nhsManagers.net | Briefing | 6 January 2017

Medicine for Managers

Dr Paul Lambden BSc MB BS BDS FDSRCSEng MRCS LRCP DRCOG MHSM FRSM

If you want a dramatic name for a disease, it is hard to imagine one better than The Black Death. The Plague was a devastating pandemic which swept across large parts of the world in the mid-fourteenth century and probably killed around 150 million people, thereby reducing the world population by around 30%. The population numbers did not recover to pre-plague levels for over 200 years. There have been smaller outbreaks in more recent centuries. The causative organism was Yersinia pestis. It is (for those who want to know) a Gram-negative cocco-bacillus of the Enterobacteriaceae family. It requires to be contained in blood to survive.

The organism has been found in a preserved flea about ten million years old

but the human strain is thought to have evolved about 10-20,000 years ago.

The French physician de Crobeil probably coined the phrase ‘Black death’ in the 12th century but contemporary writers during the period 1345-55 referred to the disease as ‘The Great Mortality’ or ‘The Great Plague’.

During the period of the mid-thirteen hundreds the disease spread across Asia, Western Asia, India and Uganda, to China and from there into Europe. Graphic accounts at the time wrote of areas of depopulation and land covered with dead bodies.

The first pandemic lasted from about 1348 to about 1355. This was followed by what is known as the second pandemic but which was serious recurrences of the illness lasting several years at a time between the 1360s and the 1660s. A third pandemic struck China in around the 1850s which spread through Asia and is said to have killed ten million people in India alone. More recently, there have been many smaller outbreaks and, in the early part of the twentieth century in Australia, the infection killed over a thousand people.

Medicine for Managers articles are not intended to be a source of medical advice. Their purpose is to familiarise the non-medical reader about current key medical disorders. Any medical or medicinal products mentioned by name are examples only and should not be regarded as an endorsement of their use.

The PlagueRecently I was driving and listening to Radio 4 about the possibility of a medically-induced apocalypse. The possible events that could overwhelm mankind were being considered and inevitably the discussion turned to the increasing ineffectiveness of antibiotics. Could we have another plague, promoted by absence of effective treatment? I didn’t know much

In England, the disease was probably endemic between the 1340s and and the late 1660s and may have killed over two million people during that time. It started in a south coast port brought in from overseas by ship and spread to Bristol as a bubonic form in about 1348 and it is said to have struck with ‘shocking force’. It spread from the south northwards mutating into the pneumonic form as it went. It reached Scotland in 1350. Many populations of 3-500 people were either completely decimated or wiped out. It was not surprising that disease of all types spread so easily when the towns were as described by Holt and Rosser (The English Medieval Town 1990) “Filth running in open ditches in the streets, fly-blown meat and stinking fish, contaminated and adulterated ale, polluted well water, unspeakable privies, epidemic disease – were experienced indiscriminately by all social classes”. When the disease reached London, it is thought to have killed 50% of the population. When it reached Scotland it was described by the population as “the foul death of England”.

Similar outbreaks were reported in major cities throughout Europe.

The disease is spread by a flea, which bites a

human and contaminates the wound with regurgitated blood. Bacteria injected spread through the lymphatic system to a lymph node where they proliferate to form a bubo which appears as a raised discrete red or even black nodule. The bacteria spread to the bloodstream causing a septicaemic plague which can then spread

generally round the body. The bacteria cause clotting within the blood vessels resulting in depletion of clotting factors and resulting in the inability of the blood to clot. Passing blood through all routes therefore occurred resulting in death, commonly within twenty-four hours of the first onset of symptoms.

The plague organisms also attacked the lungs causing a pneumonic form with coughing and sneezing causing lung destruction and coughing up blood (haemoptysis). Death occurred within one to four days and without effective treatment is virtually 100% fatal.

Other forms of the disease, resulting from the part of the body attacked by the infection, was a disease rather like tonsillitis and another which was a meningitic form. However, any part of the body could be attacked and the outcome was as serious no matter which site was affected.

