Infectious: A Doctor's Eye-Opening Insights into Contagious Diseases

happened.

INTRODUCTION

Human history shapes, and is shaped by, infectious diseases. Where the movement of human populations into tribes, villages, towns and cities allowed the emergence of modern culture, it also afforded microorganisms new opportunities. Typhoid, cholera and plague only appeared when the density of human habitation reached a critical point. SARS, MERS, avian influenza and Ebola are just variations on what may be the same Malthusian theme.

Infections can be caused by a myriad of bacteria, fungi, viruses and parasites, and spelling some of their names still trips me up. They range in size from the submicroscopic to those easily seen with the naked eye. For 150 years, medicine has been learning about these human pathogens (disease-causing agents) and how to deal with them.

It has been a wonderful journey, each step made possible by the successive development of new technologies. Refinements in the light microscope allowed the detection of the largest of our tiny companions (the parasites and bacteria), while the invention of the electron microscope in the early 20th century revealed the structure of viruses. The discovery of the double-helix structure of DNA in the 1950s heralded the scientific revolution that has allowed us to unravel the genetic code of our microscopic competitors – and, as it turns out, friends.

In more recent times we have been unearthing tantalising information about the thousands of bugs in the human body that have not been associated with human infectious disease in the past. These non-pathogenic (non-disease-causing) organisms, which number in the trillions in each of us, make up what is known as the human microbiome, and the way we interact with them very likely plays an important role in many non-infectious human diseases.

I have never tired of infectious diseases because I have had to apply more than just my knowledge of the biology of the bugs that cause them¹. Not only do we have to know about the human who has the bug, we need to know how infected people within the population interact with each other. While some infections are spread from person to person (e.g. colds, measles and chickenpox), some start in animals before going person to person (e.g. Ebola and bird flu), others jump from an animal to a human but stop there (e.g. Lyme disease and Q fever), and some just live quietly in their human host until one day they start to make a noise (e.g. group A streptococcus and meningococcus). Epidemics, such as the recent Ebola outbreak in Africa, terrify people, but ‘boring’ infections like Staphylococcus aureus (which doctors simply call Staph aureus or golden staph) and Escherichia coli (generally known as E. coli) cause more suffering and death in the developed world than the headline-grabbers ever do.

Infectious disease is the public health specialty par excellence. We can successfully change the course of an epidemic by altering the way humans behave (e.g. safe sex and needle exchange for HIV), by vaccinating them (smallpox and polio), by engineering their environment (housing, sewerage and clean water), or by treating them (meningococcal disease and HIV). The implementation of some or all of these methods during the 20th century led to a remarkable decline in the burden of infectious diseases in the developed world. The developing world, of course, remains a completely different story.

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From a purely intellectual perspective, bugs are great fun to get to know. I have tried throughout this book to bring them to life by giving them humans to live on. In many instances the microbes are there to form a backdrop to a discussion of broader issues that challenge contemporary Western medicine and society. How, for example, does the evidence-based medicine movement counter the emergence of half-baked ideas and pseudoscience? How do doctors maintain their integrity in the face of powerful pharmaceutical industry and medical appliance marketing? How do we train medical people to meet the needs of a society that no longer blindly accepts our nostrums?

This book is divided into three themed sections: the first focuses mainly, but not exclusively, on the bugs themselves; the second on the last gleam of twilight for antibiotics; and the third on the disturbing tendency of some patients and doctors to diagnose and treat diseases that either don’t exist or, if they do, should never be looked for.

In the 1960s it was widely believed that the Age of Infections was over and that the next challenges for medicine were the so-called lifestyle conditions such as cancer and heart disease. The emergence of hundreds of new infections since then demonstrates that we must never take our relationship with our ubiquitous invisible neighbours for granted, and that the social response to a new infection must be as nuanced as that of each individual’s immune response. In chapter 1, ‘Ebola and other natural born killers’, I look at the most recent epidemic of Ebola virus in Western Africa and try to examine it from a historical rather than hysterical perspective.

While my mother was worried about all things microbial, my father sat at the other end of the anxiety spectrum. Although I didn’t realise it at the time, I had in him the perfect medical tutor from an early age, and in chapter 2, ‘Taught by an expert’, I look at just one of his encounters with an infectious agent, his struggles with shingles.

