Update VII: SARS now looks to be much more infectious than previously thought. See my later post Fears Grow That SARS May Spread Into Pandemic. Also read below for historical context about previous epidemics.
There is a new deadly strain of some kind of pathogen (its not yet clear if its an influenza but it is suspected to be a virus of some kind) has been making some people sick and it appears to have originated in Guangdong province China. The illness is being called atypical pneumonia or Severe Acute Respiratory Syndrome (SARS). The nature of the illness has started to raise alarms.
Before we get to that lets put it in perspective by taking a brief look at most famous and deadly influenza outbreak recorded in modern history. The lethality of that outbreak explains why public health officials become very worried when new strains of pathogens with increased lethality are reported.
The Epidemic spread quickly around the earth. In all, some 525 million people were infected by the virus, with about 21 million people dying. That was more than twice the number who had been killed during the Great War. In many countries public gatherings were forbidden. The Flu was especially devastating on many people as they welcomed back their men from the war, overjoyed that they had managed to survive the slaughter that was the war. But their joy soon turned to grief when they found out that their men had brought the virus back with them, and it would not only kill them but also other family members.
The flu may really have originated in Tibet but the first known concentration of deaths from it occurred in Spain and hence its called the Spanish Flu. The estimates of how many died from it vary from 20 to 40 million. Spanish Flu struck down people in the prime of life.
Spanish Influenza swept the entire globe in the years 1918-1920, leaving a billion people sick, more than half of the worid's population at that time. It killed at least 30 million people, threc times the death toll of World War l (Wilton 1993). A study for Norway has recently resulted in an upward revision of the death toll. The suggested estimate is 14 676, twice as high as the most frequently cited figure (Mamelund 199Sa). The socio-economic impact of the flu was also considerable. One reason for this is that the flu took its greatest toll among people in their most productive ages (20-40 years, especially men), i.e. that part of life when people tend to marry and have children (Mamelund 1998a).
The 1918 Spanish flu was one of the most contagious viruses ever known. It killed as many as 40 million people in the winter of 1918 and 1919, more than died in the First World War.
Flu strains vary considerably in their lethality. Spanish flu belongs to the Type A strain. Type A strains are usually more lethal than other types. See here and here for information about influenza types and how they mutate to form new strains. A later type A influenza strain killed hundrends of thousands in 1968:
Hong Kong Flu - Common name for the influenza A strain that killed nearly 750,000 people around the world in the 1968 pandemic
Influenza mutates. Some mutations are more lethal than others. As Spanish flu demonstrated, some can be incredibly lethal. Should we be worried that a new influenza strain might pop up and kill millions including members of our families and circles of friends? Well, on one hand we have more advanced medical technologies. You might think we could much better handle a new strain that was as harmful as the Spanish flu. But keep in mind that if a significant portion of the population gets sick all the hospital beds will fill up and there won't be enough respiratories and other modern medical equipment to go around. Also, we don't have highly effective treatments to use against viruses that compare to the antibiotic drugs that are effective for use against most bacteria (though the rise of drug resistant bacterial strains is making bacterial infections a growing concern).
Another problem we have is that cars and airplanes move more people around the globe and much faster than was the case over 80 years ago. So new disease strains can spread rather rapidly and can reach even remote places.
Still, its not all doom and gloom. The best way to avoid dying or getting very sick from a disease is to avoid exposure in the first place. The biggest advantage we have are far better ways to isolate ourselves from sick people. For instance, we live in less dense housing. Accounts of the 1918 epidemic describe immigrant families living in crowded New York City tenements where lots of people breathed each other's air. Individual families just had to have one member come home with the disease and soon ten or twenty others were all exposed to it and likely other people walking up and down the same staircases were exposed as well. By contrast, today we have smaller families and on average a much lower number of people living in each dwellling and more square feet of living space per person.
If it was suspected that some deadly disease on the order of the 1918 flu epidemic was on the scene then the most rational response would be to quickly and calmly reorder society in ways that would reduce risks of exposure. With this in mind one of the strangest (at least to my American eyes) things I saw riding subways and trains in Japan were people wearing surgical masks. Either they were sick and didn't want to pass their illness on to others or they wanted to avoid breathing in particles of influenza and cold viruses coughed into the air by others. Such a practice is easy to adopt. The inconvenience would be fairly minor and it beats dying. Even if there was a shortage of surgical masks all matter of cloth can be adapted to that purpose.
