INFLUENZA: HISTORY, BIOLOGY AND ANIMALS

INFLUENZA

Influenzas are diseases — often highly infectious ones — caused by viruses that spread easily from one human to another through tiny droplets emitted from the nose and mouth. Symptoms include fever, lethargy, nausea and weakness and can last from one to several days. Sometimes the fever can be quite high.

Influenza (the flu) can be very dangerous. Each year it infects 30 million to 60 million people. killing 36,000 of them, most of them elderly. The great pandemic of 1918 killed between 15 million and 50 million people. Seasonal flu kills or contributes to the death of about 500,000 people a year, 90 percent of them frail elderly people. The influenza death rate is typically higher among the old, very young and frail.

The word “influenza” comes from the Italian word for “influence” or “visitation.” Flu vaccines are made of viruses grown in fertilized chicken eggs. Influenzas usually strikes in the flu season in the winter. The strains often originate in China and then become widespread in North America and Europe. In some years flu strains are mild and not widespread. In other years strains can be quite virulent and even lethal and spread to epidemic or even pandemic levels. One of the primary dangers of influenza and one reason its can spread so widely and so quickly is that people become infectious before they know they are sick.

The flu spreads easily through tiny droplets that are exhaled by carriers and picked up by others through inhalation or touching surfaces that have come in contact with the flu virus. Influenzas constantly appear in new forms because the influenza viruses are prone to mutation. The viruses have the ability to jumps from species to species and can mutate very quickly so that no one ever completely immune. Influenza can spread quickly in this day and age of transoceanic flights, crowded places, people and animals having close contact, and people from all over the world mixing.

The World Health Organization estimates that annual influenza epidemics infect 5-15 percent of the world population each year, cause 3-5 million cases of severe illness and 250,000-500,000 deaths. About 300 million people get the flu vaccine each year. Without it, says Smith, a person can expect to catch the flu about once every 10 years. New flu vaccines given each year typically includes a cocktail of three strains, and the scientists try to predict which strains will cause the most trouble each year. [Source: Maggie Fox, Reuters, April 17, 2008]

Websites and Resources Centers for Disease Control and Prevention (CDC) cdc.gov/DiseasesConditions ; World Health Organization (WHO) fact sheets who.int/news-room/fact-sheets ; National Institute of Health (NIH) Library Medline Plus medlineplus/healthtopics ; Merck Manuals (detailed info many diseases) merckmanuals.com/professional/index

Influenza Biology

Most flus have two proteins, hemagglututinin (H) and nuramnidase (N) on their outer shells that act like hooks and allow them to invade other cells and invade the lungs. Together H and N provide the virus’s chemical appearance and identity to the immune system. Influenza viruses are in a constant state of mutation and evolution. They lose and attract genetic material easily. When they infect a cell their chromosomes fall apart and make copies and more viruses, which can spread in the body and also change,.

There are number of different strains of virus. Some don’t event cause sickness. Strains of flu are named for the two proteins on their surface (H and N) and are identified with H and N protein numbers. The strain that causes bird flu in humans is H5N1. There are 15 forms of H and N proteins in the most populous class of flu viruses — influenza A (less common and less dangerous influenza B has only one type of H and N). When a virus with a new H-N combinations appears immunity to old forms of the H-N viruses don’t work.

All flus are believed to have originated with ducks or waterfowl. Many carry the virus without getting sick. Strains among wild ducks spread through feces shed in the water but don’t affect the ducks because they have a resistance to the disease. Infected birds migrate and bring the disease to new places. If they had been dead or seriously ill they couldn’t spread it. When the disease comes in contact chickens who have no resistance they became very sick. Human influenza is takes around three days to make people ill, thus giving them ample time to infect others.

