Cholera Lecture Notes PDF

Academic logo TEAM443 MICROBIOLOGY Cholera Prof Ali & Fawzia Objectives - Recall the epidemiology of cholera and history of cholera - Recall the microbiological characteristic of cholera - Describe the pathogenesis of cholera - Describe the clinical features of cholera - Describe the metho...

Academic logo TEAM443 MICROBIOLOGY Cholera Prof Ali & Fawzia Objectives - Recall the epidemiology of cholera and history of cholera - Recall the microbiological characteristic of cholera - Describe the pathogenesis of cholera - Describe the clinical features of cholera - Describe the methods for laboratory diagnosis - Recall the management of cholera and control of outbreak Any future corrections will be in the editing file, so please check it frequently Color Index: Main text Important Doctor Notes Males slide Females slide Extra Cholera Cholera A water borne live threatening diarrheal disease Cholera is not a zoonotic disease, and it has nothing to do with animals (source of infection is human feces). Caused by ○ Vibrio Cholerae which is Short curved, Comma shaped Gram -ve rods (oxidase positive) Epidemiology ○ Found in salt and freshwater. ○ leads to outbreak and epidemic. Characteristics {7} ○ Has many serotypes based on O-antigen ○ O 1 and O 139. ○ Produce a non-invasive enterotoxin. ○ Can be prevented by good sanitation system. Discovery {1} John Snow discovered an outbreak in London 1854 It was related to broad street pump sewage contamination Removal of the pump handle ➝ end of the outbreak Epidemiology {2},{3},{4} A O139 (recently in 1992 in Asia only): - Contained in India, Bangladesh. B V. cholera O1 and O139 serogroup organisms are the causes of epidemic cholera. C Seven major outbreaks. D O1 (from 1817 till now): - Classical: 1 case per 30-100 infections - El Tor: 1 case per 2-4 infections (Seventh pandemic) E Majority in India, Sub-Saharan Africa, Southern Asia. F Endemic in > 50 countries. G Each year 3-5 millions cases result in 100,000 deaths. Infectivity Period of infectivity during acute stage till recovery ( end one to three weeks ) Infected person can produce up to 20 L of 10⁹ CFU/ml/day Has high infectious dose NOT like Shigella Infectious dose 10⁶-10¹¹ colony-forming units, Due to harsh environment of the intestine( ie. temperature and stomach acidity and Bile salts, organic acid in intestine) Transmission & Clinical manifestation Transmission 1 Sewage or infected person contaminate water supply, and Not well established sewage system and water treatment. {8} -{12} Blood group O>> B > A > AB (There’s No strong evidence) Children, elderly and people with less gastric acidity are at higher risk than others.{11} Undercooked shellfish Common in summer grows in brackish estuaries and coastal seawaters, often in close association with copepods or other zooplankton. Fecal-oral transmission through contaminated food or water From human to human through stool by his contaminated hands Clinical manifestation - Ranges from a few hours to 5 days (range 1-3 days) ○ Depending on gastric acidity and initial infectious dose. ○ Majority have mild, or no symptoms at all ● 75% asymptomatic ● 20% mild disease ● 2-5% severe Pathogenesis Pathogenesis Toxin ○ Vibrio cholerae uses toxin-coregulated pili (TCP) to colonize the human intestine. ○ Cholera results from secretory diarrhea caused by the actions of cholera toxin (CT) on intestinal epithelial cells. ○ CT is an adenosine diphosphate – ribosylating enzyme that leads to chloride, sodium, and water loss from intestinal epithelial cells 1. Cholera toxin binds to Monosialoganglioside (GM1) which is a glycosphingolipid on the surface of epithelial cells. Mechanism {10} 2. The toxin must undergo cleavage of the active, A1 component(CTA1), which goes on to constitutively activate the Gs protein 3. Nicotinamide adenine dinucleotide (NAD), mediated by CTA1 becomes Adenosine diphosphate (ADP)-ribose & binds to G protein 4. G protein regulates adenylyl (adenylate) cyclase activity (AC). 5. Elevation in the intracellular cyclic adenosine monophosphate (cAMP) concentration. 