Spillover: Animal Infections and the Next Human Pandemic (21 page)

Science is a process performed in laboratories and in the field, but it’s also a conversation conducted through the journals. Being part of this conversation is especially important, even in the age of email, if a scientist is separated by distance from most of his or her peers. Within that context, Singh and Cox-Singh had followed the second paper with an article in still another journal, summarizing their discoveries, reviewing previous knowledge, and offering some concrete recommendations. It was labeled “Opinion,” a cautious editorial disclaimer, but it was really much more than that: a deeply informative overview, a thoughtful essay, and a warning. There was no list of coauthors; Cox-Singh and Singh spoke together, alone. The piece appeared in print not long before I met them, and I was carrying a copy.

Plasmodium knowlesi
malaria, they wrote, is not a new emergent infection of humans. It has been getting into people for some while but it was overlooked. Three kinds of Asian primate serve as its reservoir hosts: the long-tailed macaque, the pig-tailed macaque, and the banded leaf monkey. Other monkeys, still unidentified, might be harboring the parasite too. Transmission from monkey to monkey (and from monkey to human) occurs by way of mosquitoes belonging to one group of closely related species,
Anopheles leucosphyrus
and its cousins, including
Anopheles latens
in Borneo.
Anopheles latens
is a forest-dwelling mosquito accustomed to biting macaques, but it will bite humans too, if presented with the necessity and the opportunity. As humans have increasingly entered the Bornean forests—killing and displacing macaques, cutting timber, setting fires, creating massive oil-palm plantations and small family farm plots, presenting themselves as an alternative host—both the necessity and the opportunity have increased. (Borneo has been deforested at a high rate within recent decades, to the point that its forest coverage is now less than 50 percent; meanwhile the island’s human population has grown to about 16 million. Cox-Singh and Singh didn’t cite these facts but clearly had them in mind.) Given such circumstances, Cox-Singh and Singh wrote, “
it is possible that we are setting the stage for a switch
of host for
P. knowlesi
, similar to the one postulated for
P. vivax.
” A host switch, they meant, from macaques to humans.

They expressed the same concern to me. “Have we created this nice opening for
knowlesi
to come into?” It was Cox-Singh voicing the question. By “opening” she meant an ecological opportunity. “What’s a mosquito going to do? If we start taking so much of the habitat, will the mosquito adapt then to being in a less-forest environment?”

She let that thought trickle off, paused, and then started again. “I honestly believe we’re at a sort of critical point. And we should be watching. We should be watching the situation very, very carefully,” she said. “And hopefully nothing will happen.” But of course, as she well knew, something always does happen. It’s just a question of what and when.

31

M
onths and years after my conversation with Balbir Singh and Janet Cox-Singh, I was still wondering about
Plasmodium knowlesi
. I remembered a curious point the two scientists had made: that, unlike other malaria parasites,
P. knowlesi
is capable of reproducing in several kinds of primate. Its tastes in warm-blooded hosts are eclectic. It infects long-tailed macaques and pig-tailed macaques and banded leaf monkeys without distressing them much. It infects humans, sometimes, causing malaria that can be severe. It infects rhesus macaques—as laboratory experiments have shown—killing them quickly and surely. Further experimental work has revealed that it can infect a wide range of primates, including marmosets from South America, African baboons, and other kinds of Asian macaque. So with regard to hosts for the asexual phase of its life cycle—the sporozoite-to-gametocyte phase, occurring in mammalian blood and livers—it is a generalist. Generalists tend to do well in changing ecological circumstances.

