Smallpox, Syphilis and Salvation

by Sheryl Persson

  In 1894 during the Chinese epidemic, Dr Mary Miles, a physician working in Canton, had reported on the widespread death of rats during plague epidemics. But people assumed the rats caught the disease from humans. Robert Koch had also pointed to rats as the cause. In 1897, a Japanese physician, Masanori Ogata, wrote: ‘One should pay attention to insects like fleas for, as the rat becomes cold after death, they leave their host and may transmit the plague virus directly to man.’[33] Someone was needed to put all the clues together. In the United States, Paul Louis Simmond collated various observations and experimented with the bacillus, rats and fleas, observing that rat fleas bit people and that a sick animal could not transmit the disease if it didn’t have fleas. Simmond’s conclusions, published in 1898, were ridiculed (as was so often the case), but in 1905 a British commission published similar findings. The commission issued another report in 1908 that confirmed Simmond’s conclusions without crediting him. At last the blame was directed where it belonged. Fleas transmitted bubonic plague, not rats or humans.

  The last plague pandemic ended in China and India in the late 1800s but sporadic outbreaks continued to occur throughout the twentieth century. In 1899 the plague was carried to America by stowaways on a ship sailing from Hong Kong to San Francisco. The following year there were outbreaks of plague in Portugal and Australia and another scare in San Francisco when during an autopsy a city health officer found organisms that looked like plague bacilli in the body of a deceased Chinese man. In the next few years over 100 people died from plague in San Francisco. An effort was made to quarantine and clean up parts of the city, but in 1906, when San Francisco was devastated by an earthquake, people were left homeless and so were the rats.

  During the rebuilding program thousands of people lived in refugee camps that were highly conducive to rat and flea infestations. In 1907 new cases of plague were reported. Armed with the new knowledge about the method of transmission, officials launched a different kind of campaign: they offered a bounty on rats. A similar rat-catching campaign had been used successfully to fight plague in New Orleans and it proved successful again in San Francisco.[34] The widespread outbreak was brought to a halt in 1909.

  There were outbreaks of plague in other parts of the world as well. China was particularly hard hit. In 1910, the year after plague had been controlled in San Francisco, 60,000 people died in Manchuria of the pneumonic strain. Ten years later in 1920 it struck Manchuria again, killing just as many. Much more recently, in the summer of 1994, 5000 cases of pneumonic plague occurred in Surat in India, killing approximately 100 people.[35] According to World Health Organization figures there are 2500 new cases of the bubonic plague annually and 180 annual deaths, of which 75 per cent occur in Africa.

  ***

  Today plague is successfully treated with antibiotics although about 1 in 10 cases can still be fatal because rapid diagnosis is essential. Despite the great inroads since Yersinia pestis was outed by Kitasato and Yersin, plague remains endemic in many countries in Africa, in the former Soviet Union, the Americas and Asia. It also exists in animal populations across vast areas of southern and central Russia; Mongolia; parts of China and southern Asia; southern and east Africa including Madagascar; North America; Mexico; the Andes and the mountains of Brazil. There are no plague-infected animal populations, however, in Europe or Australia.

  In 1996 the World Health Organization, after having recorded 24,000 plague cases over a fifteen-year period, reclassified the plague as a ‘reemerging disease’. Like tuberculosis, it is making a comeback. The WHO continues to report on and monitor outbreaks of plague in various parts of the world. This was the case in Zambia in 2001, and Malawi and India in 2002. In the Indian village of Hat Koti in Himachal Pradesh sixteen cases of pneumonic plague were confirmed.[36] Under the guidance of the National Institute of Communicable Diseases (NICD) the local health administration took various measures, including vaccination and fumigation, to control the spread of the disease.

  The Algerian Ministry of Health reported an outbreak of plague in June 2003 in Tafraoui, on the outskirts of Oran. Of the ten cases there were eight cases of bubonic plague and two of septicaemic plague, one of which was fatal. Patients were treated with antibiotics and once again preventative measures stopped the spread.[37] Overall in 2003, nine countries reported 2118 cases of plague and 182 deaths. This is a far cry from the Great Mortality of the fourteenth century.

