Hong Kong Flu Still Poses Pandemic Threat


JAMA: The Journal of the American Medical Association Vol. 288 No. 19, November 20, 2002


Brian Vastag

WashingtonIn December 1997, news watchers were confronted with sobering images of government workers in Hong Kong slaughtering 1.4 million chickens in a massive effort to prevent avian influenza from spreading through the densely populated city and, potentially, across the globe.

Earlier that year, what was later identified as a strain of influenza previously known to infect birds, but not people, had sent 18 patients to Hong Kong hospitals. The first case led to the death of a 3-year-old boy, followed by the deaths of five other patients.



Chickenson their feet and on the rackfor sale at a shop in Hong Kong. In June 2001 and May 2002, a total of 4 million chickens were destroyed there to stanch the potential spread of influenza. (Photo credit: Corbis)

Somehow the virus had jumped species. Working with the US Centers for Disease Control and Prevention (CDC), Hong Kong health officials began implementing a control plan designed to obviate such drastic measures in the future.

It didn't. In June 2001, and again in May 2002, a total of 4 million chickens in Hong Kong were destroyed to stanch potential pandemics. Both cullings were precipitated by detection of influenza virus in Hong Kong poultry, said John Siu-Lun Tam, PhD, a professor of microbiology at the Chinese University of Hong Kong, during a scientific session at the meeting of the World Medical Association held here in October.

And although angst over the specter posed by bioterrorism dominated the meeting, a CDC official warned that the threat of an influenza pandemic is still "very real." Such a worldwide outbreak would dwarf the influenza epidemics that sweep through the United States every winter, said Nancy Cox, PhD, chief of the influenza branch of the National Center for Infectious Diseases at the CDC.

While a typical flu season claims about 20 000 US lives annually, a pandemic could provoke 207 000 deaths, 734 000 hospitalizations, and 42 million outpatient visits, estimated Cox and CDC colleagues Martin Meltzer, PhD, and Keiji Fukuda, MD (Emerg Infect Dis. 1999;5:659-671).

"It would be extremely overwhelming," said Cox.




EMERGING STRAINS



The worst influenza pandemic of the 20th century (in 1918) spread so quickly that it claimed 20 million lives worldwide. The other two influenza pandemics of the past century, in 1957 and 1968, led to many fewer deaths, but still killed 70 000 and 34 000, respectively, in the United States alone. And while the winter flu preys mainly on the elderly and others with weakened immune systems, pandemics lead to a higher proportion of deaths among children and young adults, said Cox. Most of those killed in 1918 were working-age adults.

Methods to predict the where and when of a pandemic have not advanced appreciably since the 1918 pandemic. Cox warned that new strains can emerge suddenly and unpredictablytwo factors that differentiate a pandemic (extensive emergence of a virulent new strain) from an epidemic (localized circulation of a known strain).

The 1997 Hong Kong outbreak caused such intense concern not only because the strain was new, but also because it apparently jumped directly from poultry to people. In the past, influenza watchers thought that to infect people, any new avian strain would first have to spread through herds of pigs. Susceptible to both bird and human influenza, the animals act as incubators of virulent strains, said Cox. As the porcine immune system fights infection, avian and human viruses shuffle genes in a sort of natural genetic engineering that can breed deadlier varieties.

But since people in Hong Kong prefer poultry to pork, pigs were not suspected in the 1997 "bird flu" cases. Instead, epidemiological investigations isolated domestic birds as the common link. The index case, a 3-year-old boy, often played with pet ducks. Twelve of the other 17 patients had handled poultry in the week prior to becoming ill. A recently published study confirmed the potential for chicken-to-human transmission, finding antibodies to the 1997 strain in 10% of 1523 Hong Kong poultry workers (J Infect Dis. 2002;185:1005-1010).

Conditions are ripe for nonoccupational exposure as well, said Tam. "There is a strong emphasis on freshness," he said, and customers like to pick up and inspect live chickens at the 930 poultry markets in the city. "They touch the neck and blow on the other end to see how good it is," he said, holding up and turning his hands as if looking at the bird's rear. Prior to 1997, Tam said, conditions at the markets were unsanitary, with feathers and feces abundant.

