Sections

Cholera

Workup

Approach Considerations

Definitive diagnosis is not a prerequisite for the treatment of patients with cholera. The priority in management of any watery diarrhea is replacing the lost fluid and electrolytes and providing an antimicrobial agent when indicated.

According to World Health Organization (WHO) standard case definition, a case of cholera is suspected when the following conditions are met:

In an area where the disease is not known to be present, a patient aged 5 years or older develops severe dehydration or dies from acute watery diarrhea
In an area with a noted cholera epidemic, a patient aged 5 years or older develops acute watery diarrhea, with or without vomiting

In endemic areas, biochemical confirmation and characterization of the isolate are usually unnecessary. However, these tasks may be worthwhile in areas where Vibrio cholerae is an uncommon isolate. If identification of the organism is required, direct microscopic examination of stool (including dark-field examination) is indicated, along with Gram stain, culture, and serotype and biotype identification.

Polymerase chain reaction (PCR) tests for identifying V cholerae have been developed. These have a high degree of sensitivity and specificity. At present, however, such tests are used for screening of food samples.

Stool Examination

Vibrio cholerae is a gram-negative curved bacillus that is motile by means of a single flagellum. Laboratory diagnosis is required not only for identification but also for epidemiological purposes (see the image below).

Electron microscopic image of Vibrio cholera.

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Although observed as a gram-negative organism, the characteristic motility of Vibrio species cannot be identified on a Gram stain, but it is easily seen on direct dark-field examination of the stool.

Stool Culture

V cholerae is not fastidious in nutritional requirements for growth. However, it does need an adequate buffering system if fermentable carbohydrate is present because viability is severely compromised if the pH is less than 6, often resulting in autosterilization of the culture. Many of the selective media used to differentiate enteric pathogens do not support the growth of V cholerae.

Routine differential media

Colonies are lactose-negative, like all other intestinal pathogens, but sucrose-positive. When plated onto triple-sugar iron agar to screen for Salmonella and Shigella species, the organism gives the nonpathogenic pattern of an acid (yellow) slant and acid butt because of fermentation of the sucrose contained in triple-sugar iron agar.

Unlike other Enterobacteriaceae, V cholerae is oxidase-positive; hence, in countries where selective media are not available and cholera is not endemic, V cholerae should be suspected if any motile, oxidase-positive, gram-negative rod isolated on routine differential media from the stool of a patient with diarrhea produces an acid reaction on triple sugar iron agar.

Alkaline enrichment media

As Vibrio has the ability to grow at a high pH or in bile salts, which inhibit many other Enterobacteriaceae, peptone water (pH 8.5-9) or selective media containing bile salts (eg, thiosulfate-citrate-bile-sucrose-agar [pH 8.6]) are recommended to facilitate isolation and lab diagnosis. On thiosulfate-citrate-bile-sucrose-agar, the sucrose-fermenting V cholera grow as large, smooth, round yellow colonies that stand out against the blue-green agar.

Serotyping and Biotyping

Specific antisera can be used in immobilization tests. A positive immobilization test result (ie, cessation of motility of the organism) is produced only if the antiserum is specific for the Vibrio type present; the second antiserum serves as a negative control. Vibrio antisera may be unavailable in countries where cholera is not endemic. In endemic regions, this is an excellent quick method of identification, even in small laboratories.

Classic and El Tor biotypes also can be identified using the same method. This is useful for epidemiologic studies.

Hematologic Tests

The major hematologic derangements in patients with cholera derive from the alterations in intravascular volume and electrolyte concentrations.

Hematocrit, serum-specific gravity, and serum protein are elevated in dehydrated patients because of resulting hemoconcentration. When patients are first observed, they generally have a leukocytosis without a left shift.

Metabolic Panel

Serum sodium is usually 130-135 mmol/L, reflecting the substantial loss of sodium in the stool.

Serum potassium usually is normal in the acute phase of the illness, reflecting the exchange of intracellular potassium for extracellular hydrogen ion in an effort to correct the acidosis.

Hyperglycemia may be present, secondary to systemic release of epinephrine, glucagon, and cortisol due to hypovolemia.

Patients have elevated blood urea nitrogen and creatinine levels consistent with prerenal azotemia. The extent of elevation depends on the degree and duration of dehydration.

A reduced bicarbonate level (< 15 mmol/L) and an elevated anion gap occur as a result of increases in serum lactate, protein, and phosphate levels. The arterial pH is usually low (approximately 7.2). Calcium and magnesium levels are usually high as a result of hemoconcentration.

Treatment & Management

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Media Gallery

Electron microscopic image of Vibrio cholera.
Scanning electron microscope image of Vibrio cholerae bacteria, which infect the digestive system.
This scanning electron micrograph (SEM) depicts a number of Vibrio cholerae bacteria of the serogroup 01; magnified 22371x. Image courtesy of CDC/Janice Haney Carr.
This patient with cholera is drinking oral rehydration solution (ORS) in order to counteract the cholera-induced dehydration. Image courtesy of the CDC.

