Bacillus anthracis

Bacillus anthracis Gram stain ©1999 Kenneth Todar University of Wisconsin Department of Bacteriology

Disease	Anthrax
Natural Hosts	Sheep, cattle, and other grazing animals including bison, elk, kudu, and wildebeest; spores can be found in meat, milk, hides, and hair of infected animals
Incubation Period	Dependent on mode of exposure
Symptoms	Anthrax bacteria left exposed to light and air for over two hours form spores; it is the spores that are used in biological weapons, and are often implicated in natural outbreaks. Spores can be ingested, inhaled, or inoculated into minor skin abrasions. In a biological warfare scenario, weapons would burst to create an aerosol of airborne spores, leading to inhalation anthrax. During inhalation anthrax's initial phase, spores are carried to the lymph nodes, causing nonspecific flu-like symptoms; mild fever, malaise, fatigue, cough, and in some cases a sense of pressure on the chest. This phase can last for several days, or for as little as 24 hours. The second phase develops suddenly and is characterized by severe shortness of breath; hypotension and shock occur. Perspiration is often profuse. The second, acute phase typically lasts less than 24 hours and usually ends in death despite any treatment.
Treatment	Penicillin, ciprofloxacin, and doxycycline are the drugs of choice. Tetracyclines, erythromycin, or chloramphenicol could also be used. Treatment with antibiotics must begin prior to the onset of symptoms and must include vaccination prior to discontinuing their use.
Fatality Rate if Untreated	5 percent (cutaneous) 25‚75 percent (ingestion ) 70‚80 percent (inhalation)

History

The anthrax bacillus was the first bacterium shown to be the cause of a disease. In 1877, Robert Koch grew it in pure culture, demonstrated its ability to form spores, and produced anthrax by injecting it into animals. The first vaccine against anthrax was developed by Louis Pasteur. Anthrax is thought by some to have been the biblical fifth plague of Egypt.


Robert Koch's original micrographs of the anthrax bacillus
photograph provided by Professor Kenneth Todar
University of Wisconsin Department of Bacteriology

Anthrax was tested as a biological warfare agent by Unit 731 of the Japanese Kwantung Army in Manchuria during the 1930s; some of this testing involved intentional infection of prisoners of war, thousands of whom died. Anthrax, designated at the time as Agent N, was also investigated by the Allies in the 1940s. The British army tested experimental anthrax weapons on Gruinard Island, off the northwest coast of Scotland, in 1943. Gruinard was burned over at least once, yet as of late 1980s it was still too heavily contaminated with spores to allow unprotected human access, indicating the hardiness of anthrax spores. B. anthracis was part of the US stockpile prior to its destruction in 1972

Natural Outbreaks of Anthrax

Anthrax, also known as Woolsorter's disease, is an occupational disease of farmers, slaughterers, skinners, hide workers, tanners and woolworkers. These individuals are exposed to spores found in meat, bones, hides, or hair of infected animals that are inhaled or come into contact with small abrasions on the skin. In over 95% of cases the infection is cutaneous.

Cutaneous anthrax differs from inhalation anthrax because it is typically noticed when a raised, inflamed pimple appears about three days after exposure. It quickly acquires a small halo of clear blisters, followed by the formation of a coal-black scab, or eschar, in the center where the inflammation first occurred. Swelling often affects the whole of the affected limb adjacent to the lesion, with a varying degree of redness surrounding the blisters and the scab.


Photograph © Department of Pathology
University of Kansas School of Medicine

Anthrax can also be spread through the consumption of meat from infected animals, resulting in intestinal infection. This form of anthrax takes the form of severe watery diarrhea. Anthrax spores can be killed by heat, which prevents a greater incidence of food-borne infections in areas where anthrax is common.

