Pandemic influenza

It's been a busy week so far. Yesterday morning I was invited to give a keynote address to open a two-day national workshop on pandemic influenza, convened by the Public Health Agency of Canada. I chose to widen the scope to talk about pandemics in general and to consider some broader issues than control of pandemic influenza. It was a very interesting workshop, which included the perspectives of the World Health Organization, the UK and the USA. Here is the text of my opening talk, which seemed to find favour with many participants who spoke to me afterwards and at the dinner last night.

Historical and other aspects of pandemic disease

The struggle for supremacy between mankind and infectious microbes has fascinated me since I was a medical student nearly 70 years ago. Pandemics are an aspect of this struggle, in which, for a time, microbes gain the upper hand. The world’s population passed 7 billion in October 2011. A crowded world is heating up, its infrastructure is deteriorating, and millions are restlessly moving. UNHCR reported 47 million refugees in 2010; at least that many or more migrated from rural to urban areas. Every year about 200 million migrate internationally, and 600 million or more travel internationally by air. Future pandemics are a certainty, probably soon, perhaps due to new pathogens. Some pandemics have affected the course of history and probably will again in future. Difficult moral and ethical issues can arise in epidemic and pandemic disease control.

Ancient fears and superstitions

A large outbreak of an often mysterious disease that strikes people down seemingly at random has always been a terrifying phenomenon. Such events were explained in ancient times as god’s punishment for the people’s sins, the work of the devil or evil spirits, probably summoned by malign individuals like witches, or those perennial scapegoats, the Jews. Someone had to be blamed and punished, so witches were burnt at the stake, Jews were driven out of the community. Pandemics, even localized epidemics, still have the power to awaken atavistic fears among ignorant and superstitious people, as they did in the Middle Ages. People look for scapegoats, try to find someone to blame. They turn to fundamentalist aspects of faith, make sacrifices to appease vengeful evil spirits or the wrath of god. The economy suffers, hurting those who worship Mammon.

An Adelaide GP’s perspective on the 1958 Asian influenza pandemic

My experience as a GP (family doctor) in Adelaide in the 1958 pandemic of Asian influenza shaped my career. In June 1958, I was 8 1/2 years out of medical school, 4 years in general practice in Adelaide. Asian influenza reached Australia in early winter, in June. In Melbourne, the eminent virologist Macfarlane Burnett (later a Nobel laureate) headed the Walter and Eliza Hall Institute at the University of Melbourne and working with Frank Fenner at the Commonwealth Serum Laboratories, began preparing a vaccine. Small quantities of the vaccine reached Adelaide in July, and were given to highest priority public officials, including ambulance attendants, emergency room staff, police (but not GPs). In July, August, early September, my partners and I worked nonstop. We did a lot of house calls in those days; during that pandemic I did up to 30 house calls on many days, as well as seeing patients in my office. Public service radio announcements urged people with flu symptoms to avoid public places like hospital emergency departments (but not GPs’ waiting rooms!). Worldwide deaths in the 1957-58 influenza pandemic were over 2 million. The pandemic struck close to home. It killed two young health professionals I knew very well: a nurse in the maternity department of the hospital where I did most of my obstetrics, and an ambulance driver with whom I played golf. Both had flu vaccine a few days earlier…

In October after the pandemic receded I fell critically ill with a non-bacterial pneumonia. I and my doctor thought for a few days that I would die. I had a daughter aged 10 months and my wife was pregnant with our second child. It was a career changing experience. During my convalescence I thought deeply about what to do with the rest of my life: I decided to leave general practice where I was happy, financially secure, and I’m told, was regarded as a good doctor. Instead I decided to train in public health sciences, especially epidemiology, with the aim of keeping people healthy rather than waiting for them to get sick. That career change brought me to Ottawa 42 years ago.

Pandemic diseases in historical perspective

The outcome of many wars has been determined more by pathogenic micro organisms than by military strategy, tactics, bravery, or superior weapons. The plague that afflicted Athens at the end of the first year of the Peloponnesian War (426-425 BCE) was described in detail by the historian Thucycides, who was there and got the plague, but fortunately survived it. It was not a pandemic but a localized epidemic, probably louse-borne typhus. The next historically memorable epidemic (or pandemic) was the plague of Justinian, emperor of Constantinople; this afflicted the Empire of Byzantium in 541-542 CE, and was probably bubonic and pneumonic plague.

The Black Death, bubonic, pneumonic and septicemic plague devastated Asia Minor and all of Europe in 1347-1350. That pandemic killed up to 30% of the people of Europe and may have set back the advance of civilization by several hundred years. That was followed in 1485 by the first wave of a mysterious contagious disease called the sweating sickness (or ‘sweats’). This caused severe epidemics in Britain and Europe until 1551, after which it disappeared forever. We have no idea what this was. It might have been a variety of influenza but contemporary accounts don’t sound like influenza. Several medieval epidemics of smallpox and typhus were widespread pandemics.

