Cholera

Infectious Agent

Cholera is an acute bacterial intestinal infection caused by toxigenic Vibrio cholerae O-group 1 or O-group 139. Many other serogroups of V. cholerae , with or without the cholera toxin gene (including the nontoxigenic strains of the O1 and O139 serogroups), can cause a choleralike illness. Only toxigenic strains of serogroups O1 and O139 have caused widespread epidemics and are reportable to the World Health Organization (WHO) as “cholera.” V. cholerae O1 is the source of an ongoing global pandemic, while the O139 serogroup remains localized to a few areas in Asia.

V. cholerae O1 has 2 biotypes, classical and El Tor, and each biotype has 2 distinct serotypes, Inaba and Ogawa. The symptoms of infection are indistinguishable, although more people infected with the El Tor biotype remain asymptomatic or have only a mild illness. Globally, most cases of cholera are caused by O1 El Tor organisms. In recent years, an El Tor variant that has characteristics of both classical and El Tor biotypes and may be more virulent than older El Tor strains has emerged in Asia and has spread to Africa and the Caribbean. This strain is responsible for the epidemic on Hispaniola and may cause a higher proportion of severe episodes of cholera and higher death rates.

Transmission

Toxigenic V. cholerae O1 and O139 are free-living bacterial organisms found in fresh and brackish water, often in association with copepods or other zooplankton, shellfish, and aquatic plants. Cholera infections are most commonly acquired from drinking water in which V. cholerae is found naturally or into which it has been introduced from the feces of an infected person. Other common vehicles include fish and shellfish. Other foods, including produce, are less commonly implicated. Direct transmission from person to person, even to health care workers during epidemics, has been reported but is not frequent.

Epidemiology

Cholera is endemic in approximately 50 countries, primarily in Africa and South and Southeast Asia, and can emerge in dramatic epidemics, although most cases go unreported. In October 2010, a large cholera epidemic began in Haiti and spread to the Dominican Republic and Cuba; it is now endemic in Hispaniola, and occasional small outbreaks occur in the Dominican Republic and in Cuba. Sporadic cases associated with travel to or from cholera-affected countries continue to occur.

From 2010 through 2014, 91 cases of cholera were confirmed in the United States among people who had traveled internationally in the week before illness. Of these, 75% were associated with travel to the Caribbean, and 10% were associated with travel to India or Pakistan; other travel destinations reported included countries in Southeast Asia and West Africa. Risk of infection is highest for travelers to countries where cholera is endemic or where there is an active epidemic. The risk is increased for those who drink untreated water, do not follow handwashing recommendations, do not use latrines or other sanitation systems, or eat raw or poorly cooked food, especially seafood. Health care and response workers in cholera-affected areas, such as in an outbreak or after a disaster, may also be at increased risk of cholera. People who have low gastric acidity or those with blood type O are at higher risk of severe cholera illness. Travelers who observe safe food, water, sanitation, and handwashing recommendations while in countries affected by cholera have virtually no risk of acquiring cholera.

Clinical Presentation

Cholera most commonly manifests as watery diarrhea in an afebrile person. Infection is often mild or asymptomatic, but it can be severe. Severe cholera is characterized by acute, profuse watery diarrhea, described as “rice-water stools,” often accompanied by nausea and vomiting, and can rapidly lead to severe volume depletion. Signs and symptoms include tachycardia, loss of skin turgor, dry mucous membranes, hypotension, and thirst. Additional symptoms, including muscle cramps, are secondary to the resulting electrolyte imbalances. If untreated, rapid loss of body fluids can lead to severe dehydration, hypovolemic shock, and death within hours. With adequate and timely rehydration, case-fatality ratios (CFRs) are <1%.

Diagnosis

Cholera is confirmed through culture of a stool specimen or rectal swab. Cary-Blair medium can be used for transport, and selective media such as taurocholate-tellurite-gelatin agar and thiosulfate-citrate-bile salts agar may be used for isolation and identification. Reagents for serogrouping V. cholerae isolates are available in state health department laboratories. Culture-independent diagnostic tests do not yield an isolate for antimicrobial susceptibility testing and subtyping and should not be used for routine diagnosis. All isolates obtained in the United States should be sent to CDC via state health department laboratories for identification and virulence testing. Cholera is a nationally notifiable disease.

Treatment

Rehydration is the cornerstone of cholera treatment. Oral rehydration solution and, when necessary, intravenous fluids and electrolytes, if administered in a timely manner and in adequate volumes, will reduce CFRs to <1%. Antibiotics reduce fluid requirements and duration of illness and are indicated in conjunction with aggressive hydration for severe cases and for those with moderate dehydration and ongoing fluid losses. Whenever possible, antimicrobial susceptibility testing should inform treatment choices. In most countries, doxycycline is recommended as the first-line antibiotic treatment for adults, and azithromycin is recommended for children and pregnant women. Multidrug-resistant isolates are emerging, particularly in South Asia, with resistance to quinolones, trimethoprim-sulfamethoxazole, and tetracycline. The strain from Hispaniola is also multidrug resistant; however, it is still sensitive to doxycycline and tetracycline. Zinc supplementation reduces the severity and duration of cholera and other diarrheal diseases in children living in resource-limited areas.

Prevention

Food and Water

Safe food and water precautions and frequent handwashing are critical in preventing cholera (see Chapter 2, Food & Water Precautions). Chemoprophylaxis is not indicated.