Karen Kaplan wrote in the Los Angeles Times, “The influenza virus is a simple device. Each spherical flu particle contains eight strands of RNA, which have instructions for making 10 proteins. One of them, hemagglutinin, forms spikes on the virus' outer shell to help it attach to a host cell. Once inside, the virus hijacks the cell's machinery to copy itself hundreds of times. Another protein on the outer shell, neuraminidase, helps the new virus particles detach from the host so they can find fresh cells to invade. [Source: Karen Kaplan, Los Angeles Times, January 10, 2006]

“These two proteins define a flu's character. Scientists have identified 16 types of hemagglutinin, or H, and nine kinds of neuraminidase, or N. The particular combination is what gives a flu its name. The power of influenza lies in its endless pursuit of change. Unlike more complex organisms, whose genetic code is stored in DNA, flu viruses have RNA, which cannot copy itself reliably. Each mutation changes the shape of the H and N proteins, and over time, the immune system fails to recognize them. This genetic "drift" is why the flu vaccine must be updated every year. Even small drifts enable viruses to sicken millions of Americans each winter and kill an average of 36,000.

“A more dramatic event is a "shift," which occurs when two flu viruses infect a cell at the same time and swap entire strands of RNA. The mixing could involve two kinds of human flu, or it could include strains from birds, pigs, horses, seals, whales or other animals. The most dangerous scenario is for a human virus to exchange its H -- or both its H and N -- with an animal equivalent. The combination probably would create a new strain, and no one would be immune. It would take months to develop a vaccine. That is precisely the scenario that makes scientists fearful of H5N1.

Influenza Treatment and Prevention

The reason that we are able to easily fend off most influenzas is that our bodies have seen most flu viruses before or at least viruses similar enough to them that our immune system can muster an appropriate response. Deadly influenzas are the ones that are different enough from the others that the immune system has difficulty providing protection. Many of these are caused by viruses that have made a recent leap from another species to humans.

Many flu vaccines are made from viruses grown in fertilized chicken eggs. Because flus are always changing, new vaccines have be created each flu season for the flu strains that are expected to be a problem. The reason that we are able to easily fend off most flus is that our bodies have seen them before or at least ones similar enough to them that our immune systems can muster an appropriate response. Flus that are deadly are the ones that are different enough from the others that our immune system can not adequately provide protection. Many of these are flus that have made a recent leap from another species to humans.

Important factors in controlling the disease include: 1) the availability of health services: 2) effectively using prevention strategies; 3) effectively using treatment strategies; and 4) availability of effective vaccines.

Studies have shown that the old fashion shot-in-the arm delivery system for flu vaccines is more effective than nasal sprays in adults. Internasal vaccines such as FluMist are primarily marketed for children but widely used by adults too.

Countries and institutions are sometimes reluctant to share virus samples because the samples can be used to make vaccines, with those given the samples potentially profiting from and getting credit for a new vaccine whole those giving the sample are deprived of profits and credit.

Influenzas That Originate in China

Most strains of influenza from the past and virtually all new strains of the disease originated in China. By one estimate 80 percent of the influenzas that appeared in the last couple of decades originated in southern China, particularly in Guangdong, where there are millions if ducks, chicken, pigs and other animals believed to be the source of many of the flu-causing germs. [Source: Tim Appenzeller, National Geographic, October 2005]

Genetic analysis by teams who published their work in the magazine Nature and Science in 2008 indicates that flu viruses evolve freshly somewhere in East or Southeast Asia every year and fan out from there around the globe, for nine months or so, and then die out. One team led by Professor Edward Holmes of Pennsylvania State University cannot pinpoint the source but says both H3N2 and H1N1 strains of influenza appear to arise every year from a 'reservoir', perhaps in the tropics. A second team led by Dr Colin Russell and Professor Derek Smith of the University of Cambridge analysed 13,000 samples of H3N2 flu taken since 2002. These researchers demonstrate this source must be in east and southeast Asia, perhaps a different place every year. [Source: Maggie Fox, Reuters, April 17, 2008]

Maggie Fox of Reuters wrote: Many experts have long believed Asia, and specifically China, to be the source of most influenza viruses. Others hypothesised that flu viruses migrate back and forth between the northern and southern hemispheres, or that they cooked year-round in the tropics, to pop out every once in a while to the rest of the world, Russell says. "We find that viruses come out of east and southeast Asia as a region each year and it is not any one particular country that is the continual source of influenza viruses," he says. "So it is not as simple as saying out of China, because out of China is not the whole story."

