4 flu mutants

Seven eminent virologists discuss the implications with Down To Earth

By Pranay Lal
Published: Monday 15 March 2004

4 flu mutants

-- The current influenza epidemic in the us, the avian flu and severe acute respiratory syndrome (sars) in Southeast Asia are infectious diseases that have rapidly evolved, taking national and global health systems by surprise. Such infections emerge in one corner of the globe and hitchhike into new areas, often causing great mortality. At least four pandemics of influenza have occurred in the 20th century. The 1918-1919 "Spanish flu" was the most severe: an estimated 21 million people died. According to recent studies, the explosive spread of the pandemic was enabled by the unique virulence acquired by the virus. Virologists now reveal the 1918 influenza strain underwent subtle alterations that enabled it to bind with deadly efficiency to human cells, while retaining the basic properties of the avian virus from which it evolved.

Such changes in the degree of virulence of flu viruses have caused major concern to virologists. The surface antigens of viruses -- haemagglutinin (h) and neuraminidase (n) -- periodically undergo change, apparently due to sequential evolution within immune or partially immune populations. At irregular intervals of 10 to 40 years, viruses showing major antigenic differences from prevalent subtypes appear. Genetic recombination (an exchange of a gene segment) between influenza viruses or re-arrangement of genes, inside the lungs of a human or bird, can spur the evolution of a deadly new form. Deletions and insertions of genes also occur with consummate ease in viruses. Two researchers at the University of Toronto, Canada have found that the evolution of the sars virus -- though unrelated to the flu family -- may be an amalgam of two different viruses: one from birds, the other from mammals.

Birds, specifically shorebirds and waterfowl, are a reservoir of influenza a viruses. Such viruses are excreted in the faeces of infected birds, and spread to other susceptible avian species through contamination of water in farms along the flyways of migratory bird populations. So far, reports of natural human infections with avian influenza viruses have been rare (excepting the 1997 Hong Kong h5ni outbreak and the recent h5ni outbreak in Vietnam). It was believed avian influenza viruses have limited ability to replicate in human hosts, but this was belied after sporadic infections in humans during the current epidemic. The viruses can acquire one or more genes from a human influenza virus in order to cross the species barrier more efficiently. Pigs can simultaneously host the avian and mammalian flu viruses and offer opportunities for genetic reassortment. Since pigs and birds are often reared and sold together in wet markets in Southeast Asia, the possibility of crossover is high. Last year's sars epidemic and the recurrence of avian and human flu calls for closer surveillance of animal reservoirs and human cases. A paper in the British Medical Journal (January 2004) calls for stricter sanitary standards for "wet" (or animal) markets in Southeast Asia. Certainly, the successive emergence of deadly fevers indicates a failure of global health governance. We are living in a time when four different strains of the flu virus are making their rounds: will we suffer a mortal pandemic?

How dangerous are the flu virus strains?
What should we do?
The answers

Viruses from domestic poultry species have potential to cause pandemics in humans
-- robert g webster
Rose Marie Thomas professor of virology, St Jude Children's Research Hospital, Memphis, usa, and Director, World Health Organization's Collaborating Center on the Ecology of Influenza Viruses in Lower Animals and Birds

Flu keeps knocking on the door. In the past year the influenza virus emerged in Holland. The h7n7 virus spread to chicken farms and infected the eyes of more than 800 humans. It also transmitted human-to-human and one person died. This was controlled by the use of vaccines and antivirals. The outbreak of the Fujian (h3n2) virus has caused mortalities in England, Scotland and possibly also in Colorado, usa but will not cause a pandemic. It is not a novel strain but a variant of what we have seen in past years. However, that doesn't mean that it is going to be so benign. We have to realise that in the inter-pandemic periods, influenza can be very, very serious. In fact, in some inter-pandemic years, the disease can be more serious than in a pandemic year. We mustn't think that because flu has been mild for the last three years we're going to get away with it for the next three years.

For a pandemic to occur, a virus has to come into a population and compete with a virus that's already there. I guess an argument can be made that a weaker flu season would make it easier for a new virus to come in. Viruses from domestic poultry species have potential to cause pandemics in humans. In recent years, there have been increasing numbers of reports of influenza viruses in chicken populations, which never used to be the case. Perhaps there is an evolution of viruses occurring out there and they are moving, not just in numbers but also to a wider range of hosts. The number of newly emerging infectious diseases each year tends to go up, not down. Scientists are worried that h5n1 could morph into a human superflu, like the 1918 influenza pandemic which killed about 20 million people. That could happen if h5n1 swaps genes with a garden-variety of human flu germ inside the body of one of its victims -- an adaptation that might let it jump from person to person.

Except for Canada where everyone is recommended vaccines, no country has made organised efforts to combat the flu. Unfortunately, no country has yet invested in stockpiling -- not even Canada. Without a stockpile you're left without anything to do. The first response to any emerging influenza strain is to use an antiviral. We know that the vaccine is not going to be perfect. Vaccines should, however, be taken because you will get some protection.

We know very little about flu viruses
-- chwan-chuen king
National Taiwan University, Taiwan

When it comes to flu viruses, nothing can be ruled out. The past epidemics happened when virology was still a nascent discipline; so we know very little about flu viruses. The World Health Organization (who) says that that human-to-human transmission has not been confirmed. But is the who aware of all the human cases so far? It is quite likely that it might not be aware of the cases that have occurred in Vietnam and China. Since we had avian (h5n1) and human (h3n2) flu, close contacts between the two viruses can create a novel virus. If this novel virus has a human flu gene, as the 1957 or 1968 epidemics show, it will spread rapidly among human population.

