10.11 CHOLERA
Cholera is an ancient killer disease, with many pandemics recorded in different parts of the world with very high mortality. In India. Disease is currently endemic throughout the country, with intermittent focal outbreaks.
Epidemiology: Cholera is caused by different strains of vibrio cholerae 01, a gram-negative motile, slightly curved rods with polar flagellum.
V. cholerae 01 has two major biotypes—classical and El Tor vibrio, subdivided into many serotypes (serovars) according to somatic antigens—mainly the ogawa, inaba and hikojima strains.
Current infections in India are mainly caused by El Tor biotype and ogawa serotypes. Last two decades have seen emergence of a new virulent strain V. cholerae 0139 from Chennai, responsible for the many outbreaks in India and south Asia.
Source of infection is an asymptomatic carrier or a case, and infection is transmitted feco-orally after ingestion of contaminated water or food. Period of infectivity is 7-10 days for a case, though chronic carrier state may continue for gt;10 years.
Cholera affects all age groups with highest attack rate and more severe disease in children. Most outbreaks begin in summer or rainy season, with two important risk factors—poor sanitary conditions and large congregations of people, e.g. in fairs, kumbhs, etc.
Etiopathogenesis: V. Cholera, on reaching the small intestine, proliferate and colonize the duodenum/ jejunum to produce various enterotoxins. Two important enterotoxins include:
a. A cholera toxin, which activates adenylate cyclase to raise cyclic AMP levels in intestinal mucosa, with decreased sodium and chloride absorption as well as increased chloride secretion.
b. A zonula occludens toxin (zot), which alters the intercellular tight junctions to increase intestinal mucosal permeability and leakage of water and electrolytes into lumen.
Clinical manifestations depend on the type of strain, dose of organisms and age of the patient. El Tor infections are frequently asymptomatic (gt;95%) as compared to classical Vibrio (lt;20%).
A typical case present after an incubation period of 6 hours - 5 days, with 3 stages:
a. Stage of evacuation characterized by abrupt onset of profuse, painless, watery diarrhea (rice-water stools) with fishy odor and vomiting.
b. Stage of collapse due to extensive fluid and electrolyte loss with severe dehydration, shock, hypothermia, renal failure and acidosis. Patient develops intense thirst and muscular cramps due to dyselectrolytemia, and gradually becomes disoriented or stuporus. Purging can continue for as long as one week, unless untreated patients die due to dehydration and acidosis.
c. Stage of recovery in survivors begins with decreased frequency, better consistency, appearance of color (bile) in stools and improved hydration.
However, classical presentation is seen in only 10-15% cases while other children present with milder nonspecific diarrhea and recover within 1-3 days.
Diagnosis should be suspected in any case from endemic region, presenting with profuse diarrhea and/or ricewater stools. Confirmation requires:
• Direct stool microscopy (hanging-drop preparation) under dark-field illumination for motile Vibrio, which appear like many shooting stars in the dark sky. Motility ceases on mixing with polyvalent anti-Vibrio
sera. Stools should be collected before antimicrobial therapy on a transport media, e.g. Venkatraman- Ramakrishnan media or alkaline-peptone water and transported to the laboratory immediately for direct motility examination and culture.
• Stool cultures are necessary for confirmation, biotyping, sero-typing and phage-typing of infections for epidemiological purpose. Cultures are done on bile-salt agar media, e.g. thiosulfate citrate bile sucrose (TCBS), after initial enrichment in peptone-water tellurite media.
• Serological tests are not useful except for epidemiological studies and molecular identification with PCR-DNA probes is possible but rarely used.
Management: Prompt management is essential to reduce mortality, prevent further transmission and control the outbreak and includes:
• Fluid and electrolyte therapy: Over 90% cases of cholera can be managed with ORS alone, which should be started as early as possible and given ad libitum with minimum 75 ml/kg during first 24 hours plus 50-100 ml after each stool. IV fluid therapy with Ringer lactate is required in cases with: (a) severe dehydration and shock, (b) persistent vomiting, and
(c) altered sensorium (see Ch 7.7 for fluid therapy).
• Antimicrobial therapy: Antibiotics shorten the course of illness and reduce the risk of transmission. Drugs of choice, in order of preference, are PO Tetracycline 50 mg/kg/day q6hr or PO Erythromycin 50 mg/kg/ day q6hr, both for 3 days. Single dose PO Ciprofloxacin 20 mg/kg or Azithromycin 20 mg/kg are equally effective.
• Continuous monitoring for intake/output of fluids, hydration status and electrolyte disturbances.
• Adequate parenteral nutrition in critically sick children, though oral feeds should be started as soon as possible.
• Treatment of complications, e.g. (a) circulatory shock, (b) electrolyte disturbances, e.g. hypokalemia due to excessive stool loss or hypocalcemic tetany due to persistent vomiting, (c) acidosis, (d) hypoglycemia, (e) neurological depression due to hypovolemia and hypoxia, and (f) pulmonary edema due to fluid overload.
Prevention: Control of cholera outbreak is a major public health exercise, involving:
• Immediate notification to the authorities,
• Early detection of cases and asymptomatic carriers by contact-stool examinations and door-to-door survey in affected locality,
• Public health measures to improve sanitary conditions and excreta disposal,
• Proper disposal/disinfection of infectious biomedical waste,
• Vaccination is recommended only in special circumstances, e.g. residents and travellers of highly endemic regions and high-risk settings for outbreaks, e.g. kumbh. It should not be used as outbreak control measure.
Two types of whole-cell killed oral cholera vaccines are available, of which only a bivalent vaccine (Shanchol) containing V. cholerae 01 (classic and El Tor) and V. cholerae 0139 serotypes is licensed in India, to be given orally as two doses at two weeks interval, only beyond two years of age.
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