6. water and electrolyte shift from the cell to the intestinal lumen, This results in extremely watery diarrhea accompanied by electrolyte imbalances Mild disease Cholera gravis More severe symptoms due to Rapid loss of body fluids: Vomiting. Symptoms {9} Rapidly lose more than 10% of body weight. Cramps. Dehydration and shock. Watery diarrhea[1] (1L/hour): with flecks of white mucus (rice watery stool) & a fishy odor.{3} Sunken eyes[2], and ↓skin turgor[3] (tenting), cold and clammy. Anuric & lactic acidosis (Kussmaul breathing)[4]. ↓ Ca++ and K can lead to ileus, muscle pain, spasm, & even tetany. Hypoglycemia ➔ seizure or comma. Cardiac and Renal failure. Aspiration pneumonia. Water Loss Mortality 1 liter/hour. 6 liters/hour (107-9 vibrios CFU/mL). Death occurred in (18 hours - several ○ Death within 2-12 hours or less. days) if not treated due to ○ Mortality 50-60% without treatment. dehydration. ○ Mortality <1% with rehydration. Diagnosis{5},{6} Suspect in severe diarrhea with dehydration. Other non-invasive bacterial, ETEC and viral gastroenteritis might have similar presentation. Complete history and physical examination. Insert central line for IV fluid, collect blood for basic routine tests ( chemistry and hematology). Send stool for smear and culture on special media. Culture not routinely performed, you have to request it Dark field microscopy (motile shooting stars) Gram stain : curve Gram Negative bacilli Culture on thiosulfate citrate bile sucrose (TCBS) agar-yellow colonies Recovery of organisms can be enhanced by enrichment of stool in alkaline peptone water (60-100%) ◎ Vibrio cholera is highly motile, Gram-negative, curved or comma shaped rods/bacilli with a single polar flagellum. Types of cholera O 139 serogroup appeared in Bangladesh 1992 Biotype O 1 antigen El Tor Classical Biotype O 1 antigen Classical El Tor Non-O1, Non-O139 Serogroup Serotype Antigen Ogawa A,B Inaba A,C Hikojima A,B,C Ogawa A,B Inaba A,C Hikojima A,B,C Has polysaccharide capsule but does not have O1 antigen Most are CT (cholera toxin) negative and are not associated with epidemic disease. Cholera Treatment Rehydration and antimicrobial therapy {13} Rehydration Antibiotics - Rehydration should be started immediately before confirming the diagnosis - Either oral rehydration if the patient can tolerate it (not vomiting) or start IV rehydration. - Decrease mortality from 50% to 1 % - Give 1.5 time the amount lost. - Start when 10% of total body weight lost. - Patients recovered within 3-6 days. - Oral Rehydration Salt (ORS) by WHO and UNICEF one pack in 1 liter contain NaCl, KCl, NaHCO3, glucose - IV use either Ringer’s lactate, Saline or Sugar and water - Reduce the recovery time to 2-3 days - Decrease infectivity - Azithromycin single-dose is often the preferred therapy especially in children, - or Ciprofloxacin - or Tetracycline , Doxycycline Bioterrorism agents It was skipped by Prof.Ali Ease of dissemination with low technology Silent dissemination Simplicity of production in large quantities at minimal expense Ease of procurement Prevention {14} Wash your hand frequently Boil water and chlorination. Cook all types of food very well. Disrupt fecal-oral transmission if present Water Sanitation/ treatment Avoid salad, ice and iced food Vaccination {15} Killed Whole-cell Vaccines Live Attenuated Vaccines Adult 50% protection for 6 months 60% protection for 2 years Children aged 2-5 < 25% protection protection rapidly declines after 6 months Doses Multiple doses - Side effects - Mild diarrhea, abdominal cramping International Effort WHO: Global Task Force on Cholera Control Reduce mortality and morbidity Provide aid for social and economic consequences of Cholera CDC U.N.: GEMS/Water Global Water Quality Monitoring Project Addresses global issues of water quality with monitoring stations on all continents Dr Notes 1. History of cholera, known from 1800 by the epidemiologist John snow in “Thames/times river” in London, 2 different companies distribute water from there, John did an epidemiological study he collected all these cases(people who died/ and with no symptoms/ and with diarrhoea) he collected all necessary info from them and marks them on a map (London map around the river or -broad way-) He also did a calculations for the relative risk (it’s relative because it’s -cohort study-number of people who drunk from the pump in the top of river and whose drunk from the bottom (according to water companies that distribute water), so then he reported to close broadways and then the outbreak stopped! 