N. Gopal Raj

The new H1N1 virus, which threatens to set off an influenza pandemic, is a mishmash of swine, human and bird flu genes drawn from two flu strains that infected pigs. But it is still not clear where the new virus first made its leap from pigs into humans.

It was only about a month ago — on April 15 — that the Centre for Disease Control and Prevention (CDC) in the U.S. first isolated the new flu virus from a sample taken from a 10-year-old boy in California. Alarm bells went off when some days later exactly the same strain was found in people with severe respiratory illness in neighbouring Mexico.

Since then, scientists have scrutinised the genes of the new virus, which U.N. agencies have labelled Influenza A (H1N1). Flu viruses have their genes in eight segments. If two or more strains of flu infect the same animal, their progeny can receive a mix of these segments. Pigs are a particular problem because apart from swine flu viruses, they can also carry human and bird flu viruses.

In two papers recently published in the New England Journal of Medicine, the U.S. scientists have shown that the new H1N1 virus has drawn six of its genes from flu viruses that were circulating in North American pigs and two genes from a Eurasian swine flu strain. The North American swine viruses were themselves a mix of pig, human and bird flu virus genes. These North American swine viruses had sporadically infected humans but had not become contagious enough for sustained transmission.

The new H1N1 virus has never been seen before, either in humans or in animals, observed Michael Shaw of the CDC, a co-author of one of the papers. “There’s clearly a gap in the surveillance because there are no really close relatives [of this virus], nothing that we can say was an immediate precursor,” he said at a recent press briefing. Yet, the genetics of the virus and its behaviour showed that “it was already well-adapted for transmission in humans before it popped up in this particular case,” he added.

However, the inability to identify a direct ancestor means that the new H1N1 virus need not have originated in the pig farms of Mexico, the country that has so far reported the earliest cases of people catching this virus.

Concerned over course of disease

According to the New Scientist magazine, two British scientists estimated that the new virus might have started circulating among humans in January this year and perhaps even as early as September 2008. Nicholas Grassly of Imperial College London and Andrew Rambaut of the University of Edinburgh based their estimate on the mutations found in nearly a dozen virus samples from Mexico and the U.S.

However, at a time when a pandemic appears imminent, public health officials and doctors are currently more concerned about the course of disease once the virus gets into people.

In Mexico, the disease was mild in the majority of those infected by the new H1N1virus, said Sylvie Briand, who currently heads the Global Influenza Programme at the World Health Organisation (WHO).

A recent review of severe cases of disease in Mexico showed that those with chronic underlying conditions, such as diabetes, tuberculosis and cardiovascular disease, were at risk of developing complications, she told journalists during a press briefing recently. This, however, was close to the pattern seen with seasonal flu too. But, in addition, some previously healthy, young Mexicans too had developed severe pneumonia and died as a result, she added.

In Mexico, bacterial pneumonia has not been a major factor in the cases of severe disease and death, according to Dr. Briand.

An influential paper published last year in the Journal of Infectious Diseases had concluded: “The majority of deaths in the 1918–1919 influenza pandemic likely resulted directly from secondary bacterial pneumonia.” The 1918 pandemic, which was caused by a H1N1 flu virus, was the most severe of the three pandemics that occurred in the 20th century.

Rather, Mexicans had developed viral pneumonia that progressed into acute respiratory distress, said Dr. Briand. The major cause of death was respiratory failure and major organ failure, she added.

In the U.S., the majority of those infected by the new H1N1 virus had symptoms that were typical of seasonal influenza, said Fatimah Dawood of the CDC. The three most common symptoms were fever, cough and sore throat, she told reporters recently.

Dr. Dawood is the first author of a paper published in the New England Journal of Medicine that analysed 642 confirmed cases of infection that occurred in the U.S. between mid-April and early May.

But, in addition, diarrhoea and vomiting had also been observed in several patients. This led Dr. Dawood and her colleagues to warn the medical community that the disease could potentially spread through viruses shed in the faeces. Flu viruses are thought to be mainly transmitted through droplets expelled when an infected person coughs.

The New England Journal of Medicine has made the latest papers as well as other material about the H1N1 flu virus available at a new website: http://h1n1.nejm.org/