I remembered also a vivid illustration from their overview article. It was a sketched map of the region, showing India, Southeast Asia, and the island realm of which Borneo sits at the center. The map showed, at a glance, how widely
Anopheles leucosphyrus
mosquitoes and long-tailed macaques are distributed. A solid line demarcated the native range of the mosquitoes, encircling southwestern India and Sri Lanka in a small loop, separate to themselves, and then a much larger, irregular loop sprawling over the map like a monstrous continental amoeba. The larger loop encompassed Bhutan and Myanmar and half of Bangladesh; the northeastern Indian states, including Assam; southern China, including Yunnan and Hainan and Taiwan; Thailand and Cambodia and Vietnam and Laos; all of Malaysia, all of the Philippines; and most of Indonesia, stretching eastward beyond Bali and Sulawesi. The area within that line, by my rough calculations, contains about 818 million people—that is, roughly one-eighth of the world’s human population, living within the greater ambit of
Anopheles leucosphyrus
mosquitoes. The distributional range of the long-tailed macaque was also traced on the map: a line of dashes, encircling almost the same area as the mosquitoes’ range, though not quite so large.

Would it be excessive to say that those 818 million people are all at risk of
P. knowlesi
malaria? Yes, it would. For one thing, long-tailed macaques are only patchily present within that vast area; they live mainly in edge habitats, where human-modified landscape meets forest. For another thing, the level of human jeopardy depends on other factors besides the geographical ranges of the mosquitoes and the monkeys. It depends on whether those mosquitoes come out of the forest to bite humans, and whether people go into the forest to be bitten. It depends on whether sizable expanses of forest are left standing within that region and, if not, how the mosquitoes react. As deforestation proceeds, do the forest mosquitoes go extinct, or do they adapt? It depends on whether the parasite becomes so well established within human populations that monkey hosts are no longer necessary. It depends on whether the parasite colonizes a new vector, achieving transmission via some other kind of mosquito—members of a species more willing to seek out humans in their longhouses, their villages, their cities. In other words, it depends on chance and ecology and evolution.

Awareness of
P. knowlesi
malaria, thanks in large part to Singh and Cox-Singh, has begun to spread. What’s harder to know is whether the parasite itself is spreading. Reports have appeared in the journals, documenting a few cases throughout the wider region. There was a Bangkok man who spent several weeks in a forested area of southern Thailand and got bitten by mosquitoes at dawn and dusk. There was a young soldier in Singapore who had trained in a forest full of mosquitoes and macaques. There were five cases from Palawan, a heavily forested island in the Philippines. There was an Australian man who worked in Kalimantan (Indonesian Borneo), near a forested area, and later sought treatment at a hospital in Sydney. There was a Finnish tourist who spent a month in Peninsular Malaysia, including five days in the jungle without a bed net, and then turned up sick in Helsinki. There have been cases from China and Myanmar. They all tested positive for
P. knowlesi
. No one knows how many more cases have gone unreported or unrecognized.

We are a relatively young kind of primate, we humans, and therefore our diseases are young too. We have borrowed our troubles from other creatures. Some of those infections, such as Hendra and Ebola, visit us only occasionally and, when it happens, arrive soon at dead ends. Others do as the influenzas and the HIVs have done—take hold, spread from person to person, and achieve vast, far-flung, enduring success within the universe of habitat that is us.
Plasmodium falciparum
and
Plasmodium vivax
, from their origins in nonhuman primates, have done that also.

Plasmodium knowlesi
may be at a transitional stage—or anyway, a straddling stage—and we can’t know its future plans. It’s a protist, after all; it doesn’t
have
plans. It will simply react to circumstances. Possibly it will adapt to the changing trend among primate hosts—fewer monkeys, more humans—as its plasmodium
cousins have adapted over the epochs. Meanwhile it serves as a nice reminder of what’s crucial about any zoonosis: not just where the thing comes from but how far it goes.

IV

DINNER AT THE RAT FARM

32

I
n late February 2003, SARS got on a plane in Hong Kong and went to Toronto.

