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Next pandemic overdue, bird flu a likely candidate |
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ASIA PACIFIC SOCIETY for Medical Virology president Prof Emeritus Datuk Dr Lam Sai Kit provides some food for thought on a possible bird flu pandemic. theSun: How do we know a pandemic is looming? What are the signs? How worried should we be? A pandemic or global epidemic, by definition, implies a severe disease which appears on multiple fronts, affecting many countries, with high morbidity, i.e. infecting a large population and high mortality or increased number of deaths. Since influenza historically has been known to cause pandemics (three in the last century) and is a virus known to undergo frequent antigenic changes, it is anticipated that the present avian influenza strains, especially H5N1, are likely to be the candidate for the next pandemic strain. It has been over 30 years since the last pandemic and we are due for another one! The latest data on avian flu affecting humans in several countries in the region with high mortality is therefore a cause for concern. Fortunately, the last criteria before declaring a pandemic has not been met, namely high infectivity in humans globally. This means the virus H5N1 still remains very much species-specific, affecting birds, both domestic and wild types, and there is still little evidence of human-to-human transmission. It is appropriate to sound the early warning of an impending pandemic since influenza viruses, being RNA viruses, are known to mutate and undergo genetic reassortment to give rise to new strains. One of these genetic changes could lead to a strain that will spread easily among humans. It will be too late to take action once the pandemic starts. As to being worried or not, it depends on the day-to-day situation through global monitoring. If the situation remains as it is today over the next three to four months (the northern winter months), with very few human cases and deaths, then we can remain hopeful that the pandemic will not take place. Let us remain hopeful but vigilant. However, should a pandemic happen, it will spread much faster than in 1918 during the first flu pandemic because of the speed of travel. We are looking at days instead of months. How do we know that it is the H5N1 virus which will be the cause of the pandemic? Any of the avian influenza strains (H5, H7, H9) which have shown evidence of being capable of infecting humans can pose as a candidate for pandemic flu although the evidence to date points to H5 being the most likely candidate. The high mortality rate due to H5 (over 50% of infected cases die) makes this a much feared candidate compared to other avian strains. There is no certainty that it will be H5 and this makes it a dilemma for vaccine manufacturers and early preparation and production for a pandemic vaccine. What if a lot of resources are pumped into preparing this vaccine and then the pandemic is caused by another strain? Vaccine manufacturers are not prepared to take this risk and would rather wait for the pandemic strain to be declared before starting to make the vaccines. Fortunately, the technology is in hand to prepare pandemic vaccines within a few, say six, months. The issue of preparing a pandemic vaccine is not so much the lack of science but economics. Vaccine manufacturers are reluctant to invest in a vaccine for a pandemic which may not occur, or if there is a mismatch of strains. At the moment, vaccine companies can produce 250-300 million flu shots a year (catering for 5% of global population only) but in a pandemic, the world will need billions of doses. The surge capacity is just not there. In the light of such a shortage, the ethical and moral question arises as to who should be entitled to it at the national level. We are in a race against time where pandemic vaccine production is concerned! Can we prevent a pandemic especially with today's technologies both in surveillance and medical advances? It has been shown over the last few years (since H5N1 was first identified in HK in 1997) that culling of domestic birds has been very successful in preventing spread. This is still an important step to take. It is sad that there are countries which are unwilling to be totally committed to take this measure due to the cost and the lack of money for compensation. Vaccination of domestic birds using avian bird vaccines (not for human use) has also been recommended under circumstances and preliminary results have shown promise. It is now one of the recommendations of WHO to prevent avian flu spread. New technologies will make the preparation of pandemic vaccines for human use a reality as shown by the rapidity with which a candidate pandemic vaccine strain became available within four weeks using a new molecular technique known as reverse genetics. This was done by the St Jude Children's Research Hospital in Memphis, Tennessee. Clinical trials on this and other H5 vaccines are ongoing in several countries.
