para>Cholera in 3rd trimester of pregnancy is associated with greater dehydration and may lead to stillbirth. High level of dehydration is the greatest risk for poor fetal outcome.
Pediatric Considerations
EPIDEMIOLOGY
- Predominant age: all ages
- Predominant sex: male = female
- 75% of patients infected with V. cholerae do not develop symptoms. Patients continue to shed the organism in their feces for 1 to 2 weeks after infection.
- 80% of clinical cases are mild to moderate; 20% are severe with high fatality rates if untreated.
- Most U.S. cases are acquired through international travel.
- El Tor type (O1) of V. cholerae is the predominant biotype and is responsible for the most recent epidemic (1).
- New serotype now in Bangladesh, India (0139). Important because of lack of efficacy of standard vaccine. Several new variants have also been reported in Asia and Africa.
- Usual course: acute, chronic, and relapsing
- In the early stages, severely affected patients can lose 1 L/hr of body fluids (1).
Incidence
Since 1817, seven cholera epidemics have occurred (1).
Prevalence
An estimated 100,000 deaths and 3 million cases annually (2)
ETIOLOGY AND PATHOPHYSIOLOGY
- After ingesting an infectious dose (>108 organisms) through contaminated food/water sources, the organism reaches the small intestine where V. cholerae (O-group 1) produces an enterotoxin (CTX) promoting copious fluid secretion into the intestinal lumen.
- Toxicity is mediated by A1 enterotoxin subunit, which increases cyclic adenosine monophosphate (cAMP) production. This results in a reduction sodium and chloride absorption by intestinal microvilli and an increase in fluid excretion (massive watery diarrhea).
- The incubation period is 12 hours to 5 days, with a median of 1.5 days (1).
RISK FACTORS
- Traveling or living in epidemic/endemic areas
- Exposure to contaminated food or water
- Person-to-person transmission (rare)
- In endemic areas, low socioeconomic status children <5 years old who do not breast feed are at highest risk.
- Cases are more severe in patients with blood group O compared with AB (cholera toxin takes longer to penetrate mucous layer of small bowel in patients with blood types A, B, and AB who have blood group antibodies in the mucosal layer [1]).
- Reduced gastric acid secretion: medications, gastrectomy
GENERAL PREVENTION
- Water purification
- Appropriate public sanitation
- Proper food selection and preparation (e.g., no unpeeled raw fruits or vegetables, no raw or undercooked seafood)
- Enteric precautions
- Chemoprophylaxis for exposed contacts is not routinely recommend (3)[C].
- Natural infection confers long-lasting immunity.
- Nutrition:
- WHO recommends zinc supplementation in children 12 months to 5 years who are nutritionally deplete (low-socioeconomic status vs. stunted growth) at a dose of 20 mg/day in order to reduce the incidence and prevalence of acute infectious diarrhea (1)[A].
- Prophylactic vaccine
- Not recommended for routine traveler's diarrhea or dysentery (2)[A]
- Concomitant administration with yellow fever vaccine may decrease response to yellow fever.
- Newer oral killed whole-cell vaccines, Dukoral and Shanchol/mORCVAX, provide longer immunity in adults, often up to 2 years from a single dose and up to 3 to 4 years with annual boosters (1)[A]. WHO recommends use in endemic areas (1)[C].
- Several prior vaccines are no longer available.
COMMONLY ASSOCIATED CONDITIONS
Increased risk of disease with gastric achlorhydria
DIAGNOSIS
HISTORY
- History of travel to endemic area and exposure to contaminated food/water source
- Abrupt onset of explosive, painless watery diarrhea ("rice-water stools"ť) without tenesmus
- Abdominal discomfort, vomiting, audible bowel sounds
- Anorexia, lethargy, apathy, malaise, listlessness
- May have sudden diuresis followed by progressive oliguria, anuria, and subsequent thirst
- Weakness and prostration
- Seizures are possible as dehydration progresses.
PHYSICAL EXAM
- Vital signs consistent with progressive dehydration (tachycardia, hypotension). Fever is common. As course worsens, patients become hypoxic (cyanotic) and hypothermic.
