THREE
BUGS IN THE AIR

ON MARCH 8, 2003, a forty-four-year-old man sat in the emergency department of a busy community hospital in Toronto, Ontario. He was coughing and feverish. His sister sat with him for a few hours but then had to leave to look after their mother’s funeral. Their mother had died just three days before; the coroner had concluded that the cause of death was a heart attack brought on by the severe viral infection she had been suffering from a few days before her passing. She had just returned from a visit to her native Hong Kong and surely had picked up the bug there. That and the long trip had worn her out.

The young man had started feeling unwell about a day before his mother died. He lived in the same house as his parents, along with his wife, their young son, and his brother. Now he would miss the funeral while he lay on a stretcher in the crowded emergency ward. There were no beds available in the hospital, so he spent the night coughing into his oxygen mask in the small observation area he shared with six others. Little did they know that SARS, the biggest and most frightening outbreak in Canada since the 1918 influenza pandemic, had been unwittingly unleashed upon the City of Toronto.

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MANY VIRUSES AND bacteria can be transmitted through the air, but the ones we encounter most often are the group known as respiratory viruses. These highly contagious bugs attach to the cells lining the upper respiratory tract, which includes the mouth, nasal passages, throat, and upper airways of our lungs. Once they have invaded these outer protective cells they cause what we in the medical community call “upper respiratory tract infections” or URIs. This group of infections includes the common cold, ear infections (otitis media), sinusitis, rhinitis, and bronchitis. Almost all coughs, sneezes, runny noses, earaches, and sore throats are caused by this tenacious group of viruses.

The most common URIs are caused by a variety of rhinoviruses and adenoviruses. These small RNA viruses can mutate rapidly in order to evade the defences of our immune systems. This is why adults can catch two or three colds a year and children commonly experience up to a dozen colds or URIs annually. Let’s consider some of these infections in more detail and look at the measures we can take to prevent them.

The Common Cold

The common cold has been around as long as humans have recorded history, and we are as far from a cure now as we were back in ancient times. The common cold, or acute viral nasopharyngitis, is a pesky combination of sore throat, runny nose, nasal congestion, sneezing, and coughing that lasts about a week in most people, although some symptoms can linger for two weeks or more. These ever-changing viruses are highly contagious, and spread through the air when someone coughs or sneezes. We can also inadvertently inoculate ourselves by touching our eyes or mouth with contaminated hands. For most of us a cold is little more than an annoyance, but the infection can be more severe in infants and young children when it can be accompanied by a fever and rash. And its impact on society is startling, to say the least.

Over the centuries many medical researchers have devoted their time to investigating the common cold with hopes of finding a cure. In the eighteenth century scientist, inventor, and founding father of the United States of America Benjamin Franklin set his sights on this ubiquitous illness. Even though viruses would not be discovered for another 150 years, Franklin was convinced that the common cold was somehow transmitted through the air. He observed that “people often catch cold from one another when shut up together in small close rooms, coaches, etc., and when sitting near and conversing so as to breathe in each other’s transpiration.” His recommendation for prevention and cure: exercise, bathing, and moderation in consumption of food and drink.

In the postwar England of 1946, the U.K. Medical Research Council set up a Common Cold Research Unit. By the 1950s researchers at the unit had discovered that the cause of the disease was a bug they called rhinovirus. Despite years of intense research, they were never able to find a cure. They did, however, do some promising work on zinc gluconate lozenges, medicinal tablets that have some benefit in preventing and treating rhinovirus infections only. The unit was closed down in 1989.

In the 1960s the Common Cold Centre at Cardiff Univer­sity attempted to answer the age-old question: Does cold cause colds? They subjected volunteers to acute chilling of the feet for several hours, then monitored them for the next week to see if they developed cold symptoms. Interestingly, while the subjects of the study reported some cold symptoms, testing showed that they were not in fact infected with any of the cold viruses. Other studies since have shown no higher rates of infection in people who are chilled.

The American chemist and double Nobel Laureate Linus Pauling was also interested in finding a cure for the common cold. He was convinced that high doses of vitamin C were the remedy, and he wrote a book in 1970 called Vitamin C and the Common Cold, which outlined this theory. Unfortunately his results were never replicated in further studies, and vitamin C has since fallen out of favour as a cure. It is a testament to Pauling’s influence that vitamin C is still widely believed to prevent or treat colds, though it is no longer taken in the large doses he espoused.

We now know that the common cold is caused by more than ten different types of rhinovirus as well as a variety of other viruses, including coronaviruses, adenoviruses, para­influenza virus, respiratory syncitial virus, and some enteroviruses. With more than a hundred respiratory viruses causing colds, it is no wonder that a cure is elusive. In the United States alone a hundred million people a year visit a doctor to receive treatment for the common cold. As a result, more than 150 million workdays are lost and as many as 180 million school days are missed at a cost of somewhere around $20 billion every year. In addition to the economic impact, as many as a third of patients are prescribed antibiotics, which are medications developed to fight bacterial, not viral infections. These prescriptions have led to over $1.1 billion in unnecessary costs and, more ominously, to the development of antibiotic-resistant strains of bacteria. Americans also spend in the vicinity of $3 billion a year on over-the-counter medications and $400 million on prescription medications, all for symptomatic relief of the common cold.

We have tried everything from vitamin C to echinacea to zinc to lemon tea, not to mention pharmaceuticals such as decongestants, cough suppressants, antihistamines, and anti-inflammatories. Recent studies have shown that these medications have little benefit and can be downright dangerous for young children; the infant versions of these medications have been removed altogether from pharmacy shelves. In the end, the only certain cure we have for the common cold is time. Far better, then, to prevent catching a cold in the first place.