Vaccine

No country or territory requires vaccination against cholera as a condition for entry. CVD 103-HgR, a single-dose oral cholera vaccine (Vaxchora, PaxVax), is licensed and available in the United States. The vaccine was previously marketed under the names Orochol and Mutacol in other countries. Vaxchora was approved in June 2016 for use in adults ≥18 years of age.

Indications

The Advisory Committee on Immunization Practices (ACIP) recommends CVD 103-HgR vaccine for adult travelers (age 18–64 years) to an area of active cholera transmission. An area of active cholera transmission is defined as a province, state, or other administrative subdivision within a country with endemic or epidemic cholera caused by toxigenic V. cholerae O1 and includes areas with cholera activity within the last year that are prone to recurrence of cholera epidemics; it does not include areas where rare sporadic cases have been reported.

The vaccine is not routinely recommended for most travelers from the United States, as most do not visit areas with active cholera transmission.

Vaccine Efficacy

Adults aged 18–45 years who received Vaxchora were protected against severe diarrhea after oral V. cholerae O1 challenge at 10 days and at 3 months after vaccination (vaccine efficacy 90% and 80%, respectively). In adults aged 46–64 years, vibriocidal antibody seroconversion rates, the best available marker for protection against cholera, were noninferior to the response seen in adults aged 18–45 years.

Vaccine Administration

Vaxchora is administered in a single oral dose, which consists of ingestion of the entire contents of 1 double-chambered sachet. Vaxchora should be taken at least 10 days before potential cholera exposure. Eating or drinking should be avoided for 60 minutes before and after oral ingestion of Vaxchora. Prepare and administer Vaxchora in a health care setting equipped to dispose of medical waste.

Booster Doses

The safety and efficacy of revaccination with CVD 103-HgR have not been established.

Vaccine Safety and Adverse Reactions

Serious adverse events were rare among recipients of Orochol and Mutacol, the previously marketed formulation of the CVD 103-HgR vaccine. Systemic adverse events, which may include diarrhea and headache, occur at similar rates in Vaxchora recipients and nonrecipients.

Precautions and Contraindications

Vaxchora is contraindicated in people with a history of severe allergic reaction to any ingredient of Vaxchora or to a previous dose of any cholera vaccine. A study with the older formulation of CVD 103-HgR showed that concomitant use of chloroquine decreased the immune response to the vaccine; therefore, antimalarial prophylaxis with chloroquine should begin no sooner than 10 days after administration of Vaxchora. Coadministration of mefloquine and proguanil with CVD 103-HgR did not diminish the vaccine’s immunogenicity. Antibiotics may decrease the immune response to CVD 103-HgR, so vaccine should not be administered to patients who have received antibiotics in the previous 14 days.

Vaxchora is not currently licensed for use in children <18 years of age. No information is available on the use of Vaxchora during pregnancy or lactation. The safety and effectiveness of Vaxchora have not been established in immunocompromised people. There was no difference in adverse events reported among HIV-positive recipients of an older formulation of the CVD 103-HgR vaccine and those who received placebo.

Vaxchora may be shed in the stool for at least 7 days, and the vaccine strain may be transmitted to nonvaccinated close contacts. Clinicians and travelers should use caution when considering whether to use the vaccine in people with immunocompromised close contacts.

CDC website: www.cdc.gov/cholera

Bibliography

  1. Chen WH, Cohen MB, Kirkpatrick BD, Brady RC, Galloway D, Gurwith M, et al. Single-dose live oral cholera vaccine CVD 103-HgR protects against human experimental infection with vibrio cholerae O1 El Tor. Clin Infect Dis. 2016 Jun 1;62(11):1329–35.  [PMID:27001804]
  2. Danzig L, editor. Vaxchora™ clinical data summary. Meeting of the Advisory Committee on Immunization Practices; 2016 February 24; Atlanta, GA.
  3. Gaffga NH, Tauxe RV, Mintz ED. Cholera: a new homeland in Africa? Am J Trop Med Hyg. 2007 Oct;77(4):705–13.  [PMID:17978075]
  4. Harris JB, Larocque RC, Charles RC, Mazumder RN, Khan AI, Bardhan PK. Cholera's western front. Lancet. 2010 Dec 11;376(9757):1961–5.  [PMID:21112083]
  5. Harris JB, LaRocque RC, Qadri F, Ryan ET, Calderwood SB. Cholera. Lancet. 2012 Jun 30;379(9835):2466–76.  [PMID:22748592]
  6. Kollaritsch H, Que JU, Kunz C, Wiedermann G, Herzog C, Cryz SJ, Jr. Safety and immunogenicity of live oral cholera and typhoid vaccines administered alone or in combination with antimalarial drugs, oral polio vaccine, or yellow fever vaccine. J Infect Dis. 1997 Apr;175(4):871–5.  [PMID:9086143]
  7. Loharikar A, Newton AE, Stroika S, Freeman M, Greene KD, Parsons MB, et al. Cholera in the United States, 2001–2011: a reflection of patterns of global epidemiology and travel. Epidemiol Infect. 2015 March;143(4):695–703.  [PMID:24865664]
  8. Schilling KA, Cartwright EJ, Stamper J, Locke M, Esposito DH, Balaban V, et al. Diarrheal illness among US residents providing medical services in Haiti during the cholera epidemic, 2010–2011. J Travel Med. 2014 Jan-Feb;21(1):55–7.  [PMID:24383654]
  9. World Health Organization. Cholera, 2014. Wkly Epidemiol Rec. 2015 Oct 2;90(40):517–28.  [PMID:26433979]

Authors

Karen K. Wong, Erin Burdette, Eric D. Mintz