by David Isaacs
When I was a young doctor, bacterial meningitis was a common and much-feared disease in infants and preschool-age children, and the hospital where I work would look after 20 to 25 children with meningitis every year. The children would frequently develop fever, a bulging fontanelle and a stiff neck, and would often have convulsions or just look ill and unresponsive. Feeling helpless, their parents would watch aghast what was happening to their beloved child.
Nowadays, although our hospital admits more children than ever before, we may not see a single child with bacterial meningitis all year. The difference is immunisation.
The commonest cause of meningitis by far is an organism called Haemophilus influenzae type b (Hib for short). Before a vaccine was developed, some 5 to 10% of children with Hib meningitis would die and about 20% would be left with permanent brain damage, which could result in cerebral palsy, epilepsy, deafness, blindness and intellectual impairment. Hib can also cause a life-threatening illness called epiglottitis, a severe swelling of the top of the windpipe, which can cause a child to suffocate, as with diphtheria. Children can also get other nasty infections from Hib, including pneumonia, osteomyelitis and septic arthritis (acute infections of the bone and joints, respectively).
Before immunisation began in the 1990s, over 500 children under five years old in Australia developed severe Hib infections each year. Aboriginal children were particularly susceptible. In the United States, 20,000 children per year had Hib infections, a high proportion of them indigenous children. The reasons indigenous children worldwide are at increased risk are unclear, though the causes are probably mainly environmental, such as closer family contact and factors related to social disadvantage.
Following the introduction of vaccines in both countries, Hib disease is now vanishingly rare. Australia introduced Hib vaccines into the routine schedule in 1993, and within a short time there was a 95% decrease in incidence. Most of our young doctors have never seen a child with Hib meningitis, and I have not seen one for more than 20 years.
Incidentally, Hib incidence in Australia fell much more quickly than expected, to the extent that even unimmunised children are now less likely to get Hib infection. This is an example of vaccine-induced herd immunity (which we looked at in Chapter 1). It happens with Hib vaccine because the vaccine gets rid of Hib from immunised children’s noses, and the main way Hib is transmitted between children is through their nasal secretions.
Hib immunisation is not yet available universally, and much of the world is not so lucky: in 2000, experts estimate over 8 million children developed Hib infection worldwide and 370,000 of them died. However, by 2016, global efforts to bring Hib vaccine to the developing world had ensured that 191 countries had Hib vaccine in their routine childhood immunisation schedules. Global coverage of Hib vaccine was 70%, but with considerable inequity: the coverage was 90% in the Americas but only 28% in the Western Pacific. However, considerable recent progress has been made in Southeast Asia, where the proportion of children immunised against Hib rose from 56% in 2015 to 80% in 2016. At this rate it may be possible to eradicate Hib disease from the world.
The other major causes of bacterial meningitis in infants and young children are organisms called Streptococcus pneumoniae (pneumococcus for short) and Neisseria meningitidis (meningococcus). Although as the name suggests the main disease caused by pneumococcus is pneumonia, when it causes meningitis it is actually the most devastating of the three organisms. The mortality is higher and children who recover are more likely to be left with brain damage.
Immunisation against pneumococci with the best vaccines available, so-called conjugate pneumococcal vaccines, was introduced into the routine Australian childhood schedule in 2001 and has been highly effective. Conjugate pneumococcal vaccines are increasingly being introduced into developing countries through philanthropic funding of vaccine programs. Pneumococcal immunisation provides another example of vaccine-induced herd immunity: when the conjugate vaccine is introduced routinely in infancy, the incidence of pneumococcal disease also falls in the unimmunised population.
Meningococcal meningitis has a lower mortality than Hib or pneumococcal meningitis, but sometimes you can die or be maimed for life from meningococcal bloodstream infection before you have the chance to develop meningitis.
Marty Mayfield was a teenager who lived for skiing. He dreamed of being selected for the Australian Olympic Team. Every holiday he would train with an elite squad. At age 17, when he was at a ski training camp, he began to feel exhausted and ached all over. He was sure he had the flu. But in a matter of hours a rash appeared on his legs and he was rushed to hospital and went into a coma. In his dreams he had lost his legs and was floating in the sky.
