by David Isaacs
The surgeons’ logbooks showed the reason. Before 1850, ship voyages from England to Australia took about six months. If measles broke out, the only people safe from infection were those who had had measles before. Otherwise measles spread like wildfire, killing 1 in 10 infected. By the time the ships reached Australia everyone was either dead or immune, and there was no measles virus left to transmit.
The year 1850 was the very year that faster and larger American clippers started plying the voyage from England to Australia. They almost halved the time of the journey, which meant that some people were still infectious with measles when the ships arrived. Other factors in spreading measles to Australia were the removal of restrictions on the number of children permitted on ships and the huge influx of immigrants trying to get rich during the Gold Rush.
One dose of measles vaccine or a vaccine such as measles-mumps-rubella (MMR) vaccine protects at least 95% of those vaccinated against clinical measles. Measles vaccine was licensed in the United States in 1963 and the number of measles cases and measles deaths plummeted within four years. Over 35 million cases of measles are estimated to have been prevented in the United States since then. Measles vaccine was registered in Australia in 1968 and routine childhood immunisation started in 1970 in all States and Territories except New South Wales, where it started in 1972.
MMR vaccine is given at an age when children often catch virus infections in daycare or from older siblings. If a child develops new symptoms soon after receiving MMR vaccine, these symptoms may be caused by the vaccine (true adverse effect) or may be due to a different virus infection (coincidental).
A 1986 study in Finland neatly teased out this issue. The authors recruited 581 pairs of twins due to receive MMR vaccine and gave one twin of each pair the vaccine and the other twin a placebo injection in a randomised double-blind controlled trial. (We heard about these in Chapter 5.) Three weeks later, the twins received the other injection, so that each child ended up receiving one dose of MMR and one of inactive placebo.
The researchers then compared the children’s symptoms following MMR vaccine with those following the placebo. Children given the placebo had as many episodes of diarrhoea and vomiting and as many episodes of coughing and wheezing as children given MMR vaccine, showing that these symptoms were likely to be coincidence; the child was going to show them anyway. MMR vaccine was found to be significantly more likely than placebo to cause fever and rash about a week after the injection, so it was a true adverse effect due to a mild case of measles.
In 1980, before the measles vaccine was widely available, an estimated 2.6 million children died in the world each year from measles. Although that number has fallen by about 95% since then, it means that, based on WHO estimates, 134,200 children died from measles in 2015, or 367 children every day – an unacceptably high number.
Measles can still, in this day and age, kill or maim a child in any country in the world. But numbers alone do not do justice to the horror of the disease. I have seen previously healthy, chubby children whose brains were destroyed by measles encephalitis, the disease that killed Roald Dahl’s daughter Olivia. If they survived, they could not speak or walk. I have seen children so badly infected by measles pneumonia that they had to be artificially paralysed and put on a ventilator in our intensive care unit.
In Africa, measles is a major killer. Children who are not already malnourished when they catch the disease are more susceptible to diarrhoeal illnesses and are at risk of dying for up to a year after they recover from measles. In 1974, I did my medical student elective in Moshi in Tanzania, at the foot of Mount Kilimanjaro. In the mission hospital there, I saw wards of children dying from measles pneumonia despite the antibiotics we gave them. Sometimes measles ate away their cheeks, a condition called ‘noma’. I saw an attractive young girl brought into the hospital with half her head wrapped in a shawl. When I removed the shawl, there was a gaping hole in her cheek through which I could see her teeth and tongue.
There is only one strain of measles and no animal population harbouring the disease, which means it should be possible to get rid of measles altogether through immunisation. The WHO hopes to eradicate measles from five global regions by 2020, and eventually from the entire world. The reason we have not succeeded in doing so already is that measles is much more infectious than smallpox and spreads more readily and more rapidly.
