Cholera

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 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.

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.

Genetics

Because cholera pathophysiology involves chloride loss at the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel, it is hypothesized that those heterozygous or homozygous for mutations in CFTR have less severe cholera disease.

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.
  • Vaccines
    • No vaccines are available in the United States.
    • Whole cell killed oral cholera vaccines have 52% efficacy in preventing cholera over the subsequent year, but protective efficacy is lower in children <5 years of age at 38%. In some studies, vaccine efficacy remains this high up to 5 years after vaccination.
    • Single-dose oral vaccines with a vaccine efficacy ranging from 40–80% are also being studied.
    • 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 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.

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.

Commonly Associated Conditions

Cholera occurs in healthy individuals.

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