It was the emergence of cholera in Peru in January 1991 that compelled the World Health Organization and the global medical community to take notice of Colwell’s message.
The global Seventh Pandemic of cholera35 began in the Celebes Islands in 1961, with the new strain, dubbed Vibrio cholerae 01, biotype El Tor. By the late 1970s the El Tor microbe had made its way into all the developing coastal countries of southern Asia and eastern Africa, and it was impossible to control it. It would not be until the 1991 Peruvian outbreak, however, that WHO and health experts would publicly acknowledge what Colwell had been saying for years: namely, that the El Tor strain was particularly well equipped, genetically, for long-term survival inside algae.
Since the early 1980s Colwell had been collaborating with the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh, eventually becoming its research chair. There, in the heart of cholera endemicity—perhaps the cradle of all cholera epidemics36—Colwell and her colleagues discovered that the El Tor strain was capable of shrinking itself 300-fold when plunged suddenly into cold salt water. In that form it was the size of a large virus, very difficult to detect. But the presence of hibernating cholera vibrio in a water source, or inside algae, could be verified by simply taking a sample and, in the laboratory, changing the conditions: add nitrogen, raise the temperature, decrease the salinity, and bingo! instant cholera.
They further discovered that the vibrios could feed on the egg sacs of algae: up to a million vibrios were counted on the surface of a single egg sac.37 That explained why health authorities couldn’t manage to eliminate El Tor once it had entered their communities. The organism simply hid in algal scum floating atop local ponds, streams, or bays, lurking until an opportune moment arrived for emergence from its dormant state.38
When El Tor hit the coastal parts of Peru in early 1991 the country was caught completely unprepared for such an occurrence. In Peru’s hot summer January—made hotter still by an El Niño event—a Chinese freighter arrived at Callao, Lima’s port city. Bilge water drawn from Asian seas was discharged into the Callao harbor, releasing with it billions of algae that were infected with El Tor cholera.39
The first human cases of the disease offered the microbes terrific opportunities for spread in Peru. A national summertime delicacy was ceviche, or mixed raw fish and shellfish in lime juice. The bilge-dumped vibrio had quickly infected Peru’s shellfish, so uncooked ceviche represented an ideal vehicle of transmission.
The second ideal opportunity for transmission of the microbes was provided by Lima’s largely unchlorinated water supply. Because of both cost constraints and U.S. Environmental Protection Agency documents that indicated there was a weak connection between ingesting chlorine and developing cancer, Peru had abandoned the long-standing disease control practice of using the chemical to disinfect public drinking water. Later, CDC studies would show that the majority of Peru’s cholera microbes were transmitted straight into people’s homes, dripping from their water faucets.
The first cholera cases hit Lima hospitals on January 23; days later cholera broke out some 200 miles to the north in the port town of Chimbote.
As the El Niño water spread out along the Pacific coast of the continent, carrying with it bilged algae, cholera appeared in one Latin American port after another.40 Eleven months into the Western Hemisphere’s pandemic, cholera had sickened at least 336,554 people, killing 3,538. Throughout those months the microbe’s emergence was aided by obsolete or nonexistent public water purification systems, inadequate sewage, and airplane travel. Cases reported in the United States involved individuals who boarded flights from Latin America unaware that they were infected, and fell gravely ill either in flight or shortly after landing.41
Colwell and her colleagues demonstrated that the vibrio in the algae and those recovered from ailing patients were genetically identical. Further, they showed that the El Tor substrain, Inaba, which was raging across Latin America, possessed genes for resistance to the antibiotics ampicillin, trimethoprim, and sulfamethoxazole. The same substrain was highly antibiotic-resistant in Thailand, where it was invulnerable to eight drugs.42
In Latin America the epidemic raged on well into 1994, with, according to WHO officials, “no end in sight.†More than $200 billion would be spent by Latin American governments by 1995, according to the Pan American Health Organization, for emergency repairs of water, sanitation, and sewage systems. Only about 2 percent of all cholera cases were actually reported to authorities, WHO said, and across the continent 900,000 cases were officially reported as of October 1993, involving more than 8,000 deaths. Officially reported numbers of cholera cases were so grossly understated that, by 1994, the only accurate statement one could make was this: between January 1991 and January 1994 millions of Latin Americans fell ill with cholera, thousands died, and the epidemic continues.
