Diversity in TB bacteria hinders rapid diagnosis in West Africa

Worldwide, Mycobacterium tuberculosis (Mtb) is responsible for the vast majority of tuberculosis (TB) cases. However, there are several other closely related mycobacterial species that cause TB, all part of the Mycobacterium tuberculosis complex (Mtbc).

One of them, Mycobacterium africanum (Maf), causes up to 40 per cent of TB cases in West Africa. TB diagnosis across Africa relies largely on tests optimised to detect Mtb.

A study led by the Medical Research Council Unit, The Gambia and the Antwerp Institute of Tropical Medicine, Belgium, published in PLOS Neglected Tropical Diseases now suggests that in West Africa tests to identify Mtbc in culture miss a substantial fraction of cases, with dire consequences for the patients and for TB control efforts.

Concerned about substantial discrepancies in samples from West Africa between the sputum-based results and the results of rapid tests, Florian Gehre, who is affiliated with MRC and ITM, and colleagues undertook a systematic evaluation of two commonly used rapid TB tests. Both tests detect the product of the mycobacterial mpt64 gene.

The researchers started by comparing the abundance of mpt64 gene product in sputum samples of patients with untreated pulmonary TB caused by Maf 2 (the Maf strain common in The Gambia) or Mtb.

Samples from five patients with Maf 2 TB, they found, had about 2.5 times less mpt64 gene product than those from six patients whose disease was caused by Mtb.

They then prospectively analysed culture isolates from 173 patients with one of the rapid tests, the BD MGITTM TBc ID kit. All of the patients had positive sputum microscopy, and cultures were negative for a second test that detects contamination by unrelated bacteria.

Based on the results, 22 per cent of Maf 2 patients, and 10 per cent of Mtb patients would have been wrongly classified as having non-TB mycobacteria if the tests had not been repeated after Day zero.

At the end of the 10-day window recommended by the BD MGITTM TBc ID manufacturer, 16 per cent of all Maf 2 samples remained negative, compared with only two per cent of Mtb samples.

Their findings, the researchers say, “indicate that MPT64 tests need to be cautiously used in settings where Maf 2 is common.”

However, they also recognize that “given the relatively low cost, limited technical expertise and shorter turnaround time associated with using rapid speciation tests compared to alternative speciation methods, MPT64 rapid tests will likely remain one of the preferred options for timely diagnosis of suspected TB despite the possibility of false negative results.”