Its arrival in Canada was unheralded but then, within days, it began to make itself felt. It killed the seventy-eight-year-old grandmother who had carried it into the country, killed her grown son a week later, and spread through the hospital where the son had received treatment. Rather quickly it infected several hundred other Toronto residents, of whom thirty-one eventually died. One of the infected was a forty-six-year-old Filipino woman, working in Ontario as a nursing attendant, who flew home to the Philippines for an Easter visit, started feeling sick the day after arrival (but remained active, shopping and visiting relatives), and began a new chain of infections on the island of Luzon. So SARS had gone halfway around the world and back, in two airline leaps, over the course of six weeks. If circumstances had been different—less delay on the ground in Toronto, an earlier visitor headed from there to Luzon or Singapore or Sydney—the disease could have completed its global circuit far more quickly.

To say that “SARS got on a plane,” of course, is to commit metonymy and personification, both of which are forbidden to the authors of scientific journal articles but permissible to the likes of me. And you know what I mean: that what actually boarded an airplane in each of those cases was an unfortunate woman carrying some sort of infectious agent. The seventy-eight-year-old Toronto grandmother and the younger nursing attendant remain anonymous in the official reports, identified only by age, gender, profession, and initials (like BW the malarious surveyor), for reasons of medical privacy. As for the agent—it wasn’t identified and named until weeks after the outbreak began. No one could be sure, at that early stage, whether it was a virus, a bacterium, or something else.

In the meantime it had also arrived in Singapore, Vietnam, Thailand, Taiwan, and Beijing. Singapore became another epicenter. In Hanoi, a Chinese American businessman who brought his infection from Hong Kong became ill enough to merit examination by Dr. Carlo Urbani, an Italian parasitologist and communicable-diseases expert stationed there for the World Health Organization. Within ten days the businessman was dead; within a month, Dr. Urbani was too. Urbani died at a hospital in Bangkok, having flown over for a parasitology conference in which he was never able to take part. His death, because of his much-admired work within WHO, became a signal instance of what emerged as a larger pattern: high rates of infection, and high lethality, among medical professionals exposed to this new disease, which seemed to flourish in hospitals and leap through the sky.

It reached Beijing by at least two modes of transport, one of which was China Airlines flight 112, from Hong Kong, on March 15. (The other route into Beijing was by car, when a sick woman drove up from Shanxi province seeking better treatment in the national capital; how she had become infected, and whom she infected in turn, is a different branch of the story.) Flight CA112 took off from Hong Kong that day carrying 120 people, including a feverish man with a worsening cough. By the time it landed in Beijing, three hours later, twenty-two other passengers and two crewmembers had received infectious doses of the coughing man’s germs. From them it spread through more than seventy hospitals just in Beijing—yes,
seventy
—infecting almost four hundred health-care workers as well as other patients and their visitors.

Around the same time, officials at WHO headquarters in Geneva issued a global alert about these cases of unusual pulmonary illness in Vietnam and China. (Canada and the Philippines weren’t mentioned because this was just before their involvement was recognized.) In Vietnam, said the statement, an outbreak had begun with a single patient (the one Carlo Urbani examined) who was “
hospitalized for treatment of severe, acute respiratory syndrome
of unknown origin.” The little comma after “severe” reflects the fact that those three adjectives and one noun hadn’t yet been codified into a name. Several days later, as the pattern of hopscotching outbreaks continued to unfold, WHO issued another public statement of alarm. This one, framed as an emergency travel advisory, marked the transformation of a descriptive phrase into a label. “
During the past week,
” it said, “WHO has received reports of more than 150 new suspected cases of severe acute respiratory syndrome (SARS), an atypical pneumonia for which cause has not yet been determined.” The advisory quoted WHO’s director-general at the time, Dr. Gro Harlem Brundtland, speaking starkly: “This syndrome, SARS, is now a worldwide health threat.” We had all better work together, Brundtland added (and do so quickly, she implied), to find the causal agent and stop its spread.

Two aspects of what made SARS so threatening were its degree of infectiousness—especially within contexts of medical care—and its lethality, which was much higher than in familiar forms of pneumonia. Another ominous trait was that the new bug, whatever it might be, seemed so very good at riding airplanes.