In tropical regions, flu tends to break out in the rainy season. "In east and southeast Asia there is a there a lot of variability in the timing of the rainy season and the timing of the epidemic," Russell says. "Bangkok and Kuala Lumpur are only [1100 kilometres] apart but they have their flu epidemics at completely different times of year." This means flu epidemics can be occurring almost year-round in Asia, he says. Then the viruses die out every year in the Americas, Europe, Australia and the rest of Oceania, making these areas "evolutionary graveyards", Russell says. Even if travellers carry the flu viruses back from the Americas to Asia, for example, people living in Asia are already immune to those particular variants.

Influenza and Animals

Many influenzas are thought to have evolved in places where farmers keep ducks, chickens and pigs together. Pigs and ducks, common on Chinese farms, carry flu viruses, and perhaps they are where the new strains first get cooked up. In southern China, where many of the world's newest influenzas originate. a typical two-room brick house is occupied by a family on the top floor and animals on the bottom floor. Viruses grow well in hot climates and are active in live animal markets, where viruses can spread from animal to animal

Unlike most viruses which only infect a couple of species, flu viruses can strike a variety of animals including humans, horses, pigs, seals and many species of birds. When animals of different species are intermixing as they do in China it creates a situation in which viruses are being exposed to many kinds of different genetic material, making it possible for new strains to evolve.

Ducks and shorebirds carry flu viruses that are not harmful to them but can kill chickens and sometimes people. Southern China lies along a major fly route for water fowl migrating to and from Siberia. New flu viruses are thought to arrive in the area with waterfowls and are transferred to poultry in the area.

Pigs can carry flu viruses found in both humans and ducks. Scientists believe that many new flu strains evolve first in birds who pass the viruses on to domestic ducks. The viruses are then picked up by pigs and passed on to humans. Some think pigs act as a “mixing vessels,” taking on bird viruses from ducks and flu virus from farmers, allowing the flu viruses to “reassort,” creating a new potentially-lethal hybrid.

Pigs not only pass on flu viruses to humans they pick them up from humans and pass them on to other pigs which can pass them on to humans in the same or mutated forms. Pigs are quintessential disease transmitters, They eat almost anything and rub against each frequently, making it easy to pass on diseases. Their stomach are tough and can host all kinds of microbes without bringing any harm to themselves. That is why since ancient times many people either did not eat pork or at east didn’t eat it uncooked. Gregory Gay, a researcher at the University of Florida, has shown that 12 percent to 21 percent of Iowa pig farmers have antibodies to United States pig influenza viruses. This work suggests that workers may pass these infections on to their families but usually the pig viruses advance no further than that.

Large-scale animal farms are emerging as a potential breeding and staging area for dangerous influenzas. Animals are packed very close together and can easily spread diseases among each other very quickly.

Early History of the Flu

In 412 B.C., Hippocrates described an outbreak a disease that was probably influenza in the city of Perinthus. It was the first recorded incident of the flu. Some scholars believe the disease may have contributed to the fall of Athens. The disease is believed to have originated with ducks, which were first domesticated around 2500 B.C.

There have been at least 30 pandemic of influenza, caused by strains of flu in which humans had little immunity. A flu-like “sweating sickness” swept through Britain in 1485, leaving many people dead. A common treatment was bleeding victims. The first recorded pandemic was an outbreak that occurred n 1580 in Europe and parts of Asia and Africa. In 1889, an unknown influenza subtype, called the Russian flu, began in Central Asia and spread to Europe and parts of Asia and Africa. It killed roughly 1 million people. In 1955 avian flu was found to be caused by the most virulent of the three forms of virus, influenza A.

Scientists say that flu pandemics occur on average about three times a century. The H2N2 strain that appeared in 1957 in southern China triggered a pandemic of “Asian flu — that killed 70,000 people in the United States alone, and around 1 or 2 million worldwide. It was created by a bird flu and human flu that swapped genes, probably after infecting a pig.

The Hong Kong flu in 1968 was caused by H3N2. It killed about 750,000 to 1 million people worldwide. Again, it was caused when bird and human influenzas swapped genes, probably after infecting a pig. The strain was similar enough to the 1957 strain that people had some immunity reducing the number of deaths. Many deaths were blamed on an inadequate supply of vaccine.