Since then, the city's health department has mandated new hygiene and safety standards. Ducks and geese, which serve as the natural reservoir for the 15 known strains of influenza A, are now shipped and slaughtered separately from chickensto interrupt the first link in the pandemic chain, said Tam.

New surveillance measures at the Chinese border, where 85% of the poultry consumed in Hong Kong originates, have also taken effect. Each arriving flock is quarantined, tested, and held for 2 days. Flocks with one or more sick birds are rejected while clean flocks move to a central wholesale warehouse, where they wait 2 days more.

"Four days is the time it takes a chicken to die" from influenza, said Tam. If a bird is still flapping at the retail market, it is probably not infected.

On the farms where the rest of Hong Kong's chickens come from, any sign of infectionsick birds, positive antibody testsleads to a quick slaughter and ring vaccination of birds at surrounding sites.

Despite these measures, which have gradually been phased in over the past 5 years, the health department again resorted to massivealthough not massively publicizedcullings in 2001 and 2002. Questioned by a meeting attendee about this, Tam said that the prevalence of the virus type detected in 1997 is too widespread to eliminate completely. "We see this as a problem for the region, not just Hong Kong," he said. "We tell people that we cannot eliminate [the virus], that we are trying to reduce the source to prevent human cases."




INCREASED SURVEILLANCE



Fortunately, the 1997 virus apparently never acquired the ability to spread from person to person, although a shred of evidence from a study of household contacts of patients suggests that such transmission is possible. Researchers found antibodies against the bird flu strain in a household member who had no contact with poultry (J Infect Dis. 1999;180:1763-1770). Concern that a mutation fostering airborne human transmissibility could arise, making the final link in the pandemic chain, has the Hong Kong health department, the CDC, and the World Health Organization constantly searching for methods to improve surveillance, detection, vaccination, and treatment.

The region that includes southern China and Hong Konga historical, although altogether not well understood, source of new influenza variantsis high on WHO's hot list. With WHO's support, the city's surveillance system, widely credited for halting the 1997 outbreak, has been expanded and now includes 111 sentinel physicians.

In 1999, the sentinels and other local hospitals and clinics sent 17 351 specimens to a central laboratory for influenza testing. The health department collects and disseminates influenza information, including reports on extant subtypes, on a weekly basis.




BLIP ON SURVEILLANCE RADAR



In March 1999, the system flagged another new influenza strain found in samples from two sick children, although the source was never identified, said Cox. A cohort study found no evidence of person-to-person transmission, but an epidemiological investigation revealed that 23% of one group of poultry workers tested positive for exposure (Emerg Infect Dis. 2002;8:154-159). The strain was found in Asian poultry and pigs, but has not reappeared in Hong Kong's clinics. This odd blip on the surveillance radar is a testament to influenza's unpredictability.

That blip also prompted the CDC to develop vaccine for the strain; Cox said that three candidate vaccines are approaching human trials. But even while the development of a vaccine targeting this novel strain is moving forward, vaccine production remains the "Achilles' heel of pandemic preparation," said Cox. With current technology, manufacturers need 8 months to produce 250 million doses of trivalent influenza vaccine, which typically comprises the three strains that experts believe (based on surveillance of strains circulating worldwide) constitute the most likely threat for the following winter.

Cox guaranteed that in the event of a pandemic, which could spread globally in a few months, "there won't be enough [vaccine] to go around." She called for the development of "a library of candidate vaccines on the shelf, ready to go," as well as expedited research into advanced production methods, such as cell-based cultures. In an age of sequenced genomes, influenza vaccine is still produced relatively crudely, inside incubated chicken eggs.

