Basics
Description
- Cholera is an acute-onset infection producing profuse secretory diarrhea with the potential for epidemic spread.
Epidemiology
- Diarrheal disease, including cholera, is the 2nd leading cause of mortality in children <5 years old worldwide.
- The first 6 recorded cholera pandemics occurred prior to 1923, but the current 7th pandemic began in 1961 and has continued through several waves of global transmission.
- Most cholera occurs in Asia and Africa, but Vibrio cholerae is now endemic in many countries. Regions previously free of cholera have become susceptible to severe outbreaks, as occurred in Haiti in 2010.
- In the United States, most cases result from travel. Cases have been reported in the Gulf Coast of Louisiana and Texas related to undercooked shellfish consumption.
- Case fatality rates are ~1% with timely treatment but can rise to 35-50% in severe cases in extremely resource-limited settings.
Incidence
- Although underreported, approximately 2.8 million cholera cases occur in endemic countries annually, with an additional 87,000 cases annually in nonendemic countries.
- An estimated 91,000 deaths occur in endemic countries annually.
Prevalence
- Given the relatively short duration of illness and lack of chronic carrier state, cholera prevalence generally matches its incidence.
Risk Factors
- Inadequate drinking water and sanitation increase transmission; peri-urban slums, refugee camps, disaster areas, etc., are high risk for cholera epidemics.
- Floods and surface water temperature changes lead to increased cholera density.
- Low gastric acidity (which decreases killing of ingested organisms), blood group O, and retinol deficiency are risk factors.
- Young children are at risk for severe cholera.
General Prevention
- Transmission
- Hand washing after defecation and before food preparation is essential. Boiling or disinfection of water also prevents infection.
- Thorough cooking of shellfish (which can be naturally contaminated) prevents infection.
- During travel to endemic areas, avoid swimming or bathing in fresh water.
- Report confirmed cholera cases to the local department of health.
- Antibiotic prophylaxis of cholera contacts is debated but was shown in a meta-analysis to prevent disease among the contacts (relative risk, 0.35; 95% CI, 0.18-0.66), although the analysis noted a risk of bias.
- Vaccines
- No vaccines are available in the United States.
- Whole cell killed oral cholera vaccines have 52% (95% CI, 35-65%) efficacy in preventing cholera over the subsequent year, but protective efficacy is lower in children <5 years of age at 38% (95% CI, 20-53%).
- Herd immunity occurs among unvaccinated people living near vaccinees.
Pathophysiology
- Infection follows ingestion of large numbers of organisms from contaminated water or food (raw or undercooked shellfish and fish, or room temperature damp vegetables).
- The infectious dose for severe cholera is ~108 organisms but can be as little as 103 organisms in young children or those with decreased gastric acidity (such as those on acid suppression or after certain meals).
- The typical incubation period is usually 2-3 days but ranges from ~12 hours to 5 days.
- 75% are infected asymptomatically; symptomatic illness ranges from moderate to severe.
- Cholera toxin is the key virulence factor responsible for the profuse watery diarrhea.
- Cholera toxin has 1 A and 5 B subunits.
- The B subunits facilitate toxin attachment to intestinal cells.
- The A subunit activates adenylate cyclase, increasing intracellular levels of cyclic adenosine monophosphate (cAMP), which causes chloride and sodium to be secreted into the gut lumen.
- Water follows via osmosis.
- Severely ill patients can progress rapidly to dehydration, circulatory collapse, and death.
- Symptomatic patients may shed as many as 1010-1012 organisms per liter of stool and will shed organisms for 2 days to 2 weeks.
Etiology
- V. cholerae is a curved, motile gram-negative rod. Over 200 serogroups exist, but only serogroups O1 and O139 cause epidemics.
- V. cholerae serogroup O1 is divided into 2 biotypes: classical and El Tor. The classical biotype was formerly predominant, but the El Tor biotype is causing the 7th pandemic.
- V. cholerae serogroup O139 was first identified in 1992 and resembles the O1 El Tor biotype but possesses a distinct lipopolysaccharide and capsule.
- Humans are the only known host, but organisms can also exist freely in water, potentially contaminating fish and shellfish.