Often a rise in transmissibility is accompanied by a decrease in virulence. This is what happened with milder pandemics, such as the 1957 episode of H2N2 and the 1968 outbreak of H3N2. Anjana Ahuja wrote in The Times, “The logic is that a virus that wipes out its host also wipes out its main vehicle for replication and transmission, so for a virus to be “successful” — such as HIV, which is still with us 25 years after emerging — it cannot be too virulent. [Source: Anjana Ahuja, The Times, October 30, 2006]

In 1977, H1N1 appeared again. By that time nearly everyone under 20 had never been exposed it and it caused a mini-pandemic. In 1976 a strain of swine flu appeared in New Jersey and 40 million Americans got vaccinations. In 2003 there was an outbreak of the highly pathogenic H7N7 strain of bird flu among birds in Germany and the Netherlands. More than 30 million birds were culled in the Netherlands. The highly pathologic H7 and H5 strains of bird flu — which are rare but lethal, killing 80 percent to 100 percent of birds infected — caused major outbreaks in the United States in 1924, 1983 and 2004.

H-N viruses are plentiful in other species, particularly birds. They can cause great damage in poultry industry and sometimes — as is the case with H5N1 — make the species leap from birds to humans. The creation of potent flu viruses is especially dangerous in today’s world, where people and birds are crossing borders and can easily spread disease.

Spanish Flu Pandemic in 1918-1919

The great pandemic of 1918 that killed between 15 million and 50 million people was caused by H1N1, a new flu strain that was identified in 1930 and later called swine flu. The flu was called the Spanish flu because the king of Spain got it not because it originated there. The disease was very deadly. It killed five to twenty percent of the people who caught it, some in two or three days. Some people woke up healthy, developed a severe headache and joint pain and were dead by bedtime.

It is estimated that 500 million people caught the 1918 flu. In many cases victims died after the virus multiplied rapidly in the lungs and provoked an immune system response that devastated the lung’s dedicate tissues and caused them to fill with bloody fluid, turning victims a sickly purple color and causing them to suffocate to death from the fluid in their lungs.

It is not clear where the H1N1 virus originated. The outbreak reached pandemic levels in Europe and thrived in conditions created by World War I, where sick and wounded men were packed together. Many victims were young adults who normally shrug off the flu. By the time it had run is course it had spread across the globe. Except for a few Pacific islanders everyone on Earth was exposed to the disease and half got sick.

The first Spanish flu case was reported at Fort Riley, Kansas, where U.S. Army Private Albert Gutchell checked into a camp hospital complaining of fever, headaches and sore throat. A minute later another such soldier appeared. By noon 107 had showed up. By the end of the week, there were 522 cases. At the end the month, over 1000. The disease then moved to other army camps then to an auto plant in Detroit. Then New York and Minneapolis. The mass movements of men in connection with World War I helped spread the influenza around the world. Publicity about the flu was kept to a minimum so as not to upset moral during war. The disease got it name perhaps from the fact that Spain, which was not involved in World War I, was one of the few countries that published casualty figures ascribed to the disease.

Wendy Orent, an author of books on diseases and viruses, wrote in Los Angeles Times, the 1918 flu — was formed in the massive disease factory of the Western Front of World War I. Why was it a disease factory? Because soldiers were crowded into close quarters that were the perfect environment for the flu to mutate into something highly virulent. When a soldier got deathly ill, there was no place to move him, and he remained packed tightly in among the other soldiers. [Source: Wendy Orent, Los Angeles Times, January 15, 2012]

Book:“The Great Influenza: The Epic Story of the Deadliest Plague in History” by John M. Barry, Penguin Books, 2005

Devastation Caused by the Spanish Flu Pandemic in 1918-1919

The Spanish flu pandemic was described by Lynette Iezooni, author of “Influenza 1918: The Worst Epidemic in American History” as “the most catastrophic season of death in human history. Estimates of the death toll range from 40 million to 100 million, no one really knows for sure. More than 20 million are believed to have died in India alone, Victims often died with blood coursing out of their mouths and died hours after showing their first symptoms. Coffins piled up in cities. Guards were posted to keep them from being stolen.”

