The Pandemic Century

by The Pandemic Century- One Hundred Years of Panic, Hysteria

  By now, it was becoming clear that Legionnaires’ disease was closely associated with hotels, hospitals, and other large buildings. But though it was suspected that cooling towers and modern air conditioning systems facilitated the spread of the organism, attempts to isolate L. pneumophilia from the cooling towers of hospitals failed. Then, in 1978 came a breakthrough with the report of an outbreak in the heart of Manhattan’s garment district. By September, the CDC had identified seventeen cases, the majority of them centered around a building on 35th Street between Seventh Avenue and Broadway. On the CDC’s advice, the city ordered businesses in the immediate vicinity to switch off their air conditioners. The agency then collected epidemiological samples from nearby buildings, including the cooling tower on the roof of Macy’s Department Store located directly opposite the building on 35th Street. The sample tested positive for Legionella, but the CDC did not have sufficient epidemiological evidence to say the Macy’s cooling tower was to blame. However, earlier that year, investigators had attended another outbreak at the Indiana Memorial Union and recovered L. pneumophila from the Union’s cooling tower, so it was pretty obvious that cooling towers were responsible for many of the outbreaks. In addition, scientists found a nearby stream teeming with other species of the same bacteria, suggesting that the organism was widespread in the environment.

  Currently, the genus Legionella comprises nearly forty different species and sixty-one serogroups.* However, it is one species, L. pneumophila, that is responsible for 90 percent of Legionnaires’ disease cases. A facultative intracellular parasite, it is unable to grow outside of cells. Instead, it has evolved to live in natural aquatic environments, such as lakes, streams, ponds, and ground water. These environments are teeming with amoeba and protozoa that routinely ingest other ubiquitous bacteria as food. However, Legionellae are able to evade these microbial processes and “trick” the amoeba into ingesting them. Once inside an amoeba, the bacterium multiplies intracellularly before releasing dozens of newly formed Legionellae into the water. The new organisms then try to trick other amoebae into ingesting them. In this way, Legionellae are considered “Trojan horse” bacteria.

  Under natural conditions, water rarely reaches the temperatures necessary for the bacteria to multiply (Legionellae grow best at temperatures of 72°F to 113°F), ensuring that populations are kept to safe levels. Man-made environments are different, however. Hotels, hospitals, and other large buildings are home to a number of devices that utilize water at ideal temperatures for the growth of Legionella bacteria. These include showerheads, hot tubs, whirlpool spas, water fountains, humidifiers, misting equipment, and architectural fountains. Cooling towers are of particular concern because the pools of warm water are open to the atmosphere—indeed, Legionella bacteria have been repeatedly isolated from the biofilms of slime and encrusted sludge on top of such towers, with some surveys indicating that as many as half of all cooling towers in the United States may be contaminated with the organisms. If such towers are not regularly serviced, this contaminated water can be aerosolized into microscopic droplets containing Legionella, enabling the organism to be drawn directly into a person’s lungs. One way this may occur is during the cooling process, when warm water from the condenser or chiller unit is sprayed across the fill at the top of a cooling tower, splintering the water into tiny droplets. While most of the water returns to the collecting pan to be circulated to the heat source to cool refrigerant from the air conditioning unit, some of the water is aerosolized, resulting in the production of a fine mist at the top of the tower. If a drift eliminator is not fitted to the tower or the eliminator is inadequate, this mist may then be drawn into nearby air intake vents and air shafts. Under certain temperature conditions, the mist can also cascade down the side of the building to ground level, from where it may be drawn in through open windows or inhaled by passing pedestrians. A third possible route of contamination is the pipework supplying potable water to showers and so forth, especially where hot water systems are run intermittently and water is left to stand for long periods in pipes. Finally, in theory, contamination can also occur if there is a direct link from the water tower to the chilled water supply of an air conditioning unit.

  One reason Legionella is so dangerous is that the same strategy that enables the organism to evade ingestion by amoebae also enables the organism to escape attack by the alveolar macrophages, the body’s first line of defense against lung infections. Instead, Legionellae multiply within the cells of the alveoli, before spilling out and colonizing other lung cells. If other host defense responses are not activated in time, the result is pneumonia and systemic illness.

  In the United States, the incidence of Legionnaires’ disease varies from state to state, with the highest incidence being recorded in the summer and fall. Those aged sixty and over are at greatest risk, especially if they suffer from chronic lung disease or have other underlying medical conditions. The disease also occurs more frequently in men than women, though whether this is due to the higher prevalence of cigarette smoking and lung disease in men, or some other predisposing factor, is not known (cigarette smokers have a two- to fourfold higher risk of developing Legionnaires’ disease than nonsmokers). Hospitals present a particular risk because of inadequate servicing of hot water systems and the way that such settings bring together large numbers of immunocompromised patients. Confined to their beds for long periods in wards, these patients, many of whom may be suffering from other conditions and have compromised immune systems, present the organism with the ideal host. Surveys have also found that modern medical technologies such as immunosuppressive therapies, intubation, anesthesia, and the placing of nasogastric tubes, also increase the risk of pneumonias due to Legionnaires’ disease.

