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Cholera: Questions & Answers

ABOUT CHOLERA

Cholera is an acute intestinal infection caused by the bacterium Vibrio cholerae. It is caused by the O1 and O139 serogroups of V. cholerae which produce a toxin, and this is responsible for the clinical symptoms associated with the disease. Other serogroups exist, however these do not produce the disease known as cholera.

Rita Colwell has shown that sequencing data confirms V. cholerae is a "versatile organism", (1) able to live in several habitat types, as well as to infect the human gastrointestinal tract. In the water column, the presence of cholera is shown to be associated with copepods, a marine plankton that is dependent upon water temperature, and the food supply of copepods, which is related to algae, which blooms robustly with sediments and contaminents, including feces.

While cholera is able to infect an individual directly through exposure to the pathogen in the environment, it is also spread through consumption of contaminated food or drinking water, and person-to-person contact. These factors are all potentially related to daily interactions one has with other individuals and households. Studies have shown that disease diffusion in social networks is affected by geographic space and the local environment.

Among people who develop symptoms, experts report 70% to 80% have mild or moderate symptoms, while the rest may develop acute watery diarrhoea with dehydration. Severe dehydraton can lead to death if untreated.

People with low immunity – such as malnourished children or people living with HIV – are typically at a greater risk of death if infected. (2)


HAITI CHOLERA

V cholerae O1 is classified into 2 major biotypes: classic and El Tor. Currently, El Tor is the predominant cholera pathogen. Organisms in both biotypes are subdivided into serotypes according to the structure of the O antigen, as follows:

  • Serotype Inaba - O antigens A and C
  • Serotype Ogawa - O antigens A and B
  • Serotype Hikojima - O antigens A, B, and C

According to lab reports from the Centers for Disease Control and Prevention, the cholera strain causing the current outbreak in Haiti is most similar to cholera strains found in South Asia: Vibrio cholerae serogroup 01, serotype Ogawa. O1 strains of cholera are known to be of epidemic and pandemic potential.

PATHOPHYSIOLOGY (3)

According to an article published in emedicine, by Sajeev Handa, Director, Division of Hospital Medicine, Department of Medicine, Rhode Island Hospital, the infectious dose of bacteria required to cause clinical disease varies by the mode of administration. If ingested with water, the infectious dose is 103 -106 organisms. When ingested with food, fewer organisms (102 -104 organisms) are required to produce disease.

The use of antacids, histamine receptor blockers, and proton pump inhibitors increases the risk of cholera infection and predisposes patients to more severe disease as a result of reduced gastric acidity. The same applies to patients with chronic gastritis secondary to Helicobacter pylori infection or those who have undergone a gastrectomy.

V cholerae O1 and V cholerae O139 cause clinical disease by producing an enterotoxin that promotes the secretion of fluid and electrolytes into the lumen of the small intestine. The enterotoxin is a protein molecule composed of 5 B subunits and 2 A subunits. The B subunits are responsible for binding to a ganglioside (monosialosyl ganglioside, GM1) receptor located on the surface of the cells that line the intestinal mucosa.

The activation of the A1 subunit by adenylate cyclase is responsible for the net increase in cyclic adenosine monophosphate (cAMP). cAMP blocks the absorption of sodium and chloride by the microvilli and promotes the secretion of chloride and water by the crypt cells. The result is watery diarrhea with electrolyte concentrations isotonic to those of plasma.

Fluid loss originates in the duodenum and upper jejunum; the ileum is less affected. The colon is usually in a state of absorption because it is relatively insensitive to the toxin. However, the large volume of fluid produced in the upper intestine overwhelms the absorptive capacity of the lower bowel, resulting in severe diarrhea.

The enterotoxin acts locally and does not invade the intestinal wall. As a result, few neutrophils are found in the stool.

Dr. Hanada reports Toxigenic V cholerae O1 has been shown to survive in crabs boiled for 8 minutes (4), but not in crabs boiled for 10 minutes. Transmission via direct person-to-person contact is rare. 
Please see attached pdf DETERMINATION OF THE THERMAL DEATH OF VIBRIO CHOLERAE IN CRAYFISH MEAT HOMGENATE.

It is of interest that V cholerae is unable to survive in an acidic environment. Therefore, any condition that reduces gastric acid production increases the risk of acquisition. In addition, although the pathophysiology is not understood, individuals with blood group O are at increased risk of developing El Tor cholera.


SYMPTOMS OF CHOLERA

Most people infected with cholera bacterium have mild diarrhea or no symptoms at all. The CDC reports estimates of 7% of people infected with Vibrio cholerae 01 have illness requiring treatment at a health center. Cholera patients should be evaluated and treated quickly. With proper treatment, even severely ill patients can be saved. Prompt restoration of lost fluids and salts is the primary goal.


SYMPTOMS OF MODERATE OR SEVERE CHOLERA

- Profuse watery diarrhea
- Vomiting
- Leg cramps

SIGNS AND SYMPTOMS OF DEHYDRATION

- Restlessness and irritability
- Sunken eyes
- Dry mouth and tongue
- Increased thrist
- Skin goes back slowly when pinched
- Decreased Urine
- Infants: decreased tears, depressed fontanels

SEVERE DEHYDRATION SYMPTOMS

- Lethargy or unconsciousness
- Very dry mouth and tongue
- Skin "tents-up" when pinched (goes back VERY slowly)
- Weak or absent pulse
- Low blood pressure
- No or minimal urine


CAN CHOLERA BE PREVENTED?

