by David Isaacs
A large randomised controlled trial in Bangladesh showed that inactivated killed influenza vaccine protected pregnant women and also protected more than half their infants from catching influenza in their first six months after birth. A similar trial in South Africa found that the vaccine protected about half of all pregnant women against influenza, and their infants were half as likely to catch the virus.
There are a couple of myths about influenza vaccines. The first myth, propagated by some doctors, is that the vaccine does not work. It is true that the vaccine does not prevent all influenza. The proteins in the virus change a little each year, a phenomenon known as antigenic drift. For this reason, a new influenza vaccine is produced each year under the aegis of the WHO, based on the likely circulating strains of influenza. The vaccine will contain three or four different strains. In practice the match between the vaccine and the strains that actually circulate varies from year to year, so the vaccine’s efficacy varies too. Critics often point out correctly that influenza vaccine is less effective than vaccines against diseases like measles, but sometimes we have to live with imperfection, until we can do better.
It is also true that people with weakened immune systems, such as cancer patients and the elderly, do not respond as well to the vaccine, even though they are the people who need it most because influenza is more severe if your immune system is weakened. (Stronger influenza vaccines are available now and may be the answer – we’ll look at influenza and the elderly in Chapter 10.)
The second myth is that influenza vaccines actually cause influenza. In fact, most of them are inactivated influenza vaccines, which contain only proteins and so are incapable of causing influenza.
There are a number of possible reasons for feeling like these vaccines have given you the flu. It could be chance: you may be unlucky enough to catch a respiratory virus infection soon after receiving the flu vaccine. It could also be that your body’s immune response to the vaccine causes fever and aches, although controlled studies show this is not much more common than if you are given a placebo.
The influenza vaccine is extremely safe during pregnancy. Inactivated influenza vaccine has been recommended for pregnant women in the United States since 1960, so there is a long history of its use and good data to show that it does not cause problems to mother, foetus or newborn baby. Influenza vaccine has been given safely to Australian women for over 20 years, and the vaccine is in the lowest risk category for medicines in pregnancy.
Several studies have shown that the vaccine does not increase the rate of miscarriage, stillbirth or birth defects. In fact, a meta-analysis (combining the results of all similar studies) found that pregnant women given influenza vaccine were less likely to have a stillbirth than those not given the vaccine. Influenza vaccine is also extremely cheap, at around $10 a dose or less.
For pregnant women, being protected by influenza vaccine is far better than remaining unvaccinated.
Whooping cough
As already discussed, whooping cough (pertussis) is a life-threatening disease in the first months of life. Between 1980 and 1989, the United States reported 77 deaths from pertussis, of which 61 were infants under three months old.
I discussed the difference between whole-cell and acellular pertussis vaccines in Chapter 7. The acellular pertussis vaccines currently used in much of the industrialised world are less likely than the whole-cell vaccines to cause adverse effects such as fever. On the downside, the protection they provide is relatively short-lived. This is why pertussis continues to circulate.
At least two, preferably three, doses of pertussis vaccine are needed for adequate protection. But clinical trials show that newborn babies do not respond to the vaccine. The earliest time when babies can be immunised is at six weeks, and the second dose is given between 10 weeks and three or four months of age.
It is not surprising that most infants catch whooping cough from a parent, sibling or grandparent. One way of trying to protect infants has been to immunise their close relatives, a strategy given the touching name ‘cocooning’. This practice was adopted briefly in some places, including Australia and the United States, but unfortunately it has been difficult to prove that it works well.
A more effective intervention is to immunise mothers in late pregnancy. Pertussis vaccine is rarely marketed on its own nowadays, but is usually combined with diphtheria and tetanus vaccines into the triple DTP vaccine, or sometimes with other vaccines.
An average of four people die of whooping cough each year in the United Kingdom, but 14 babies under three months old died in an outbreak in 2012. In October 2012, the United Kingdom Department of Health introduced an emergency program to administer a vaccine containing tetanus, diphtheria, pertussis and polio vaccines (Tdap-IPV) to all pregnant women between 28 and 32 weeks’ gestation.
A study of over 26,000 pregnant women, of whom almost two-thirds received the vaccine, showed that it was over 90% effective in preventing pertussis in infants aged less than two months old whose mothers were immunised at least a week prior to delivery. The United Kingdom has continued the program and it has been 95% effective in reducing infant deaths from pertussis.
A safe option
Immunising mothers-to-be during pregnancy has been shown to be very effective in protecting their newborn babies against some potentially devastating infections. The vaccines also protect the women themselves. Despite understandable concerns about the safety of vaccines in pregnancy, large studies have shown that the vaccines currently recommended in pregnancy are extremely safe as well as effective.
CHAPTER 10
Vaccines for the elderly
Increasing life expectancy has revealed the extent to which our immunity wanes with age: a phenomenon sometimes given the disrespectful name of ‘immunosenescence’. Our immunity gets worse with time in the same way as we lose our memory; it forgets as much as our brain does.
Doctors can boost waning immunity in the elderly with vaccines, but we are faced with the obstacle that our immune system responds less well to vaccines as we grow older.