The last twenty years have seen major advances in the way we can treat deadly infections such as HIV and viral hepatitis, yet virtually no progress has been made for many common and annoying infections. The common cold is rarely discussed at medical conferences but it remains one of the few infectious diseases I can be confident that every reader will have had. I received more local and international interest in a short piece I wrote for The Conversation² on the difference between a cold and the flu than I had for any academic paper I have ever published on things as serious as HIV, syphilis, gonorrhoea and hepatitis. Which, I must admit, I found a little deflating. Still, there is much nonsense circulating about the common cold, so in chapter 3, ‘Hard cold facts’, I take a look at its history and the evidence for and against its treatment. In chapter 4, ‘Of lice and men’, I look at a condition that receives almost no research attention and is seen as little more than a nuisance to everyone except the people it affects.

My belief in science forms the backbone of this book, and a defence of the scientific method is to be found in every chapter. But the practice of medicine requires much more than dispassionate observation, careful experimentation and the analysis of large datasets. Sir William Osler, whose death features in chapter 5, ‘A typical pneumonia?’, wrote that ‘he who studies medicine without books sails an uncharted sea, but he who studies medicine without patients does not go to sea at all’. Those who resisted the late-20th-century rise of evidence-based medicine warned of doctors who would be slaves to statistics and who would try to fit their patients into theoretical models and ‘cookbook’ treatment plans. This technocratic dystopia has not appeared, but finding the balance between the art and science of medicine is one of the profession’s continuing challenges. Somehow we have to learn to integrate the personal experience that comes from being with sick people and the evidence derived from rigorous scientific enquiry.

One important lesson from science is the growing resistance of bacteria to our treatments. We can all help slow the resistance movement by not expecting an antibiotic for diseases that won’t respond to them. Unfortunately, it isn’t always easy to determine which conditions need them and which don’t. In chapter 6, ‘Just a sore throat’, I explore some of the reasons the prescription of antibiotics became so free and easy, while in chapter 7, ‘Antibiotic mythbusting’, I look at seven misconceptions about antibiotics I commonly hear from my patients and, I am afraid to say, my colleagues.

If you haven’t been hiding away playing Call of Duty for the past ten years you will be aware that the world is running out of antibiotics. Their obsolescence is an ineluctable consequence of a fundamental biological mechanism – evolution. In his Nobel acceptance speech in 1945, Sir Alexander Fleming, the discoverer of penicillin, predicted that Staph aureus would soon develop resistance to the drug. (He even gave ironic advice on how to accelerate the process, so you can’t say you weren’t warned.) Now we’re living with its offspring, methicillin-resistant Staphylococcus aureus (MRSA). In chapter 8, ‘Resistance is futile’, I have outlined the current state of antibiotic resistance in what I hope is sufficient depth to reveal the underlying mechanisms but also in a light enough way to keep me writing and you reading.

The scientific research that underpins medical practice has usually taken at least a decade to move from peerreviewed medical journals to the bedside – and it is sometimes an unsatisfactory transition. Many of the things that seemed so clear in the laboratory are diluted and confused when complex biology meets the chaos of human society. Plausible associations are commonly identified between exposures (e.g. a drug, a vaccine, radiation) and illnesses (e.g. birth defects, autism and cancer), but association does not necessarily mean causation. It would seem axiomatic that deciding if a treatment is effective would be a basic requirement of modern medicine, but readers may be shocked at the number of treatments offered to patients that have never been subjected to the necessary scrutiny of a randomised clinical trial. In chapter 9, ‘Evidence-based medicine – in its place’, I give a potted history of modern epidemiology (the study of diseases in populations) and its love child, evidence-based medicine, and outline the way clinical trials work. Here you can learn some skills that will help you avoid the statistical traps into which many patients – and doctors – have fallen. In chapter 10, ‘A spot diagnosis’, I highlight some of the pitfalls of antibody testing, using an Australian tick-borne disease as an example.

While the discovery of previously unknown pathogens – and the re-emergence of old ones – is of real concern for global health, the self-misdiagnosis of infectious diseases has become a widespread and disturbing distraction. There is, for example, no question that Lyme disease is an important infection in the United States and Europe, but there is no microbiological evidence of it existing in Australia. Yet, excluding the cases picked up in these places, each year hundreds of Australians believe they have acquired Lyme disease locally. Most suffer from a variety of non-specific complaints, none of which is consistent with Lyme disease as it is seen anywhere else, and many look for a doctor who will prescribe months or even years of intravenous antibiotics. In chapter 11, ‘Lyme is the new black’, I look for the evidence of the disease’s presence in Australia and show the considerable harm that may arise from the inappropriate use of antibiotics in its treatment.

Some of the conditions infectious diseases doctors are consulted about are not necessarily caused by an infectious agent, and therefore we cannot always offer treatment. We are often asked, for example, to see people who have a collection of symptoms that may meet the definition of chronic fatigue syndrome (CFS). This illness can be triggered by a wide variety of conditions – Lyme disease being one of the infectious ones. Even though the infection may have occurred in the distant past, the fact that it appeared to trigger their current symptoms prompts sufferers to seek treatment for it in the present. In chapter 12, ‘I’m so tired my mind is on the blink’, I discuss how a desire for certainty where there is none has resulted in hundreds of thousands of people looking for the wrong treatments for more than three decades.

