# Outbreak Caused by Multidrug-Resistant Mycobacterium Tuberculosis with Unusual Combination of Resistance Mutations, Northern Argentina, 2006–2022

Roxana Paul, Federico Lorenzo, Beatriz López, María Gabriela Alegre, David

Couvin, Nalin Rastogi, Laura Pérez-Lago, Darío García de Viedma, Ana

Gamberale, Norma González, et al.

► To cite this version:

Roxana Paul, Federico Lorenzo, Beatriz López, María Gabriela Alegre, David Couvin, et al. Outbreak Caused by Multidrug-Resistant Mycobacterium Tuberculosis with Unusual Combination of Resistance Mutations, Northern Argentina, 2006–2022. Emerging Infectious Diseases, 2025, 31 (3), pp.601-606. 10.3201/eid3103.241272. hal-05028188

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# Outbreak Caused by Multidrug-Resistant *Mycobacterium Tuberculosis* with Unusual Combination of Resistance Mutations, Northern Argentina, 2006–2022

Roxana Paul,<fnref n="1" /> Federico Lorenzo,<fnref n="1" /> Beatriz López, María Gabriela Alegre, David Couvin, Nalin Rastogi, Laura Pérez-Lago, Darío García de Viedma, Ana Gamberale, Norma González, Domingo Palmero, Silvia Altabe, Norberto Simboli, Noemí Kaoru Yokobori

To reconstruct transmission chains of the multidrug-resistant tuberculosis Ch strain, which harbors a unique combination of resistance mutations, we analyzed genomes of 25 isolates from 12 patients with diagnosis during 2006–2022 in Chaco Province, Argentina. Amplification of resistance, high mortality rates, and indications of a wider outbreak raise concerns for surveillance programs.

Argentina is considered a mid-incidence country for tuberculosis (TB); 1% of multidrug-resistant (MDR) cases persist in Argentina. The northern province of Chaco, a province with a top 5 TB burden (1), had a low number of MDR TB cases and no prior evidence of local transmission (2). MDR TB can affect patients beyond the well-established risk groups, making clinical suspicion essential where universal drug-susceptibility testing (DST) is unavailable. Whole-genome sequencing (WGS) enables timely and precise molecular drug-resistance profiling, but genotype/phenotype correlations need further research, especially for rapidly emerging resistance to second-line drugs (e.g., bedaquiline and linezolid) (3).

To reconstruct the transmission chains and drug-resistance profiles, we used WGS to analyze an MDR TB outbreak in Resistencia, Chaco Province, Argentina. The study was performed in accordance with the Helsinki Declaration as revised in 2013. The Research Ethics Committee of the Instituto Nacional de Epidemiología, ANLIS “Dr. Jara,” Buenos Aires, Argentina, approved the project and waived the informed consent requirement (project code YOKOBORI05/2022).

## The Study

During 2018–2019, our laboratory received 9 MDR *M. tuberculosis* isolates from 3 patients of Resistencia, Chaco, that had unexpectedly inconsistent PCR-based resistance profiles for rifampin and isoniazid in isolates from the same patient and between 2 patients with close epidemiologic links (Appendix 1, https://wwwnc.cdc.gov/EID/article/31/3/24-1272-App1.pdf; Appendix 2, https://wwwnc.cdc.gov/EID/article/31/3/24-1272-App2.xlsx). A preliminary genetic analysis showed simultaneous presence of the mutations *rpoB_Asp435His*, *rpoB_His445Asp*,

Author affiliations: Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. C. G. Malbrán,” Buenos Aires, Argentina (R. Paul, F. Lorenzo, B. López, N. Simboli, N.K. Yokobori); Programa de Control de Tuberculosis, Chaco, Argentina (M.G. Alegre, S. Altabe); Université des Antilles, Guadeloupe, France (D. Couvin); Institut Pasteur de Guadeloupe, Abymes, Guadeloupe (D. Couvin, N. Rastogi); Hospital General Universitario Gregorio Marañón, Madrid, Spain (L. Pérez-Lago, D. García de Viedma); Instituto de Investigación Sanitaria Gregorio Marañón, Madrid (L. Pérez-Lago, D. García de Viedma);

Instituto de Salud Carlos III, Madrid (D. García de Viedma); CIBER Enfermedades Respiratorias, Madrid (D. García de Viedma); Hospital Muñiz, Buenos Aires (A. Gamberale, D. Palmero); Instituto Vaccarezza, Buenos Aires (A. Gamberale, D. Palmero); Hospital General de Niños “Pedro de Elizalde,” Buenos Aires (N. González); National Scientific and Technical Research Council, Buenos Aires (N.K. Yokobori)

DOI: https://doi.org/10.3201/eid3103.241272

<footnote n="1">¹These first authors contributed equally to this article.</footnote>
fabG1-inhA_t-8c, and katG_Ser315Thr. We studied that possible outbreak because of the unusual combination of mutations, the extended resistance profile, and the critical disease in young patients with no relevant comorbidities (Table 1).