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As for surveillance, the use of polymerase chain reaction is the cornerstone for the identification of the flu viruses, whether they are H1, H3, H5 or other bird strains. We cannot assume that a patient with influenza symptoms is having the avian form. Tests must be conducted using PCR or similar technologies to confirm this finding. If the wrong assumption or diagnosis is made, then there will be a hefty price to pay for unnecessary culling. Medical advances have led to effective antiviral being made available against influenza. Unfortunately, antiviral are rather specific and useful against some strains and not others. The much touted Tamiflu (oseltamivir) is effective against influenza A viruses and is considered the front line for treatment of avian flu. However, recent reports of genetic changes in avian H5 influenza virus leading to possible resistance to Tamiflu is a cause for concern and require further surveillance a n d study. A recent paper (October 2005) published by the St. Jude Children's Hospital, Memphis, USA, showed that amantadine-resistant variants among avian viruses with potential pandemic potential (H5, H7 and H9 haemagglutinin subtypes) have started surfacing. The antiviral drug amantadine is still effective against H3N2, the current strain of influenza virus (non-avian) but not the avian strain. Tamiflu is the drug of choice for avian flu despite some reports of possible resistance and side effects (behavioral changes and suicidal tendency). Is it worth making a vaccine now? The only way to stop an influenza pandemic has to be through vaccination. We cannot go on culling animals to prevent the spread! However, because of the uncertainty of which strain to use, there is hesitancy in making the pandemic flu vaccine. When the pandemic virus has been identified, it will take several months to get the production going. The problem will be getting enough doses for the whole world. Even with the traditional flu vaccines, there is a problem of producing enough, what more a new vaccine? Recommendations will have to be drawn up to see how best to make use of this vaccine. In the light of anticipated global shortage by the few commercial companies making them, mainly in developed countries, developing countries are urged to consider producing their own vaccine for national needs. What are the recommended steps in containing the virus? Is it any different from how we contained the Nipah virus? Culling, quarantine measures, changing agricultural practices, preventing contacts between infected birds and humans, surveillance, all these are recommended. Nipah was also a zoonotic disease (common to humans and animals) involving mainly pigs as distinct from avian flu. However, culling was also used to prevent spread. This is an important step in all zoonotic diseases, including mad cow disease. It is certainly an expensive step to take but useful as a stopgap measure. Indonesia says culling would be an economic disaster and so it has stuck to disinfecting potential areas. Would that be adequate? Can disinfectants kill viruses? The main reason why Indonesia is not following strictly international guidelines of culling is because of economics as they cannot afford compensation of culled birds. Disinfection is part and parcel of the fight against this disease. It must be remembered that a lot of virus particles are discharged by infected birds into the environment and disinfection will prevent spread. Certainly disinfection can kill viruses in the farming environment (and also in market places, hence the success in HK in stopping the outbreak). It was also used during the Nipah outbreak. Can the H5N1 virus be killed? How? H5N1, like almost all viruses, are not very stable outside of the host (animal or man). They do not thrive in the environment for very long and most are killed within minutes in the tropical heat. That is why close personal contact with an infected person is the easiest way to spread the germ. Frequent hand washing and improving personal hygiene are important steps to take to avoid catching the flu. We need to increase our awareness about the spread of influenza through educational campaigns. H5N1 in certain aquatic birds (ducks and wild birds) can spread the virus because they remain symptom free. This is where the danger lies if ducks rather than chickens are infected. What is so great about Tamiflu? What about the side-effects? If every country stockpiles now and the pandemic does not occur, would it be a waste? Tamiflu is the frontline drug in the fight against H5N1 and is very much part of the national plan of preparedness in the face of the pandemic threat. Tamiflu (and the chemically related zanamivir known as Relenza) belong to a class of drugs known as neuraminidase inhibitors. They do not eliminate the virus, but they reduce its release from infected cells by blocking a key viral enzyme. If taken within 48 hours of the onset of symptoms the earlier the better they reduce the duration of symptoms and also limit the severity, such as pneumonia. Side-effects to Tamiflu are generally mild and the drugs have a long shelf-life for at least 10 years without losing their activity. |
It is, however, not wise for individuals to stock up on this drug. It is a prescription drug and should not be available over the counter at pharmacies like aspirin. Even if you manage to get a supply of this scarce and expensive drug, do you know when to take it? It is not a vaccine which gives protection for several months. How long can you afford to take this expensive drug? What about the problem of resistance if not taken as prescribed? What about possible side-effects as suggested in two cases in Japan? Tamiflu should be used as part of the national preparedness plan, not by individuals. Doctors will prescribe it based on clinical needs and risk assessment (person with flu-like symptoms and history of contact with H5 patient or infected birds). Not otherwise. Self-medication is a no-no! What can people do to minimize the effects of a pandemic or avoid being infected by the flu virus? We have heard the WHO recommending various preparedness plans. These plans, which include stockpiling of Tamiflu and building up infrastructure and surge capacity, for example, increasing hospital beds, equipment, etc, are varied, based on national resources but serve as useful guidelines. However, individuals must also have what I call individual preparedness plans. Do we, as individuals, know what to do when a pandemic is declared? Don't leave it only to the government to fight the pandemic. Every individual should help to reduce the chance of getting infected by this wily virus and thus contribute to reducing morbidity and mortality. We must start thinking about individual preparedness, just in case. Many lessons were learnt during the SARS outbreak and these lessons must be put to use to prevent ourselves from getting infected with pandemic flu. During a worse-case scenario of a pandemic, there will be panic and social upheaval and advice will be given not to go to crowded places. We should, therefore, stock up on essentials to reduce trips to markets as soon as a pandemic is declared. We should have a list ready and it should include a supply of face masks, for example. Any other advice? Stay optimistic! Being the ever optimist, I am hoping that the next pandemic will not occur in the coming winter. Why so? Well, the avian flu virus, although having been around for eight years, has not undergone sufficient genetic changes to make easy human-to-human transmission. We are still reporting individual cases and deaths, one here, one there. To date, there have been only about 120 human cases with over 60 deaths. If this trend persists, then it is not likely that we will face a pandemic in the next few months. Moreover, every case with rare exceptions can be traced to contact with infected chickens or other domestic birds, indicating that it is still very much an animal-human transmission. This will not lead to a pandemic. Let us hope it stays that way, thus giving the world a window of opportunity to be better prepared when the pandemic really hits us. By then we should have better capacity to tackle the pandemic, including the production of new vaccines and antivirals. The virus has not changed sufficiently to become resistant to Tamiflu. With the stockpiling of the drug, nationally, regionally and globally, it is hoped that enough will be made available to treat cases at source (no matter which country and whether affordable or not) and thus stop the virus in its tracks. Delaying the onset of a pandemic will allow better supply of this precious commodity. It is a hopeful sign when global partners are talking about sharing resources, including Tamiflu stockpile, to stop the outbreak at source to prevent a pandemic from taking place. Lessons from previous avian flu outbreaks, especially the successful control in Hong Kong in 1997, and lessons from SARS, will be harnessed and used to control the spread (of the disease).
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