Influenza, HIV, Ebola, and now Zika. Hardly a year goes by without some new viral epidemic making the news and spreading anxiety. What is going on? In order to begin to understand this, it may be helpful to employ a historical perspective.
One of the few lectures that I can claim to have had a lifelong influence on me was delivered by the professor of medicine in Liverpool, Lord Cohen, when I was a clinical student there in 1960. He pointed out the importance of the environment in which we live to health and disease, and drew attention to the work of a French/American scientist, René Dubos, who had studied the inter-relations of soil organisms while searching for a treatment for tuberculosis. He understood that the bacteria and other microbes in the soil were in competition with each other and, in defence of their patch, could produce defensive or aggressive chemicals to ward off competitors.
This led him and his colleagues to discover some of the first antibiotics. From an instinctive belief that medicine is a system for curing ill people, I started to think of it as part of an evolutionary mechanism whereby we humans were enhancing our chances of survival and reproduction. The world, our immediate environment, and even our own bodies are inhabited by an enormous variety of organisms, some of which are potentially harmful or even fatal, some neutral, and some beneficial or essential. We are but a part of our environment and, like all other animals and micro-organisms, have to find our place and hang on to it. Competition is all around us.
Before the invention of the microscope some philosophers had supposed that minute organisms might exist but, after Leeuwenhoek first demonstrated them with his microscope in the 1670s, there was a slow appreciation that such little creatures (he called them animalcules) might be responsible for putrefaction and even disease by contagion. However, it was not until the 19th century that micro-organisms were first demonstrated to cause disease, first in the 1830s when an estate manager showed that silkworms dying of a disease called muscarine were found to harbour a fungus that could transfer the disease to other silkworms, followed by the identification of fungi in the skin of people with ringworm.
In the 1850s Pasteur started his experiments on fermentation and sterilisation, leading to investigation of another silkworm disease, then chicken diseases and how to immunise against them, and then the human and cattle disease, anthrax, the first to which he was able to produce a vaccine. Finally, in the 1880s, he produced a vaccine against rabies which famously he was able to use to prevent the disease in two boys who had been bitten by rabid dogs. In this case, Pasteur had been unable to see the organism through the microscope and used an extract of infected brain tissue for his vaccine, a technique analogous to the earlier use of cowpox matter to immunise against smallpox. In both cases the organism was too small to be seen under the light microscope; it was a virus, and did not become visible until the invention of the electron microscope in the 1930s.
The larger organisms, bacteria, had been able to be grown and studied in the laboratory from the time of Pasteur, but viruses are unable to reproduce on their own, needing a plant or animal cell to parasitise. The word virus is derived from the Latin for poison, and their presence in disease was inferred from experiments that showed them to pass through bacterial filters and still cause disease on inoculation into plants or animals. Over the course of the 20th century it became apparent that these tiny particles of protein and genetic material were the most abundant organisms on earth, present in pretty well every living organism yet not able to live and reproduce independently, and sometimes could cause disease. My own pet virus, probably acquired as a schoolboy playing in the front row of a rugby scrum, lives in the nucleus of a nerve at the base of my brain and still reminds me of its presence by producing a periodic cold sore on my face. No doubt its offspring cause similar symptoms in some of those whose faces have come into contact with mine over the years. That is how infectious organisms work to ensure their survival.
Micro-organisms have evolved an extraordinary variety of mechanisms in order to survive. For viruses and bacteria, the main one is genetic mutation, and since they reproduce rapidly this is very effective in overcoming any defences a new host organism may direct at them. The obvious example is the development of resistance to antibiotics or antiviral drugs. Another is development of a protective capsule against immune defences. Mutation and the ability of some viruses to exchange genetic material are the reasons scientists have such problems in predicting and preventing influenza pandemics, and why such pandemics occur.
If you think about it, sometimes we can provide special help to the germs ourselves. Plagues and epidemics have punctuated and influenced man’s history on the planet. The Black Death, bubonic plague, syphilis, tuberculosis, cholera and typhoid all have appeared in epidemics related to overcrowding, warfare, and migration of people. Poor hygiene and waste disposal remain a problem, increasing risk of epidemics in many parts of the world, especially now among the mass of displaced populations.
