U.S. public health authorities are investigating two cases of swine flu in unrelated children in California, a development that has officials in Canada and elsewhere on alert.
Discovery of the two cases, in children who apparently had no contact with pigs or with each other, suggests there probably has been some person-to-person spread of swine flu viruses, officials of the U.S. Centers for Disease Control said Tuesday.
Whether the viruses continue to spread isn't currently known.
"The investigation is not finished. It's ongoing. But of course not having that direct swine link does raise additional questions and does suggest that there may have been human-to-human transmission. And so it basically ratchets it (concern) up a bit," said Dr. Nancy Cox, head of the CDC's influenza division.
"I think this is one of those situations where everyone will want to stay tuned."
U.S. officials notified the World Health Organization of the cases last Friday, as required under the International Health Regulations. That treaty stipulates that countries must notify the WHO when they see cases of infectious diseases that pose an international threat, such as novel subtypes of influenza with pandemic potential.
Dr. Keiji Fukuda, a senior official of the WHO, said there is no need at this point to raise the global pandemic alert level.
The world is currently in phase 3 of a six phase alert scale because of ongoing sporadic cases of H5N1 avian influenza. Phase 3 means there are occasional human cases of influenza with a subtype with pandemic potential, but that there is no ongoing transmission.
"All things considered, based on what we already know about H1 (swine) infections and that they occur, I'm pretty comfortable that the right steps are being taken," said Fukuda, an influenza expert who is the WHO's acting assistant director general for health security and the environment.
Canada became aware of the situation when WHO was notified, said Dr. Arlene King, director general of the Public Health Agency of Canada's centre for immunization and respiratory infectious diseases.
King said no cases of infection with this particular swine flu virus have been spotted in Canada, but the public health network across the country has been put on the lookout.
"The labs are on alert and have been asked to send any non-subtypable influenza viruses ... to the National Microbiology Laboratory for testing and review," King said, adding they have also been asked to report if they can't identify a pathogen found in samples taken from a patient with flu-like symptoms, or have surveillance information indicating unexpected increases in illness.
The cases involved a boy, 10, from San Diego County and a nine-year-old girl from Imperial County, both of whom have recovered from their illnesses.
The two, who live over 150 kilometres apart, became ill at the end of March and sought care from clinics involved in an influenza surveillance program. Those clinics tested for flu; when they found viruses that didn't match known human viruses, they alerted authorities.
Given that most people with flu aren't tested, the CDC's Dr. Lyn Finella called the discovery of the swine flu infections "a very fortunate lightning strike."
Human infections with swine flu viruses are not unprecedented. A scientific paper published in 2007 recorded 50 known cases of human swine flu infections, in the U.S., Canada, the Netherlands and several other countries.
And most famously, a cluster of swine flu cases at Fort Dix, N.J., in 1976 triggered concerns a pandemic might be emerging. Vaccine was made and 47 million people were vaccinated against a pandemic that did not materialize.
Canada sees about one human case of swine flu a year, King said. And the CDC officials said until a couple of years ago, the U.S. averaged one case every year or two. But since December 2005, there have been 14 cases, including these children.
In most of the recent cases, direct exposure to pigs could be established. And when cases were caused by H1N1 viruses, those viruses were relatively closely related. Not so in the viruses responsible for the infection in these children.
The viruses, which were described as very similar to one another, have unusual properties never seen before in swine flu viruses, the CDC said.
Two of the genes of the viruses were from swine viruses that normally circulate in Eurasia, a finding that has added to the level of interest and concern. And the hemagglutinin -- the H in a flu virus's name -- has a lot of mutations when compared to other swine H1N1 viruses, Cox said.
"It's different enough so that we're going to be looking very carefully at properties like receptor binding properties, growth kinetics. We'll be doing some animal model experiments and so on," she noted.
In California, health officials are investigating with help from the CDC, checking the children's contacts and looking for others who may have also been infected.
The CDC said in both cases, two family members were also sick around the time of the confirmed infections, but none of those four people was tested at the time for influenza.
Blood samples have been taken from those four and other people who have been in contact with the children; the blood samples will be tested for antibodies to these swine flu viruses, though results may not be available for some time, Finelli said.
The investigation has also spread to Texas, because the 10-year-old boy travelled by plane on April 3, while he was still ill. He and a brother who travelled with him remain in Texas, the CDC said.
Experts say it is not clear whether a swine flu virus of the H1N1 subtype could trigger a human pandemic at this point in time.
Human H1N1 viruses have been circulating around the world for decades, so there is a lot of immunity to those viruses in the population. But it's not yet known how much protection previous exposure to human H1N1 viruses -- or to vaccine made to protect against them -- would offer against these novel swine viruses.
"I think that the 100 per cent accurate answer is that nobody knows," Fukuda said from Geneva.
"But I think the other part of that answer is that if there's great enough antigenic distance between the current circulating H1 (human) viruses and for example a swine H1 virus, then there's no reason why it wouldn't behave in a pandemic fashion."
The term "antigenic distance" means how closely related viruses are to each other from the point of view of whether antibodies to one offer cross protection to another. If viruses are antigenically similar, there should be good cross protection.
But if there is great antigenic distance between human H1N1s and these swine flu viruses, the swine viruses would have greater potential to cause human illness.
Cox said that the CDC will be testing blood samples from people of a variety of age groups to try to get a sense of how much of the population might be vulnerable to these viruses. That work, which will take some time, should give a clearer picture of how much of a threat the viruses might pose if they are still circulating.