Scanning electron micrograph of Mycobacterium tuberculosis bacteria, which causes TB.Credit: NIAID

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A common rapid molecular test delivers the wrong results in a proportion of patients with drug-resistant tuberculosis (TB), leading to ineffective treatment, a population level genomic analysis study in southern Mozambique has shown.

Led by Mariana López and Iñaki Comas at the Institute of Biomedicine in Valencia (IBV), in collaboration with Centro de investigação de Saúde de Manhiça (CISM), Maputo, Mozambique, the team used whole genome sequencing (WGS) to study the antibiotic resistance mutations in two cohorts of isolates from tuberculosis patients.

Although routine molecular diagnostic test (GenExpert) has the advantage of being fast, it misses some resistances which has caused multi-resistant outbreaks circulating in Eswatini and South Africa, two countries that border Mozambique.

“We wondered whether these clones were present in Mozambique, and whether the limitations of diagnostic tests were a problem in the study region,” says Mariana López, the co-lead author.

Using genomic sequencing technology, the team characterized drug resistance profiles from more than 600 patient samples collected during two studies in southern Mozambique in 2018, and in 2014.

“The genomic analysis reveals that there are circulating strains resistant to first line drugs that are not detected by front line diagnostics,” says Iñaki Comas, a principal investigator at Institute of Biomedicine in Valencia, who co-led the study.

“This, combined with high transmission of tuberculosis in the area, draws a dangerous scenario where drug resistance can expand under the radar,” he added.

The team identified 30 intercountry clusters involving at least one Mozambican strain and one or more from others. The clusters involved 52 Mozambican samples and 150 from surrounding countries, mainly South Africa (73) and Eswatini (40) but also from Botswana, Malawi, and Zimbabwe; with a cluster size range of 2–35 samples.

The study highlights the role of whole genome sequencing as an evaluation tool of the performance of point of care diagnostics in clinical settings and for surveillance of drug resistance, Comas noted.