Shingles (zoster)
As we learned in Chapter 7, shingles (zoster) is a blistering, painful skin eruption, usually on one side of the body, caused by the reactivation of the chickenpox virus. The incidence of shingles increases with age: about a quarter of all people will have at least one attack of shingles in their lifetime, rising to half of all people who reach 85 years old.
Shingles and chickenpox are both caused by the varicella zoster virus (VZV). When we recover from chickenpox, the virus does not go away but lies dormant (latent) in our nerve cells. The rash may even recur in the same place in some people. Things known to increase the risk of shingles are stress and other impairments of the immune system, such as cancer, some drugs or old age.
Grandparents in close contact with young children are less likely to develop shingles than people of the same age who have no contact with young children. When children catch chickenpox for the first time, they expose others to it, including grandparents. This acts like a vaccine, boosting the elderly person’s immune response to the virus and making it less likely that they will develop shingles. This is because a healthy immune system ‘remembers’ the chickenpox virus and keeps it in check.
The severity of shingles also increases with age. For reasons nobody has ever been able to explain, children almost never get post-herpetic neuralgia – the severe, prolonged nerve pain following a bout of shingles – whereas the condition can devastate the physical, psychological, functional and social lives of the elderly. This in turn may precipitate major depression; some patients even commit suicide.
As our population has aged, the need to boost immunity with a zoster vaccine has become increasingly apparent. The first zoster vaccines were really just highly concentrated varicella vaccine; they contained the same live attenuated VZV virus, grown in the same way, but 14 times as much of it. A new zoster vaccine made from purified VZV protein plus an adjuvant has been used in rece
nt clinical trials. Studies of both types of vaccine show that people over 60 years old given zoster vaccine were half as likely as those given a placebo to develop zoster over the following three years.
There are problems with zoster vaccines, however. One is cost: the current vaccine is very expensive, although in the light of the often life-wrecking human cost of zoster, several countries, including the United States, the United Kingdom and Australia, have assessed it as cost-effective and elected to pay for it. Another problem is that because of waning immunity (immunosenescence, if you must), the vaccine becomes less effective with age, yet the highest incidence of zoster occurs among older people. Deciding on the optimum age to give the vaccine – based on both waning efficacy and increasing incidence – involves complex calculations. We know protection from the vaccine is likely to wane with time and the VZV virus stays in our nerves forever, so we may find we will need to give extra booster doses of zoster vaccine as people age, incurring additional expense.
In 2013, England introduced routine herpes zoster vaccine for adults aged 70, with a phased catch-up program for those aged 71 to 79. After three years, there were an estimated 17,000 fewer episodes of herpes zoster and 3300 fewer episodes of post-herpetic neuralgia in a population of 5.5 million.
When varicella immunisation is introduced for the whole child population, as has been done in the United States, Canada, Australia and several countries in Europe and the Middle East, chickenpox does not circulate nearly as much as previously. There is a risk that decreased exposure to natural chickenpox will mean the elderly will have less boosting of their immunity and be more likely to develop shingles. Because of this concern, the United Kingdom has not introduced routine childhood varicella immunisation.
The British fears are supported by data from Australia showing a slow but steady rise in the incidence of shingles since 2005, when routine childhood varicella immunisation was introduced. On a more optimistic note, modelling predicts that the incidence of shingles will plateau in Australia after 30 years, then decline to levels far lower than without varicella immunisation. In the United States, though, shingles incidence appears unaffected by the introduction of chickenpox vaccine. Modelling is not a perfect science and what happens in the real world can vary depending on unexpected or unexplained circumstances.
Influenza
People of any age from infancy to old age can die from seasonal influenza, but mortality is highest in the elderly.
There is strong evidence that older people can derive some protection from annual influenza immunisation. Most first-world countries recognise this by paying for annual influenza immunisation for the elderly.
Scientists have made various attempts to improve the vaccine’s effectiveness. One is the manufacture of a live attenuated influenza vaccine that is given intranasally (squirted up the nose). This vaccine works well in children but has no advantages over the killed vaccine in the elderly, and is not used for them. (For safety reasons, it is not used for pregnant women either.)
Other approaches have been to add adjuvants that boost the immune response (adjuvanted influenza vaccines) and to increase the dose of antigens (high-dose inactivated influenza vaccines). Both these vaccines improve protection by about a quarter, but have a higher cost. As we heard in Chapter 1, the elderly can also be protected against influenza by immunising schoolchildren, through herd immunity.
In 2018, the Australian Government paid for all people over 65 years old to receive either an adjuvanted or a high-dose influenza vaccine for free. The long-term routine use of these vaccines will depend on balancing the increased protection against the increased cost. Since influenza vaccines are unlike most vaccines, in that they have to be given annually, any variation in cost is a recurring one.
Pneumococcus
Sir William Osler (1849–1919) was a famous Canadian physician who is sometimes known as the Father of Modern Medicine. He once called pneumonia ‘the friend of the aged’ – often expressed as ‘the old man’s friend’ – because of the disease’s propensity to hasten demise.
