Science


SARS Science Review 2003

Early in 2003 two viruses merged to jump the species gap. The resulting virus had the ability to affect humans and SARS (Severe Acute Respiratory Syndrome) was borne. But what are the global implications of this event writ large? And for those reading this article in 2003, should you go to the Toronto, 2003 Worldcon? Jonathan Cowie reviews the science.

Origins. Some time around the closing months of 2002, viruses were on the move jumping species. Then a rare, event took place when two viruses that hosted two distinct groups of animals (birds and mammals), merged. Such species-jumping events are rare but they are not unique. Strains of human flu do occasionally originate from viruses from birds, transferring to pigs and then to humans. In east Asia, humans in large numbers live with ducks and pigs and this combination of factors is one of the main reasons why new flu strains regularly emerge from that part of the World and often go on to infect 5-15% of the global population giving a median figure for annual infection of about 600 million. The economic cost of flu outbreaks is also considerable and in the US alone is estimated at US$71 - 167 billion (2003) a year.

Equally rare, but equally not unique, is this merging of two viruses. This can happen when two different viruses infect the same cell. You see, all a virus is is a rolled up strand of genetic material (either DNA or RNA) surrounded by a protective sugar-protein coat. Your cells are different. Your genetic material sits in each of your cells' nucleus and then biochemical messages are sent from the nucleus to other parts of your cell to make other biochemicals that enable your cell to work. What a virus does, being the ultimate parasite, is infect your cell and then use its genetic material to run your cell for its own purposes (primarily for the virus to reproduce). So simple and neat is this that a number of the few of us bioscientists who seriously contemplate alien biologies, consider that viruses will be virtually ubiquitous on living worlds. Having said that their genetic material may not necessarily be restricted to DNA or RNA: one can imagine other workable biochemical compositions for genetic material. As regards this business of two different viruses merging, this could take place when both viruses infect the same cell and, having divested themselves of their respective sugar-protein coats, merge their genetic material. And voila - allowing for a certain amount of compatibility (for starters both viruses must either be RNA or DNA, and not one of each) - hey presto, a new virus never before seen appears. This originating event for the SARS virus is thought to have taken place in the Chinese province of Guangdong probably routing between poultry, pigs and humans (though the exact originating species is still (june 2003) being investigated). It marked the start of an epidemic of a lethal disease.

And so it was that on 12th March 2003 the World Health Organization (the UN health information processing and policy agency) issued a global alert about cases of atypical pneumonia in Viet Nam, Hong Kong Special Administrative Region (with the coincidental abbreviation of SAR) and China, especially its Guangdong province. (Ref: WHO press release 22 (2003).)

What type of virus is the SARS virus? On 16th April 2003 the World Health Organization announced the results of rare close collaboration of 13 laboratories from 10 countries (Canada, China, France, Germany, Great Britain, Hong Kong SAR, Japan, the Netherlands, Singapore, and the USA). The combined-effort lab results showed that the SARS virus is a coronavirus. Known coronaviruses usually cause little worse than the common cold in humans, however it is also known that there are nastier versions that infect birds and other mammals: avian infectious bronchitis virus for example.

Transmission risks. Human coronaviruses can survive on dry surfaces for up to three hours, they are not normally transmitted through the air unless carried in tiny droplets as produced by a sneeze or a cough. So very close contact with a patient is the normal means of transmission and is (at the time of writing early summer 2003) how the SARS virus appears to be spreading.

But is there a risk of catching SARS on a plane? So far (May 2003) there has been no record of anyone catching SARS on a plane. However there is a record of people catching it sharing a (hotel) lift. Therefore if anyone does ever catch SARS on a plane the likelihood is that they will do so either because someone vociferously sneezed without using a handkerchief right next to you, or because you have just entered the confines of, say, the aircraft toilet immediately after a SARS carrier has sneezed within it. The virus enters the body through the nose or throat. So if you are not near a sneezing person spewing an aerosol of virus particles into the air, then the big risk is touching surfaces that have been exposed to the virus in the past couple of hours and then transferring the virus to your face. So antiseptic wipes are a help. With flu there is usually an incubation period of between one and four days before the person develops symptoms. Someone suffering from influenza can be infectious from a day before symptoms manifest to up to seven days after. For SARS the incubation period is longer is typically between two and eleven days. Subsequently the fever hits with temperatures exceeding 38 degrees Centigrade, breathing difficulties then increase and the patient has extreme lethargy. A few patients get diarrhoea.

