by David Isaacs
DA Henderson, leader of the WHO’s Smallpox Eradication Unit, recognised de Quadros as being not only a great epidemiologist but also a fearless and inspirational leader. DA had recruited de Quadros in 1971 to help eliminate smallpox in Ethiopia, which was fighting a prolonged civil war with Eritrea. Six of de Quadros’s teams were kidnapped by armed rebels, who also commandeered a United Nations helicopter with its pilot on board. De Quadros helped negotiate the return of the health workers and the pilot, all of whom resumed their work in the field. DA Henderson later said: ‘That’s a measure of the dedication he inspired. Even that helicopter pilot vaccinated the rebels who held him.’
Progress in eradicating polio stagnated in the early years of the new millennium in countries where there was conflict, political instability, limited access to remote regions, and poor healthcare systems. Immunisation levels fell in the tribal areas of Pakistan in 2009 when an influential local Muslim cleric, Maulana Fazlullah, launched a campaign against polio vaccination. His daily sermons, broadcast on radio and through mosque loudspeakers, denounced it as an American plot to sterilise Muslim children and reduce the Pakistani population. The Pakistani Taliban leadership campaigned against the vaccination programs, and appeared to target female healthcare workers.
Conspiracy theories about vaccination were given huge momentum in July 2012, when it was discovered that the United States Central Intelligence Agency (CIA) had recruited the assistance of a Pakistani doctor, Shakil Afridi, in mounting a fake hepatitis B immunisation campaign, in order to track down Osama bin Laden, former leader of al-Qaeda. Immunisation advocates were horrified that the CIA would jeopardise trust in immunisation in such a cynical fashion. The CIA argued that the ends justified the means. The relatives of immunisation workers killed in Pakistan by the Taliban would probably disagree.
Salma Farooqi, 30 years old, a dedicated nurse and mother of five, was famous for years of tireless work immunising children against polio in the town of Peshawar near the Khyber Pass. At 1am on Sunday 23 March 2014, armed men stormed her house, tied up other members of her family and took her away. The next day her body was found in a field 4 kilometres away. She had been tortured and repeatedly shot.
Over the previous two years, more than 30 Pakistani vaccinators had been killed by the Taliban. Some 100,000 of the polio vaccinators were teenage girls and young women, Pakistan’s ‘Lady Health Workers’. Salma knew the risks, which makes her extraordinary courage all the more praiseworthy.
In Nigeria, too, polio vaccinators have been targeted and killed by extremists. On 8 February 2013, nine young women giving polio vaccinations were killed by gunmen in an area in Northern Nigeria known to have been targeted by Boko Haram. Just days afterwards, a controversial Islamic leader claimed that polio was caused by contaminated medicine.
Yet even in such war-ravaged countries there are glimmers of hope. From January 2016, the Taliban blocked polio immunisation in Kunduz province in northern Afghanistan, saying they would only resume immunisation if the WHO built a clinic in the remote Char Data district to treat civilians and soldiers wounded by American bombs. The WHO does not run trauma clinics and was unable to comply, but this left 170,000 children in Kunduz province unimmunised.
In April 2017, elders in a remote village in the region were devastated when a 14-month-old became paralysed by polio. She was the third child in the village to be paralysed that year. In desperation the elders appealed to the Taliban.
Qari Bashir, the province’s Taliban health chief, was sceptical that the WHO truly had the interests of Afghan children at heart. ‘Every day the Americans are bombing Afghan children. I don’t think that [the little girl’s paralysis] was so important to them,’ he said.
Amazingly, though, Bashir listened to the elders’ plea, took pity on them and allowed polio immunisation to resume. It is a poignant illustration of how humanity can trump politics.
The strategy the WHO calls the ‘polio endgame’ has not proved easy. We have already heard that OPV vaccine can very rarely (1 in 2.5 million doses) cause vaccine-associated paralytic poliomyelitis (VAPP). In a poorly immunised population the VAPP strain can spread to unimmunised children and adults and cause a small cluster of cases. This is called circulating vaccine-derived poliovirus, or cVDPV. To eradicate polio completely – both wild-type and vaccine-derived polioviruses – the world will need to change from OPV to IPV, because IPV cannot lead to cVDPV.