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Table 1. Assessment of the Patient With Diarrhea for Dehydration (based on WHO classification)

Sensorium	Eyes	Thirst	Skin Pinch	Decision
Abnormally sleepy or lethargic	Sunken	Drinks poorly or not at all	Goes back very slowly (>2 sec)	If the patient has 2 or more of these signs, severe dehydration is present
Restless, irritable	Sunken	Drinks eagerly	Goes back slowly (< 2 sec)	If the patient has 2 or more signs, some dehydration is present
Well, alert	Normal	Drinks normally, not thirsty	Goes back quickly	Patient has no dehydration

Table 2. Fluid Replacement for Dehydration

Severe dehydration	Intravenous (IV) drips of Ringer Lactate or, if not available, normal saline and oral rehydration salts as outlined below	100 mL/kg in 3-h period (in 6 h for children < 1 y) Start rapidly (30 mL/kg within 30 min, then slow down) Total amount for first 24 h: 200 mL/kg
Some dehydration	Oral rehydration salts (amount in first 4 h)	Infants < 4 mo (< 5 kg): 200–400 mL Infants 4–11 mo (5–7.9 kg): 400–600 mL Children 1–2 y (8–10.9 kg): 600–800 mL Children 2–4 y (11–15.9 kg): 800–1200 mL Children 5–14 y (16–29.9 kg): 1200–2200 mL Patients >14 y (≥30 kg): 2200–4000 mL
No dehydration	Oral rehydration salts	Children < 2 y: 50–100 mL, up to 500 mL/day Children 2–9 y: 100–200 mL, up to 1000 mL/day Patients >9 y: As much as wanted, up to 2000 mL/day

Table 3. Approximate Amount of Oral Rehydration Solution to Administer in the First 4 Hours

Age	< 4 mo	4-11 mo	12-23 mo	2-4 y	5-14 y	≥15 y
Weight	< 5 kg	5-7.9 kg	8-10.9 kg	11-15.9 kg	16-29.9 kg	≥30 kg
ORS solution in mL	200-400	400-600	600-800	800-1200	1200-2200	2200-4000

Table 4. Estimate of Oral Rehydration Solution Packets to Be Administered at Home

Age	Amount of Solution After Each Loose Stool	ORS Packets Needed
< 24 mo	50-100 mL	Enough for 500 mL/d
2-9 y	100-200 mL	Enough for 1000 mL/d
≥10 y	As much as is wanted	Enough for 200 mL/d

Table 5. Oral Replacement Solution for Maintenance of Hydration

Age	Amount of Solution After Each Loose Stool
< 24 mo	100 mL
2-9 y	200 mL
≥10 y	As much as is wanted

Table 6. Antimicrobial Therapy Used in the Treatment of Cholera*

Antibiotic	Single Dose (PO)	Multiple Dose (PO)
Doxycycline^†	7 mg/kg; not to exceed 300 mg/dose^‡	2 mg/kg bid on day 1; then 2 mg/kg qd on days 2 and 3; not to exceed 100 mg/dose
Tetracycline^†	25 mg/kg; not to exceed 1 g/dose^‡	40 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Furazolidone	7 mg/kg; not to exceed 300 mg/dose	5 mg/kg/d divided qid for 3 d; not to exceed 400 mg/d
Trimethoprim and sulfamethoxazole	Not evaluated	< 2 months: Contraindicated ≥2 months: 5-10 mg/kg/d (based on trimethoprim component) divided bid for 3 d; not to exceed 320 mg/d trimethoprim and 1.6 g/d of sulfamethoxazole
Ciprofloxacin^§	30 mg/kg; not to exceed 1 g/dose^‡	30 mg/kg/d divided q12h for 3 d; not to exceed 2 g/d
Ampicillin	Not evaluated	50 mg/kg/d divided qid for 3 d; not to exceed 2 g/d
Erythromycin	Not evaluated	40 mg/kg/d erythromycin base divided tid for 3 d; not to exceed 1 g/d
^* Antimicrobial therapy is an adjunct to fluid therapy of cholera and is not an essential component. However, it reduces diarrhea volume and duration by approximately 50%. The choice of antibiotics is determined by the susceptibility patterns of the local strains of V cholerae O1 or O139. ^† Tetracycline and doxycycline can discolor permanent teeth of children younger than 8 years. However, the risk is small when these drugs are used for short courses of therapy, especially if used in a single dose. ^‡ Single-dose therapy of these drugs has not been evaluated systematically in children, and recommendations are extrapolated from experience in adults. ^§ Fluoroquinolones (eg, ciprofloxacin) are not approved in the United States for use in persons younger than 18 years. When given in high doses to juvenile animals, they cause arthropathy. Clinical experience indicates that this risk is very small in children when used for short courses of therapy.

Table 7. WHO Guidelines for Cholera Management

Steps in the treatment of a patient with suspected cholera are as follows:

1. Assess for dehydration (see Table 1)

2. Rehydrate the patient and monitor frequently, then reassess hydration status

3. Maintain hydration; replace ongoing fluid losses until diarrhea stops

4. Administer an oral antibiotic to the patient with severe dehydration

5. Feed the patient

More detailed guidelines for the treatment of cholera are as follows:

Evaluate the degree of dehydration upon arrival

Rehydrate the patient in 2 phases; these include rehydration (for 2-4 h) and maintenance (until diarrhea abates)

Use the intravenous route only (1) during the rehydration phase for severely dehydrated patients for whom an infusion rate of 50-100 mL/kg/h is advised, (2) for moderately dehydrated patients who do not tolerate the oral route, and (3) during the maintenance phase in patients considered high stool purgers (ie, >10 mL/kg/h)

During the maintenance phase, use oral rehydration solution at a rate of 800-1000 mL/h; match ongoing losses with ORS administration

Discharge patients to the treatment center if oral tolerance is greater than or equal to 1000 mL/h, urine volume is greater than or equal to 40 mL/h, and stool volume is less than or equal to 400 mL/h.