The Mycobacteria Service, Instituto Nacional de Enfermedades Infecciosas, ANLIS “Dr. C. Malbrán,” Buenos Aires, Argentina, the national reference laboratory for TB diagnosis, has kept an MDR genotyping database, representing nationwide cases, since 2003. After intense screening of our databases, on

the basis of rifampin and isoniazid molecular resistance patterns; province of origin; epidemiologic link, genotype, or both, we identified 29 candidate isolates from 12 patients. Twenty-four isolates were available for WGS analysis (Appendix 1); we assigned an identification number to each isolate. We performed phenotypic DST when we received the isolates unless otherwise stated (Appendixes 1, 2), and we compared spoligotypes with those in the SITVITEXTED database (Appendix 3, https://wwwnc.cdc.gov/EID/article/31/3/24-1272-App3.pdf).

<table><caption>**Table 1.** Characteristics of patients at time of diagnosis of MDR-TB infection with Ch strain, Argentina, 2006–2022*</caption><thead><tr><th>ID</th><th>Residence</th><th>Year</th><th>Age, y/sex</th><th>DR profile†</th><th>DR status</th><th>HIV status</th><th>Comments</th></tr></thead><tbody><tr><td>1</td><td>Resistencia, Chaco</td><td>2006</td><td>57/M</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Unknown</td><td>Index case-patient. No previous treatment records. Died 2 months after diagnosis. Treatment was with INH, RIF, PZA, EMB, and STR.</td></tr><tr><td>2</td><td>Resistencia, Chaco</td><td>2008</td><td>NA/F</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Negative</td><td>Mother of patients 3, 4, and 9. Worked as a nurse at hospital where patient 1 was assisted. Self-administered the second-line drugs. Smear positive for AFB until 2011.</td></tr><tr><td>3</td><td>Resistencia, Chaco</td><td>2010</td><td>14/M</td><td>STR, INH, RIF, EMB, PZA, ETH (2LI, FLQ)</td><td>MDR (pre-XDR)</td><td>Negative</td><td>Son of patient 2. Hepatotoxicity associated with TB drugs. Poor adherence to treatment. Problematic substance use. Died in 2016.</td></tr><tr><td>4</td><td>Resistencia, Chaco</td><td>2010</td><td>16/M</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Negative</td><td>Son of patient 2. Hepatotoxicity associated with TB drugs.</td></tr><tr><td>5</td><td>Resistencia, Chaco</td><td>2014</td><td>66/M</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>Pre-XDR</td><td>Unknown</td><td>Grandfather of patient 6. Repeated treatment changes, suboptimal treatment.</td></tr><tr><td>6</td><td>Resistencia, Chaco</td><td>2014</td><td>15/F</td><td>STR, INH, RIF, EMB, PZA, ETH, FLQ (LZD‡)</td><td>Pre-XDR (XDR)</td><td>Negative</td><td>Granddaughter of patient 5. Her mother, who had lupus, and brother died of TB (Appendix 2, https://wwwnc.cdc.gov/EID/article/31/3/24-1272-App2.pdf). Discharged in 2016 after sputum tested negative. Relapsed in 2017. Referred to a hospital that specialized in DR-TB in Buenos Aires in 2019. Poor adherence to treatment. Smoker.</td></tr><tr><td>7</td><td>Corrientes, Corrientes</td><td>2014</td><td>52/M</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Positive</td><td>Died in 2015.</td></tr><tr><td>8</td><td>Resistencia, Chaco</td><td>2017</td><td>43/F</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Unknown</td><td>TB diagnosed in 2016. Had contact with a TB patient in 1999, but the association with the outbreak is unknown.</td></tr><tr><td>9</td><td>Resistencia, Chaco</td><td>2017</td><td>18/F</td><td>STR, INH, RIF, EMB, PZA, ETH (CAP, ETH)</td><td>MDR</td><td>Negative</td><td>Daughter of patient 2. Irregular treatment and poor adherence. Died in 2021.</td></tr><tr><td>10</td><td>Resistencia, Chaco</td><td>2018</td><td>16/F</td><td>STR, INH, RIF, EMB, PZA, ETH, FLQ (CFZ, BDQ§)</td><td>Pre-XDR (XDR)</td><td>Negative</td><td>Friend of patient 6, who visited her frequently. Repeated treatment changes. Admitted to a pediatric hospital in Buenos Aires in 2019, where she received CFZ/BDQ. Patient complied with treatment; her condition improved, and she was discharged in December 2019. Relapsed and died in 2020 during social isolation because of COVID-19 pandemic.</td></tr><tr><td>11</td><td>Resistencia, Chaco</td><td>2020</td><td>24/F</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Negative</td><td>Irregular treatment. Problematic substance use.</td></tr><tr><td>12</td><td>Del Viso, Buenos Aires</td><td>2021</td><td>21/M</td><td>STR, INH, RIF, EMB, PZA, ETH</td><td>MDR</td><td>Unknown</td><td>Patient was unavailable for follow-up until mid-2022 when he started second-line treatment. Former resident of Resistencia and declared the same address of patient 2 and her family, but their exact relationship is unknown.</td></tr></tbody></table>