The pandemic lasted for 18 months. At first there was nothing particularly deadly about the disease and most of the victims were healthy young men who recovered unscathed. Then a mutation, believed to have occurred in Brest, France in August, happened that made the disease a killer. Victims of this strain coughed violently, ran high fevers and discharged blood. Many came down with pneumonia and turned purple, downing in their own fluids. Doctors and nurses were struck down the disease. Health care systems were overwhelmed. Bodies lay uncollected in homes for days. People were given useless vaccinations with bacteria and told smoking cigarettes would kill the germs. Effective measures like wearing masks were not taken. People became so afraid victims died of starvation because family members were too afraid to bring them food.

One quarter of the population of the United States came down with the disease, including U.S. President Woodrow Wilson and aviator Amelia Earhart, and 675,000 died. From 1917 to 1918 the life expectancy in the United States dropped by 12 years. The disease ran its course not coincidentally around the time World War I ended. Even with all the advances of modern medicine, Christopher Murray of the Harvard Initiative of Global Health estimated in 2006 that an outbreak of Spanish flu could kill 51 million to 81 million today. Investigations into the 1918 pandemic have revealed it was caused by an H1N1 influenza virus that had affected pigs and thus was not so different from the virus that caused the flu epidemic in 2009.

Unusually, many of the victims of the 1918-1919 pandemic were young and healthy, people who are usually more resistant to disease. The disease seemed to cause an overaction in the body’s immune system as evidenced by the amount of fluid found in the bodies of victims. The pandemic ended when so many people had become infected the disease burned itself out. Tools that could have halted or slowed its spread — antiviral drugs and respirators — were not available.

A/H1N1 Flu Epidemic in 2009

A/H1N1 flu — erroneously known as swine flu — is a strain of influenza that first appeared in Mexico in April 2009 and quickly spread around the world. As of April 2010, A/H1N1 flu had reached 212 country and territories and killed an estimated 17,700 people. The World Health Organization (WHO) said it would take at least a couple years to come up with sound casualty numbers.

Scientists later said the A/H1N1 flu was a genetic mix of two swine virus with some genetic elements from human and avian flu. There were worries it might mutate — perhaps by infecting a pig and being pickedd up gain by humans — and becoming more deadly as was the case with the 1918 pandemic. In the end the flu turned out be highly contagious but less lethal than the common seasonal flu. Wendy Orent, author of a book on diseases, wrote in the Los Angeles Times, that scientists learned “you don’t need a radical mutation in a flu virus to produce a pandemic. All you need is enough change within a surface protein for a new strain to blow past acquired immunity and blaze around the world.”

Many millions of people caught the disease but a relatively small percentages died, As of May 2010, the Centers for Disease Control and Prevention estimated 11,690 Americans had died from A/H1N1 flu. In a “normal” flu season about 36,000 Americans die.

The A/H1N1 flu pandemic was as severe as influenza outbreaks in 1957 and 1968 and turned out be an unusual threat to healthy, young adults. Less elderly people died than during earlier flu outbreaks presumably because they had developed some immunity from being exposed to previous influenzas. The A/H1N1 flu virus had similarities to other H1N1 flu virus. Consequently anyone wh was exposed to one of these other H1N1 flu virus was likely to have some immunity to the A/H1N1 flu virus.

Origin of the A/H1N1 Flu Epidemic in 2009

The world first heard of A/H1N1 flu in late April 2009 when the U.S. Centers for Disease Control and Prevention announced that seven people were infected with new strain of influenza. The next day the Mexican government said that 68 people suspected of being infected with the new flu had died and 1,004 had contacted the disease. Three days after that the WHO raised the global alert to Phase 4 and just two days later raised it Phase 5 after the first death was reported in the United States.

After that the new flu spread quickly from the Americas to Europe , New Zealand, Middle East and Asia. By the end of the first week of May it had been reported in 22 countries. In Cairo, the Egyptian government ordered the slaughter of 300,000 pigs in the predominately Muslim and non-pork-eating country. One Islamic group called it “God’s revenge against infidels.” The WHO raised the warning to Phase 6 and declared full-blown pandemic in June.

People at the Center for Disease Control and Prevention realized something serious was up when it found that samples sent to it by the Mexican Health Ministry matched samples of new virus found the the San Diego area. The sample arrived from Mexico on April 13 just as U.S. President Barrack Obama was preparing to visit Mexico. One member of his advance team brought the disease back to Washington.

