Cholera

Definition

Problem Statement

• For 2019 alone, WHO received notification of 9,23,037 cases from 55 countries, including 2,420 deaths.
• The true burden is estimated at 1.3-4.0 million cases and 21,000-1,43,000 deaths annually.
• Two serogroups - O1 and O139 - cause outbreaks. O1 causes the majority; O139 was first identified in Bangladesh in 1992 and is confined to South-East Asia.
• Non-O1 and non-O139 V. cholerae can cause mild diarrhoea but do not generate epidemics.
• New El Tor variant strains detected in parts of Asia and Africa cause more severe cholera with higher case fatality rates.
• Global warming creates a favorable environment for the bacteria.
• Cholera transmission is closely linked to inadequate environmental management - peri-urban slums, areas after disasters, and displacement camps are at highest risk.
• Cholera remains a global threat to public health and a key indicator of lack of social development.

India

• Since El Tor biotype was introduced in 1964, West Bengal lost its reputation as the "home of cholera."
• The El Tor biotype has completely replaced the classical biotype; most isolates today belong to serotype Ogawa.
• In 2018, approximately 651 cholera cases were reported with 6 deaths - majority from Uttar Pradesh (153), Delhi (134), West Bengal (126), and Gujarat (106).

Epidemiological Features

• The introduction of cholera into any country cannot be prevented, but it creates a problem only where sanitation is defective.
• Epidemics are characteristically abrupt, reach a peak quickly, and subside gradually as the "force of infection" declines - they are self-limiting due to acquisition of temporary immunity and a large number of subclinical cases.
• The force of infection has two components: through water and through contacts. Elimination of contaminated water does not immediately end an outbreak - a "tail" of epidemic continues via contact transmission.
• In endemic areas, cholera shows seasonal fluctuations unlike typhoid fever. Seasonal patterns vary by region and have changed over time.

Etiology and Agent Factors

• A Gram-negative, comma-shaped, motile organism with a single polar flagellum.
• Grows in alkaline media (pH 8.0-9.5); alkaline peptone water is the enrichment medium.
• Three biotypes of V. cholerae O1: Classical, El Tor, and the 7th Pandemic El Tor variant.
• Two main serotypes: Ogawa and Inaba (Hikojima is intermediate).
• Classical and El Tor biotypes differ biologically but cause similar disease.

• Survives in water for 2-14 days (or longer in favorable conditions).
• Destroyed rapidly by drying, sunlight, and disinfectants.
• The El Tor biotype survives longer in the environment than the classical biotype.

Source of Infection

1. Cases - both clinical and subclinical (ratio of clinical to subclinical is 1:25 in El Tor; about 1:5 in classical cholera).
2. Carriers - a very important source of infection, especially with El Tor.
   • Incubation carriers
   • Convalescent carriers
   • Healthy/contact carriers
   • Chronic carriers (rare; V. cholerae can persist in the biliary tract)

Modes of Transmission

1. Water - the most important vehicle. Contaminated drinking water, ponds, rivers, and wells.
2. Food - contaminated cooked foods, raw vegetables, fruits, seafood (shellfish especially), and street foods.
3. Contact (direct fecal-oral) - through soiled hands, shared utensils, or direct contact with patients.
4. Flies - mechanical vectors that can carry organisms from excreta to food.
5. Vomitus - can also act as a source of infection.

Host Factors

• Age: All age groups are susceptible; in endemic areas, children are more affected.
• Immunity: Natural infection confers immunity, but it is not long-lasting. Both humoral and local (intestinal IgA) immunity play a role.
• Gastric acid: Acts as a natural barrier - hypochlorhydria (e.g., in persons on antacids, post-gastrectomy, or with H. pylori) increases susceptibility.
• Blood group O: Associated with increased susceptibility to severe disease, especially with classical biotype.

Environmental Factors

• Poor sanitation, lack of safe drinking water, improper sewage disposal, overcrowding, and poverty.
• Seasonal factors: rainfall, temperature, and flooding influence incidence.
• Large gatherings, fairs, pilgrimages, and disasters are classic settings for cholera outbreaks.