The single most important and effective measure we can take to prevent transmitting those pesky cold viruses is to wash our hands. Washing your hands with warm water and soap or cleaning them with an alcohol-based hand sanitizer at least five times every day reduces the risk of catching the common cold or spreading infection to others. Antibiotics are not going to help and may cause more harm in the long run. And remember that old saying, “Feed a cold and starve a fever”? While there is no scientific evidence to back it up — at least not the starving bit — I personally would never underestimate the healing power of chicken soup to provide comfort and relieve suffering.

Influenza

Another respiratory virus that routinely causes serious illness is influenza or, more correctly, the family of influenza viruses. There are three types that we need to be concerned about: influenza A, B, and C. Of these the most serious by far is influenza A, which has been known to cause worldwide pandemics. This highly contagious disease likely originated in wild aquatic birds such as ducks or geese, but it can also be found in pigs and, less commonly, dogs, horses, camels, ferrets, cats, seals, mink, whales, and no doubt other species that have not yet been tested. Influenza B, on the other hand, affects mostly humans, and the only other species shown to have contracted the infection is, somewhat surprisingly, seals. Influenza C viruses rarely cause disease in humans (occasionally they affect pigs); its symptoms are similar to those of the common cold. It is influenza A’s unique ability to spread to a vast array of species that makes it especially dangerous to humans.

Influenza, or “the flu,” is a particularly nasty combination of fever, chills, cough, shortness of breath, muscle aches, weakness, and headaches. In young children this viral infection can also cause nausea and vomiting; it is sometimes confused with “stomach flu,” or gastroenteritis, which is caused by other viruses that attack the gut. “The flu” really refers to the respiratory disease caused specifically by the influenza viruses, and its symptoms tend to be much more severe than those caused by the common cold or the many troublesome stomach bugs. In young children, the elderly, and anyone whose immune system is weak or has been compromised, influenza can lead to more serious infections such as sinusitis, bronchitis, ear infections, and even pneumonia.

Influenza A was first described by the Greek physician Hippocrates more than 2,400 years ago. The first detailed record of an outbreak was made in 1580 and describes the spread of the disease from Asia through Africa to Europe. In Rome more than eight thousand people perished, and in several Spanish cities populations were wiped out entirely by this devastating disease. Throughout the seventeenth, eighteenth, and nineteenth centuries influenza epidemics continued to decimate populations, and during the 1900s there were three major worldwide outbreaks or pandemics. The most notorious was the Spanish flu of 1918–19, which killed an estimated forty million people around the world. In 1957 the Asian flu killed as many as two million people, and in 1968 the Hong Kong flu was responsible for one million deaths.

Today influenza continues to have a devastating effect on populations throughout the world. This is because every year the influenza viruses change enough to evade our immune systems and cause sickness and death. Annual or seasonal influenza generally peaks in the winter, which in the northern hemisphere is from October to March and in the southern hemisphere from June to September. The WHO estimates that 5 to 15 percent of the world’s population is affected by influenza every year, with three to five million severe cases requiring immediate medical attention or hospitalization and 250,000 to 650,000 cases resulting in death. In the developed world most of the hospitalizations and deaths occur in the elderly and chronically ill, those whose immune systems are unable to fight off the virus.

We know much less about influenza’s impact on the developing world, but we do know that the viruses cause illness year-round in many tropical regions. We also know that influenza’s attack rates and mortality rates in developing countries have been shockingly high. One such outbreak in Madagascar in 2002 caused severe illness in twenty-seven thousand people, and eight hundred died in just under three months, despite rapid intervention. This is just one example of the devastating effect of influenza on a vulnerable population with limited access to health care. The numbers are staggering, and they have triggered a great deal of public health research in the past twenty-five years to try to reduce both the annual impact of influenza outbreaks and the potential impact of the next pandemic.

Influenza was first discovered in 1931 by the American pathologist and virologist Richard Shope, who found the virus in pigs. Shortly thereafter, in 1933, British scientist Patrick Laidlaw from the Medical Research Council in the U.K. was the first to isolate the virus in humans. By 1944 the first influenza vaccine had been developed at the University of Michigan by Thomas Francis Jr., an American physician, virologist, and epidemiologist. Much of his research was funded by the U.S. Army, which was anxious to develop a vaccine for a disease that had caused unparalleled damage to the military during the Spanish flu pandemic at the end of the First World War.

Influenza viruses have been described by researchers at the WHO as “promiscuous, sloppy, and capricious.” They are considered “promiscuous” because their RNA is broken into eight small pieces instead of being one long strand, which allows these viruses to trade bits of genetic material with each other. The gene swapping, or reassortment, gives birth to a new, hybrid influenza virus that can evade the immune system’s defences. This process is known as a “genetic shift,” and as we say in the business, “shift happens.” When it does happen, pandemics can follow.

Influenza viruses are labelled “sloppy” because having only a single strand of genetic material (RNA) means they can replicate rapidly and without the hindrance of a double-checking mechanism. So when they do replicate, errors, or small mutations, are common. These frequent small errors in the virus’s genes means that it will “drift,” or change a bit, every year, which explains why a new vaccine must be developed every year to combat the latest circulating strains of influenza.

Finally, these “capricious” viruses can slow down their replication process in order to adapt to their new environment. This process, called adaptive mutation, allows a virus to acclimatize to its human host and then spread easily and rapidly to other human hosts. All in all, this unpredictable bug has evolved — and continues to evolve — rapidly, to the consternation of scientists and public health officials the world over. It truly is a moving target.

In order to obtain some understanding of the changing virus and what strains are causing illness in people, the WHO established the Global Influenza Surveillance Network, with 115 national influenza centres in eighty-four countries. Each laboratory monitors the strains of influenza circulating in its area of the globe, checking for drifts and for the more worrisome and potentially deadly shifts. Twice a year scientists from the network hold a meeting to determine which viral strains will make up the next season’s influenza vaccines, one for the northern hemisphere and one for the southern hemisphere.

