by David Isaacs
This was illustrated with a vengeance in Russia and surrounding countries as recently as the 1990s. The Soviet Union introduced routine childhood immunisation in the late 1950s, but poor health infrastructure meant that cases of diphtheria still occurred in the 1970s and 1980s. After the Soviet Union was dissolved in 1991, health services broke down and there were massive diphtheria outbreaks in Moscow and St Petersburg, as well as in the Ukraine and Belarus. Between 1991 and 1996, over 140,000 people fell ill and more than 4000 died. Almost all the cases occurred in unvaccinated children and adults. The epidemic was eventually halted by producing more diphtheria vaccine and by improving public health infrastructure.
Vaccine opponents often claim that infectious diseases were disappearing before immunisations were introduced, due to improved living standards, and that all you need to avoid infection is good nutrition and tender loving care. Yet these victims were not starving or even hungry; they simply became infected with the organism that causes diphtheria. This sad saga was a lesson, if one was needed, of the value of immunisation, the rapidity with which previously feared diseases can return if we stop immunising, and the fact that these diseases cannot be prevented by adequate nutrition alone.
Thanks to immunisation, no Australian child has died from diphtheria for more than 25 years. But there is no reason to be blasé. If you think you are safe if you remain unimmunised in Australia, think again. Australia has had an average of five cases per year in the last four years, after only 13 in the previous 23 years.
The most recent Australian to catch diphtheria, in January 2018, was a previously healthy unimmunised 27-year-old man from Cairns in Far North Queensland. He died in Brisbane Hospital.
We do not know whether this recent rise in diphtheria in Australia is due to people who catch diphtheria overseas then bring it home to infect others, or whether it is because unimmunised people are being infected with home-grown bugs. But the message is clear: diphtheria has not gone away. If you want to be protected against it, get yourself and your children immunised.
CHAPTER 7
The golden age of immunisation
Nowadays we take our children to the doctor for their routine immunisations with no thought of what went into making those vaccines. Routine childhood vaccination against diphtheria and tetanus commenced in the early 1940s in Australia. By 1949, pertussis vaccine had been added to create a ‘triple vaccine’ called DTP (diphtheria-tetanus-pertussis), with the aim of reducing the number of injections a child receives.
When my children were infants in the 1980s, they were injected with three doses of the DTP triple vaccine, and ate three doses of OPV polio vaccine on a sugar lump. At 15 months they got measles vaccine.
My first grandson, born in 2014, was given three doses of a hexavalent or six-in-one vaccine as a baby that protected him against diphtheria, tetanus and pertussis, as well as Haemophilus influenzae type b (Hib) – previously the most common cause of childhood meningitis – and hepatitis B. The vaccine included inactivated polio vaccine (IPV) instead of giving it by mouth. However, he did receive rotavirus vaccine by mouth to protect him against the nastiest cause of infant gastroenteritis. Later he received MMR vaccine against measles, mumps and rubella, and immunisations to protect him against varicella (chickenpox), meningococcus – which causes meningitis – and pneumococcus – which causes pneumonia or meningitis. When he is in secondary school he will receive human papillomavirus vaccine (HPV) to stop him from getting cancer of the penis or anus and to help protect any future female sexual partners against cancer of the cervix. My grandson will be protected against 14 diseases altogether, compared with the five his mother was vaccinated against. That is a huge step forward.
We owe a debt of gratitude to the scientists of the late 19th and early 20th centuries who helped usher in the golden age of immunisation that has now lasted the best part of a century.
As we saw in Chapter 2, smallpox vaccine was the first vaccine to be used to immunise whole populations, starting around 1800. However, smallpox vaccine had been developed because of the similarity between the highly pathogenic smallpox virus and the less pathogenic cowpox virus. This was not a route to developing vaccines that was available for other diseases.
The next major leap was the concept of attenuation developed by Louis Pasteur in the 19th century, which we heard about in Chapter 3. Pasteur’s discovery is the basis for the viral vaccines we currently use against measles, mumps, rubella, polio (the OPV form), chickenpox, rotavirus and tuberculosis.
