Phrenic Crush

For something to return, it has first to go away. In Asia, Africa and Latin America, TB never did go away; in richer countries it was only driven down to lurk in the places inhabited by society’s rejects. It didn’t disappear completely from among society’s paid-up members: its germs sleep in me today. I have a Ghon focus in my left lung, a collection of cells, some from my immune system, which wall off the tubercle bacilli that infected me more than half a century ago during my childhood in the North of England. Calcium salts have built up and settled in it over the years, so it shows on a chest X-ray.

The tubercle bacillus grows very slowly; its epidemics take centuries and the disease it causes is usually chronic. The age of the celebrity sufferer or victim is long since over: George Orwell, Vivien Leigh and Eleanor Roosevelt were the last. It is not surprising, then, that it’s hard to attract media attention to tuberculosis. Every day, more than five thousand people die from the disease, most of them young adults, yet it barely registers on the political consciousness.

The mid-Victorian Anglo-Irish physicist, adulterer and writer Dionysius Lardner was the first to explain why this might be so. In an article on railway safety in The Museum of Science and Art (1854-56), he wrote:

In the modes of travelling used before the prevalence of railways, accidents to life and limb were frequent, but in general they were individually so unimportant as not to attract notice, or to find a place in the public journals. In the case of railways, however, where large numbers are carried in the same train, and simultaneously exposed to danger, accidents, though more rare, are sometimes attended with appalling results. Much notice is therefore drawn to them. They are commented on in the journals, and public alarm is excited.

Events in New York during the late 1980s and early 1990s played this role for tuberculosis, and Deborah and Rodrick Wallace recount some of them in their chapter in Matthew Gandy and Alimuddin Zumla’s book. Cutbacks in control programmes, reductions in treatment facilities, a decaying of the culture of infection control in institutions, the provision of giant ‘concentration’ shelters for the homeless and a decline in the quality and quantity of housing for the poor came together to reverse the long-term decline in the incidence of tuberculosis that in the 1960s had been seen as heralding the imminent extinction of the disease. HIV made things even worse. Its attack on the immune system converts tuberculosis from a chronic into an acute disease, of the sort that in the old days would have been called ‘galloping’. Many New York patients died within six months of being infected, not only because they were HIV-positive but because their TB had been caused by a strain of the bacillus that was resistant to all the main anti-tuberculous drugs. If ever there was a time to panic, it was now. The multi-drug resistant (MDR) strain got into 23 New York prisons, where it killed 34 people. It spread with ease in hospitals, and travelled from New York to Florida, Nevada, Georgia and Colorado. All this stimulated political action: the New York Bureau of Tuberculosis Control budget rose from $4 million to $40 million; Rikers Island, which holds 15,000 inmates and where the incidence of tuberculosis had risen from 152 per 100,000 in 1986 to 500 per 100,000 in 1990, spent $60 million on control measures. The New York outbreak peaked in 1992, with 441 cases. Their number then fell by more than 35 per cent per year. New York was lucky. Most of the MDR spread had been in hospitals, where infection control procedures could be effectively improved by technical measures; and there was money.

Léopold Blanc and Mukund Uplekar start their chapter on ‘The Present Global Burden of Tuberculosis’ with the fact that nearly a third of the world’s population – two billion people – is infected with tuberculosis; that eight million develop the active disease every year; and that two million die. The disease is commonest in developing countries in Africa, Asia and the Americas, and rarest in Western Europe, Australia, New Zealand, Japan and North America. It was not always so. In 1997, well after Aids had taken hold, the number of new cases in Africa was estimated (after correcting for the incompleteness of official statistics) to be 259 per 100,000 of population. In Scotland in 1887, the death rate was 308 per 100,000, greatly in excess of the estimated death rate of 88 per 100,000 in Africa 110 years later. It is well under one per 100,000 in Scotland today.

Why is this the case? ‘There is an increasing awareness,’ Zumla and Gandy write in the book’s closing sentence, ‘that the failure to control TB worldwide is a direct consequence both of poor political leadership and the burden of poverty borne by the great majority of its sufferers.’ So did Scotland and the rest of the industrialised world reduce TB by good political leadership and the reduction of poverty? The answer is complicated, and Matthew Gandy’s chapter, ‘Life without Germs’, helps to explain why. He cautiously introduces the McKeown thesis. In his now notorious The Modern Rise of Population (1976), Thomas McKeown proposed that in countries such as Britain population growth in recent centuries followed improvements in nutrition. Central to his thesis is the notion that better food reduced the mortality from infections, notably those like tuberculosis. This is contested, not so much because of its arguments about food, which cannot be ignored, but because it rejects a role for hospitals and doctors in reducing mortality in the 19th century and the first thirty years of the 20th, a period when death rates plummeted. For tuberculosis, they had been falling rapidly ever since records began in the 1830s. McKeown’s proposition was seen as an insult by public health professionals; it still is. What about sanatoria and all the other public health and medical measures, particularly those prompted by the discovery of the tubercle bacillus by Robert Koch in 1882? Were they all without merit?

