Background Triple-reassortant swine influenza A (H1) viruses — containing genes from avian, human, and swine influenza viruses — emerged and became enzootic among pig herds in North America during the late 1990s.

Methods We report the clinical features of the first 11 sporadic cases of infection of humans with triple-reassortant swine influenza A (H1) viruses, occurring from December 2005 through February 2009, until just before the current epidemic of swine-origin influenza A (H1N1) among humans. These data were obtained from routine national influenza surveillance reports and from joint case investigations by public and animal health agencies.

Results The median age of the 11 patients was 10 years (range, 16 months to 48 years), and 4 had underlying health conditions. Nine of the patients had had exposure to pigs, five through direct contact and four through visits to a location where pigs were present but without contact. In another patient, human-to-human transmission was suspected. The range of the incubation period, from the last known exposure to the onset of symptoms, was 3 to 9 days. Among the 10 patients with known clinical symptoms, symptoms included fever (in 90%), cough (in 100%), headache (in 60%), and diarrhea (in 30%). Complete blood counts were available for four patients, revealing leukopenia in two, lymphopenia in one, and thrombocytopenia in another. Four patients were hospitalized, two of whom underwent invasive mechanical ventilation. Four patients received oseltamivir, and all 11 recovered from their illness.

Conclusions From December 2005 until just before the current human epidemic of swine-origin influenza viruses, there was sporadic infection with triple-reassortant swine influenza A (H1) viruses in persons with exposure to pigs in the United States. Although all the patients recovered, severe illness of the lower respiratory tract and unusual influenza signs such as diarrhea were observed in some patients, including those who had been previously healthy.