One of the key pieces of data that the Global Influenza Surveillance Network has uncovered are two proteins coded in the eight genes of the influenza A virus. These viruses have two surface proteins: the H protein, or hemagglutinin, which allows the virus to bind to blood cells, and the N protein, or neuraminidase, which allows the release of progeny virus from the infected cell. There are limited known combinations of these proteins, and to a large extent they determine whether the virus will be effective and efficient in infecting people. So far we know there are sixteen H types (H1–16) and nine N types (N1–9); all of the possible H and N combinations are found in aquatic birds, but only a few are known to cause infections in humans.

Scientists have adopted a somewhat complex naming system to be able to tell if the same, slightly different, or entirely new strains of influenza A are spreading among populations. The circulating influenza A viruses are named for their H and N type, as well as for where they originated and in what year. Since 1977 we have seen two slightly different strains of influenza A — influenza A/Wisconsin/67/2005 (H3N2) and influenza A/Brisbane/59/2007 (H1N1) — and one strain of influenza B, influenza B/Florida/4/2006. The H3N2 strain was composed of a virus with H3 and N2 proteins, was first found in Wisconsin in 2005, and was the sixty-seventh strain seen that year. A cousin of the H3N2 virus that has the genes for the H1 and N1 proteins was first detected in Brisbane, Australia, in 2007, and was the fifty-ninth strain detected that year.

Influenza B viruses don’t change as rapidly and descend primarily from two main lines, Victoria and Yamagata. The viruses were named after the areas in which they were first detected: Victoria, Australia, and Yamagata, Japan. The Florida strain found in 2006 was a slight drift along the Yamagata line. While the coding system may seem complex, it provides a clear common language for scientists worldwide, allowing them to exchange valuable information about potential new strains from around the globe.

The Rise of Bird Flu

So far, only influenza A strains with H1, H2, and H3 proteins are known to cause epidemic disease in people. But viruses with all the H and N protein types can cause disease in domestic poultry, and on a few occasions these infections have spilled over to humans. In 2003 four people developed eye infections after being exposed to an outbreak of influenza H7N7 on chicken farms in British Columbia, and an outbreak of H9N2 in poultry in the Netherlands that same year caused mild infections in several people and resulted in one death, a veterinarian who had visited an affected barn.

The process of breeding poultry in high-density environments to produce more meat has led to the loss of the genetic diversity that once protected the birds from infections. Avian influenza outbreaks now happen with greater frequency in poultry operations because of this industrialization. Some of these viruses cause mild disease. The chickens may become lethargic and produce fewer eggs; these are called “low-pathogenic strains.” Less common are the “high-pathogenic strains” of influenza A, which first cause sniffles and then roar through poultry barns, rapidly killing the captive birds. The issue that concerns the WHO and public health doctors around the world is that if one of these highly pathogenic strains can make the leap — by reassortment or mutation — to becoming effective at infecting humans, we may have the next influenza pandemic on our hands.

Our first brush with this potential disaster came in 1997, when a new strain of influenza A was discovered in poultry in the wet markets of Hong Kong. This H5N1 strain infected eighteen people, mostly children; all of them were admitted to hospital, and six died. This incident alarmed public health officials worldwide. Not only was the mortality rate astonishingly high, but those who succumbed to the disease died of a strain of influenza thought not to affect humans. Clearly this was something new and dangerous.

The WHO worked with local authorities and in three days destroyed more than 1.5 million chickens infected by or exposed to the new virus. Their actions may have averted a pandemic, and they certainly raised the collective consciousness of health officials around the world. Since then the WHO has been developing emergency response systems for future threats and encouraging governments to plan and prepare for another potentially deadly global crisis. Some experts feel that another influenza pandemic is inevitable and that the capricious, sloppy, promiscuous influenza virus is lying in wait for the ideal circumstances to wreak havoc on populations around the world. As some have said, “The clock is ticking. We just don’t know what time it is.”

Adding fuel to the fire was the re-emergence in 2003 of the nasty influenza A H5N1 strain that caused such concern in Hong Kong in 1997. The virus first spread in China, and by the time public health officials became aware of the situation, the disease had spread to chickens, ducks, and geese in Vietnam, South Korea, Thailand, and Indonesia. Over the next five years this new H5N1 strain spread to poultry across Southeast Asia and to Russia, Eastern Europe, Europe, the Middle East, and some countries in Africa. So far the only areas of the globe spared from avian influenza H5N1 have been the Americas.

The first human cases of avian flu were reported in 2003 in Vietnam. By 2008 over 387 people in fifteen countries were known to have contracted this new strain of influenza, and about 60 percent died from the virus. In addition, while thankfully still rare, there have been cases of human-to-human transmission in families in Thailand and Indonesia. If this new H5N1 strain can mutate or reassort with a human strain, it may just develop the capacity to spread rapidly and efficiently among populations — and most people will have no immunity to it.

The Fight Against Influenza

Scientists have been trying to develop a vaccine against influenza H5N1 since the disease first appeared in Hong Kong more than ten years ago. Influenza vaccines are developed by growing the virus in eggs, killing the virus, and then extracting the proteins for the vaccine. The body’s immune system recognizes these proteins and develops neutralizing antibodies that protect us against infection from the virus. But the H5N1 strain has proven so deadly that even small amounts of the virus kill the eggs when injected. New techniques of growing the virus in cell lines look promising, but so far there is no effective immunization for this deadly strain.

The other tool in our armamentarium is a class of medications called neuraminidase inhibitors (NIs). First developed in the late 1990s, these drugs work by blocking the N protein and preventing the newly replicated virus from leaving the infected cell. Currently there are two NIs on the market: zanamivir (brand name Relenza®), a powder that is administered through an inhaler, and oseltamivir (brand name Tamiflu®), which comes in pill form. While NIs can’t stop the spread of influenza, they can reduce the length of time patients suffer from the disease and decrease the chance of contracting secondary infections such as bacterial pneumonias.