It would take the best part of a century for Louis Pasteur’s brilliance to come to full fruition. The golden age of immunisation and widespread control of major infectious diseases did not start until the mid-20th century. Throughout the 19th century, however, scientists made vital progress in growing and understanding the bacteria that can cause devastating human diseases. This was essential groundwork that enabled the later development of vaccines. German microbiologists played an important role, although scientists in France and Italy also made significant contributions.
In this chapter, I will consider the extraordinary progress we have made in developing vaccines to help keep our children healthy throughout life.
Tetanus
Edwin Smith was an enigma. Born in Orlando, Florida, he became a scholar, specialising in Egyptian antiquities, but was not averse to dabbling in a bit of antiques forgery. In 1862, while in Luxor, he bought a papyrus from a dealer called Mustapha Aga. The papyrus was long but in poor condition, and was written in a script Smith could not read. He kept the papyrus until he died, when his daughter gave it to the New York Historical Society, which had it translated in 1930. The translation showed that it was a medical text – but one completely unlike the few other surviving Egyptian medical texts, which are based on magic.
The Edwin Smith Papyrus, as it is now called, is the oldest known treatise on surgery and may have been a military surgical manual. It describes 48 patients – probably all soldiers – in remarkable clinical detail, using an almost contemporary scientific approach. It dates to 1600 BC, but the writing is hurried and contains multiple errors. Experts believe it is plagiarised from an even older papyrus attributed to the great Egyptian physician Imhotep, who lived 1000 years earlier.
The papyrus includes the first known description of tetanus (the terms tepau and metu have no modern equivalents):
If you find in that patient that his flesh has developed heat under the wound which is in the tepau of his skull. That man, he has developed toothache under the site of that injury. You put your hand on him and you find his brow is wet with sweat. The muscles (metu) of his neck are taut, his face is flushed, his teeth and his back. The odour inside his braincase is like sheep/goat excrement. His mouth is bound, his eyebrows drawn, his face as if he was weeping.
The toothache resulting from the soldier’s clenched jaw was due to tetanus, also known as ‘lockjaw’. His facial expression was the sardonic grimace or smile known as the risus sardonicus; tetanus was also called ‘the grinning death’. Hippocrates recognised the clinical features of agonising muscle spasms in the war-wounded 1000 years after the Egyptians, and named the disease tetanos, meaning ‘muscular spasm’.
Tetanus is a truly frightening disease, characterised by muscle rigidity and convulsive spasms. The muscle stiffness often involves the jaw and neck and then becomes generalised. At its worst, patients with spasms of the spine will arch themselves into a position called opisthotonus.
Physicians may have known millennia ago of the link between tetanus and war wounds, but it is only a little over a century since scientists showed that the cause of tetanus in fact lies in the very ground on which we walk, and in the soil where our wounded fell.
In the late 1880s, a German Jewish doctor, Arthur Nicolaier, isolated a toxin from soil with similar properties to strychnine, which would later be shown to be tetanus toxin. The tetanus vaccine we have used for almost a century is a toxoid made by treating tetanus toxin with formaldehyde (similar
to the diphtheria toxoid).
Nicolaier was a highly influential physician. He was appointed as Professor of Medicine in Berlin in 1921, but was removed from his post by the Nazis in 1933, and committed suicide in 1942 when about to be sent to Theresienstadt concentration camp. How tragic that a man whose work led to the development of a tetanus toxoid vaccine that protected World War II troops against a horrible, painful death should lose his own life at the hands of the Nazis.
The link between tetanus and war is a poignant one. The disease is caused by a nerve toxin produced by the bacterium Clostridium tetani, which grows in the gut of cattle and horses, so it is widely distributed in the soil in farming areas. Hence a field of war is a breeding ground for tetanus, particularly if the field has been manured.
The warfare creates the wounds that allow the tetanus organism to enter the body and set up an infection, which in turn generates the tetanus toxin that attacks the nerves.