By the end of 2016, 173 countries were using IPV in their routine immunisation schedules. There has been great pressure on the supply of IPV: it costs more, and it has to be delivered via injection by qualified health staff.
Yet perseverance is vital. Modelling studies estimate that if we stopped immunising against polio now, there would be 200,000 new cases within five years.
Polio eradication is tantalisingly close. When it is achieved, it will be one of the greatest human achievements, to be placed alongside the elimination of smallpox with justifiable pride.
CHAPTER 5
Tuberculosis, the great equaliser
Yet the captain of all these men of death that came against him to take him away was the consumption, for it was that that brought him down to the grave.
The Life and Death of Mr Badman, John Bunyan (1626–1688)
For some inexplicable reason, tuberculosis (TB) is often linked with romance. Lord Byron is partly to blame; he was an incurable romantic who had fantasies of dying slowly from tuberculosis in order to impress his many mistresses.
Henry David Thoreau – American poet, philosopher, emancipist and eternal optimist – caught TB when he was 18 and it plagued him on and off until he died from it in 1862, aged 44. Yet he once wrote: ‘Decay and disease are often beautiful, like the pearly tear of the shellfish and the hectic glow of consumption.’
Consumption is an old name for tuberculosis, deriving from the fact that it is a slow disease that causes the sufferer to become thinner and thinner, as if consumed by it. The name suggests a dallying, dreamlike death, rather than the true picture of terminal tuberculosis, which is a death characterised by starvation, weakness, exhaustion and depression. Other archaic names for tuberculosis were ‘the phthisis’, which means wasting, and ‘the white plague’ and ‘the white death’, so called because of the pallor caused by anaemia due to chronic tuberculosis.
Tuberculosis is and always was a horrible, debilitating disease, and it has killed more people than any other infectious disease in history. It has affected the world in myriad ways, leaving its imprint on humankind in real life, in literature, in the visual arts and in science. In Nicholas Nickleby, Charles Dickens called it ‘a dread disease’ that ‘medicine never cured’ and ‘wealth never warded off’, an illness ‘in which death and life are so strangely blended, that death takes the glow and hue of life, and life the gaunt and grisly form of death’.
Wealth never warded it off because TB was no respecter of class; most other infections were diseases of the poor, but TB was feared by everyone because it could kill anyone. When American author Susan Sontag was being treated for cancer she wrote a book, Illness as Metaphor, in which she likened 20th-century cancer to 19th-century tuberculosis. Both are ‘obscene in the original meaning of that word: ill-omened, abominable, repugnant to the senses’. As Siddhartha Mukherjee wrote when comparing TB and cancer in his wonderful book The Emperor of All Maladies, ‘Both drain vitality: both stretch out the encounter with death; in both cases, dying, even more than death, defines the illness.’
John Keats might have been a romantic poet, but TB wrecked his short life. His father died after a fall from a horse when Keats was eight, then his mother died from TB when Keats was 14. After that his grandmother looked after John and his three younger siblings. Keats studied medicine at Guy’s Hospital in London, but found that his studies got in the way of his first love, writing poetry. So he dropped out of medical school and pursued a career as a writer. John’s favourite brother, George, migrated to the United States, but his investments f
ailed and both he and his wife Georgina died penniless and racked with tuberculosis. John nursed his other dying brother, Tom, until Tom too succumbed to tuberculosis at age 19.
In 1820 John Keats started coughing and getting weaker and weaker. At first he was brave. In his famous poem ‘Ode to a Nightingale’, which he composed while reclining in the shade of a plum tree in his Hampstead garden, he wrote:
Darkling I listen; and, for many a time
Call’d him soft names in many a mused rhyme
To take into the air my quiet breath;
I have been half in love with easeful Death.
Yet easeful death did not come easily. Twice John Keats coughed up huge volumes of blood. He was persuaded that Italy would be good for his health and moved to an apartment next to the Spanish Steps in Rome. On the sea voyage and again in Rome he tried to persuade his dear friend and travelling companion Joseph Severn to give him laudanum (opium) – supposedly to relieve his pain, but in truth to end his suffering. Keats would sometimes cry when he woke up and found he was still alive. He often asked: ‘How long is this posthumous existence of mine to go on?’
