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Novel Swine-Origin Influenza A (H1N1) Virus Invest. Emergence of a Novel Swine-Origin Influenza A (H1N1) Virus in Humans. 10.1056/NEJMoa0903810
submited by kickingbird at May, 9, 2009 7:49 AM from 10.1056/NEJMoa0903810

Background On April 15 and April 17, 2009, novel swine-origin influenza A (H1N1) virus (S-OIV) was identified in specimens obtained from two epidemiologically unlinked patients in the United States. The same strain of the virus was identified in Mexico, Canada, and elsewhere. We describe 642 confirmed cases of human S-OIV infection identified from the rapidly evolving U.S. outbreak.

Methods Enhanced surveillance was implemented in the United States for human infection with influenza A viruses that could not be subtyped. Specimens were sent to the Centers for Disease Control and Prevention for real-time reverse-transcriptase–polymerase-chain-reaction confirmatory testing for S-OIV.

Results From April 15 through May 5, a total of 642 confirmed cases of S-OIV infection were identified in 41 states. The ages of patients ranged from 3 months to 81 years; 60% of patients were 18 years of age or younger. Of patients with available data, 18% had recently traveled to Mexico, and 16% were identified from school outbreaks of S-OIV infection. The most common presenting symptoms were fever (94% of patients), cough (92%), and sore throat (66%); 25% of patients had diarrhea, and 25% had vomiting. Of the 399 patients for whom hospitalization status was known, 36 (9%) required hospitalization. Of 22 hospitalized patients with available data, 12 had characteristics that conferred an increased risk of severe seasonal influenza, 11 had pneumonia, 8 required admission to an intensive care unit, 4 had respiratory failure, and 2 died. The S-OIV was determined to have a unique genome composition that had not been identified previously.

Conclusions A novel swine-origin influenza A virus was identified as the cause of outbreaks of febrile respiratory infection ranging from self-limited to severe illness. It is likely that the number of confirmed cases underestimates the number of cases that have occurred.

Triple-reassortant swine influenza viruses, which contain genes from human, swine, and avian influenza A viruses, have been identified in swine in the United States since 1998,1,2 and 12 cases of human infection with such viruses were identified in the United States from 2005 through 2009.3 On April 15 and April 17, 2009, the Centers for Disease Control and Prevention (CDC) identified two cases of human infection with a swine-origin influenza A (H1N1) virus (S-OIV) characterized by a unique combination of gene segments that had not been identified among human or swine influenza A viruses. As of May 5, 2009, cases of human infection with the same novel virus have also been identified in Mexico, Canada, and elsewhere. We report the first 643 confirmed cases of human infection with this virus in the United States.


Patients in Outbreak

On March 30, 2009, in San Diego County, California, a 10-year-old boy with asthma (Patient 1) had an onset of fever, cough, and vomiting. On April 1, he was evaluated in an urgent care clinic, where he received treatment for his symptoms. He recovered from the illness within approximately 1 week. An influenza A virus that could not be sub-typed was identified from a nasopharyngeal specimen that was collected from Patient 1 as part of a clinical trial to evaluate an experimental diagnostic test. As specified by the study protocol, the specimen was then sent to a reference laboratory for further testing and was found to be positive for influenza A virus but negative for both human H1 and H3 subtypes, with the use of real-time reverse-transcriptase–polymerase-chain-reaction (RT-PCR) testing. On April 15, the CDC received the clinical specimen and identified a novel influenza A (H1N1) virus of swine origin. On the same day, the CDC notified the California Department of Public Health, and an epidemiologic investigation was initiated by state and local health department officials and animal health officials. A viral isolate was found to contain genes from triple-reassortant swine influenza viruses that were known to circulate among swine herds in North America and two genes encoding the neuraminidase and matrix proteins that were most closely related to genes of viruses obtained from ill pigs in Eurasia, according to results available in GenBank.

On March 28, 2009, in Imperial County, California, a 9-year-old girl (Patient 2) without an epidemiologic link to Patient 1 had an onset of cough and fever. Two days later, she was taken to an outpatient clinic that was participating in an influenza surveillance project. A nasopharyngeal swab was collected at the clinic. Patient 2 was treated with amoxicillin–clavulanate, and she had an uneventful recovery. The nasopharyngeal specimen was sent to the Naval Health Research Center in San Diego, where an influenza A virus that could not be subtyped was identified. The specimen was shipped to the CDC, where it was received on April 17, and a novel influenza A (H1N1) virus of swine origin was identified. The genotype of the virus was similar to that of the virus isolated from the sample obtained from Patient 1. On April 17, both cases were reported to the World Health Organization (WHO), according to the provisions of the International Health Regulations.

Epidemiologic investigation of Patients 1 and 2 revealed that neither patient had a recent history of exposure to swine. According to protocol, the identification of these two epidemiologically unlinked patients with novel S-OIV infection prompted the CDC to notify state and local health departments, which initiated case investigations and implemented enhanced surveillance for influenza A viruses that could not be subtyped. The CDC issued recommendations to clinicians, asking that they consider the diagnosis of S-OIV infection in patients with an acute febrile respiratory illness who met the following criteria: residence in an area where confirmed cases of human infection with S-OIV had been identified, a history of travel to such areas, or contact with ill persons from these areas in the 7 days before the onset of illness. If S-OIV infection was suspected in a patient, clinicians were asked to obtain a nasopharyngeal swab from the patient and to contact their state and local health departments in order to facilitate initial testing of the specimen by RT-PCR assay at the state public health laboratory. State public health laboratories were asked to send all specimens identified as influenza A viruses that could not be subtyped to the CDC for further investigation. Additional cases were identified with the use of a nationally standardized case definition of confirmed swine influenza A (H1N1) virus infection, which was defined as an acute febrile respiratory illness with the presence of S-OIV confirmed by real-time RT-PCR, viral culture, or both.

This report was exempt from the requirement for institutional review, and the privacy rule of the Health Insurance Portability and Accountability Act did not apply since it was a public health investigation.

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