Study probes patterns in previous triple-reassortant swine flu infections

May 7, 2009 (CIDRAP News) – Triple reassortant swine influenza A viruses that contain genes from avian, human, and swine influenza viruses emerged and became predominant in North American pig herds by the late 1990s and have been detected in humans 11 times since 2005, authors from the Centers for Disease Control and Prevention (CDC) and state health departments reported today.

The first such infection in humans was reported to the CDC in 2005, and in June 2007 human infection with novel influenza A viruses was classified as a notifiable disease in the United States, according to the group's findings that appeared today in an early online edition of the New England Journal of Medicine. Their report describes epidemiologic and clinical data from 11 cases reported to the CDC from December 2005 through February 2009

Viruses in all 11 cases were subtyped at the CDC with real-time reverse-transcription polymerase chain reaction (RT-PCR) and the hemagglutinin-inhibition assay. Complete genome sequence analysis was performed on viruses from respiratory fluid samples to determine if the virus was a triple reassortant.

According to surveillance reports and investigation by state health departments of two of the earlier cases, the median age of the patients was 10 years (range, 16 months to 48 years), and 8 patients were younger than 18. All lived in the Midwestern or southern United States.

Nine of the patients had been exposed to pigs to various degrees at sites ranging from pig farms to a custom slaughtering house. In 8 of the 11 cases, pigs reportedly showed signs of respiratory illness. Exposure wasn't known for one of the patients, and another was epidemiologically linked to a person with a suspected infection, suggesting human-to-human transmission of the triple reassortant swine flu virus.

Among the clinical findings, 4 of the 11 patients had underlying medical conditions, and at least 3 had received the current season's influenza vaccine. More detailed information was available for 10 of the patients. Symptoms included fever, cough, headache, sore throat, and diarrhea. The median fever was 103.5°F. Incubation ranged from 3 to 9 days.

Among four hospitalizations, two were severe: a 48-year-old woman with an underlying health condition and a 26-year-old woman who was previously healthy. All of the patients fully recovered.

Tests showed that 10 of the patients were infected with triple-reassortant swine flu A H1N1, and 1 was infected with the H1N2 subtype. Analysis of virus hemagglutinin genes from five of the patients found that the viruses came from two different phylogenetic lineages circulating in North American swine.

Preliminary data suggest no cross-reactivity between ferret antisera against the triple-reassortant isolates and the seasonal influenza A viruses, the authors reported. Isolates from all 11 patients were susceptible to older antiviral drug group called the adamantanes as well as the newer neuraminidase inhibitors.

The authors concluded that the incubation for the triple-reassortant influenza appeared longer than for seasonal flu and that some of the patients had severe lower respiratory illness and signs that are unusual for influenza, such as diarrhea.

Reasons for increased case reports since 2005 are unclear, but the authors suggested that improved surveillance and testing and new requirements for reporting might have played a role, though a true increase in human infections may have stemmed from changes in zoonotic transmission.

They advised clinicians to consider animal influenza infections in patients presenting with febrile respiratory illnesses, especially when human influenza viruses are not circulating.

"Our findings underscore the need for close communication and collaboration between human and animal health agencies for ongoing surveillance, investigation, research, prevention, and control efforts," the group wrote.

Shinde V, Bridges CB, Uyeki TM, et al. Triple-reassortant swine influenza A (H1) in humans in the United States, 2005-2009. N Engl J Med 2009 Jul 2 early online edition published May 7 [Full text]

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