By, KALLIANPUR. VAIBHAV. V

1. The Vibrio cholera By, KALLIANPUR. VAIBHAV. V

2. HISTORY. • 1816-1826 - First cholera pandemic: Previously restricted, the pandemic began in Bengal, and then spread across India by 1820. 10,000 British troops and countless Indians died during this pandemic. The cholera outbreak extended as far as China, Indonesia (where more than 100,000 people succumbed on the island of Java alone) and the Caspian Sea before receding. Deaths in India between 1817 and 1860 are estimated to have exceeded 15 million persons. Another 23 million died between 1865 and 1917. • 1829-1851 - Second cholera pandemic reached Russia, Hungary (about 100,000 deaths) and Germany in 1831, London (more than 55,000 persons died in the United Kingdom) and Paris in 1832. In London, the disease claimed 6,536 victims; in Paris, 20,000 succumbed (out of a population of 650,000) with about 100,000 deaths in all of France.

3. 1852-1860 - Third cholera pandemic mainly affected Russia, with over a million deaths. • 1863-1875 - Fourth cholera pandemic spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims fell victim to the disease. Cholera claimed 90,000 lives in Russia in 1866. The epidemic of cholera that spread with the Austro-Prussian War (1866) is estimated to have claimed 165,000 lives in the Austrian Empire. Hungary and Belgium both lost 30,000 people and in the Netherlands 20,000 perished. In 1867, Italy lost 113,000 lives. • 1881-1896 - Fifth cholera pandemic; According to Dr A. J. Wall, the 1883-1887 epidemic cost 250,000 lives in Europe and at least 50,000 in Americas. Cholera claimed 267,890 lives in Russia (1892); 120,000 in Spain; 90,000 in Japan and 60,000 in Persia. In Egypt cholera claimed more that 58,000 lives. The 1892 outbreak in Hamburg, Germany killed 8,600 people. Although generally held responsible for the virulence of the epidemic, the city government went largely unchanged. This was the last serious European cholera outbreak.

4. 1899-1923 - Sixth cholera pandemic had little effect in Europe because of advances in public health, but major Russian cities (more than 500,000 people dying of cholera during the first quarter of the 20th century) and the Ottoman Empire were particularly hard hit by cholera deaths. • 1961-1970s - Seventh cholera pandemic began in Indonesia, called El Tor after the strain, and reached Bangladesh in 1963, India in 1964, and the USSR in 1966. • January 1991 to September 1994 - Outbreak in South America, apparently initiated when a ship discharged ballast water. Beginning in Peru there were 1.04 million identified cases and almost 10,000 deaths. The causative agent was an O1, El Tor strain, with small differences from the seventh pandemic strain. In 1992 a new strain appeared in Asia, a non-O1, (NAG) named O139 Bengal. It was first identified in Tamil Nadu, India and for a while displaced El Tor in southern Asia before decreasing in prevalence from 1995 to around 10% of all cases

5. Misconceptions in the Past. • Miasma Theory • The theory that diseases were caused by miasma or bad air arising from organic decay, filth, or other conditions of the local environment. ‘All smell is disease.’ English Sanitary reformer Edwin Chadwick, 1842

6. V. cholerae Basics V. cholerae • Gram-negative • 2 chromosomes • Polar monotrichous • Asporogenous • Curved rod • Ferments glucose, sucrose, and mannitol

7. V. cholerae Classification Scheme NON-TOXIGENIC TOXIGENIC I define Vibrios! I’m an O1 or O139 Strain I may not be O1, Or O139! (but I can still stir up trouble)

8. Toxigenic V. cholerae O139 O1 Division into 2 biotypes inaba ogawa hikojima A & C A & B (A little C) Antigens A, B, C Classification Scheme Division into 2 epidemic serotypes Classical El Tor Each O1 biotype can have 3 serotypes Division into ribotypes

9. Of the more than 200 strains that have been identified, only O1 and the newly emerged O139 have been associated with severe disease and cholera outbreaks. • In any epidemic, one strain predominates. • There is a complex classification system. V. cholera is divided into two epidemic serotypes - O1 and O139 (there are many other environmental serotypes).. • The O1 strain predominated as the primary epidemic strain until 1992. The Classical biotype was responsible for the first six pandemics until it was replaced by the El Tor biotype in 1961. • The Classical and El Tor biotypes are further divided into three ribotypes based on the antigens they present: Inaba (A&C antigens); Ogawa (A & B antigens); and Hikojima (A&B&C antigens). • The O139 serotype replaced the O1 serotype as the predominant pandemic strain in 1992 when it emerged in Southeast Asia and became the primary strain.

