Plagues: old and new

Stories of untreatable new diseases, from Aids to Ebola to Creutzfeldt-Jakob, fill the headlines. Might they foretell epidemics on the scale of the Black Death, and even the end of the human race? Or is modern medicine a match for such outbreaks? Christopher Wills, considers the evidence
May 19, 1996

Throughout our history, diseases have come and gone. Leprosy, which was widespread in Europe during the middle ages, inexplicably disappeared-though it remained a terrible scourge in much of the rest of the world. Between the end of the 15th century and the middle of the 16th century a mysterious disease called the sweating sickness broke out repeatedly in England and Wales. In 1529 it spread to the continent and then, somehow, burnt itself out. We have no idea what it was-the best guess is a viral encephalitis carried by mosquitoes. In the 17th century, bubonic plague, which had broken out repeatedly since the Black Death 300 years earlier, disappeared from Europe. All these diseases vanished without the aid of antibiotics or anything much in the way of public health measures.

These were large events, for which we have some documentation. There is no doubt that other diseases, some known and many unknown, have appeared and disappeared in the long history of the crowded and filthy cities of Europe. I emphasise how little we know about that distant time, because the situation has now changed completely. Today, the global village responds to every report of a disease, real or imagined, and prophecies of doom are everywhere.

In spite of what appears to be a recent upsurge of disease, in the last few years there has been only one plague in the classic sense of appearing from nowhere and spreading swiftly. This was the outbreak of cholera in South America in 1991, which affected half a million people and caused 5,000 deaths before it gradually faded away. But during this same period there have been many outbreaks of other diseases, so numerous as to constitute a kind of rash of mini-plagues.

In general, the world community has reacted swiftly to these dangers. In Rwanda, cholera and typhus were swiftly controlled in the refugee camps, in spite of the dreadful conditions there. The outbreaks of Ebola haemorrhagic fever in Zaire and elsewhere over the last decade, which have caused only a few hundred deaths, were contained not by medicine, but by keeping family members away from victims, and protecting health workers from victims' blood. This broke the cycle of infection.

Two apparent outbreaks of bubonic plague in India in 1994 were contained in part by airlifts of millions of tetracycline tablets into the affected regions. One of these outbreaks, which resulted in several dozen deaths in the crowded industrial city of Surat, appears to have been the highly contagious pneumonic form of the disease. But to put these outbreaks in perspective, and underline the ability of antibiotics and rapid communications in controlling such epidemics, it must be remembered that bubonic plague has until very recently been a huge cause of death in India. During the first decade and a half of this century-only a long human lifetime ago-there were horrific epidemics of plague in India's largest cities. Together, they killed an astonishing 12.5m people, one quarter as many deaths as during Europe's Black Death. Although poverty, illiteracy and squalor are still widespread, India has come a long way since those unimaginably dark days.

The reactions of authority have not always been so swift and successful. One of the most depressing of the recent stories of emerging and re-emerging diseases has been a frightening climb in the incidence of diphtheria in Russia. Since 1991, diphtheria has increased more than tenfold, and has been the cause of over 2,000 deaths. This eminently preventable childhood disease thrives in conditions of dirt, poverty and ignorance, and can break out when the percentage of immunised children drops below a critical level. Until the epidemic was well advanced, little had been done in Russia to control the disease. To make matters worse, nationalist periodicals spread rumours that immunisation was a plot hatched in the west. There are now belated attempts to immunise huge numbers of children and adults in Russia and the Ukraine. The World Health Organisation recommends a 95 per cent immunisation rate for children to ensure that diphtheria does not reappear. During the breakup of the Soviet Union the rate dropped to 68 per cent, low enough to help trigger the epidemic. Most adults, too, have either lost their immunity or never been immunised. The picture is often as bad in the west. In the US only 44 per cent of children have been fully immunised, and at least 60 per cent of adults do not have levels of antibodies sufficient to ward off the disease. It may only be a matter of time until diphtheria breaks out in poverty stricken regions of the US.

Mad Cow hysteria

At the moment, the epidemic which has caught everyone's attention is mad cow disease. It is unclear whether this neuro-degenerative disease, which has spread from sheep to cows, has also spread to humans as well. About a dozen unusual cases of Creutzfeldt-Jakob disease, unusual because they involve young people, have appeared during the last year in Britain. There is a real possibility that these cases may have resulted from eating infected beef. The mode of transmission of the disease is utterly different from anything we have encountered before, and the details have resisted the best efforts of scientists. There is, however, growing evidence that it is caused when brain cells accidentally absorb, perhaps from another animal, a collapsed and insoluble form of a protein very similar to one that is normally present in the brain. These alien protein molecules cause the normal protein molecules in the brain cell to collapse, and trigger an eventually lethal chain reaction. The collapsed proteins, known as prions, which are the agents of transmission, are not living, and are not destroyed by cooking temperatures. Press reports have suggested that as many as 50,000 people in Britain are in danger of contracting Creutzfeldt-Jakob disease from eating infected beef. This is patent nonsense. The disease is very difficult to transmit, even among animals, and all the evidence suggests that in humans it requires a rather unusual genetic predisposition-only rare forms of the protein, possessed by a few of us, are susceptible to collapse. But, whether mad cow disease has triggered a collapse of proteins or not, it has opened the eyes of those of us who had innocently supposed all this time that cows eat grass. Alas, not only do cows in the US continue to eat rendered sheep products (though a ban on this practice is now being debated), they are even compelled to eat each other. About 15 per cent of the cattle carcasses in the US are recycled as cattle feed. This is a sure recipe for the transmission of disease, since prions and diseased organisms can be easily transmitted among members of the same species.

