Transcript Document

Cholera
Rose Lee and Ricardo Lé
January 14, 2008
Cholera: The Illness
Clinical Features
 Acute diarrhoeal infection
 Diarrhoea leads to death by
dehydration and kidney failure
(stool output can reach 0.51L/hour) - hypotension,
tachycardia, and vascular collapse
 Short incubation period (2 hours to 5
days)
 75% of those infected do not develop
symptoms
 100-1000 organisms may cause disease,
although a million are needed to
consistently infect
Transmission
 Direct fecal-oral contamination or
ingestion of contaminated water and
food
 Linked to inadequate environmental
management (lack of safe water and
sufficient sanitation)
 Human-Human contact does not spread
the bacterium
Treatment
 Up to 80% of cases can be treated
through oral rehydration salts
 Severe cases require intravenous fluids
(Ringer lactate)
 Antibiotics can diminish duration of
diarrhoea, reduce volume of rehydation
fluids needed, and shorten duration of
V.cholerae excretion
Parenteral Vaccine
 2 doses administered 2 weeks apart
 Efficacy of approximately 50%
 Protection hardly exceeds 6 months
 Does not prevent transmission of
infectious agent
 Not recommended for general public
health use
Killed WC/rBS Vaccine
 Killed whole-cell V.cholerae in
combination with a recombinant Bsubunit of cholera toxin
 Safe in pregnancy and breastfeeding
 Efficacy of approximately 50% after 3
years
 Only significant side-effects are mild
gastrointestinal disturbances, and
toleration is great for HIV-positive
subjects
Live, attenuated
CVD 103-HgR Vaccine
 Protection as early as 1 week after
vaccination, with >90% protection
against moderate or severe cases
 Protection lasts at least 6 months,
further data is unknown
 Unknown efficacy for children
under 2
 No adverse side-effects
Major Issues in Vaccines
 Preventative (other measures)
 Parenteral: low efficacy, short
duration
 WC/rBS: 2 doses (logistics)
 CVD 103-HgR: Long term results?
 Inefficient for O139 or children <2
 Need more tests and trials.
Prevention
 Basic health education and
hygiene
 Mass chemoprophylaxis
 Provision of safe water and
sanitation
 Comprehensive Multidisciplinary
Approach: water, sanitation,
education, and communication
Control of Spread
 Set up treatment centres for
prompt treatment.
 Sanitary measures.
 Comprehensive surveillance data
(adapt to each situation) for a
comprehensive multidisciplinary
approach.
Vibrio Cholerae
The Organism
Type of Bacterium
 Gram negative (LPS cell wall)
 Type of Gammaproteobacteria
 Distinguishing factors: Oxidase-
positive, motile via polar flagellum,
and both respiratory and
fermentative metabolism.
 Simple growth requirements
History of Cholera
 First observed in India then S. Asia
 Discovered conclusively in 1883 by
Koch
 Spread to Europe and Americas from
1817. 6 epidemics by 1990s.
 7th epidemic in 1961 of El Tor biotype
 Spread across Asia, Middle East, Africa,
and parts of Europe
Some Definitions:
 Strain: Subset of a bacteria differing from
same species.
 Biotype: Same genotype, but different
phenotype.
 Serotype: Closely related microorganisms
distinguished by a characteristic set of
antigens.
 Many strains of Vibio cholerae.
 O antigens distinguish 139 serotypes:
O1 (3 biotypes—each has “classical” or
El Tor phenotype), O139 Bengal.
 O139 is a new serological strain with
unique O-antigen (no residual
immunity from O1)
Differences
 El Tor strain is more virulent
(replacing classical):
 Lower ratio of cases to carriers
 Longer duration of carriage after
 Survives longer in extraintestinal env
 O139 Bengal (derived from El Tor)
 Different antigenic structure on LPS
 Distinct polysaccharide capsule
 Possess all El Tor virulence
Virulence Factors
 Cholera toxin
 Tcp pili
 Aggregation, adhesion
 Flagellum
 withstand propulsive gut
 Resistant to bile salts in intestines
 If escapes low pH of stomach, easy to survive in
intestines
Cholera toxin
 Potent exotoxin
 multimeric protein complex of five binding
subunits (B) and one enzymatic (A) subunit.
 B subunits bind to intestinal epithelia
cell and A1 subunit enter cell and
activates adenylate cyclase enzyme.
 A1 catalyzes ADP-Ribose attachment to Gs Gi cannot
hydrolyze GTP to inactivate adenylate cyclase.
 cAMP produced at high rate. Triggers Cl- into intestines.
 H O, Na+, bicarbonate, and other electrolytes follow
2
Colonization
 Adhesins
 Tcp pili, hemagglutinin, acf gene
products
 Neuraminidase
 Motility
 Chemotaxis
 Toxin production
Regulation
 Enterotoxin is a product of ctx
genes regulated by transcription
 Environmental signals
-Temperature, pH, osmolarity, amino acids
 ToxR regulatory protein activated
-Induces positive control, binds to DNA
 Genes for attachment and toxin
production transcribed
Ecology
 Can exist in dormant state
 Conversion to infectious state:
-increase Temp, pH, nutrients.
-decrease salinity
 Can shift to “rugose form”:
exopolysaccharide production for cell
aggregation, resists chlorine
On our mission we came across a village
in rural Bangladesh. It is very small
but very crowded with poor water
sanitation and irrigation systems.
Its position is dangerously close to the
urban slums that have had cholera
outbreaks within the past few months.
Luckily, there has been no reported
cases of cholera so far within the last 6
months… but now we have some
decisions to make.
Discussion Question 1
 What is our plan of action in
regards to this village?
- Where should the emphasis be placed on
protecting a population before an
outbreak occurs? Vaccination or
sanitation?
- What are the pros and cons of each?
Discussion Question 2
 Unfortunately, while the members
were debating, an outbreak occurred
in this village. What is the plan now?
-What is the best hybrid solution for controlling
a cholera outbreak? You have short time and
limited resources.
Discussion Question 3
 The outbreak has been controlled for
the moment. What should be the
long-term plan for this population?
Discussion Question 4
 What are your sentiments and
policies regarding cholera around
the world? How do you feel about
the importance each of these as
aspects?
 Scientific Lab Research
 Field Work
 Infrastructure of Sanitation
 Education