First Isolation of a Oseltamivir-Resistant Influenza A... : The Pediatric Infectious Disease Journal (original) (raw)

Letters to the Editor

First Isolation of a Oseltamivir-Resistant Influenza A (H1N1) Strain in Argentina

Cané, Alejandro MD; Casanueva, Enrique MD; Iolster, Tomás MD; Sticco, Nicolas MD; Richards, Lucía MD; Sosa, Patricia MD; Pontoriero, Andrea PhD; Avaro, Martín BSc; Zcech, Andrea BSc; Carabajal, Eliana BSc; Campos, Ana BSc; Baumeister, Elsa PhD; Diez, María Avila BSc; Rojas, María BSc; Rivarola, Manuel Rocca MD

Infectious Diseases Section Department of Pediatrics (Cané, Casanueva)

Pediatric Intensive Care Unit (Iolster)

Department of Pediatrics (Sticco)

Bone Marrow Trasplantation Unit Hospital Universitario Austral (Richards, Sosa)

Respiratory Viruses Service Department of Virology National Institute of Infectious Diseases (ANLIS) “Carlos Malbrán” Buenos Aires, Argentina (Pontoriero, Avaro, Zcech, Carabajal, Campos, Baumeister)

Virology Laboratory Department of Virology (Diez, Rojas)

Department of Pediatrics Hospital Universitario Austral Derqui-BuenosAires, Argentina (Rivarola)

The Pediatric Infectious Disease Journal 29(4):p 384, April 2010. | DOI: 10.1097/INF.0b013e3181cd7244

To the Editors:

Community isolates of the influenza A (H1N1) virus related to the ongoing pandemic have been found to be susceptible to oseltamivir.1 This is the first observation of resistance to oseltamivir in a pandemic influenza A (H1N1) virus in Argentina.

The mutation consists of the substitution of histidine to tyrosine at amino acid position 275 (H275Y) in the neuraminidase segment of the gene. This mutation could be observed in individuals taking oseltamivir. Furthermore, a theoretical possibility exists that oseltamivir-resistant may be acquired through reassortment in the future.

We report a 3-year-old child who received unrelated bone marrow transplantation. He developed upper respiratory tract infection. According to epidemiologic data (influenza A H1N1 pandemic), we obtained respiratory secretions samples to detect flu through real-time polymerase chain reaction (RT-PCR) and he received treatment with oseltamivir. He continued oseltamivir prophylaxis. Due to another febrile episode with respiratory distress, oseltamivir was increased to treatment dosage for 10 days. We demonstrated persistence of influenza A by RT-PCR, despite treatment and prophylaxis strategies. Weekly RT-PCR test were performed. The first negative result for influenza A H1N1 was obtained almost 70 days after first isolation.

We confirmed the viral genome of the H1N1 influenza in 3 samples of respiratory secretions by a RT-PCR following the CDC protocol.1 We also amplified and sequenced the segment that encodes for the viral neuraminidase containing the 275 position.2 We demostrated a H275Y mutation associated with oseltamivir resistance.3

Comment: We confirmed oseltamivir-resistant 2009 pandemic influenza A (H1N1) virus infection in an immunocompromised Argentinean child who received oseltamivir. Neither mutations were found in surveillance specimens from sentinel sites, suggesting that it were not widespread in Argentina.

This case highlights a potentially adverse outcome from oseltamivir chemoprophylaxis. World Health Organization reported oseltamivir resistance in patients who developed pandemic H1N1 infection while receiving oseltamivir chemoprophylaxis.2 We think, our patient developed resistance while receiving a subtherapeutic once a day chemoprophylaxis dosage, rather than the appropriate treatment.

Postexposure chemoprophylaxis should be reserved for high-risk patients for influenza-related complications who had contact with someone infected with influenza. Emphasis on early treatment, should reduce opportunities for development of oseltamivir resistance.4 In our opinion, chemoprophylaxis should not be used for prevention among healthy persons. Patients receiving antiviral treatment should be instructed to contact a physician if symptoms worsen. Chemoprophylaxis failure is known to occur even without antiviral resistance.5 However, if symptoms develop during chemoprophylaxis, providers should consider the possibility of antiviral resistance.

Alejandro Cané, MD

Enrique Casanueva, MD

Infectious Diseases Section Department of Pediatrics

Tomás Iolster, MD

Pediatric Intensive Care Unit

Nicolas Sticco, MD

Department of Pediatrics

Lucía Richards, MD

Patricia Sosa, MD

Bone Marrow Trasplantation Unit Hospital Universitario Austral

Andrea Pontoriero, PhD

Martín Avaro, BSc

Andrea Zcech, BSc

Eliana Carabajal, BSc

Ana Campos, BSc

Elsa Baumeister, PhD

Respiratory Viruses Service Department of Virology National Institute of Infectious Diseases (ANLIS) “Carlos Malbrán” Buenos Aires, Argentina

María Avila Diez, BSc

María Rojas, BSc

Virology Laboratory Department of Virology

Manuel Rocca Rivarola, MD

Department of Pediatrics Hospital Universitario Austral Derqui-BuenosAires, Argentina

REFERENCES

1.CDC. Drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. MMWR Morb Mortal Wkly Rep. 2009;58:433–435.

2.Tommy WC, Leung Amy LS, Tai Peter KC, et al. Detection of an oseltamivir-resistant pandemic influenza A/H1N1 virus in Hong Kong. J Clin Virol. 2009;46:298–299.

3.World Health Organization. Pandemic (H1N1) 2009: update 60. Geneva, Switzerland: World Health Organization; 2009. Available at: http://www.who.int/csr/don/2009_08_04/en/index.html.

4.World Health Organization. Influenza A (H1N1) NA-H274 detailed pyrosequencing protocol for antiviral susceptibility testing. Geneva, Switzerland: World Health Organization; 2009. Available at: http://www.who.int/csr/resources/publications/swineflu/NA_DetailedPyrosequencing_20090513.pdf.

5.Cowling BJ, Fang VJ, Riley S, et al. Estimation of the serial interval of influenza. Epidemiology. 2009;20:344–347.

© 2010 Lippincott Williams & Wilkins, Inc.