<footnote>*BDQ, bedaquiline; CAP, capreomycin; CFZ, clofazimine; DR, drug resistance; EMB, ethambutol; ETH, ethionamide; FLQ, fluoroquinolone; INH, isoniazid; NA, not available; MDR, multidrug-resistant; pre-XDR, pre-extensively drug-resistant; PZA, pyrazinamide; RIF, rifampin; STR, streptomycin; XDR, extensively drug-resistant.; 2LI, second-line injectable drugs.</footnote>

<footnote>†Consolidated DR profiles based on phenotypic and molecular test results. STR was tested phenotypically in all isolates until 2017. The DR profile and DR status of the last isolate are indicated between brackets.</footnote>

<footnote>‡Confirmed phenotypically.</footnote>

<footnote>§Tested retrospectively after the detection of the *Rv0678_114dupIC* mutation by whole-genome sequencing.</footnote>
<figure><img src="image_2.png" /><figcaption>**Figure 1.** Maximum-likelihood phylogenetic tree of the 24 isolates from the MDR *Mycobacterium tuberculosis* outbreak strain Ch, Chaco, Argentina, 2006–2022, analyzed by whole-genome sequencing. Each patient is represented by a colored dot. Labels indicate the patient and isolate identification numbers. Blocks indicate the resistance-conferring mutations detected in each isolate, as indicated below the tree. Scale bar indicates number of substitutions per variable site. MDR, multidrug-resistant.</figcaption></figure>

All patients were residents of Resistencia, except for a patient from the neighboring Corrientes city and a former resident of Resistencia who received their diagnoses in Buenos Aires (Table 1; Appendix 3). Patient 2, a healthcare worker at the hospital where patient 1 was assisted, was the mother of patients 3, 4, and 9. Patient 6 was the granddaughter of patient 5 and frequently visited her friend, patient 10. The remaining epidemiologic links were unknown. Five patients were teenagers at the time of diagnosis (Table 1).

WGS showed a monophyletic group (Figure 1; Appendix 2). We named the clone the Ch strain, and it belonged to lineage 4.1.1 and to the spoligotype international type (SIT) 119 of the X1 family. The highest number of SIT119 clones in the SITVITEXTEND database in the region, without association with MDR, is in Brazil (Appendix 3). The median pairwise single-nucleotide polymorphism distance among the

first isolates from each patient was 3 (range 0–6) (Appendix 2), excluding isolate 8.1, which was 15 single-nucleotide polymorphisms (range 12–17) apart from the others. The most ancestral isolate belonged to the index case-patient, whose diagnosis was made in 2006. Despite the patient having no history of TB treatment, that isolate had the 8 resistance mutations common to the cluster, including the double mutations for isoniazid and rifampin (Table 2; Figure 1), suggesting that the outbreak could have been more extended. Patient 3 was probably the source of 3 secondary pre-extensively drug-resistant cases in the second subcluster. Isolates from the patients with the most recent diagnoses (patients 11 and 12) were closer to the first subcluster (Figure 1).

