Web cbwinfo.com

Key Diagnostic Tests.

• Diarrhea with rice water stools.
• Detection of bacteria in excreta (by staining or motility test)
• Excreta are essentially free of red or white cells

Symptoms and effects.

Cholera is an acute disease of the gastrointestinal system (digestive tract) of man. There is a sudden onset with nausea, vomiting, profuse watery diarrhea, rapid loss of body fluids, electrolyte imbalance, toxemia, and collapse. Infection usually comes through contact with contaminated fecal matter or contaminated water. The incubation period is 1-5 days (average of 3 days). The loss of water arises from effects of a bacterial toxin on the small intestine rather than the large intestine (as is typical in diarrhea).

An adult cholera victim. The hands show wrinkled skin, known as the "Washer Woman's sign" because the body has lost so much water that it cannot maintain cell turgor and the skin collapses.

Source: Centers for Disease Control Public Health Image Library Image #1939.

Medical and Physical Countermeasures.

Vaccination (Immunoprophylaxis)

A vaccine is available for those considered at risk of exposure. However, it only provides 50% protection and last for no more than six months. The initial vaccination is followed by a second one 4 weeks later and a booster every six months thereafter.

Antibiotics

Treatment with tetracycline (500 mg every 6 hours for 3 days) increases the effectiveness of rehydration by killing the microorganism and hence lowering the volume and duration of the diarrhea. Ciprofloxacin can also be used 500 mg every 12 hours for 3 days or erythromycin at 500 mg every 6 hours for 3 days is also effective.

Supportive care

The first requirement is to replace lost body fluids and electrolytes (salts). Oral rehydration can be used but in severe cases with persistent vomiting or high rates of stool loss it may be necessary to use intravenous fluid replacement.

Decontamination

The organism is readily killed by steam, dry heat, boiling, common disinfectants, and by chlorination or ozonization of water.

Vibrio cholera can survive temperatures of up to 117°C (275°F) and thrives in salty water or water contaminated with organic matter for up to six weeks. The organism cannot survive in pure water and so is a poor candidate for contamination of chlorinated water supplies in most countries. It could be used against forces in the field away from water purification facilities or against poor areas lacking safe water supplies.

Terrorist Acquisition and Attempted Use.

• No specific incidents known.

Antibiotic Resistance.

Some cholera outbreaks show sporadic cases of antibiotic resistance. However, these are not classical cases of acquired antibiotic resistance and the resistance does not spread and stabilize in V. cholera populations.

The consensus is that V. cholera does not support the replication of plasmids and that it is therefore unlikely that antibiotic resistance will be a problem in the event of its use as a biological weapon.

Return to Top

The History and Natural History of Cholera.

Cholera was first seen to infect humans in 1817 in the Ganges delta of Bengal where abundant organic material in the brackish waters of the delta that came from the burgeoning city of Calcutta allowed it to flourish. Prior to this, the bacterium appears to have been quite harmless to man, and many samples isolated from the wild are still harmless. The difference between the pathogenic and non-pathogenic strains is the presence of a set of genes encoding the cholera toxin. The genes appear to have come from another, unidentified and likely to remain so, species of bacterium by a mechanism known as transposition. Transposition is carried out by vagabondish pieces of DNA called transposons that carry a small number of genes that give new properties to a recipient microorganism and genes that give it the ability to move between hosts. Transposons are of particular concern to medicine because they often carry genes for antibiotic resistance and can play a role in the rapid spread of resistance to a new antibiotic across species boundaries.

The disease spread rapidly from India in the first of seven cholera pandemics, ending short of Western Europe in 1823. The second pandemic began in 1826, reaching Moscow in 1830 and London by 1832.

The disease killed quickly and efficiently as the loss of fluids in almost continual watery diarrhea (rice water stools) caused the blood to become almost syrup-like in consistency and confounding the classical treatment of bleeding for many disease. About half of all victims died with their faces sunken and black-rimmed eyes, often looking like corpses before death and with a cold, clammy skin. Victims suffered violent convulsions of the leg and stomach muscles, with some still twitching so violently after death that they threw off their winding sheets.

The disease was blamed upon any vulnerable minority, notably Jews and Gypsies, as the disease ravaged the uneducated poor. Riots, assaults upon doctors and conspiracy theories abounded. Cholera was killing more people per month in London in the mid-19th Century than did the plague during the Great Plague of 1665.

The disease was finally beaten back in Britain by taking away the shelter from which it would launch its anabasis - the water supply. Slowly, and often against opposition in the name of individual liberty, improved personal hygiene was made fashionable. Sewer systems and water treatment facilities were built and the water and waste were separated. Chemical treatment, notably chlorination, killed the bacterium in the water supply, making it safe to drink.

Outbreaks in London in 1849 and 1854 were landmarks in the study of disease when the famous London physician and pioneer of anesthesia, Dr. John Snow, used the occurence of clusters of disease to identify a common factor and source of the disease, a contaminated well. Taking the well out of service by removing the pump handle abruptly stopped further cases of the disease.

The bacterium was first seen in water in 1854, but it took thirty years to demonstrate that it was the causative agent.

Simply giving water to dehydrated patients did not work as they lost it as rapidly as it was given. Early Russian attempts at transfusion showed a little success, but it took until the 1960's to develop the simple, cheap and effective mixture of salts and glucose that could be given orally to control water loss and save many lives for pennies apiece. The mechanism by which the bacterium stimulates the intestine to start pumping out fluids is now well understood at the molecular level.

Even as the battle was being won against the original Vibrio cholerae, known as serotype 01, new, hardier strains began to appear. The pandemics of the mid-20th Century were found to be due to a variant called "El Tor" and more recently serotype 0139 has been implicated in an eighth pandemic that began in the 1990's.

The complete DNA sequence of the genome of V. cholerae El Tor was published in August 2000. The genome is unusual for a bacterium in that it has two distinct chromosomes.

The fact that Vibrio cholerae survives in untreated water makes it an attractive weapon in underdeveloped areas and in areas where the infrastructure has already been damaged by war. Japan is claimed to have experimented extensively with it during its invasion of China and it has been claimed that it actually used it in an extensive campaign in 1942.

Chinese forces were being resupplied by the British and US through Burma (now Myanmar) by a major airlift known as "flying the hump." In an effort to disrupt the operation on the Chinese side using V. cholerae in Yunnan province, where supplies were landed and distributed. In early 1942, a subsidiary of Unit 731, Unit 113, campaigned along the Nu river contaminating water supplies as it went, A major bombing raid on the city of Baoshan largely destroyed the city and ceramic bombs were used to contaminate the ruins with bacteria. The combination of destruction and contamination created a tide of refugees who carried agents with them. Between May and June 1942, approximately 60,000 are believed to have died of cholera as a result of these attacks. A similar campaign was conducted against Communist forces in Yunnan province in 1943 with up to 200,000 dying as a result. The agent was spread by a number of means, including deliberate contamination of water supplies and leaving contaminated food and water for refugees.