  In 1978, the CDC held an international meeting to review what had been learned about Legionella, its epidemiology, and its ecology. By now, McDade had perfected a technique for visualizing the organism using a special silver stain that colored the walls of the Gram-negative bacteria. Meanwhile, other researchers were learning how to cultivate it on charcoal yeast agar, a special medium supplemented with iron and cysteine. In addition, using a fluorescent-antibody staining technique, CDC researchers had demonstrated that organisms observed by pathologists in lung tissue recovered from Legionnaires in Philadelphia were in fact L. pneumophila. Unfortunately, however, the final piece of evidence—Legionellae from the water tower on the roof of the Bellevue—eluded investigators as the hotel had now been closed and the tower and the air conditioning units thoroughly cleaned. Nevertheless, in light of the outbreaks seen at hospitals and other buildings in the United States, Fraser had little doubt that the hotel’s water tower had been to blame. Noting that the convention had coincided with a marked temperature inversion in Philadelphia, he speculated that this inversion could have caused mist from the tower to come across the edge of the roof and “cascade down the side of the building.” In this way, the contaminated air could have enveloped people on the sidewalk and been sucked into the lobby through a vent near the ground floor, thus accounting for both the cases observed among delegates and the Broad Street pneumonias. There were two further pieces of evidence implicating the Bellevue. The first was the discovery of antibodies to Legionella in eleven members of another convention group that had visited the hotel two years earlier and whose members had suffered similar fevers and pneumonias. The second was a survey of hotel staff who had been employed at the hotel at around the same time. They also had antibodies to Legionella. This suggested that hotel staff had been exposed from time to time and had managed to acquire immunity, which was why so few of them had succumbed to the infection in 1976. By contrast, the Legionnaires had no such history of exposure.

  THE LEGIONNAIRES’ disease outbreak is a classic example of how new technologies and changes to the built environment designed to improve hygiene and ameliorate the conditions of life are constantly giving rise to new threats to health and well-being. It also illustrates how, in certain political an
d cultural contexts, epidemics that might otherwise have gone unnoticed can command wide public attention and provoke considerable anxiety.

  L. pneumophila has been around for millennia, but it was not until we began building cities and equipping buildings with indoor plumbing and hot water systems that we presented the bacterium with a new ecological niche in which to prosper. And it was not until we added other luxuries, such as air conditioning, showers, humidifiers, and misters, that we gave the bacterium an efficient way to aerosolize and colonize the human respiratory tract. Even so, it took several years for doctors and public health experts to wake up to the pathogenic threat posed by the presence of this ancient organism in the heart of modern metropolises.

  One reason is that prior to the invention of a method for culturing the bacterium and diagnosing Legionella infections, Legionnaires’ disease was indistinguishable from other atypical pneumonias for which a causative agent had yet to be identified. This made it largely invisible to physicians and respiratory disease experts who believed that pneumonia was mostly a problem of the past. Even where outbreaks were sufficiently unusual to draw the attention of doctors and public health experts, as had been the case at St. Elizabeths Hospital in 1965 and Pontiac, Michigan in 1968, investigations were inconclusive and had reached dead ends. This might also have been the fate of the CDC’s inquiry into the outbreak at the Bellevue. That it was not is due, first, to its occurrence at a time of acute national anxiety about another epidemic disease, and second, to the intense media interest in the outbreak, sparked both by the focus on swine flu and by the fact that the victims were a venerated and vulnerable section of the American population. However, for all the resources at the CDC’s disposal, in the final analysis these factors might have counted for nothing had it not been for the determination of one scientist and his willingness to set aside preconceived notions and patterns of thought.

  By 1976, medical researchers were confident that they had identified all the leading causes of pneumonia and that, in any case, the condition responded to treatment with penicillin or one of the new generation of antibiotics, such as erythromycin and rifampicin. What few realized was that only half of sporadic pneumonia cases could be determined with existing diagnostic tests, much less that there had been several outbreaks for which a causal agent had never been identified. When examining pathology specimens and bacterial cultures, laboratory technicians had been taught to look, first, for the pneumococcus and, if that was absent, other known bacterial and mycobacterial causes of the disease. Using long-established culturing and staining techniques, it was possible to grow these bacteria on laboratory media and then color them with Gram stains or other common dyes. But what of an organism that could not be cultivated on the usual media and which, because it lacked a cell wall, could not be easily visualized with existing stains either? What, in other words, of an unknown unknown? This was the problem that confronted McDade when, using a stain developed for rickettsia, he peered through his microscope and spotted a faint rod-shaped organism growing in clusters. Because the organism did not conform to any of the known bacterial causes of pneumonia, McDade’s colleagues insisted it must be a “contaminant.” That is what their experience of cultivating bacteria in guinea pigs and their microbiology training had taught them. By contrast, McDade’s mind was unprepared by previous experience for such an observation, and the more he ruminated on it the more he became concerned. What if it was the stain and not experimental error that had brought the bacteria to light, and what if his observation was not an anomaly? Thus it was that a chance observation led McDade in the direction opposite to that of his colleagues and to an eventual resolution of the problem.

