CHOLERA

BY: Jaydeep Jhala 2012A5PS922P

PATHOGEN:
Cholera is an infection of the small intestine caused by the bacterium Vibrio cholerae. Vibrio cholerae is a Gram-negative, comma-shaped bacterium. Some strains of V. cholerae cause the disease cholera. V. cholerae is facultative anaerobic and has a flagellum at one cell pole. During infection,V. cholerae secretes cholera toxin, a protein that causes profuse, watery diarrhea. Colonization of the small intestine also requires the toxin coregulated pilus (TCP), a thin, flexible, filamentous appendage on the surface of bacterial cells. The main reservoirs of V. cholerae are people and aquatic sources such as brackish water and estuaries, often in association with copepods or other zooplankton, shellfish, and aquatic plants. Cholera infections are most commonly acquired from drinking water in which V. cholerae is found naturally or into which it has been introduced from the feces of an infected person. Other common vehicles include contaminated fish and shellfish, produce, or leftover cooked grains that have not been properly reheated. Transmission from person to person, even to health care workers during epidemics, is rarely documented.

SYMPTOMS:
Cholera is an acute, diarrheal illness caused by infection of the intestine with the bacterium Vibrio cholerae and is transmitted by contaminated food or water. The infection is often mild or without symptoms, but sometimes it can be severe. Approximately 5-10% of persons will have severe cholera which in the early stages includes:

profuse watery diarrhea, sometimes described as rice-water stools, vomiting rapid heart rate loss of skin elasticity dry mucous membranes

low blood pressure thirst muscle cramps restlessness or irritability

Persons with severe cholera can develop acute renal failure, severe electrolyte imbalances and coma. If untreated, severe dehydration can rapidly lead to shock and death. Profuse diarrhea produced by cholera patients contains large amounts of infectious Vibrio cholerae bacteria that can infect others if ingested, and when these bacteria contaminate water or food will lead to additional cases. Dispose of human waste appropriately to prevent the spread of cholera.

TREATMENT:
1) Rehydration therapy Rehydration is the cornerstone of treatment for cholera. Oral rehydration salts and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce fatalities to well under 1%. Low-osmolarity oral rehydration solution and cereal-based oral rehydration solution are the preferred replacement fluids for most patients. However, a modified rehydration solution called ReSoMal was formulated for rehydration of severely malnourished children. Breastfed children should also continue to breastfeed. Other types of fluids, such as juice, soft drinks, and sports drinks should be avoided. Safe (treated) water should be used to prepare oral rehydration solutions.

Reassess the patient every 1-2 hours and continue hydrating. The volumes and time intervals shown are guidelines provided on the basis of usual needs.
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If necessary, the rate of fluid administration can be increased, or the fluid can be given at the same rate for a longer period, to achieve adequate rehydration. If hydration is not improving, give fluids more rapidly. 200ml/kg or more of intravenous fluids may be needed during the first 24 hours of treatment. Similarly, the amount of fluid can be decreased if hydration is achieved earlier than expected.

Switch from intravenous hydration to oral rehydration solution once hydration is improved and the patient can drink. This will conserve IV fluids and reduce the risk of phlebitis and other complications. Nasogastric tubes can be used to administer oral rehydration solution if patient is alert but unable to drink sufficient quantities independently.

Patients should continue to eat a normal diet and breastfeeding children should continue to breastfeed during rehydration.

2) Antibiotic Treatment
Recommendations for the Use of Antibiotics for the Treatment of Cholera:

1)Oral or intravenous hydration is the mainstay of cholera treatment. 2) In conjunction with hydration, treatment with antibiotics is recommended for severely ill patients. It is particularly recommended for patients who are severely or moderately dehydrated and continue to pass a large volume of stool during rehydration treatment. Antibiotic treatment is also recommended for all patients who are hospitalized. 3) Antibiotic choices should be informed by local antibiotic susceptibility patterns. In most countries, Doxycycline is recommended as first-line treatment for adults, while azithromycin is recommended as first-line treatment for children and pregnant women. During an epidemic or outbreak, antibiotic susceptibility should be monitored through regular testing of sample isolates from various geographic areas. 4) None of the guidelines recommend antibiotics as prophylaxis for cholera prevention, and all emphasize that antibiotics should be used in conjunction with aggressive hydration. 5) Education of health care workers, assurance of adequate supplies, and monitoring of practices are all important for appropriate dispensation of antibiotics. Background 1. Mainstay of cholera treatment is hydration Intravenous and oral hydration are both associated with greatly decreased mortality and remain the mainstay of treatment for cholera.
2. Antibiotic effectiveness for the treatment of cholera

Antibiotics have been used as an adjunct to hydration treatment for cholera since 1964. Findings from randomized controlled trials evaluated the effectiveness of selected antibiotics on three main outcomes: stool output, duration of diarrhea, and bacterial shedding.These studies compared outcomes for cholera patients who were given both intravenous (IV) fluids and antibiotic treatment with those given IV fluids only. Findings indicate that antibiotics reduced volume of stool output by 8-92%, duration of diarrhea by 50-56%, and duration of positive bacterial culture by 26-83%. Antibiotic use for moderately and severely ill patients is also likely to reduce resource requirements. By decreasing duration of diarrhea and stool volume, antibiotics result in more rapid recovery and shorter lengths of inpatient stay, both of which contribute to optimizing resource utilization in an outbreak setting.