10. Modes of Transmission • Water (infectious dose = 109) • Food (infectious dose = 103) • Person-to-person

11. Sudden, large outbreaks are usually associated with water supply contamination. V. cholera transmission has also been linked to drinking water drawn from shallow wells, rivers or streams, and even to bottled water and ice. • Food is the other important source of V. cholera transmission. Seafood, especially raw or undercooked shellfish harvested from sewage-contaminated beds or environments where V. cholera naturally occurs, has repeatedly been shown to be a source of V. cholera infection. • V. cholera grows well on moist, alkaline foods from which other competing organisms have been eliminated by cooking. • Fruits and vegetables grown in sewage and eaten without cooking or other decontamination are potential vehicles for cholera transmission. • Freezing foods or drinks does not prevent cholera transmission. • Person-to-person contact has not been shown to occur, but may, according to the WHO, still be a possible source of infection.

13. Life cycle in humans • Host drinks water • Bacteria conserve energy during the passage through the stomach, most die • Surviving bacteria reach the intestine, produce flagella • Propel themselves through the mucus of the sm. intestine • Bacteria produce toxin causing diarrhea • Feces carry new bacteria back into drinking water

14. Clinical Manifestations

15. After gaining entry into the host through ingestion, the organism colonizes the epithelial lining of the small intestine. The incubation period is one to five days, and patients are symptomatic for two to seven days. The production of Cholera Toxin, induces most of the symptoms associated with the disease cholera. For serious cases, death can occur as a result of hypovolemic shock within two to four hours of colonization. • Two case types: • Mild cases (90%) are difficult to distinguish from normal diarrheal diseases. • Severe cases (10%) are associated with painless, watery diarrhea and vomiting with as much as 20 L/dayfluid loss in as little as three to four hours, leading to hypovolemic shock. Severe dehyrdration results in muscle cramps, loss of skin turgor, scaphoid abdomen and weak pulse. • 3. The onset of diarrhea in cholera allows for the rapid dissemination of copious quantities of this organism into the environment.

16. Known Virulence Factors • Integrons • Toxins • CT • HA Protease • RTX Toxin • ACE and Zot • Adherence/Adhesins • Accessory Colonization Factors (ACF) • OmpU & other Omp Proteins - outer membrane proteins • Mannose-fucose-resistant cell hemagglutinin & Mannose sensitivev hemagglutinin (Faruque, 2002) • Toxin Co-regulated Pilus (TCP)

17. CT TOXIN • CT is an A-B type toxin encoded by genes located on phage CTX • V. cholerae Toxicity • CT does the dirty work. The organism never invades the cell. • The catalytic A subunit activates cAMP production • High intracellular cAMP results in the secretion of chloride ions, bicarbonate and water.

18. WHO IS AT RISK ? • When cholera appears in epidemic form in an unexposed population, it can affect all age groups since adults haven’t had the chance to acquire immunity. In contrast, in areas of endemic disease, most of the adult population has gained some degree of natural immunity because of illness or repeated asymptomatic infections. • In endemic areas, usually children and the elderly are the most at risk for infection. The elderly are more at risk because they have lower gastric production and waning immunity. • The poor are at a greater risk because they often lack safe water supplies, and may depend on street vendors or other unregulated sources of food and drink. • Group O blood group highest risk.

19. Microbiological & Molecular Methods of Detection • Microbiological culture-based methods using fecal or water samples • Rapid Tests • Dark-field microscopy • Rapid immunoassays • Molecular methods - PCR & DNA probes

20. Treating Cholera

22. CHEAPEST BUT BEST TREATMENT.

23. Antibiotics are not necessary for most V. cholerae infections; however, they usually decrease the volume and duration of diarrhea and the period of Vibrio excretion. • Antibiotics, when prescribed, should be ones to which the infective strain is susceptible because resistance is a growing problem. • The susceptibility of infectious strains should be determined at the beginning of an epidemic using the standard disk diffusion test or by broth microdilution. • For severe cases, tetracycline is the most-often prescribed antibiotic. • Other antibiotics that are prescribed: cotrimoxazole, erythromycin, doxycycline, chloramphenicol, and furazolidone

24. Preventing Cholera: Vaccines • Orochol • Contains 2x108 viable cells of attenuated strain CVD 103-HgR in a lyophilized form • Oral immunization of children older than 2 • Subunit A of the cholera toxin (CT) has been removed • Dukoral • Protects against O1 Inaba and Ogawa, Classical & El Tor strains • Contains 1x10 heat/formalin killed cells of strain WC/rBS Image from: http://www.pharmeragroup.com/dukoralb.htm

25. Epidemic Control Measures • Hygienic disposal of human waste • Adequate supply of water • Good food hygiene • Thoroughly cooking food • Eating food while it’s hot • Preventing cooked foods from contacting raw foods (including water or ice) • Avoiding raw fruits or vegetables • Washing hands after defecation & before cooking

28. THANK YOU FOR YOUR ATTENTION.