Laboratory Strengthening

Effective laboratories are essential to tuberculosis control not only for diagnosing infectious cases, but also for detecting multidrug-resistant strains of TB. Since 2004 The Union's Laboratory Strengthening Programme has offered technical assistance, provided training and conducted operational research to strengthen national laboratory networks and improve their performance. Activities are conducted or coordinated primarily from the Mycobacteriology Unit of the Institute of Tropical Medicine in Antwerp, Belgium, where most of The Union laboratory staff is based.

Improving TB diagnosis with smear microscopy

Diagnosing infectious tuberculosis is the first step in TB control, and the most appropriate way to do this is to examine sputum smears under a microscope to detect acid-fast bacilli (AFB). Standardised techniques for smear microscopy have been available for many years, but the low detection rate of overall TB cases, not just the most infectious smear-positive ones, is recognised as one of the primary obstacles to successful worldwide TB control. New and far more efficient
techniques such as LED fluorescence microscopy have come within reach of the low-income countries in recent years, and The Union is in the forefront to promote their widespread use and to solve the remaining logistical hurdles as the probably most efficient and widely applicable method to reduce the proportion of cases remaining undetected by the conventional technique. As most recent achievements in this area, The Union laboratory team has been the lead for the development of new tools meant to improve microscopy. Together with experts from other organizations, the old microscopy guides of both The Union and WHO were completely revised and will soon be replaced by one common new guide, incorporating many changes in a highly practical format that can be taken over by countries without modifications. A second new product is a guide for evaluation of microscopy networks, meant to prepare networks rather than individual small laboratories for accreditation. Both projects were USAID/TBCARE sponsored.

Monitoring quality of drug susceptibility testing (DST)

As part of the WHO/Union Global Project for Surveillance of TB Drug Resistance, The Union's collaborating laboratory in Antwerp annually organises rounds of proficiency testing to assure quality of drug susceptibility testing. This starts among labs of the Supra-National TB Reference Laboratory Network or SRLN. National Reference Laboratories are also subject to quality controls, using the same panels, as well as rechecking of routine results. Since 2007, the test panels have included not only strains resistant to first-line drugs (multidrug-resistant TB or MDR-TB), but also second-line drugs (extensively drug-resistant TB or XDR-TB), and in future this will be extended to pyrazinamide and molecular DST  techniques. The panel rounds have also brought to light hitherto unrecognised problems with the main first-line drug, rifampicin, leading to investigations into its causes and possible solutions. Particularly in this era with a change of emphasis towards molecular diagnosis of TB, these efforts have led to important practical conclusions regarding the gold standard, which may make straightforward the use of rifampicin resistant results obtained for instance by the Xpert MTB/RIF system.   

Testing for MDR- and XDR-TB

The Union has focused on building laboratories' effectiveness and efficiency in identifying MDR- and XDR-TB since 2008. The goal has been to find a more efficient strategy for surveillance of resistance to the main first- and second-line drugs, in addition to providing rapid and accurate diagnosis of individual cases. At the same time The Unions' laboratory team has successfully developed a short and highly effective treatment regimen for MDR-TB in Bangladesh, together with the
Damien Foundation. The full involvement of the Antwerp SRL has been instrumental in this endeavour, and also to study the resistance determinants for its outcome in all details. This and other work will allow defining more precisely the settings in which the regimen can be expected to yield equally good results. Building further on these achievements, the lab team in Antwerp is now responsible for coordination, quality assurance and reference lab tests for The Union's STREAM clinical trial.

With the spread of multidrug-resistant TB, laboratories are under increasing pressure to identify these bacilli by drug susceptibility testing (DST). The Union laboratory team has been exploring new techniques based on microscopy, suitable for screening and even presumptive diagnosis of severely drug resistant TB at intermediate level laboratories lacking the safety and infrastructure needed for conventional DST.

Building a network of expert laboratories

Another goal has been to expand the SRLN and increase its capacity to monitor and support national tuberculosis programmes (NTP) in middle- and low-income countries and help them achieve and maintain international quality
standards. A new supra-reference laboratory (SRL) was thus created in Thailand in 2006, while Benin, Uganda and Tanzania were intensively tutored between 2007 and 2010, in collaboration with the Amsterdam KIT (Koninklijk Instituut voor de Tropen). As a result of these efforts, Uganda was declared a full SRL by WHO early 2013, and officially obtained laboratory accreditation a bit later. Also Benin was accepted as candidate-SRL by WHO in 2011 and continues to prepare for accreditation. Thanks to these USAID-funded TBCARE projects, both Uganda and Benin already provide support to several countries in their region by means of training, courses, technical assistance visits etc.