Trends of Two Epidemic Multidrug-Resistant Strains of Mycobacterium tuberculosis in Argentina Disclosed by Tailored Molecular Strategy

Johana Monteserin Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;
Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina;

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Laura Pérez-Lago Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;

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Noemí Yokobori Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;
Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina;

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Roxana Paul Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;

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Sandra Rodríguez Maus Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;

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Norberto Simboli Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;

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Vegard Eldholm Norwegian Institute of Public Health, Oslo, Norway;

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Beatriz López Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;

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Darío García de Viedma Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain;
CIBER Enfermedades Respiratorias, CIBERES, Madrid, Spain

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Viviana Ritacco Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina;
Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina;

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Two Mycobacterium tuberculosis strains—M (sublineage 4.1) and Ra (sublineage 4.3)—have long prevailed in Argentina among patients with multidrug-resistant tuberculosis (MDR-TB). Recently, budget constraints have hampered the surveillance of MDR-TB transmission. Based on whole-genome sequence analysis, we used M- and Ra-specific single nucleotide polymorphisms to tailor two multiplex allele-specific polymerase chain reactions (PCRs), which we applied to 252 stored isolates (95% of all newly diagnosed MDR-TB cases countrywide, 2015–2017). Compared with the latest data available (2007–2009), the M strain has receded (80/324 to 20/252, P < 0.0001), particularly among cross-border migrants (12/58 to 0/53, P = 0.0003) and HIV-infected people (30/97 to 7/74, P = 0.0007), but it still accounts for 4/12 new cases of extensively drug-resistant TB. Differently, the Ra strain remained stable in frequency (39/324 to 33/252) and contributed marginally to the extensive drug-resistance load (1/12). Our novel strategy disclosed recent trends of the two major MDR-TB strains, providing meaningful data to allocate control interventions more efficiently.

Author Notes

Address correspondence to Darío García de Viedma, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, C/Dr. Esquerdo 46, Madrid 28007, Spain, E-mail: dgviedma2@gmail.com or Viviana Ritacco, Servicio de Micobacterias, INEI ANLIS, Vélez Sarsfield 563, Buenos Aires C1282AFF, Argentina, E-mail: vivianaritacco@gmail.com.

Financial support: This work was supported by the ERANet-LAC (TRANS-TB-TRANS Project ELAC2015/T08-0664), the ISCIII (AC16/00057, 15/01554, 16/01449, 18/00599, CP15/00075, and contract number MS15/00075), and the ANPCyT (grant number PICT-2016-3219). This work was cofunded by European Regional Development Funds from the European Commission: “A way of making Europe”.

Authors’ addresses: Johana Monteserin, Noemí Yokobori, and Viviana Ritacco, Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina, and Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina, E-mails: johamonteserin@gmail.com, kaoru.noemi@gmail.com, and vivianaritacco@gmail.com. Laura Pérez-Lago and Sandra Rodríguez Maus, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, E-mails: lperezg00@gmail.com and srodriguezm86@gmail.com. Roxana Paul, Norberto Simboli, and Beatriz López, Instituto Nacional de Enfermedades Infecciosas ANLIS, Buenos Aires, Argentina, E-mails: rpaul@anlis.gov.ar, nsimboli@anlis.gov.ar, and bealopez@anlis.gov.ar. Vegard Eldholm, Norwegian Institute of Public Health, Oslo, Norway, v.eldholm@gmail.com. Darío García de Viedma, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain, and CIBER Enfermedades Respiratorias, CIBERES, Madrid, Spain, E-mail: dgviedma2@gmail.com.

These authors contributed equally to this work.

These authors contributed equally to this work.

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