Until that method is replaced, then, Cox suggested an answer to the public health community's version of the hoary chicken-and-egg riddle: stockpiles of egg vaccine first, before another outbreak of chicken virus.

http://jama.ama-assn.org/issues/v288n19/ffull/jmn1120-1.html

Spanish Influenza Outbreak, 1918 by Sarah Cummings

"In the midst of perfect health, in a circumscribed community... the first case of influenza would occur, and then within the next few hours or days a large proportion- and occasionally every single individual of that community- would be stricken down with the same type of febrile illness, the rate of spread from one to another being remarkable... Barrack rooms which the day before had been full of bustle and life, would now converted wholesale into one great sick room, the number of sick developing so rapidly that hospitals were within a day or two so overfull that fresh admissions were impossible."
- Dr. Herbert French to the British Ministry of Health (Hoehling,18)

Between the months of August and November of 1918, Spanish influenza spread quickly across the United States and around the world in epidemic proportions. The disease was thought to have been brought from country to country by sea-faring vessels passing through major port cities around the world, with illness striking men of French troops, the British Royal Navy, civilians in America, and more. The Public Health Service sanitation officer and member of the First Navy District, Dr. William M. Bryan, was aware of the conditions in Boston and was worried by them, where hot, dusty, and dry conditions exacerbated the problem, forcing sailors and soldiers into crowded conditions in Boston, where the close conditions and poor housing aided in the quick spread of influenza from person to person (23).

Although influenza itself did not cause the deaths, but caused the pneumonia which did cause deaths, the number of deaths were still striking and rising. The deaths of three men in one afternoon in Quincy, Massachusetts caused the public to take notice. Bostonís church closed on September 22 to keep the public separated from each other (33). The disease proceeded to cause death in large numbers throughout the country. At one point, Philadelphia was stricken with 289 deaths within 24 hours(71).

If the problems involving the quick spread of the disease could have been foreseen, it would have been wise to take precautions concerning the close quarters in the major port town of Boston. There may have been a way to separate people to a greater degree and not allow them to be on such close terms that they could have passed the virus so quickly from one to another. A larger number of available places to board, though impractical, would have been helpful because the disease would have had more difficulty spreading than in the close confines that existed. These precautions, however, would not have had a great effect on stopping the progress of the disease at large, for the epidemic was so widespread. It was very easy for people to carry the virus from a boat into a city, and spread it to other people, who would then travel across the country. The short incubation period kept infected people from travelling too far, but the ease with which the influenza spread from person to person caused the outbreaks to occur at large frequency.

There were many opinions concerning the ways in which to prevent the spread of the disease to individuals. The use of the face mask by medical professionals was a controversial issue. Some believed that the mask would protect from the spread of infection, while others believed that the mask would not help at all. Influenza is spread through coughs, from one mouth to another, so masks would have been helpful in preventing infection of health care workers. Masks would have also been helpful for preventing the spread of pneumonia, which actually killed more people than the actual influenza virus itself. Those who did not wear masks put themselves at risk in an ineffective action. In some places, "open-faced sneezers" (81), were fined or sometimes jailed. The law began to take public health into its own realm. Different approaches for infection prevention were taken at military training camp on Goat Island, in San Francisco, where vaccines were given and objects such as drinking fountains and telephones were sterilized (35). These methods did not involve infringement upon the rights of the individual while attempting to protect the larger population, and were socially just methods of prevention. The vaccinations, however, would only be helpful if the patient had not yet developed influenza, but would aid in keeping the numbers down on the spread of infection. Sterilizations were non-invasive methods of increasing the sanitary conditions, which would also keep down the likelihood of infection.

The same group in Goat Island, San Francisco, was quarantined to isolate the infection. Because the island was a military training camp, the men there were separated from the rest of their families, and the imposed quarantine isolated them. They were unable to be with their familiesin San Francisco. Had the influenza outbreak been selective and small in size, only occurring at the Goat Island training camp, the quarantine may have been necessary and effective. The incubation period and length of the course of disease for influenza are relatively short, and the isolated incident could have been controlled and stopped. The outbreak of influenza was not contained to the training camp, though. Quarantine was actually imposed to keep influenza out of the community, and while it was extremely effective at doing so, those soldiers released from the camp quickly picked up the infection from San Francisco. The quarantine was less effective than intended, and bordered on being a socially unjust response. Because the quarantine on the island was unlikely to have stopped the spread of the infection in the rest of the world, it seemed an unnecessary measure biologically, and an unjust measure socially. As soon as the men were released from quarantine, they were exposed to the disease. In order to have been effective, the quarantine would have had to been imposed for a greater length of time, and until influenza had been eradicated from surrounding areas.

