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Flu Alarm that Fell Flat

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Governments in North America ignored warnings that a swine flu strain was circulating in pig farms.

Canadian paediatrician Joan Robinson’s long-planned holiday to Mexico wouldn’t have been jeopardised and the world may not have been teetering on the brink of a pandemic had authorities acted on her words of caution.

Robinson’s late-June vacation destination is at the centre of a potentially pandemic flu outbreak, which has now spread to 14 other countries in five continents, apart from reportedly killing 160 people since mid-April. Her government, like many others, has issued a travel advisory to avoid non-essential travel to Mexico for a while.

Ironically, Robinson, professor of paediatric infectious diseases at the University of Alberta, Canada, had warned as early as February 2008 that a swine flu strain capable of human-to-human transmission is circulating in North America, particularly in some Canadian pig farms.

No one knows whether it is the same flu strain that’s wreaking havoc now as flu viruses mutate notoriously fast. But had the authorities listened to her, the world wouldn’t have been caught by surprise.

Robinson got a whiff of the trouble brewing when a seven-month-old baby living on a community pig farm was diagnosed with a mild swine flu attack in 2006. Subsequently, her team screened 90 people, who lived on the farm, to find 54 of them positive to the strain. Her paper, in early 2008, called for monitoring pig farm workers in Canada and other countries as part of their national influenza pandemic preparedness plans.

“Countries did not take up any surveillance of swine workers, probably because the number of human swine flu symptomatic cases until 2009 was so small that experts did not think this was an important part of pandemic planning,” she told KnowHow. Early recognition of swine strains becoming virulent is key to infection control as well as vaccine development, she said.

Robinson wasn’t alone in waving the red flag. Gregory Gray, director of the Center for Emerging Infectious Diseases at the University of Iowa College of Public Health, reported in 2006 that some pig farmers and meat processing workers they studied had elevated levels of antibodies against swine flu in their blood — an indicator that they were exposed to the flu virus. More importantly, a team of researchers from St. Jude Children’s Research Hospital in Memphis picked up signals as early as 1998 that flu viruses in pigs were swapping their genetic material, triggering the possibility of newer — maybe more lethal — strains being in circulation.

Thanks to the H5N1 avian flu outbreaks reported in different parts of the world since 2003, including India, the world is better prepared to deal with the emerging crisis. In less than a week of the outbreak being confirmed, the World Health Organization warned that a pandemic is imminent. “It is because of the concerns with the H5N1 virus that we have been able to pick up this outbreak relatively early, and we are much better prepared because of that,” said Michael Osterholm, who heads the Center for Infectious Disease Research and Policy at the University of Minnesota.

International public health experts have enough reasons to be alarmed.

For one, the influenza virus is very unpredictable. A flu strain may be harmless, but a slight change in its genetic composition can turn it into an extremely virulent variety. “The flu virus constantly surprises us,” said Nancy Cox who heads the flu division at the Center for Disease Control and Prevention (CDC) at Atlanta. The source of this surprise — not really a pleasant one though — is the ability flu viruses have to swap their genetic material when two or more of them co-habit. “Analysis of the early isolates suggests that the genetic make up of this new virus is a mixture of the avian, swine and human viral genomes. It is too early to tell how this virus evolved,” said Ram Sasisekharan, professor of biological engineering at Massachusetts Institute of Technology, US.

Then, the fact that the virus originated from pigs was the biggest worry for public health authorities. Pigs have been the ideal mixing vessel for flu viruses afflicting different species: humans, birds and pigs. While it is very rare for other species to accommodate more than one flu strain at any point in time, pigs do that happily, that too without being sick.

Further, the 1918 Spanish flu which killed anything between 50 million and 100 million across the globe too was of swine origin. The similarities, however, seem to end there. Though they are both H1N1 viruses, the novel swine flu does not appear to share any of the genetic markers of the virulence that 1918 pandemic flu virus possessed, according to a CDC statement.

But, there is one thing that makes virologists happy. Genetic analysis of the strains isolated from affected countries — Mexico, the US, New Zealand, Canada, the Netherlands and Germany — indicates that the strain has so far stayed steady, and hasn’t mutated. All genes of these strains have 99 per cent to 100 per cent similarity. This makes producing a vaccine easier, said Cox.