World War I saw widespread tetanus in all its horror. A century before, a muzzle-loading musket could fire four shots a minute to a distance of less than 100 metres. By the early 20th century, machine guns could fire hundreds of rounds a minute over several thousand metres. The war wounds these guns inflicted were often contaminated by soil in the heavily fertilised fields of Flanders and northern France. A third of all British soldiers wounded in 1914 were racked by the muscle spasms of tetanus within days. More than half of all the soldiers who developed tetanus in World War I died.
A French veterinarian, Edmond Nocard, had shown in 1897 that tetanus antitoxin could treat tetanus or prevent it in the war-wounded. After the initial catastrophic mortality in the early months of World War I, soldiers with contaminated wounds were given prophylactic injections of anti-tetanus horse serum. This preventative treatment dramatically reduced the incidence of tetanus on both sides of the conflict. There were occasional deaths from anaphylactic reaction to the horse serum, but historians estimate that the use of antitoxin after those first disastrous months saved the lives of as many as half a million wounded soldiers.
In the early 1920s, another French veterinarian, Gaston Ramon, developed a method for treating tetanus toxin with formaldehyde to make it less potent, leading in 1924 to the development of tetanus toxoid vaccine by his colleague Pierre Descombey. This is the tetanus toxoid vaccine we still use for routine immunisations in childhood. We also use a ‘booster’ dose of tetanus toxoid vaccine to increase immunity in a child or adult who suffers a tetanus-prone injury, such as a deep cut sustained on a sports field, or a battlefield wound contaminated with soil.
Tetanus toxoid vaccine was of major importance and used by virtually all countries in World War II. Only a handful of individuals died from tetanus throughout the entire war.
An important aspect of tetanus immunisation is that tetanus is acquired through a contaminated wound, and is not passed from person to person – a person with tetanus cannot infect another person. A child who has not received any childhood immunisations is not protected against tetanus, no matter how many other children have been immunised.
I have seen tetanus in African newborns who caught it from their mothers at birth because their cut umbilical stump was traditionally packed with mud. The newborns were rigid, and if someone made a loud sound, such as shutting a door noisily, they all started to spasm at once. Almost all such newborns die. (I’ll talk about this more in Chapter 9, on vaccines and pregnancy.)
I have seen it in a few older unimmunised children. A sevenyear-old girl whom I helped treat in Oxford was admitted to hospital with what was first thought to be epilepsy. A physician who had seen tetanus in Africa witnessed the girl go into an arching spasm when the door banged and correctly diagnosed tetanus. She had caught it when her parents had her ears pierced in an Oxfordshire marketplace. Her spasms were excruciatingly painful, but at least she survived. Not all children do.
Geriatricians see tetanus in elderly men and women who were never immunised and are infected when gardening; the recipe is a simple prick from a rose-thorn and just a whiff of manure. An unimmunised child or adult who cuts their foot on a rusty nail is also at risk (as we will hear in Chapter 13).
Whooping cough
Whooping cough, or pertussis, has been recognised since the Middle Ages. The term whooping cough, which was sometimes written as ‘hooping cough’, was first recorded in England in 1190. The word ‘pertussis’ is Latin for ‘forceful cough’, and the ‘whoop’ of whooping cough describes the characteristic intake of breath (inward gasp) at the end of each bout of coughing. Another name was ‘chin-cough’. The Scots called it ‘the kink’, meaning a fit or paroxysm. The bouts, or paroxysms, of uncontrollable coughing may end in convulsions (fits).
Although they could describe the disease well, pre-20th century physicians had some strange ideas on how to treat it. Nicholas Culpeper, a 17th-century herbalist, suggested that rosemary should be ‘taken in a pipe, as tobacco is taken’ by both adults and children suffering from whooping cough. Purgatives and emetics were often prescribed, and the use of diuretics and bleeding by leeches were also commonplace. In 1726, a Dr Willis recommended giving a child with whooping cough a ‘sudden fright’. He also used ‘cupping’, an ancient, painful and ineffective remedy that involves applying cups emptied of air to the body, thereby creating suction and raising welts or blisters. Dr Willis favoured cupping round the neck, behind the ears and under the armpits. Around the same time there was a fashion for treating children with infusions containing hemlock, which is a bit of a ‘kill or cure’ approach – hemlock was the poison the ancient Greek philosopher Socrates famously drank to carry out his own death sentence.