The Sverdlovsk Anthrax Outbreak

An outbreak of anthrax occurred during April, 1979, among people who lived or worked in a narrow zone downwind of a Soviet military microbiology facility in Sverdlovsk (now Ekaterinburg) Russia. In addition, livestock died of anthrax within a larger downwind zone. The facility was suspected by western intelligence of being a biological warfare research facility. Intelligence analysts attributed the outbreak to the accidental airborne release of anthrax spores. The Soviets maintained that the outbreak was due to ingestion of contaminated meat purchased on the black market. Finally, in 1992, President Yeltsin of Russia admitted that the facility had been part of an offensive biological weapons program, and that the disease in animals and people resulted from an accidental release of anthrax spores.

Clostridium botulinum

Disease	Botulism
Natural Hosts	Typically formed in improperly processed home canned foods
Incubation Period	12-36 hours
Symptoms	Infant botulism results from an infection of the gut with C. botulinum. As the bacteria grow in the infant's gut, they produce a toxin that has its principle effect on the nervous system. Infant botulism has a wide range of symptoms including difficulty breathing, visual disturbances, poor feeding and poor reflexes. In contrast, foodborne botulism results from eating the preformed toxin made by the bacteria in contaminated food. The symptoms of food-borne botulism include blurred or double vision, general weakness, poor reflexes, difficulty swallowing and sometimes death.
Treatment	antitoxin is indicated for probable foodborne cases
Fatality Rate if Untreated	70 percent

C. botulinum produces the botulinum toxin, which is a neurotoxin responsible for the symptoms of botulism. The bacteria per se is not a biological agent; rather, the isolated toxin is generally considered to be the biological warfare agent.

Francisella tularensis

Disease	Rabbit fever, Francis' disease, deer-fly fever, O'Hara disease, tularemia
Natural Hosts	Wild rabbits; also hares, muskrats, and beavers; can also be transmitted by flies, mosquitoes, and ticks.
Incubation Period	2-10 days
Symptoms	When tularemia infection is transmitted through a scratch or bite, a sore usually appears at the site where the bacteria entered the body. This is usually accompanied by swelling of the draining lymph nodes. Swallowing the bacteria directly from infected meat (or untreated water while in an area where animals are commonly infected) may cause throat infection, stomach pain, diarrhea, and vomiting. Inhaling the infectious material by breathing dust particles from contaminated soil or from handling contaminated skins can produce fever and a pneumonia-like illness.
Treatment	Streptomycin is the drug of choice; Gentamicin is an acceptable alternative.
Fatality Rate if Untreated	5 percent for naturally-acquired tularemia; the pneumonic form of the disease would likely be higher

Tularemia eschar at the site where F. tularensis penetrated the skin:


Photograph © Department of Pathology
University of Kansas School of Medicine.

F. tularensis was part of the US stockpile prior to its destruction in 1972.

Brucella

Disease	Undulant fever, Mediterranean fever, Malta fever, brucellosis
Natural Hosts	swine, goats, cattle, and sheep
Incubation Period	3 days to several weeks
Symptoms	The symptoms include weakness, headache, high fever, chills, body and joint aches, chills, depression, nausea, weight loss. Chronic undulant fever is characterized by periods of normal temperature between acute attacks; symptoms may persist for years, either continuously or intermittently.
Treatment	Broad-spectrum antibiotics
Fatality Rate if Untreated	5 percent for B. suis, higher for B. abortus and B. melitensis

The significant strains of Brucella include:

• B. abortus, occurring naturally in cattle and sheep; this strain has the most serious effects in humans and is the most severe biological warfare threat.
• B. melitensis, occurring naturally in sheep and goats
• B. suis, occurring naturally in swine, was part of the US stockpile prior to its destruction in 1972.

Vibrio cholerae

Disease	Cholera
Natural Hosts	Human; transmitted by eating food or drinking water contaminated by the feces or vomitus of someone infected with cholera. Current research also implicates shellfish in an estuarine environment; this is as yet poorly understood but may involve the plankton on which the shellfish feed.
Incubation Period	2 to 3 days
Symptoms	Severe gastroenteritis; the symptoms include mild to severe watery diarrhea, vomiting, and dehydration (fluid loss of up to 1 liter per hour).
Treatment	Intravenous or oral replacement of fluids and salts; antibiotics
Fatality Rate if Untreated	Over 50 percent

Natural Outbreaks of Cholera

Cholera pandemics are a relatively modern phenomenon; relatively rapid, global transportation and increased concentrations of population in large urban centers seem to have emerged at about the same time as pandemic cholera. It is believed that cholera has been endemic in India for many centuries. All the major cholera pandemics began in the subcontinent, often spreading along trade routes, among religious pilgrims, and among soldiers returning from foreign wars.

• The first great cholera pandemic, probably originating near Calcutta in 1817, spread to southeast Asia, Japan and China and lasted until 1823. It is believed that an exceptionally cold winter in 1823-24 kept the pandemic from reaching Western Europe.
• The second cholera pandemic began in Bengal and spread through India in 1826, reaching Afghanistan in 1827, Moscow in late 1830, England in 1831, New York by way of Canada in 1832, and from there throughout most of the U.S. The second pandemic lasted until 1837.
• The third major cholera pandemic reached Europe and the U.S. in 1848. The English physician John Snow observed during the 1848 London epidemic that the disease was spread by contaminated water. Snow made the connection that all of the infected households obtained drinking water from the same well.
• The fourth cholera pandemic began in 1863, spread first to the Middle East, and then into the Mediterranean. It spread to New York on a ship from France in October 1865. Before the pandemic ended in 1866, tens of thousands died; however, for the first time, public health reforms kept the death toll lower than it otherwise would have been. Another epidemic affected the Mississippi and Ohio valleys in 1873.
• A fifth cholera pandemic began in 1881 and lasted until 1896. Improved sanitation kept it from reaching many European cities, and improved diagnosis and quarantine measures kept it from reaching the U.S. During this wave, German physician Robert Koch discovered that Vibrio cholerae caused the disease.
• A sixth pandemic began in 1899, also affecting Asia but failing to reach western European or the U.S., again due to developments in water treatment and sanitation.
• The seventh, most recent pandemic began in Indonesia in 1961 and reached Peru and neighboring countries in 1991. It continues with periodic outbreaks in many areas of the world where clean water is not always available. The Peruvian outbreak coincided with a halt in that country's water chlorination program.
• Epidemic cholera in 1992 in India and Bangladesh, has spread to other countries in Southern Asia. This outbreak is caused by a new strain of toxigenic Vibrio cholerae, and is feared to be the beginning of the eighth cholera pandemic.

V. cholerae was spread by the Germans in 1915 in Russia and Italy in an attempt at biological warfare.

Chlamydia psittaci

Disease	Psittacosis
Natural Hosts	Parrots, parakeets, and other birds; transmitted by handling the blood, tissues, feathers, and discharges from infected birds, or by breathing in dust particles from the dried droppings of infected birds.
Incubation Period	4 to 15 days
Symptoms	The symptoms include fever, headache, loss of appetite, vomiting, neck and back pain, muscle aches, chills, fatigue, and cough. In severe cases, extensive pneumonia may develop and be fatal (rarely).
Treatment	Doxycycline or erythromycin
Fatality Rate if Untreated	Rare

Shigella dysenteriae

Disease	Bacillary dysentery, shigellosis
Natural Hosts	Preschool-age children; fecal-oral transmission
Incubation Period	1 to 3 days
Symptoms	The symptoms include fever, nausea, vomiting, abdominal cramps, watery diarrhea, and occasionally, traces of blood in the feces.
Treatment	Intravenous or oral replacement of fluids and salts; ampicillin
Fatality Rate if Untreated	1-10 percent

Staphylococcus aureus

 
Photograph © Department of Pathology
University of Kansas School of Medicine.

Disease	Staphylococcal gastroenteritis; Toxic shock syndrome
Natural Hosts	Humans; also cows, fowl, and dogs
Incubation Period	1-6 hours
Symptoms	The major symptoms for food-borne infection are nausea, vomiting, abdominal cramping, and diarrhea.
Treatment	Methicillin or vancomycin
Fatality Rate if Untreated	Rare for food-borne infection, 3-5 percent for toxic shock syndrome

Staphylococci can be found on the skin and mucosa of many healthy humans. Sneezing and coughing can contaminate food. Animal-contaminated milk and eggs can also be a source of infection. Many outbreaks have been produced by consumption of inadequately refrigerated raw milk or cheeses. In developing countries, where refrigeration after milking is often inadequate, milk and milk products may be an important source of staphylococcal infection. In the U.S, unrefrigerated cream puffs or potato salad at summer picnics are common sources.

If temperature and humidity are favorable, one or more strains of S. aureus can multiply in the food and produce enterotoxin proteins, including staphylococcal enterotoxin B. Once made, the toxin is not destroyed even if the food is subjected to boiling while being cooked. Thus, the toxin may be found in the food where no live organisms are present. An important factor in food-borne incidents is holding food at room temperature, which permits multiplication of staphylococci. Other toxins in addition to SEB include SEA, SEC, and SEE, as well as TS T-1, the toxin produced in toxic shock syndrome. S. aureus is not considered to be a potential biological warfare agent; it is the isolated toxin that is a potential agent.

Yersinia pestis

Disease	Plague, black death
Natural Hosts	Rodents; transmitted by flea bites
Incubation Period	2 to 7 days
Symptoms	The most common form of plague is bubonic plague which affects the body's lymph nodes. The first symptoms of bubonic plague include the sudden onset of fever with painful swelling of the lymph nodes, called bubos in the areas of the draining lymph nodes (typically, in the groin, armpit, or neck). Chills, muscle-aches, weakness, fatigue, nausea, and headache may also occur. When the infection begins in or spreads to the lungs, the disease is called pneumonic plague. Pneumonic plague produces pneumonia that is highly contagious and often fatal. The pneumonic form of plague is characterized by fever, swelling of the lymph nodes, cough, chest pain, and frequently, blood in the sputum.
Treatment	Streptomycin or gentamicin, started within 24 hours of onset of symptoms, can reduce the fatality rate to 5-10 percent
Fatality Rate if Untreated	30-75 percent for bubonic plague, 95 percent for pneumonic plague

Plague is called the black death because the blood coagulates inside the circulatory system, leading to areas of skin necrosis.

History

The plague has been known since roughly 1000 BC; China has had epidemics dating from 224 BC. The plague appears first in the West in the 1st century A.D., when an epidemic occurred in Libya, Egypt and Syria. The "plague of Justinian" began in Egypt and Ethiopia in 542, and raged through the Eastern Roman Empire in 542-543. Approximately 300,000 people died in Constantinople during the 542; Justinian was stricken, but survived. This was the first pandemic caused by Y. pestis. Subsequent outbreaks included epidemics in Rome in 590, killing Pope Pelagius II, and again in 680. In 746 to 748, plague again struck Constantinople.

The most devastating pandemic of all time was medieval outbreak of plague. It was first noted in the summer of 1346, during a siege of the Genoese colony at Caffa on the north shore of the Black Sea. Caffa was under siege by the Tartars (the descendants of Genghis Khan's Mongol horde who ruled much of Russia). During the siege, corpses of plague victims were catapulted into the town, in a medieval example of biological warfare. From Caffa, the defeated refugees sailed for Italy. As the refugees fled, the pandemic spread to:

October 1347	Messina
January 1348	Genoa, Marseilles, Valencia
winter of 1348	Venice, Pisa, Florence
summer of 1348	Paris
end of 1348	southern England
1349	northern England, Germany, the Balkans
1350	Scotland, Denmark, Russia

The great pandemic petered out in 1352, having killed one-fourth to one-third of the population of Europe and Asia, with up to 70 percent fatalities in some cities.

Y. pestis returned several more times to Europe:

• outbreaks in London in 1499, 1563, 1578, 1625, and 1636
• outbreaks across Europe in 1590-1610
• repeated outbreaks during the Thirty Years War in Germany, 1618-48
• outbreaks in France in 1625-40
• The "Great Plague" of London in 1665
• outbreaks in the Ottoman Empire and Austria in 1679
• outbreaks in France in 1720, centered on Marseille

The third plague pandemic began in the interior of China in the 1850s, reaching the coast in the 1880s, and spreading from there rapidly around the world, including epidemic outbreaks in India, North Africa, and South America. A severe outbreak occurred in Hawaii in 1899, and San Francisco in 1900-1904, and again in 1907-1909. Officially this pandemic was not considered over until 1959, a century after it started.