Influenza and cholera are the best known among lethal pandemics in the past 200 years, a period during which we have had good clinical and statistical records, and increasingly good microbiological and immunological tools. This combination has removed much, but not all, of the superstition, hysteria, ‘fear of the unknown’, victim-blaming and stigmatizing that often occurred during lethal outbreaks of contagious diseases in earlier times.

Cholera has swept across the world in seven pandemic waves since the early 19th century; the seventh cholera pandemic seems to be subsiding now, apart from sporadic outbreaks in Haiti and refugee communities in Africa; but no doubt we haven’t seen the last of cholera.

Influenza

Hippocrates (4th Century BCE) described a disease that sounds very like modern influenza and several writers described outbreaks in Europe as early as 1580. The first European occurrence that we can confidently call pandemic influenza was in 1830-1833. A pandemic in 1880-1882 invaded Europe from Russia. About the same time there were influenza epidemics in China and India. The first truly global pandemic was the ‘Spanish’ Influenza in 1918-1919. This attacked predominantly young people (born after 1882) and had a case fatality rate of at least 2% in people aged under 40. Estimates of worldwide deaths vary from 20 to 100 million. It certainly killed more than all killed in the Great War of 1914-18.

Several potentially catastrophic pandemic waves of influenza have fizzled out or been aborted since 1976, most recently swine (H1N1) and avian influenza (H5N1) which had a higher case fatality rate. We can’t know for certain, but strain-specific vaccines and other counter-measures like isolating and killing infected domestic poultry flocks may have aborted or prevented what could otherwise have become major pandemics possibly with high case fatality rates.

Since its onset in the early 1980s, the HIV/AIDS pandemic has killed about 35-40 million people, but the epidemiology, natural history, and control measures for HIV/AIDS are so different from other pandemics that they require separate discussion, and I won’t go into details. The threat remains real from outbreaks of new and emerging pathogens that could be natural or man-made.

Pandemic disease as a war weapon

In North America and in Australia in early colonial times, blankets used by smallpox patients were given to indigenous aboriginal tribes with the deliberate aim of infecting them with smallpox. These were genocidal acts of biological warfare. About 300 years earlier, the spectacular success of the Spanish invaders against the Aztec empire in Mexico was due less to their guns and steel swords than to the viruses of measles and smallpox that they brought with them; the Spanish invaders were resistant to these viruses but the Aztecs were not, and were decimated. The Spaniards did this unwittingly, but during the plague of Justinian a thousand years earlier, corpses of plague victims were catapulted into besieged cities in Asia Minor with the deliberate intention of starting a plague epidemic. Infected corpses have been dropped down wells to contaminate drinking water since biblical times, so this is an ancient aspect of military tactics. In World War II, the Japanese experimented with plague, and Winston Churchill’s government experimented with anthrax among other organisms, rendering an island near the entrance to the Firth of Forth unfit for human occupancy– it was still “Off Limits” when I worked at the University of Edinburgh in 1965-69. Other nations also experimented with highly contagious pathogens, and no doubt continue to do so. A terrorist group or a small, weak nation with malice aforethought could severely damage a larger, wealthier, well-armed nation, using biological weapons. My son had 30 years in the Canadian forces and worked among other things on security threats to Canada; he told me that NDHQ (like the CIA and NSC in USA) takes this threat seriously – although they haven’t taken the Canadian people into their confidence about this. (The public might be more cooperative with pandemic control measures if they knew about such threats).

Pandemic disease in food crops

The famine in Ireland in 1845 was man-made but it was potentiated by potato blight, a fungus disease that wiped out the harvest of potatoes upon which Irish peasants and city people depended for their survival. One reason I deplore the infatuation of agribusiness with genetically modified food crops such as corn is that these monocultures could be terribly vulnerable; they might be susceptible to invasion by virus, bacteria or fungus which could destroy in one blow the food crops of an entire region. This nightmare scenario is less likely to occur if we encourage biodiversity, avoid monoculture and genetically modified food crops. This biological reality seems to be better understood in Europe than in USA and Canada. However, I don’t really know what I’m talking about here. These may be the ravings of an old man in the process of losing his marbles, so ignore me, or heed me as you wish.

Living in harmony with pathogenic organisms

The laws of evolutionary biology dictate that we can never win a war against pathogenic organisms using antibiotics and anti-viral agents. Micro organisms have generation times of minutes or less in favorable conditions, so resistant strains rapidly evolve. History and headlines every day tell us that humans have never yet learnt how to live in harmony with enemies of our own kind. But we have learnt and continue to learn how to live in harmony with many of our microbial enemies. Safe food and water, kitchen hygiene, vaccines, sera, antibiotics, window screens, bed nets and condoms have enabled us to co-exist with an increasingly wide range of pathogens. Recent genome studies offer great promise of future developments, including creation of non pathogenic strains of dangerous pathogens that could “out-breed” the pathogenic varieties, and genetically enhanced resistance to pathogens like common cold viruses.