  In February 2005, WHO received reports of 61 deaths of pneumonic plague in the Democratic Republic of Congo and dispatched a multi-disciplinary team to deal with the outbreak. The WHO was still dealing with outbreaks of plague there in late 2006; control has proved difficult because of the country’s ongoing internal conflict.[38] Various news sources reported on 19 April 2006 that in Los Angeles a woman had been admitted to a hospital with a fever, swollen lymph nodes and several other symptoms, the first case of bubonic plague in Los Angeles County since 1984. The woman was successfully treated with antibiotics. In 2006 there were two deaths attributed to plague in New Mexico, the first fatalities in that state in twelve years.[39] With plague still present in animal populations in various countries, humans remain at risk.

  Today the control of bubonic plague does not rely on the vaccine developed by Waldemar Haffkine in 1896. With various modifications a plague vaccine was available until the mid 1990s, but because of short-term effectiveness and many side-effects, production ceased. Plague vaccination is no longer recommended for immediate protection in outbreak situations except as a prophylactic measure for high-risk groups such as laboratory personnel who are constantly exposed to the risk of contamination. Surveillance strategies and a range of control measures—taking precautions against flea bites, avoiding direct contact with infective tissues and people infected with pneumonic plague—are tools used by the WHO and other health agencies for preventing outbreaks of plague.

  In 2005 the World Health Organization introduced the Epidemic and Pandemic Alert Response, the aim of which is to prepare for global health emergencies by ensuring there are adequate laboratory capabilities and warning and alert systems in place, by implementing national and international training programs and by developing standardised methods for responding to epidemics. The category of epidemic diseases includes plague but also emerging diseases such as SARS, avian influenza and viral haemorrhagic fevers which have been the cause of panic in recent years.[40]

  Despite the breakthroughs achieved by scientists like Waldemar Haffkine, the struggle for existence between humans and disease is far from over. The WHO continues to build on the discoveries of the medical pioneers to ensure that the world never again experiences the horror of a pandemic such as the Great Mortality. Sadly, the medical miracles performed by scientific geniuses a century ago have been undermined. As with smallpox, bubonic plague has a reputation for being used as a biological weapon and in the current climate of the early 21st century the threat has not lessened.

  Historical accounts from Mediaeval Europe detail the use of infected animal carcasses and human bodies to contaminate enemy water supplies during times of war. Particularly gruesome are accounts of plague victims being tossed by catapult into cities under siege. During the Japanese occupation of Manchuria from the early 1930s until the end of World War II, the Japanese army developed weaponised plague. Civilians and prisoners of war were deliberately infected with plague bacterium and some were dissected in macabre experiments while still living and conscious. Science is not always used for the greater good. It has been suggested that after World War II both the United States and the Soviet Union developed methods for weaponising pneumonic plague including strains resistant to antibiotics. More recently, developments in genetic engineering have led to new experimentation and there is fear that strains of plague bacilli resistant to all drugs, including penicillin, may have been developed.

  The disappearance of three mice infected with Yersinia pestis in September 2005 from a Public Health Research Institute laboratory located at the Univ
ersity of Medicine and Dentistry of New Jersey was cause for alarm. The laboratory conducts anti-bioterrorism research for the United States government. Authorities launched a search for the animals and an investigation into how they might have escaped.[41] Suggestions ranged from the feasible to the very worrying: the mice may have been stolen; the mice may have cannibalised each other; the mice were ‘unaccounted for’ due to a paperwork error. The institute’s director said that the disappearance was more likely the result of ‘an honest mistake’, a response which probably requires some qualification. Some experts expressed surprise at the idea that the mice could escape because of the tight security at the lab, which is categorised as biosafety level 3 out of a possible 4.[42] Although the issue was played down—the public were assured that the mice posed very little risk even if they had escaped—the FBI joined in the investigation, as did the Centers for Disease Control and Prevention.