Finally Severn wrote: ‘Keats raves till I am in a complete tremble for him . . . I lifted him up in my arms. The phlegm seem’d boiling in his throat, and increased until eleven, when he gradually sank into death, so quiet, that I still thought he slept.’
John Keats was just 25. He was buried in Rome, and at his last request was placed under a tombstone with no name or date, only the words ‘Here lies One whose Name was writ in Water.’ There is nothing romantic about tuberculosis.
Still, operas continued to romanticise tuberculosis in the mid-19th century, until realism eventually held sway. In Giuseppe Verdi’s La Traviata, which premiered in 1853, the wealthy heroine Violetta becomes more sensitive after catching TB. By 1896, in contrast, Giacomo Puccini portrays tuberculosis as a disease of poverty in La Bohème. His heroine Mimi dies destitute. Mimi’s lover Rodolfo abandons her, probably from fear of catching her infection: ‘Amo Mimi, ma ho paura’ (‘I love Mimi, but I am afraid’), he sings. But this is opera, and he returns to her, only to find her dying with her tiny hands frozen. There is romance and tragedy in La Bohème, but the tuberculosis is part of the tragedy, not of the romance. Chopin aged 39, Purcell at 36, Paganini at 58 and Stravinsky at 89 – all died of tuberculosis. In the 19th century, tuberculosis was the main killer in Europe and the United States: every year 1 in every 40 people died from TB, the white plague.
The origins of tuberculosis
Tuberculosis is as old as humanity. For a while experts thought TB originated less than 6000 years ago. However, more recent genetic analysis of strains of TB suggests the organism first emerged in humans in Africa around 70,000 years ago, was carried by people who migrated into Europe and Asia, and began to infect people during the Neolithic period (roughly 10,000 to 2000 BC). It wasn’t until large numbers of people began living in close proximity, however, that it spread widely.
In an extraordinary multidisciplinary research paper published in 2016, Australian authors hypothesised, on the basis of mathematical modelling, epidemiology, evolutionary genetics and paleoanthropology, that TB might have emerged at the time when humans learned how to control the use of fire. They argued that controlled use of fire altered lifestyle and provided ideal conditions for Mycobacterium tuberculosis to evolve because from then on people would huddle together round fires, often in caves, and cough on each other.
One of the fascinating things about human infectious diseases is that many of them come from animals or birds. Influenza originated in birds and pigs before infecting humans. The hepatitis B, polio and HIV viruses all derived from viruses that infected monkeys and apes before reaching humans. Measles virus came from the rinderpest virus of cattle. But TB is unusual, in that genetic studies suggest it emerged in humans before it appeared in any animals, and spread later to cows, and even later to animals like badgers when they came into close contact with cattle.
Mycobacterium tuberculosis is usually caught through being inhaled. It can cause severe lung disease, but it can also spread to the lymph nodes. The commonest site for enlarged lymph nodes is the neck. Indeed, the name tuberculosis (first used in 1839) comes from the Latin tuberculum, meaning a small tuber, because infected neck nodes were thought to look like small vegetable tubers.
It has long been recognised that people could develop enlarged, rubbery, painless swellings in the neck that could rupture, discharging blood-stained pus and leaving the neck chronically scarred by festering sores. This condition was known in the Middle Ages as ‘scrofula’, from the Latin scrofa, a breeding sow. (The link between a sow and TB is puzzling. Some point out that scrofula means ‘female piglet’, but pigs do not get TB. My own suspicion is that it gained this name because the udders of a breeding sow lie in a line that resembles the line of enlarged neck nodes in TB.)
Another name for scrofula was the ‘king’s evil’, and it was said in centuries past that it could be cured by royal touch, supposedly a divine gift from God. The practice began in France, persisting from King Clovis in the fifth century to Louis XVI, who was beheaded during the French Revolution in 1793. It was said that Henry IV (reigned 1589–1610) would touch and heal as many as 1500 scrofulous citizens at a sitting.
