidemic of drug-resistant tuberculosis, including the design of new regimens for the treatment of TB and DR-TB.
c. TB Supranational Reference Laboratory Network (SRLN)
To support the work of the Global Project, the TB Supranational Reference Laboratory Network (SRLN) was created in 1994. Originally, the SRLN constituted fourteen laboratories, volunteering their institutional capacity and own resources to support the Global Project. Between 1994 and 2012, the SRLN was expanded to 33 laboratories (SRLs), largely driven by regional initiatives and institutional interest in joining the network. To ensure proficiency in the SRLN, it was agreed that all SRLs would participate in annual proficiency testing (PT) for drug susceptibility testing using standardized strain panels.
The SRLN continues to be the backbone of the Global Project; and given the pressing need for scaling up laboratory services, an expanded focus for SRL activities and involvement is required. Individual SRLs and the Network are a great technical resource for laboratory scale-up, capacity development in countries and provide truly unique support to the drug resistance surveillance activities in countries. Funding technical support from SRLs to NRLs is essential to meet the necessary scale up of diagnostic laboratory services needed for proper TB control, DRS and introduction of novel TB testing technologies.
Each SRL is linked to one or more countries with a formal Memorandum of Understanding with the Ministry of Health. The SRL therefore represents the preferred technical partner identified by the Ministry of Health to develop national laboratory capacity for TB and strengthen drug-resistant TB surveillance and diagnosis.
d. TB Laboratory Strengthening Technical Assistance (TA)
Sustained and prolonged technical assistance (TA) is considered integral to the success of scaled-up laboratory services. SRLs are supporting primarily current drug resistance surveillance and quality assurance of drug susceptibility testing activities and have not been sufficiently resourced to assist countries with the expansion of routine diagnostic services, technology transfer and implementation of novel, rapid TB diagnostics, external laboratory quality assurance, or training.
The vast majority of technical assistance provided by the SRLN has been as a result of individual and/or institutional commitment and many of the SRLs need to be commended for the work that they have achieved in supporting laboratories in their linked countries with minimal or no funding. Urgently addressing the issue of sustained and adequate funding for the SRLN - given the demand and scope of laboratory strengthening services required - is therefore critical if targets for global scale-up of laboratory capacity are to be achieved.
Sustained TA has to be built upon on-going interaction between the SRLs and the NRLs, thus benefitting from the existing links and working relationships. Specific areas of technical assistance required to build laboratory capacity include the following:
The need for rapid implementation necessitates that this technical support will involve both in-country hands-on training with the continuous monitoring of performance with implementation of these new tools through quality assurance mechanisms and follow-up technical assistance visits.