What is the SARS mortality rate? As of April 2003 SARS had a mortality rate in developed countries of about 6-9% (May 2003 data below). This compares with a mortality rate of about 2.5% for the Spanish flu epidemic of 1918 that killed some 40 million people. Having said that, there is poor reporting from the rural (and indeed some urban) parts of China. These areas have less adequate medical resources and so in all probability are experiencing a higher mortality rate. It also needs to be remembered that antivirals and assisted respiratory devices were not available back at the time of the 1918 flu epidemic. A report in April 2003 in the British Medical Journal estimated that some 15% of SARS infected cases might need intensive care. To put the mortality of the 2003 SARS epidemic into some sort of context we need to bear in mind that of the 5-15% of the global population affected by flu every year there is an associated global mortality of between 250,000 and 500,000: a mortality rate of about 0.5%. Most deaths from influenza in developed nations are associated with the over 65s. Similarly with SARS, age seems to be a related factor affecting mortality. The actual reported figures for 31st March 2003 were 1,622 people infected in 14 countries with 58 deaths. By mid-May, just 6 weeks later, this had risen by some 380% to 7,860 infected and mortality by over 1,000% to 642 people. However since then the spread of the virus began to slow, though by early June the toll stood at 8,384 infected and 770 dead.

Treatment. In the west SARS treatment usually includes giving a broad antiviral agent such as ribavarin at 8mg/kg body mass every 8 hours intravenously, or 1.2g every 12 hours orally. Hydrocortizone may also be provided to reduce inflammation. Finally, antibiotics are given to combat opportunistic bacterial secondary infections. Those requiring intensive care may also require a period (days) of forced ventilation such as using an iron lung.

So what are the SARS risks of going to the 2003 Toronto Worldcon? As at April 24th there were some 139 cases and 15 deaths in Toronto compared to over 3,700 cases in Hong Kong and (so they then said) China, but reporting from China is suspect. The Toronto outbreak has been reasonably contained, so provided one avoids going to the infected areas (primarily two hospitals) the SARS risk is relatively low. This does not mean it is zero, just as the risk of getting killed by being run over in a car in Toronto is not zero, but the risk of car-death is so low so as not to put off travellers. The important things if you are going to the Worldcon is to ensure that the World Health Organization (WHO) does not have adverse travel advice and that you have health insurance cover. Both these are prudent precautions and you would be wise to take them. At the time of writing the WHO does not have any restrictive advice for travelling to Toronto, though in the UK at least, the health insurance situation is less clear. Having said that, most insurance companies record their telephone calls so you can call them to confirm what your policy will cover. Importantly get them to confirm that if you do go to Canada and meet with a non-SARS related health incident that your health insurance will cover you. Ask them to confirm that the call is being recorded and note their advice and date and time of the call.

So am I going to the Worldcon? I certainly hope to subject to health insurance and the WHO status. However if I do not go then I loose my hotel bill and my air flight which have already been paid and total (UK Pounds) £1,000! Yes, I am prepared to make the gamble.

What are the future global risks from SARS and other infectious outbreaks? New strains of existing diseases occur all the time. With influenza one or two strains of global concern emerge virtually annually. However major reconfiguration of influenza genetic material is rarer and the merging of two quite different viruses (normally infecting different, but overlapping, groups of species) resulting in global concern is rarer still. Major genetic re-configuration of influenza-A (one of two categories causing human disease) has occurred three times in the 20th century. The 1918/19 Spanish flu, the 1957 Asian influenza, and the 1968 Hong Kong influenza outbreaks. More recently, in 1997 and 2003, there have been limited outbreaks of re-configured influenza viruses directly transmitted from birds to humans in the Hong Kong Special Administrative Region, but these outbreaks were curtailed by prompt action of poultry culls and other measures.

In terms of the longer-term prognosis, it is most unlikely that we will get rid of SARS. We will have to learn to live with it and to accept that travelling to parts of the World (such as E.Asia) one has the risk of catching it. Control in industrialised temperate nations is more likely. Industrialised nations have the health-care resources and the temperate climate may provide an annual seasonal check. However the really big questions relate to whether there will be other outbreaks of new infectious agents with significant mortality?

The answer to this last is that outbreaks of novel infections are not new. So we can say with certainty that something like (or unlike) the 2003 SARS outbreak will happen again: you can count on it. Some of these will have a smaller biomedical impact on humans than SARS currently does. Equally others will have a greater effect.