Commonly Associated Conditions
Cholera occurs in healthy individuals. �
Diagnosis
History
- Vomiting and profuse watery diarrhea: Severe illness is characterized by voluminous watery diarrhea (up to 1 L per hour) flecked with mucus ("rice-water stools"�).
- Sick contacts with similar symptoms: Cholera epidemics can spread rapidly.
- Exposures
- Return from travel within the last 5 days: Cholera is endemic in much of the world; the incubation period is typically 2-3 days.
- Patient's water source: Contaminated water serves as a reservoir.
- History of inadequately cooked shellfish: Shellfish (e.g., oysters, crabs) can harbor the organism.
Physical Exam
- Patients with cholera display signs of dehydration (tachycardia, dry mucous membranes, sunken fontanel or eyes, loss of skin turgor, lethargy) varying with severity.
- Arm and leg cramps occur due to secondary hypokalemia and hypocalcemia.
- Fever and obtundation secondary to hypoglycemia are more common in children.
Diagnostic Tests & Interpretation
Lab
- Cholera is a generally clinical diagnosis.
- Electrolytes, BUN, creatinine, serum calcium, and glucose can be useful if available. Acidosis can occur from stool bicarbonate losses and lactic acidosis from poor perfusion.
Imaging
- No imaging is required for diagnosis.
Diagnostic Procedures/Other
- Use selective media (thiosulfate citrate bile salts sucrose agar) to isolate V. cholerae. Alert the microbiology laboratory if culture testing for V. cholerae is desired.
- Serologic testing on acute and convalescent sera is also available through the Centers for Disease Control and Prevention (CDC).
- Stool culture may not always be positive in suspected cases of cholera, and rapid dipstick methods to identify cholera toxin and lipopolysaccharide, direct fluorescent antibody assays, and polymerase chain reaction (PCR)-based diagnostic methods also exist and are being studied.
Pathologic Findings
- Diagnosis can also be made with the identification of darting, curved bacilli in 400 � darkfield microscopy of stool.
Differential Diagnosis
- Other Vibrio species can cause gastroenteritis (commonly caused by V. parahaemolyticus but also by V. fluvialis, V. hollisae, and V. mimicus) or wound infections and sepsis (V. vulnificus). Of these, only V. parahaemolyticus and V. vulnificus cause outbreaks.
- Additional intestinal bacterial pathogens include Aeromonas, Campylobacter, Clostridium difficile, Escherichia coli, Listeria, Plesiomonas, Salmonella, Shigella, Vibrio species, and Yersinia.
- Other viral and parasitic pathogens include amebiasis, adenovirus types 40 and 41, Cryptosporidium,Cyclospora, Giardia, norovirus, and rotavirus.
Treatment
Medication
First Line
- Give antibiotics as an adjunct to fluid replacement for those with severe cholera.
- Single-dose doxycycline in those >8 years of age
- Alternately, single-dose azithromycin in children <8 years of age and pregnant women
- Ciprofloxacin is another alternative.
- Single-dose azithromycin can reduce symptom duration by 50% and may reduce excretion of the organism to 1-2 days.
- V. cholerae isolates resistant to sulfonamides and tetracyclines are common. Resistance to fluoroquinolones, macrolides, and β-lactams is increasingly reported.
- Administer zinc for 10-14 days: 10 mg/24 h for those <6 months of age and 20 mg/24 h for those 6 months to 5 years of age.
- Consider vitamin A supplementation for children in developing countries.
- Avoid antiemetics and antimotility agents.
Additional Treatment
General Measures
- The mainstay of cholera treatment is rapid rehydration, accounting for both initial and ongoing fluid losses.
- Patients with moderate disease may require only oral rehydration solutions (ORS).
- Administer ORS in frequent small sips to those with vomiting. These solutions should contain at minimum 75 mEq/L of sodium to replete the significant sodium losses associated with cholera.
- ORS with total osmolality ≤270 mOsm/L is associated with increased risk of biochemical hyponatremia but not with other symptomatic outcomes compared to ORS ≥310 mOsm/L in a meta-analysis of a few existing trials.
- Those with more severe disease (volume loss >10%) require intravenous (IV) fluids.
Issues for Referral
Specific follow-up is unnecessary. �
Additional Therapies
During outbreaks, rapid institution of improved sanitation and safe water availability are critical to decrease the extent of the outbreak. �
Inpatient Considerations
Initial Stabilization
Rapid correction of severe (>10%) dehydration is critical. �
Admission Criteria
Admit those requiring IV fluids. �
IV Fluids
- Dhaka solution is an optimal IV fluid containing dextrose and more bicarbonate and potassium than lactated Ringer (LR).
- LR is an acceptable, more available alternative; D5LR contains 5% dextrose.
- Normal saline lacks potassium and bicarbonate and is second-line.
Nursing
- Measure ongoing fluid losses carefully.
- Use contact precautions for infected infants and children who are incontinent of stool.
Discharge Criteria
Discharge rehydrated patients able to maintain hydration orally. �
Ongoing Care
Follow-up Recommendations
Patient Monitoring
In the untreated patient, the typical period of V. cholerae shedding is 1-2 weeks. Asymptomatic carriage is uncommon. �
Diet
Resume a high-energy diet immediately after the initial fluid deficit is replaced. Infants should be encouraged to breastfeed. �
Patient Education
- Improved sanitation and safe drinking water can help prevent future episodes.
- Secondary transmission can occur in households with affected members if strict hand washing and hygiene is not followed.
Prognosis
For patients with prompt rehydration, the prognosis is very good regardless of whether antibiotic treatment is given. �
Complications
- The main complications are those of severe dehydration: renal failure, thrombosis, stroke, and cardiovascular collapse.
- Cholera itself causes no complications.
Additional Reading
- Ali �M, Lopez �AL, You �YA, et al. The global burden of cholera. Bull World Health Organ. 2012;90(3):209-218A. �[View Abstract]
- Harris �JB, LaRocque �RC, Qadri �F, et al. Cholera. Lancet. 2012;379(9835):2466-2476. �[View Abstract]
- Musekiwa �A, Volmink �J. Oral rehydration salt solution for treating cholera: ≤270 mOsm/L solutions vs ≥310 mOsm/L solutions (review). Cochrane Database Syst Rev. 2011;(12):CD003754. �[View Abstract]
- Reveiz �L, Chapman �E, Ramon-Pardo �P, et al. Chemoprophylaxis in contacts of patients with cholera: systematic review and meta-analysis. PLoS One. 2011;6(11):e27060. �[View Abstract]
- Sinclair �D, Abba �K, Zaman �K, et al. Oral vaccines for preventing cholera (review). Cochrane Database Syst Rev. 2011;(3):CD008603. �[View Abstract]
Codes
ICD09
- 001.9 Cholera, unspecified
- 001.0 Cholera due to vibrio cholerae
- 001.1 Cholera due to vibrio cholerae el tor
- V02.0 Carrier or suspected carrier of cholera
- V01.0 Contact with or exposure to cholera
- 001.1 Cholera due to vibrio cholerae el tor
- 001.9 Cholera, unspecified
- V06.0 Need for prophylactic vaccination and inoculation against cholera with typhoid-paratyphoid [cholera + TAB]
- V03.0 Need for prophylactic vaccination and inoculation against cholera alone
- 001.0 Cholera due to vibrio cholerae
- E979.6 Terrorism involving biological weapons
- 978.2 Poisoning by cholera vaccine
- E948.2 Cholera vaccine causing adverse effects in therapeutic use
- V74.0 Screening examination for cholera
ICD10
- A00.9 Cholera, unspecified
- A00.0 Cholera due to Vibrio cholerae 01, biovar cholerae
- A00.1 Cholera due to Vibrio cholerae 01, biovar eltor
SNOMED
- 63650001 Cholera (disorder)
- 240350003 Cholera - non-O1 group vibrio (disorder)
- 81020007 Cholera due to Vibrio cholerae El Tor
FAQ
- Q: What foods should I avoid while traveling?
- A: Foods associated with cholera include untreated or unboiled water and ice, undercooked fish and shellfish, raw vegetables, food from street vendors, and cooked food stored at ambient temperature.
- Q: Does cholera pose a risk to pregnant patients?
- A: Given the severe fluid losses, cholera can be life threatening to the fetus; fetal loss occurs in up to 50% of women in their 3rd trimester despite aggressive fluid resuscitation.
- Q: What is the risk of developing cholera among household contacts of those with disease?
- A: Up to 50% of household contacts may develop diarrheal symptoms, typically within 2 days of exposure to the index case.