Clinical Features

1. Asymptomatic/subclinical infection - the most common form, especially with El Tor.
2. Mild cholera - watery diarrhoea, no significant dehydration.
3. Moderate cholera - profuse watery diarrhoea, some dehydration.
4. Severe cholera (cholera gravis) - sudden onset of profuse "rice water" stools, painless, effortless; projectile vomiting; rapid and severe dehydration causing:
   • Intense thirst, dry mucous membranes
   • Sunken eyes, hollow cheeks
   • Decreased skin turgor ("washerwoman's hands")
   • Muscle cramps (due to electrolyte loss)
   • Suppression/absence of urine
   • Tachycardia, hypotension, shock
   • Hoarse voice, loss of consciousness in terminal stages
   • CFR without treatment: 30-40%

Pathophysiology

Laboratory Diagnosis

1. Dark-field microscopy - shows characteristic "shooting star" motility of vibrios; inhibited by adding specific antiserum (Faden reaction / Immobilization test).
2. Culture:
   • Direct plating on TCBS (Thiosulphate Citrate Bile Salt Sucrose) agar - yellow colonies.
   • Enrichment in alkaline peptone water (pH 8.6) for 6 hours, then subculture on TCBS.
3. Biochemical identification: Sugar fermentation, oxidase test, string test (mucoidity in 0.5% sodium deoxycholate).
4. Serological typing with O1 and O139 antisera.
5. Phage typing - performed at the National Institute of Cholera and Enteric Diseases, Kolkata.
6. Rapid tests - dipstick tests now available for field diagnosis.

Differential Diagnosis

• Acute gastroenteritis from other causes (E. coli, Salmonella, Rotavirus)
• Poisoning (arsenic, organophosphate)
• Other causes of secretory diarrhoea

Treatment

1. Oral Rehydration Therapy (ORT)

• For mild-to-moderate dehydration.
• WHO-ORS composition: NaCl 3.5 g, KCl 1.5 g, NaHCO₃ 2.5 g (or trisodium citrate 2.9 g), Glucose 20 g per litre of water.
• Low-osmolarity ORS (Na 75 mmol/L) is now recommended by WHO.

2. Intravenous Rehydration

• For severe dehydration or when oral route is not feasible (persistent vomiting).
• Ringer's Lactate is the fluid of choice.
• Hartmann's solution or normal saline can be used.

3. Antibiotics (Adjuncts to therapy)

• Started after vomiting stops (usually after 3-4 hours of ORT).
• Reduce the duration of diarrhoea and vibrio excretion.
• Commonly used: Fluoroquinolones, Tetracycline, Azithromycin, Ampicillin, TMP-SMX.
• Avoid: Antidiarrhoeals, antiemetics, antispasmodics, cardiotonics, corticosteroids.
• If diarrhoea persists after 48 hours, antibiotic resistance should be suspected.

Control of Cholera

1. Case Management

• Immediate rehydration therapy.
• Isolation and notification.
• Disinfection of stools, vomitus, linen, and utensils.

2. Contact Management

• Surveillance of household contacts for 5 days.
• Chemoprophylaxis (tetracycline or doxycycline) for close contacts in high-risk situations - though mass chemoprophylaxis is not recommended.

3. Water Control

• Safe water supply is the most important intervention.
• Emergency: properly treated water with free residual chlorine in covered, narrow-mouthed containers.
• Boiling or chlorination for rural areas.
• Long-term: permanent piped water supply.

4. Food Control

• Prohibit sale of street food during outbreaks.
• Proper cooking and storage of food.
• Avoid raw vegetables, unpeeled fruits, and raw shellfish.

5. Excreta Disposal

• Provision of sanitary latrines.
• Safe disposal of human excreta to prevent contamination of water and soil.

6. Fly Control

• Environmental sanitation to reduce fly breeding.
• Use of fly screens, disposal of garbage.

7. Health Education

• Handwashing with soap after defecation and before meals.
• Safe water and food hygiene practices.

8. Vaccination

• Two WHO-prequalified OCVs are currently available:
  • Dukoral (WC-rBS vaccine): Two doses, 1 week apart; 85-90% efficacy for 6 months; licensed for travelers.
  • Shanchol / mORCVAX: Bivalent (O1 + O139); two doses, 2 weeks apart; provides 65-85% efficacy; used in mass vaccination campaigns.
• OCVs are used as an additional tool in endemic/epidemic settings, not a substitute for sanitation.
• Parenteral (injectable) cholera vaccines are no longer recommended - they confer only 50% efficacy for 3-6 months.

9. Epidemiological Investigation

• Define extent of outbreak.
• Identify modes of transmission.
• Institutions assisting: National Institute of Communicable Diseases (Delhi), All India Institute of Hygiene and Public Health (Kolkata), National Institute of Cholera and Enteric Diseases (Kolkata - WHO International Centre for Vibrios).

10. International Measures

• Cholera is a notifiable disease under International Health Regulations (IHR).
• Countries are required to notify WHO of confirmed cases.
• International Certificate of Vaccination for cholera is no longer required by any country.

Pandemic History

• 1st-6th pandemics (1817-1923): caused by classical biotype.
• 7th pandemic (1961-present): caused by El Tor biotype; originated in Indonesia (Sulawesi), spread globally; continues to this day.
• In 1992, a new serogroup O139 (Bengal) emerged in South Asia and was feared to trigger an 8th pandemic, but did not.