- Decreased skin turgor (washerwoman's fingers)
- Distant heart sounds, dysrhythmias (electrolyte imbalance)
- Increased (early in course) or decreased bowel sounds (later) depending on state of hydration
- Sunken eyes
- Weak peripheral pulses
DIFFERENTIAL DIAGNOSIS
Other causes of severe diarrhea and dehydration (e.g., Shigella, Escherichia coli, gastroenteric viruses)
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Stool culture: on selective media (thiosulfate citrate bile salts sucrose [TCBS]) (1)
- Typed antisera-specific agglutination
- Rapid tests: Crystal VC rapid dipstick test 97% sensitive, 71-76% specific; useful to confirm outbreak in nonendemic area (1)[B]
- Dark-field microscopy: characteristic Vibrio motility in stool (1)
- Increased vibriocidal antibodies in nonimmunized patient
- Laboratory features of severe dehydration:
- Acidosis, hypokalemia, hyponatremia, hypochloremia, hypoglycemia, specific gravity elevated on urinalysis, polycythemia on CBC
Test Interpretation
Biopsy of small bowel mucosa: Organism adheres to mucosa which remains intact; increased cellularity of the lamina propria and increased vascular congestion. Lymphoid hyperplasia in Peyer patches, spleen, and mesenteric lymph nodes.
TREATMENT
- Primary goal is to replenish fluid losses. With proper treatment, fatality rates are <1%.
- Two phases of rehydration: initial and maintenance (4)[C]
- Evaluate initial level of dehydration (current vs. prior weight). Initial rehydration (first 2 to 4 hours) and maintenance (until diarrhea abates). Oral route is preferred if tolerated.
- Replace fluids intravenously in moderately dehydrated patients who can't tolerate oral fluids.
- Severely dehydrated: An infusion rate of 100 mL/kg/hr over 3 to 5 hours is advised.
- The maintenance phase for patients with high stool purge (i.e., >10 mL/kg/hr)
- Maintenance phase: Use oral rehydration solution (ORS) at a rate of 800 to 1,000 mL/hr. Match ongoing losses with ORS intake.
- Register output and intake volumes on predesigned charts and periodically review.
- Reduced-osmolarity ORS may cause low-blood sodium levels with cholera.
- Discharge patients to the treatment center if oral tolerance is ≥1,000 mL/hr, urine volume is ≥40 mL/hr, and stool volume is ≤400 mL/hr.
GENERAL MEASURES
- Rehydrate as above
- Cholera treatment centers (CTC) in epidemic settings
MEDICATION
First Line
- Oral rehydration salts (ORS)
- ORS commercial brands available or prepared using 1 L of water with 6 tsp of sugar and 1/2 tsp of salt.
- Oral rehydration salt formula from the WHO (4)[C], per liter
- Sodium chloride 3.5 g
- Potassium chloride 1.5 g
- Glucose 20 g
- Trisodium citrate 2.9 g
- Rehydration for severely dehydrated patients
- IV rehydration (Ringer lactate) is followed by oral or nasogastric administration of glucose or sucrose-electrolyte solution.
- Nutrition: Zinc (20 mg daily) decreases duration and severity of diarrhea in patients who are nutritionally depleted.
- Antibiotics
- Moderate/severe disease: Antibiotics reduce the duration of symptomatic cholera by 1.5 days and limit life-threatening dehydration (5)[A].
- For adults and children >8 years old: doxycycline (Vibramycin): 300 mg once or 100 mg BID for 3 days or tetracycline 50 mg/kg/day in 4 equally divided doses (max 500 mg/dose) for 3 days (5)[A]
- For children
- 3 years or older, able to swallow pill: tetracycline 12.3 mg/kg q6h for 3 days or azithromycin 20 mg/kg — 1 not exceeding 1 g (5)[A]
- <3 years old or unable to swallow tablet: suspension form
- Pregnancy: erythromycin 500 mg q6h for 3 days or azithromycin 1 g PO single dose (6)[C]
- Contraindications: tetracycline, doxycycline: pregnancy risk Category D
- Precautions: tetracycline, doxycyline: may cause photosensitivity
- Significant possible interactions: antacids, dairy products, or iron can decrease absorption of tetracycline.
Second Line
- Adults: ciprofloxacin 1 g PO single dose or azithromycin 1 g PO single dose (5)[A]
- Children: ciprofloxacin 20 mg/kg single dose or doxycycline 4 to 6 mg/kg single dose; suspension if not able to swallow tablets (5)[A]
- Precautions: Doxycycline has been associated with a low risk of dental staining in children, but benefits outweigh risks in treatment of cholera (6)[C].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Outpatient for mild cases; inpatient for moderate to severe cases
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Bed rest until symptoms resolve and strength returns
Patient Monitoring
Observe patient until symptoms are resolved.