33

H
ong Kong wasn’t the origin of SARS, merely the gateway for its international dispersal . . . and very
close
to its origin. The whole phenomenon had begun quietly, several months earlier, in the southernmost province of mainland China, Guangdong, a place of thriving commerce and distinctive culinary practices, to which Hong Kong is attached like a barnacle to the belly of a whale.

Once a British colony, Hong Kong in 1997 was subsumed into the People’s Republic of China—but subsumed on a special basis, retaining its own legal system, its capitalist economy, and a degree of political autonomy. The Hong Kong Special Administrative Region, which includes Kowloon and other mainland districts as well as Hong Kong Island and several other islands, shares a border with Guangdong and a fluid exchange of visitors and trade. More than a quarter million people cross that border by land travel every day. Despite the easy commercial relations and visiting privileges, though, there’s not much direct contact between Hong Kong officialdom and Guangdong’s provincial capital, Guangzhou, a city of 9 million people that sits about two hours by road from the crossing. Political communications are filtered through the national government in Beijing. That constraint applies also, and unfortunately, to the scientific and medical institutions in both places—such as Hong Kong University, with its excellent medical school, and the Guangzhou Institute of Respiratory Diseases. Lack of basic communication, let alone resistance to collaborative work and sharing of clinical samples, caused problems and delays in responding to SARS. The problems were eventually solved but the delays were consequential. When the infection first crossed the border, from Guangdong to Hong Kong, very little information crossed with it.

Guangdong is drained by the Zhu (Pearl) River, and the whole coastal area encompassing Hong Kong, Macau, Guangzhou, and a new border metropolis called Shenzhen, as well as Foshan, Zhongshan, and other surrounding cities, is known in English as the Pearl River Delta. On November 16, 2002, a forty-six-year-old man in Foshan came down with fever and respiratory distress. He was the first case of this new thing, so far as epidemiological sleuthing can determine. No samples of his blood or mucus were later available for laboratory screening, but the fact that he triggered a chain of other cases (his wife, an aunt who visited him in the hospital, the aunt’s husband and daughter) strongly suggests that SARS was what he had. His name too goes unmentioned, and he has been
described simply as
a “local government official.” The only salient aspect of his profile, in retrospect, is that he had helped prepare some meals, of which the ingredients included chicken, domestic cat, and snake. Snake on the menu wasn’t unusual in Guangdong. It’s a province of ravenous, unsqueamish carnivores, where the list of animals considered delectable could be mistaken for the inventory of a pet store or a zoo.

Three weeks later, in early December, a restaurant chef in Shenzhen fell ill with similar symptoms. This fellow worked as a stir-fry cook, and though his tasks didn’t include killing or gutting wild animals, he would have handled their chopped and diced pieces. Feeling sick in Shenzhen, he commuted home to another city, Heyuan, and sought medical treatment there at the Heyuan City People’s Hospital, where he infected at least six health-care workers before being transferred to a hospital in Guangzhou, about 130 miles to the southwest. One young doctor who rode to Guangzhou in the ambulance with him also became infected.

Not long afterward, during late December and January, other such illnesses started occurring in Zhongshan, sixty miles south of Guangzhou and just west across the Pearl River Delta from Hong Kong. Within the next several weeks, twenty-eight cases were recognized there. Symptoms included headache, high fever, chills, body aches, severe and persistent coughing, coughing up bloody phlegm, and progressive destruction of the lungs, which tended to stiffen and fill with fluid, causing oxygen deprivation that in some cases led to organ failure and death. Thirteen of the Zhongshan patients were health-care workers and at least one was another chef, whose bill of fare included snakes, foxes, civets (smallish mammals, distantly related to mongooses), and rats.

