Defeating the Ministers of Death

by David Isaacs

  Only occasionally does the pneumococcus spread to the lungs to cause pneumonia, or via the bloodstream to cause meningitis. If that kills the host, the pneumococcus also dies.

  ‘Why did my child get that infection?’ parents of seriously infected children often ask. Why indeed? Infectious disease doctors teach that an infection occurs as a result of three main factors.

  The first is the host. The host may be particularly susceptible to infection: infections are more common in very young babies and the very elderly because the immune system works less efficiently at the extremes of life. Infections are also more common and more severe in ‘immunocompromised’ people – those whose immune systems are weakened by certain drugs, by pregnancy, or even by other infections, such as HIV infection.

  The second factor is the organism: some organisms are far more virulent than others. People almost never die from being infected with the common cold virus but almost never recover from rabies virus infection.

  The third factor is the environment: you cannot catch malaria without being bitten by a mosquito; you cannot catch tuberculosis without being coughed on by someone with pulmonary tuberculosis or without drinking tuberculosis-infected milk; and you are more likely to develop pneumococcal pneumonia if you or your parents smoke. We cannot always answer the question ‘Why did my child get that infection?’, but when we can, we usually find the infection is due to interactions between two or three of these factors.

  Knowing the reasons people catch infections helps us prevent them. We can influence the environment, for example through improved sanitation and cleaner air, to try to prevent exposure to organisms. We can destroy the organisms causing bacterial infections with antibiotics. We can also influence the host. It is a truism that prevention is better than cure, but arguably our most powerful tool is the use of immunisation to educate the host’s immune system and prevent infections.

  How immunisation works

  Writing about the Plague of Athens, Thucydides observed:

  Yet it was with those who had recovered from the disease that the sick and the dying found most compassion. These knew what it was from experience, and had now no fear for themselves; for the same man was never attacked twice – never at least fatally.

  Thucydides had recognised two important things: firstly people who had been infected were much less likely to catch the infection again, and secondly if they did get re-infected, the infection was less severe. We would express the first observation as the concept of immunity to infection, and the second as the concept that the immune system can reduce the severity of re-infection.

  The reason children who have had measles do not get it a second time is that their immune system remembers the measles virus for the rest of their life. If they are exposed to measles virus again, even as an adult, their immune system destroys the virus before it can reinfect them. There are some infections we can catch a second time as our immunity wanes – for example, respiratory syncytial virus (RSV) infection, which can give infants a nasty lung condition – but repeat infections are less severe because the immune system remembers and kicks in.

  Immunisation works by taking an organism, modifying it so that it is less virulent, then giving the modified organism to a person to stimulate their immune system. Vaccines can either prevent infections or make them less severe. Measles vaccine protects over 95% of people immunised against infection. Chickenpox vaccine is only 80 to 85% effective in preventing infection, but immunised children who do catch chickenpox have a much milder infection than unimmunised ones, with fewer spots, less fever and far fewer complications.

  People sometimes get confused between immunisation and vaccination. Vaccination refers to the physical process of giving a vaccine. Immunisation refers to the way a vaccine stimulates a person’s immune response to provide protection against infection. But since the whole point of giving a vaccine is to induce an immune response, there may be little point in maintaining the distinction, and many of us use the two words interchangeably. When we immunise we are stimulating a specific immune response, meaning the immune system learns to protect against that particular organism but not against other unrelated organisms.

  Another important concept is herd immunity: immunising a proportion of the population gives some protection against the disease to unimmunised people. The term was first used in 1923, and derives from the concept of a herd of buffalo that form a circle, with the strong on the outside protecting the weak on the inside. Other terms for herd immunity include ‘population immunity’ and ‘community immunity’, a term that rhymes but has little else to commend it.

  If there is a large outbreak of, say, measles, once almost everyone has been infected, they are immune and the disease stops circulating. At this point, even susceptible children do not get infected. This is natural herd immunity.

  There are some people who doubt the existence of vaccine-induced herd immunity. However, there is clear evidence that it occurs, although its extent varies from disease to disease, depending on how infectious the disease is and how protective the vaccine. Tetanus immunisation only protects the person immunised, and provides no herd immunity whatsoever, because there is no person-to-person spread and the responsible organism comes not from humans but from the soil.

  In contrast, schoolchildren but not the elderly were routinely immunised against influenza in Japan for 25 years from 1962 to 1987, yet rates of influenza among the elderly were low. When Japan stopped immunising schoolchildren against influenza, rates of influenza in the elderly rose three- or four-fold. When school-based immunisation was reintroduced, influenza rates in the elderly fell again. The clear implication is that influenza circulates in schoolchildren, who can infect the elderly; immunising schoolchildren against influenza thus also protects the unimmunised elderly. This is a classic example of vaccine-induced herd immunity.