Perhaps the most important piece of advice an older doctor can give to a younger one is the Latin aphorism primum non nocere – first do no harm. The meaning is often lost on the enthusiastic novice, who wants to help by doing. But experience, painfully earned in the course of a medical lifetime, teaches those of us at the other end of the line that if you’re not careful you can hurt as many as you help. Yet again and again, with the best of intentions, we make new mistakes in novel settings. In chapter 13, ‘Eleven grams of trouble’, I discuss the pros and cons of prostate-cancer screening, prompted by my experiences of patients who have developed life-threatening infections as a result.

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The psychologist and science writer Steven Pinker has asserted that, in terms of our risk of suffering a violent end, there has never been a safer time to be alive.³ I think it is reasonable, in the West at least, to make a similar claim for the contemporary risk of dying from an infection. But there are several dark thunderclouds on the horizon for which we need to prepare with a degree of urgency. This book will, I hope, equip you to weather the coming storms.

Part I

The Age of Infections

1

EBOLA AND OTHER NATURAL BORN KILLERS

'We ... certify that smallpox has been eradicated from the world.'

WORLD HEALTH ASSEMBLY, 9 DECEMBER 1979

The parchment scroll upon which this statement is written was signed by the twenty members of a World Health Organization (WHO) committee in Geneva. The signature at the top is that of the late Frank Fenner, emeritus professor at the Australian National University and former head of the John Curtin School of Medical Research in Canberra. Fenner, a world-renowned virologist, was the chair of the group that had been convened to decide when one of the most dread infectious diseases on the planet had finally been eradicated. Two years earlier a 23-year-old hospital cook, Ali Maow Maalin, had contracted smallpox in Somalia after he came into contact with two children with the disease from a nomad encampment. Despite having worked as a smallpox vaccinator in the past, Maalin himself was not vaccinated, and his fifteen minutes of contact with the children was enough. After he became unwell and the diagnosis was confirmed, Maalin was confined to his home and 54 777 people in the surrounding houses and villages were vaccinated.¹ In the two years that followed, no new case of naturally acquired smallpox had been found anywhere in the world.²

When Fenner addressed the World Health Assembly in May 1980 to officially announce the eradication of smallpox, I was in my third year of medical studies. I had just read an article on the demise of the disease written by Hugh Newton-John, who was locally famous for being the older brother of Olivia and, more importantly for me, a physician at Fairfield Infectious Diseases Hospital in Melbourne where I would be training in the coming years.³ The news that the disease was gone was exciting to my naive medical sensibilities and, like many people, I had a feeling that we were at the beginning of the end of the Age of Infections.

The panoply of new antibiotics and vaccines that had appeared in the decades following the Second World War had begun to neutralise community fear of infectious diseases. The terror inflicted by a polio epidemic was something no Australian mother of children born in the 1960s had to experience, scarlet fever was rare, diphtheria was gone and tetanus going. Even the diseases that were thought to be inevitable in childhood – measles, mumps and rubella – were disappearing. Cancer and heart disease were emerging as the big killers: forget about germs, said the leaders of medicine, it’s our lifestyle that needs to change. It was, of course, a premature claim of mission accomplished.

In the 1960s and 1970s the emergence of a number of infectious diseases previously unknown to science tempered the medical triumphalism. An epidemic of arthritis and neurological symptoms associated with a distinctive rash occurred in a town called Lyme on the east coast of the United States (see chapter 12, ‘Lyme is the new black’). Dozens of young women, first in the States but then in other countries, had contracted a sometimes lethal condition known as toxic shock syndrome, found to be the result of a toxin produced by the common bacterium Staph aureus that contaminated their tampons. An epidemic of hepatitis (now known to be caused by the hepatitis B and hepatitis C viruses) had appeared in recipients of blood transfusions and wherever intravenous drug use was becoming fashionable.

But the newly discovered infectious diseases that concerned health authorities most in the 1970s were the viral haemorrhagic fevers (VHFs), the deadliest of which is Ebola.

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In the forty years since the discovery of the Ebola virus there have been at least twenty significant outbreaks, with a total of 3000 reported infections. In March 2014 the WHO announced that there was an evolving epidemic of Ebola in Guinea in West Africa. The case-fatality rate (the percentage of people who die as a result of the disease) ranged from 50 to 90 per cent depending on the care provided to those affected. It spread to involve Liberia and Sierra Leone, with a handful of cases in Nigeria, Mali and Senegal. It would soon become the largest Ebola epidemic in history.

