cholera rose lee and ricardo lé january 14, 2008 rose lee and ricardo lé january 14, 2008
TRANSCRIPT
CholeraCholera
Rose Lee and Ricardo Lé
January 14, 2008
Rose Lee and Ricardo Lé
January 14, 2008
Cholera: The IllnessCholera: The Illness
Clinical Features
Acute diarrhoeal infectionDiarrhoea leads to death by
dehydration and kidney failure (stool output can reach 0.5-1L/hour) - hypotension, tachycardia, and vascular collapse
Clinical Features
Acute diarrhoeal infectionDiarrhoea leads to death by
dehydration and kidney failure (stool output can reach 0.5-1L/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
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
TransmissionTransmission
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
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
TreatmentTreatment
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
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 VaccineParenteral 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
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 VaccineKilled WC/rBS Vaccine
Killed whole-cell V.cholerae in combination with a recombinant B-subunit 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
Killed whole-cell V.cholerae in combination with a recombinant B-subunit 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
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
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 VaccinesMajor Issues in Vaccines
Preventative (other measures)Parenteral: low efficacy, short
durationWC/rBS: 2 doses (logistics)CVD 103-HgR: Long term results? Inefficient for O139 or children <2Need more tests and trials.
Preventative (other measures)Parenteral: low efficacy, short
durationWC/rBS: 2 doses (logistics)CVD 103-HgR: Long term results? Inefficient for O139 or children <2Need more tests and trials.
PreventionPrevention
Basic health education and hygieneMass chemoprophylaxisProvision of safe water and
sanitationComprehensive Multidisciplinary
Approach: water, sanitation, education, and communication
Basic health education and hygieneMass chemoprophylaxisProvision of safe water and
sanitationComprehensive Multidisciplinary
Approach: water, sanitation, education, and communication
Control of SpreadControl of Spread
Set up treatment centres for prompt treatment.
Sanitary measures.Comprehensive surveillance data
(adapt to each situation) for a comprehensive multidisciplinary approach.
Set up treatment centres for prompt treatment.
Sanitary measures.Comprehensive surveillance data
(adapt to each situation) for a comprehensive multidisciplinary approach.
Vibrio CholeraeVibrio Cholerae
The Organism
Type of BacteriumType of Bacterium
Gram negative (LPS cell wall)Type of GammaproteobacteriaDistinguishing factors: Oxidase-
positive, motile via polar flagellum, and both respiratory and fermentative metabolism.
Simple growth requirements
Gram negative (LPS cell wall)Type of GammaproteobacteriaDistinguishing factors: Oxidase-
positive, motile via polar flagellum, and both respiratory and fermentative metabolism.
Simple growth requirements
History of CholeraHistory of CholeraFirst observed in India then S. AsiaDiscovered conclusively in 1883 by
KochSpread to Europe and Americas from
1817. 6 epidemics by 1990s.7th epidemic in 1961 of El Tor biotypeSpread across Asia, Middle East,
Africa, and parts of Europe
First observed in India then S. AsiaDiscovered conclusively in 1883 by
KochSpread to Europe and Americas from
1817. 6 epidemics by 1990s.7th epidemic in 1961 of El Tor biotypeSpread 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.
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)
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)
DifferencesDifferences
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
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 FactorsVirulence Factors
Cholera toxinTcp 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 toxinTcp 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 toxinCholera 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.
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. H2O, Na+, bicarbonate, and other electrolytes follow
A1 catalyzes ADP-Ribose attachment to Gs Gi cannot hydrolyze GTP to inactivate adenylate cyclase.
cAMP produced at high rate. Triggers Cl- into intestines. H2O, Na+, bicarbonate, and other electrolytes follow
ColonizationColonization
AdhesinsTcp pili, hemagglutinin, acf gene
productsNeuraminidaseMotilityChemotaxisToxin production
AdhesinsTcp pili, hemagglutinin, acf gene
productsNeuraminidaseMotilityChemotaxisToxin production
RegulationRegulation
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
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
EcologyEcology
Can exist in dormant stateConversion to infectious state:
-increase Temp, pH, nutrients.-decrease salinity
Can shift to “rugose form”: exopolysaccharide production for cell aggregation, resists chlorine
Can exist in dormant stateConversion 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.
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 1Discussion 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?
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 2Discussion 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.
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 3Discussion Question 3
The outbreak has been controlled for the moment. What should be the long-term plan for this population?
The outbreak has been controlled for the moment. What should be the long-term plan for this population?
Discussion Question 4Discussion 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
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