From an evolutionary point of view, successful organisms cause their host to pass them on, usually by making the host ill; the cold virus makes us sneeze, the tuberculosis bacterium makes us cough, the syphilis bacterium causes sores and spreads by sexual contact, and so on. These survival tricks also give us the opportunity to prevent the disease, by knowing how spread occurs, and that is the origin of public health. So when a new plague appears a great effort is made to understand its cause and methods of transmission. This has been dramatically illustrated by the HIV epidemic; a primarily sexually transmitted infection, whose control is dependent on public health interventions while scientists work to find appropriate anti-viral drug regimens and ultimately a vaccine.
Only one viral disease, smallpox, has so far been eradicated, as a result of an effective cheap vaccine used in a world-wide public health strategy of vaccination. It is hoped that poliomyelitis may go the same way, although conflicts and displacement of populations in the few remaining endemic areas are hindering its final eradication. Attempts to use drug therapy to eradicate tuberculosis and public health measures to eradicate malaria have failed from human intransigence and lack of effective vaccines – the world’s greatest killers survive.
The greatest weapon microbes have is mutation, while ours is scientific ingenuity. As each new plague arrives we have to understand it and develop a strategy to protect ourselves. Ebola remains frightening; probably spread from bush animals in Africa to humans, extraordinarily infective in its new hosts, particularly after they have died, and able to spread rapidly by air travel world-wide. Desperate measures were required to contain it and there were many deaths amongst heroic individuals caring for sufferers. Work is continuing to find an effective vaccine and anti-viral drugs, and much depends on the success of the former endeavour and a strategy to vaccinate those at risk.
Increasingly, laboratory science in the rich world and basic, well-coordinated public health in the poor world need to cooperate to control these new infectious diseases.
The latest epidemic poses a problem long foreseen in relation to climate change. Mosquitoes are one of the earth’s most successful organisms, thriving in all climates from the arctic to the tropics. Like us, they catch diseases but unlike us they require blood as a food. Like humans, mosquitoes are adapted to their different habitats and migrate when climate or ecological conditions change. In different parts of the world their feast of blood introduces different microbes into them and those microbes have evolved to use the mosquito as their own aeroplane to another host.
Over time, many parasites have evolved the requirement for one stage of their life cycle to be held in one creature and the next in another. The malaria organism, a protozoon, moves from mosquito gut to its salivary glands, to the blood then liver of the person or animal it infects, then back to the blood to await its next transfer, changing its appearance at each move. Malaria, once common in southern Europe, was removed by public health measures to reduce the standing water that the mosquito needs for its own larval stages.
Different mosquito species have different preferences for blood and carry different diseases. One species, Aedes aegypti, is found throughout the tropics and may carry a number of different parasites including the Dengue and Chikungunya viruses that cause febrile illnesses, often with unpleasant complications, and now Zika virus.
Those of us who live in the comfortable West may easily dismiss these diseases as just part of the reason the poor world is poor, the lot of those who have to bear the greatest burden of misfortune and poverty. Until, that is, they are visited on us. It is then that we notice those unpleasant complications. Zika was known as a cause of a mild febrile illness in Africa in the 1950s then south-east Asia in the 1970s until it spread to South and Central America, the Caribbean and towards the southern USA in 2015. It was then noticed that where epidemics of the infection were occurring, there were also unusual numbers of children born with small brains and also unusual numbers of people who had developed a form of paralysis called Guillane-Barré syndrome.
This is what is called an ecological association, not proving that one causes the other but suggestive that it might. A mosquito bite in these regions of the world during pregnancy could condemn the unborn child to a lifetime of severe incapacity, or could result in you or me being paralysed. Similar associations were reported in French Polynesia; this was sufficient for WHO to declare an emergency and to issue instruction on precautions to avoid infection.
Aedes aegypti doesn’t live in the UK, fortunately, so we are not at risk unless we travel to zones where it does. For now our mosquitoes are just a nuisance, but the climate is warming and air travel is commonplace so it is not possible to predict what may happen in the future. But if you are travelling to any of the 38 (and counting) countries where Zika is being reported or other countries in the tropics or sub tropics where Zika is sure to emerge, and especially if you may be pregnant, read more at this link: www.fitfortravel.nhs.uk, for up to date advice.