PLAGUES, PESTILENCES AND INFLUENZA About human progress, science, education and confronting real issues in a pragmatic and co-operative way Peter C. Doherty, University of Melbourne, Peter C. Doherty, University of Melbourne, Australia, and St Jude Children’ ’s Research s Research Australia, and St Jude Children Hospital, Memphis TN. Hospital, Memphis TN.
THE “SQUISH” EFFECT apoptosis, zeosis Video by Misty Jenkins and Nigel Waterhouse QuickTime™ and a Cinepak decompressor are needed to see this picture. Watch the big cell in the middle of the field, then the little guy that sneaks in from the top left
LIVE BIRD MARKET HONG KONG 1998
The extremely H5N1 influenza virus has been spreading in birds since 1997,with devastating consequences. So far, this has primarily been an avian infection, but it has also killed domestic and zoo cats. To date, about 130 people have died, a mortality of greater than 50% in those who have been infected. There isn’t much evidence of silent, “background” infection.
Until very recently human H5N1 infections have been considered to go from bird to person, but: Influenza A viruses mutate at a very high rate, and there is a possibility that it may change genetically in such a way that it spreads easily from human to human IF that happens and it does not at the same time attenuate, we could be looking at a catastrophic pandemic with >30% mortality. There is no guarantee that will occur, and we could duck the bullet..keep your finger’s crossed !
The last time that humans had an infectious disease disaster with 30-50% mortality rates was towards the end of the dark ages, the era when authority, precedent and “revealed truth” ruled, at least in Europe. The Black Death probably contributed to the end of the 1,000 year dark age while, perversely, the more enlightened Arab world was on the point of regressing into a more authoritarian mode
Since 1979, a t least 30 new diseases have transmitted to people from what are known (or presumed) to be wild animal reservoirs. This adds to a long list of well-established zoonoses. The problems are exacerbated by the massive increase in the size of the human population and the pressure that this exerts on natural environments. Since 1900, our numbers have increased from 1.6 billion to 6.4 billion. The human population at the time of Christ is calculated at about 300 million.
HIV/AIDS may have moved into humans from the practice of harvesting “bush meat” Beatrice Hahn at the University of Alabama found the precursor of HIV in chimpanzees by sampling feces and urine. The virus causes a mild infection in Chimps. Perhaps someone cut their hand while butchering a Chimp. This could have been happening for millenia. Who would have noticed the death of an African village in earlier times? What was lacking was long distance truck drivers and people traveling on Jumbo Jets to spread HIV globallly. Another possibility is that the availability of hypodermics allowed “traditional medicine” practitioners to inject people with Chimp tissues
A MODERN PLAGUE: THE SARS EPIDEMIC The first cases were identified in Guangdong Province, China in November 2003, and characterized as a severe influenza- like disease The infection was spread by people going home for the Chinese New Year. The peak of the outbreak was Feb 9 2003, with 50 cases being reported a day.
Food animal handlers were some of first SARS patients and had a higher incidence of SARS than others in China. Normile and Enserink, Science 301, July 18, 2003 The likely sources of infection was the Himalayan masked palm Civet cat. The human virus has a 29 bp deletion when compared to the animal isolates. It now seems that it came originally from bats
TRIUMPHS AND DISASTERS We were extremely fortunate that the infection did not spread to any countries that have degraded medical systems, and poorly functioning civil administrations. It would have been catastrophic if the virus had become established in a situation where there were large numbers of immunosuppressed people eg in countries with high AIDS prevalence. The disease also had a massive emotional impact, and the resultant fear caused economic problems that went far beyond the severity of the problem.
The economic costs were enormous SARS Cases 8437 Deaths 813 Countries 32 Cost US$20 + Billion
BOTTOM LINE: WE CAN WORK TOGETHER The SARS experience provides a very good example of the way that science protects humanity. This epidemic was handled professionally and well by the established global influenza network operating out of the Geneva-based World Health Organization of the United Nations. The scientists used both classical and avant garde virology techniques, and the relatively low infectivity of the virus allowed quarantine measures to work. It is a great example of both internationalism and the application of science at its best.
Influenza is very different from, and much more dangerous than, SARS. The virus grows very quickly and, unlike the situation with SARS, people are very infectious before they feel ill. Family members are often the first to be infected. Though quarantine worked with SARS, it isn’t clear that it would be effective with “flu.
Influenza kills 20-30,000 Americans each year. About 40,00 die in road accidents THE 1917-18 PANDEMIC KILLED about 40 MILLION PEOPLE, MANY MORE THAN DIED IN THE 1914-1918 WAR. Measures based on quarantine, wearing masks and modifying behavior were largely ineffectual. Global mortality was 2.5%
THE 1918 INFLUENZA OUTBREAK SEEMED TO TARGET HEALTHY ADULTS. This could be due To “cytokine shock” in those with healthy, young immune systems
THE WAY WE WERE, and now The first human influenza virus was not isolated until 1933, 15 years after the great pandemic, when Christopher Andrewes, Wilson Smith and Patrick Laidlaw transmitted it to ferrets. The ferrets fulfilled Koch’ postulates by transmitting it to Charles Stuart Harris Jeffrey Taubenberger and others have reconstructed the 1918 virus by PCR from fixed tissues at the AFIP and from frozen bodies in Alaska. It is extremely virulent in mice, and looks like it came into the human population from birds
Influenza vaccines are generally effective provided they target the “right” flu virus. The problem is that the virus changes, and we get new pandemics every 2 years or so Influenza vaccines are generally made by growing the virus in embryonated hen’s eggs, killing it with formalin then cleaning the product up in different ways One reason the H5N1 bird flu is so scary is that the virus kills the eggs before new virus is made…no virus…no vaccine This problem has been solved by using a new technique called “reverse genetics”. These new flu vaccines are GMOs, and thus require careful testing before use
New generation flu vaccines are also being grown in tissue culture (MDCK) cells. The US government has so far allocated $2 billion dollars for this effort In addition, “cold adapted vaccines” that grow in the 33 0 C environment of the upper respiratory tract but not in the 38 0 C lung (“flu mist”) are now in use in the USA. Any H5N1 vaccines of this type will be GMOs At present, we could only make enough vaccine to protect about a billion of the 6 billion people on the planet, but that capacity is being increased
The other protection we have Is afforded by the specific anti- influenza “designer”drugs, “Relenza”and “Tamiflu”….. zanamavir and oseltamivir These are taken at the onset of symptoms, and both shorten the course and limit the severity of the disease. Governments are stockpiling them in sufficient quantities to, at least, treat key personnel. This should be thought of as a national defence initiative Tamiflu and Relenza are in short supply, but they should hopefully be available before too long for purchase (on prescription) as an insurance policy
Influenza is well understood and science has given us strategies to counter this disease The problem is logistic: these viruses are constantly mutating and, if the bird flu does break though in humans it could be months before we have enough vaccine to protect all Australians, let alone to help people in developing countries. Drugs may work, but there isn’t enough drug available, and the virus could mutate. Buy a bio-security mask, rubber gloves and stockpile canned tuna fish?
If we do get a rapidly spreading, highly lethal, influenza epidemic, the protective and health services will rapidly be over-whelmed. Local, and individual action will be enormously important. State education authorities, independent schools and universities should all have disaster plans in place. Those plans should be widely shared, as it is possible that responsible individuals may be dysfunctional. Key personnel should have trained back-ups The best protective measure will be to diminish inter- personal contact. The institutions should close, and the students stay at home
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