Authorities at Guangdong’s provincial health bureau noticed the Zhongshan cluster and sent teams of “experts” to help with treatment and prevention, but nobody was really an expert, not yet, on this mystifying, unidentified disease. One of those teams prepared an advisory document on the new ailment,
labeling it “atypical pneumonia”
(
feidian
in Cantonese). That was the phrase, a common though vague formulation, used weeks later by WHO in its global alert. An atypical pneumonia can be any sort of lung infection not attributable to one of the familiar agents, such as the bacterium
Streptococcus pneumoniae
. Applying that familiar label tended to minimize, not accentuate, the uniqueness and potential severity of what was occurring in Zhongshan. This “pneumonia” was not just atypical; it was anomalous, fierce, and scary.

The advisory document, which went to health offices and hospitals throughout the province (but was otherwise kept secret), also supplied a list of telltale symptoms and recommended measures for controlling against wider spread. Those recommendations were too little and too late. At the end of the month, a seafood wholesaler who had recently visited Zhongshan checked into a Guangzhou hospital and triggered the chain of infections that would circle the world.

This seafood merchant was a man named Zhou Zuofeng. He holds the distinction of being the first “superspreader” of the SARS epidemic. A superspreader is a patient who, for one reason or another, directly infects far more people than does the typical infected patient. While
R
0
(that important variable introduced to disease mathematics by George MacDonald) represents the average number of secondary infections caused by each primary infection at the start of an outbreak, a superspreader is someone who dramatically exceeds the average. The presence of a superspreader in the mix, therefore, is a crucial factor in practical terms that might be overlooked by the usual math. “
Population estimates of
R
0
can obscure
considerable individual variation in infectiousness,” according to J. O. Lloyd-Smith and several colleagues, writing in the journal
Nature
, “as highlighted during the global emergence of severe acute respiratory syndrome (SARS) by numerous ‘superspreading events’ in which certain individuals infected unusually large numbers of secondary cases.” Typhoid Mary was a legendary superspreader. The significance of the concept, Lloyd-Smith and his coauthors noted, is that if superspreaders exist and can be identified during a disease outbreak, then control measures should be targeted at isolating those individuals, rather than applied more broadly and diffusely across an entire population. Conversely, if you quarantine forty-nine infectious patients but miss one, and that one is a superspreader, your control efforts have failed and you face an epidemic. But this useful advice was offered from hindsight, in 2005, too late for application to the fishmonger Zhou Zuofeng in early 2003.

No one seems to know where Mr. Zhou picked up his infection, though presumably it wasn’t from seafood. Fish and marine crustaceans have never been implicated among the possible reservoirs for the pathogen causing SARS. Zhou ran a shop in a major fish market, and possibly his sphere of activities intersected with other live markets, including those that offered domestic and wild birds and mammals. Whatever its source, the infection took hold, went to his lungs, caused coughing and fever, and drove him to seek help at a Guangzhou hospital on January 30, 2003. He remained at that hospital only two days, during which he infected at least thirty health-care workers. His condition worsening, he was transferred to a second hospital, a place that specialized in handling cases of atypical pneumonia. Two more doctors, two nurses, and another ambulance driver were infected during his transfer, as Zhou gasped for breath, vomited, and spattered phlegm around the ambulance. At the second hospital he was intubated to save him from suffocation. That is, a flexible tube was inserted deep into his mouth, past his glottis, and down his windpipe into his lungs, to help with breathing. This event represents another important clue toward explaining how SARS spread so effectively through hospitals around the world.

Intubation is a simple procedure, at least in theory, but it can be difficult to execute amid the gag reflexes, sputters, and expectorations of the patient. The task was especially hard with Zhou, a portly man, sedated and feverish, and though his disease hadn’t yet been identified, the attending doctors and nurses seem to have had some sense of the danger to which they were being exposed. They knew by then that this atypical pneumonia, this whatever, was more transmissible and more lethal than pneumonias of the common sort. “
Each time they began to insert the tube
,” according to an account by Thomas Abraham, a veteran foreign correspondent based in Hong Kong, there was “an eruption” of bloody mucus. Abraham continues: