Web cbwinfo.com

Key Diagnostic Tests.

• The "classic" combination of signs is a rose-colored rash, relative bradycardia and leukopenia and prolonged fever. This combination is only rarely seen
• Isolation of Salmonella typhi from blood, bone marrow, or stool samples;
• Relative leukopenia;
• Serology is not always helpful.

Symptoms and effects.

After an incubation period of 7-14 days, a systemic (involving the whole body) infection develops with symptoms including a prolonged fever (40-41°C, 104-106°F lasting up to 6-8 weeks), general malaise, and chills, swelling of the lymph nodes, rose-colored spots on the chest and abdomen that can become hemorrhagic, swelling of the spleen, ulceration of the intestines, and constipation or diarrhea. The disease can kill (about 10-20% mortality if untreated), and is extremely incapacitating to those who survive.

The disease can take 3-4 weeks to run its course and patients with complications will need extensive monitoring and may need surgery for damage to the gastrointestinal tract or peritonitis.

Return to Top

 Medical and Physical Countermeasures.

 Vaccination (Immunoprophylaxis)

There now is an oral typhoid vaccine and a new single dose injectable vaccine that produces fewer side effects than the older two dose injectable vaccine. Both vaccines are equally effective and offer 65-75% protection against the disease.

Antibiotics

• Amoxicillin
• Cefotaxime
• Chloramphenicol
• Cotrimoxazole
• Fluoroquinolines, e.g ciprofloxacin.

Antibiotic resistance in S. typhi is well known and antibiotic resistance should be tested before beginning therapy

Supportive care

Anti-inflammatory steroids delivered intravenously to combat inflammation. Complications including bowel perforation should be treated surgically as clinically necessary.

Decontamination

Contaminated materials can be cleared by pasteurization, treatment with phenolic detergents, cooking, or boiling. S. typhi is susceptible to many disinfectants, including 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde, iodines, phenolics, formaldehyde

Agent Properties and Potential Uses

Salmonella typhi can spread rapidly through foods such as milk and shellfish and water. It has typically been contracted from contaminated water or through the use of contaminated water. Effective water monitoring and purification are key elements in control of the disease.

It can also be communicated between people and through contaminated objects. The bacterium is relatively hardy and can survive in water for 2-3 weeks. One pound of cells could effectively contaminate 1.5 to 2 million gallons of water. Contamination of the water supply is a likely route of attack with S. typhi, although it could also be delivered as an aerosol.

Terrorist Acquisition and Attempted Use.

• In 1972, arrested members of an extremist group, "The Order of the Rising Sun," were found to have cultures of S. typhi that they intended to contaminate the water supplies of major mid-western U.S. cities including Chicago and St. Louis.
• In September 1984, the Rajneesh cult of Antelope, Oregon is believed to have contaminated salad bars in local restaurants with the closely-related Salmonella enterica serovar typhimurium in an attempt to influence the outcome of a local election. Seven-hundred and fifty people were affected and the outcome of the operation was the collapse of the cult.

Antibiotic Resistance.

The genus Salmonella has been intensively studied by bacterial geneticists and molecular biologists and the transmission of antibiotic resistance within and into and out of the genus has been studied for many years.

As a Gram-negative bacillus, Salmonella is closely related to the molecular biologist's favorite Escherichia coli (there is even a large and authoritative textbook on the genetics of E.coli and S. typhimurium) and this makes it a prime candidate for engineering of antibiotic resistance in the development of a biological weapon.

Return to Top

The History and Natural History of Typhoid Fever.

Typhoid appears to be a disease that has been associated with man since close to the first appearance of hominids and it may have first infected human ancestors anywhere from 200,000 to two million years ago. The bacterium can survive in contaminated water, but does not have any host other than man. There are over 1,000 different strains of the bacterium of which only a few cause typhoid. A closely related bacterium Salmonella typhimurium causes a similar disease in the mouse, but does not affect man and the combination of the pathogen and the mouse is used as a model to study the human disease.

The primary target of the disease is the intestine. It attacks through tissues that are a part of the immune system called Peyer's patches. These tissues on the inner surface of the intestine are normally the first line of defense against food and water-borne infection, but the typhoid bacterium subverts them. It does not have the cell surface features that normally trigger a defensive response but it can fool the cells of the patches to take it in without attacking it. The infected tissue become inflamed and the intestine begins to lose function, leading to diarrhea or constipation. There may be bleeding of the intestine leading to bloody stools. In severe cases, the disease may punch holes in the intestine leading to peritonitis (infection of the abdominal cavity) and death.

Even if the patient recovers from the infection, it may leave residual damage, such as the formation of attachments of the damaged areas of the intestine to the abdominal wall, or the development of a chronic infection that leads to the patient becoming a carrier.

Typhoid Mary.

The most notorious carrier, but by no means the most destructive, was Mary Mallon: known as Typhoid Mary. She worked as a cook in domestic service in and around New York at the beginning of the 20th Century. She may have been the source of infection for several hundred people. Fifty cases and five deaths can be confirmed as being associated with her. Photographs of her show a well-kept and healthy woman who was also described as educated and literate. She was however, a woman of strong beliefs, stubborn and uncooperative.

Typhoid was a fact of life in the early 20th Century and public health authorities in New York actually had a fairly benign attitude towards carriers. People who agreed to give up jobs involving the handling of food were released from quarantine in return for occassional supervision to ensure compliance. Compliance was far from good and a large number absconded or broke the agreement. Public health authorities tried to convince Mary to either give up working as a cook or to have her gall bladder, the seat of chronic typhoid infection, removed. Mary had agreed to become a laundress but absconded and returned to work as a cook under a false name. She was detained for a second time after being identified during the investigation of another typhoid outbreak. This turned out to be a life sentence. She died of a stroke after 23 years in quarantine.

Mary refused to believe that she was a carrier because she had never suffered from the disease. The conventional wisdom of the time was that one could only become a carrier after suffering from the disease and Mary was actually the first case of a healthy carrier of an infectious disease to be demonstrated in the United States. She was not the only carrier in the New York area at the time: the estimate was that there were 2,000-4,000 typhoid carriers in New York City and there were also between 2,000 and 4,000 typhoid cases in New York every year. Mary had been responsible for only a handful of cases but she had left a clear trail that led an independent epidemiologist straight to her. Preliminary tests showed that she was excreting very large numbers of typhoid bacilli in her feces. Her refusal to have her gall bladder removed was perhaps not unreasonable. Surgery was still something of a gamble and there was no guarantee that the removal of the gallbladder would stop her being a carrier.

At the time of her first arrest there was at least one other carrier, a man called Tony Labella, who had caused more cases of typhoid (120) and deaths(7) than Mary and who was also under investigation. He fled to New Jersey and was no more cooperative than Mary but when brought back to New York he was allowed to work as a laborer in return for weekly meetings with public health officials.

This chronic infection appears to be peculiar to isolates from temperate climate zones. Mary was an immigrant from Ireland and she continue to secrete Salmonella typhi in her stool until she died. Strains native to Africa do not give rise to chronic infection. The commonest group of carriers are women in their 50's with gallstones.

Unit 731.

The Japanese biological warfare operation Unit 731 contaminated rivers on the border between Manchuria and the Soviet Union with Salmonella typhi during fighting in the region in 1939. The effort appears to have been without any effect as Soviet forces under the legendary General Georgi Zhukov inflicted a major defeat on the Imperial Japanese Army. Unit 731 was therefore unable to assess the effectiveness of the effort.