DIET
Small, frequent meals when vomiting stops and appetite returns
PATIENT EDUCATION
- Centers for Disease Control and Prevention (CDC): Traveler's Information Hotline: 404-332-4559 (available 24 hours via a touch-tone telephone)
- International Association for Medical Assistance to Travelers, 417 Center St., Lewiston, NY 14092; 716-754-4883
PROGNOSIS
- Prompt PO or IV treatment saves lives.
- Antibiotic treatment reduces duration and infectivity.
- Mortality is <1% with appropriate supportive care.
- Mortality is higher (50%) with untreated hypovolemic shock.
COMPLICATIONS
- Hypovolemic shock. "Cholera sicca"ť occurs when fluid accumulates in the intestinal lumen (without diarrhea) causing circulatory collapse.
- Chronic biliary infection
- Intermittent stool shedding
REFERENCES
11 Harris JB, LaRocque RC, Qadri F, et al. Cholera. Lancet. 2012;379(9835):2466-2476.22 Nickonchuk T, Lindblad AJ, Kolber MR. Oral cholera vaccine for traveler's diarrhea prophylaxis. Can Fam Physician. 2014;60(5):451.33 Reveiz L, Chapman E, Ramon-Pardo P, et al. Chemoprophylaxis in contacts of patients with cholera: systematic review and meta-analysis. PLoS One. 2011;6(11):e27060.44 World Health Organization. The Treatment of Diarrhoea: A Manual for Physicians and Other Senior Health Workers. 4th rev. Geneva, Switzerland: World Health Organization; 2005.55 Leibovici-Weissman Y, Neuberger A, Bitterman R, et al. Antimicrobial drugs for treating cholera. Cochrane Database Syst Rev. 2014;(6):CD008625.66 Pan American Health Organization. Recommendations for clinical management of cholera. http://www.paho.org/hq/index.php?option=com_docman&task=doc_view&Itemid=0&d=10813&ng=en. Accessed 2015.
ADDITIONAL READING
- Ali M, Lopez AL, You YA, et al. The global burden of cholera. Bull World Health Organ. 2012;90(3):209A-218A.
- Azman AS, Rudolph KE, Cummings DA, et al. The incubation period of cholera: a systematic review. J Infect. 2013;66(5):432-438.
- Cholera vaccines: WHO position paper. Wkly Epidemiol Rec [in English, French]. 2010;85(13):117-128.
- Ciglenecki I, Bichet M, Tena J. Cholera in pregnancy: outcomes from a specialized cholera treatment unit for pregnant women in L ©og ˘ne, Haiti. PLoS Negl Trop Dis. 2013;7(8):e2368.
- Graves PM, Deeks JJ, Demicheli V, et al. Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected). Cochrane Database Syst Rev. 2010;(8):CD000974.
- Gregorio GV, Gonzales ML, Dans LF, et al. Polymer-based oral rehydration solution for treating acute watery diarrhoea. Cochrane Database Syst Rev. 2009;(2):CD006519.
- Hirschhorn N, Chowdhury AK, Lindenbaum J. Cholera in pregnant women. Lancet. 1969;1(7608):1230-1232.
- Liberato SC, Singh G, Mulholland K. Zinc supplementation in young children: a review of the literature focusing on diarrhoea prevention and treatment. Clin Nutr. 2015;34(2):181-188.
- Sinclair D, Abba K, Zaman K, et al. Oral vaccines for preventing cholera. Cochrane Database Syst Rev. 2011;(3):CD008603.
- Walton D, Suri A, Farmer P. Cholera in Haiti: fully integrating prevention and care. Ann Intern Med. 2011;154(9):635-637.
SEE ALSO
Diarrhea, Acute; Oral Rehydration
CODES
ICD10
- A00.9 Cholera, unspecified
- A00.0 Cholera due to Vibrio cholerae 01, biovar cholerae
- A00.1 Cholera due to Vibrio cholerae 01, biovar eltor
ICD9
- 001.9 Cholera, unspecified
- 001.0 Cholera due to vibrio cholerae
- 001.1 Cholera due to vibrio cholerae el tor
SNOMED
- Cholera (disorder)
- Cholera due to Vibrio cholerae O1 Classical biotype (disorder)
- Cholera due to Vibrio cholerae El Tor
CLINICAL PEARLS
- Personal (food and water selection/preparation; hand hygiene) and public sanitation are central to cholera prevention.
- The current cholera vaccine is not indicated to prevent routine traveler's diarrhea but is recommended by WHO for use in endemic areas.
- During acute cholera infection, patients may lose as much as 1 L of stool per hour. Prompt rehydration is essential. ORS are preferred.