If that is true, the scientists may have to find why the same strain is behaving differently in two different populations. While the number of deaths in Mexico is frightening, there hasn’t been any serious case outside Mexico. While 159 people reportedly died in Mexico (but of these only sixteen are laboratory-confirmed swine flu deaths), there was only one death outside: in the US.

What, however, is puzzling is that the 159 deaths have come from some 2,500 cases reported in Mexico, pointing to a very high fatality rate (the ratio between number of cases and deaths). The Mexican government has stopped reporting suspected cases and deaths since April 30, 2009.

Some of the questions scientists already asking are: Is this because a huge number of Mexicans have been infected? Is that because many of the deaths in Mexico are due to other causes, since only a minority of the people who died were actually tested for swine flu? Is that because Hispanic people have a different response to this virus than white people do? Is that because Mexicans were more likely to be infected by a household member and most others were infected by more casual contact, and so got a smaller dose of the virus? How capable is this virus of efficiently spreading from person to person multiple times?

“Until we have answers to some of these questions, we do not know if the current outbreak will be over shortly (the 1976 US swine flu outbreak lasted 21 days) or will ultimately prove to be a pandemic,” said Robinson.

According to Wendy Barclay, a flu virologist at the Imperial College in London, the outbreak in Mexico may not have such a high case fatality rate. “We don’t know how many people may have been infected but didn’t get very ill,” he says. Every normal pandemic has a case fatality rate of 1 to 2 per cent. “This is the type of figure that governments should have planned for in any pandemic,” Barclay told KnowHow. “But anything beyond 5 per cent could be really bad.”

Sources: The Telegraph (Kolkata, India)

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How WHO Measures a Pandemic

The World Health Organization has six phases of pandemic alert to assess the potential for a new global flu outbreak. Swine flu has raised the level to phase 5.

— Phase 1. There are no viruses circulating in animals that have been reported to cause infections in humans.

— Phase 2. An animal flu virus has caused infections in humans in the past and is considered to be a potential pandemic threat.

Phase 3. An animal or mixed animal-human virus has caused occasional cases or small clusters of disease, but the virus does not spread easily. The world is currently in phase 4, with H5N1 bird flu viruses sporadically infecting humans and occasionally spreading from human to human.

— Phase 4. The new virus can cause sustained outbreaks and is adapting itself to human spread.

— Phase 5. The virus has spread into at least two countries and is causing even bigger outbreaks.

— Phase 6. More outbreaks in at least two regions of the world; the pandemic is under way.

The World Health Organization raised its pandemic alert level to 5, signaling that the swine flu virus is becoming increasingly adept at spreading between humans. That signals governments they should ready their pandemic preparedness plans and increase detection systems for potential cases.

Phase 6 means there is transmission in at least two regions of the world and that a pandemic is under way.

With an elevated pandemic alert level, WHO might also issue travel advisories, warning against nonessential travel to regions battling outbreaks, trade restrictions, the cancellation of public events or border closures.

During the SARS outbreak in 2003, WHO travel advisories drastically slashed travel to affected regions, curtailing the outbreak

Sources
: Los Angeles Times

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Chemical that Can Stop Flu Spread Found

Scientists in Hong Kong and the United States have identified a synthetic compound which appears to be able to stop the replication of   influenza viruses, including the H5N1 bird flu virus.

The search for such new “inhibitors” has grown more urgent in recent years as drugs, like oseltamivir, have become largely ineffective against certain flu strains, like the H1N1 seasonal flu virus. Experts now question how well the drug would stand up against H5N1, should it unleash a pandemic.

Researchers in Hong Kong and the US found 20 compounds catalogued with the US National Cancer Institute that could potentially restrict the proliferation of the H5N1

Sources:The Times Of India

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A Shot for All

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A vaccine in the making — equally effective for birds, men and other mammals — offers a shield against another outbreak of bird flu.

……………...CLICK & SEE

Of all the viruses that can cause a devastating pandemic (worldwide outbreak), the influenza virus is the most likely to cause one. Influenza is a tricky disease to control. The world has already seen several outbreaks, of which the influenza pandemic in 1918 was the most serious: at least 20 million people died all over the world then. There were pandemics in 1957, 1968 and 1977, but of much less severity.

Recently, avian influenza (or bird flu) has emerged as a candidate that can cause a serious pandemic. Experts warn that another outbreak is imminent and we have only limited ability to control it if one breaks out. However, several vaccines — now in the laboratory stage — offer hope.