Once chlorine was vigorously introduced into Peruvian water supplies, the 01 strain proved fairly resistant to the chemical.43
Though it was obvious to scientists all over the Americas by 1992 that the El Tor epidemic had succeeded in becoming endemic cholera in much of Latin America largely because the microbe was carried in algae, the real challenge to rigid old analyses of the spread of the vibrio came in December 1992 when an entirely new strain of cholera emerged in Madras, India. Dubbed Bengal cholera, or V. cholerae 0139, the newly emergent microbe competed with El Tor for control of the Bay of Bengal ecology. By June 1993 Bengal cholera had claimed over 2,000 lives and caused severe illness in an estimated 200,000 people. It had spread across much of the coastal region of the Bay of Bengal, encompassing the Indian metropolises of Calcutta, Madras, Vellore, and Madurai, as well as most of southern Bangladesh.44
This new Bengal cholera appeared to be spreading far faster than the Seventh Pandemic. It took three years for that cholera strain to spread from India to Thailand, but the Bengal cholera had already turned up in Thailand’s capital, Bangkok, by mid-1993, and threatened to spread nationwide, according to researchers from Mahidol University in Bangkok.
In March the leading hospital in Dhaka was treating 600 Bengal cholera cases a day—three times their normal daily cholera rate. In rural parts of Bangladesh cholera victims were reportedly falling ill at rates up to ten times those seen with the previous year’s classic cholera outbreak.
Prior to the Bengal cholera outbreak there were two types of cholera in the world: classic and El Tor. Classic cholera, which was endemic in parts of India and Bangladesh, was extremely virulent and easily passed from one person to another via contact with microscopic amounts of feces. The El Tor type, in contrast, was less virulent but could survive in the open environment far longer. A hallmark of the El Tor strain was its ability to move in the open oceans, as a silent passenger inside algae.
The Bengal cholera appeared to represent a combination of characteristics found in both the El Tor and the classic vibrio. Researchers from the International Centre for Diarrhoeal Disease Research in Bangladesh reported that the new mutant “may be hardier than and probably has survival advantage over†the classic strain of the bacteria. They found thriving colonies of the Bengal organism in 12 percent of water samples they tested, and the bacterial toxin was in 100 percent of all waters examined in Bangladesh.
One genetic trait was clearly missing in the new Bengal strain: that which coded for antigens that were usually recognized by the human immune system. As a result, people did not seem to have antibodies to the new mutant, and even adults who had survived previous cholera outbreaks appeared to be susceptible to the Bengal strain.
Genetic analysis of the new mutant vibrio suggested a terrible scenario: that it was essentially the El Tor strain possessing the virulence genes of classic cholera. As such, it would represent an entirely new class of cholera microbe, the like of which had never been seen. The emergence of 0139 “hit epidemiologists and physicians l
ike a two-by-four between the eyes, because there is no explanation for its emergence and spread but ecology,†Colwell said in the fall of 1993.
In 1993 Colwell teamed up with two Cambridge, Massachusetts, physicians to try to pull together the Big Picture, an explanation of how global warming, loss of oceanic biodiversity, ultraviolet radiation increases, human waste and pollution, algal blooms, and other ecological events joined forces. Together, they theorized that the cholera microbe defecated by a man in Dhaka, for example, got into algae in the Bay of Bengal, lay dormant for months on end, made its way via warm water blooms or ship bilge across thousands of miles of ocean, and killed a person who ate ceviche at a food stand in Lima. Drs. Paul Epstein and Timothy Ford, both members of a group of physicians and scientists at the Harvard School of Public Health calling themselves the Harvard Working Group on New and Resurgent Diseases, were convinced that essential to protecting their Boston patients in the twenty-first century was a better understanding of what was transpiring in the oceans. They saw a complex interplay at work, involving global climate changes, pollution, and the microorganisms.