Y. pestis was tested as a biological warfare agent by Unit 731 of the Japanese Kwantung Army in Manchuria during the 1930s. The Japanese air-dropped fleas infected with Y. pestis in a weapons test on Ningpo, China, in 1940. Many Chinese civilians were infected with plague; approximately 500 fatalities resulted.

Burkholderia mallei

Disease	Glanders
Natural Hosts	Horses, donkeys, and mules; transmitted to humans by inhalation of bacteria in aerosols or dust or contact with infected animals
Incubation Period	3 to 6 days
Symptoms	Pulmonary form: cough, nasal discharge, acute or chronic pneumonia Cutaneous form: multiple purulent cutaneous eruptions, often following lymphatics
Treatment	Sulfadiazine may be effective in some cases. Doxycycline, rifampin, trimethoprim-sulfamethoxazole, and ciprofloxacin have been effective in experimental infection in hamsters.
Fatality Rate if Untreated	95 percent

Burkholderia pseudomallei, a saprophyte of soil and water in tropical areas of southeast Asia, causes a glanders-like disease called mellioidosis. This disease may take a rather benign pulmonary form, but may also develop into a rapidly fatal septicemia. According to the US Department of Agriculture, glanders was eradicated from the US animal population in 1934.

German saboteurs employed B. mallei as a biological weapon during World War I. At that time, horses and mules were very important battlefield resources, bringing supplies to the front and moving artillery. Cultures confiscated from the German legation in Bucharest, Romania, were identified as B. mallei, and livestock were infected in Mesopotamia, France, and Argentina. Before the United States entered the war, German saboteurs are believed to have inoculated horses destined for export with B. mallei. It is known that many horses died at sea, or were dying when then arrived in Europe.

Salmonella typhi

Disease	Typhoid fever
Natural Hosts	Humans; transmitted by eating or drinking food or water contaminated by the stool of infected individuals, such as shellfish taken from sewage-contaminated waters or fruits and vegetables fertilized with human feces
Incubation Period	1 to 3 weeks
Symptoms	Typical symptoms include sustained fever, headaches, constipation (reported to occur more often than diarrhea in adults), fatigue, and fleeting rose-colored spots, especially on the abdomen. The symptoms can be mild to very severe.
Treatment	Antibiotics, some strains are resistant to chloramphenicol.
Fatality Rate if Untreated	10 percent

Typhoid fever is caused by Salmonella typhi, which is also known a S. typhosa; it is a different disease from typhus, which is caused by Rickettsia typhi(endemic typhus) and Rickettsia prowazekii(epidemic typhus), both of which are spread by lice.

Major typhoid fever outbreaks have been associated with war, including outbreaks among the army of the Holy Roman Emperor Henry IV as he attempted to conquer Rome in 1081, the First Crusade in Syria in 1098 after the siege of Antioch, and the armies of the American Civil War in 1861-65. Typhoid fever is also noted because it can be spread by asymptomatic carriers. The best known of these carriers was "Typhoid Mary" Mallon, who worked as a cook in New York and Maine. Typhoid Mary was taken into custody by New York health officials after she was identified as the source of at least 28 infections, beginning about 1900 and lasting until 1907. She was placed in quarantine on 20 March 1907 after providing a stool sample that contained high levels of S. typhi. In 1910, she was released after she promised she would never again prepare food for others and would return every three months to the Health Department laboratory. However, she subsequently returned to her former occupation, working as a cook under assumed names in New York City. In 1915 she was identified as the source of 25 more cases among the doctors and staff of Sloane Maternity Hospital in New York City. She was quarantined at North Brother Island for the remainder of her life. Unofficially, she is also believed to be responsible for an epidemic in 1903 in Ithaca, New York, which spread to the community and caused 1,400 cases of typhoid fever.