With pulmonary tuberculosis, there is no doubt that what doctors did to patients before the discovery and development of the main anti-tuberculosis drugs after World War Two – streptomycin, rifampicin and isoniazid – was, on balance, harmful. The best that sanatoria such as Nordrach in the Black Forest and its British imitators, Nordrach-on-Mendip in Somerset and Nordrach-on-Dee in Aberdeenshire, did was to prevent their sequestered inmates from coughing bacilli over the public at large. The Edinburgh system of ‘zomotherapy’, the eating of raw meat, usually in the form of uncooked beef sandwiches, cured nobody. Linda Bryder’s excellent Below the Magic Mountain (1988) is full of other revelations, of regimes such as that at Frimley Sanatorium, for instance. Not only were visitors banned (‘talking and laughing aggravate a cough and so induce auto-inoculation’), and letters censored to prevent worry caused by bad news, hard manual labour was prescribed by the medical superintendent. Men and women were pictured in the press under the caption ‘Pickaxe Cure for Consumptives’. Frimley was for the working classes; fee-paying patients in other sanatoria exchanged pickaxes for golf clubs.

The worst came after the First World War with the enthusiastic application of ‘collapse therapy’, in which the tuberculous lung was ‘rested’ by the injection of air between the lung and the chest wall (artificial pneumothorax, or AP), or by crippling the diaphragm by damaging its nerves (the ‘phrenic crush’), or by blowing air into the peritoneum. Most savage of all and permanent (APs needed regular topping up) was the removal of ribs: ‘thoracoplasty’. These treatments had some benefits: they raised the professional status of tuberculosis doctors because they now administered specialised and dangerous procedures, and stimulated the development of chest surgery. But the benefits for patients, even those who survived the deliberate reduction of respiratory capacity, were few, apart from raising their status in the sanatorium. Bryder quotes from an account of 1939: ‘Thoracoplasty cases looked down unchallenged from the height of their surgical experience . . . a cut above the plain AP . . . APs placed phrenics in the apprentice class. All who were having active treatment gazed with disdain on those . . . on rest.’

It would be wrong to claim, however, that medical science had not made any progress against tuberculosis before the advent of effective drugs. The most important measure was milk pasteurisation. Invented at the end of the 19th century, pasteurisation was liked by milk processors because it extended shelf life; it also killed the tubercle bacillus. Tuberculosis was rampant in British cows until the middle of the 20th century. The slowness with which pasteurisation was adopted, because of vigorous campaigns by lobbyists who believed that ‘nature’ shouldn’t be tampered with, condemned many people to death. Between 1912 and 1937, 65,000 died from milk-borne tuberculosis in England and Wales.

Tuberculosis does not confine itself to the lungs; it can affect just about any organ. The crippled children and adult hunchbacks familiar from Victorian images were attacked by tubercle bacilli carried in the blood to their bones and joints. They were among the earliest beneficiaries of Lister’s revolutionary introduction of antiseptic surgery in 1867. The first antiseptic operation ever performed, apart from the dressing of wounds, involved the incision and draining of a psoas abscess. This is a condition in which the destruction of vertebrae by the tubercle bacillus stimulates the production of pus, which tries to escape along the psoas muscle that runs down the front and side of the backbone into the groin. In Lister’s first case, a 25-year-old woman, the pus had built up and pointed – formed a swelling – at the front of her thigh. Letting the pus out had previously sentenced such patients to death because other bacteria would inevitably enter the wound and spread up into the abscess cavity, causing an uncontrollable and eventually lethal infection. In this case, it did not happen, even though the abscess contained more than a pint of thin and curdy pus.