When the new strain of influenza H5N1 emerged in 2003 in Southeast Asia, NIs were used to treat patients, but with limited success. The crisis triggered governments of developed countries to stockpile NIs (mostly oseltamivir because of its easy-to-use pill form) to safeguard against an avian flu pandemic. But supplies are limited, and there is no guarantee the medication will work.

Key members of the WHO and governments from around the world are locked in an ongoing debate about whom the medications ought to go to if a pandemic should break out and how they will be distributed. Should the medication be used to treat those who have contracted the illness or should they be given to health-care workers and other key people who will be needed to provide care? There are no easy answers to this difficult ethical question, and a lot more thought and discussion need to take place before we can determine which plan will benefit the most people.

To complicate matters further, the Global Influenza Surveillance Network discovered that the circulating strains of influenza were developing resistance to oseltamivir. In 2008 researchers in Denmark discovered a mutation in a strain of H1N1 that allowed it to resist the effects of oseltamivir. Since then scientists have uncovered this mutation in varying degrees around the world, from 10 to 15 percent of the strains in North America to 100 percent of the viruses tested in South Africa. Knowing what we do about the remarkable adaptability of the top executives of Microbes Inc., it should come as no surprise that these viruses have already found ways to foil this drug. It does, however, lead to considerable uncertainty about our ability to protect people against the next pandemic.

Mexico and the Swine Flu

While all eyes were on the East, a new strain of influenza was quietly evolving in Mexico. On April 20, 2009, officials sent samples from fifty-one young Mexicans hospitalized with severe pneumonia to the National Microbiology Laboratory in Canada, with an urgent request to help identify the bug that was causing the illness. Doctors in Mexico City had alerted national public health authorities a few days earlier that previously healthy young people were being admitted to their hospitals with severe atypical pneumonias. Some required ventilators to help them breathe and several had died. Influenza season had come late in Mexico; cases of influenza-like illness started to rise by mid-March and then increased dramatically throughout April. Fear sprang up that this severe illness was being caused by a new and deadly bug.

Public health authorities quickly scanned other hospitals in and around Mexico City. Sure enough, doctors in the surrounding area also reported treating young people, mostly between the ages of twenty-five and forty-four, with severe respiratory illness. Mexican health authorities reported to their colleagues in Canada about two clusters of illness: one in Mexico City, where 120 people had fallen ill and thirteen had died, and another about 150 kilometres north of the city, in San Luis Potosí, where fourteen people had severe illness and four had died. The Canadian laboratory set out to find the cause of the disease and within days identified a new strain of influenza in eighteen of the original fifty-one samples that had been sent to them from Mexico. What they discovered was a triple reassortment; somehow the bug had picked up genes of avian, human, and swine origin to form a brand-new combination. Although this new virus was technically an influenza A H1N1 strain, it was not the same as the human H1N1 that had been causing illness for the past few years. This new bug quickly became known as swine flu because the major new genetic pieces originated from pigs. By the time that it was discovered, however, none of the cases in Mexico had had contact with swine before falling ill; the virus had become well adapted to transmit between people.

While Mexican and Canadian health officials were deciphering this new virus, the U.S. CDC were investigating something new of their own. They had received two flu samples from unrelated children in California that were unusual. The first was from a ten-year-old boy in San Diego County who had become ill with fever, coughing, and vomiting on March 30, 2009. He was taken to an urgent-care clinic on April 1 for assessment. A swab was taken at the clinic as part of a clinical trial to evaluate a new influenza test. The child recovered uneventfully, but he tested positive for a new type of influenza A that couldn’t be identified. The local investigators sent the sample to the CDC for further evaluation.

The second sample was from a nine-year-old girl who lived in Imperial County, California. On March 28 she became ill with a cough and fever and on March 30 was taken to a clinic for treatment. The clinic was participating in a special influenza surveillance project, so a swab was taken from the girl. She was treated and recovered, but her test also showed an unusual strain of influenza A that could not be identified. It too was sent to the CDC laboratory for more detailed tests.

On April 17 the CDC announced that both specimens had been identified as a new strain of influenza A H1N1, but the virus was of swine origin, not human. Public health officials and scientists from Mexico, the United States, Canada, and the WHO collectively held their breath. Were these new strains the same, and did this mean that a new influenza virus that was causing severe disease in Mexico had already spread to the U.S.? Within days the answer came back: yes, the two strains were the same, and yes, not only were people contracting the virus in the U.S. but the infection was also widespread throughout Mexico and cases were being reported in Canada too.

The WHO raised its pandemic alert level to four and then to five after it became apparent that this new strain was causing illness in hundreds of people across North America. Although initially most who contracted the infection had travelled to Mexico, by the end of April it was clear that this influenza was being passed between people in communities across the continent. Most cases in Canada and the U.S. were relatively mild; very few people needed hospitalization and there were even fewer deaths. In Mexico a more detailed epidemiologic investigation revealed that thousands of people across the entire country were ill with this new infection; the young people with severe illness were just the tip of the iceberg. In early May the WHO reported that twenty-nine countries around the world had officially declared 3,440 confirmed cases of the swine flu and forty-eight deaths, but sustained transmission beyond travellers was still confined to North America.

It is hoped that, as the influenza season wanes in North America, this new strain will wane as well. But what will happen when influenza season ramps up again in the fall? Will this strain come back in a more virulent form and cause severe infections and deaths? A look at past pandemics shows this scenario to be a possibility. The Spanish influenza pandemic of 1918–19 made its first appearance as a relatively mild influenza that caused disease in Europe in May and June 1918. But the virus came back with a vengeance in the fall, causing the worst pandemic in recorded history and killing millions around the world. The medical community is watching closely to see what happens in the southern hemisphere in the next few months as they enter their influenza season. If the swine flu starts picking up and causing more severe illness in Australia and New Zealand, it may be a harbinger of the fall season in the northern hemisphere.

