Bacteria

ANTHRAX

Anthrax bacteria occur worldwide. The organisms known as Bacillus anthracis may ordinarily produce disease in domesticated as well as wild animals such as goats, sheep, cattle, horses, and swine. Humans become infected by contact with infected animals or contaminated animal products. Infection occurs mainly through the skin and rarely by breathing spores or swallowing them. Spores exist in the soil and become active when the organisms in the carcass are exposed to air.

Apart from biological warfare, anthrax in humans is rare. In the United States, only 127 cases of anthrax appeared in the early years of the 20th century and dropped to about 1 per year during the 1990s.

Signs and symptoms

Skin anthrax (cutaneous): Infection begins when the spores enter the skin through small cuts or abrasions. Spores then become active in the host (human or animal) and produce poisonous toxins. Swelling, bleeding, and tissue death may occur at the site of infection.

• More than 95% of the cases of anthrax involve the skin. After a person is exposed, the disease first appears in 1-5 days as a small pimple-looking sore that progresses over the next 1-2 days to contain fluid filled with many organisms. The sore is usually painless and it may have swelling around it. Sometimes the swelling affects a person's entire face or limb.
  
  
• Victims may have fever, feel tired, and have a headache. Once the sore opens, it forms a black area of tissue. The black appearance of the tissue injury gives anthrax its name from the Greek word anthrakos meaning coal. After a period of 2-3 weeks, the black tissue separates, often leaving a scar. With adequate treatment, less than 1% of people infected with skin anthrax die.

Inhalation anthrax: In inhalation anthrax, the spores are inhaled into the lungs where they become active and multiply. There they produce massive bleeding and swelling inside the chest cavity. The germs then can spread to the blood, leading to shock and blood poisoning, which may lead to death.

• Historically known as woolsorter's disease (because it affected people who work around sheep), inhalation anthrax can appear anywhere within 1-6 days, or as long as 60 days after exposure. Initial symptoms are general and can include headache, tiredness, body aches, and fever. The victim may have a nonproductive cough and mild chest pain. These symptoms usually last for 2-3 days.
  
  
• Some people show a short period of improvement. This is followed by the sudden onset of increased trouble breathing, shortness of breath, bluish skin color, increased chest pain, and sweating. Swelling of the chest and neck may also occur. Shock and death may follow within 24-36 hours in most people with this type of infection.
  
  
• Anthrax is not spread from person to person. Inhalation anthrax is the most likely form of disease to follow a military or terrorist attack. Such an attack likely will involve the aerosolized delivery of anthrax spores.

Mouth, throat, GI tract (oropharyngeal and gastrointestinal): These cases result when someone eats infected meat that has not been cooked sufficiently. After an incubation period of 2-5 days, victims with oropharyngeal disease develop a severe sore throat or sores in the mouth or on a tonsil. Fever and neck swelling may occur. The victim may have trouble breathing. GI anthrax begins with nonspecific symptoms of nausea, vomiting, and fever. These are followed in most victims by severe abdominal pain. The victim may also vomit blood and have diarrhea.

Diagnosis

Doctors will perform various tests, especially if anthrax is suspected.

• With skin anthrax, a biopsy is taken of the sore (lesion), and lab tests are performed to look at the organism under a microscope and confirm the diagnosis of anthrax.
  
  
• The diagnosis of inhalation anthrax is difficult to make. A chest x-ray may show certain signs in the chest cavity. Cultures (growing the bacteria in a lab and then examining them under a microscope) are minimally helpful in making the diagnosis. Blood tests may also be performed.
  
  
• GI anthrax also is difficult to diagnose because the disease is rare and symptoms are not always obvious. Diagnosis usually is confirmed only if the victim has a history of eating contaminated meat in the setting of an outbreak. Once again, cultures generally are not helpful in making the diagnosis.
  
  
• Meningitis (brain swelling) from anthrax is difficult to distinguish from meningitis due to other causes. A spinal tap may be performed to look at the person's spinal fluid in identifying the organism.

The most useful microbiologic test is the standard blood culture, which is almost always positive in victims with anthrax throughout their bodies. Blood cultures should show growth in 6-24 hours and if the laboratory has been alerted to the possibility of anthrax, biochemical testing should provide a preliminary diagnosis 12-24 hours later. However, if the laboratory has not been alerted to the possibility of anthrax, there is the chance that the organism may not be identified correctly.

