Human cases of influenza A (H3N2) variant appear on the rise

CDC. MMWR. 2011;60(early release):1-4.

In the last 4 months of 2011, the CDC received reports of 12 cases of human infections with influenza A (H3N2) variant viruses that have the matrix gene from swine-origin influenza A and pandemic influenza A 2009 viruses, according to a recent report from the CDC.

Only 35 cases have been reported in the United States since 2005, but the frequency with which they have been detected increased in 2011, according to an early-release Morbidity and Mortality Weekly Report.

“When different influenza viruses simultaneously infect a single host (eg, a human or swine), exchange of genetic material can occur, resulting in a new influenza virus,” the MMWR report said. “Depending on the antigenic distance between the new virus and recently circulating seasonal viruses, little or no immunity might exist in the human population. Influenza A (H3N2)v viruses resulted from reassortment of influenza A (H1N1)pdm09 viruses with swine influenza A (H3N2) viruses.”

The 12 cases occurred in Indiana, Iowa, Maine, Pennsylvania and West Virginia. Eleven of the patients were children, and six of the 12 patients reported no recent exposure to swine.

The most recently reported cases occurred in an adult man from Indiana with occupational exposure to swine and two children in West Virginia who regularly attended the same day care. Three of the 12 patients were hospitalized, and all have recovered fully.

The adult patient reported direct contact with swine during his work in the week before illness onset and said he did not wear any personal protective equipment because the swine did not exhibit signs of illness.

The cases in the two children from West Virginia who attended the same day care are likely unrelated because the symptom onset dates are more than 10 days apart.

“This represents a scenario of limited human-to-human transmission occurring in a day care setting,” according to the report in MMWR. “Therefore, clinicians also should consider the possibility of influenza A (H3N2)v infections in patients who have not had exposure to swine, particularly young children in those states where influenza A (H3N2)v cases have been reported.”

Nonhuman influenza virus infections rarely result in human-to-human transmission, but the implications of sustained ongoing transmission between humans is potentially severe. For this reason, according to the CDC, prompt and thorough identification and investigation of sporadic human infections with novel influenza viruses are needed to reduce the risk for sustained transmission.

According to the MMWR report, swine-origin influenza viruses identified in humans are now referred to as “variant” viruses and denoted with a “v.” Influenza viruses identified in swine populations will continue to be referred to as “swine influenza” viruses.

This change in nomenclature follows an announcement by WHO of a decision to standardize nomenclature for the pandemic influenza A (H1N1) 2009 virus, which has had diverse names, as influenza A (H1N1)pdm09.

Per the new naming convention, these H3N2 viruses will now be referred to as “influenza A (H3N2) variant viruses with genes from avian, swine and human viruses” and will be abbreviated as “A(H3N2)v” for scientific use and “H3N2v” for general public use. The 12 patients mentioned in the MMWR report with A(H3N2)v infections also have the M gene from the A(H1N1)pdm09 virus.

This change is a result of discussions among WHO, the World Organization for Animal Health, the Food and Agriculture Organization, CDC and other US agencies.

Pedro A. Piedra

It is interesting to note that prior to the pandemic influenza A (H1N1) 2009, there was a report citing an increase in human infections caused by triple-reassortant swine influenza A (H1) viruses in the United States (Shinde V. N Engl J Med. 2009;360:2616-24). Most of these cases were associated with exposure to pigs. These triple reassortant influenza A (H1) viruses were different from the H1N1 swine influenza virus that caused the 2009 pandemic. On Sept. 2, 2011, approximately 2 years after the pandemic with influenza A (H1N1) 2009 virus, the CDC reports on two unrelated cases of young children infected with a swine-origin influenza A (H3N2) virus (CDC. MMWR. 2011;(Early release)60:1-4). Human infection with a swine-origin influenza A (H3N2) virus occurs infrequently. Exposure to pigs with a respiratory illness is often the source of the infecting virus.

What is unique about these two cases is the infecting virus and the potential for human to human transmission. This swine influenza (H3N2) virus had acquired the matrix (M) gene from the pandemic influenza A (H1N1) 2009 virus and the remaining seven genes from the swine influenza A (H3N2) virus circulating in North American pigs. One of these two children had no direct exposure to pigs or had visited an agricultural fair where direct exposure might have occurred. This suggested the possibility of human-to-human transmission.

The most recent update by the CDC on the swine-origin influenza A (H3N2) virus, which was recently renamed to influenza A (H3N2)v, reports on 12 known human cases that were identified in five states (CDC. MMWR. 2011;(Early release)60:1-4). Eleven of these cases occurred in children, three resulted in hospitalization and in six cases there were no link to pig exposure. To date, all patients have had complete recovery. These 12 cases seem to have occurred more frequently than what would have been expected from previous reports on swine-origin influenza A viruses. The likelihood that limited human-to-human transmission occurred also raises the specter of a new influenza virus having the potential to spread among the human population. To date, transmission within humans has been limited. With the advent of the influenza season, an additional recombination event could result in an influenza A (H3N2)v with improved potential for spread within humans. It will be important to continue to monitor for human cases of influenza A (H3N2)v. The CDC has an approved FDA rRT-PCR assay that can identify presumptive cases of influenza A (H3N2)v. These cases need to be investigated and confirmed by the CDC.

Pedro A. Piedra, MD
Infectious Diseases in Children Editorial Board

Disclosure: Dr. Piedra reports no relevant financial disclosures.

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