DESCRIPTION

Cholera is an acute-onset infection producing profuse secretory diarrhea with the potential for epidemic spread.

EPIDEMIOLOGY

• Diarrheal disease, including cholera, is the second leading cause of mortality in children <5 years old worldwide.
• The first 6 recorded cholera pandemics occurred prior to 1923, but the current seventh 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 since 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.

ETIOLOGY

• V. cholerae is a curved, motile gram-negative rod. >200 serogroups exist, but only serogroups O1 and O139 cause epidemics.
• V. cholerae serogroup O1
  • Divided into two biotypes: classical and El Tor
  • The classical biotype was formerly predominant, but the El Tor biotype is causing the seventh pandemic.
• V. cholerae serogroup O139
  • First identified in 1992
  • 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.

RISK FACTORS

• Inadequate drinking water and sanitation increase transmission (e.g., peri-urban slums, refugee camps, disaster areas) 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, HIV infection, and retinol deficiency are risk factors.
• A meta-analysis demonstrated that factors associated with increased risk of symptomatic cholera included less than secondary school education, unimproved water sources, use of open container or bucket water storage, consumption of food outside the home (e.g., street foods), and household contact with cholera. Reduced risk of symptomatic cholera was associated with water treatment (including boiling and chlorination), breastfeeding (vs. bottle feeding), and hand washing.
• Young children are at risk for severe cholera.
• Emerging metagenomic data suggest that intestinal carriage of certain bacterial species are associated with developing or resisting cholera infection after exposure.

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, although the analysis noted a risk of bias.
  • Mobile health education programs to improve household sanitation have been shown to reduce diarrhea and improve health among contacts of diarrhea cases in low-resource settings.
• Vaccines
  • One single-dose live oral cholera vaccine (lyophilized CVD 103-HgR) administered ≥10 days before potential exposure is approved by the U.S. Food and Drug Administration (FDA) for adults 18 to 64 years traveling to cholera endemic areas, but its availability may be limited.
  • Whole cell killed oral cholera vaccines have overall 58% efficacy in preventing cholera over the subsequent 2 years, but protective efficacy is lower in children <5 years of age at 30%. In some studies, vaccine efficacy remains high up to 5 years after vaccination, but immunity generally wanes over the 2 years after vaccination.
  • Single-dose oral vaccines create protection in approximately 50–80% of individuals across studies but do not appear to provide sustained protection for 2 years in children <5 years old.
  • Single-dose vaccines have been used in the context of an outbreak setting with high efficacy.
  • Herd immunity occurs among unvaccinated people living near vaccinees.
  • Meta-analysis suggests that adverse pregnancy outcomes are not increased after oral cholera vaccination.

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 (e.g., persons on acid suppression medication or after certain meals).
• The typical incubation period is usually 2 to 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 1A and 5B 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 to 10¹² organisms per liter of stool and will shed organisms for 2 days to 2 weeks.

COMMONLY ASSOCIATED CONDITIONS

Cholera occurs in healthy individuals.