When he woke from the coma, his father was sitting by the bed. He was fighting back emotion and trying to tell Marty something.
‘I know, Dad. I’ve lost my legs, haven’t I?’
Marty was determined to become a medical student to prevent this from happening to others. He was equally determined to ski again.
I met Marty when, as a medical student, he applied to do a research project with me on fever and rash. ‘I’m particularly interested in this topic because I had meningococcal infection myself,’ he told me as he sat in my room.
‘At least it didn’t have any lasting effects on you,’ I said.
‘Except for my legs,’ he replied casually, and lifted his trouser bottoms to show me two artificial legs. Marty had just returned from Vancouver, where he had won the silver medal in downhill skiing at the Paralympics.
Meningococcal infection can occur in outbreaks. It can hit teenagers and university students, unlike Hib and pneumococcal meningitis, which are diseases of pre-school children. It can kill or maim within hours. As such, meningococcal infections tend to get more publicity than Hib or pneumococcal infections, but we now have vaccines against all three. They are not perfect and they do not yet prevent every case, but they certainly prevent the vast majority.
All the organisms that cause childhood meningitis, Hib, pneumococcus and meningococcus, get in through the victim’s nose. Often they just stay happily inside the nose, lazing in a warm bath of mucus, reproducing intermittently, and doing the host no harm whatsoever. All right for some. But if the organism moves to the nose of a new host who has never experienced it before, it can sometimes pass through the nose lining (nasal mucosa) and get into the blood vessels to cause bloodstream infection (septicaemia, which in the case of meningococcus is called meningococcaemia).
Meningococcal septicaemia can clot up big blood vessels, causing loss of large areas of skin and underlying tissue, which will need skin grafts if the child recovers. At its worst the child can lose limbs, sometimes all four. As with Marty, the infection can be so rampant that a child, young adult or older person can go from well to moribund in a matter of hours. Sometimes it is so fulminant (severe) that even immediate diagnosis and treatment with penicillin, the most effective antibiotic, cannot save the person’s life. Meningococcal infection is one of the most feared of all infections.
Pneumonia
The lung infection pneumonia was described by the ancient physician Hippocrates, but he called it a disease ‘named by the ancients’, so it had clearly been around long before the fifth century BC. In the 12th century, the medieval Jewish philosopher and physician Maimonides wrote: ‘The basic symptoms that occur in pneumonia and that are never lacking are as follows: acute fever, sticking pleuritic pain in the side, short rapid breaths, serrated pulse and cough.’ The pleura is the membrane surrounding the lung, and when it becomes inflamed, as can happen with pneumonia, it hurts a lot to cough or take a deep breath, a condition called pleurisy.
Before the advent of antibiotics to treat pneumonia it had a high mortality rate, and in 1918 the legendary Canadian physician Sir William Osler described it as the ‘captain of the men of death’. Even now, pneumonia is a major cause of child hospitalisation throughout the world, and kills over a million children a year, 95% o
f them in developing countries.
Pneumococcus (Streptococcus pneumoniae), one of the causes of meningitis, is the major cause of bacterial pneumonia. Susceptibility depends on age, with the highest rates in infancy and again in old age, as immunity wanes. The other major risk factor is tobacco smoke, either through smoking or through living with a smoker. Aboriginal people are at particularly high risk of pneumococcal infection throughout their lives, partly due to tobacco smoke exposure and other associations with disadvantage. We have had effective vaccines against pneumococcus only since the year 2000, but they are now included in the routine childhood schedule in all industrialised countries and increasing numbers of developing countries.
In infancy, pneumonia is usually caused by a virus called respiratory syncytial virus (RSV); despite many years of effort by some of our best scientists, we have not been able to develop an effective vaccine against it. RSV was first isolated from chimpanzees with colds in 1956 and from human infants a year later.