This begs the question of whether you want your ‘friend’ to help you die; you might prefer to hang around a little longer. (It also begs the question of why the old man’s friend excludes women.) Osler worked before antibiotics or vaccines against pneumonia were available; nowadays, the fatalistic concept of pneumonia as a good exit strategy for the elderly is rarely felt to be appropriate.
As we heard in Chapter 7, the influenza virus is a major cause of pneumonia in the elderly. But another important cause is a bacterium called Streptococcus pneumoniae, or pneumococcus (from the Greek pneumon, lung, and kokkos, grain or seed). There are many different strains of pneumococcus, depending on their different outer sugar capsule. Pneumococci tend to be seen in pairs, so used to be called diplococci (‘double seeds’).
The highest incidence of pneumococcal infection is in infants, who can get meningitis as well as pneumonia, and in the elderly, who tend just to get pneumonia. Pneumococcal pneumonia can be treated with antibiotics, but has a high mortality rate in the elderly.
There are two major types of vaccine against pneumococcal infection. Pneumococcal polysaccharide vaccine (PPV) was first developed in 1945, and is made from the bacteria’s purified sugar coating. (Polysaccharide is a scientific name for sugar.) The most commonly used vaccine contains 23 different sugars from 23 different strains of pneumococcus and is sometimes called 23v-PPV (23-valent pneumococcal polysaccharide vaccine). This vaccine certainly works reasonably well in young and middle-aged adults, but its effectiveness in the elderly is controversial.
Polysaccharide vaccines are now being replaced by conjugate vaccines in which the polysaccharide sugar capsules are conjugated (chemically joined) to proteins. This technique has been important for developing vaccines against three organisms that can cause meningitis in babies: pneumococcus, meningococcus and Hib. The same conjugate pneumococcal vaccines that work well in infancy also work well in old age. They are more expensive than polysaccharide vaccines, but prices can often be negotiated. Some countries such as Australia and the United States have changed from pneumococcal polysaccharide (PPV) to pneumococcal conjugate vaccines (PCV) for the elderly, and other countries are highly likely to follow suit.
Pneumococcal conjugate vaccine had been introduced in 134 countries by the end of 2016; the WHO estimated that global coverage in 2016 was 42%.
Tetanus
Elderly adults occasionally develop tetanus from a dirty wound – often, if they are keen gardeners, a rose-thorn prick contaminated by soil containing manure. Antibody levels tend to fall with time after immunisation, but those with low levels who have been immunised have ‘immune memory’ that can boost their antibodies.
Tetanus is rare in well-immunised populations. However, some elderly people have never been immunised, and many of them do not know it. For this reason, booster immunisations that include tetanus (usually diphtheria-tetanus-pertussis vaccine) are recommended for the elderly in many countries every 10 years.
Maintaining immunity
Our immune system is weakest and we are most susceptible to infections at the extremes of life. Immunisation reduces the likelihood that the elderly will catch life-threatening infections like influenza and pneumococcal pneumonia, or fall prey to debilitating shingles.
As French singer Maurice Chevalier said: ‘Old age isn’t so bad when you consider the alternative.’ But good health in old age is a whole lot better than bad health, particularly if the bad health could easily have been prevented by immunisation.
CHAPTER 11
The tragedies and the frauds
The history of immunisation has been punctuated by tragedies and the victims have mainly been children. Some tragedies came about as scientists and researchers wrestled with technology, or struggled to understand the complexity of the human immune response. Some occurred because of well-meaning but ill-founded fears about vaccine safety. And at least one came about because of fraud.
/> Early tragedies in the United States
As we learned in Chapter 6, the German physiologist Emil von Behring proved that horse serum containing diphtheria antitoxin could help infected children recover from diphtheria. He later showed that tetanus antitoxin horse serum could protect war-wounded men against tetanus. For these discoveries he was awarded the Nobel Prize in 1901. Ironically, it was in that very year that the first major vaccine tragedy – relating to the same two diseases – occurred.
On 19 October, a St Louis physician, Dr RC Harris, was called to the home of Bessie Baker, a young girl who had diphtheria. He gave her an injection of diphtheria antitoxin and told her parents she would soon be entirely well. He also injected her two younger siblings with antitoxin to protect them from developing diphtheria.
Four days later he returned to the house. In an interview in the St Louis Post Dispatch, Dr Harris was quoted as saying: ‘There I found that the little girl was suffering from tetanus (lockjaw). I could do nothing for her. The poison was injected so thoroughly into her system that she was beyond medical aid.’ The spasms of her face and throat muscles would have been agonising. Within a week her two siblings also died from tetanus.
The antitoxin Dr Harris had given to the three children had been made by injecting diphtheria toxin into a retired milk-wagon horse called Jim. Jim had produced about 30 litres of antitoxin in three years, which had saved many children’s lives. But alas, Jim had contracted tetanus and had had to be put down. Horses can catch tetanus through infected cuts or, as is most likely in Jim’s case, through eating contaminated soil or droppings. Some serum taken from Jim two days before he was destroyed should have been discarded, but had unwisely been used to make the diphtheria antitoxin that killed the three Baker children and 10 other children in St Louis who were given the same antitoxin.