Vibrio Cholera

Clinical Manifestation and

Defenses:






CHOLERA
Clinical Manifestations
Cholera victims are infected when they ingest an
infectious
dose of the bacterium V. cholerae

Most V. Cholera infections are asymptomatic (75%)
- 1 case per 30 to 100 infections in the E1 biotype
- 1 case per 2 to 4 infections with the classical biotype

Cholera is not transmissible person-
to-person, but can easily be spread
through contaminated food and water
Incubation Period
Ranging from a few hours to 5 days
Most cases presenting within 1-3 days

As expected for organisms passing through the
gastric barrier, the incubation period is shortest
when:
highest dose of ingested organsim
High gastric pH
Infectious Dose
Infectious dose ranges from 10
6
10
11
colonizing
units
The high level is necessary as the bacteria must
survive the gastric acid barrier as the bacterium
is sensitive to acidic conditions
Additionally, V. cholerae must penetrate the
mucus lining the coats the intestinal epithelium,
the bacterium adheres to and colonizes the
epithelial cells of the small intestine.
Symptoms
Diarrhea may be
sudden or gradual
Rapid onset of water
associated with stool
Vomiting, frequently
watery, is common
and may begin before
or after diarrhea.
** Fever is infrequent since
cholera is not invasive infection

Abdominal cramping
Severe Disease
Cholera Gravis
Notable for how quickly healthy person becomes ill
Patients present after a few hours with massive
volume loss
500 1000 ml per hour, can rapidly lose more than
10% of their body weight
Mortality
Circulatory collapse from dehydrating effects of the
pathogen
Cholera Gravis
Severest form of cholera
Infection in 2% of infected individuals
Patients with blood type O most susceptible
Characterized by voluminous expulsion of
electrolyte-rich fluid in patients stool
Amounts greater or equal to patients blood volume
Responds well to rehydration therapies
In areas where not available, death rates are
astronomical
Complications: Severe Disease
Complications result from massive volume and
electrolyte loss as the Cholera stool contains high
concentrations of sodium, potassium, chloride, and
bicarbonate

Therefore in addition to volume depletion, which can
cause renal failure, additional complications can
occur:
Hypokalemia: causes arrhythmias, ileus, leg cramps
Metabolic Acidosis: due to phosphate moving out of cells
Hypoglycemia: mental status changes and seizures
Hypotension: due to water loss
Hypofusion of critical organs
Mortality
In untreated patients, mortality can reach 50-
70%
Risk much higher in children
10x greater than adults
As well as pregnant women
50% risk of fetal death in 3
rd
trimester
Patients can die within 2-3 hours of first sign
of illness also seen from 10 hours- several
days
Diagnosis
Cholera should be considered in all cases with
severe watery diarrhea and vomiting
However, there are no clinical manifestations
that can distinguish cholera from other
infectious causes of severe diarrhea
Differential Diagnosis include:
Enterotoxigenic e. Coli
Bacterial food poisoning
Viral gastroenteritis
Visible Symptoms
These include:
Sunken eyes and cheeks
Decreased skin suppleness
Dry mucous membranes
Urine production is sharply
decreased or stopped altogether
Renal failure is the most common
complication seen in recent outbreaks
Diagnosis continued
Dehydrating diarrhea may be more common in
children but adults should be questioned as to
recent trips to Africa, Asia and central America
Additional questions asked about ingestion of
undercooked or raw shellfish
Laboratory Diagnosis
Made through isolation of bacteria from extra-
intestinal environment or stool samples
Specimens are collected
Gram Stain show sheets of curved Gram negative
rods
Untreated patients have 10
6
to 10
8
organisms / mL
Important to start treatment before the cause of
infection is identified: death can occur within
hours

Labroratory Diagnosis Cont.
Vibrios often detected by dark field or phase
contrast microscopy of stool
Organisms are motile, appearing like shooting
stars
When plated on sucrose dishes, yellow colonies
appear confirming cholera present
Additional methods of detection include PCR and
monoclonal antibody-based stool tests.
Treatment
The course of treatment is decided by the
degree of dehydration
Three options prove most effective:
Oral Rehydration
Intravenous Rehydration
Antimicrobial Therapy
Oral Rehydration
Oral Rehydration Solutions (ORS) have reduced
mortality from cholera from over 50% to less
than 1%.
ORS utilizes the fact that sodium and water
absorption in the small intestine is facilitated by
glucose and occurs in the presence of cholera
toxin
Used when the dehydration is less than 10% of
body weight

