An outbreak of extensively drug-resistant tuberculosis among a Portuguese family

<b>Introduction:</b> Drug-resistant tuberculosis usually occurs with inadequate adherence to treatment (acquired resistance). However, MDR/XDR tuberculosis may also be caused by direct infection with a resistant strain (transmitted resistance). Methods and results: We report the clinical and genetic characteristics of XDR-TB cases among a Portuguese family between 2010 and 2013. An outbreak involving four cases of XDR-TB has been detected in three members of the same family and in a close contact. The index case (case 1) was a 34 years old male, drug‑addict, HIV positive, with pulmonary and meningitis TB diagnosed in 2000 - M.tuberculosis with Susceptibility testing (DST) showing susceptibility to all first-line drugs. In 2010 he was diagnosed XDR-TB with relapse in 2012 (DST revealed the same pattern in both occasions: resistance to H, R, Z, E, S, Am, Cm, Eto, Ofx; sensitivity to PAS, Cs and Lzd). In 2012 -2013 his two brothers (21 years old male -case 2; 31 years old female -case 3) and his girlfriend (23 years old -case 4) were diagnosed with XDR TB. DST resistance pattern was similar in all four cases (resistance to H, R, Z, E, S, Am, Cm, Eto, Ofx). Isolates of all four cases harboured identical gene mutations in the genes rpoB and inhA. For transmission confirmation purposes, whole-genome sequencing (WGS) confirmed the resistance profile and genetic relatedness of 3 of the cases (Case 1, 3 and 4). Genotyping of case 2 is ongoing. <b>Conclusion:</b> The distinction between acquired resistance and transmitted resistance is made by the history of previous treatment or by genotyping the different strains - if two people have strains with the same genotype, transmission can be assumed, as occurred in this family.