Scientists are now working to grow the virus in the lab — the first step in making a new vaccine that may be ready in time for the next flu season. But big dilemmas remain: If we put all our efforts towards a new vaccine, how will that affect our ability to produce a vaccine for the other flu strains that are still circulating and causing people to get sick and die? As well, this new swine influenza H1N1 is sensitive to the NIs (oseltamivir and zanamivir), so how should we use the stockpiles that countries have amassed? Will this new strain be the cause of the next big pandemic or will it just fade away? For now we are watching closely and making preparations for the worst-case scenario. Only time will tell.

So what can we do to protect ourselves and our families when so much is unknown? Like the common cold, influenza spreads when someone who is infected with the virus coughs or sneezes. The virus can also remain active on surfaces such as doorknobs and taps or in a drop of water or mucus for anywhere from a few minutes to several hours. Our best and perhaps only defence is what we in the medical field call “respiratory etiquette.” This means covering your mouth when you cough or sneeze, preferably with a tissue that can be disposed of immediately. If you don’t have a tissue, cough or sneeze into your sleeve. It sounds funny, but this technique keeps those flu bugs from flying into the air and infecting others. The next step is to wash your hands or use alcohol-based hand rubs to stop the spread by direct contact and to kill any viruses that may linger on your hands. Finally, stay at home if you have a fever. A fever is a sure sign your body is fighting off something that could be passed on to others. These three measures may be our first and perhaps only line of defence against the next influenza pandemic.

The SARS Story

While the world’s disease detectives were on the hunt for shifting influenza viruses, SARS emerged quietly and lethally in the rural areas of China’s Guangdong Province. While public health officials’ attention was turned towards the new H5N1 avian flu that was causing severe respiratory disease in people in China, researchers believe that two or more coronaviruses mutated to create a virulent new bug. Before the emergence of SARS, coronaviruses were known to cause only mild colds in people. They have since proven to be a greater cause for concern.

Guangdong Province, and in particular its capital city, Guangzhou, is known throughout China for restaurants that serve highly prized wild animal meat. People from across the country flock to the area to dine on these extravagant meals. Everything from poisonous snakes to bears to exotic animals such as the Chinese ferret badger, raccoon dog, and Himalayan masked palm civet cat is on the menu. The latter three species are often infected with coronaviruses, and one of them was likely the source of the nasty human illness we now know as SARS.

When epidemiologists traced the origin of the SARS outbreak in 2003, they found the first cases in cooks who worked in the exotic restaurants in Guangdong. They also came across densely crowded markets crammed full of caged wild animals. When SARS first appeared in November 2002, most patients were treated at a local hospital in Guangzhou. Rumours started circulating in health-care chatrooms: something new and deadly had emerged in the region. But when pressed for information by the WHO, the Chinese government would say only that there was a small outbreak of “atypical pneumonia” that they believed was caused by an unusual bacterium called Chlamydia pneumoniae. Early in 2003 they reported that the outbreak was over, and in the end resulted in three hundred cases and only five deaths.

Despite the government’s efforts to assuage concerned citizens, the rumours persisted. Health officials in the neighbouring cities of Hong Kong and Shanghai began monitoring hospitals for cases of severe respiratory infections. The City of Shanghai actually developed a detailed and effective surveillance program for this new infection, which probably saved it from a more devastating outbreak of SARS. Despite these precautionary measures, there was no way of tracking the tens of thousands of people who travelled to and from Hong Kong every day. The virus made its way undetected into the territory in February 2003.

SARS began its global journey in the breathing passages of a Guangzhou doctor who travelled to Hong Kong for a family wedding. He had been treating patients who had contracted this new infection and was mildly unwell when he landed in Hong Kong. He then checked into the Metropole Hotel — now infamous in international epidemiology circles — where he stayed in room 911 on the ninth floor. Over the next few days his condition worsened, and on February 22, 2003, he was admitted to a local hospital.

Two people who had visited with the doctor on the ninth floor were admitted to hospitals just days later, and this unleashed the largest outbreak of SARS in Hong Kong. One traveller who also had a room on the ninth floor returned to Vietnam and spread the contagious disease there, while another ninth-floor resident returned to Singapore with the same deadly consequences. One young man flew home to San Francisco, but thankfully the disease did not spread there. A couple arrived in Vancouver and were promptly isolated by hospital staff after describing their recent travel and stay at the Metropole Hotel; transmission in this case was limited as well.

But when an elderly woman and her husband flew home to Toronto after spending three nights on the ninth floor of the Metropole Hotel, the woman became ill. She went to see her family doctor, who reassured her that she had a viral infection and counselled her to rest. Tragically, she died at home on March 5, 2003. The coroner stated that her death was due to her heart condition, which was most likely aggravated by diabetes and the viral infection she had recently contracted. What her family understood was that she had died in her bed from a heart attack.

Three days later the woman’s eldest son, who lived in the same house as his mother along with his wife and young child, fell ill. He was taken to the local hospital and admitted with pneumonia on March 8. The forty-four-year-old man’s illness did not raise any alarm bells at the hospital, and nobody thought to place him in isolation — he had not travelled in six years, and it was not uncommon for patients to contract respiratory infections during the winter months in Toronto.

The man was placed in an observation area with six other people until a room became available in the main ward of the hospital. Thirty-nine hours later he was transferred to the intensive care unit. The ICU doctor was worried that the patient might be suffering from tuberculosis, a disease still seen all too frequently in the multi-ethnic population that lived in the area. He put the man in an airborne-infection isolation room to protect the other patients and staff, and notified the local public health department. Unfortunately, however, SARS had already spread to at least fifteen people by that time. The largest outbreak of the disease outside Asia had been unleashed.

