CHOLERA
Cholera is an acute diarrheal disease that can, in a matter of hours, result in profound, rapidly progressive dehydration and death.
ETIOLOGY AND EPIDEMIOLOGY - V. cholerae -155 serogroups. Divided into those that agglutinate in antisera to the O1 group antigen (V. cholerae O1) and those that do not (non-O1 V. cholerae). Serogroup O1 was, until the emergence of serogroup O139, the exclusive cause of epidemic cholera. v. cholerae O139 (also called V. cholerae Bengal)
V. cholerae O1 exists in two biotypes, classical and El Tor,. Each biotype is further subdivided into two serotypes, termed Inaba and Ogawa.
Ingestion of water/food contaminated by human No known animal reservoir. ID50 is reduced in hypochlorhydric persons, in those using antacids, and when gastric acidity is buffered by a meal. In endemic areas, the disease is more common in the summer and fall months. In endemic areas, children < 2 years of age are less likely to develop severe cholera than are older children, perhaps because of passive immunity acquired from breast milk.; those with type O blood are at greatest risk, while those with type AB are at least risk.
PATHOGENESIS - Contaminated food / water --- Adherence to the intestinal epithelium - mediated by the toxin-coregulated pilus (TCP) -- intestinal colonization --- produces CTX,[monomeric enzymatic moiety (the A subunit) and a pentameric binding moiety (the B subunit) ] -- B pentamer binds to GM1 ganglioside (toxin receptor) on the surface of jejunal epithelial cells & makes delivery of the A subunit to its cytosolic target -- activated A subunit (A1) irreversibly upregulates the cyclase catalytic subunit --- intracellular accumulation of high levels of cyclic AMP ---- cyclic AMP inhibits the absorptive sodium transport system in villus cells and activates the excretory chloride transport system in crypt cells ----- accumulation of sodium chloride in the intestinal lumen ---- water moves passively to maintain osmolality --- isotonic fluid accumulates in the lumen --- watery diarrhea results
Unless the wasted fluid and electrolytes are adequately replaced, shock (due to profound dehydration) and acidosis (due to loss of bicarbonate) follow.
Increasing evidence indicates that CTX also enhances intestinal secretion via prostaglandins and/or neural histamine receptors.
CLINICAL MANIFESTATIONS - incubation period - 24- to 48-h. Sudden onset of painless watery diarrhea & is often followed by vomiting. If fluids and electrolytes are not replaced, hypovolemic shock and death ensue. Fever is usually absent. Muscle cramps due to electrolyte disturbances are common. The stool has a characteristic appearance: a nonbilious, gray, slightly cloudy fluid with flecks of mucus, no blood, and a somewhat sweet, inoffensive odor -- "rice-water" stool . Clinical symptoms parallel volume contraction: At losses of 3 to 5% of normal body weight, thirst develops; at 5 to 8%, postural hypotension, weakness, tachycardia, and decreased skin turgor are documented; and at 10%, oliguria, weak or absent pulses, sunken eyes (and, in infants, sunken fontanelles), wrinkled ("washerwoman") skin, somnolence, and coma are characteristic. Complications derive exclusively from the effects of volume and electrolyte depletion and include renal failure due to acute tubular necrosis. Thus, if the patient is adequately treated with fluid and salt, complications are averted and the process is self-limited, resolving in a few days.
Laboratory data - elevated hematocrit ; mild neutrophilic leukocytosis; elevated levels of BUN and creatinine; normal Na /K /Cl; a markedly reduced HCO3 level (15 mmol/L); and an elevated anion gap (due to increases in serum lactate, protein, and phosphate). Arterial pH is usually low (about 7.2).
DIAGNOSIS - It can be detected directly by dark-field microscopy on a wet mount of fresh stool, and its serotype can be discerned by immobilization with Inaba- or Ogawa-specific antiserum. Culture media- thiosulfate-citrate-bile salts-sucrose (TCBS) agar
TREATMENT - Cholera is simple to treat; only the rapid and adequate replacement of fluids, electrolytes, and base is required.
It has been proved conclusively that fluid may be given orally (takes advantage of the hexose-Na+ cotransport mechanism). Since Na+ losses in the stool are high, a fluid containing Na+ at 90 mmol/L has been recommended by WHO
Severely dehydrated patients – IVF : RL - must be used with additional potassium supplements, preferably given by mouth. The total fluid deficit in severely dehydrated patients (10% of body weight) can be replaced safely within the first 4 h of therapy, half within the first hour. Thereafter, oral therapy can usually be initiated, with the goal of maintaining fluid intake equal to fluid output.
Antibiotic : reduces duration and volume of fluid loss and will hasten clearance of the organism from the stool. Single-dose tetracycline (2 g) or doxycycline (300 mg) / Ciprofloxacineither in a single dose (30 mg/kg, not to exceed a total dose of 1 g) or erythromycin (a total of 40 mg/kg daily in three divided doses for 3 days) is a clinically effective substitute. For children, furazolidone and trimethoprim-sulfamethoxazole
PREVENTION - Provision of safe water and facilities for sanitary disposal of feces.
Two types of oral cholera vaccines are under development.
1. killed : two formulations A. killed whole cell + nontoxic B subunit of CTX (WC/BS) and
B. composed solely of killed bacteria. The protective efficacy of WC/BS was superior to that of WC during the initial 8 months of follow-up (69 versus 41%) but equivalent or inferior thereafter. Immunity was relatively sustained in persons vaccinated at an age of 5 years but was not well sustained in younger vaccinees.
Strain CVD 103-HgR, an oral live cholera vaccine licensed for immunization of travelers in Europe, this vaccine is more effective against classical than against El Tor cholera.
Composition of World Health Organization ORS
Constituent Concentration, mmol/L
Na+ 90
K+ 20
Cl 80
Citratec 10
Glucose 110
If prepackaged ORS is unavailable, a simple homemade alternative can be prepared by combining 5 g NaCl (about 1 level teaspoon) with either 50 g precooked rice cereal or 40 g sucrose in 1 L of drinking water. In that case, potassium must be supplied separately (e.g., in orange juice or coconut water).