By August 2014, when there had been 1440 cases and 826 deaths, the WHO declared a Public Health Emergency of International Concern. There are many endemic diseases across Africa that kill more people annually than Ebola had by then, or would go on to do. The US Centers for Disease Control and Prevention estimates that there are 100 000–300 000 Lassa fever cases each year in Africa, with around 5000 deaths. In Sierra Leone and Liberia it is responsible for 10–16 per cent of hospital admissions.⁴ In 2013, malaria killed nearly 600 000 people in Africa – at least fifty times the final Ebola death toll. So why did an Ebola epidemic of that size trigger an international response when so many other deadly African infectious diseases don’t?

Ebola draws attention to itself. Throughout history the diseases that are clearly contagious and rapidly fatal – such as cholera, the Black Death, smallpox and influenza – have caused the greatest stir. The time between exposure to a patient with the illness and the onset of symptoms is so short that it is easy to see the association, even if the exact means of transmission is not as obvious. Nearly 50 per cent of people with Ebola die within days of becoming ill and they have always had direct contact with an infected person. It takes much more sophisticated analysis to work out the cause of a disease with a longer incubation period or where mild cases and asymptomatic disease (where the infected person shows no symptoms but develops antibodies and therefore immunity to the infection) are common. Tuberculosis (TB), today a paradigmatic example of an infectious disease, was thought to be an inherited condition until the 19th century. Hepatitis B has been present in human populations for tens of thousands of years and kills nearly 800 000 people worldwide each year. But because it rarely causes symptoms in newborns and children, the ages when most transmission occurs, its existence was not even suspected until 1885, when an outbreak of jaundice occurred in Germany in the adult recipients of contaminated smallpox vaccinations.⁵

The developed world is, by and large, unmoved by the fact of deadly endemic African diseases. It was only the fear of what Ebola might do out of Africa that stirred the West into action. Indeed, by the time the WHO announced its Public Health Emergency of International Concern, the virus had established itself in the crowded urban areas of three African countries, and by the time an intensive and coordinated response could be mounted, the epidemic had grown exponentially.⁶ Ebola epidemics occur not because of a lack of expensive (or even cheap) drugs or intensive care units, but simply due to the fundamental inadequacy of the health infrastructure in most parts of Africa. Small Ebola outbreaks are inevitable but they persist because of a lack of adequate protective equipment for healthcare workers, such as gowns, goggles, masks and gloves. The safe containment and interment of the bodies of those who have died is a major issue in any setting of mass death – but never more so when the specific rituals of grieving in the affected countries promote close contact with the infectious secretions of the dead. Had basic medical equipment been available earlier and the education about burials started sooner, the epidemic would never have reached the heights it did.

Indeed, the epidemic of Ebola disease was almost dwarfed by the epidemic of Ebola panic that was transmitted by traditional and social media across the Western world, especially in the United States. While the general population could be excused for believing that a local epidemic would be triggered by an imported case, the response of some healthcare workers in the West was at best ignorant, at worst shameful. Even though the resources available for infection control in the developed world meant that the risk of transmission was remote, there were reports of doctors and nurses saying they would not come to work if there was a case of Ebola in their facility. Infection-control practitioners, who had struggled for decades to convince anyone that germs can be passed from one patient to another on the hands of healthcare workers, were accused of not adequately preparing their staff for Ebola. As had been the case with SARS in 2004, we had to relearn the sad fact that a risk of transmitting infection to a patient often produces a tepid response but a risk of catching something from a patient provokes an immediate and intense call to arms. Nevertheless, it was true that healthcare workers were not adequately trained to safely use the personal protective equipment required, and hospitals had to hurriedly train their staff and adopt the protocols recommended by the Centers for Disease Control and the WHO. For all the fear and loathing, only three cases of transmission to healthcare workers occurred outside of Africa – two in the United States and one in Spain. All survived.

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Although VHFs such as Ebola are caused by a range of viruses with distinct structures, epidemiologies (behaviour within populations) and means of transmission, they have a number of features in common. They are all RNA viruses (viruses in which the genetic material is carried by the singlestranded molecule ribonucleic acid – RNA – rather than the double helix of deoxyribonucleic acid – DNA); they are usually confined to specific geographic areas; and, with few exceptions, humans are not their natural host. Most notably, they are among the deadliest of all known infections.

A VHF usually begins as a severe but non-specific flu-like illness. Most sufferers will develop dehydration and profoundly low blood pressure, which leads to failure of the lungs, kidney