  Legionnaires’ disease also illustrates the role of medical technology and human behavior in shaping our interactions with pathogens. It was not simply that water towers and air conditioning systems afforded an old bacterium a new place in which to breed; to provoke an outbreak, the bacterium also had to meet a group of highly susceptible individuals. This happened first at hospitals and medical centers, where the expansion in intensive care beds in the 1960s and the growing number of elderly or mentally ill patients receiving institutional treatment increased the bacterium’s chances of finding an appropriate host. However, it also occurred at meatpacking plants and other large industrial premises with chiller units. And, of course, it also happened at luxury hotels and other large buildings with cooling towers and state-of-the-art air conditioning systems. The Bellevue was not alone in installing a Carrier refrigeration unit in the 1950s. In 1952, in preparation for that year’s Republican and Democratic conventions, engineers from the Carrier Company brought air conditioning to the International Amphitheatre in Chicago. Six years later, Carrier installed similar units in the Fidelity Building in Los Angeles, making it the first fully air-conditioned office building in California. By the end of the decade, air conditioning had also arrived in domestic homes, fueling migration to Florida and other “Sun Belt” states. The result was that by 1969, when Carrier announced that the towers of New York’s World Trade Center would be cooled and heated by its equipment, no American office or home, large or small, was considered complete without air conditioning.

  At the time, of course, no one realized that cooling towers and air conditioners presented an infectious disease risk. This only became significant after January 1977, when Joe McDade’s isolation of L. pneuomophila resulted in the discovery of the organism in other buildings across the United States. Once L. pneuomophila had been identified, researchers were able to show it submitted to treatment with erythromycin and rifampicin, drugs that quickly became the standard therapy. The result is that today Legionellae are recognized around the world as an important cause of community-acquired pneumonia outbreaks, prompting routine checks on the cooling towers of hotels and hospitals. That is not to say the threat has disappeared: despite the wider availability of diagnostic tests, Legionellae are thought to be responsible for around 2 percent of pneumonia cases in the United States annually (around 50,000 cases). Moreover, outbreaks continue to occur with disturbing regularity wherever public water management standards or the inspection and cleaning of private water towers is found wanting. For instance, between 2014 and 2015, ninety people in Flint, Michigan, contracted Legionnaires’ disease and twelve died after the town switched its water source from Detroit’s system to the Flint River. And in 2015, New York City experienced the largest Legionnaires’ outbreak in its history when the organism sickened 133 people living in apartment blocks in the South Bronx, killing 16. It later transpired that the source of the outbreak was a hotel water tower teeming with Legionella bacteria. In the most recent period for which figures are available—2000 to 2014—the CDC recorded almost a threefold increase in cases of legionellosis, which comprises both Legionnaires’ disease and Pontiac fever, across the United States. Of these, 5,000 cases a year were due to Legionnaires’ alone and the mortality rate was 9 percent. Of course, not all these outbreaks were the result of poorly maintained water systems or aging plumbing. America’s aging population, the wider availability of diagnostic tests, and more reliable reporting to local and state health departments and the CDC most likely also played a role. A further factor may be climate change: as summers become hotter and unseasonably warm temperatures continue into the fall, the more likely it is that plumes of contaminated water will issue from water towers unless effective chlorination and other disinfectant measures are taken. Unfortunately, all too frequently, they are not.

  To the extent that Legionnaires’ disease tapped into Cold War fears about biological weapons and chemical toxins, it seemed to hark back to the preoccupations of the 1950s; hence, Congress’s concern that it was a “missed alarm.” But to the extent that it was a disease completely new to medical science, and one that could be traced to new technologies and alterations to the built environment, it seemed to represent a new paradigm of public health, one that would become increasingly relevant in the closing decades of the twentieth century
. Indeed, by 1994, with the publication of Laurie Garrett’s The Coming Plague, Legionnaires’ disease was being seen as one of a series of “emerging infectious diseases” (EIDs), whose appearance was threatening to undo the medical advances of the postwar years and, with it, the certitude that advanced industrialized societies no longer needed to fear the plagues that had bedeviled previous eras. That the outbreak in Philadelphia in 1976 had coincided with the emergence the same year of a new viral hemorrhagic fever at a remote mission hospital in Yambuku, Zaire, close to the Ebola River, only served to underline these parallels; hence, the disease’s inclusion in an iconic list of EIDs drawn up by the Institute of Medicine in 1992. The authors’ biggest concern, however, was not Legionnaires’ disease or Ebola, but HIV, a previously unknown virus that had first become visible to medical science in around 1981, and which by 1992 was recognized as the agent of one of the largest pandemics in history.

  * A serogroup is a group of bacteria that share a common antigen.

  CHAPTER VI

  AIDS IN AMERICA, AIDS IN AFRICA