Patient Presentation
A 17-year-old male came to clinic for travel immunizations before a medical mission to Haiti for 2 weeks. His father was a health care provider and had traveled to Haiti on two previous trips, but this trip was to spend more time in more rural locations. His father had been to the travel clinic and had received cholera vaccine along with malaria prophylaxis. He was current with typhoid vaccine. The pertinent physical exam showed a healthy teenager with normal vital signs and growth parameters in the 75-95%. His examination was normal.

The diagnosis of a healthy male was made. The pediatrician reviewed the Centers for Disease Control website for current immunization recommendations for Haiti. The teenager was current with his standard vaccinations and received typhoid vaccine and malaria prophylaxis along with counseling regarding using insect repellent, safe water and hygiene practices. “Unfortunately you just turned 17, and the cholera vaccine in the United States is only for those over 18 years, so I can’t give it to you. It’s really, really important that you use safe water and wash your hands well, ALL THE TIME,” the pediatrician emphasized. The father said that he had been making his son practice at home using bottled water for drinking, toothbrushing and preparing meals. “It’s a lot of work to fill up the bottles from the faucet and practice, but I don’t want to get sick so I guess its okay,” the teen obliged.

Discussion
Cholera is caused by more than 200 serogroups of Vibrio cholerae, a Gram-negative rod that is waterborne. Only two (serogroup O1 which causes about 99% of the cases, and O139) cause disease. There are biotypes of each of these serotypes. The only known hosts are humans. The organism colonizes the epithelial lining of the gut. Cholera toxin is produced by some species and if produced binds to specific receptors on host cells, activating a series of steps which cases massive loss of sodium, potassium, chloride, hydrogen carbonate, and fluids in vomitus and feces. A review of causes of diarrhea can be found here.

More than 1 billion people are at risk for cholera in endemic countries with an estimated 2.86 million cases and ~95,000 deaths annually Cholera is endemic in sub-Saharan Africa and Asia but has areas that have become epidemic such as Haiti and Yemen in the past few years. Studies in Africa have an incidence of < 0.3/10,000 which increased to 20/10,000 during epidemics. About half of the cases and deaths are in children < 5 years of age. For travelers from non-endemic countries cholera is rare with a risk of 0.01-0.001% per month of stay in a developing country. Cholera is rare in the United States with < 25 cases/year reported with most occurring among travelers to epidemic or endemic cholera.

Cholera is spread by direct fecal-oral and contaminated water or food routes thus the risk of cholera increases in areas where crowding, lack of access to clean water, sanitation and health care are issues. Incubation period is < 24 hours to 5 days. Only 1-25% of those exposed actually develop disease. Of those that are symptomatic, 10-20% experience severe disease. Symptomatic patients produce watery diarrhea sometimes referred to as "rice water stools." Emesis can also occur. Symptoms last 1 to a few days. Patients can have profuse fluid loss of up to 0.5 – 1.0 liters/hour and obviously severe dehydration is a major cause of morbidity and mortality if not promptly and aggressively treated. Healthy persons have been known to die within 24 hours of symptom onset because of the complications of dehydration.

Risk factors for cholera include number of bacteria ingested, lack of immunity from prior disease or vaccination, lack of passive immunity for newborn infants because of lack of breastfeeding, pregnancy, immunocompromised state (especially HIV), malnourishment, blood group O, and decreased ability to make gastric acid which neutralizes the bacteria. High concentrations of the bacteria is found in feces, and often vomitus also. There is some data suggesting “…that passage through a human host transiently increases the infective potential of V. cholerae by creating a hyperinfectious state that is maintained soon after shedding, and which may contribute to the epidemic spread of the disease.”

The diagnosis standard is by culture, but polymerase chain reaction testing and other rapid diagnostic testing is also available. Treatment is by rapid and aggressive administration of fluid and electrolytes. In patients with mild to moderate dehydration, oral rehydration with low osmolarity oral rehydration solution (ORS) is standard. The lower osmolarity compared to standard ORS decreases emesis. For severe dehydration, intravenous fluid administration with correction of electrolytes is imperative. Antibiotics are given to hospitalized patients during epidemics which decreases the symptom duration, stool volume, and length of time the active pathogen is excreted which reduces transmission and hospital length of stay. Doxycycline is usually the first choice, but ciprofloxacin or azithromycin are used in doxycycline-resistant areas. Unfortunately drug-resistance is common.

