How clean is too clean?
Another possibility for broad resistance to several infections is a more aggressive immune system. Our immune system must be carefully balanced. If the immune system is too cautious in reacting, infections may win; if it is too trigger happy, we can damage our own tissues. Clearly, the optimal setting depends on the likelihood of encountering dangerous infectious diseases. Thus, urban plagues might have favored an overenthusiastic immune system. Although this was beneficial at the time, its legacy could be an increased level of autoimmune problems. These range from allergies and asthma to arthritis and multiple sclerosis. Autoimmune problems are most prevalent in industrial nations where overcrowding was worst; they are much rarer in Third World populations.
Another viewpoint on the higher frequency of autoimmune problems in advanced nations is the level of hygiene. Eating dirt is not generally recommended in manuals on the care of babies and small children, but mounting evidence suggests it might not be such a bad idea. When children are fed sterilized food, given too many antibiotics, and vaccinated instead of gaining immunity from natural infections, the immune system develops in a lopsided manner. This correlates with the increasing frequency of immune system disorders in industrialized nations. Children who develop immunity by natural exposure rarely suffer from these afflictions. Moreover, the culprits favored by tradition—pollution, dust mites, toxic chemicals, and colds—have now largely been exonerated. Although it would be silly to expose infants to sources of dangerous infection, some sort of exposure to “clean” dirt might not be a bad thing.
Where are we now?
For better or worse, we are living under artificial conditions far different from those of our hunter-gatherer ancestors. We have also been genetically modified in ways that we are just beginning to glimpse. So, what of the future? We consider our future conflict with infection in the final chapter.
11. Emerging diseases and the future
Pandemics and demographic collapse
Today our planet holds approximately 6 billion humans and 5 × 1030 (5 million trillion trillion) bacteria. We are outnumbered by nearly 1021 (1 sextillion) to 1. At the moment, we are catching up. But will this trend last? The human population does not climb smoothly. Periods of growth are followed by population crashes. When will the next population implosion happen? How?
The earliest major population collapse for which we have reliable records occurred in the Roman Empire as a combined result of the unidentified pestilences of 165 A.D. and 251 A.D. The plague of Justinian, which began in 542, with secondary epidemics until 750, was another period of major population decline in Europe and the Middle East. Both population and prosperity increased from the mid-700s to the mid-1300s. In England, the population expanded roughly threefold from 1000 A.D. to 1348, to reach roughly four million. It then collapsed to less than half of this due to the Black Death and regained its 1348 level only in the early 1600s, some 250 years later. Europe, North Africa, the Middle East, and China suffered similar catastrophic die-offs during the same period. In the New World, these multiple die-offs combined into one spectacular population crash when the diseases of the Old World were imported into the Americas, beginning in 1492.
Since around 1600, despite the ravages of tuberculosis and other infections, the population of most parts of the world has steadily increased. Today the threat from infectious disease is growing. The industrial nations are shielded by wealth and technology from the infections that assault the poor nations. Yet despite the poverty, crowding, malnutrition, and lack of hygiene, the populations of the Third World nations continue to rise. Whether we are likely to succumb to some new plague in the near future and suffer another major population collapse is hotly debated.
The various types of emerging diseases
The widespread publicity given to AIDS, mad cow disease, and Ebolavirus has set a trend. Virtually every infection now clamors to be accredited as an emerging disease. Diphtheria is increasing in the former Soviet Union, and syphilis is increasing among American homosexuals. Are these emerging diseases? Not really. Localized lapses in social order or hygiene provide familiar diseases with the opportunity to briefly expand. However, the idea of emerging disease implies something truly novel that threatens a world grown smug in the belief that infectious disease has been conquered. Changes in one or more of four major areas can qualify a disease as novel.
Genuine emergence of a novel infection is rare. Many so-called emerging diseases have survived unnoticed for many years and only recently come to our attention as a result of changing conditions. Others are truly novel and have emerged by a combination of genetic changes and movements between host species, the most clear-cut case being AIDS.
Changes in knowledge
Many “novel” diseases have clearly been around for a while but were only identified recently. Previously unnoticed diseases include Legionnaire’s disease and Lyme disease. A hundred years ago, deaths from Legionnaire’s disease would have been attributed to tuberculosis. The decline in tuberculosis means that rare diseases affecting the lungs are more likely to be noticed. Similarly, the decline in yellow fever, due to vaccination, has revealed many less common tropical fevers that were once lumped together with yellow fever. Conditions such as diarrhea or hepatitis that have been known for a long time are caused by multiple infectious agents. Many of these have only recently been individually identified, including hepatitis viruses C to G.
Other diseases went unnoticed because they occurred only in out-of-the-way places or among low-status people. Frontiersmen and American Indians have undoubtedly suffered from sporadic cases of Lyme disease for centuries, but the disease was investigated only when it began to affect leisured landowners.
Changes in the agent of disease
Totally novel diseases such as AIDS and mad cow disease appear from time to time. These infectious agents are of recent origin, and there has never been a recorded outbreak before our own time. Mad cow disease, though bizarrely unique, causes few deaths. Its main effects have been economic.
As agents of a catastrophic die off, these two diseases share the same drawback: ineffective transmission. If AIDS were spread by insects or mad cow disease wafted through the air like measles, we would be in real trouble. Perhaps most diseases with efficient distribution mechanisms are already in circulation. Diseases still lurking in the shadows are probably obscure for a good reason—they can’t effectively transmit themselves to humans. Although novelty dominates the headlines, I believe that greater real danger comes from known diseases that transmit themselves efficiently. If measles or flu changed to become highly virulent, we might face a real possibility of a major die-off.
Old diseases can evolve to protect themselves against human counterattack. They might gain resistance to antibiotics or change their surface components to outwit the immune system. Influenza virus changes its surface properties for each new epidemic, and AIDS virus mutates so rapidly that multiple variants appear within a single patient.
Old diseases can evolve new means of attack. They might acquire novel virulence factors (such as with E. coli O157) or reshuffle their genes, creating virulent variants from time to time, as occurs with flu. Other diseases venture into new territory by changing the tissue invaded. A good example is the evolution of the spirochete that causes the skin disease yaws into syphilis, which specifically affects the genital regions.
Changes in the human population
Humans with defective immune systems provide easy opportunities for infection. The AIDS epidemic has created by far the largest number of immune-compromised victims. This, in turn, has allowed the spread of many novel opportunistic diseases. However, the use of drugs whose side effects harm the immune system and the increasing numbers of older people also contribute. Malnutrition also makes humans more susceptible to many infections. Denser human populations allow more virulent variants of a disease to spread, as discussed in Chapter 3, “Transmission, Overcrowding, and Virulence.” This is espec
ially true of the growing cities of the Third World, where poor hygiene exacerbates the effect.
Genetic alteration of humans might protect against one problem but increase vulnerability to others. A single copy of the cystic fibrosis mutation protects against diseases such as typhoid and cholera, but if both copies of the gene are defective, the lungs become more susceptible to infection by a variety of bacteria.
Multiple genetic changes have occurred within historical times that make most Europeans relatively resistant to smallpox, measles, tuberculosis, and many other diseases. Because we do not know the identity of most of these mutations, we remain in the dark about any possible side effects.
Changes in contact between victims and germs
A variety of factors can greatly change the probability of an infectious microbe finding suitable victims. Natural disasters such as earthquakes, floods, hurricanes, and storms provide temporary opportunities for disease to spread. Generally, when the disaster is past, associated infections fade away, too. Changes in climate have more permanent long-term effects. In particular, higher temperatures allow insects to spread into new regions, carrying with them diseases such as malaria or yellow fever.
Old diseases can make a comeback due to a breakdown in public health caused by wars, revolutions, and political upheavals. Disruption of vaccination programs after the collapse of the Soviet Union resulted in an upsurge of diphtheria.
Opening up new land for settlement or clearing forest for agriculture brings people into contact with previously unknown diseases, such as Ebolavirus. More serious in practice are irrigation projects that create new bodies of standing water. These permit the spread of mosquitoes carrying malaria, yellow fever, and dengue fever. Deforestation also helps the spread of disease-carrying insects. Even technological advances can backfire. More efficient food technology relies on processing larger volumes. This allows localized bacterial contamination to spread more widely, resulting in the massive meat recalls of recent years. Air-conditioning opened new opportunities for Legionnaire’s disease.
The supposed re-emergence of tuberculosis
Tuberculosis is not an emerging disease. Indeed, it scarcely merits classification as re-emerging. We include it here because of the publicity it receives. Tuberculosis spread through the cities of Europe during the industrial revolution. By the mid-twentieth century, when the first effective antibiotics appeared, the tuberculosis epidemic was already largely burned out in Europe. A colossal death toll over the past few hundred years had killed off most people who were sensitive. Antibiotic therapy merely finished off the tail end of the epidemic in the industrial nations. Today only an estimated 10% of the white population is susceptible to tuberculosis.
Thus, tuberculosis is not re-emerging; the epidemic that started in seventeenth-century Europe did not end; it merely vanished from the advanced nations. Today it is moving inexorably across the world and is still expanding among populations who have not been previously exposed. Today tuberculosis accounts for around three million deaths annually, most in the Third World. Data from Chicago in the 1920s showed that tuberculosis was six times worse among blacks than whites. Remember that some 75% of American whites are descendents of Europeans who entered the United States between the American Civil War and World War I. The whites thus came from a pre-exposed population, whereas the blacks did not. After World War II, tuberculosis found fresh victims in the crowded slums of expanding Third World cities. Susceptibility is greatly increased by the protein-poor diets often found in poor countries where little meat is eaten.
Diseases are constantly emerging
Quite frequently, die-offs occur among wild animals. Most of these are not noticed. Most that are noticed, usually by local farmers or hunters, are not recorded, and most of those recorded are never explained. For example, in 1994, bald eagles in Arkansas came down with a mystery disease and many died. Some die-offs are probably the result of new diseases. Perhaps an existing infection mutates to a more lethal form, or perhaps a disease crosses over from another animal. This new disease is so virulent that it wipes out most of the population and then, with no more victims to infect, goes extinct itself. This undoubtedly happened many times to early human settlements in the days before the human population was dense enough to keep new diseases in circulation. For every disease that emerges successfully, many must make abortive attempts. Even if a disease ultimately emerges into new prominence or jumps into a new host, it might make many tries before it succeeds. Let’s look at some recent candidates for fame and glory.
Lassa fever, Hantavirus, and Ebolavirus are three of the emerging viruses to hit the headlines recently. All three are harbored by small animals with large populations. Lassa and Hanta are carried by rodents, and Ebola most likely by bats. As with the Asian marmots that harbor the Black Death, the natural hosts for Lassa, Hanta, and Ebola suffer relatively mild disease. Man is very susceptible, and the death rates during the reported outbreaks are in the same range as for bubonic plague.
These three, together with Junin, Machupo, Marburg, O’nyong Nyong, and several other novel viruses, were mostly identified more than 25 years ago. However, it wasn’t so much the viruses that emerged—it was the emergence of cell culture techniques for viruses in the 1950s that allowed the identification of exotic viruses in remote parts of the world. Before this, viruses had to be grown in fertilized chicken eggs, an extremely laborious and clumsy procedure that was not always successful. Few novel viruses of major significance have appeared in the last 25 years, although there have been new outbreaks of those listed earlier in new places (for example, Hantavirus in the United States in 1993). Most recently, Lujo virus, a relative of Lassa fever, emerged in Southern Africa in late 2008.
Despite the hype, these novel viruses have had little global impact. About 50 million people die each year on Earth. Of these, about 16 million succumb to infections, with AIDS, malaria, and TB accounting for roughly 3 million each. Deaths per year from the newly emerging viruses are numbered in the hundreds. For example, between its emergence in 1976 and the outbreak in 1996, there were approximately 1,000 official cases of Ebolavirus infection, with an overall death rate of 80%. Undoubtedly several thousand more victims died unreported in isolated villages; nevertheless, in global terms, these numbers are negligible.
How dangerous are novel viruses?
Should we be alarmed about these novel viruses? Worried, yes—panicked, no. Consider Lassa fever, discovered in 1969 in Lassa, Nigeria. Like Ebolavirus, Lassa fever virus has undoubtedly been around for much longer. Sporadic outbreaks in isolated areas must have occurred from time to time without drawing attention. Earlier outbreaks were probably misdiagnosed as severe cases of malaria or yellow fever. In its natural hosts, small rodents, Lassa fever often causes mild long-term infections. The virus emerges in the urine and can be breathed in by humans under dry, dusty conditions. In humans, Lassa fever is virulent and short-lived—as is the patient, in the majority of cases. Human survivors also excrete virus particles in their urine for up to a month after infection.
The story is similar for Ebolavirus, named after the Ebola River in Zaire. Bats can be infected with Ebolavirus, whereas many other animals, including rodents, cannot. As expected for the natural host, bats allow the virus to replicate but do not fall severely ill. Outbreaks of Ebolavirus in the Sudan were traced to a cotton factory whose rafters were home to thousands of bats. An outbreak in Uganda was traced to the bat-infested Kitum Cave. Despite this, no bats trapped near these human outbreaks actually carried Ebolavirus. So although bats are the chief suspects, the case remains unproven.
However, despite being highly lethal, Ebolavirus is not especially infective until the final stages, when the blood is full of virus and the patient bleeds from all the bodily orifices. Obviously, at this stage, the patient is immobile. Lassa fever and Hantavirus are much the same. Exposure to blood or tissue samples has infected health workers, but casual contact rarely transfers the virus. During the 1995 Ebolavirus o
utbreak in Zaire, of 28 relatives who stayed in the hospital to help nurse the sick (often sharing the same room or even the same beds), 17 got Ebola. Of 78 who just visited, none fell ill. Similarly, in 1990, an American returning to Chicago from Nigeria was hospitalized and died of Lassa fever. No one else was infected, although no special precautions were taken because the infection was identified only after he died.
Lassa, Ebola, and Hantavirus are not as evil as originally believed. Mild versions of all three viruses are surprisingly widespread. Investigations during the 1980s in the rain forests of Cameroon found that 15% of the pygmies had antibodies to Ebolavirus in their blood, implying that they had been infected. No massive death toll was noted. Similarly, screening of large numbers of Africans from Nigeria and nearby nations found many who had signs of having been infected with Lassa fever but remembered only mild illnesses.
Another factor contributing to the panic of the early Lassa and Ebola outbreaks was their artificial spread by hospitals. Thus, many victims of the 1976 Ebola outbreak in Zaire were infected while in the hospital. Viruses from patients infected with Ebola were transferred to others by reusing hypodermic needles that were improperly sterilized. Less than 10% of those who got Ebola injected directly into their bloodstream survived. Of those who caught Ebola from another person, between 40% and 50% survived. Similar scenarios are seen with Lassa fever. Thus, these diseases are less dangerous when spread by natural means.
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