sábado, 28 de noviembre de 2009

Outbreak of Antiviral Drug–Resistant Influenza A | CDC EID

EID Journal Home > Volume 15, Number 12–December 2009

Volume 15, Number 12–December 2009
Outbreak of Antiviral Drug–Resistant Influenza A in Long-Term Care Facility, Illinois, USA, 2008
Nila J. Dharan,1 Monica Patton,1 Alicia M. Siston,2 Julie Morita, Enrique Ramirez, Teresa R. Wallis, Varough Deyde, Larisa V. Gubareva, Alexander I. Klimov, Joseph S. Bresee, and Alicia M. Fry
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (N.J. Dharan, M. Patton, T.W. Wallis, V. Deyde, L.V. Gubareva, A.I. Klimov, J.S. Bresee, A.M. Fry); and Chicago Department of Public Health, Chicago, Illinois, USA (A.M. Siston, J. Morita, E. Ramirez)

Suggested citation for this article

An outbreak of oseltamivir-resistant influenza A (H1N1) occurred in a long-term care facility. Eight (47%) of 17 and 1 (6%) of 16 residents in 2 wards had oseltamivir-resistant influenza A virus (H1N1) infections. Initial outbreak response included treatment and prophylaxis with oseltamivir. The outbreak abated, likely because of infection control measures.

Outbreaks of influenza virus infection cause illness and death, especially among residents of long-term care facilities (LTCFs). In addition to annual vaccination and infection control measures, antiviral agents for treatment and prophylaxis are useful components for control of influenza outbreaks in LTCFs (1–4), especially in years with vaccine strain mismatches (4).

Two classes of antiviral agents are licensed for use in the United States: adamantanes (amantadine and rimantadine) and neuraminidase inhibitors (oseltamivir and zanamivir). Circulation of influenza A viruses resistant to both classes of antiviral agents, A (H3N2) to adamantanes and A (H1N1) to oseltamivir, was reported during the 2007–08 influenza season (5). We describe an outbreak of illness in an LTCF caused by 2 influenza viruses, an oseltamivir-resistant A virus (H1N1) and an adamantane-resistant A virus (H3N2), during January 2008.

The Study
The LTCF in Illinois provides housing, healthcare services, and recreational activities for residents with neurologic and developmental medical conditions. During the outbreak, the LTCF housed 583 residents. Building A, the main site of the influenza outbreak, housed 108 residents in 6 wards; 104 (96%) received the 2007–08 influenza vaccine. Of the 685 LTCF employees involved in direct patient care, 385 (56%) received the 2007–08 influenza vaccine on site.

We defined a confirmed case as a positive rapid or reverse transcription–PCR result for influenza virus from January 20 through February 8, 2008, in a resident of the LTCF. Surveillance for new case-patients included obtaining a nasopharyngeal specimen from all residents with new onset of fever or respiratory symptoms or any unusual behavior within 24 hours after illness onset. All specimens were tested by using the QuickVue A and B Influenza Test (Quidel, San Diego, CA, USA). A second specimen was obtained from all persons with positive rapid test results and some (57%) from persons with negative results for confirmation of influenza virus infection and virus subtyping by reverse transcription–PCR. Medical records, vaccination records, resident activity, and visitor logs were reviewed.

Testing for antiviral drug resistance was conducted directly on clinical specimens by pyrosequencing as described (6,7), including identification of the oseltamivir resistance–conferring H274Y mutation in the neuraminidase gene of influenza viruses (H1N1) (H275Y in N1 numbering) and the adamantane resistance–conferring mutations in the matrix 2 protein (7,8). The HA1 portion of the hemagglutinin (HA) gene of the outbreak viruses was sequenced and compared with those of epidemiologically relevant viruses.

Phylogenetic analysis of HA1 was performed by using MEGA version 4.0.1 software (9). A phylogenetic tree was inferred by using maximum composite likelihood available in MEGA version 4.0.1. The outbreak investigation was considered a public health response and granted exemption from review by the Institutional Review Board of the Centers for Disease Control and Prevention.

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