In Epstein’s view, algal blooms were giant floating gene pools in which antibiotic-resistance factors, virulence genes, and plasmids moved about between viruses, bacteria, and algae. He thought that ultraviolet radiation might be hastening the mutational pace. And terrestrial microbes were constantly being added to the gene pool, he said, in the form of human waste and runoff.45
Epstein lobbied scientists working in fields as varied as oceanography, atmospherics, satellite imagery, plankton biology, and epidemiology to find ways to collaborate, and answer questions about the links between the marine environment and human health. Epstein discovered that many other scientists had already reached the conclusion that changes in global ecology—particularly those caused by warming—were too often working to the advantage of the microbes.
For example, at Yale, where he still ran the Arbovirus Laboratory, Robert Shope was considering the impact of global warming on disease-carrying insects. On the basis of his nearly forty years of arbovirus research, Shope was convinced that even a minor rise in global temperature could expand the territory of two key mosquito species: Aedes aegypti and A. albopictus. Both species were limited geographically in the 1990s by climate. A. aegypti couldn’t withstand prolonged exposure to temperatures below 48°F and died after less than an hour of 32°F weather. A. albopictus was only slightly heartier in cold climes. As a result, in the Northern Hemisphere A. aegypti couldn’t live above 35°N latitude, or roughly the levels of Memphis, Tennessee, Tangier, Morocco, and Osaka. A. albopictus couldn’t survive above 42°N latitude during the 1990s, roughly equivalent to Madrid, Istanbul, Beijing, and Philadelphia.
Shope expected that warming would allow both mosquito species to comfortably move northward, invading population centers such as Tokyo, Rome, and New York. A. albopictus, the Asian tiger mosquito, could carry the dengue virus. A. aegypti was more worrisome because it carried both dengue and yellow fever; the latter was typically fatal 50 percent of the time.46 Historical analysis seemed to confirm such a hypothesis, as malaria had shifted geographically over the millennia in accordance with major climate changes.47
British experts on insect-borne diseases felt certain that global warming would greatly expand the territory and infectivity ratio of the East African tsetse fly, which carried the trypanosomes responsible for sleeping sickness. The researchers concluded that even a moderate increase—on the order of 1° to 2°C—could result in a higher rate of disease spread because the tsetse flies were known to be more active, to feed at a higher pace, and to process trypanosomes more rapidly at higher ambient temperatures. Thus, each tsetse fly could infect more people daily.48
The same principles held true for Anopheles mosquitoes and the spread of malaria. In 1993, Uwe Brinkmann, who headed the Harvard Working Group on New and Resurgent Diseases, was trying to figure out ways to predict not only latitude movements of mosquitoes in response to global warming but also their altitude changes. He felt there was an urgent need for research to determine which factors played a greater role in limiting Anopheles activities at altitudes above 500 feet: air pressure or cooler temperatures. If the latter was more important, he predicted, malaria could quickly overtake mountainous areas of Zimbabwe, Botswana, Swaziland, Rwanda, Tanzania, Kenya, and other geographically diverse parts of Africa. Further, the disease might with global warming climb its way further up the foothills of the Himalayas, the Sulaiman Range, the Pir Panjal, and other mountainous regions of Asia.
A detailed WHO Task Group report in 1990 offered a broader range of expected disease impacts from global warming. Even a moderate net temperature increase—on the order of 1°C—would alter wind patterns, change levels of relative humidity and rainfall, produce a rise in sea levels, and widen the global extremes between desert regions and areas afflicted with periodic flooding. These conditions would, in turn, radically alter the ecologies of microbes that were carried by insects. Furthermore, expected changes in vegetation patterns could, the WHO Task Group said, radically alter the ecologies of microbe-carrying animals, such as monkeys, rats, mice, and bats, bringing those vectors into closer proximity to Homo sapiens.49
There was also a strong consensus among immunologists that heightened exposure to ultraviolet light—particularly UV-B radiation—suppressed the human immune response, thus increasing Homo sapiens’ susceptibility to all microbes.50 Just as PCBs and other hydrocarbon pollutants were thought to have played a role in increasing microbial susceptibility in marine mammals, so many physicians felt there was ample evidence that air, water, and food pollutants affected the human immune system.