In 1898, one doctor reported:
There are many curious customs and superstitions existing even in this enlightened age, and among the most peculiar are some practised by the peasants of Ireland for the cure of various complaints. In certain districts of that country whooping cough is treated in quite a unique manner. A few months ago much amusement was caused by a case which came before the Coroner’s Court in Belfast, in which whooping cough was treated in a child by passing the sufferer three times under a donkey . . . Some donkeys are believed to be possessed of curative virtues in a much higher degree than are others. A man living in County Cork owned an animal which could boast of more than a local reputation. This man used to lead his donkey through the streets of the City of Cork, crying out: ‘Will any one come under my ass for the chin-cough?’
Whooping cough classically causes epidemics every three to four years. During an epidemic most susceptible children are infected before the disease burns itself out. As new children are born, the number of susceptible children mounts gradually until there are enough for the next epidemic to occur. Primary-school-age children are most commonly affected, but people of any age can catch pertussis, from newborn to elderly.
It often goes unrecognised in adults. I remember seeing a dentist friend doubled over in an uncontrollable bout of coughing.
‘How long have you had that cough?’ I asked suspiciously.
‘Three weeks.’
‘Have your children been coughing too?’
‘Yes, for a month.’
‘I think you’ve got whooping cough.’
‘Thank goodness. I can’t breathe and I thought I was dying.’
Adults don’t die from pertussis, but what the Chinese accurately call the 100-day cough can be so troublesome they sometimes wish they could. Infants younger than three months can die from the condition. Older infants and children get uncontrollable bouts of coughing that cause them to go blue in the face and often vomit. The coughing keeps the child and the whole family awake at night for weeks, until everyone is completely exhausted.
The organism that causes whooping cough was first grown in 1906 by Belgians Jules Bordet and Octave Gengou. It was given the name Bordetella pertussis, which honours Bordet, but they both got their names on the medium they developed for growing the organism, Bordet-Gengou medium. Unusually, it cont
ains potato. I can’t help wondering if one of them accidentally spilt their lunch onto the tissue-culture plate and found it was the ideal culture medium.
Whole-cell vaccines made from inactivated pertussis in culture started to be developed just before World War I. The whole-cell vaccine got its name because whole killed cells of Bordetella pertussis were used to make the vaccine. The so-called acellular pertussis vaccines used in most industrialised countries nowadays are made from a small number of the organism’s proteins, not the whole organism. The first licensed pertussis vaccine was made by an American paediatrician, Leila Denmark, in the early 1930s. She was just the third woman ever to graduate in medicine from the University of Georgia, and was quite a character. She was ahead of her time in saying that pregnant women should not take certain medicines, adults should not smoke around children, and too much sugar was harmful – even on her 100th birthday, she refused to eat cake. All of this seemed to work, as she lived to the venerable age of 114.
Pertussis vaccination programs were started in Australia in 1942. Australia introduced the DTP (diphtheria-tetanus-pertussis) triple vaccine in 1953, both in the routine infant immunisation program and in schools.
Meningitis
The moon carries the masks of meningitis into bedrooms, fills the wombs of pregnant women with cold water and, as soon as I’m not careful, throws handfuls of grass on my shoulders.
The Public, Federico García Lorca (1898–1936)
What remained was a pale, prematurely aged face, a gruesome mask with simplified features, in which nothing could be read but pain and disgust and profound horror.
Rosshalde, Hermann Hesse (1877–1962)
In his short novel Rosshalde, Hermann Hesse describes the death of young Pierre from meningitis. But doctors my age do not need to read classic literature to know about meningitis.