The majority of published studies exploring effectiveness of antibiotics for cholera patients have been done in patients who were adequately rehydrated. In these studies, there was no mortality and therefore the impact of antibiotics on mortality cannot be assessed. In the absence of adequate rehydration, antibiotics alone are not sufficient to prevent cholera mortality.

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Antibiotic regimens for the treatment of cholera

Tetracycline has been shown to be effective treatment for cholera and is superior to furazolidone, cholamphenicol and sulfaguanidine in reducing cholera morbidity. Treatment with a single 300mg dose of doxycycline has shown to be equivalent to tetracycline treatment. Erythromycin is effective for cholera treatment, and appropriate for children and pregnant women . Orfloxacin , trimethoprim-sulfamethoxazole (TMP-SMX) , and ciprofloxacin are effective, but doxycycline offers advantages related to ease of administration and comparable or superior effectiveness. Recently, azithromycin has been shown to be more effective than erythromycin and ciprofloxacin and is an appropriate first line regimen for children and pregnant women. 4.
Antibiotic resistance

Resistance to tetracycline and other antimicrobial agents among V. cholerae has been demonstrated in both endemic and epidemic cholera settings. Resistance can be acquired through the accumulation of selected mutations over time, or the acquisition of genetic elements such as plasmids, introns, or conjugative elements, which confer rapid spread of resistance. A likely risk factor for antimicrobial resistance is widespread use of antibiotics, including mass distribution for prophylaxis in asymptomatic individuals. Antibiotic resistance emerged in previous epidemics in the context of antibiotic prophylaxis for household contacts of cholera patients .

3) Zinc Treatment
A study in Bangladesh showed that zinc supplementation significantly reduced the duration and severity of diarrhea in children suffering from cholera . The study was conducted with 179 children, 3-14 years old, who were admitted to a hospital within 24 hours of the onset of cholera symptoms. In the study, all children received antibiotics and rehydration therapy as needed, but those in the intervention group also received zinc supplementation. Children who received zinc supplementation had 8 fewer hours of diarrheal illness and 10% less diarrheal stool volume, on average. Zinc has also been shown to have a similar effect in children with diarrhea caused by infections other than cholera, and is recommended for the treatment of pediatric diarrhea more generally.

MANAGEMENT OF DISEASE:

If you have oral rehydration solution (ORS), start taking it now; it can save your life.

Go immediately to the nearest health facility. Continue to drink ORS at home and while you travel to get treatment. Continue to breastfeed your baby if they have watery diarrhea, even when traveling to get treatment.

Five Basic Cholera Prevention Messages

1. Drink and use safe water

Bottled water with unbroken seals and canned/bottled carbonated beverages are safe to drink and use. Use safe water to brush your teeth, wash and prepare food, and to make ice. Clean food preparation areas and kitchenware with soap and safe water and let dry completely before reuse.

To be sure water is safe to drink and use: Boil it or treat it with a chlorine product or household bleach. If boiling, bring your water to a complete boil for at least 1 minute. To treat your water with chlorine, use one of the locally available treatment products and follow the instructions. For a list of products distributed by country, visit CDCs Safe Water System website. If a chlorine treatment product is not available, you can treat your water with household bleach. Add 8 drops of household bleach for every 1 gallon of water (or 2 drops of household bleach for every 1 liter of water) and wait 30 minutes before drinking. Always store your treated water in a clean, covered container.

2. Wash your hands often with soap and safe water

Before you eat or prepare food Before feeding your children After using the latrine or toilet After cleaning your childs bottom After taking care of someone ill with diarrhea

3. Use latrines or bury your feces (poop); do not defecate in any body of water

Use latrines or other sanitation systems, like chemical toilets, to dispose of feces. Wash hands with soap and safe water after defecating. Clean latrines and surfaces contaminated with feces using a solution of 1 part household bleach to 9 parts water.

What if I dont have a latrine or chemical toilet?

Defecate at least 30 meters away from any body of water and then bury your feces. Dispose of plastic bags containing feces in latrines, at collection points if available, or bury it in the ground. Do not put plastic bags in chemical toilets. Dig new latrines or temporary pit toilets at least a half-meter deep and at least 30 meters away from any body of water.

4. Cook food well (especially seafood), keep it covered, eat it hot, and peel fruits and vegetables

Boil it, Cook it, Peel it, or Leave it. Be sure to cook shellfish (like crabs and crayfish) until they are very hot all the way through.
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5. Clean up safelyin the kitchen and in places where the family bathes and washes clothes

Wash yourself, your children, diapers, and clothes, 30 meters away from drinking water sources.

Vaccines:
Currently, there are two oral cholera vaccines available, Dukoral (manufactured by SBL Vaccines) which is World Health Organization (WHO) prequalified and licensed in over 60 countries, and ShanChol (manufactured by Shantha Biotec in India), which is licensed in India and is pending WHO prequalification. Because the vaccine is a two dose vaccine, multiple weeks can elapse before persons receiving the vaccine are protected. Therefore, vaccination should not replace standard prevention and control measures In addition, I do not recommend cholera vaccines for most travelers, nor is the vaccine available in the U.S.. This is because the available vaccines offer incomplete protection for a relatively short period of time.