  The mice have not been located. There are suggestions that research into plague and plague vaccines has tripled in the United States following the fears of bioterrorism sparked by September 11. Whatever the trend, it is impossible to know how many laboratories throughout the world currently hold infected animals—potential escapees.

  In October 2001, the science journal Nature announced that the complete genetic structure of the plague bacilli had been unravelled by scientists at the Sanger Centre in Cambridge in the United Kingdom.[43] Brendan Wren, a scientist who helped to sequence the DNA of the plague bacterium, said that the ‘missing mice’ incident was extraordinary, but he pointed out that there are many animals in the wild that carry the bacterium. The real worry he noted is that there may be animals carrying a plague bacterium that has been engineered in a clandestine laboratory to be resistant to any form of treatment.

  It is not all doom-saying, however. According to the leader of the team that sequenced the 4.65 million DNA letters, the successful unravelling of the complete genetic structure of Yersinia pestis will be ‘the basis of all future work’ on plague.[44] It is critical for the design of more effective antibiotics and vaccines to treat the disease. The knowledge is also insurance against potential new plague threats whether created by natural selection or weapons of bioterrorism, a concept that would have been anathema to Alexandre Yersin, Shibasaburo Kitasato and Waldemar Haffkine. To these scientists, plague was a scourge of nature. Their concern was to save humanity, not destroy it.

  POSTSCRIPT

  Alexandre Yersin lived a simple life in Nha Trang and was respected by people in the region for his humility and for all that he did to improve their lives. The locals affectionately called his home Lau Ong Nam, ‘Home of Fifth Uncle’ (the First Uncle is Ho Chi Minh, the man who led Vietnam to independence from France) and it has become a national shrine. His legacy is remembered in many different ways in Vietnam today. Throughout the country there are many towns where streets are still named after this selfless scientist. In 1935 the municipal authorities in Da Lat established a school, the Lycée Yersin, to honour Yersin’s medical achievements. The French international school in Hanoi, Lycée Français Alexandre Yersin, is named in his honour. And in Nha Trang, every year on the first day of March, over 50 years after Yersin’s death, many of the local people still come to his grave, bringing joss sticks and fruit as offerings to show their gratitude to this dedicated scientist.

  CHAPTER 5

  BANISHING THE ‘STRANGLING ANGEL’

  DIPHTHERIA, TETANUS AND BEHRING’S BLOOD SERUM THERAPY

  Both Pam and Poppy became very ill with sore throats and could hardly swallow ... In spite of my mother’s and Betty’s round the clock nursing, poor Pam died a week later followed by Poppy the day after ... my mother was in a state of deep shock and had been confined to bed by the doctor but worse still it was feared that Mary the baby had also caught the dreaded diphtheria ... We must have a curse on us.[1] BENJAMIN EDWARD WALKER

  The disease diphtheria swept through Europe during the seventeenth century and struck the American colonies in the eighteenth century, killing 1 in 10 of its victims. Tragically most of them were children, their deaths usually the result of suffocation. Diphtheria, an upper respiratory tract infection, was called the ‘strangling angel’ because it came unexpectedly and took so many young lives. Tetanus, an acute infectious disease that was also rampant at that time, had another name as well. It was dubbed ‘lockjaw’ because of the uncontrollable and painful muscle spasms it induced in its victims. With both these diseases it was the manner of death that was most frightening.

  The discoveries of ‘cures’ for tetanus and diphtheria are inextricably linked, not only because of the scientists involved in discovering treatments to combat these diseases but also because of the science that made the cures possible in the late 1800s. The lead roles in this story are taken by the German physician Emil von Behring, whose brain-child was Serum Therapy—treating tetanus and diphtheria using antitoxic blood serum—and the Japanese bacteriologist Shibasaburo Kitasato, who began working on tetanus five years before he discovered the cause of bubonic plague.

