With the influenza season over in the temperate Northern Hemisphere, and just getting under way on the other side of the world, scientists are watching the A(H1N1) swine flu virus to see where it goes next and whether it will reassort with other flu viruses, or mutate, to cause more severe disease or acquire resistance to antiviral drugs.Some researchers are warning, however, that such changes might be more likely to occur not in the northern or southern temperate zones where flu is seasonal, but in the narrow, often-overlooked belt of tropical countries where flu circulates all year round.
"We should be getting the message across that it is probably in the tropical countries, more than in the Southern Hemisphere, that this virus will be going through some reassortment contortions in the coming months," says Ken Shortridge, a veteran of flu research in China and southeast Asia, now retired in New Zealand.
Outbreaks of the new virus have so far been largely confined to the Northern Hemisphere, and public-health officials are crossing their fingers that as summer approaches outbreaks may wane — although that is far from a given. That would buy time for a new vaccine to become available just before the expected wave of new cases next winter.
European Union countries have so far succeeded in holding the virus at bay by intensively tracking the first cases imported from abroad, and treating those patients and their contacts with antiviral drugs. Many low-income countries in the south will not have the resources for such a strategy, says Jeremy Farrar, director of the Oxford University Clinical Research Unit in Ho Chi Minh City, Vietnam. "This inevitably means that when this highly transmissible virus arrives in a densely populated country with more limited resources, it will spread rapidly and many, many thousands of people will be infected," he says.
Scientists have been frustrated by their inability to predict the behaviour of flu viruses, although they are more prepared now for a pandemic than ever before. When the last flu pandemic occurred, in 1968, researchers did not have the web or the molecular-biological and genomic tools to track the disease. "It's the first time in history that we have been able to watch a potentially pandemic virus unfold in advance of a pandemic," says Shortridge. "This is a magnificent advance, but we are still feeling our way."
Jimmy Smith, a member of the World Bank's global H1N1 and H5N1 flu task force in Washington DC, says there are three immediate priorities: "Surveillance, surveillance and surveillance." That includes not only detailed epidemiological analysis of human cases and their clinical spectrum and age profiles, but also more detailed monitoring of animal flu viruses, in particular in pigs and poultry. Intensive surveillance of cases will need to be sustained for at least two years before any conclusions can be drawn as to the severity of the virus, says Keiji Fukuda, acting assistant director-general of the World Health Organization's (WHO's) Health Security and Environment division. "Pandemics do not occur in a couple of days," he says.
In the tropics and the Southern Hemisphere, the infrastructure for surveillance capacity in low-income countries has improved greatly over the past five years because of the need to deal with the threat of H5N1 avian influenza, including expanding the WHO's Global Influenza Surveillance Network. But progress has been slow, and there is still insufficient capacity in many countries, particularly in rural Asia and Africa. The World Bank is in the process of ramping up funding for flu surveillance for Mexico and any other countries that request it, says Smith.
Surveillance is not just academic; it is key to getting early warnings of events that call for swift adaptations of control strategies. Swine flu is currently sensitive to the antiviral drug oseltamivir (Tamiflu), for example, but seasonal H1N1 is resistant. Were the new virus to acquire resistance, that would render redundant the Tamiflu stockpiled by many nations as part of their pandemic plans.
Tropical countries may be pivotal in such changes. "Tropical zones are the black box of influenza," says Antoine Flahault, dean of the French School of Public Health in Rennes and Paris. Tropical southeast Asian countries in particular are a hotbed of flu viruses, ranging from H9N2 in children in Hong Kong and China, to H6N1 in birds and, by far the most prevalent, H4N6 in ducks and other waterbirds. The threat of reassortments occurring in poor tropical countries is compounded by the fact that humans tend to live in close proximity with livestock. "If it reassorts, who knows what could result," says Shortridge.
Change in focusIn a 1988 workshop, Shortridge, along with Alan Kendal, then director of influenza at the US Centers for Disease Control and Prevention in Atlanta, Georgia, first drew attention to the tropics as likely to be the main reservoir for the mixing of flu viruses. Nonetheless, the tropics are largely relegated to an afterthought in textbooks and papers about flu, with most attention being given to seasonal flu in the temperate regions, where most flu researchers work. "Articles about flu in the tropics tend to get glossed over," says Shortridge.
Two flu genome papers published last year, however, provide strong genetic evidence for mixing and mutation in the tropics, to yield new future strains. "All the interesting stuff happens in these tropical reservoirs, with the temperate epidemics in both the Northern and Southern Hemispheres being spillovers from that," says Oliver Pybus, an evolutionary geneticist at the University of Oxford, UK, and co-author of one of the papers.
The logical conclusion, he says, is that although surveillance is needed in temperate countries in the Southern Hemisphere during the upcoming flu season, deep sampling of tropical regions would be even more helpful. "But unsurprisingly, surveillance has historically been best in rich countries" that tend to be in temperate latitudes, he says.
On 22 May, Margaret Chan, director-general of the WHO, told the annual meeting of the World Health Assembly — the agency's supreme decision-making body — that nations must unite to help poor countries in the Southern Hemisphere implement control measures. "I strongly urge you to look closely at anything and everything we can do, collectively," she said, "to protect developing countries from, once again, bearing the brunt of a global contagion."
http://www.nature.com/news/2009/090527/full/459490a.html
