Bug and Superbug

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19th century novels are full of ineffective physicians and apothecaries holding court at the bedside of fictional heroes and heroines, holding their hands, feeling pulses, prescribing tonics and making pronouncements as they survive or perish. The diseases are almost always infections.

“Consumption” is a common choice (Wikipedia has a whole page on TB in popular culture here ). Smallpox (e.g. Bleak House), typhoid (e.g. Study in Scarlet), measles (e.g. Middlemarch) and plenty of other unnamed maladies also appear. Sir Arthur Conan Doyle, author of the Sherlock Holmes stories, who worked as a GP, wrote a series of medical short stories about syphilis, which at the time was untreatable and fatal.

Infectious diseases make good novel-fodder, since the pattern of illness tends to be worsening, crisis with suspense, then recovery or death. You have to look a lot harder to find representations of today’s common chronic diseases. The “popularity” of infectious diseases in 19th century literature does not just represent the whim of authors – in the UK, serious infectious diseases were far more common then than now.

The first vaccine, using cowpox to protect against smallpox, was invented in the 18th century, but the industrialisation of vaccination occurred during the mid-20th century, with vaccines to measles, mumps, rubella, diphtheria and polio becoming available. Meanwhile, the first antibiotics had come into use in the 1930s, penicillin reached clinical use in the 1940s, and in the 1950s there was a glut of new antibiotics appearing. By the 1960s there was a growing feeling that the bugs were being beaten.

50 years later, although huge steps forward have been made in many areas of medicine, it would be hard to find a scientist or doctor who believes that the bugs are beaten.

Here are five reasons why the mid-century optimism was misplaced:

  1. Medicine wasn’t doing all the heavy lifting

The century-long decline in infectious diseases had many causes, and science and medicine was only partly responsible. Improved nutrition led to more resilience against disease, sanitation prevented contamination of drinking water with infectious waste, improved living conditions reduced transmission of infections. Wide exposure to bugs probably increased our resistance by a process of natural selection (the most susceptible to diseases died, and the most resilient to infection survived). McKeown’s famous analysis of TB death rates over more than a century showed a decline that predates vaccination, antibiotics, and even the identification of the causative bacteria (see graph below).

TB graph

But there’s only so far that living standards, sanitation etc can improve, and infections will continue to be passed around unless we stop breathing on, touching and having sex with each other. And our “improved” nutrition has caused a spike in different kinds of disease – hypertension, diabetes, obesity.

  1. New diseases have appeared on the scene

The most obvious, and the most important new kid on the block is HIV/AIDS. This infectious disease took everyone by surprise in the 1980s, and it took years of desperate research before treatments became available. Despite huge investments, a vaccine remains elusive. And because HIV damages the immune system, it allows other infections a back door to infect more people.

Another very topical disease that wasn’t known about in the 1960s is Ebola. It was identified in the 1970s (having been brought back from Africa to Europe in a thermos flask on a passenger plane) and sporadic outbreaks occurred until the most recent one in, beginning in 2014, which has killed around 10,000 people so far.

Zika virus has also hit the headlines recently. It was discovered decades ago, but festered in obscurity until a recent outbreak in South America was linked with birth defects. There is no treatment and no vaccine available.

  1. Bugs have become Superbugs

Tuberculosis has been treatable with antibiotics since 1947. Mckeown’s graph, from 1975, predicted that TB deaths would cease by 1990.

But TB has changed. Today’s bacteria and their ancestors have been exposed to so many antibiotics, that they have evolved to be more resistant. Some extremely resistant forms of TB are now untreatable with any antibiotics, bringing us back to medicine of the 1940s. Some forms of gonorrhoea are also untreatable with any antibiotics. Common bacteria like Staph Aureus, which live on our skin and usually doesn’t cause us any problems, have built up resistance to antibiotics, turning them into potential killers that are very hard to treat.

And the bugs aren’t just resistant to a single antibiotic – often drug resistance comes as a comprehensive package, and the multi-resistant superbugs are a significant challenge to modern medicine.

  1. Medical progress has faltered

There is an interesting figure (copied here) of the dates of discovery of the various types of antibiotics. The 20 year period following the second world war saw the discovery of 11 classes of antibiotics. But the 20 year period from 1990 to 2010 saw none.

ABX graph

The bacteria are evolving, and we are not keeping up with them.

  1. Success breeds failure

In many countries antibiotics are available to buy without a prescription. Even in countries where you need a prescription, doctors aren’t good at saying no to requests, even when they don’t think antibiotics are necessary. Farmers routinely give antibiotics to prevent infections in their animals, helping them grow bigger in a shorter time. Often, the drugs are a substitute for good animal welfare, which is a more expensive and humane way of preventing infections.

The more we use these drugs, the more chances we give the bugs to evolve to beat them. And because bugs reproduce so quickly, they can evolve very fast – much faster than we can.

Vaccines don’t seem to become less effective with repeated use. But now that the diseases they prevent have become rarer (due to the success of the vaccines and other factors) people have started to question whether they are needed. I wrote a blog post about the measles vaccine here. Since I wrote that post, America had its first measles death in over a decade, unquestionably linked to low vaccine uptake in that region

So what needs to be done? Here are five things that could help…

  1. Prevention is better than cure

When you have a vaccination for a particular disease, you are (hopefully) preventing yourself from catching the disease. But for infectious diseases, the effect can be greater than that. If you did catch the illness, you would probably pass it on to someone else. Possibly many people. In a population all treated with an effective vaccine, spread of a disease from person to person is prevented. This is how smallpox was eradicated. While treatment encourages treatment resistance, prevention does not.

Prevention doesn’t have to mean vaccination – mosquito nets are the most cost-effective preventative measure for malaria. And good sanitation and hygiene, which many of us now take for granted, can still be life-savers. The ebola outbreak in Africa was controlled mainly by aggressive isolation tactics to prevent spread of the infection. We need to use the same aggressive isolation techniques to stop the spread of the superbugs.

  1. Use the antibiotics that we have sensibly

Antibiotics must be used. But we need to remember that each time we hand out a prescription for antibiotics, we’re providing a better environment for bacteria to evolve drug-resistance. The problem is made worse when people don’t use the drugs correctly. For instance, TB requires treatment for 6 months to be cleared. Taking only some of the course helps the bacteria grow resistant to those drugs.

As for the routine use of antibiotics in farms, that is crazy. Farmers use more antibiotics per year on their cattle, pigs and chickens than people do. And the more antibiotics we pump out there, the more opportunities the bugs have to evolve resistance. While you probably can’t go out and buy some penicillin if you feel like it, a pig-farmer can buy as much as he wants. There’s an article with more detail about this problem here

  1. Make new drugs and vaccines

There has been a plateau in development of new antibiotics, but the science of drug development has leapt forward during the last 20 years, with hundreds of new drugs arriving on the market. None of the revolutionary new drugs have been antibiotics. But there must be more to discover.

Vaccines are still appearing on the market. For instance, a vaccine for Meningitis B has just been developed, and is now part of the routine vaccination programme in the UK. An ebola vaccine was created in the space of months, during the worst period of the recent ebola outbreak, and seems to be very effective.

Vaccines for killer diseases like HIV and malaria are among the holy grails of medicine, and this quest is ongoing; there’s no end in sight. But we’ll never have vaccines for all the infections out there.

  1. Work together

Drug resistance is an international problem. Each day, millions of bugs and superbugs travel on trans-continental flights with their human hosts. This means that one region’s misuse of antibiotics has implications all over the world.

This is not a problem that can be solved without massive cooperation. No-one can solve it on their own. If only we were better at working together…

  1. Prepare for the worst

We’ve known about antibiotic resistance for decades. In fact, the very first antibiotics in clinical use (the sulphonamides) were introduced in 1937, and resistance was first described by 1939. George Orwell, the author of 1984 and Animal Farm, died of TB in 1950 despite treatment with antibiotics, and probably had an early resistant form. Untreatable TB is on the rise, and we must expect this problem to grow.

The pre-antibiotic era seems unimaginable to most people alive today. Conan Doyle’s fictional syphilitic, diagnosed just before his wedding, and told there is no cure, commits suicide. Thomas Mann’s mountain-top tuberculosis hospital tries unsuccessful treatment after unsuccessful treatment on its many dying patients. The role of doctors was limited to diagnosis, hand-holding, prescribing ineffective tonics and waiting to see if the crisis would pass. Antibiotics seemed like a miracle – magic bullets that only killed the bugs, but not their hosts.

Let’s hope we don’t find ourselves looking back on the golden age of antibiotics from a future hinterland of darkness.

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