Chapter 4 Travel-Related Infectious Diseases
Hammad S. N’cho, Karen K. Wong, Eric D. Mintz
Please note: As of December 2020, the maker of the cholera vaccine will temporarily stop making and selling this vaccine. The cholera vaccine may be in limited supply or unavailable.
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 spread to Africa and the Caribbean. This strain is responsible for the epidemic on Hispaniola and appears to cause a higher proportion of severe episodes of cholera with the potential for higher death rates.
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 infrequent.
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 at much lower levels in Haiti and the Dominican Republic, though small outbreaks still occur. Sporadic cases associated with travel to or from cholera-affected countries in Asia and Africa continue to occur.
From 2010 through 2016, 107 cases of cholera were confirmed in the United States among people who had traveled internationally in the week before illness. Of these, approximately 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 both East and West Africa. There is a risk of cholera infection for travelers to areas where cholera is endemic or where there is an active epidemic. This 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 undercooked 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 consistently observe safe food, water, sanitation, and handwashing recommendations while in countries affected by cholera have virtually no risk of acquiring cholera.
Cholera most commonly manifests as acute watery diarrhea in an afebrile person. Infection is often mild or asymptomatic, but it can be severe. Severe cholera is characterized by profuse watery diarrhea, described as “rice-water stools,” often accompanied by nausea and vomiting, that 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, the case-fatality ratio is <1%.
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 (CIDT) do not yield an isolate for antimicrobial susceptibility testing and subtyping. Reflex culture to recover an isolate should be performed when a diagnosis of V. cholerae is derived from a CIDT, and the isolate should be forwarded to a public health laboratory for additional characterization. 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.
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 case-fatality ratios 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.
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.
No country or territory requires vaccination against cholera as a condition for entry. CVD 103-HgR, a single-dose oral cholera vaccine (Vaxchora, Emergent BioSolutions), 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.
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. A list of countries where cholera vaccine can be considered for travelers is found at wwwnc.cdc.gov/travel/diseases/cholera. However, cholera activity may be found only in certain parts of a country or in certain settings, and information about places with cholera activity may be incomplete because of variations in surveillance and reporting. Additional country-specific information may be found on the country-specific travel pages.
The vaccine is not routinely recommended for most travelers from the United States, as most do not visit areas with active cholera transmission.
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.
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.
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
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