Rapid diagnostic tests for anthrax and its proteins include polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and direct fluorescent antibody (DFA) testing. Currently, these tests are only available at national reference laboratories.

Treatment

• Inhalation anthrax: As previously stated because inhalation anthrax moves quickly throughout the body, doctors will begin antibiotic treatment right away even before a firm diagnosis is made through lab testing.
  
  
  • Ciprofloxacin (Cipro), doxycycline (Vibramycin), and penicillin are FDA-approved antibiotics for treatment of anthrax. Experts currently recommend ciprofloxacin or other drugs in the same class for adults who are assumed to have inhalation anthrax infection. Penicillin and doxycycline may be used once organism culture sensitivities are known.
    
    
  • Traditionally, ciprofloxacin and other antibiotics in that class are not recommended for use in children younger than 16-18 years because of a weak theoretical link to permanent joint disorders. Balancing these small risks against the risk of death and the possibility of infection with a resistant strain of anthrax, experts recommend that ciprofloxacin nonetheless be given to children in appropriate doses.
    
    
  • Because there is a risk the infection will recur, victims are treated with antibiotics for at least 60 days.
  
  
• Skin anthrax: Treatment of skin anthrax with antibiotics generally prevents the disease from progressing to the entire body although the black tissue and scar continue to form. Although previous guidelines have suggested treating skin anthrax with 7-10 days of therapy, recent recommendations suggest treatment for 60 days in the setting of bioterrorism, thus assuming the person may also have been exposed to inhalational anthrax.
  
  
• In pregnant women, experts recommend that ciprofloxacin be given after exposure as a preventive medication following exposure to an anthrax attack.

Prevention

After exposure, the antibiotics ciprofloxacin, or doxycycline may be prescribed by a doctor and the medications are usually taken for 60 days. A vaccination series to protect against anthrax consists of 6 injections given over a period of 18 months, followed by booster shots every year.

If a biological warfare attack is expected or may have occurred, people who have not had the vaccine may be given ciprofloxacin or doxycycline for at least 4 weeks.

For more on anthrax, see Anthrax.

PLAGUE

Plague is another infection that can strike humans and animals. It is caused by the bacteria Yersinia pestis, which has been the cause of 3 great human pandemics in the 6th, 14th, and 20th centuries. Throughout history, the oriental rat flea has been largely responsible for spreading bubonic plague. After the flea bites an infected animal, the organisms can multiply inside the flea. When an infected flea attempts to bite again, it vomits clotted blood and bacteria into the victim's bloodstream and passes the infection on to the next victim, whether small mammal (usually rodent) or human.

Although the largest outbreaks of plague have been associated with the rat flea, all fleas should be considered dangerous in areas where plague may be found. The most important vector (a vector is an animal that can transmit the disease) in the United States is the most prevalent flea of rock squirrels and California ground squirrels. The black rat has been most responsible worldwide for the continuing spread of plague in urban epidemics.

Signs and symptoms

People infected with plague may suddenly develop high a fever, painful lymph nodes, and have bacteria in their blood. Some victims with the bubonic form of the disease may develop secondary pneumonic plague (a disease similar to pneumonia). Plague is contagious and when the victim coughs, plague can spread. Pneumonic plague is the most severe form of the disease and if untreated, most people die.

As few as 1-10 organisms are enough to infect humans or other animals including rodents. During the early phase, the germs usually spread to lymph nodes near the bite, where swelling occurs. The infection then spreads to other organs such as the spleen, liver, lungs, skin, mucous membranes, and later, the brain.

In the United States, most victims with human plague have the bubonic form. If the organisms were used as a biological warfare agent, it most likely would be spread through the air and inhaled by victims. The result would be primary pneumonic plague (epidemic pneumonia). If fleas were used as carriers of disease, bubonic or septicemic (blood infection) plague would result.

• Bubonic plague: Swollen lymph nodes (called buboes) develop 1-8 days after exposure. Their appearance is associated with the onset of sudden fever, chills, and headache, which often are followed by nausea and vomiting several hours later. The buboes become visible within 24 hours and cause severe pain. Untreated, septicemia (blood poisoning) develops in 2-6 days. Up to 15% of bubonic plague victims develop secondary pneumonic plague and thus can spread illness from person to person by coughing.
  
  
• Septicemia plague: Septicemia plague may occur with bubonic plague. The signs and symptoms of primary septicemic plague include fever, chills, nausea, vomiting, and diarrhea. Later, bleeding in the skin may develop, hands and feet may lose circulation, and tissue may die.
  
  
• Pneumonic plague: Pneumonic plague may occur primarily from inhaling organisms in the air or from exposure to infected blood. Victims typically have a productive cough with blood-tinged sputum within 24 hours of symptom onset.

Diagnosis

The diagnosis of bubonic plague may be made if the victim has painful lymph glands and other common symptoms, especially if the victim has been exposed to rodents or fleas. But if the victim is not in an area where plague is present and symptoms are typical of other illnesses, the diagnosis may be difficult.

The doctor may view under a microscope a sample of sputum from a productive cough or the fluid from a swollen lymph gland.

Samples may grow in the laboratory and indicate plague within 48 hours and blood tests may also be performed.

Treatment

Victims of suspected plague will be isolated for the first 48 hours after treatment begins. If pneumonic plague is present, isolation may last for 4 more days. Since 1948, streptomycin has been the treatment of choice for plague but other antibiotics may be given.

If treated with antibiotics, buboes typically become smaller in 10-14 days and do not require drainage. Victims are unlikely to survive primary pneumonic plague if antibiotic therapy is not begun within 18 hours of the beginning of symptoms. Without treatment, 60% of people with bubonic plague die, and 100% with pneumonic and septicemic forms die.

Prevention

Fleas always must be targeted for destruction before the rodents, because killing rodents may release into the environment massive amounts of infected fleas, which will be hungry for a blood meal and, in the absence of rodents, the fleas will seek out any warm-blooded animal including humans and infect them. Pesticides have been successful in getting rid of rats and other animal hosts. Public education about how plague spreads is an important part of prevention.

People who have been exposed to pneumonic plague and those who have been exposed to organisms in the air may be treated with antibiotics such as tetracycline or doxycycline for 6 days.

Contacts with victims who have bubonic plague do not need preventive medication. But people who were in the same environment as those who are infected may need preventive antibiotics. A previously FDA-approved plague vaccine is no longer manufactured. It was useful against the bubonic form of plague but not the more serious pneumonic (lung) form of plague, which is the kind most often expected in a terrorist incident. A new vaccine effective against all varieties of plague is under development.

Only those at high risk for plague should be given the vaccine. This might include military troops and personnel working in areas where plague exists and lab personnel working with the organism. The current vaccine against bubonic plague by flea bite does not have the same effectiveness against the organisms released in the air.

For more on plague, see Plague.

CHOLERA

Cholera is an acute and potentially severe gastrointestinal disease (stomach and intestines) caused by the bacteria Vibrio cholerae. This agent has been investigated in the past as a biological weapon. Cholera does not spread easily from human to human, so it appears that major drinking water supplies would have to be profusely contaminated for this agent to be effective as a biological weapon.

Cholera normally can infect water or food that becomes contaminated by human bowel waste. The organism can survive for up to 24 hours in sewage and as long as 6 weeks in certain types of relatively impure water containing organic matter. It can withstand freezing for 3-4 days, but it is killed readily by dry heat, steam, boiling, short-term exposure to ordinary disinfectants, and chlorination of water.

The toxin causes a person's intestines to create massive amounts of fluid that then produces thin, grayish brown diarrhea.

Signs and symptoms

Depending on how many organisms a person drinks or eats, the illness could begin within 12-72 hours. The symptoms start suddenly with intestinal cramps and painless (rice-water appearing) diarrhea. Vomiting, feeling ill, and headache often accompany the diarrhea, especially early in the illness.

Fever is rare. If untreated, the disease generally lasts 1-7 days. During the illness, the body loses great amounts of fluid, so it is important during recovery to replace fluids and balance electrolytes (such as sodium and potassium).

Children may experience seizures and cardiovascular imbalances severe enough to cause heart problems. The rapid loss of body fluids often leads to more severe illness. If not treated, up to half of children with cholera may die.

Diagnosis

The doctor may examine a sample of the stool under a microscope to confirm the diagnosis. Symptoms alone are usually enough to identify cholera.

Treatment

Fluids and electrolytes need to be replaced because the body has lost large amounts of fluids through the vomiting and diarrhea. Doctors may encourage the person to drink, but if someone continues to vomit or has frequent stools, an IV may be used to replace the fluid lost.

Antibiotics such as tetracycline or doxycycline shorten the duration of diarrhea and reduce fluid losses. The antibiotics ciprofloxacin or erythromycin also may be used for a few days.

Prevention

A live vaccine is available for use in those considered to be at risk for exposure. The vaccine is protective for only about half of those immunized, and protection lasts for no more than 6 months. The vaccination schedule is an initial dose followed by another dose 4 weeks later, with booster doses every 6 months.

An inactivated oral vaccine is safe and provides rapid short-term protection. It requires 2 doses and has about 85% efficacy lasting 2-3 years for 2 different types of cholera.

TULAREMIA

Tularemia is an infection that can strike humans and animals. It is caused by the bacterium Francisella tularensis. The disease causes fever, localized skin or mucous membrane ulcerations, regional swelling of lymph glands, and occasionally pneumonia.

G.W. McCay discovered the disease in Tulare County, California, in 1911. The first confirmed case of human disease was reported in 1914. Edward Francis, who described transmission by deer flies via infected blood, coined the term tularemia in 1921. It has been considered an important biological warfare agent because it can infect many people if dispersed by the aerosol route.

Rabbits and ticks most commonly spread tularemia in North America. In other areas of the world, tularemia is transmitted by water rats and other aquatic animals.

The bacteria are usually introduced into the victim through breaks in the skin or through the mucous membranes of the eye, respiratory tract, or GI tract. Ten virulent organisms injected under the skin from a bite or 10-50 organisms breathed into the lungs can cause infection in humans. Hunters may contract this disease by trapping and skinning rabbits in some parts of the country.

Signs and symptoms

Tularemia can be divided into 2 forms: the ulceroglandular (75% of cases) and typhoidal (25% of cases). Victims with the ulceroglandular type have sores on the skin or mucous membranes, large lymph nodes, or both. Those with typhoidal tularemia have smaller lymph nodes and no skin sores.

After 3-6 days, people with the ulceroglandular form of the disease develop a group of symptoms: fever, chills, headache, cough, and muscle aches. They may also have chest pain, vomiting, joint pain, sore throat, abdominal pain, diarrhea, shortness of breath, back pain, or neck stiffness.

A sore up to an inch across may appear on the skin in about 60% of people and is the most common sign of tularemia. If the bite associated with infection was from an animal carrying the disease, the sore is usually on the upper part of a person's body, such as on the arm. If the infection came from an insect bite, the sore might appear on the lower part of the body, such as on the leg.

Enlarged lymph nodes are seen in about 85% of victims and may be the initial or the only sign of infection. Although enlarged lymph nodes usually occur as single lesions, they may appear in groups. Enlarged lymph nodes may come and go and last for as long as 3 years. When swollen, they may be confused with buboes of bubonic plague.

Sore throat and other complications may occur in up to 25% of people with tularemia.

People with either type of tularemia may develop pneumonia. They may have a productive or nonproductive cough and possibly chest pain, shortness of breath, and vomit blood.

Diagnosis

Tularemia can be diagnosed by growing the bacteria in the laboratory from samples taken of blood, ulcers, sputum, and other body fluids. Blood tests may not be helpful.

Treatment

Victims with tularemia who do not receive appropriate antibiotics may have a prolonged illness with weakness and weight loss. Treated properly, very few people with tularemia die. A 14-day course of streptomycin is effective treatment for tularemia. Gentamicin is also effective. Although tetracycline and chloramphenicol have also been found effective, they are associated with significant relapse rates.

Although laboratory-related infections with this organism are common, human-to-human spread is unusual. Victims do not need to be isolated from others.

Prevention

An antibiotic given after exposure to tularemia is difficult, because the ideal drug, streptomycin, must be given by injection. Tetracycline is effective after exposure to an aerosol of tularemia if given within 24 hours of the exposure and taken for 14 days.

A vaccine has been developed and used in humans since 1940. In the 1960s, a more purified vaccine was developed. Extensive studies have demonstrated that the vaccine protects humans against the organism released into the air. Immunization with the vaccine prevents the typhoidal type and lessens the effects of the ulceroglandular form of tularemia.

BRUCELLOSIS

Brucellosis is an infection of domesticated and wild animals that can be transmitted to humans. It is caused by an organism of the genus Brucella. The organism infects mainly cattle, sheep, goats, and other similar animals causing death of developing fetuses and genital infection. Humans, who usually are infected incidentally by contact with infected animals, may develop numerous symptoms in addition to the usual ones of fever, general illness, and muscle pain.