The World Health Organization says "Yes", and of course, this means do not ingest the bacteria, which in high risk areas requires one be scrupulous and take basic precautions: washing of hands, especially before food preparation and eating; thorough cooking of food (perhaps for 8 minutes or more if shell fish or crabs are on the menu) and consumption while hot; boiling, filtering, or chemical treatment of drinking water; and use of sanitary facilities and use of soap with clean water, or waterless hand sanitizer if soap/clean water is unavailable. IF no soap or sanitizer is available, scrub hands often with ash, or sand, and rinse with safe water.

  • Drink only water that has been boiled, filtered sufficient to strain out the cholerea bacterium, or disinfected with chlorine, iodine or other suitable products. Beverages such as hot tea or coffee made from boiled water, wine, beer, carbonated water or soft drinks, and bottled or packaged fruit juices are usually safe to drink.
  • Avoid ice, and popsicles, unless you are sure that it is made from safe water and fruit not contaminated with water (from rinsing, or otherwise).
  • Eat food that has been thoroughly cooked and is still hot when served. Cooked food that has been held at room temperature for several hours and served without being reheated can be an important source of infection.
  • Avoid raw seafood and other raw foods. The exceptions are fruits and vegetables that you have peeled or shelled yourself.
  • Boil unpasteurized milk before drinking it.
  • Ice cream from unreliable sources is frequently contaminated and can cause illness. If in doubt, avoid it.
  • Be sure that meals bought from street vendors are thoroughly cooked in your presence and do not contain any uncooked foods.

V cholerae is unable to survive in an acidic environment. Therefore, any condition that reduces gastric acid production increases the risk of acquisition. In addition, although the pathophysiology is not understood, individuals with blood group O are at increased risk of developing El Tor cholera.


DIAGNOSIS OF CHOLERA

Diagnosis is generally confirmed via identification of V cholerae in the stool. The organism may be detected directly with dark-field microscopy examination of a wet mount of fresh stool; chaotic motility is observed. The serotype may be determined by immobilization with Inaba-specific or Ogawa-specific antiserum.

Laboratory isolation requires a selective medium. V cholerae grows as a flat, yellow colony on thiosulfate-citrate-bile salts-sucrose agar or taurocholate-tellurite-gelatin agar.

More recently, polymerase chain reaction (PCR) has been used with a high degree of sensitivity and specificity.

 

TREATMENT OF CHOLERA

The goal of thereapy is to replenish fluids lost due to vomiting and diarrhea.
Many Patients can be rehydrated entirely with oral rehydration solutions (ORS)
Even if the patient gets intrevenous (IV) rehydration, he/she should start drinking ORS as soon as he/she is able.

ORS, which is essentially a mixture of salt, water, and sugar, has earned the label "a simple solution" because it is made from basic, inexpensive ingredients, and can be easily learned. However, it is the position of the CDC that an appropriate oral rehydraton salt solution such as Rehydralyte or WHO Formula Oral Rehydration Salts (ORS) be used, since these are assured to contain the proper balance of electrolytes.

Patients with sever dehydration of those with intractable vomiting need intravenous therapy with Ringer's lactate solution. IV fluid should be given quickly to restor the circulation, followed by oral fluids as soon as possible.

HOW MUCH FLUID SHOULD BE GIVEN?

Fluid replacement needs to be individualized, based upon the the degree of dehydration. Severely dehydrated adults may require several liters of fluid immediately to restore adequate circulation volume. It is important to remember that cholera patients will have significant on-going fluid losses that also need to be monitored, and replaced.


Antibiotic treatment is less important than rehydration. However, antibiotics will decrease the duration of the illness

Antibiotics recommendations for Haiti 2010 cholera outbreak from the CDC below, including Zinc supplementation. See PDFs below for complete, downloadable posters in English, French, Spanish and Haitian Creole.

antibiotics cdc recommendation

(5) Above graphic taken from CDC poster- Defeating Cholera:Clinical Presentation and Management for Haiti Cholera Outbreak, 2010.



Articles Referenced:

1) Rita Colwell: Infectious disease and environment: cholera as a paradigm for waterborne disease - http://scielo.isciii.es/scielo.php?pid=S1139-67092004000400008&script=sci_arttext

(2) Source: WHO fact sheet no. 107, June 2010 - http://www.who.int/mediacentre/factsheets/fs107/en/index.html

 (3) Sajeev Handa: Cholera - http://emedicine.medscape.com/article/214911-overview

(4) Robert M. Grodner and Arthur Hinton, Jr: DETERMINATION OF THE THERMAL DEATH OF VIBRIO CHOLERAE IN CRAYFISH MEAT HOMGENATE - pdf attached.

(5) CDC Poster - Defeating Cholera:Clinical Presentation and Management for Haiti Cholera Outbreak, 2010.PDF