Because of this high infectiousness, at least 93% of children need to be immunised to achieve herd immunity and prevent measles from circulating in a community. When this high level is achieved, as it has been in most parts of the United States and Australia, measles no longer circulates. However, 1 in 20 immunised children is still susceptible to infection. Thus if measles is introduced by someone from overseas it can start to circulate again. If it gets into an unimmunised or poorly immunised section of the population, such as those with cultural or religious objections, it can cause a large outbreak that will infect almost all unimmunised children and 1 in 20 immunised children.
A 2014 outbreak in Ohio infected 383 people, of whom 340 were unimmunised. Virtually all of the measles cases (99%) were among the Amish community, which has a religious objection to vaccination. Herd immunity prevented measles from spreading more extensively among the rest of the highly immunised community.
We want measles to disappear completely, like smallpox, and we may eventually succeed in making that happen. But at present, and for the foreseeable future, measles is more like diphtheria: if we let our guard down and stop immunising, it will return with a vengeance.
Mumps
The old English word ‘mump’ means to mope. I don’t know if you’re getting bored with hearing this, but Hippocrates recognised mumps about 2500 years ago. (It’s not hard to see why Hippocrates is held in such high esteem by contemporary doctors worldwide. He was a brilliant clinician, and one who thought profoundly about ethics; he also communicated well, leaving us his thoughts in writing in perpetuity.) Hippocrates described the clinical features of mumps in the first book of his work, Epidemics, and clearly explained how mumps can be complicated by orchitis (testicular inflammation):
Swellings appeared about the ears, in many on either side, and in the greatest number on both sides, being unaccompanied by fever so as to confine the patient to bed; in all cases they disappeared without giving trouble, neither did any of them come to suppuration [develop pus], as is common in swellings from other causes. They were of a lax, large, diffused character, without inflammation or pain, and they went away without any critical sign. They seized children, adults, and mostly those who were engaged in the exercises of the palestra [wrestling school] and gymnasium, but seldom attacked women. Many had dry coughs without expectoration, and accompanied with hoarseness of voice. In some instances earlier, and in others later, inflammations with pain seized sometimes one of the testicles, and sometimes both; some of these were accompanied with fever and some not; the greater part of these were attended with much suffering. In other respects they were free of disease, so as not to require medical assistance.
We now know mumps is caused by a virus with a predilection for the salivary glands, particularly the parotid gland (the largest of the salivary glands). Mumps parotitis, meaning inflammation of the parotid gland, results in a miserable child with a sore, swollen neck for a few days. But mumps virus can also cause meningitis and mumps meningitis used to be the commonest form of childhood meningitis. It has a much better prognosis than bacterial meningitis or measles encephalitis, but it still leads to headache, vomiting and a hospital admission.
Other complications of mumps are the extraordinarily painful pancreatitis (inflammation of the pancreas), orchitis (painful swelling of the testicles) in boys and young men as described by Hippocrates, and oophoritis (swelling of the ovary or ovaries, causing severe abdominal pain) in girls and young women. Orchitis can sometimes cause testicular atrophy (small testes) and sterility.
You might hope parents would be more worried about their chil
dren’s brains than their genitalia. However, when the MMR vaccine was introduced into the United Kingdom in 1988, the biggest selling point was not preventing measles encephalitis or congenital rubella or mumps meningitis, but preventing male sterility. What a surprise.
Mumps vaccines were introduced in Australia in 1980 and a combined measles and mumps vaccine was used from 1982 until 1989, when it was supplanted by measles-mumps-rubella (MMR) vaccine. The measles, mumps and rubella components of the vaccine are made by growing and then attenuating each virus; it is a live attenuated vaccine.
Rubella
Rubella is sometimes called German measles, because German physicians were the first to describe it as a separate condition from measeles and scarlet fever, which it resembled. The first clinical description of rubella was Friedrich Hoffmann’s in 1740; two other Germans, de Bergen and Orlow (their first names seem to have been lost to posterity), confirmed these clinical findings in the 1750s. Yet another German, George de Maton, suggested in 1814 that rubella was indeed different from measles and scarlet fever. An English Royal Artillery surgeon, Henry Veale, first used the name ‘rubella’ (Latin for ‘reddish’) when describing an outbreak in India in 1866.