Studies of blood group frequencies in countries around the world as long ago as the 1960s demonstrated striking differences; the occurrence of sickle cell anemia in regions where malaria had long been endemic is further evidence to support the hypothesis that regional impact of epidemic, endemic and pandemic disease in previous generations led to these differences in genetic makeup: it is caused by the impact of these diseases on particular genotypes. Plague, smallpox and influenza epidemics in particular appear to have had considerable influence on the genetic make-up, including blood group frequencies, of populations in Southern and Western Europe, Egypt and the Middle East, and India. All this was known about the time Crick and Watson discovered the DNA molecule. Since DNA analysis was perfected, further studies have enlarged our understanding of relationships between genetic makeup and susceptibility or resistance to many diseases, including those such as influenza that have the capacity to cause pandemics. Medical science will surely develop techniques of gene transplant or transfer, or other ways to manipulate the human genome so as to enhance herd immunity to specific viruses, enabling populations to live in harmony with pathogenic micro-organisms that caused devastating epidemics in earlier times.

What happens when we relax mass vaccination?

Paralytic poliomyelitis, measles, diphtheria and whooping cough epidemics occurred when mass vaccination broke down after the USSR collapsed. Small, localized outbreaks have occurred in unimmunized sub-groups such as members of the Dutch Reform Church who have religious objections to vaccines. Cases of measles, rubella and mumps occurred when parents withheld their infants from MMR and other vaccines after the scoundrel Wakefield published a paper, later shown to be fraudulent, claiming an association between MMR vaccination and autism. As formerly common infectious diseases of childhood become vanishingly rare, sporadic cases and even epidemics will return if herd immunity falls below the critical level, which can be calculated for each of these diseases, using mathematical models developed many years ago by Norman Bailey (since refined by others). One of our best defenses against epidemics is maintenance of herd immunity. This can become a challenge when the risk of an adverse reaction associated with each specific vaccine approaches (or exceeds) the risk of acquiring the disease, raising ethical dilemmas about balancing risks and harms against benefits.

Ethical and moral concerns

Fear of contagion is a variation on the theme of fear of the unknown. We think of it as an out-dated emotion but it occurred during the SARS epidemic in Toronto in 2003. ‘Contagion’ (suspected contagiousness) is stigmatizing, harmful, potentially lethal: being Chinese in Toronto during the SARS epidemic could have led to being burnt at the stake if it had happened in medieval times. These sentiments were detected on talk radio in Toronto in 2003. Epidemic control officers have a moral or ethical obligation to dispel these irrational emotions by educating the public, being open and truthful. During the SARS epidemic I was asked by the CBC to give many interviews, the aim being to educate the public and eliminate the tendency to stigmatize groups suspected of disseminating the SARS organism (at that time the nature of the organism was unknown). On one memorable morning I gave 14 separate interviews to 14 breakfast radio programs from St John’s to Victoria, White Horse and Yellowknife. The questions were much the same each time but probably correctly, the CBC producer wanted live programs aimed at the local audience, rather than a single nation-wide interview. The aim was to inform and educate, to avoid the moral problem of stigmatizing the innocent. The World Health Organization didn’t help: WHO officials should have known better: their travel advisory cost Toronto $35M/day in lost business.

The procedures of epidemic control, surveillance, locating cases, notifying, isolation, quarantine, raise ethical challenges. Surveillance reminds us of George Orwell’s 1984, that Big Brother is watching; identifying and notifying cases is potentially stigmatizing. Isolation restricts freedom of cases. Quarantine denies freedom to contacts of cases. The question pandemic control officers must ask is “How can I eliminate the risk that control measures cause harm to anyone?” Other troubling questions arise when we use the “police powers” of public health.

Philosophical considerations

One purpose of history is to help make informed guesses about the future. A few months before I graduated from medical school in 1949, I wrote a gloomy essay about future prospects for humanity. One theme I explored was what I perceived as an alarming, unsustainable population increase. In 1949 the world’s population was 2.4 billion, increasing by 20 million/year. In October 2011, the world’s population passed 7 billion, and it is increasing by 75 million/year. Demographers, agronomists, security analysts in the CIA, and other experts, agree that the world can’t sustain such increasing numbers; the population is projected to reach 9-10 billion by mid-century; at the same time we are losing agricultural land to urban sprawl, soil erosion, desertification, sea level rise, climate change; and the oceans, formerly the source of 30% of human protein needs, are depleted and polluted. Are we about to hit Thomas Malthus’s wall? Is the irresistible force of population growth hitting the immovable object of declining global resources? This is happening now in parts of the world. It is responsible for the increasing number of environmental refugees, from 5 million in 2005 to 47 million in 2010. Wait a wee while and one of the Four Horsemen of the Apocalypse will bring you down. What’s your preference? War? Famine? Pandemic Disease?

Perhaps we should welcome rather than take counter-measures next time a pandemic strikes. That would be one way to reduce the surplus population.

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Today I had to miss the second part of the workshop on pandemics to attend a U of O function at which my presence was almost mandatory; this had to do with plans for the period from now to 2020 and beyond, to which I've already contributed in a miniscule way. I was very happy to hear from a bright young man in the Development Office about the ways in which the U of O is encouraging and promoting transdisciplinary activities and groups, helping to break through the watertight compartments that sometimes block communication among disparate groups and individuals in the scholarly community.