Quarantines were also imposed in other areas. Washington D.C. enacted a law that made it illegal to appear out of doors and out of one's home. The quarantine infringed upon the personal rights of the townspeople to attempt to benefit the greater population. Again, if the outbreak had been small and easily contained, the quarantine may have been necessary and effective, but attempts to stop the greater outbreak and spread of influenza by quarantine were not necessarily useful.

Some towns closed places of public entertainment to stop the spread of the virus from person to person contact. The Pennsylvania Health Commissioner, Dr. B.F. Royer, issued a statewide ban closing theaters, saloons, schools, churches, and public meetinghouses. The move was a smart attempt to control the disease within the small town population. Because the influenza outbreak was highly contagious and easily spread by coughs, it was a good idea to keep the population of the town from congregating in large groups to prevent the spread of the outbreak around the town. Although the rights of the individuals were somewhat infringed upon in order to protect the community, the measure seems to be an appropriate response in order to sustain the disease from spreading too much within one subset of the population. The difference between this ban and the quarantine of an entire group of people is that the bans prevented large groups of people from congregating and spreading the disease within themselves, while the quarantine did not provide for that kind of protection, but attempted to keep one population from spreading the disease to the other groups of people. The ban situation is an infringement of rights, but a smaller infringement to a better end than the quarantine. The ban is therefore more socially just than the quarantine.

As the summer and fall progressed, the frequencies of the influenza outbreaks increased. Problems arose concerning available funds to counteract the spread of infection. Money sources were dwindling on local levels, supplies of medicine were growing scarce, and many health care providers were becoming sick from exposure to the virus. The shortage of money and people seemed to be inversely proportional to the frequency of infection. The Surgeon General declared that the "United States Public Health Servic ha[d] no funds for epidemic control" (53). Congress respomded quickly, granting one million dollars for aid. People in Boston were so desperate for healthcare workers that they petitioned to President Woodrow Wilson for aid. People on numerous levels began to initiate new projects to provide relief and aid. The Red Cross began collecting and supplying emergency funds to stricken areas. In Philadelphia, to combat the shortages, a telephone switchboard service was set up at the department store Strawbridge and Clothier to take in calls from the ill and reference them to the necessary resources. Churches also sprung into action, and crossed religious and social bounds to take in the ill and infirm of any creed to take care of them. The action of the community was a strong and powerful force, and it appears that issues of social injustice were overpassed in order to take care of the greater issue, which was to overcome the epidemic.

Those who remained healthy did not always strive to solely take care of the ill and nurse the community back to health, but sometimes drove wedges into interpersonal relations for personal gain. Prices for medication rose, and some found that $15 burial fees did not include the gravedigging (Hoehling, 118). In these cases, the response of some community members was not at all useful or effective in combating the disease, but instead caused greater problems to those who were in need of medication or burial.

The problems did not necessarily end when the outbreak itself ended. After the official end of the epidemic, it may be imagined that life tried to continue as usual. The places of entertainment that had been previously closed were reopened, but there were a record number of arrests for drunkenness coinciding with the reopening of pubs. In November 1918, the epidemic "ceased to exist officially" (Hoehling, 185), according to the Philadelphia department of Health and Charities. The number of casualties had been large, and had totaled 13,000 in Philadelphia. By 1919, with outbreaks gradually ending, the epidemic ceased to exist in America and around the world.



Works Cited

Hoehling, A.A. The Great Epidemic. (Boston: Little, Brown, and Company, 1961).

http://www.haverford.edu/biology/edwards/disease/viral_essays/cummingsvirus.htm

Pandemics and Pandemic Scares in the 20th Century

Historical Overview
Centers for Disease Control and Prevention

History suggests that influenza pandemics have probably happened during at least the last four centuries. During the 20th century, three pandemics and several "pandemic scares" occurred. These are described in more detail below.

1918: Spanish Flu
The Spanish Influenza pandemic is the catastrophe against which all modern pandemics are measured. It is estimated that approximately 20 to 40 percent of the worldwide population became ill and that over 20 million people died. Between September 1918 and April 1919, approximately 500,000 deaths from the flu occurred in the U.S. alone. Many people died from this very quickly. Some people who felt well in the morning became sick by noon, and were dead by nightfall. Those who did not succumb to the disease within the first few days often died of complications from the flu (such as pneumonia) caused by bacteria.