  From the time Shibasaburo Kitasato arrived in Berlin in 1885 to join Robert Koch’s team at the Berlin Institute of Hygiene it was immediately obvious that he was a superior scientist. Kitasato focused on typhoid, cholera and anthrax for the first three years after his arrival and began his research on tetanus early in 1889. In April of that year, at the eighteenth Congress of the German Surgical Association, Kitasato was able to announce that he had isolated the tetanus bacillus, Clostridium tetani, after only three months of work. It was possible for Kitasato to do this in such a short space of time because of his fastidious approach to his work. Before he began in earnest Kitasato had thought through the experiment as a whole, designed the experimental procedure and protocols and predicted the results.[2] Perhaps he applied this method later to finding the plague bacillus, which he isolated even more quickly.

  Prior to Kitasato’s breakthrough, in 1884 the Spanish researchers Antonio Carle and Giorgio Rattone had injected animals with pus from a man who had died of tetanus, and proved that the disease could be transmitted. Also that year, the Berlin physician Arthur Nicolaier produced tetanus in animals by injecting them with samples of soil, indicating that an organism was the cause. Under a microscope the tetanus bacterium looks like a slender rod and it is the toxin produced by this micro-organism that causes tetanus. The bacteria are generally found in manured soil, are sensitive to heat and cannot live in the presence of oxygen. However, Clostridium tetani can survive these conditions by developing spores that are very resistant to heat and to many antiseptics and chemicals. In fact, they can survive autoclaving (heating) at 121°C for up to 15 minutes.[3] This goes some way to explaining why tetanus has survived for aeons.

  ***

  The most common way of contracting tetanus is when the spores enter the body through a skin wound, even a simple cut or prick with a thorn. Clostridium tetani produces two exotoxins, tetanolysin and tetanospasmin. (Exotoxins are soluble toxic substances secreted by some species of bacteria that are released into the host.)The function of tetanolysin is not really known, but tetanospasmin is a neurotoxin which causes the tetanus symptoms. An interesting statistic is that, on the basis of weight, it is one of the most potent toxins known. The minimum human lethal dose is estimated to be 2.5 nanograms per kilogram of body weight (one-billionth of a gram), an amount that is almost impossible to conceive.[4]

  Tetanus can be contracted almost anywhere in the world because of the ubiquity of the spores but they are more common in hot, damp climates where the soil is rich in organic matter. This is particularly the case with manure-treated soils because the spores can be carried in the intestines and faeces of both large and small animals. Also in agricultural areas it is easy for humans to carry the organism internally and on the surface of the skin. Today, as a by-product of the society in which we live, the spores are increasingly being found in contaminated heroin. Spores can lie dormant in the soil and remain infectious for mo
re than 40 years.

  There are four different clinical forms of tetanus that humans can contract: cephalic, local, generalised and neonatal tetanus. Both the cephalic and the local form are quite rare. The generalised form of tetanus is the most common and accounts for 80 per cent of cases. The fourth type, neonatal tetanus, is a common cause of infant mortality in developing countries. Neonatal tetanus can occur when a baby’s umbilical cord is severed with an unsterilised instrument contaminated with tetani spores and when the cut is sealed with contaminated substances.[5]

  The incubation period for tetanus varies depending on how far the wound is from the central nervous system. It can be as little as three days or as long as fifteen weeks but the average is eight days. The longer the incubation period the less likely a person is to die as a result of the infection. A deep wound allows the bacteria to flourish and causes a quick, aggressive infection that is much more life-threatening. It is when the bacteria multiply in the wound that they produce tetanospasmin, the neurotoxin that attacks the nerves. Symptoms include an increase in body temperature by 2–4°C, excessive sweating, elevated blood pressure, muscle rigidity and severe muscle spasms. The spasms begin in the neck and jaw muscles, hence the name ‘lockjaw’. As the spasming spreads to other muscles, victims find it difficult to swallow and suffer breathing difficulties, and when the spasms reach the abdomen victims go into painful and powerful convulsions that can tear muscles and fracture bones.[6] It is horrifying to witness these spasms and as they progress abnormal heart rhythms can develop, causing death in many cases. For those who survive, muscle contractions and spasms last for three to four weeks but complete recovery can often take months.