A reduction of exposure between humans can be accomplished in many other ways. People who go shopping can go less often, buy more per trip, and not go during rush hours when the isles are crowded. Optional activities such as vacations, club meetings, movie outings, concert attendance, and the like can be cancelled. People who are able to work from home can stop going into the office. Another simple thing is to avoid touching surfaces in public places. If you do then wash your hands quickly (perhaps with a bottle of antiseptic fluid). Better yet, wear gloves and avoid touching surfaces in public places. Also, when out in public avoid touching your face with your hands unless you've recently washed your hands. Even the people who can not change their daily routine will be at less risk if all those who can change their daily routine do so to the extent that they can.
Okay, so lethal epidemics can still happen. But we have lots of things we can do to reduce our risks of getting seriously ill or killed in such an epidemic. With all this in mind lets look at a recent development that has health officials thinking some pretty worried thoughts.
12 March 2003 | GENEVA -- Since mid February, WHO has been actively working to confirm reports of outbreaks of a severe form of pneumonia in Viet Nam, Hong Kong Special Administrative Region (SAR), China, and Guangdong province in China.
In Viet Nam the outbreak began with a single initial case who was hospitalized for treatment of severe, acute respiratory syndrome of unknown origin. He felt unwell during his journey and fell ill shortly after arrival in Hanoi from Shanghai and Hong Kong SAR, China. Following his admission to the hospital, approximately 20 hospital staff became sick with similar symptoms.
The signs and symptoms of the disease in Hanoi include initial flu-like illness (rapid onset of high fever followed by muscle aches, headache and sore throat). These are the most common symptoms. Early laboratory findings may include thrombocytopenia (low platelet count) and leucopenia (low white blood cell count). In some, but not all cases, this is followed by bilateral pneumonia, in some cases progressing to acute respiratory distress requiring assisted breathing on a respirator. Some patients are recovering but some patients remain critically ill.
Today, the Department of Health Hong Kong SAR has reported on an outbreak of respiratory illness in one of its public hospitals. As of midnight 11 March, 50 health care workers had been screened and 23 of them were found to have febrile illness. They were admitted to the hospital for observation as a precautionary measure. In this group, eight have developed early chest x-ray signs of pneumonia. Their conditions are stable. Three other health care workers self-presented to hospitals with febrile illness and two of them have chest x-ray signs of pneumonia.
15 March 2003 | GENEVA -- During the past week, WHO has received reports of more than 150 new suspected cases of Severe Acute Respiratory Syndrome (SARS), an atypical pneumonia for which cause has not yet been determined. Reports to date have been received from Canada, China, Hong Kong Special Administrative Region of China, Indonesia, Philippines, Singapore, Thailand, and Viet Nam. Early today, an ill passenger and companions who travelled from New York, United States, and who landed in Frankfurt, Germany were removed from their flight and taken to hospital isolation.
Due to the spread of SARS to several countries in a short period of time, the World Health Organization today has issued emergency guidance for travellers and airlines.
“This syndrome, SARS, is now a worldwide health threat,” said Dr. Gro Harlem Brundtland, Director General of the World Health Organization. “The world needs to work together to find its cause, cure the sick, and stop its spread.”
There is presently no recommendation for people to restrict travel to any destination. However in response to enquiries from governments, airlines, physicians and travellers, WHO is now offering guidance for travellers, airline crew and airlines. The exact nature of the infection is still under investigation and this guidance is based on the early information available to WHO.
Countries are starting to discourage their citizens from travelling to areas where SARS has been reported. Thailand joins Singapore and Taiwan in urging their citizens not to go to Hanoi or southern China.
Passengers are being required to fill out health forms indicating whether they had been to the affected areas, and airlines have been instructed to report immediately if any passengers begin exhibiting symptoms.
The announcement follows similar moves by Singapore and Taiwan, which have both urged their citizens not to travel to Hanoi in Vietnam or southern China "unless absolutely necessary".
"It is either a new germ which hasn't caused a disease before or is a more common germ which has undergone a large change," David Bell, a public health physician at the Manila-based WHO Western Pacific office, said.
"If it is a new organism -- which has undergone significant change -- it may be more difficult to identify," warned Rob Condon, a WHO epidemiologist at the same office.
World Health Organization official David Heymann is clearly worried.