One of the most unusual aspects of the Spanish flu was its ability to kill young adults. The reasons for this remain uncertain. With the Spanish flu, mortality rates were high among healthy adults as well as the usual high-risk groups. The attack rate and mortality was highest among adults 20 to 50 years old. The severity of that virus has not been seen again.

1957: Asian Flu
In February 1957, the Asian influenza pandemic was first identified in the Far East. Immunity to this strain was rare in people less than 65 years of age, and a pandemic was predicted. In preparation, vaccine production began in late May 1957, and health officials increased surveillance for flu outbreaks.

Unlike the virus that caused the 1918 pandemic, the 1957 pandemic virus was quickly identified, due to advances in scientific technology. Vaccine was available in limited supply by August 1957. The virus came to the U.S. quietly, with a series of small outbreaks over the summer of 1957. When U.S. children went back to school in the fall, they spread the disease in classrooms and brought it home to their families. Infection rates were highest among school children, young adults, and pregnant women in October 1957. Most influenza-and pneumonia-related deaths occurred between September 1957 and March 1958. The elderly had the highest rates of death.

By December 1957, the worst seemed to be over. However, during January and February 1958, there was another wave of illness among the elderly. This is an example of the potential "second wave" of infections that can develop during a pandemic. The disease infects one group of people first, infections appear to decrease and then infections increase in a different part of the population. Although the Asian flu pandemic was not as devastating as the Spanish flu, about 69,800 people in the U.S. died.

1968: Hong Kong Flu
In early 1968, the Hong Kong influenza pandemic was first detected in Hong Kong. The first cases in the U.S. were detected as early as September of that year, but illness did not become widespread in the U.S. until December. Deaths from this virus peaked in December 1968 and January 1969. Those over the age of 65 were most likely to die. The same virus returned in 1970 and 1972. The number of deaths between September 1968 and March 1969 for this pandemic was 33,800, making it the mildest pandemic in the 20th century.

There could be several reasons why fewer people in the U.S. died due to this virus. First, the Hong Kong flu virus was similar in some ways to the Asian flu virus that circulated between 1957 and 1968. Earlier infections by the Asian flu virus might have provided some immunity against the Hong Kong flu virus that may have helped to reduce the severity of illness during the Hong Kong pandemic. Second, instead of peaking in September or October, like pandemic influenza had in the previous two pandemics, this pandemic did not gain momentum until near the school holidays in December. Since children were at home and did not infect one another at school, the rate of influenza illness among schoolchildren and their families declined. Third, improved medical care and Antibiotics that are more effective for secondary bacterial infections were available for those who became ill.

1976: Swine Flu Scare
When a novel virus was first identified at Fort Dix, it was labeled the "killer flu." Experts were extremely concerned because the virus was thought to be related to the Spanish flu virus of 1918. The concern that a major pandemic could sweep across the world led to a mass vaccination campaign in the United States. In fact, the virus--later named "swine flu"--never moved outside the Fort Dix area. Research on the virus later showed that if it had spread, it would probably have been much less deadly than the Spanish flu.

1977: Russian Flu Scare
In May 1977, influenza A/H1N1 viruses isolated in northern China, spread rapidly, and caused epidemic disease in children and young adults (< 23 years) worldwide. The 1977 virus was similar to other A/H1N1 viruses that had circulated prior to 1957. (In 1957, the A/H1N1 virus was replaced by the new A/H2N2 viruses). Because of the timing of the appearance of these viruses, persons born before 1957 were likely to have been exposed to A/H1N1 viruses and to have developed immunity against A/H1N1 viruses. Therefore, when the A/H1N1 reappeared in 1977, many people over the age of 23 had some protection against the virus and it was primarily younger people who became ill from A/H1N1 infections. By January 1978, the virus had spread around the world, including the United States. Because illness occurred primarily in children, this event was not considered a true pandemic. Vaccine containing this virus was not produced in time for the 1977-78 season, but the virus was included in the 1978-79 vaccine.

