Late yesterday afternoon a Morbidity and Mortality Weekly Report (MMWR) Dispatch appeared on CDC’s website that is unique in my experience. MMWR is usually heavily vetted and edited and nothing gets out of there fast. Indeed, in recent years, nothing at all got out of CDC very fast. And yet here is this Dispatch, with text referring to the same day of issue (April 21), reporting on two young patients with febrile respiratory illnesses, one of whose cases CDC only learned about on April 13, 8 days earlier. April 17 CDC determined that the two children, both from the San Diego, California area, were infected with a swine flu virus of a novel kind. That was five days ago. The extremely rapid publication of this MMWR is apparently a consequence of the new International Health Regulations. It’s good to see CDC take them so seriously. Are you listening Indonesia?
Both patients recovered uneventfully. Neither had been around pigs. CDC therefore considered it likely that human to human transmission was involved, although investigations are still taking place. The Dispatch was also a heads up to clinicians and health departments to be on the lookout for influenza like illnesses in patients who resided in, or had recently traveled to, southern California, or who had had recent exposure to pigs.
The discovery in both cases seems to have involved an element of luck. The first patient was seen at a clinic where some kind of investigational diagnostic device was in use. It detected influenza/A but was negative for the two subtypes of seasonal flu (H1N1 and H3N2) and for bird flu (H5N1). This made it a novel influenza virus, requiring notification of the San Diego County Health Department and further testing in more specialized laboratories, which verified it was an unsubtypable influenza A strain. The next day (April 14) CDC identified it as an H1N1 swine flu virus. Three days later (April 17) CDC received a second specimen from a 9 year old girl who had been seen at an outpatient facility that was part of an influenza surveillance project. This virus, too, had been initially unsubtypable.
Further genetic tests showed the two viruses to be similar, although not identical, pig influenza viruses. Pigs get influenza fairly often but rarely pass it on to humans. Diagnosed human swine flu infection is rarely recognized, although the one or two cases a year has increased slightly since 2005. It is usually a relatively mild illness, and almost patients give some history of contact with or proximity to pigs. So the lack of pig contact in these cases was unusual. Moreover the viruses weren’t the usual swine flu viruses, either. Most of the genes, including the hemagglutinin (HA) gene, were of the same family as seen in US pigs in the last decade, but the neuriminidase (NA) and matrix (M) protein genes were like swine flu viruses seen in Eurasia. This particular genetic combination has not previously been described and it raised the question whether a new reassortant was appearing that might become a public health problem if it could spread easily from pigs to humans and then human to human. There is no systematic surveillance of pigs in the US, however, so how new and how novel it is remains uncertain. Both of the novel isolates are resistant to the older antiviral adamantane class of drugs (M2 inhibitors). Interestingly, this year’s seasonal version of H1N1 is sensitive to the adamantanes. Resistance testing for the more recent neuriminidase inhibitors (oseltamivir/Tamiflu and zanamivir/Relenza) is in process.
Investigations so far have turned up no link between the two patients, who reside in adjacent counties. CDC and state and local health departments are making an unusually aggressive contact tracing effort. The first patient traveled with his family to Texas shortly after his illness and an AP story reports that CDC is trying to locate air crew and nearby passengers on the same flight. Family members of both patients had also been sick with respiratory symptoms on or around the same time, although no diagnostic tests were done.
Human to human spread of swine flu is unusual but not unprecedented. The most famous example was the 1976 outbreak of flu amongst army recruits at Fort Dix, NJ. Four cases and one death occurred, with evidence of person-to-person transmission both within the recruit population and outside it. After a month, the outbreak burned itself out. We still don’t know the source of the swine flu H1N1 virus, now called A/New Jersey/76 (Hsw1N1). In 1988 a pregnant woman died of influenza later determined to be a swine flu. She had visited a pig exhibition at a county fair four days before the onset of her illness. 76% of the exhibitors in the swine building developed antibodies to the virus, and several health care personnel in contact with the patient developed mild flu-like symptoms and later showed antibody evidence of infection.
However this turns out, it illustrates the value of a surveillance system. While these two cases were fortuitously caught, there was still something there to catch them. Novel influenza infections are notifiable diseases and in this case the system worked just as it should and in a timely manner. The lack of pig exposure in these two cases is clearly worrying to CDC, suggesting human to human transmission might be taking place.
So far it’s not an emergency, but it’s not business as usual, either. Hence the priority and the heads up to the medical and public health community.