"It is not a very good situation," said Dr. David L. Heymann, a top expert in communicable diseases at the health agency. "It is a very difficult disease to figure out, and this has been going on for the last 10 days to two weeks."
Influenza has not been ruled out as the cause.
Among the survivors, "no one has gotten well yet," Dr. Heymann said in an interview. "It is not clear what is going on, and it is not clear what the extent of spread will be," particularly because "these are areas where there is a lot of international travel," he added.
Dick Thompson, a WHO spokesman in Geneva, could recall no such emergency travel advisory being issued in recent memory.
"Until we can get a grip on it, I don't see how it will slow down," said Thompson. "People are not responding to antibiotics and antivirals, it's a highly contagious disease and it's moving around by jet. It's bad."
Now that so many health authorities and medical doctors are attempting to identify victims of this disease it may be possible to contain it. One advantage we have today that didn't exist over 80 years ago is that information travels even more quickly than people do. A lot of the initial victims were hospital workers. One would expect the rate of infection of health care workers to drop as they recognize the disorder more quickly and take more drastic measures to avoid exposure from infected patients. However, one concern there is that in less developed countries the health care workers may lack the kinds of facilities and supplies needed to reduce their own degree of risk. Therefore the health care workers in less developed countries may end up either spreading the disease or they may turn away the sick and therefore the sick may not be properly isolated. Whether efforts at containment will work remains to be seen.
Will this disease spread and kill massive numbers of people? Don't know. Its certainly a story to watch very carefully.
Update: Encouraging news about SARS comes from a CDC press conference. Dr. Julie Gerberding of the CDC says the pattern of transmission so far has been through close personal contact.
QUESTION: And also, do we know how contagious? I mean if I was on a subway car with someone who was ill, could I get it from them, or do you need to have that close like I'm-taking-care-of-me kind of contact.
DR. GERBERDING: What we know so far from the investigations in progress are that it's very close personal contact of the type defined by WHO as having cared for, having lived with, or having had direct contact with respiratory secretions and body fluids of a person with the diagnosis. So there is no evidence to suggest that this can be spread through breath contact or through assemblages of large people; it really seems to require a fairly direct and sustained contact with a symptomatic individual.
If pattern of transmission continues then the chances of containing the disease will be much better. If it becomes as easy to transmit as a cold or regular influenza then containment would be much more difficult and perhaps impossible. So far there has been no indication whether the disease is transmissible during the asymptomatic incubation period. Whether it is will also affect the ability to slow or stop its spread.
Update II: Even if SARS doesn't turn out to be a massive killer plague (and its pattern of transmission suggests it will not be) we are still vulnerable to being killed off by a pathogen that hops into the human population from another species and that mutates into a virulent form. We have had close calls that have been contained such as the 1997 chicken influenza that was extremely deadly in humans.
In 1997 epidemiologists and public health officials from around the world got their first glimpse¹ of an entirely new variety of human influenza. Known as subtype H5N1 for the surface proteins which the virus carries, the new strain had only ever previously been observed in birds. Ominously, the effect of H5N1 on poultry had earned it the evocative title of "Chicken Ebola." And when it surfaced in the human population of Hong Kong last year it proved to be almost as deadly.
How deadly? Even with the advantages of intensive-care treatment, fully one third of the first 18 confirmed cases never recovered. They died.
What is needed is the ability to develop and produce vaccines more rapidly. DNA vaccines are held out by some researchers as promising faster and lower cost manufacture with fewer side effects than many conventional vaccines. However, another promising approach is to use bacterial viruses knows as bacteriophages to produce vaccines very rapidly and cheaply.
BALTIMORE – March 10, 2003 – Genetically altered bacterial viruses appear to be more effective than naked DNA in eliciting an immune response and could be a new strategy for a next generation of vaccines that are easy to produce and store, say researchers from Moredun Research Institute in the United Kingdom.
"In theory, millions of doses can be grown within a matter of days using simple equipment, media and procedures," says John March, one of lead researchers presenting findings at the American Society for Microbiology's Biodefense Research Meeting.
Bacteriophages are viruses that infect bacteria but not humans. In this particular study, March and his colleagues used a bacteriophage as a vehicle for genes from hepatitis B virus in mice and compared its ability to elicit a protective immune response with a vaccine made of naked DNA. They found that not only could the bacteriophage induce an immune response, the number of bacteriophage they needed was less than 1 percent of the number of pieces of naked DNA required to mount an effective immune response.