The pervasive theme of The Return of the White Plague is that TB is a disease of poverty and of social exclusion. So where should control efforts be focused? Why do poor people still die of consumption? What are the lessons from history? In countries such as Britain, tuberculosis was converted from a chronic disease into a chronic infection. Immunological tests on the medical school class that I joined in 1957 showed that most of us had been infected without ever having developed the disease. The contrast with the 124-strong BA class at Aberdeen University exactly 90 years before – a particularly well-recorded cohort – is stark. Three died of TB while still at the university and within 40 years it had killed another 14. It was the commonest cause of death among alumni during this period, well ahead of the next contenders, fever in the tropics (four) and being shot in the US (one by Apaches and two in Texas, one accidentally and one homicidally). But the Aberdeen students of the 1860s were not poor, or victims of bad housing. Most of them were the sons of farmers, merchants, ministers and lawyers. McKeown was right in this case: their spartan Scottish student diets were not good enough to give their immune systems the strength to wall off the bacilli that were sprayed over them in the classroom and in their lodgings in the expectoration of friends and colleagues. Repeated exposure was too much for a significant minority. Diseased lungs, the result of a poor immune response, coughed out the bacilli growing in them, which in turn caused infection in others with a similar deficiency.

Getting experimental evidence from human sufferers to test this hypothesis is impossible, but it has strong support: for example, in the detailed observations made by a British medical officer during World War Two at the hospital at Tost in Germany. It had beds for 1000 Russian and 250 British prisoners. Before admission they had worked 12 hours every day (except every fourth Sunday) in stone quarries or coalmines. The Wehrmacht-determined semi-starvation diet supplied 1600 calories per day. The only difference between British and Russians was that the former had Red Cross parcels, supplying another thousand calories daily with vitamins. Twenty per cent of the Russians developed pulmonary tuberculosis; the figure for the British prisoners was 1.5 per cent.

For countries with a tuberculosis problem today, improving the diet is vital. But it will be a much harder path to follow than the one travelled in the past by countries such as Scotland. HIV has made certain of that. It puts its sufferers into a position like that of the Russians at Tost. Even the tuberculosis suffered by the two groups is similar: a rapid pneumonia with death at about six months after infection. HIV also attacks the economically active: by killing farmers, it is reversing the improvement in diet that has come from better agriculture.

The handling of HIV has been attended by scandal. Senior scientists who should know better have aided and abetted those with a vested interest in denying that it is the cause of Aids. Hundreds of thousands are dying prematurely because they cannot afford effective drugs. This replicates what happened over the years with tuberculosis, whose own particular scandal has been the misapplication and abuse of the benefits deriving from the discoveries made about it.

An early example was the Lübeck disaster of 1930. During the 1920s a tuberculosis vaccine was introduced. It used a crippled strain, the Bacille Calmette-Guérin (BCG), made avirulent by culturing it many times over for several years on a potato-based medium. The BCG used in Lübeck had been prepared in the laboratory of the municipal hospital under the control of its medical superintendent, Georg Deycke. But the laboratory was badly run and the cultures became contaminated with ‘hot’ TB strains recently isolated from patients. The vaccine was never tested for virulence before use. In early 1930, 251 infants were given it by mouth. Within a year, 71 of them had died of TB. Another 135 developed the disease, but recovered. After a long trial, Dr Deycke and the director of the Lübeck Health Office were found guilty of manslaughter, and of injury by negligence, and were sent to prison.

The Lübeck disaster was caused by the incompetence of a few, but the perpetrators of a much greater offence remain unpunished. Discovering the first anti-tuberculosis drugs and evaluating effective ways to use them rank as among the most important medical advances ever. Selman A. Waksman was awarded the 1952 Nobel Prize for the discovery of streptomycin in 1943. In 1946, Austin Bradford Hill of the Medical Research Council invented the controlled trial as a way of assessing it. Another trial in 1948 showed how to prevent the development of drug resistance during treatment by giving streptomycin simultaneously with another drug, para-amino-salicylic acid (PAS), discovered in 1946. This strategy was made more secure by the addition of even more powerful drugs to the combination, isoniazid and rifampicin. Giving three or more drugs at once should reduce to insignificance the risk of resistance developing. But in practice this principle was all too often ignored, or forgotten, or more likely not even understood, so that drugs were given piecemeal, propelling the evolution of MDR strains on a scale that has made them an important public health problem. The prologue of Gandy and Zumla’s book summarises it well:

A deep problem has been a failure to appreciate the evolutionary change that occurs in disease organisms as a direct consequence of the attempts to deal with them. In the optimistic climate of the 1950s and 1960s and beyond, public health theorists did not really consider how the bugs would react to medical practice, even though drug resistance had been reported since the late 1940s.

The Return of the White Plague would have benefited from a contribution by a bacteriologist, to explain why TB’s unholy coalition with HIV is microbiologically so successful, what the real prospects for control are and why pessimism is still in order.