Transmission of Mycobacterium tuberculosis presenting unusually high discordance between genotypic and phenotypic resistance to rifampicin in an endemic tuberculosis setting

Author(s)

Brandao, Angela Pires ^{[1, 2]} ; Watanabe Pinhata, Juliana Maira ^[1] ; Simonsen, Vera ^[1] ; Oliveira, Rosangela Siqueira ^[1] ; Ghisi, Kelen Teixeira ^[1] ; Silva Rabello, Michelle Christiane ^[3] ; Fukasava, Suely ^[4] ; Ferrazoli, Lucilaine ^[1]

Affiliation

^[1] Adolfo Lutz Inst, Sao Paulo, SP - Brazil

^[2] Fiocruz MS, IOC, Rio De Janeiro, RJ - Brazil

^[3] Fiocruz MS, Ctr Pesquisas Aggeu Magalhaes, Recife, PE - Brazil

^[4] Ctr Vigilancia Epidemiol Estado Sao Paulo, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: TUBERCULOSIS; v. 125, DEC 2020.
• Web of Science Citations: 0

Abstract

Background: Since the implementation of the Xpert MTB/RIF in Sao Paulo, Brazil, numerous Mycobacterium tuberculosis isolates presenting ``rifampicin-resistant genotype with rifampicin-susceptible phenotype{''} were observed. Objective: To evaluate the prevalence, rpoB mutations and transmission of M. tuberculosis resistant to rifampicin on Xpert MTB/RIF but susceptible on BACTEC MGIT system, in Sao Paulo state. Methods: Patients' isolates with this pattern of rifampicin discordance, collected from 2014 to 2017, had their rpoB predominant rifampicin-resistance-determining region sequenced and were genotyped by IS6110 restriction fragment-length polymorphism. Findings: The prevalence of rifampicin-discordant M. tuberculosis with genotypic resistance was 55.1% (156/283). Among the sequenced and genotyped isolates, 75.5% (111/147) were in clusters, largely associated with the type of rpoB mutation. Most isolates (98.6%; 72/73) harbouring the predominant mutation, His445Asn, were pooled into the two largest clusters, SP2ga (42/72; 58.3%) and SP5o (12/72; 16.7%). Ranking second, isolates carrying the silent mutation Phe433Phe were mostly (92.3%; 24/26) gathered into four groups of the family SP25. Conclusion: These findings suggest that this unusual high rifampicin discrepancy proportion was greatly influenced by few actively circulating clusters. Further studies on many of the rpoB mutations identified in our setting are needed to elucidate their association with phenotypic rifampicin resistance. (AU)

• FAPESP's process: 17/16082-7 - Characterization of mutations in clinical isolates of Mycobacterium tuberculosis resistant to 1st and 2nd line drugs and the relationship between mutations and phenotypic resistance levels to isoniazid.
• Grantee: Rosangela Siqueira de Oliveira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/51756-5 - Performance of methods for diagnosis of multidrug-resistant tuberculosis and Extensively Resistant. Applicability in a Reference Laboratory
• Grantee: Lucilaine Ferrazoli
• Support Opportunities: Research Grants - Research in Public Policies for the National Health Care System (PP-SUS)