A killed RSV vaccine was used in limited trials in the United States in the late 1960s. Disastrously, children given the killed RSV vaccine actually got worse-than-usual infections when they caught RSV. Two died. The trial was hastily stopped before any further children were immunised. That tragedy has led to extra caution, and is one of the reasons we have no RSV vaccine, even though RSV is a disease of global significance. (More on that in Chapter 15.)
Influenza is a major cause of pneumonia at all ages, although the mortality increases with age (as will be discussed in Chapter 10). We have vaccines against influenza, but because the influenza virus mutates (‘changes its spots’) annually, we need a new dose of influenza vaccine every year.
Tuberculosis is also a major cause of pneumonia globally, but predominantly in developing countries (as discussed in Chapter 5).
Hepatitis
Hepatitis means ‘inflammation of the liver’. It can be caused by infections, usually viruses, and sometimes by other things such as medications, autoimmune diseases and allergies. Acute hepatitis can result in a debilitating illness involving jaundice, vomiting and anorexia.
The major viruses that cause hepatitis are inventively named hepatitis A, hepatitis B and hepatitis C. We have extremely safe and highly effective vaccines against two of these – the hepatitis B vaccine was first approved in 1981 and the hepatitis A vaccine was introduced in the early 1990s. As yet there is no vaccine for hepatitis C, although vaccines are being developed and we do have new, safer oral antiviral drugs to treat the disease.
Hepatitis A is also called infectious hepatitis, and is caught by eating or drinking contaminated food (‘contaminated’ is a euphemistic way of saying that the virus is shed in a person’s faeces and spread to food). Doctors say that transmission occurs by the faecal–oral route. That is why, when it comes to food, people visiting countries with a high prevalence of hepatitis A should ‘wash it, peel it, cook it or forget it’. But travellers can be more certain of avoiding hepatitis A by getting themselves immunised with hepatitis A vaccine, or the combined hepatitis A and B vaccine.
Hepatitis B virus is also called serum hepatitis, and is acquired from injecting blood or blood products contaminated with hepatitis B virus. The virus is extremely infectious and can be passed on by contact with very small amounts of virus. It is 50 to 100 times more infectious than HIV.
Most people know that intravenous drug users are at risk of catching hepatitis B because of needle-sharing, and many look askance at anyone with chronic (long-term) hepatitis B virus infection. Hepatitis B can also be passed on in blood transfusions and contaminated blood products; in the past, before we knew the cause and how to prevent it, men with haemophilia used to catch hepatitis B from their treatment with the blood-clotting protein Factor VIII.
People with chronic hepatitis B can pass hepatitis B to their partners during sexual intercourse. In 1967, Swedish doctors reported an outbreak of 568 cases of hepatitis B infection among Swedish cross-country runners, occurring over the years 1957 to 1963. The tentative explanation was that all the runners had suffered scratches and skin lacerations, and the virus had been caught from small drops of blood on bushes, or from shared water when the runners washed together after running. Of course, it is possible that many of the runners had sex with each other, but history does not relate whether that alternative theory was even considered. Whatever the cause, there was a lot of hepatitis B transmitted between runners. (These were the days before hepatitis B immunisation was available.)
Hepatitis B can also be transmitted in contact sports. In 1982 in Japan, half of the 10 members of a high-school sumo wrestling club developed hepatitis B in one year, transmitted by a club member who was unaware he had chronic hepatitis B infection. Wrestlers in the club were known to keep wrestling even when they were injured and bleeding from skin wounds.
As recently as 2000, 11 of 65 members of a United States university football team developed hepatitis B infection. Five became acutely ill with hepatitis and six remained asymptomatic. Again, the source was a player with chronic hepatitis B infection.
The football team outbreak illustrates an important point. If an unimmunised child or adult catches hepatitis B infection, they may develop acute hepatitis (acute inflammation of the liver, causing an enlarged, tender liver and yellow jaundice), which can sometimes be fatal, or they may have a ‘sub-clinical’ infection, meaning they become infected but have no symptoms. You are much more likely to catch hepatitis B from an infected person who is perfectly well than from someone who is bright yellow. Nowadays, though, none of the athletes just described would have been infected, because they would have been immunised at birth or at school.