One of the problems of bird flu is that it affects birds as well as humans and other mammals. The virus may be slightly different in each of the animals, and it is difficult to give different vaccines for different animals during a pandemic. At the Department of Veterinary Medicine in the University of Maryland in the US, Daniel Perez and his colleagues have developed a vaccine that can control the disease in birds, humans and rodents. It is based on a region of the virus gene that is common to all the strains. “We have shown that the vaccine works in rodents and does not cause the disease,” says Perez.

This vaccine has been tested in rats but not yet in humans. Meanwhile, at the University of Pittsburgh medical college, scientists are testing a vaccine against the deadliest of all avian flu viruses, the H5N1. This is a genetically engineered vaccine that takes only 10 weeks to manufacture. The other vaccines now in the market are made using chicken eggs, and take several months to manufacture, apart from not being able to provide enough immunity. Two months ago, the institution received a $3.6 million grant to test the vaccine in non-human primates.

Currently, three companies manufacture vaccines against the avian flu virus H5N1, all of them approved in different countries in the last year and a half. Sanofi Pasteur’s vaccine was approved in the US in 2007, GlaxoSmithkline’s vaccine was approved in Europe in May this year. Australia approved a vaccine from CSL Limited. All of them are live attenuated virus — which have been so altered that they can’t cause disease — raised on chicken eggs. While all of them provide some protection, none of them can prevent a pandemic. This is because the virus mutates fast, and we do not know what strain of the virus would be involved in a pandemic.

One of the known — and fortunate — facts about the bird flu virus is its specificity. The virus that infects birds does not easily infect humans. This is why many outbreaks in birds have not resulted in human infections. Which is probably also why human to human transmission has not happened in large numbers so far.

However, such a transmission is not scientifically impossible. Since the virus mutates fast, strains of broader range can emerge. They can infect humans, pigs, rats, birds and other animals. It would be difficult, if not impossible, for us to make different vaccines for different animals. The Maryland University team has shown that it is possible to make a single vaccine effective in many animal species.

This vaccine is based on a DNA backbone that is common to all the strains. This backbone lies inside the virus and not outside. The scientists have a strain of the virus called WF10 with this backbone. They have isolated other influenza viruses that are related to this strain, including the human influenza virus. They had earlier shown that by tweaking the gene of this strain they could make a vaccine effective in birds. Now they have shown that, by further modification, this strain can protect many species against the influenza infection. In particular, they have shown that it provides protection in rats against H5N1, the most lethal strain against which human vaccines are made. Says Perez: “We have done animal trials, but we are yet to do human trials.”

There are other developments that could help in preventing a major pandemic. A series of DNA vaccines against H5N1 are also under development in several institutions. They are the Virology Research Institute in Maryland, which began clinical trials last year, the University of Pennsylvania School of Medicine, and the Rockefeller University. A DNA vaccine is a piece of DNA that can directly make the protein that produces an immune response. It is safe, because it cannot by itself cause the disease. The vaccines can be made rapidly, which is invaluable in case of an epidemic.

However, there are technical issues, which all these teams claim to have solved. If they work, we could soon have a vaccine that can be rapidly made when there is an epidemic. Let us wait and watch their progress.

Sources: The Telegraph (Kolkata, India)

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Chip That Detects Flu Within 2 hrs

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Europe‘s top semiconductor maker, STMicroelectronics, said it has developed a portable chip to detect influenza viruses including bird flu in humans.

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The device, which functions as a mini laboratory on a chip, can screen and identify multiple classes of pathogens and genes in a single test within two hours, unlike other tests available on the market that can detect only one strain at a time and require days or weeks to obtain results.

The chip can differentiate human strains of the Influenza A and B viruses, drug-resistant strains and mutated variants, including the Avian Flu or H5N1 strain. There have been 236 human deaths globally from the H5N1 strain, according to the World Health Organisation, though it remains mainly a bird virus.

“ST sees new high growth opportunities in the healthcare market, especially in areas like patient care,” said Francois Guibert, STMicro‘s Asia Pacific chief executive in Singapore on Monday marking the commercial launch.

It allows users to process and analyze patient samples — comprising human blood, serum or respiratory swabs — on a single disposable microchip.

Sources: The Times Of India