Rubella is a mild disease, with a faint rash and few complications, except occasionally a transient arthritis. The peak age range for catching it is five to nine years old. But the main reason for rubella immunisation is to prevent pregnant women from catching the disease and giving birth to infants with congenital rubella syndrome. (I will discuss rubella in detail in Chapter 9, on vaccines in pregnancy.)
Before immunisation, most girls used to catch rubella in childhood, but a small number were still susceptible as they entered child-bearing age. Australia started rubella immunisation of 12-to 14-year-old schoolgirls as a school-based program in 1971. But because boys were not immunised, rubella still circulated. This meant girls who missed out on the school program, and girls or young women who emigrated from Southeast Asia, where rubella does not circulate so much, were often non-immune and susceptible to the disease in pregnancy.
In 1989 Australia introduced measles-mumps-rubella (MMR) vaccine for all boys and girls at 12 months of age. As in the United States, Australian children are given a second dose at 18 months, to improve measles immunity. Rubella no longer circulates and congenital rubella has now virtually disappeared in Australia: there were only five children born with congenital rubella syndrome between 2001 and 2013, and all were to mothers born overseas who had not received rubella vaccine.
Varicella
The same virus, varicella zoster virus (VZV), causes both chickenpox and zoster (shingles). This is because after a child develops chickenpox, the virus can remain latent in the sensory nerves for years without causing any symptoms. But in times of stress or when the immune system is impaired, the chickenpox virus can re-emerge as shingles.
VZV is a herpesvirus and these features of latency and reactivation are common to all herpesviruses (the Greek word herpein means ‘to creep’). For example, herpes simplex virus causes a severe mouth infection in infants with ulcers of the mouth and throat. Cold sores are a reactivation of the herpes simplex virus, which has been lying latent in the nerves of the lips. Almost everyone catches herpes simplex when young, but not everyone gets cold sores. Almost everyone catches chickenpox when young, but not everyone gets shingles.
When I am feeling wicked, I ask my medical students: ‘What is the difference between herpesviruses and true love?’ The answer is that herpesviruses are forever.
Like me, you may be relieved to know that Hippocrates did not describe chickenpox – it is nice to know he was human after all. But the ancient Greeks have given us the name ‘zoster’, first used in the 19th century and taken from their word for a girdle. The word ‘shingles’ was first used in the 18th century and comes from the Latin cingulus (belt). Both refer to the most common manifestation of shingles, which is in a belt-like distribution on one side of the body, around the lower abdomen.
Nobody knows how chickenpox got its strange name. One theory is that an Old English word giccan, meaning ‘to itch’, was corrupted into ‘chicken’. In 1730, English physician Thomas Fuller published a book on rashes called Exanthemologia in which he suggested the name derived from ‘the smallness of the Specks, which our Women might fancy looked as tho’ a Child had been picked with the Bills of Chickens’. The English writer Samuel Johnson was unconvinced, and in his famous 1755 Dictionary of the English Language, he wrote that chickenpox got its name ‘from its being of no very great danger’.
Over a century later, Charles Fagge wrote in his book The Principles and Practice of Medicine (published in 1886) that the fluid-filled vesicles looked like chickpeas. Another theory is that chicken was a word for a little child and it is mostly children who catch chickenpox. Chickenpox is notoriously itchy, and the name could also be a corruption of the term ‘itching-pox’.
Jeff Aronson, an Oxford pharmacologist and wordsmith, gives his own explanation. In Shakespeare’s time there was an English gold coin called a chequeen; Shakespeare features it in his play Pericles, Prince of Tyre. The chequeen was used as currency in 15th-century India, where the name was often corrupted to ‘chickeen’ or ‘chick’. It was worth about four rupees; in other words, not very much. Aronson conjectures that this word gave rise to the name ‘chickenpox’ because chickenpox was seen as an insignificant, or cheap, infection (no pun intended) compared with smallpox.