In England, the tradition started with Edward the Confessor in the 11th century and lasted until the accession of the more down-to-earth Hanoverians in the 18th century. The English king or queen would not only touch the sufferer, but also give them a gold coin called an angel, which was actually quite valuable. William Shakespeare wrote Macbeth for King James I, who had revised the lapsed practice of the royal touch. In Act IV, Scene 3, Malcolm says: ‘A most miraculous work in this good King, which often since my here-remain in England, I have seen him do. How he solicits heaven, Himself best knows; but strangely-visited people all swollen and ulcerous, pitiful to the eye, the mere despair of surgery he cures.’
The royal touch may seem rather bizarre and improbable now, but hindsight is a wonderful thing, and many of our current ceremonies will surely amaze our descendants.
TB can spread in the bloodstream to the bones, liver and spleen. The bones of the spine can become permanently bent forward in what is called a gibbus deformity (gibbus is Latin for ‘hump’.) Some 5000-year-old Egyptian mummies show this same classic symptom of TB in their vertebral column, causing their spine to bend forward at a sharp angle like the broken branch of a tree. The Hunchback of Nôtre Dame probably had TB of the spine. Most worryingly, TB can reach the lining of the brain called the meninges and cause meningitis, a disease that kills many of its victims and often leaves survivors brain-damaged (as we’ll see in Chapter 7).
People can develop TB if they drink milk from cows infected with Mycobacterium bovis, which causes bovine TB. In this case they usually get TB of the intestines, which can also spread to the rest of the body. In the 1890s, Finland started testing cattle for TB using a technique called tuberculin testing, and managed to eliminate bovine TB. All industrialised countries now routinely use tuberculin testing on cattle and pasteurise cow’s milk, so catching TB from cow’s milk is almost unheard of in these parts of the world. However, TB can still be acquired from drinking unpasteurised milk from cows, sheep or goats in resource-poor countries.
A cure for tuberculosis
Before the 20th century, prevention of human TB was the only option. In 1882, the German physician and microbiologist Robert Koch was able to grow the organism that causes tuberculosis. With characteristic modesty, he called tuberculosis ‘Koch’s disease’ and the organism ‘Koch’s bacillus’.
Around the same time, it was confirmed that TB was contagious. Australia and other Western countries instituted public health campaigns against spitting on trams and trains and in the streets, because sputum could contain tubercle bacilli. TB affected fashion too. Reports that the bacilli could be caught in long skirts encouraged the raising of hemlines – a cartoon called ‘The Trailin
g Skirt: Death Loves a Shining Mark’ appeared in an American magazine, Puck, in 1900, showing a maid shaking off clouds of germs from her lady’s skirt, watched by a scythe-bearing Death. Heavy-boned Victorian corsets, thought to exacerbate tuberculosis by preventing breathing and cutting off circulation, were replaced by elastic ‘health corsets’. Men shaved off beards and moustaches that might harbour germs.
After World War I, French scientists Albert Calmette and Camille Guérin developed a vaccine using Mycobacterium bovis, the organism that causes TB in cows. Between 1908 and 1921, they cultured and recultured the organism 230 times to attenuate it, a technique called ‘passaging’. Their vaccine was first used in 1921 and is named, in their honour, the Bacille Calmette-Guérin or BCG vaccine. It is the oldest vaccine still in use today.
Confidence in the safety and efficacy of injected BCG vaccine was bolstered by large, carefully conducted clinical trials. The first mass BCG immunisation campaign was started in Poland in 1948.
However, the effectiveness of BCG vaccine varies. For some unknown reason, it is more effective nearer the equator and less effective in East Asia. Overall, BCG prevents about 70% of TB cases, although the efficacy varies from zero (usually where the vaccine was not preserved properly) to 80% in different studies. It is more effective in preventing severe than mild TB disease: it is 90% effective in preventing TB meningitis and disseminated TB. The vaccine is by no means perfect, and we would love a better TB vaccine, especially one that would prevent TB circulating. The protection offered by BCG vaccine is a whole lot better than none, though, and BCG vaccine is still used in developing countries worldwide. However, the lack of a vaccine that prevents transmission has necessitated the use of antibiotics in the treatment of TB. These have to be given for months, which has contributed to the worrying emergence of antibiotic-resistant tuberculosis.