The disease often becomes long-term and may return, even with appropriate treatment. The ease of transmission through the air suggests that these organisms may be useful in biological warfare.

Each of 6 different species may tend to infect certain animal species. Four are known to cause illness in humans. Animals may transmit organisms during a miscarriage, at the time of slaughter, and in their milk. Brucellosis is rarely, if ever, transmitted from human to human.

Certain species can enter animal hosts through skin abrasions or cuts, the eye membranes, the respiratory tract, and the GI tract. Organisms grow rapidly and eventually go to the lymph nodes, liver, spleen, joints, kidneys, and bone marrow.

Signs and symptoms

Victims may have a fever or a long-term infection or just a local inflammation. The disease may appear suddenly or develop slowly anywhere from 3 days to several weeks after exposure. Symptoms include fever, sweats, fatigue, loss of appetite, and muscle or joint aches. Depression, headache, and irritability occur frequently. In addition, infection of bones, joints, or the genitourinary tract may cause pain. Cough and chest pain also may be noted.

Symptoms often last 3-6 months and occasionally for longer than a year. Different species of the organism can cause different symptoms from skin sores to low back pain to liver disease.

Diagnosis

The doctor will want to know about any exposure to animals, animal products, or environmental exposures in making the diagnosis. Military troops exposed to a biological attack and who have fever are likely candidates for this illness. Environmental samples may show the presence of this organism in the attack area. Laboratory tests and cultures of blood or body fluid samples including bone marrow may be performed.

Treatment

Therapy with a single drug has resulted in a high relapse rate, so a combination of antibiotics should be prescribed. A 6-week course of doxycycline along with streptomycin for the first 2 weeks is effective in most adults with most forms of brucellosis.

Prevention

Animal handlers should wear appropriate protective clothing when working with infected animals. Meat should be well cooked, and milk should be pasteurized. Laboratory workers need to take appropriate cautions in handling the organism.

In the event of a biological attack, the standard gas mask should protect adequately from airborne species. No commercially available vaccine exists for humans.

Q FEVER

Q fever is a disease that also affects animals and humans. It is caused by the bacteria Coxiella burnetii. A sporelike form of the organism is extremely resistant to heat, pressure, and many cleaning solutions. This allows the germs to live in the environment for long periods under harsh conditions. In contrast, the disease it causes in humans is usually not harmful, although it can be temporarily disabling. Even without treatment, most people recover.

The organism is extremely infectious. The potential of the organism as a biological warfare agent is related directly to its ability to infect people easily. A single organism is capable of producing infection and disease in humans. Different strains have been identified worldwide.

• Humans have been infected most commonly by contact with domestic livestock, particularly goats, cattle, and sheep. The risk of infection is increased greatly if humans are exposed while these animals are giving birth to young. Large numbers of the germs may be released into the air as an animal gives birth. Survival of the organism on surfaces, such as straw, hay, or clothing, allows for transmission to other people who are not in direct contact with infected animals.
  
  
• People can become infected by breathing the organisms.
  
  

Signs and symptoms

Humans are the only hosts that commonly develop an illness as a result of the infection. The illness may begin within 10-40 days. There is no typical pattern of symptoms, and some people show none at all. Most people appear mildly to moderately ill.

Fever (can go up and down and last less than 13 days), chills, and headache are the most common signs and symptoms. Sweating, aches, fatigue, and loss of appetite are also common. Cough often occurs later in the illness. Chest pain occurs in a few people. Sometimes there is a rash. Other symptoms such as headache, facial pain, and hallucinations have been reported.

Sometimes problems in the lungs are seen on chest x-rays. And some people may seem to have acute hepatitis because of their liver involvement. Others may develop a heart condition called endocarditis.

Diagnosis

Blood tests may help in making the diagnosis of Q fever.

Treatment

Tetracycline has been the main drug used since the 1950s. When initiated within the first few days of the illness, treatment significantly shortens its course. Other antibiotics, such as erythromycin and azithromycin, are also effective.

People with chronic Q fever who develop endocarditis may die, even with appropriate treatment.

Prevention

Although an effective vaccine (Q-Vax) is licensed in Australia, all Q fever vaccines used in the United States are under study. Q fever can be prevented by immunization.