But what of future outbreaks ability to spread around the globe and among the population? We can say with certainty that the risk of increased spread around the globe and among the population will increase dramatically over the next four or five decades! The reasons for this are three fold. First the global population is still increasing. In the year 1850 it stood at 1.2 billion, was around the two billion mark at the turn of the century (19th/20th), reached five billion by 1987 and topped six billion at the turn of the 20th century into the 21st. Estimates for the global population for the year 2050 are between 9 and 11 billion. That is a lot of people to transmit viruses. Second, this population is not spread evenly around the World but is concentrated in mega-cities (whose population exceed 10 million). The residents of such cities with their high population densities and internal mobility (necessary for the provision of food, energy and other services) make them increasingly vulnerable to the spread of epidemics. Third, the global population is itself more mobile than ever before with air passenger transport (in terms of passenger miles) growing ahead of population growth: there are around a quarter of a million people over the North Atlantic at any one time. The thing is that not only do each of these three factors individually increase the risk of global pandemics but their effect together is multiplicative (and not simply additive). The bottom line is that just as my grandparents witnessed the 1918 global flu pandemic, so in my life I fully expect to witness other global pandemics and some with even greater mortality than 1918.

So are the World's leaders doing enough? Sadly the answer is no! Indeed this was brought home to me last year when addressing the related issue of combating the spread of antibiotic resistance. This was the last big project I did for my former employers (of some 15 years to 2003), the Institute of Biology, as Head of Science Policy and Books in representing the UK biological community to UK policy-makers. First, we held a two-day symposium to get the science sorted, and then we produced a punchy broadsheet outline the concerns and a possible way forward called Pharmageddon Now! This was launched in October 2002 at a reception at the House of Lords (the upper chamber of the UK parliament) to Parliamentarians and was mirrored by a quite separate event on Congress Hill in Washington organised by USAID (the US governmental department responsible for fostering foreign development). Then in November we held a House of Lords dinner for Parliamentarians with an interest in the topic, civil service policy-implementers, and expert scientists. At the end the results (including two key suggestions with zero tax-payer impact) were fed into a House of Lords Science & Technology Select Committee enquiry called Fighting Infection: which at the time of writing (June 2003) has yet to report. This report will be pivotal. However will politicians notice? Not if their interest in the Pharmageddon Now! venture is anything to go by. For though the event was well attended by scientists, a few Parliamentarians and members of the scientific civil service, not one Minister (or even junior Minister) participated, or sent a deputy, or wrote a letter calling for the results to be sent to their Departments. And so antibiotic resistance continues to spread, and equally so our ability to combat new infectious agents is reduced. Strangely, at a time when politicians are exercising their concern over, for example, a remotely possible meteor strike of global devastation, politicians are ignoring one of the top five mechanisms that will truly have a major deleterious impact on our global population, that of the emergence and global spread of new infectious agents. Sadly this neglect is all too typical of a range of issues from food supply to the loss of biodiversity. There really is going to have to be a major re-think among our World's leaders as to the way we manage and utilise science. One thing's for sure, the next global epidemic is coming. What's the betting I'll be discussing this in Toronto?

Jonathan Cowie

End-of-article statement. Jonathan Cowie is an environmental scientist and a 'Chartered Biologist'(C.Biol.). This article is based on a review of SARS literature between February and June 2003, published by: the World Health Organization press unit, the British Medical Journal, and the multi-disciplinary journal Nature, as well as the comments made at an April British Association for Advancement of Science SciBar meeting with UK virologist Jon Oxford and epidemiologist Roy Anderson. While the author has attempted to accurately summarise for lay people the science, responsibility for the interpretation of risk must remain with the individual reader. For example, while it would be true to say that the risk of travelling to a country and getting killed in a car accident is small (and so might not normally be the basis for cancelling one's trip), it is not zero. Similarly while the risk of visitors catching SARS in say Canada or the UK (both of whom have SARS cases mid-2003) might be considered to be very low, it is not zero. Therefore if you are worried about your personal safety due to the standard of Canadian or UK drivers, then arguably you might wish to consider avoiding going to these places that have approximately a very broadly similar order of magnitude SARS risk. If on the other hand you are not worried about such concerns, and if the World Health Organization does not have SARS-related, prohibitive travel advice to the place you are going, then you should be reassured.

STOP PRESS 5th July 2003 The World Health Organization (WHO) today declared SARS contained. Some 800 deaths and still a few hundred infected but its under control, until the next time…


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