  The concept has been likened to ‘the tragedy of the commons’, a term first used in 1833 by the English economist William Forster Lloyd in a lecture he published about population control. Lloyd used the analogy of farmers whose cattle share pasture on common land. If all the farmers behave responsibly in terms of the number of cattle they put on the commons, there is enough pasture to go round and all the cattle thrive. If one selfish farmer puts extra cattle on the land, the amount of pasture may suffice, but if every commoner adds extra cattle, the pasture will be consumed and all the cattle will starve.

  In 1969, ecologist Garrett Hardin used Lloyd’s analogy to discuss ecological problems such as overfishing the oceans. The idea has since been expanded to other situations, including immunisation. If lots of people stop immunising their children against measles, say, then the disease will return with a vengeance and cause outbreaks.

  Dangerous complacency

  Armed with this knowledge about immunisation, we are in a better position to reassure people who have misgivings about vaccines. People are understandably cautious, if not downright suspicious, about having their children injected with foreign proteins. Yet each of us when healthy carries around at least as many bacteria and other non-human cells as we have human cells. We live our entire lives in peaceful coexistence with billions of foreign organisms, which benefit us more than they attack us. The foreignness of vaccines is nothing compared with the foreignness of the organisms we all carry on and inside us.

  The vaccines we use for immunisation stimulate the host’s natural immune system, so are not totally unnatural, even if they do manipulate nature to protect humans from infection. But we manipulate nature in many ways. We use fertilisers to increase the yield of crops. We build dams to divert rivers and bridges. We manufacture cars and trains and planes to travel. To call vaccines foreign and unnatural is a fairly weak argument for not using them.

  Some immunisation sceptics say that infections result primarily from malnutrition. They argue that if people receive the correct nutrition, vaccines are unnecessary. Malnutrition certainly increases the risk of infection – and for many infections nowad
ays there is a poverty gradient, with a greater incidence and severity in low-income countries and among the poor in industrialised countries. But there are many other important factors that determine who will catch an infection.

  Sanitation is one of the most important influences on enteric diseases – diseases of the gut that are transmitted by the accidental ingestion of human faecal material. One of these is typhoid fever, which killed Willie Lincoln – he actually died from drinking water sourced from the Potomac River that was contaminated with the bacterium Salmonella typhi, which causes typhoid, not from the lack of a vaccine. Another is rotavirus, one of the most important causes of severe gastroenteritis in the world. Typhoid vaccines have long been in use, and vaccines against rotavirus have been developed and are being used in wealthy countries, and increasingly in poor countries too. But poor sanitation does not account for the spread of all diseases, and improved sanitation cannot prevent us from catching all infections.

  We underestimate infectious diseases at our peril. In 1951, Melbourne virologist and immunologist Sir Macfarlane Burnet wrote:

  If one looks around the medical scene in North America or Australia, the most important current change he sees is the rapidly diminishing importance of infectious diseases. The fever hospitals are vanishing or being turned to other uses. With full use of the knowledge we already possess, the effective control of every important infectious disease, with the one outstanding exception of poliomyelitis, is possible.

  Burnet won the Nobel Prize in 1960 for his work on immunity to infection. In 1962, his hubris persisted when he wrote: ‘One can think of the middle of the twentieth century as the end of one of the most important social revolutions in history, the virtual elimination of the infectious disease as a significant factor in social life.’ The end except for HIV infection, which had recently begun infecting humans at the time he wrote this (though it was not recognised as a new disease until 20 years later). The end except for pandemic influenza and mad cow disease and SARS (severe acute respiratory syndrome) and multi-resistant tuberculosis – to name just a few. Burnet was a genius, but he was fallible. Sadly, ‘the virtual elimination of the infectious disease’ is nowhere in sight.

  To this day, vaccine-preventable infections can kill well-nourished, healthy children, or leave them permanently brain-damaged. Olivia Dahl, daughter of renowned children’s author Roald Dahl, died from measles in 1962. ‘Olivia, my eldest daughter, caught measles when she was seven years old,’ wrote Dahl later:

  One morning, when she was well on the road to recovery, I was sitting on her bed showing her how to fashion little animals out of coloured pipe-cleaners, and when it came to her turn to make one herself, I noticed that her fingers and her mind were not working together and she couldn’t do anything. ‘Are you feeling all right?’ I asked her. ‘I feel all sleepy,’ she said. In an hour she was unconscious. In twelve hours she was dead.

  Olivia Dahl died from measles encephalitis, which occurs in about one in a thousand children who catch measles naturally. Tragically, measles vaccine had not been developed in 1962, but nowadays there is a highly effective and safe vaccine. For the rest of his life Roald Dahl became a staunch advocate for immunisation and particularly for measles vaccine.

  Measles may be vaccine-preventable, but the vaccine has to reach children to be able to protect them. The World Health Organization (WHO) has reported that measles immunisation has prevented over 20 million child deaths since the year 2000; the annual number of measles deaths globally fell by over 80% in only 15 years from 2000 to 2015. Nevertheless, over 100,000 unimmunised children still die every year from measles in resource-poor countries.

  One of the challenges with immunisation is that success can breed failure. When an effective vaccine is introduced, the targeted disease can disappear within a few years, sometimes even more quickly. Most vaccines are surprisingly safe, but no medication is totally without adverse side effects.