We would surely never have begun to understand this disease if it were not for highly sophisticated scientific techniques, and of course it hardly poses a worldwide threat, in spite of panic-stricken press reports. One shudders to think how many such illnesses were transmitted through the rubbish that people ate in previous centuries, and yet our species managed to survive.

Hot zone viruses

But what of other diseases with greater potential to cause widespread harm? A number of recent books, most notably Richard Preston's The Hot Zone, claim that our invasion of previously untouched ecosystems will trigger lethal waves of emerging viruses. This will happen when we invade the habitat of monkeys or rodents which harbour these new diseases, and then, via modern transport, spread them very quickly through our species. But Ebola, the virus most often cited as an example, luckily turns out to be transmitted only with difficulty, so that Ebola infections quickly damp themselves out. Other viruses causing diseases with severe symptoms that have emerged recently in Africa and South America have also luckily proved to be difficult to transmit. All this could change in an instant, but it seems likely that any disease causing a rapid onset of serious symptoms could be controlled.

Far more dangerous are the "insidious" diseases which develop slowly, are transmitted sexually or in other ways difficult to monitor, and are sometimes difficult to diagnose. Some of these diseases are new and some are old. Of the new diseases, Aids poses the greatest threat. It is transmitted sexually, which makes prevention difficult, and the period between the time of infection and the onset of symptoms can vary from a few years to 15 years or longer. Like syphilis, it is a slow-motion plague transmitted through activities which are not susceptible to quarantine control. It kills, not through the direct action of the virus itself, but rather through a progressive disabling of the host's immune system, leaving the victim helpless against an onslaught of diseases as common as enteric bacterial infections.

AIDS, TB and useless antibiotics

The origins of the two Aids viruses is murky, but both HIV-1 and HIV-2 have close relatives in African monkeys and apes. A close relative of HIV-1, the more dangerous of the two to humans, has been found in chimpanzees, and there is a recent report of a chimpanzee infected with a human HIV-1 virus that has started to show the symptoms of Aids. But it is not yet known whether chimpanzees are the source of the human virus or whether both they and we have been infected from some other, as yet undiscovered, source. Whatever the right answer proves to be, the Aids viruses, like Ebola, do seem to have emerged from our invasion of undisturbed ecosystems.

Yet even the spread of Aids is now beginning to show some effects of educational campaigns and a consequent change in sexual habits. Awareness of the disease in east Africa has soared. In Uganda, the hardest-hit country, between 12 and 15 per cent of people in the cities have become infected. There are encouraging signs of a downturn in infection rates among young people and particularly among pregnant women. Although no cure or immunisation is on the horizon, changes in lifestyle are already having a measurable impact on the spread of the disease. These are signs of hope in a situation which, a few years ago, was thought by some leading epidemiologists to be so desperate that it would result in a dramatic decline in population in some east African countries.

Aids is a new disease, but tuberculosis is an old one. TB is the most dangerous single disease in the world today, responsible for between 2.5m and 3m deaths a year and certainly a contributing factor in many more. The organism causing the disease is far more widespread than the disease itself-one third of the people in many underdeveloped countries harbour the bacillus somewhere in their bodies. Most are asymptomatic, but in a small fraction of cases the bacillus breaks through the host's defences, causing a wide variety of life-threatening symptoms. TB can be cured, but only through long and expensive treatment with up to four different drugs, something which most people in the world cannot afford. To make matters worse, immunisation against TB is still stuck in the scientific dark ages. The exotic new diseases have recently garnered most of the research funds, but health scientists who want to make a real impact on global mortality should concentrate their attention on TB.

What conclusion can be drawn from this bewildering zoo of illnesses? My guess is that the apparent rash of new diseases is more a reflection of greater scientific knowledge and faster communications than of any real increase. Further, the pool of new diseases is not unlimited. The few remaining undisturbed ecosystems on the planet will undoubtedly continue to be a source of novel diseases, but their numbers will diminish as we invade the last wild places. And sudden outbreaks of diseases with obvious symptoms are now controllable-even the Black Death would have succumbed if the skies had opened and rained tetracycline tablets.

There is a danger that the current generation of antibiotics will become useless as the disease organisms develop resistance-strains of the malarial parasite have now arisen which are resistant to all the current antimalarial drugs. But we will soon know the make-up of all the genes in the malaria parasite, and this knowledge will open up many new ways to attack it. As I argue in my book Plagues, the more fundamental danger to the welfare of our species lies in the insidious diseases, some with dreadfully mundane symptoms. For example, diarrhoea caused by rotaviruses causes death and brain damage among poor children everywhere in the tropics, yet little is known about this disease outside specialist circles and a recently introduced vaccine is only partially effective.

We cannot, in our global society, afford such costs. We are the first species to have the potential to break free of the cycle of poverty and ignorance, and therein lies both hope and awesome responsibility. Until very recently, disease controlled our population levels. Thankfully it no longer "solves" our current problems of population increase and environmental degradation-our global society has moved beyond the ignorance of the middle ages. We have to find other ways to control population growth, and to reach a balance between our needs and the requirements of the rest of the living world.