The world is bracing itself for the possible imminent onset of an influenza pandemic — not from the much-feared H5N1 avian flu virus that has spread across Asia, Europe and Africa since 2003, but from a novel H1N1 strain of swine flu whose leap to humans was officially confirmed last week.

Researchers are scrambling to get a better handle on the evolution and spread of the new virus. Its genetic make-up is unlike any that researchers have seen: a swine H1N1 strain that combines an existing triple assortment first identified in 1998 — including human, swine and avian influenza — with two new pig H3N2 virus genes from Eurasia, themselves of recent human origin.

"It has been mixing all over the place, and so the genetics are quite complicated," says John McCauley, a virologist at the UK Medical Research Council´s National Institute for Medical Research in London. "Where the hell it got all these genes from we don´t know," says Robert Webster, a flu virologist at St Jude Children´s Research Hospital in Memphis, Tennessee. "But this is a real super-mixed-up virus."

Many major questions about the virus remain, including its virulence and the mortality rates it causes. So far, 149 people have died from it in Mexico, with some 1,600 cases suspected there. 40 cases have been confirmed in the United States, as well as others in Spain, Canada and the United Kingdom. The White House and the World Health Organization (WHO) have declared the virus outbreaks a public health emergency; the WHO is reportedly considering raising its pandemic threat from phase 3 — a new flu virus infecting humans but limited human-to-human spread — to phase 4 or higher, on a scale where 6 represents a full-blown pandemic.

The virus seems to be spreading easily from person to person. "The scary thing is that this virus seems enormously transmissible," says Webster. The temporal and geographical spread of cases involving no contact with pigs leaves researchers with few doubts that sustained human-to-human transmission is under way.

The US Centers for Disease Control and Prevention (CDC) and the WHO are trying to nail down how many of the reported deaths in Mexico are due to swine flu and how many are due to other causes. "The spectrum of illness is still a matter of doubt and conjecture," says David Ozonoff, an epidemiologist at the Boston University School of Public Health in Massachusetts. For instance, rumours swirled that archaeologist Felipe Solis, director of the National Museum of Anthropology in Mexico City, died on 23 April as a result of the swine flu; Mexican authorities later reported he died of cardiac arrest linked to pneumonia.

No human immunity

The virus seems to have first taken hold in Mexico in mid-March; it was identified when Mexican authorities sent samples from a flu patient that it could not subtype to the Canadian Public Health Agency. The CDC announced the existence of the virus on 23 April.

The genetics of the new virus are so novel that humans are unlikely to have any immunity to it apart from some cell-mediated immunity, say scientists. The current seasonal flu vaccine, which targets a different H1N1 strain, also isn´t likely to offer any protection. Discussions are under way as to whether a new vaccine for the new swine flu strain should be produced; a decision is expected within the next two weeks. For now, the virus is treatable with the influenza drugs oseltamivir (Tamiflu) and zanamivir (Relenza).

So far, cases in the United States and elsewhere seem to have been relatively mild in comparison to those in Mexico. Tashiro Masato, a virologist at the National Institute of Infectious Diseases in Tokyo, warns against drawing any conclusions from this. He notes that the sample of cases from the United States is too small to pick up even single-digit mortality rates. If transmission rates turn out to be high, mortality rates of even a few percent could lead to millions of deaths, as in the killer pandemic of 1918.

For the moment the pathogenicity and mortality range is wide and uncertain, says McCauley, "anything between the lethal 1918 and the mild 1968 pandemic". The high transmission rates in certain areas — there are 28 cases associated with a school in New York — are worrying, says Mark Lipsitch, an epidemiologist of the Harvard School of Public Health in Boston, Massachusetts. A better idea should be forthcoming as testing ramps up, and health authorities get a better idea of the ratio of deaths to those infected.

The new virus, however, comes nowhere near the mortality rates of H5N1 which have averaged around 63% globally and reached as high as 82% in Indonesia. Even so, "the risk and threat of H5N1 remain as before", Masato warns.

Epidemiologists are largely applauding the speed and scale of the response to the swine flu outbreak since it was formally identified last week, even though Mexican and international disease surveillance systems failed to pick it up promptly at the start. That swiftness is being largely attributed to the amount of pandemic planning undertaken by the international community and individual countries since the threat of a H5N1 pandemic emerged. Gene sequences of the virus samples, for instance, have been promptly shared on the Global Initiative on Sharing Avian Influenza Data (GISAID) database.

Virologists think they may be in for the long haul. "Will this fizzle out? It doesn´t look like it to me," says McCauley. "For me this is the time to start deploying national pandemic plans — we need to act now."