  When examined in careful studies, the vast majority of these adverse effects cause no lasting damage. But when concerns are raised that a vaccine may be causing adverse effects, parents are likely to be worried. They are more likely to be anxious about a vaccine’s safety than about a disease that they have only vaguely heard about, and from which they have never seen a child suffer.

  If doctors universally believe there is no cause for concern, and tell their patients that the vaccine is safe and remind them about the severity of the disease it prevents, the public may be reassured. But when doctors are among those raising concerns, people may be confused and uncertain who to trust.

  In 1974, a major controversy was ignited in the United Kingdom when a group of doctors from the prestigious Great Ormond Street Children’s Hospital in London published a scientific paper in the country’s leading paediatric journal suggesting that whooping cough (pertussis) vaccine might cause encephalopathy (brain disease), resulting in brain damage. Other doctors also raised concerns about the vaccine’s safety.

  The scientific paper described children who had neurological problems after receiving their childhood vaccines. However, it did not include a control group and did not make it clear that when one event follows another, it does not mean the first event caused the second. Subsequent research showed that children never given the whooping cough vaccine were just as likely as immunised children to develop encephalopathy, and therefore whooping cough vaccine did not cause brain damage. But the harm was done.

  One of the most prominent and vocal of the doctors raising concerns was a Glasgow Professor of Public Health, Gordon Stewart. He had collaborated with Sir Alexander Fleming and had carried out trials of penicillin while working as a naval surgeon in World War II. Gordon Stewart was convinced that pertussis vaccine caused encephalopathy. He was smartly dressed, handsome, articulate and well spoken, with an endearing Scottish lilt, and the press loved him.

  Stewart was no charlatan or fraud. He may have been fond of publicity, but he genuinely believed that the vaccine was dangerous, although comments like ‘The risk of damage from the vaccine is now greater than the risk of damage from the disease’ did nothing for public confidence.

  Immunisation experts and epidemiologists tried to use the media to reassure the public that the risk was low and uncertain, but whenever the press covered the topic they presented both sides of the story ‘for balance’. The anti-pertussis vaccine spokesperson always seemed to be the passionate and plausible Gordon Stewart. Whatever the reasons, rates of whooping cough immunisation in the United Kingdom fell dramatically by the late 1970s, to as low as 30% in parts of Britain.

  When whooping cough immunisation had finally become available in the United Kingdom in 1950, everyone knew about the disease and the vaccine uptake was high. As a result the disease became rare. Twenty years later, parents had no memory of the horrors of having a child or a friend with whooping cough. Scared by the publicity, they perhaps understandably decided not to give their child the whooping cough vaccine. United Kingdom children in the 1970s had good diets and were well nourished, but if they were not immunised and caught whooping cough, good nutrition did not protect them. Between 1977 and 1979, over 100,000 people in the United Kingdom caught whooping cough, and at least 36 children died from it. The outbreak generated its own publicity, immunisation levels rose again and the outbreak subsided. Professor Stewart never retracted his comments, and indeed continued to publish his doubts about the vaccine’s safety on an anti-immunisation website.

  Another highly publicised vaccine scare was the postulated link between the measles, mumps and rubella (MMR) vaccine and autism, published by the United Kingdom gastroenterologist Andrew Wakefield in 1998, and subsequently shown to be based on fraudulent research. (I discuss that controversy in detail in Chapter 11.) By the mid 1990s, measles had all but disappeared from the United Kingdom due to high rates of immunisation; stories like the tragic death of Olivia Dahl had been almost forgotten. The autism scare resulted in a huge fall in measles immunisation rates in the Uni
ted Kingdom, measles returned and children died. When the research was discredited, immunisation rates improved and measles disappeared again.

  In the 1980s, Australia had a few home-grown immunisation sceptics, although the great majority of parents immunised their children. In 1996, a film-maker made a supposedly scientific documentary for the Australian Broadcasting Corporation (ABC). She interviewed people who were both pro- and anti-immunisation in equal numbers, ‘for balance’. She was pregnant with her first child, and concluded the documentary by saying that she had not yet decided whether or not to get her baby immunised. I was one of the doctors interviewed. When the documentary was shown in Australia it generated considerable debate and controversy.

  Two weeks later I was in Port Moresby, the capital of Papua New Guinea, and gave a presentation to the hospital about immunisation. A number of the audience told me they recognised me from the documentary, which had been shown that week on PNG television. They were puzzled as to why anyone would make such a film. Their wards were filled with children with severe tuberculosis, newborns dying from tetanus, and babies with severe rotavirus gastroenteritis, all preventable by immunisation. On their streets were people crippled forever by poliomyelitis. But Papua New Guinea did not have the money or the public health infrastructure to deliver vaccines effectively to its population. Papua New Guineans knew vaccines could prevent the devastating diseases they saw every day, and could not understand why anyone in Australia would dream of not immunising their child.

  Immunisation scepticism is very much a first-world problem.