The resistance mutations had high World Health Organization (WHO) confidence gradings and were concordant with the phenotypic drug-susceptibility testing results (Table 2), except for ethionamide and
<table><caption>**Table 2.** Resistance conferring mutations found in Ch strain isolates from patients with MDR-TB infection, Argentina, 2006–2022*</caption><thead><tr><th>Mutation</th><th>Drug</th><th>Confidence grading</th><th>Phenotype/genotype†</th><th>Concordance</th></tr></thead><tbody><tr><td>rpoB Asp435His</td><td>RIF</td><td>Associated with resistance-interim</td><td>24/24</td><td>Yes</td></tr><tr><td>rpoB His445Asp</td><td>RIF</td><td>Associated with resistance</td><td>24/24</td><td>Yes</td></tr><tr><td rowspan="2">fabG1-inhA t-8c</td><td>INH</td><td>Associated with resistance-interim</td><td>24/24</td><td>Yes</td></tr><tr><td>ETH</td><td>Associated with resistance-interim</td><td>3/24‡</td><td>Partial</td></tr><tr><td>katG Ser315Thr</td><td>INH</td><td>Associated with resistance</td><td>24/24</td><td>Yes</td></tr><tr><td>embB Met306lle</td><td>EMB</td><td>Associated with resistance</td><td>18/24§</td><td>Partial</td></tr><tr><td>embA c-11a</td><td>EMB</td><td>Uncertain significance</td><td>NA</td><td>NA</td></tr><tr><td>pncA Pro54Leu</td><td>PZA</td><td>Associated with resistance</td><td>24/24</td><td>Yes</td></tr><tr><td>rpsL Lys43Arg</td><td>STR</td><td>Associated with resistance</td><td>24/24</td><td>Yes</td></tr><tr><td rowspan="3">rrs a1401 g</td><td>KAN</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td>AMK</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td>CAP</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td rowspan="3">eis c-14t</td><td>KAN</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td>AMK</td><td>Associated with resistance-interim</td><td>0/1</td><td>No</td></tr><tr><td>CAP</td><td>NA</td><td>0/1</td><td>NA</td></tr><tr><td rowspan="3">tlyA Arg18stop (LoF)</td><td>KAN</td><td>NA</td><td>0/1</td><td>NA</td></tr><tr><td>AMK</td><td>NA</td><td>0/1</td><td>NA</td></tr><tr><td>CAP</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td>gyrA Asp94Ala</td><td>FLQ</td><td>Associated with resistance</td><td>10/10¶</td><td>Yes</td></tr><tr><td>rrl g2270t</td><td>LZD</td><td>Associated with resistance-interim</td><td>1/1#</td><td>Yes</td></tr><tr><td rowspan="2">Rv0678_144dupC (LoF)</td><td>BDQ</td><td>Associated with resistance</td><td>1/1</td><td>Yes</td></tr><tr><td>CFZ</td><td>Associated with resistance</td><td>1/1**</td><td>Yes</td></tr></tbody></table>

*Confidence grading according to the World Health Organization Catalogue of Mutations, 2nd Edition (3). AMK, amikacin; BDQ, bedaquiline; CAP, capreomycin; CFZ, clofazimine; EMB, ethambutol; ETH, ethionamide; FLQ, fluoroquinolone; INH, isoniazid; LoF, loss of function; LZD, linezolid; NA, not applicable; PZA, pyrazinamide; RIF, rifampin; Stop, stop codon; STR, streptomycin; 2L1, second-line injectable drugs.

†For the isolates studied by whole-genome sequencing; phenotypically resistant isolates/isolates harboring each mutation are indicated.

‡Fifteen isolates were sensitive, 5 isolates had discordant results between methods, and 1 isolate was not tested.

§Two isolates were susceptible, 3 had discordant results between proportion and MGIT methods, and 1 isolate was not studied.

¶Resistance to low dose of moxifloxacin.

\#Isolate 6.4 had a MIC of 4 mg/L for LZD (suggested cutoff value 0.5 mg/L).

**Isolate 10.4 had a MIC of 2 mg/L for CFZ (suggested cutoff value 0.25 mg/L). Phenotypic resistance to BDQ was implemented in 2021, and isolate 10.4 was tested in the light of the genomic results.

ethambutol, as expected (3). Resistance to the second-line injectable drugs was acquired independently in 3 isolates (Figure 1). Two isolates were extensively drug resistant. Isolate 6.4 had a *rrl_g2270t* mutation, which has recently been associated with linezolid resistance (3), and isolate 10.4 had the loss-of-function mutation *Rv0678_144dupC*. Resistance to linezolid and cross-resistance to bedaquiline were confirmed by phenotypic methods (Table 2). Instances of clofazimine/bedaquiline resistance were acquired shortly after their administration under strict supervision (Figure 2).