The A/H1N1 flu most likely emerged from a herd of pigs. Circumstantial evidence points to a large, high-density pig farm in the small town of La Gloria (pop. about 3,000) in Veracruz, Mexico. There according to AP about 450 people were diagnosed in late March with acute respiratory infections, and the pandemic’s “index case” — Edgar Hernandez, a five-year-old who first tested positive for A/H1N1 flu — was identified.

Exactly what happened is still unclear. Neither Edgar or his family had any contact with pigs. Some scientists think the A/H1N1 flu emerged as an amalgamation of swine, bird and human flus. Many blamed the pigs at a large industrial pig plant near Edgar’s home. Residents had complained for years about the stench and dust from the plant. Later it was revealed that Edgar was not the “index case” as other people had became sick before him.

Combating A/H1N1 in 2009

The A/H1N1 flu peaked around November 2009. That same month the disease reached the Amazon, infecting the Yanomami tribe in Venezuela. In the United States a cat and a two ferrets caught the A/H1N1 flu. The disease was found in turkeys in Chile, raising fears that it could mutate and spread via birds and emerge in a more virulent form,. Peter Palese, a virologist at Mount Sinai Hospital in New York, told Orent, “We were lucky — this was a mellow virus.”

By June 2009, drug companies were producing vaccine using conventional egg-based methods. Drug companies were careful not to make the same mistake during the 1976 swine flu scare when 40 million people were quickly immunized against a pandemic that never materialized and several hundred of the people immunized became ill with Guillain-Barre paralysis.

Poor countries didn’t have nearly the amount of Tamiflu — used to treat people who came down with the flu — and A/ H1N1 vaccines that the developing countries had. While countries like Britain, Japan and the United States had enough Tamiflu for 25 percent of their populations, poorer nations like India, Indonesia and Guatemala only had 2 percent.

Tamiflu proved to be effective in treating people that came down with A/H1N1 flu. Only a handful of Tamiflu-resistant cases of the disease appeared. Some people who had the disease and took Tamiflu died or became very sick but those who took the medication were much less likely to die or get very sick than those who didn’t.

Fighting Influenza Pandemics

The World Health Organization (WHO) pandemic alert system for new influenza strains is as follows: Phase 1): virus found circulating among animals but no infections of humans; Phase 2): an animal influenza is known to have caused an infection in humans; Phase 3): an animal- or human-animal reassortment influenza is known to have caused sporadic or clusters of infections in people, but no human-to-human transmissions have been reported; Phase 4): verified human-to-human transmissions of animal- or human-animal reassortment influenza able to cause community-wide outbreaks occurs; Phase 5) : human-to-human transmissions of the virus occur in at least two countries in one WHO’s six regions. ; Phase 6) the pandemic phase, characterized by community level outbreaks in at least one country in a different WHO region.

Preparations for a major influenza pandemic in the developed world include having: 1) systems and facilities in place that allow medical laboratories around the globe exchange samples of viruses and rigorously study them: 2) stockpiles of antiviral drugs like Tamiflu inhaler-based treatments; 3) a carefully rehearsed emergency plan for screening ports of entry, isolating suspected cases and shutting down public gatherings; and 4) arraignments with drug makers to quickly produce and distribute vaccines. Many of these measures were put in place after the 2002-2003 SARS outbreak and implemented to varying degrees during the A/H1N1 flu epidemic in 2009. In the developing world, most countries have minimal or no pandemic plans.

Drug companies typically need about four months to make a vaccine from the time they are informed about a new strain to the time the first doses are available. The primary technique is to grow virus samples using the slow and clumsy but time-tested method of producing them in the embryos of chicken eggs. If a full scale pandemic were to break out it could take 18 months to four years to produce all the necessary doses, which would probably be too late. More efficient methods are expected to reduce the time to between one and 2½ years. Under these conditions, tough decisions have to be made about who gets the doses first as they become available.

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Text Sources: Centers for Disease Control and Prevention (CDC), U.S. Department of Health and Human Services; World Health Organization (WHO) fact sheets; National Geographic, New York Times, Washington Post, Los Angeles Times, The New Yorker, Time, Reuters, Associated Press, AFP, Lonely Planet Guides and various websites books and other publications.

Last updated May 2022