Although both children and adults are able to mount antibody responses to both the organism and the toxin, they are not reliably predictive of protection against cholera.

Learning Point
Cholera vaccines are available for use in endemic and epidemic areas, and for travelers.

• Dukoral® is a whole-cell, killed, monovalent vaccine again serotype O1
  • Has a cholera toxin subunit which also has some cross-reactivity with enterotoxigenic Escherichia coli and therefore it offers some protection for this entity also
  • Given orally
    • 3 doses for children given 1-6 weeks apart for ages 2-5 years
    • 2 doses are given 1-6 weeks apart for ages 6 years and up
  • Protection is 6 months for children 2-5 years, and 2 years for those 6 years and older
  • For revaccination
    • For children 2-5 years, 1 dose can be used if given within 6 months of primary immunization, otherwise re-start primary vaccination
    • For 6 years and up, 1 dose can be used if given within 2 years of primary immunization, otherwise re-start primary vaccination
  • Licensed in countries worldwide, primarily for travelers to endemic countries but has been used for epidemics
• Shanchol™, Euvichol®, and mORCVA™ are modified whole-cell, killed, bivalent vaccine against serotypes O1 and O139
  • These 3 vaccines are based on the same strains but are available in different areas of the world.
  • Does not have cholera toxin subunit therefore is no cross-reactivity with enterotoxigenic Escerichia coli
  • Given orally
    • 2 doses given 14 days apart for ages 1 year and older
  • Protection is up to 5 years
  • Licensed in countries worldwide, for travelers and also for epidemics
• Vaxchora® is a live-attenuated single-dose oral vaccine.
  • It is the only cholera vaccine available in the United States and is given as a single oral dose to people ages 18-64 years for those traveling to cholera-affected areas.
  • Its protection is at least 3 months according to the Centers for Disease Control, but others studies have shown efficacy for 6 months.

The World Health Organization recommends during humanitarian emergencies where there is a risk of cholera but no current outbreak that oral cholera vaccine be considered as an additional measure for prevention. International workers and travelers should also use safe hygiene practices. Emergency/relief workers who would be likely to encounter patients with cholera or exposed to contaminated food and water should be vaccinated. “Vaccination is not generally recommended for long-term or short-term travelers to cholera-affected countries,….”

Other vaccines are currently being developed.

Questions for Further Discussion
1. What are good “hygiene” practices for places with risks for fecal-oral transmission of infections?
2. What are good malaria prevention practices?

Related Cases

Disease: Cholera | Traveler’s Health

Symptom/Presentation: Health Maintenance and Disease Prevention | Diarrhea

Specialty: Infectious Diseases | Travel Medicine

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Cholera and Traveler’s Health.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Tran NT, Taylor R, Antierens A, Staderini N. Cholera in Pregnancy: A Systematic Review and Meta-Analysis of Fetal, Neonatal, and Maternal Mortality. PLoS One. 2015 Jul 15;10(7):e0132920.

Das JK, Ali A, Salam RA, Bhutta ZA. Antibiotics for the treatment of Cholera, Shigella and Cryptosporidium in children. BMC Public Health. 2013;13 Suppl 3:S10.

Cabrera A, Lepage JE, Sullivan KM, Seed SM. Vaxchora: A Single-Dose Oral Cholera Vaccine. Ann Pharmacother. 2017 Jul;51(7):584-589.

Wong KK, Burdette E, Mahon BE, Mintz ED, Ryan ET, Reingold AL. Recommendations of the Advisory Committee on Immunization Practices for Use of Cholera Vaccine. MMWR Morb Mortal Wkly Rep. 2017 May 12;66(18):482-485.

Cholera vaccines: WHO position paper – August 2017. Wkly Epidemiol Rec. 2017 Aug 25;92(34):477-98.

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa