Introducing liquid culture in resource-limited countries
Worldwide, tuberculosis remains one of the primary causes of death from a single infectious agent.
One of today's major public health concerns is that since there is no cure for some multidrug-resistant strains of Mycobacterium tuberculosis (M.tb.),
the disease may spread rapidly over the globe. Pulmonary TB is the most prevalent form of the disease and can be diagnosed
through a combination of chest x-rays, sputum smear microscopy, culture samples and symptoms.
Since microscopy is only 30 – 60% sensitive, and does not distinguish the drug-sensitive from drug-resistant form
of the disease, the gold standard for TB diagnosis is the cultivation of M.tb. on a variety of different specimens.
Both solid and liquid cultures are more sensitive than microscopy and allow the use of cultivated bacteria for other studies
such as genotyping, an important technology in clinical research for the investigation of disease-associated genes
and drug susceptibility testing. Despite improvements in diagnostic technologies, a percentage of patients do not receive
bacteriological confirmation of disease and are only diagnosed on the basis of high clinical suspicion and response to anti-TB drugs.
Recent progress in the field of molecular biology and major advances in the understanding of the molecular basis of drug resistance have provided new tools for rapid and accurate diagnosis. However, the high cost of these molecular diagnostic platforms, the need for sophisticated equipment and highly trained technicians have made their implementation in low-income countries virtually non-existent.
What is FIND doing?
As a result of a special pricing agreement with Becton, Dickinson and Company (BD), the maker of the most commonly-used liquid culture system
for TB (MGIT), FIND carried out demonstration studies to examine the feasibility and potential impact of expanded use
of liquid culture for case detection and DST using BD’s liquid culture technology, which dramatically shortens mycobacterial
recovery time and improves patient management. A second novel assay, a lateral flow test for Mycobacterium tuberculosis
species identification, was also included in the demonstration projects. The rapid method launched globally by FIND
(Capilia TB from Tauns) to differentiate M. tb. complex from other mycobacterial species in culture was also found to be very effective.
The projects were run in eight countries over the period of one year and involved over 100,000 patients.
Lesotho country's laboratory
In Lesotho, it was shown that if a laboratory infrastructure is sufficiently robust, liquid culture
and liquid culture-based DST systems can be incorporated in lower income countries to effectively diagnose MDR TB
and sputum smear-negative TB in HIV-positive patients, childhood TB, and extra-pulmonary TB. As expected,
the South African studies confirmed that liquid culture was faster and more sensitive for mycobacterial isolation
than culture on solid media. This is especially important when treating drug-resistant strains of M. tb., since delays
in appropriate treatment occur only too frequently and can be lethal. Liquid systems increase the case yield by 10%
over solid media and decrease detection time, thus contributing significantly to improved patient management.
On the other hand, although liquid media systems are more sensitive than solid culture, they can be tricky to use since
they are prone to bacterial contamination, including an increased frequency of non-tuberculous mycobacterial (NTM) substances.
The WHO endorses use of liquid culture
In March 2007, study results from FIND demonstration projects showed that liquid culture and DST systems can be feasibly implemented in lower income settings and improve the diagnosis of MDR TB and AFB smear-negative pulmonary TB. The performance data from these studies were submitted to WHO for review by the Strategic and Technical Advisory Group for Tuberculosis (STAG-TB) and technical experts, who recommended the use of liquid culture for DST and rapid speciation along with rapid speciation for TB case detection in low income settings. This new formal WHO process for international policy development related to diagnostics was created in response to the emergence, after many years of stagnation, of a number of new TB diagnostic tools for the public health sector. More
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