Officials at the public health department soon realized that several members of the man’s family, including his wife, brother, sister, and even his six-month-old son, were also sick with fever and a cough. On March 13 the man succumbed to the illness, just hours after the WHO had issued its first alert about a severe new respiratory illness circulating in China and Hong Kong. Within hours of his death several family members were diagnosed with severe respiratory infections. His brother required insertion of a breathing tube; his sister and wife were sent to a different hospital. Soon after, the man’s father was hospitalized as well. The only family members spared were his sister’s two children and her husband. Thankfully, everyone else survived, but the catastrophic impact of SARS on their family was immeasurable.

On March 14, 2003, public health officials and local hospital staff held a joint press conference to alert the world of this dangerous new respiratory illness that was likely related to a similar disease first reported in Hong Kong. They were now in a race against time to find anyone who might have come in close contact with the family. Over the next few days it became clear that those who had shared the emergency-department observation area with the forty-four-year-old man were at great risk. An elderly patient who was being monitored overnight for chest pain had fallen ill; he was rushed to the hospital by ambulance but died the next day. His daughter and granddaughter also contracted SARS, but luckily survived. His wife, however, succumbed to the disease as well.

Before the outbreak was contained almost four months later, 375 people, mostly in the Greater Toronto Area, were infected with the disease, and forty-four had died. Among the deceased were two nurses who had bravely looked after the gravely ill, one family doctor who had treated some of the early cases, and a nurse’s aide who was tending her best friend’s mother. In addition, more than two thousand people who showed symptoms of the disease were examined by doctors, and more than thirty thousand were placed in quarantine — an emergency measure that hadn’t been used in Canada for almost fifty years. The negative economic impact of the outbreak cost the City of Toronto over $1 billion. Some ethnic groups, particularly Chinese communities across North America, were isolated and marginalized. Despite persistent rumours that only Asians were infected by SARS, Toronto, a truly multicultural city, proved that no one was immune to this nasty bug. By June 2003 the virus had touched every racial, religious, and ethnic group in the city.

From the outset of the crisis, public health officials and medical staff were frantically working blind. They didn’t know whether the bug was a bacterium or a virus, how it was passed between people, how long it took for someone exposed to the disease to fall ill themselves (the incubation period), or whether people could pass on the disease to others before they showed signs of sickness (as happens with bugs such as measles and chicken pox viruses). They tried every resource available to them: antibiotics, which treat bacterial infections; antivirals, in case it was a virus; interferon, a drug that works against hepatitis C; and even drugs such as steroids, which counteract inflammation in the lungs. Despite these intense efforts, nothing worked. All that could be done was to support the patient’s breathing by administering oxygen and to keep them as comfortable as possible to give their immune system time to regroup and fight off the bug.

Without laboratory test results, vaccines, and effective treatment, it was essential to break the chain of transmission. Those who had been in contact with the SARS virus were quarantined in their homes for ten days. If they remained in good health past the ten-day incubation period, they were released from isolation. If they began showing symptoms of the disease, they were sent immediately to hospital. There the health-care workers wore masks and other protective equipment to prevent them from picking up the virulent virus.

The one thing that became clear very early on was that the most effective preventive measure was to clean your hands. In some cases this was the only thing people could do. The City of Toronto’s medical officer of health, Dr. Sheela Basrur, repeatedly reminded the public and hospital staff that the best defence against SARS was respiratory etiquette: washing your hands or using alcohol-based sanitizers, covering your mouth when you cough, and staying away from others if you felt ill. From Hong Kong to Beijing to Singapore to Toronto, this message became a worldwide mantra.

By the summer of 2003 SARS had been contained. But the outbreak exposed some serious deficiencies in our hospitals and public health systems. Hospitals in North America had been built at a time when infectious diseases were no longer thought to be a threat. They were old and crowded, and ill-equipped to detect and respond to such a massive health crisis. Infection prevention and control programs had withered because of cost-saving measures, and the public health infrastructure had been reduced to its bare bones.

The devastation of the SARS outbreak and its terrible effect on communities around the world reminded governments and the general public of the cost of losing those safety nets. Several commissions in Canada, Hong Kong, and China focused on revamping the public health system to allow for early detection of contagious disease, surge capacity to respond to new threats, and investment in hospital programs to prevent and control dangerous infections. Along with these measures came a renewed awareness of the importance of basic hygiene, especially cleaning your hands, to prevent the spread of deadly disease.

TB the Terrible

Let’s take a walk down the halls of Microbes Inc. and visit the corner office of one of the most successful players in this global corporation: tuberculosis, or TB. The bug that causes tuberculosis is a bacterium called Mycobacterium tuberculosis. TB can live dormant in the bodies (usually in the lungs) of people with healthy immune systems without causing illness. We call this “latent infection.” The bacterium activates or begins the process of replication when the immune defences are down. Every year about one in ten people become sick this way, leading to one million new active cases of TB around the world.

About three-quarters of TB patients experience severe infection in the lungs, but TB can cause infection in almost every part of the body, including the lymph nodes, where it causes a disease known as scrofula; the bones of the spine, which leads to Pott’s disease; the stomach and intestines, the pleura (the lining of the lungs), the central nervous system, and the brain. There is even a form of the disease called miliary TB, which spreads throughout the entire body. Mycobacterium bovis, a cousin of the TB bacterium, primarily infects cattle, but it can spread to people through the milk of infected cows. Since Louis Pasteur developed the process of pasteurization, M. bovis has largely disappeared.

TB is highly contagious and spreads to others when someone with active disease coughs or sneezes. It is estimated that a single sneeze from a patient with TB pneumonia can contain forty thousand droplets of aerosolized bugs. While it often takes up to eight hours of direct contact with a TB patient to become infected, on average the disease spreads to ten others before the original host seeks treatment.