Another feature of global warming would be an increased dependence in wealthier nations on air conditioning. In order to conserve energy, buildings in the industrialized world had specifically been designed to minimize outward and inward air flow. It was much cheaper to heat or cool the same air repeatedly in a sealed room than to pump in fresh air from the outside, alter its temperature, circulate it throughout a structure, and at the same time expel old air. As the numbers of hot days per year increased, necessitating longer periods of reliance upon air conditioning, the economic pressures to recirculate old air repeatedly, to the limits of reasonable oxygen depletion, could be expected. Such practices for winter heat conservation in large office buildings had already been linked to workplace transmission of influenza and common cold viruses. Spread of Legionnaires’ Disease and other airborne microbes was expected to increase with global warming.
Even in the absence of serious global warming, energy conservation practices were, for purely economic reasons, spurring architects and developers toward construction of buildings that lacked any openable windows and were sealed so tightly that residents were apt to suffer “sick building syndromeâ€: the result of inhaling formaldehyde, radon, and other chemicals present in the building foundation or structure. Such chemicals posed little threat to human health if diluted in fresh air, but were significant contributors to health problems in residents and employees who inhaled levels that were concentrated in recirculated or thin air. Obviously, a building that was capable of concentrating such trace chemicals in the air breathed by its inhabitants would also serve as an ideal setting for rapid dissemination of Mycobacterium tuberculosis, if an individual who suffered from active pulmonary disease was residing or working within the structure.
The human lung, as an ecosphere, was designed to take in 20,000 liters of air each day, or roughly 60 pounds. Its surface was highly variegated, comprised of hundreds of millions of tiny branches, at the ends of which were the minute bronchioles that actively absorbed oxygen molecules. The actual surface area of the human lung was, therefore, about 150 square meters, or “about the size of an Olympic tennis court,†as Harvard Medical School pulmonary expert Joseph Brain put it.
Less than 0.64 micron, or just un
der one one-hundred-thousandth of an inch, was all the distance that separated the air environment in the lungs from the human bloodstream.
All a microbe had to do to gain entry to the human bloodstream was get past that 0.64 micron of protection. Viruses accomplished the task by accumulating inside epithelial cells in the airways and creating enough local damage to open up a hole of less than a millionth of an inch in diameter. Some viruses, such as those that caused common colds, were so well adapted to the human lung that they had special proteins on their surfaces which locked on to the epithelial cells. Larger microbes, such as the tuberculosis bacteria, gained entry via the immune system’s macrophages. They were specially adapted to recognize and lock on to the large macrophages that were distributed throughout pulmonary tissue. Though it was the job of macrophages to seek out and destroy such invaders, many microbes had adapted ways to fool the cells into ingesting them. Once inside the macrophages, the microbes got a free ride into the blood or the lymphatic system, enabling them to reach destinations all over the human body.
The best way to protect the lungs was to provide them with 20,000 liters per day of fresh, clean, oxygen-rich air. The air flushed out the system.
Dirty air—that which contained pollutant particles, dust, or microbes —assaulted the delicate alveoli and bronchioles, and there was a synergism of action. People who, for example, smoked cigarettes or worked in coal mines were more susceptible to all respiratory infectious diseases: colds, flu, tuberculosis, pneumonia, and bronchitis.
Because of its confined internal atmosphere, the vehicle responsible for the great globalization of humanity—the jet airplane—could be a source of microbial transmission. Everybody on board an airplane shared the same air. It was, therefore, easy for one ailing passenger or crew member to pass a respiratory microbe on to many, if not all, on board. The longer the flight, and the fewer the number of air exchanges in which outside air was flushed through the cabin, the greater the risk.
The Coming Plague Page 88