1997: Avian Flu Scare
The most recent pandemic "scares" occurred in 1997 and 1999. In 1997, at least a few hundred people became infected with the avian A/H5N1 flu virus in Hong Kong and 18 people were hospitalized. Six of the hospitalized persons died. This virus was different because it moved directly from chickens to people, rather than having been altered by infecting pigs as an intermediate host. In addition, many of the most severe illnesses occurred in young adults similar to illnesses caused by the 1918 Spanish flu virus. To prevent the spread of this virus, all chickens (approximately 1.5 million) in Hong Kong were slaughtered. The avian flu did not easily spread from one person to another, and after the poultry slaughter, no new human infections were found.

In 1999, another novel avian flu virus – A/H9N2 – was found that caused illnesses in two children in Hong Kong. Although both of these viruses have not gone on to start pandemics, their continued presence in birds, their ability to infect humans, and the ability of influenza viruses to change and become more transmissible among people is an ongoing concern.

http://www.cdc.gov/od/nvpo/pandemics/flu3.htm

A BRIEF HISTORY OF EPIDEMICS

THE SPANISH FLU OF 1918-1919

This pandemic was the single worst in terms of deaths in a short period of time, the bubonic plague at its peak claimed only 2 million victims a year, this modern day global disaster claimed between 20-40 million people in one year. "La Grippe" as it was known killed more people than the Great War (WW1) which lasted from 1914 to 1918 and killed 9 million men in those four years. The influenza pandemic claimed more victims in the USA than all of their armed conflicts of the 20th century and America was one of the least devastated countries on the planet with approximately 850,000 deaths from 20,000,000 cases. Of the US soldiers who died in Europe half fell to the disease. The cause of this disease is unknown but is believed to have been a mutated swine virus from China, brought about by a rare genetic shift leading to the recombination of surface proteins which led to a lack of immunity among the world population. The virus infected A fifth of the world's population and was most deadly for people aged 20-40, a change from normal influenza, which is mainly a killer of the elderly and young children. The mortality rate was 2.5% compared with 0.1% normally. The killer was not the influenza itself but the pneumonia accompanying the infection. As with the bubonic plagues of earlier centuries the disease was spread by human carriers along trade routes and shipping lines. The mass movements of the troops to and from the war aided the rapid diffusion of the disease and the conditions the men were exposed to even before they reached the front line made the job of the virus all the easier.


The name "Spanish Flu" came from the large early mortalities in Spain allegedly killing 8 million people in May 1918. However the disease first struck in a Military camp in Kansas, USA: Camp Funston. It was the morning of March 11, 1918, company cook Albert Mitchell reported to the infirmary with flu-like symptoms and was recommended bed rest. 107 soldiers were sick by noon. 522 were sick within two days, many with severe pneumonia. The disease was then reported to be breaking out in other military bases around the country. Sailors docked off the East Coast were sick in their thousands and isolated places like Alcatraz were also infected, the disease had to be airborne. Within seven days every state was affected. It then spread with the soldiers across the Atlantic infecting French troops and civilians, by mid-April China and Japan had the disease as well. The only plus point of the disease was that it peaked within two to three weeks of appearing in a city and left as quickly as it arrived. Unfortunately for the US the war brought the disease they had begun back to them, arriving in the port of Boston in September 1918. Men across the country were mobilising for the war, when they came together they brought the virus with them to infect thousands more. 200,000 people died in October 1918 alone, mainly soldiers. The Armistice Day celebrations of November 1918 were a public health disaster. Thousands of people came to watch parades and join in large parties and became infected by the sick soldiers returning from the front line where many were to weak to fight and where the disease had killed more people than their weapons could.

Hospitals the world over had their resources stretched to breaking point as many of the doctors were at the front line treating the soldiers and some of the doctors jobs at home were filled by third and fourth year medical students who hadn't joined up to the armed forces. Eighteen months after the disease struck, it disappeared never to show up again. No one knew what had happened until recently. In 1997, the lungs of an eighteen-year-old soldier killed by the disease in September 1918 were used to obtain the genetic code of the disease. Only seven percent was actually recovered but it was enough to show that the disease started as a virus passed from birds to pigs, instead of remaining stable in the bird. The pig immune system forced the virus to mutate in order to survive, and it infected humans. This kind of virus is the worst kind as there is no immunity to it in the human body.

http://www.bath.ac.uk/~ns0sjcg/website/P4.html