Throughout history TB has been given many names, from the Greek phthisis to the White Death to consumption, and today it affects one-third of the world population. The disease has been around for as long as man. Skeletal remains from as far back as 4000 B.C. have been found with evidence of the infection, as have mummies from 3000 to 2100 B.C. In 460 B.C. Hippocrates identified TB as the most widespread disease of his time. The Roman scholar Pliny the Elder even documented a cure for the disease, an odd concoction made up of “wolf’s liver taken in thin wine, the lard of a sow that has been fed upon grass and the flesh of a she-ass taken in broth.”

In 1020 the first physicians recognized that TB, or consumption, as it was known then, was highly contagious. But it wasn’t until 1839 that scientists realized tuberculosis is caused by a single bacterium. This explains why over the centuries the disease has been given so many different names. In the eighteenth century its symptoms, such as red swollen eyes, pale skin, reduced temperature, and coughing up blood, were often mistaken for vampirism. By the nineteenth century TB was thought to produce feelings of euphoria — called the “hope of the consumptive”— which was believed to have facilitated creativity in the arts. Many artists and writers who became ill with TB were thought to have experienced a burst of inspiration just before death. It was also believed that the disease made women more beautiful and men more creative.

Until the late nineteenth century TB patients were treated with rest and sunshine. The first TB sanatorium was opened in 1859 in Gorbersdorf, Germany (now in Poland), by the physician Hermann Brehmer. By that time more than a quarter of all deaths in Europe were caused by tuberculosis, and most fatalities were among the urban poor. In the early 1900s the sanitation movement was involved in establishing sanatoria for TB as well as regulations to prohibit spitting in public, which was thought to be a major means of spreading the disease. In 1907 the Lung Association started the Christmas Seals campaign to fight tuberculosis, an effort that continues in modified form today.

German physician Robert Koch first identified and described the bacterium that causes TB in 1882, and in 1905 he was awarded the Nobel Prize for his discovery. That same year Albert Calmette and Camille Guérin developed the first and to date only vaccine for TB, Bacille Calmette-Guérin (BCG). It wasn’t until 1921 that the vaccine was first tested on humans in France, and it was not until after the Second World War that BCG was used widely in the United Kingdom, Germany, and Canada. The vaccine was never widely used in the United States because public health officials were not convinced of its effectiveness. While BCG does offer some protection — particularly for children — against severe strains of the disease such as the miliary form, it is unable to prevent people from contracting the bug and it often complicated testing of patients for disease. Today BCG is still administered to children in areas where the number of cases runs dangerously high, but it has fallen out of use in many developed countries.

It wasn’t until 1946 that scientists developed the antibiotic streptomycin, the first effective treatment for the disease. But almost as soon as streptomycin became available, the TB bug began developing resistance to the drug, and before long the bacterium was able to escape the antibiotic’s killing power altogether. This is because treating TB is tricky. Not only is streptomycin a drug that is administered by injection, which must be given by a doctor or nurse, but the TB bacterium reproduces more slowly than most bacteria. Most bacteria replicate in a few minutes to a few hours, but TB, on the other hand, takes sixteen to twenty hours to reproduce and infect other cells. This means that it takes months of treatment to cure tuberculosis, while most bacterial infections are cured within a week.

In the 1950s new drugs were used in combination with streptomycin injections. The first of these was isoniazid (INH), an antibiotic in pill form, which was developed in 1952. With the advent of isoniazid, scientists thought they had finally found a cure for TB. However, most treatment regimens involved at least eighteen months of injections of streptomycin while also taking the isoniazid pills. The discovery of rifampicin (also called rifampin or RIF) in 1967 was the next big breakthrough. A combination of all three drugs meant a high probability of cure in as little as six months.

But the TB bug did not go quietly into the night. As soon as a new antibiotic was developed, the ever-changing bacterium began showing signs of resistance to the drug. In the late 1960s and early 1970s two other medications were developed: pyrazinamide and ethambutol. Current treatment for TB requires taking four drugs (isoniazid, rifampin, pyrazinamide, and ethambutol) during the first two months of treatment, then taking the two main drugs, isoniazid and rifampin, for another four months. And this is considered a short-course treatment! Despite the side effects from the antibiotics, this long and difficult treatment is our only effective means of fighting TB. All four drugs work to kill the bacterium in different ways, and because treatment and therapy run such a long course, the chances that the bug will develop resistance to all four is nearly impossible. Or so we thought.

TB the Superbug

By the 1980s we started to see the emergence of strains of TB that were resistant to isoniazid and rifampin. This bug became known as Multi-Drug-Resistant TB or MDR-TB. Without these two key drugs, treatment for MDR-TB can take more than two years and involves medications that are many times more toxic and hundreds of times more expensive then INH and RIF. In addition, doctors are forced to treat patients with injectable drugs such as the original streptomycin.

MDR-TB now causes over 5 percent of all TB cases worldwide, and in some areas the numbers can be as high as one in five cases. Over half of the cases of MDR-TB are concentrated in China and in countries of the former Soviet Union. In Azerbaijan, for example, 30 percent of TB patients have the multi-resistant form of the bug. In September 2006, reports emerged of a strain of TB in KwaZulu Natal, South Africa, that killed fifty-two of the fifty-three people who were afflicted with the disease, and death came within days. Health-care officials discovered that this deadly strain was not only resistant to INH and RIF but to just about every other drug available to effectively treat TB. This highly lethal bug, which was named Extensively Drug-Resistant TB (XDR-TB), has now spread to 145 countries around the world, including Canada, the U.S., and many European countries. It has a frightening 90 percent mortality rate in HIV patients.

In 2007 the Centers for Disease Control and Prevention issued an unprecedented global travel alert when a young man who had been diagnosed with XDR-TB flew to Europe and back, despite warnings from public health officials. Thankfully the infection did not spread, and he eventually underwent surgery as a last-resort measure to cure the disease. But the incident reminded public health officials around the world that the spread of disease can be just a plane ride away.

