Vibrio Cholera

1. Vibrio Cholera Michelle Ross, Kristin Roman, Risa Siegel

2. Clinical Manifestation and Defenses:CHOLERA

3. 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

4. Cholera is not transmissible person-to-person, but can easily be spread through contaminated food and water

5. 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

6. Infectious Dose • Infectious dose ranges from 106 1011 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.

8. 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. • Abdominal cramping ** Fever is infrequent since cholera is not invasive infection

9. 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

10. 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 patient’s stool • Amounts greater or equal to patients blood volume • Responds well to rehydration therapies • In areas where not available, death rates are astronomical

11. 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

12. 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 3rd trimester • Patients can die within 2-3 hours of first sign of illness also seen from 10 hours- several days

13. 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

14. 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

15. 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

16. 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 106 to 108 organisms / mL • Important tostart treatment before thecause of infection is identified: death can occur within hours

17. 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.

19. Treatment • The course of treatment is decided by the degree of dehydration • Three options prove most effective: • Oral Rehydration • Intravenous Rehydration • Antimicrobial Therapy

20. 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

21. 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

22. ORS

23. Intravenous Rehydration • Used in patients who lost more than 10% of body weight from dehydration or are unable to drink due to vomiting • Ringer’s Lactate used commercially in hospitals with appropriate electrolyte concentrations specified to patients needs

24. 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 =

25. 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

26. 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

27. 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

28. 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.

29. Sari Cloth Filtration:Preventative Measure Using Sari cloth to filter Water

30. 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

31. 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.

32. 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

33. 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

34. 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”

35. 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

36. 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

37. 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.”

38. Risk to New York • Over 8 million people rely on water supply • 1.3 billion gallons of drinking water daily