Using bacteriophages to deliver vaccine components offers several advantages over vaccination with naked DNA, says March. The DNA is protected inside the protein shell of the virus making it longer lasting and easier to store. In addition, bacteriophages have a large cloning capacity, making large-scale production cheap, easy and extremely rapid – important attributes considering the current bioterrorism threat when sudden demands may be placed on vaccine stocks.
In order to produce vaccines the vaccines first must be developed. One has to have a design for a vaccine. Therefore the other needed element of a fast response strategy for new strains of influenza and even for new kinds of pathogens is to have high isolation labs that are equipped to rapidly take apart a pathogen and to develop vaccines for it. See my recent post United States Lacks Sufficient Biodefense Lab Space. What is needed is not just ultra-secure and ultra-isolated lab space. The labs would need to be equipped with or be located near labs that capabilities to do DNA sequencing, protein sequencing, protein structure determination and other relevant capabilities. Properly designed and equipped such labs could work on longer term problems between crises but when a deadly naturally occurring or man-made pathogen threatened to cause massive numbers of fatalities the best microbiologists and virologists could staff them and work to develop vaccines and drugs.
Update III: The illness may be caused by a paramyxovirus.
There is a long list of other candidates, with a family of microbes called the paramyxoviruses "certainly ranking on the top of most people's thoughts," said Klaus Stohr, a WHO virologist and epidemiologist who is helping to direct the investigation.
Update V: To reiterate for those who are worried that SARS could become an enormous killer: It is spreading slowly. It appears to require fairly close contact to catch it. It does not appear to be as easily transmitted as many cold and influenza viruses. In a March 17, 2003 press conference Dr. Julie Gerberding, Director of the Centers for Disease Control and Prevention, says SARS is not being transmitted by casual contact. (bold emphases mine)
We know that the disease is so far limited to people who have had very close contact with cases. Most of the individuals are health care personnel who have been in direct contact with either the patient or body fluids from the patient. We also know that household contacts are at risk, particularly if they've had direct and sustained contact with sick individuals.
So far the cases are limited, as Secretary Thompson said, to individuals who have either lived in parts of Asia that are affected, or who have recently traveled from those areas.
We believe the incubation period is approximately 2 to 7 days, although as new information unfolds, that may be updated. So the travel advisories that have been issued stipulate that individuals returning from those areas with fever and respiratory symptoms within 7 days of their departure should seek medical attention to be sure that they are not in the early stages of this syndrome.
We also know that there is no evidence so far that persons not in direct contact with suspect cases are at risk. We have not identified any people with casual contact or indirect contact. I think we were reassured by the investigation here in Georgia, where there was an individual who acquired this infection presumably from family members, was here in this city while sick, was involved in activities that involved exposure to others in a workplace setting, and there is no evidence of spread from that kind of contact in the workplace.
Nevertheless, I stress again this is an ongoing investigation. We certainly don't have all the information we need to know to have certainty about any of these issues, and we will just simply have to update you as we go forward.
The most important thing that we need to do is to prevent spread of this infection, and I'll tell you some of the things we're doing about that right now. But the second most important thing is to figure out what's causing. This appears to be a contagious infectious disease, and as I said, limited to health care personnel and close household contacts. That suggests spread by the droplet route, and that's why our infection control precautions emphasize prevention of droplet spread through the use of face shields and gowns and gloves.
Update VI: The disease is increasingly looking like it is not spreading. Victims are popping up in more countries but the vast bulk of them all were infected in China or Vietnam. Therefore a general outbreak all around the world is looking less likely. Now that the knowledge about its symptoms has been widely disseminated victims are rapidly isolated and health care workers protected from exposure. Hopefully this trend will continue and the disease will be contained. The disease increasingly looks like a new pathogen
"As time goes by that is increasingly likely, simply because so many people have run so many tests," said Iain Simpson, a spokesman for the World Health Organisation (WHO).
"If it is something we already knew about we would almost certainly have identified it," he told Reuters.
While this disease looks like it is going to be successfully contained it should serve as a wake-up call that we are ill-equipped to deal with a deadly disease that spreads easily and that does break out into the general population. Some day a much more deadly influenza strain will cross over from fowl or swine into humans and as of yet we are unprepared to effectively deal with that eventuality.
Update VII: SARS now looks to be much more infectious than previously thought. See my later post Fears Grow That SARS May Spread Into Pandemic.
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