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DESPITE ALL OF our efforts over the past fifty years, tubercu­losis is still the single most successful infectious disease on our planet. In 1993 the WHO declared TB a global health emergency, and since then a program has been established to provide treatment to infected people in areas of the world where the disease is most rampant. This includes most countries in Africa as well as India, Pakistan, China, and many countries in Southeast Asia. While TB has become a distant nightmare for those who live in countries such as the United States and Canada, the devastation it still causes in countries such as South Africa, Mozambique, Russia, and China is almost unfathomable.

In 2007 the WHO estimated that there were 14.4 million active cases of TB around the world, with 9.2 million new cases in that year alone. This means that the TB bacterium infects a new person about every second! That same year 1.7 million people died from TB; the vast majority of these deaths were in Africa and Asia, where access to effective treatment is limited and many are also battling HIV and AIDS. Eighty percent of TB cases worldwide occur in just twenty-two countries.

As the SARS outbreak reminded us, no country is immune to infectious disease. In the twentieth century TB single-handedly killed more than a hundred million people. Where TB a generation ago was a widespread illness affecting every community in North America, it has now become a disease mostly of immigrants and, tragically, of aboriginal communities. Although we don’t see too many cases in North America (about 2,000 are reported in Canada each year, which works out to about seven cases out of 100,000 people; it’s about five per 100,000 in the United States), over 90 percent of those afflicted with TB in Canada in 2006 were immigrants from countries where TB still reigns strong. Some of those countries, such as Swaziland, have rates as high as 1,202 cases per 100,000 people.

Thankfully, in Canada and other Western countries treatment is available for TB and it is free for everyone. In addition, public health workers are able to prevent the disease by providing medication to those who have come in contact with a TB patient. Unfortunately many countries are unable to provide the same level of care, despite the WHO global initiative. This lack of access to hospitals and treatment facilities will allow TB to continue to thrive in many parts of the world for years to come.

The Tale of Diphtheria

The final stop on our tour of the respiratory division of Microbes Inc. is with a bug that was cited by The Guinness Book of World Records as “the most resurgent disease” on the planet. Diphtheria is an infection of the upper respiratory tract caused by the bacterium Corynebacterium diphtheriae. The disease was first described in the writings of Hippocrates in the fourth century B.C. and is also found in ancient Syrian and Egyptian scripts. In 1926 the French physician Pierre Bretonneau named the disease after the Greek word for leather. Diphtheria was common in France at the time, and one of its trademark symptoms is the thick, leather-like membrane that forms in the back of the throat, cutting off the airway and eventually leading to death.

During the seventeenth century diphtheria epidemics swept through Europe. The disease was known as “el garotillo” (the strangler) in Spain, and by the 1730s diphtheria had spread to North America, where it became known as “the strangling angel of children” for killing as many as 80 percent of those infected who were under the age of ten. In the 1880s the American physician Joseph O’Dwyer developed a breathing tube specifically for treating diphtheria patients. By the 1890s the German doctor Emil von Behring had developed an antitoxin serum treatment for the infection; he eventually went on to develop the first vaccine for the disease in 1913. In 1920 there were more than 200,000 cases of diphtheria in the United States with up to 15,000 deaths. Routine immunization programs were introduced that same decade, but they did not extend as far north as Alaska.

In January 1925 twenty-five children in Nome, Alaska, fell ill with the deadly bacterium. Nome at the time had a post–gold rush population of about two thousand, many of whom were native Alaskans or Inuit who had not yet been immunized against the disease. The closest treatment centre was in Anchorage, and the closest train station, Nenana, was over a thousand kilometres (674 miles) away across the bleak and frozen tundra. The local doctor put out a call to alert the authorities, and the precarious situation for those twenty-five children soon headlined news reports across the country.

A supply of the antitoxin was located in Anchorage and delivered by train to Nenana. From there, twenty-one volunteers ferried the precious antidote by dog-sled relay to Nome, using the regular mail route, the Iditarod Trail. The trip normally took on average twenty days to complete; the fastest trip ever recorded was nine days. Each volunteer team took on a leg of the trail, passing the priceless cargo on to the next team, day and night. The last leg of the journey fell to a Norwegian man named Gunnar Kaasen, whose lead dog, a black husky named Balto, forged ahead through a raging blizzard, with blinding snow and temperatures as low as minus 60 degrees Celsius.

Finally, in the early morning of February 2, the life-saving serum reached Nome. The trek had taken 127 ½ hours, a miraculous five and a half days. Kaasen and Balto became international heroes, and nowhere was their story better received than in New York City, where a statue of Balto still stands in Central Park. The annual Iditarod dog-sled race from Anchorage to Nome continues to commemorate this incredible journey.

Today diphtheria has been conquered in much of the world. By the late 1990s the disease had all but vanished, and from 2000 to 2007 only five cases were reported in the United States. But the bug was not about to give up. Events in some places of the world have conspired to allow its resurgence on a grand scale. Since the fall of the USSR in the early 1990s, diphtheria has re-emerged at epidemic levels in many of the former Soviet states. In 1991 two hundred cases of diptheria were reported for all of the Soviet Union; by 1998 the International Red Cross estimated that there were 200,000 cases of the disease in the same area, with 5,000 recorded deaths. In the 2000s all five cases of diphtheria in the United States were contracted by travellers returning to the former Soviet Union. When public health and immunization programs were decimated by economic and social turmoil, diphtheria had found its chance to thrive once again.

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THE BUGS THAT spread through the air are a varied and storied group. While we have by no means covered them all, the ones presented here are classic examples of the range and reach of respiratory bugs. They affect everyone, everywhere, and can cause unparalleled devastation. Vaccination is available for a few, but in many cases our best defence brings us back to the basics: wash your hands at least five times a day, cover your mouth when you cough, and stay away from others when you are sick. These few simple rules will keep us in good stead as we move on to the next division of Microbes Inc., the bugs that live in our food and drink.