Cholera

Summary

Signs and Symptoms: Incubation period 4 hours to 5 days; average 2-3 days. Asymptomatic to severe with sudden onset. Vomiting, headache, intestinal cramping with little or no fever followed rapidly by painless, voluminous diarrhea. Fluid losses may exceed 5 to 10 liters per day. Without treatment, death may result from severe dehydration, hypovolemia and shock.

Diagnosis: Clinical diagnosis. ‘Rice water’ diarrhea and dehydration. Microscopic exam of stool samples reveals few or no red or white cells. Can be identified by darkfield or phase contrast microscopy, and by direct visualization of darting motile vibrio.

Treatment: Fluid and electrolyte replacement. Antibiotics (tetracycline, ciprofloxacin or erythromycin) may shorten the duration of diarrhea and, more importantly, reduce shedding of the organism.

Prophylaxis: A licensed, killed vaccine is available but provides only about 50 percent protection that lasts for no more than 6 months. Vaccination schedule is at 0 and 4 weeks, with booster doses every 6 months.

Isolation and Decontamination: Standard Precautions for healthcare workers. Personal contact rarely causes infection; however, enteric precautions and careful hand-washing should be employed. Bactericidal solutions (hypochlorite) would provide adequate decontamination.

OVERVIEW

Vibrio cholerae is a short, curved, motile, gram-negative, non-sporulating rod. There are two serogroups, O1 and O139, that have been associated with cholera in humans. The O1 serotype exists as 2 biotypes, classical and El Tor. The organisms are facultative anaerobes, growing best at a pH of 7.0, but able to tolerate an alkaline environment. They do not invade the intestinal mucosa, but rather "adhere" to it. Cholera is the prototype toxigenic diarrhea, which is secretory in nature. All strains elaborate the same enterotoxin, a protein molecule with a molecular weight of 84,000 daltons. The entire clinical syndrome is caused by the action of the toxin on the intestinal epithelial cell. Fluid loss in cholera originates in the small intestine with the colon being relatively insensitive to the toxin. The large volume of fluid produced in the upper intestine overwhelms the capacity of the lower intestine to absorb. Transmission is made through direct or indirect fecal contamination of water or foods, and by heavily soiled hands or utensils. All populations are susceptible, while natural resistance to infection is variable. Recovery from an attack is followed by a temporary immunity which may furnish some protection for years. The organism is easily killed by drying. It is not viable in pure water, but will survive 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 to 4 days. It is readily killed by dry heat at 117 ° C, by steam and boiling, by short exposure to ordinary disinfectants, and by chlorination of water.

HISTORY AND SIGNIFICANCE

This agent has purportedly been investigated in the past as a biological weapon. Cholera does not easily spread from person-to-person. Therefore, to be an effective biological weapon, major drinking water supplies would need to be heavily contaminated. Recent naturally occurring cholera epidemics in South America have shown the devastating consequences of this disease. Cholera spread quickly in Peru and neighboring countries, despite all attempts to curb the epidemic at an early stage. Over 250,000 symptomatic cases have been reported in Peru alone, and the epidemic has spread to other countries. The rate of symptomatic to asymptomatic cases is 1:400, a factor mitigating against effective use of cholera as a BW agent.

CLINICAL FEATURES

Cholera is an acute infectious disease, characterized by sudden onset with nausea, vomiting, profuse watery diarrhea with 'rice water' appearance, the rapid loss of body fluids, toxemia, and frequent collapse. Mortality can range as high as 50 percent in untreated cases.

DIAGNOSIS

After an incubation period varying from 4 hours to 5 days (average 2-3 days), presumably dependent upon the dose of ingested organisms, onset is usually rather sudden, although the clinical manifestations range from an asymptomatic carrier state to severe illness. Initially the disease presents with intestinal cramping and painless diarrhea. Vomiting, malaise and headache often accompany the diarrhea, especially early in the illness. If fever is present, it is usually low grade. Diarrhea may be mild or profuse and watery, with fluid losses exceeding 5 to 10 liters or more per day. Electrolyte loss can explain almost all clinical signs and symptoms. Without treatment, death may result from severe dehydration, hypovolemia and shock.

On microscopic examination of stool samples there are few or no red cells or white cells and almost no protein. The absence of inflammatory cells and erythrocytes reflects the non-invasive character of V. cholerae infection of the intestinal lumen. The organism can be identified in liquid stool or enrichment broths by darkfield or phase contrast microscopy, and by identifying darting motile vibrio. The organism must be transported using Cary-Blair medium and then streaked for isolation onto TCBS (Thiosulfate Citrate Bile Salt Sucrose) medium. Bacteriologic identification is not necessary to treat cholera, as it can be diagnosed clinically.

MEDICAL MANAGEMENT

Treatment of cholera depends primarily on replacement of fluid and electrolyte losses. This is best accomplished using oral rehydration therapy with the World Health Organization solution (3.5 g NaCl, 2.5 g NaHCO3, 1.5 g KCl and 20 g of glucose per liter). Intravenous fluid replacement is occasionally needed in patients with persistent vomiting or high rates of stool loss (>10ml/kg/hr). Antibiotics will shorten the duration of diarrhea and thereby reduce fluid losses. Tetracycline (500 mg every 6 hours for 3 days) or doxycycline (300 mg once or 100 mg every 12 hours for 3 days) is generally adequate. However, due to widespread tetracycline resistance, ciprofloxacin (500 mg every 12 hours for 3 days) or erythromycin (500 mg every 6 hours for 3 days) should be considered. For pediatric treatment, tetracycline (50 mg/kg/d divided into 4 doses x 3 days) can be used, as dental staining has only occurred after > 6 courses of treatment lasting 6 or more days. Alternates are erythromycin (40 mg/kg/d divided into 4 doses x 3 days), trimethoprim 8 mg and sulfamethoxazole 40 mg/kg day divided into 2 doses x 3 days, and furazolidone (5 mg/kg/d divided into 4 doses x 3 days or 7 mg/kg x one dose).

PROPHYLAXIS

Vaccine: A licensed, killed vaccine is available for use in those considered to be at risk of exposure, however, it provides only about 50 percent protection that lasts for no more than 6 months. The vaccination schedule is an initial dose followed by a second dose 4 weeks later, with booster doses every 6 months. An inactivated oral vaccine (WC/rBS), which is licensed in Europe, is safe and provides rapid short-term protection. Licensure in the US is anticipated. WC/rBS requires 2 doses and has approximately 85% efficacy lasting 2-3 years for both El Tor and classical biotypes. Live attenuated oral vaccines show much promise, and one, CVD 103-HgR (classical biotype), will probably be available by 1999. There are no O139 serogroup vaccines close to licensure, and none of the above mentioned vaccines provide cross-protection against O139. Primary infection with V. cholerae O1 serogroup also provides no immunity against O139.

Prevention: Since the major biological threat from this organism appears to be sabotage of food and water supplies, it would seem justified to state that optimal prophylaxis in these circumstances would not be of a medical nature but would be proper safeguarding of these supplies to prevent the sabotage. The best way to prevent cholera in an endemic environment is to avoid contaminated water, ice, fruits, vegetables and also raw or undercooked seafood. Personal contact rarely causes infection because of the high inoculum required for infection; however, enteric precautions and careful hand-washing should be employed. Bactericidal solutions (hypochlorite) would provide adequate decontamination.