Cholera: Causes, Symptoms, Diagnosis and Treatment

Cholera is an acute infectious disease targeting the lower intestines, characterized by severe diarrhea, vomiting, muscle cramps, reduced urine output, and rapid onset of collapse. This formidable disease leads to massive fluid loss, causing severe dehydration and, if untreated, can result in death within hours.

Etiology

• Site: Gastrointestinal Tract (GIT)
• Agent: Vibrio cholerae

Morphological Characteristics

Vibrio cholerae are Gram-negative, curved rod-shaped bacteria, non-capsulated, non-sporulating, and motile via a polar flagellum, typically found as single cells.

Cultural Characteristics

1. Vibrio cholerae forms smooth, convex, and round colonies that appear opaque and granular under transmitted light.
2. They can grow on various media, including those enriched with bile salts and asparagine.
3. On Thiosulfate Citrate Bile Salt (TCBS) agar, they produce distinctive yellow colonies.
4. These bacteria are highly susceptible to acidic environments, thriving best at a pH range of 8.5 to 9.5.

Biochemical Characteristics

Vibrio cholerae ferments sucrose and maltose but not arabinose. They are oxidase-positive, distinguishing them from other Gram-negative enteric bacteria. Some strains are halotolerant, while others are halophilic, requiring NaCl for growth.

Antigenic Characteristics

• Vibrio cholerae possesses two main antigens: flagellar (H) and somatic (O).
• The H antigen is heat-labile and common across all Vibrios.
• The O antigen, heat-stable and polysaccharide-based, classifies the bacteria into six serogroups with over 60 serotypes.
• Epidemic cholera is primarily caused by a single serotype, subdivided into two biotypes:
  1. Classical
  2. El Tor
• El Tor biotypes differ from classical ones by their ability to lyse goat or sheep erythrocytes in the Grieg test.
• The 01 serotypes have two or three antigenic factors: A, B, and C.
  1. Factors A and B are present in serotype Ogawa.
  2. Factors A and C are found in serotype Inaba.
  3. Factors A, B, and C are present in serotype Hikojima.

Cholera Toxin

Vibrio cholerae produces an enterotoxin called Choleragen, a polymeric protein of approximately 84,000 daltons, comprising two domains:

1. Domain A: Weighs 28,000 daltons, crucial for the toxin's biological activity.
2. Domain B (Choleragenoid): Weighs 56,000 daltons, responsible for binding the toxin to host cell receptors and is immunologically active.

Additionally, Vibrio cholerae produces Zonula Occludens Toxin (ZOT), which disrupts tight junctions between enterocytes, facilitating water and electrolyte loss.

Mode of Action of Toxins

The B subunit of the toxin facilitates the attachment of the toxin to the small intestine's epithelial cells and promotes the entry of the A subunit. The A subunit alters the regulatory protein activity that controls adenylate cyclase. This enzyme converts ATP to cyclic AMP, increasing cyclic AMP levels and causing severe water and electrolyte loss, leading to diarrhea and potentially fatal dehydration and acidosis.

Pathogenesis

Cholera typically emerges in epidemic conditions such as overcrowding, floods, wars, and famines, with humans as the sole natural hosts. Infection requires ingestion of 10^8 to 10^10 organisms, usually through contaminated water or food. The bacteria proliferate in the small intestine, producing Choleragen, which induces a substantial secretion of isotonic fluid into the intestinal lumen.

Clinical Findings

The incubation period ranges from a few hours to four days, followed by sudden onset of symptoms including nausea, vomiting, diarrhea, abdominal cramps, rapid dehydration, and significant fluid and electrolyte loss. Without treatment, the mortality rate can be as high as 25% to 50%.

Laboratory Diagnosis

Diagnosis involves:

• Physical Examination: Stool analysis.
• Microscopy: Direct and darkfield or phase contrast microscopy to detect motile Vibrios.
• Culture: Rapid growth on peptone agar and TCBS at near pH 9, with colonies visible after 18-24 hours.
• Agglutination: Tests using anti-O group serum and biochemical reactions.

Epidemiology

Humans are the only hosts for cholera, with transmission occurring via contaminated water, food, or flies. In outbreak situations, 1% to 5% of exposed susceptible individuals develop the disease, with the carrier state typically lasting 3 to 4 weeks.

Prevention

1. Ensure a clean water supply and treat water before distribution.
2. Properly manage sewer systems.
3. Maintain personal hygiene and sanitation.

Treatment

Cholera treatment focuses on rehydration using Oral Rehydration Salts (ORS) containing sodium chloride, sodium bicarbonate, potassium chloride, and glucose. During epidemics, 80-90% of diarrhea patients can be managed with oral rehydration alone, while severely dehydrated patients may require intravenous fluids.