When a town was affected by the plague, officials would hire ‘plague doctors’ to treat and

Medicine for Managers articles are not intended to be a source of medical advice. Their purpose is to familiarise the non-medical reader about current key medical disorders. Any medical or medicinal products mentioned by name are examples only and should not be regarded as an endorsement of their use.

manage the victims of the illness. They were generally second-rate doctors who were paid to look after any and all affected citizens who were ill. They often supplemented their salaries by selling to patients false cures and offering poor advice. In the seventeenth century, these plague doctors began wearing a mask with a

bird-like beak in an attempt to prevent them being afflicted by the disease, which they believed to be airborne. It was thought that the plague was spread by miasma, a noxious form of bad air. The beak contained aromatic herbs and spices and the other garments worn were also impregnated with aromatic compounds. Although the ‘beak doctor’ has become an iconic feature of the plague, there is no evidence that it was worn during the fourteenth century pandemic. It is reportedly the invention of Dr de Lorme in 1619 with the mask and thick, large waxen coat providing head to toe protection. It is known to have been worn in Italy during the plague of 1665 which killed 150,000 people in Rome and 300,000 people in Naples.

Could the plague come again? The sixty-four thousand dollar question. Yersinia pestis continues to cause sporadic infections but modern treatment is effective and the organism can be

destroyed by moxifloxacin and some other antibiotics. Antibiotics have transformed our lives, treating and curing people of diseases which were repeatedly fatal only seventy-five years ago. It is hard now to consider a world without penicillin but Fleming discovered it only in 1928, well into the lives of some of our friends or family. Other antibiotics followed but it is salutary to remember that the first methicillin-resistant Staphylococcus aureus was identified in 1968 and resistance is now seen to virtually all antibiotics.

So why is this resistance developing. There are a number of reasons

1. Abuse. Fleming himself expressed concern about the public demanding antibiotic for everything. He was right. The number of prescriptions for antibiotics is huge and many are for self-limiting or viral illness where the contribute little or nothing to recovery.

2. Inappropriate Prescribing. This prescribing contirbutes to the development of resistant strains. They may be for the wrong infection, for the wrong type of organism, when there is no organism causing the disease or in inadequate dosage so that resistant forms can survive and multiply. This latter cause may be aggravated by patients stopping their course of antibiotic prematurely because they feel better. In many countries, antibiotics are available on sale over the counter without a prescription.

3. Agricultural use. Up to 80% of antibiotics are used in animals. They allegedly improve the health of animals but the drugs used on animals are ingested by humans or are passed out of animals and collect in ground water which ultimately may get into the drinking water. Some antibiotics are sprayed

Medicine for Managers articles are not intended to be a source of medical advice. Their purpose is to familiarise the non-medical reader about current key medical disorders. Any medical or medicinal products mentioned by name are examples only and should not be regarded as an endorsement of their use.

on fruit trees as pesticides. Repeated low dose exposure to antibiotics provides an ideal environment for the development of resistant strains.

4. Decline in New Antibiotics. The great period of antibotic development has gone. Many pharmaceutical companies have ceased research on antibiotics. Research teams have been disbanded. Funding cuts and financial crises have had their effect. Between 1980 and 1984, 19 new antibiotics were introduced; 1990-1994, 11 new antibiotics; 2000-2004, 4 new antibiotics were introduced. Only 3 were introduced in the four years leading to 2010 although, between 2010 and 2014, the number released was 6. Antibiotics are not now as profitable as drugs for chronic conditions.

5. Regulation. Part of the problem in point 4. above relates to increased regulation and difficulties experienced by pharmaceutical companies in their countries of research and manufacture when they try to expand their market across other countries. Factors frustrating antibiotic progress include bureaucracy, differences in clinical trial requirements, regulatory and licensing rules and lack of communication between government agencies.

These and other factors will, contribute to the development of a bacterium which is resistant to everything we have got. A global pandemic of Staphylococcus aureus or an Enterococcus is the most likely. Tuberculosis may have a renaissance. Sexually transmitted diseases may increase out of control. Campylobacter, salmonella and streptococci may all lead to epidemics or pandemics. And yes, Yersinia pestis, which completely destroyed whole

populations and left urban areas as ghost towns, could come back.

Overall, emerging resistant bacteria could cause a catastrophe, maybe not next year or the year after or even in twenty years’ time, but it will come because bacteria have enormous capacity to mutate. Whichever antibiotic they are exposed to, they will learn to live with. Let us hope that the world realises it before it is too late so that the prediction can be consigned to a last paragraph in an article about the plague!

paullambden@compuserve.com

Medicine for Managers articles are not intended to be a source of medical advice. Their purpose is to familiarise the non-medical reader about current key medical disorders. Any medical or medicinal products mentioned by name are examples only and should not be regarded as an endorsement of their use.