However, we do not know how long this will take, or the exact conditions under which a novel virus can become virulent. For example, will new strains start alternating in summer and winter in different hemispheres? To take care of such unpredictability, poultry farmers need to be educated about good hygiene and farm management. In addition, farmers with symptoms of human flu should not work with domestic animals at all. Another challenge is to develop vaccines that have wide coverage to different flu strains.

Infected pigs can provide a medium for adaptation of the avian flu virus with human influenza virus
-- luis p villarreal
Director, Center for Virus Research, University of California, Irvine

Circumstances that facilitate unimpeded growth and variation of h5 flu in commercial flocks would greatly increase the gene pool and genetic diversity of the current h5 virus. Moreover, increased human contact with these infected birds would create a selective environment favouring the evolution of a human-adapted h5 version of the virus. Once such a virus comes into existence, it would be hard to prevent a pandemic.

There is a possibility of genetic exchange between the h5n1 and the influenza a (h3n2) viruses. This is the reason many worry about pigs becoming effective reservoirs and becoming h5 infected. Infected pigs would provide a medium for adaptation of the avian version to a human influenza. Normally this has occurred by mixing viruses. But I am not convinced that this can only happen in such a way. With large h5 virus populations, the possibility of direct adaptation from avian to human becomes much more likely.

There is probably no way to prevent some re-emergence of influenza viruses as they persist in inapparent states in their natural (non-human) host. However, in such states they cannot replicate in humans. So monitoring initial human infections and preventing human-to-human transmission can prevent epidemics.

Domestic birds, however, should be vaccinated since the h5 virus is better adapted to replicate in them directly from its natural water fowl host. Human vaccination (for either sars or avian influenza) would not be efficient, but a vaccine needs to be developed in case the viruses adapt better to human transmission.

There is a good chance that a virus that transmits more easily from humans-to-humans can be crested
-- adolfo garca-sastre
Associate Professor, Department of Microbiology, Mount Sinai School of Medicine, New York, USA

It is highly unlikely that the avian flu will become more virulent (even now, it is highly virulent). But since conditions of genetic exchanges between the viruses are propitious, there is good chance that a virus that transmits more easily from human-to-human might be created. If this virus retains the h5 strains, then a new pandemic strain might arise. Again, I consider it unlikely that the new strain will be more virulent than any of the two parents. But if it retains the virulence of the avian parent, then it will be very devastating.

Poultry units of both government and private sector should be monitored
-- sira abdul rahman
Retired dean, Bangalore Veterinary College and Secretary, Commonwealth Veterinary Association, Bangalore

If the h5ni virus comes in contact with a human virus there is possibility of genetic exchange between the two viruses and the hybrid would be very virulent. So poultry production units of both the government and private sector in the country need to be monitored carefully. This responsibility should be entrusted to the state veterinary directorates and all poultry deaths in the country must be examined and tested for avian flu. Imports of all poultry and poultry products and feed, which could be inimical to human health, should be banned.

From the public health perspective, establish an international link to countries such as Canada and Australia which are preparing vaccines to prevent the infection if it occurs. Poor health and nutritional status, hygiene, behaviour and practices can spur the spread of flu viruses. No amount of preparedness could combat the initial mortality until the population gets immune to the strain. It would be logistically impossible to vaccinate the entire population.

So far the virus has not been found in Indian birds. This offers us an opportunity to export our poultry products.

The likelihood of a new strain of virus is rife
-- ren snacken
Head of department of epidemiology, Scientific Institute of Public Health Brussels, Belgium

The mutations, which allow human-human transmission of avian influenza, can occur sporadically (it depends on the virus load which was probably important). Such a phenomenon was first suspected during the bird flu in Hong Kong (1997) and then in The Netherlands (2003).

For an infection to become lethal and widespread, it will need to graduate to infect human-to-human in a sustainable manner. Once this happens, no prediction can be made about the virus's virulence (higher or lower). But again, a new strain takes only one or two generations to switch its virulence and therefore it is not necessary that only a stable single strain might be formed.

Winters are the best period for the circulation of human viruses. So, the likelihood of a reassortment of viruses -- a totally new strain emerging from exchange of human and bird viruses -- is rife while h5n1 (avian influenza virus) is still circulating. It is interesting that three different strains are actively circulating in three different corners of the globe. The real challenge for epidemiologists and public health experts would be to restrict them from intermixing.

Human-animal interface should be closely monitored
-- maria pittman
Directorate general for health and consumer Protection, European Commission

The virus could mutate in a way it could sporadically infect humans -- as it has done so far. It could also acquire the capacity to spread easily from human-to-human, if an infected person is also simultaneously infected with influenza. This dual infection might cause a "new" virus to appear, against which there would be little or no protection for humans. So human-animal interface should be closely monitored.

The eu and the oie have initiated urgent action. On the anvil are plans to broaden the definition of the disease to include "low" pathogenic avian influenza of h5 and h7 subtypes (that can mutate) to strains highly pathogenic for poultry. This will enable regular surveillance and ensure that poultry is vaccinated against it.

Today, national borders do not bind the industry --hatcheries, feed factories and slaughterhouses are all segregated. Also, the density of poultry holdings has increased drastically in especially Asian and African countries. So the possibility of the disease crossing national boundaries, via infected birds and also via indirect contacts (vehicles, crates, persons), is rife. Some scientists also suggest that global warming and possible changes to the routine migratory routes of birds can influence the spread of avian influenza and other flu-like diseases to newer areas. Recent studies on an infected falcon in Hongkong suggests that wild birds -- so far regarded as carriers of the low pathogenic form of avian influenza -- might also get infected by the highly pathogenic form and possibly contribute to the spread of disease.

Subscribe to Daily Newsletter :

Comments are moderated and will be published only after the site moderator’s approval. Please use a genuine email ID and provide your name. Selected comments may also be used in the ‘Letters’ section of the Down To Earth print edition.