It is rather wonderful that we will never know which of these inventive suggestions is correct, but we do know chickens have nothing material to do with chickenpox.
As noted earlier, in the 18th century physicians thought wrongly that chickenpox was a mild form of smallpox. (Varicella, another name for chickenpox, means ‘little smallpox’.) Just as wrong-headed were some of the methods used to treat it. In County Down in Ireland during the 19th century, remedies for chickenpox included ‘two kinds of food obtained from two first cousins who are married, and soup made from the tails of mice’.
In fact, although they both cause pocks, smallpox and chickenpox are caused by very different viruses. It was not until 1888 that a German physician, Janus von Bokay, reported a number of cases of children who developed chickenpox two weeks after being in contact with someone with zoster, suggesting they had caught chickenpox from that person and that chickenpox and zoster were caused by the same virus.
Chickenpox or varicella is usually a fairly mild if annoying illness. A young child is covered in very itchy spots, mainly on the trunk and face. They may also be in the throat or on the eyelids, which can make the child miserable. The skin sores can become infected but serious complications like pneumonia or encephalitis (inflammation of the brain) are rare.
So, why would we immunise against chickenpox? Many Western countries say it is too expensive and have decided against it. Countries that opt to immunise do so mainly because people who are immunocompromised can get severe chickenpox and even die from it, and because immunisation against chickenpox reduces the later risk of shingles.
The chickenpox vaccine is a live attenuated virus vaccine. It was developed in Japan and was commercially available from 1984. It was used in Japan and Korea from 1988 and in the United States from 1995, and was introduced into the routine immunisation schedule in Australia in 2003.
Since 2013, Australia has given varicella vaccine in the form of a new quadrivalent four-in-one measles-mumps-rubella-varicella (MMRV) vaccine at 18 months, which reduces by one the number of injections a child gets. The United States recommends a second dose of varicella vaccine to boost immunity, but Australian authorities have ruled that the second dose is a costly luxury and decline to pay the price asked by vaccine companies.
Human papillomavirus
Human papillomavirus (HPV) vaccines are some of the newest and most exciting to be introduced. The excitement is because these vaccines protect women against cancer of the cervix, one of the commonest cancers for women after breast cancer.
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br /> Yet, as I will discuss in later chapters, HPV immunisation is controversial in many parts of the world. The cervix is the doorway to the womb, and anything to do with sex excites controversy. Fortunately, Australians are more pragmatic than those in some other places. Australia was the first country in the world to introduce routine HPV immunisation of 12- to 13-year-old girls in a highly successful school-based program that started in 2007. It was also the first country to introduce routine HPV immunisation of 12- to 13-year-old boys in 2013, partly to protect against rare anal and penile cancers but mainly to protect girls, as with the rubella vaccine. The reward has been a significant fall in pre-malignant cervical lesions. In 2018, almost 1000 women in Australia will develop cervical cancer and just over 250 will die from it. Research predicts that due to HPV vaccine use, cervical cancer will become a ‘rare cancer’ in Australia in 2020 (defined as fewer than 6 new cases per 100,000 women annually) and fall below the elimination threshold of 4 per 100,000 by 2028, and that by 2066 Australia will be the first country in the world to eliminate cervical cancer.
Looking ahead
We often take immunisation for granted. But it is extraordinary to reflect on the diseases we can now prevent, and the way vaccines have transformed our lives in less than a century. Leading United States epidemiologists have estimated that 103 million cases of childhood disease have been prevented by immunisation since 1924 (95% of the infections that would have occurred without immunisation), and 26 million of them in the last decade alone (99% of the infections that would otherwise have occurred) – and that is just in the United States.
I call this the golden age of immunisation, although goodness knows what name others will come up with if we make even more progress. The present is exciting; the future could be breathtaking.