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Cholera

Presentation

History

After a 24- to 48-hour incubation period, symptoms begin with the sudden onset of painless watery diarrhea that may quickly become voluminous and is often followed by vomiting. The patient may experience accompanying abdominal cramps, probably from distention of loops of small bowel as a result of the large volume of intestinal secretions. Fever is typically absent.

However, most Vibrio cholerae infections are asymptomatic, and mild to moderate diarrhea due to V cholerae infection may not be clinically distinguishable from other causes of gastroenteritis. An estimated 5% of infected patients will develop cholera gravis, ie, severe watery diarrhea, vomiting, and dehydration.

Diarrhea

Profuse watery diarrhea is a hallmark of cholera. Cholera should be suspected when a patient older than 5 years develops severe dehydration from acute, severe, watery diarrhea (usually without vomiting) or in any patient older than 2 years who has acute watery diarrhea and is in an area where an outbreak of cholera has occurred.

Stool volume during cholera is more than that of any other infectious diarrhea. Patients with severe disease may have a stool volume of more than 250 mL/kg body weight in a 24-hour period. Because of the large volume of diarrhea, patients with cholera have frequent and often uncontrolled bowel movements.

The stool may contain fecal material early in the course of clinical illness. The characteristic cholera stool is an opaque white liquid that is not malodorous and often is described as having a “rice water” appearance (ie, in color and consistency, it resembles water that has been used to wash or cook rice).

Vomiting

Vomiting, although a prominent manifestation, may not always be present. Early in the course of the disease, vomiting is caused by decreased gastric and intestinal motility; later in the course of the disease it is more likely to result from acidemia.

Dehydration

If untreated, the diarrhea and vomiting lead to isotonic dehydration, which can lead to acute tubular necrosis and renal failure. In patients with severe disease, vascular collapse, shock, and death may ensue. Dehydration can develop with remarkable rapidity, within hours after the onset of symptoms. This contrasts with disease produced by infection from any other enteropathogen. Because the dehydration is isotonic, water loss is proportional between 3 body compartments, intracellular, intravascular, and interstitial.

Physical Examination

Clinical signs of cholera parallel the level of volume contraction. The amount of fluid loss and the corresponding clinical signs of cholera are as follows:

3-5% loss of normal body weight - Excessive thirst
5-8% loss of normal body weight - Postural hypotension, tachycardia, weakness, fatigue, dry mucous membranes or dry mouth
>10% loss of normal body weight - Oliguria; glassy or sunken eyes; sunken fontanelles in infants; weak, thready, or absent pulse; wrinkled "washerwoman" skin; somnolence; coma

Assessment for Dehydration

The World Health Organization has classified dehydration in patients with diarrhea into the following 3 categories, to facilitate treatment (see Table 1):

Severe
Some (previously termed moderate, in the WHO criteria)
None (previously termed mild, in the WHO criteria)

Children without clinically significant dehydration (< 5% loss of body weight) may have increased thirst without other signs of dehydration. In children with some (ie, moderate) dehydration, cardiac output and vascular resistance are normal, and changes in interstitial and intracellular volume are the primary manifestations of illness. Skin turgor is decreased, as manifested by prolonged skin tenting in response to a skin pinch (the most reliable sign of isotonic dehydration), and a normal pulse.

For the skin pinch, it is important to pinch longitudinally rather than horizontally and to maintain the pinch for a few seconds before releasing the skin. The skin pinch may be less useful in patients with marasmus (severe wasting), kwashiorkor (severe malnutrition with edema), or obesity.

In adults and children older than 5 years, other signs of severe dehydration include tachycardia, absent or barely palpable peripheral pulses, and hypotension.

Tachypnea and hypercapnia also are part of the clinical picture and are attributable to the metabolic acidosis that invariably is present in patients with cholera who are dehydrated.

Metabolic and systemic manifestations

After dehydration, hypoglycemia is the most common lethal complication of cholera in children. Hypoglycemia is a result of diminished food intake during the acute illness, exhaustion of glycogen stores, and defective gluconeogenesis secondary to insufficient stores of gluconeogenic substrates in fat and muscle.

Cholera causes bicarbonate loss in stools, accumulation of lactate because of diminished perfusion of peripheral tissues, and hyperphosphatemia. Acidemia results when respiratory compensation is unable to sustain a normal blood pH.

Hypokalemia results from potassium loss in the stool, with a mean potassium concentration of approximately 3.0 mmol/L. Because of the existing acidosis, however, children often have normal serum potassium concentrations when first observed, despite severe total body potassium depletion.

Hypokalemia develops only after the acidosis is corrected and intracellular hydrogen ions are exchanged for extracellular potassium. Hypokalemia is most severe in children with preexisting malnutrition who have diminished body stores of potassium and may be manifested as paralytic ileus.

Rehydration therapy with bicarbonate-containing fluids can also produce hypocalcemia by decreasing the proportion of serum calcium that is ionized. Chvostek and Trousseau signs are often present, and spontaneous tetanic contractions can occur.

Pediatric patients

In pediatric patients, the primary signs are similar to those in adults. However, children with severe cholera may present with signs that are rarely seen in adults. A child with cholera is usually very drowsy, and coma is not uncommon. In addition, pediatric patients may have convulsions that appear to be related, in part, to hypoglycemia because patients exhibit some response to intravenous dextrose. Another significant difference from the adult presentation is that children are often febrile.

Cholera sicca

Cholera sicca is an old term describing a rare, severe form of cholera that occurs in epidemic cholera. This form of cholera manifests as ileus and abdominal distention from massive outpouring of fluid and electrolytes into dilated intestinal loops. Mortality is high, with death resulting from toxemia before the onset of diarrhea and vomiting. The mortality in this condition is high. Because of the unusual presentation, failure to recognize the condition as a form of cholera is common.

Table: Assessment for Dehydration

Table 1. Assessment of the Patient With Diarrhea for Dehydration (based on WHO classification) (Open Table in a new window)

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

Differential Diagnoses

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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.