O.R.S.
The World Health Organization recommends
a solution containing:
3.5 g sodium chloride
2.9 g trisodium citrate/ sodium
bicarbonate
1.5 g potassium chloride
20 g glucose or 40 g sucrose
Per liter of water
Min. of 1.5 x the stool volume losses should be
administered
Commercially sold over-the-counter as
rehydralyte
ORS
Intravenous Rehydration
Used in patients who lost more than 10% of
body weight from dehydration or are unable
to drink due to vomiting
Ringers Lactate used commercially in
hospitals with appropriate electrolyte
concentrations specified to patients needs
Intravenous Rehydration
Additional Options
Saline can be used, however, bicarbonate
and potassium losses are not being replaced
Glucose in water; this does not replace the
sodium, bicarbonate, or potassium losses
Dosage =
Antimicrobial Therapy
Seen as an adjunct to appropriate rehydration
Reduce the volume of diarrhea by a half and the
duration of excretion to about 1 day, therefore,
they lower the expense of treatment and play a
role in cholera control.
Due to short duration of illness, antibiotics not
highly recommended:
High cost -- Antibiotic Resistance
Limited gain from usage

Dosage Antibiotic Agents
Given orally when vomiting
stops.
Tetracycline is the standard
treatment
Administered in single dose
primarily to prevent spread
of secondary infection
WHO guidelines
Tetracycline Resistance
Many strains of V. Cholerae now harbor plasmids
carrying multiple antibiotic resistances.
Fluoroquinolones are now an effective
alternative in regions where tetracycline
resistance is common
Prevention
V. Cholerae is spread through contaminated
food and water, therefore, prevention
depends upon the interruption of fecal-oral
transmission
Anti-biotic prophylaxis, vaccines and
surveillance of new cases are the answer to
preventing the spread of disease.
Sari Cloth Filtration:
Preventative Measure
Using Sari cloth to filter
Water
Antibiotic prophylaxis
The World Health Organization recommends
prophylaxis if 1 household member in a family
becomes ill.
Mass administration of antibiotics to a whole
community is not effective nor recommended
Vaccines
Two types of cholera vaccines are currently
approved for use in humans.
Killed-whole-cell formulation: killed bacterial
cells from both biovars of serovar 01 and purified
B subunit of the cholera toxin.
Provides immunity to only 50% of adult victims and
to less than 25% of child victims.
Live-attenuated vaccine, genetically engineered
Provides >90% protection against classical biovar
and 65-80% agaisnt E1Tor biovar.
Vaccines: Problems
The live vaccine is associated with certain
problems:
Side Effects:
Cause mild diarrhea, abdominal cramping and slight fever
Possible virulence of live strain
Upon infection of the vaccine strain by cholera toxin

Surveillance
In the United States, cases of cholera must
be reported to local and state health
departments
Bacterial isolates sent to the state health
department and Centers for Disease Control (CDC)
for testing and conformation of Cholera toxin
World wide surveillance is monitored by the
World Health Organization (WHO), tracking
potential outbreaks
Weaponization: Task Force on
Cholera
1992
WHO Global Task Force
on Cholera Control
aim was to reduce
mortality and morbidity
associated with the
disease and to address
the social and economic
consequences of cholera
Weaponization: Preventative
Measures
Global Water Quality Monitoring Project
(GEMS/WATER)
addresses global issues of water quality through a
network of monitoring statins in rivers, lakes,
reservoirs, and groundwater on all continents
Weaponization: Historical
Perspective
WWI
allegations that Germany tried to spread cholera in
Italy
1930s
Japan dropped bombs on Chinese that released
cholera, among other biological pathogens.

1980-1993
S. Africa Biological Weapons Program
included Bacillus anthracis, Vibrio cholera, and
Clostridium species
Weaponization: Means to Increase
Virulence
amplify and insert virulent portion of the
genome into another pathogen for either
dispersion via aerosolization or water
contamination that is contagious

V. cholerae is particularly well adapted to
its lifestyle in both the aquatic
environment and as an enteric pathogen.
Risk to New York
Over 8 million
people rely on
water supply

1.3 billion gallons
of drinking water
daily