No compensatory mutations were found in *rpoC* or *rpoA*. Because both mutations in *rpoB* are expected to have a mild to high fitness cost (4), their simultaneous presence could constitute a unique compensatory mechanism.

Patient 1 died shortly after diagnosis. The mother of patient 2 had received a TB diagnosis in 2010 but refused treatment and died in 2011. The mother and the brother of patient 6 died in 2013 (Appendix 2). Isolates from those patients were not available. Because isolates 3.2, 5.1, and 6.1 were identical (Figure 1), the other 2 relatives could have acquired their infection from patient 3 (Figure 2), but their epidemiologic link remains unknown. Their close relationship, the contemporarity, and their fatal outcomes strongly suggest that those

patients were part of the outbreak (Figure 2). Patient 9 probably experienced relapse from latency and infected patient 12, who lived at the same address before moving to Buenos Aires. Their relationship remains unclear. Patient 2 administered the medication to her family, including the injectable drugs. Some regimens, especially in the first years of the outbreak, were suboptimal and underwent multiple changes. Reports suggest that empathy from some healthcare providers had been insufficient. Three cohabitants received chemoprophylaxis with isoniazid, and no active disease has been reported (Appendix 2).

## Conclusions

The MDR Ch outbreak strain, with its epicenter in Resistencia, Chaco, belonged to the X1, SIT 119 spoligotype, which is infrequent in Argentina (5,6) (Appendix 3). The X family has been associated with high transmissibility (7,8), and SIT119 could have been imported from Brazil, considering the frequent cross-border movements to and from Chaco (Appendix 3). Further phylogenomic studies are warranted to determine the precise origin of that MDR strain.

Several factors converged in the outbreak. It started as intrahospital transmission to a healthcare worker, who spread the disease to her cohabitants (Figure 2).
<figure><img src="image_3.png" /><figcaption>**Figure 2.** Schematic representations of the timeline and epidemiologic links of the MDR *Mycobacterium tuberculosis* outbreak with strain Ch, Chaco, Argentina, 2006–2022. Two subclusters were defined according to the phylogenetic analysis (Figure 1). The symbols represent epidemiologic events. Patients represented with squares were identified as part of the outbreak after comprehensive epidemiologic research in the light of the genomic results (Appendix 2, https://wwwnc.cdc.gov/EID/article/31/3/24-1272-App2.pdf). They had received a clinical diagnosis, and the drug susceptibility profiles were not available. Dot colors represent the drug-resistance status and the mutation found. The exact date of the events indicated with a question mark is unknown. Black arrow indicates administration of bedaquiline to patient 10, and the red arrow indicates implementation of phenotypic drug-susceptibility testing for that drug in Argentina. MDR, multidrug resistant; WGS NA, whole-genome sequence not available; XDR, extensively multidrug resistant.</figcaption></figure>

Despite her background, the family was poorly recep-
tive to and not compliant with treatment. On the other
hand, some healthcare workers were not appropriately
prepared to manage MDR TB. Delayed diagnosis, poor
compliance, and administration of suboptimal regimens
led to long periods of culture positivity, amplification of
resistance, and an alarmingly high mortality rate (53%).
In addition to lack of effective drugs, host and bacterial
genetic factors could have played a role. Several patients
were relatives, which suggests genetic susceptibility to
TB. Conversely, the observed mortality rate suggests
higher virulence of the Ch strain. Although challenging
to assess their relative effect, those biological and soci-
etal factors collectively shaped the outbreak outcome.

We gained valuable insights from our study. The
phylogenetic analysis strongly suggests additional
missing cases, and although no new cases were di-
agnosed, MDR TB surveillance in Chaco must be
strengthened. Of note, Ch genotype can be suspected
by detecting the *rpoB* double mutation through Gen-
eXpert and other molecular tests (data not shown).
Next-generation tools, including novel drugs and

WGS, are available, but clinical suspicion of MDR-
TB remains crucial for their effective use. Continuing
education and active engagement of healthcare pro-
fessionals and the community are vital for managing
future outbreaks.

Acknowledgments

We thank Susana Imaz for the helpful discussion.

This work was supported by PICT-2021-I-GRF1 TI-00049 of the Agencia I+D+i, Argentina. The funder had no role in study design. The authors have no relevant financial or nonfinancial interests to disclose.

Raw sequences were deposited in the European Nucleotide Archive. Accession numbers are available in Appendix 1.

About the Author

Mrs. Paul is a professional of the Servicio de Micobacterias, INEI, ANLIS Dr. "C. G. Malbrán" and the Hospital Piñero, Buenos Aires, Argentina, with a research interest in the microbiological diagnosis of mycobacterial diseases.
## References

1. Argentina Ministerio de Salud. Boletín N° 7 tuberculosis y lepra en la argentina coordinación de tuberculosis y lepra [cited 2024 Nov 30]. https://www.argentina.gob.ar/sites/default/files/2024/04/boletin_tuberculosis_2024_1642024.pdf

2. Ritacco V, López B, Ambroggi M, Palmero D, Salvadores B, Gravina E, et al.; National TB Laboratory Network. HIV infection and geographically bound transmission of drug-resistant tuberculosis, Argentina. Emerg Infect Dis. 2012;18:1802-10. https://doi.org/10.3201/eid1811.120126

3. World Health Organization. Catalogue of mutations in *Mycobacterium tuberculosis* complex and their association with drug resistance, 2nd ed. [cited 2024 Nov 30]. https://www.who.int/publications/i/item/9789240082410

4. Gagneux S, Long CD, Small PM, Van T, Schoolnik GK, Bohannan BJM. The competitive cost of antibiotic resistance in *Mycobacterium tuberculosis*. Science. 2006;312:1944-6. https://doi.org/10.1126/science.1124410

5. Yokobori N, Paul R. Informe técnico sobre la tuberculosis multidrogorresistente en la Argentina, 2023 [cited 2024 Nov 30]. https://sgc.anlis.gob.ar/handle/123456789/2618

6. Monteserin J, Paul R, Gravina E, Reniero A, Hernandez T, Mazzeo E, et al. Genotypic diversity of *Mycobacterium tuberculosis* in Buenos Aires, Argentina. Infect Genet Evol. 2018;62:1-7. https://doi.org/10.1016/j.meegid.2018.04.006

7. Comín J, Cebollada A, Ibarz D, Viñuelas J, Vitoria MA, Iglesias MJ, et al. A whole-genome sequencing study of an X-family tuberculosis outbreak focus on transmission chain along 25 years. Tuberculosis (Edinb). 2021 Jan:126:102022.

8. Bishai WR, Dannenberg AM Jr, Parrish N, Ruiz R, Chen P, Zook BC, et al. Virulence of *Mycobacterium tuberculosis* CDC1551 and H37Rv in rabbits evaluated by Lurie's pulmonary tubercle count method. Infect Immun. 1999;67:4931-4. https://doi.org/10.1128/IAI.67.9.4931-4934.1999

Address for correspondence: Noemí Kaoru Yokobori, Servicio de Micobacterias, Departamento de Bacteriología, INEI, ANLIS "Dr. C. G. Malbrán." Vélez Sarsfield 563, Ciudad Autónoma de Buenos Aires, C1282AFF, Argentina; email: nyokobori@anlis.gob.ar

# etymologia revisited

## Coronavirus

The first coronavirus, avian infectious bronchitis virus, was discovered in 1937 by Fred Beaudette and Charles Hudson. In 1967, June Almeida and David Tyrrell performed electron microscopy on specimens from cultures of viruses known to cause colds in humans and identified particles that resembled avian infectious bronchitis virus. Almeida coined the term "coronavirus," from the Latin *corona* ("crown"), because the glycoprotein spikes of these viruses created an image similar to a solar corona. Strains that infect humans generally cause mild symptoms. However, more recently, animal coronaviruses have caused outbreaks of severe respiratory disease in humans, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and 2019 novel coronavirus disease (COVID-19).

## References:

1. Almeida JD, Tyrrell DA. The morphology of three previously uncharacterized human respiratory viruses that grow in organ culture. J Gen Virol. 1967;1:175-8. https://doi.org/10.1099/0022-1317-1-2-175

2. Beaudette FR, Hudson CB. Cultivation of the virus of infectious bronchitis. J Am Vet Med Assoc. 1937;90:51-8.

3. Estola T. Coronaviruses, a new group of animal RNA viruses. Avian Dis. 1970;14:330-6. https://doi.org/10.2307/1588476

4. Groupe V. Demonstration of an interference phenomenon associated with infectious bronchitis virus of chickens. J Bacteriol. 1949;58:23-32. https://doi.org/10.1128/JB.58.1.23-32.1949

https://wwwnc.cdc.gov/eid/article/26/5/et-2605_article

<figure><img src="image_4.png" /></figure>

Originally published
in May 2020