Most people with acute (short-term) hepatitis B recover after weeks of being unwell, and remain immune, but some will die rapidly from liver failure. A few will develop chronic hepatitis B infection, although the commonest way of developing this is at birth, if you are unfortunate enough to have a mother with chronic hepatitis B. People with chronic hepatitis B infection are often perfectly well for years, but the virus is living in their liver and in their bloodstream, and can eventually damage the liver. Chronic inflammation of the liver can lead to cirrhosis or to liver cancer. Liver cirrhosis causes massive build-up of fluid in the abdomen (ascites) and can lead to blood vomits (haematemesis) and early death. I will discuss how hepatitis B immunisation prevents liver cancer in Chapter 8.
Gastroenteritis
Rotavirus is the most virulent cause of gastroenteritis (gastro). There is a strong Australian connection here, because rotavirus was first identified in 1973 by an Australian team, including Ruth Bishop, a virologist, and Graeme Barnes, a gastroenterologist. They detected viruses in the intestinal cells of children with gastroenteritis. Initially they called them ‘duoviruses’ because they came from the duodenum. Later the viruses were renamed ‘rotaviruses’ because of their wheel-like structure (rota is Latin for ‘wheel’). This was a vital step on the road to developing a rotavirus vaccine.
Rotavirus is a virus that almost all infants catch. It infects the gastrointestinal tract (gut) and causes vomiting, profuse watery diarrhoea, abdominal pain and fever. Infants and young children are most likely to become ill, although older children and adults can also catch rotavirus. The most severely affected infants have to be admitted to hospital for rehydration, often using a drip to give intravenous fluids.
For a long time gastroenteritis was the major killer of young children worldwide, leading to the deaths of some 5 million infants and toddlers a year, and rotavirus is still a big killer of children in developing countries. In 2013, an estimated 215,000 children under five died from rotavirus gastroenteritis, 195,000 in developing countries and 20,000 in industrialised countries.
For a long time the WHO focused on improved treatment using oral rehydration solutions containing sugar, salt and water. However, deaths due to rotavirus infection continued to occur. Rotavirus vaccines were developed as live attenuated vaccines that are given orally, so that
the vaccine virus can stimulate an immune response in the gut. They have led to a marked drop in diarrhoeal diseases and in hospitalisations for rotavirus.
There were one or two deaths from rotavirus each year in Australia before the introduction of rotavirus vaccine in 2006, and half of those were Aboriginal children. In the United States there were 20 to 60 deaths each year, and Native American and Alaskan Native children were at higher risk. This may have been due to close living conditions, but essentially rotavirus gastroenteritis is a disease of poverty. Social disadvantage increases susceptibility to infection – a persisting gap between rich and poor that needs to be addressed. Immunisation is a powerful way of narrowing that gap.
By 2016, rotavirus vaccine had been introduced into 90 countries, of which 68 had achieved over 50% infant coverage. The WHO estimated rotavirus vaccine global coverage at 25% in 2016.
We will hear more about rotavirus in Chapter 11.
Measles
Measles will always show you if someone isn’t doing a good job on vaccinations. Kids will start dying of measles.
Bill Gates, founder of Microsoft (born 1955)
Few adults nowadays and almost none of our junior doctors have seen measles. Most children with measles are very miserable but recover, and people sometimes play down the severity of the disease and the need for the vaccine. But at its worst, measles was and still is a fearsome disease. A ninth-century Iranian physician, Muhammad ibn Zakariya al-Razi, was the first person to distinguish measles from smallpox.
Although smallpox came to Australia with the First Fleet in 1788 and decimated the local Aboriginal population within a year, measles did not come with the First Fleet. An Australian epidemiology research student, Beverley Paterson, determined to discover when measles first arrived in Australia, took on the arduous and inventive step of searching the logbooks of ship surgeons on voyages from England to Australia between 1829 and 1882. She also examined quarantine records. She found that no ship passengers were quarantined with measles before 1850, but ships arriving after that had many passengers who needed quarantining because of measles.