2. Most outbreak have been seen in Haiti, Katrina in America, Also in Yemen (No available safe drinking water, so one case can infect all the population! 3. Why do we fear cholera? First, vibrio is very rare in Saudi Arabia, BUT when foreigners come from (Bangladesh, Africa, Kenya) they could have cholera. ◎ SAQ or MCQ :When there’s a Question like, someone came from outside Saudi Arabia, from (devolving country/ war/ Earthquakes/ Floods/ hurricanes) And he’s having diarrhoea (this diarrhoea characterised by the following: 1. Large Amount diarrhoea 2. Mucus (flex white mucus) /Rice like (These are very important clues that tell you this case is cholera) 4. In Saudi Arabia (yes we don’t have cholera cases) but we have lots of foreigners almost 50% of the population! And they go and come back again, there’s also “‫ ” ﺣﺠﺎج وﻣﻌﺘﻤﺮﯾﻦ‬that come every year, that’s why we have to have all tools and laps ready to identify cholera. 5. In laps When there’s vibrio in media, does this mean it’s cholera only? Or could it be other thing? There’s lots of Vibrio bacteria other than (vibrio cholera). Some laps make mistakes when they see “vibrio” in media they report it as vibrio “cholera” and it turns out that it’s not cholera! This is why in vibrio we always make sure it’s “cholera” (How? There’re some tests to confirm that, check point 6..) 6. As we mentioned when vibrio appears in media (as yellow colonies) how to know it’s vibrio “cholera”? Some important tests can be used: - string test (appears like thread/string colonies) - Shooting star (when you put the colonies on slide and add normal saline it move fast just like shooting star!) so lap is important 7. Characteristics of Vibrio cholera: - Gram negative, Non lactose fermentative, curved, motile, comma shaped - Grow on TBCA media (yellow), Positive string test, Oxidase positive Dr Notes 8. What is the source? Contaminated drinking ***water*** Not from hands because it has high infectivity unlike shigella. 9. clinical presentation: Short Incubation period, (Large Amount/ flex mucus watery diarrhoea) ○ It must be mentioned in the question that it’s (Large/flex) and the patient is coming from outside Saudi Arabia (Travelled) 10. Pathogenesis: Produce mucus so has (Cytotoxin and enterotoxin) there will be destruction in mucosa because of binding of organism so nutrients (Na, K) will not go inside cell and will stay in lumen, water will follows (osmolarity) -> diarrhoea. 11. Risk factors: In general, anyone living in (countries with disasters) one of the important risk factors also, people taking antacids get sick with lower Infectious dose. 12. Why we don’t have cholera? Why it’s in developing/wars countries? Because they “drink contaminated water” from "‫ "اﻟﻤﺠﺎري‬there will be sewage then it goes with the drinking water. 13. Treatment: - We treat to kill organism and decrease symptoms and prevent from infection - Doxycycline but ‫“ اھﻢ ﺷﻲ‬Fluids “: ○ If there’s available IV line: low mortality rate (specially that not all people get sever disease only 2-5%). ○ If there’s NO available IV line: High mortality rate, when patient has the diarrhoea → hypovolemic shock (in wars/ poor countries) (there’s no IV lines) ,even when you give him fluid orally he cannot he will vomit → these cases needs fast intervention unlike Salmonella typhi ‘week’, here it’s only hours leads to→ multi Organ failure, it’s irreversible so No good survival (cardiac, Renal, Liver failure and they will have lactic acidosis. They might also have decreased mentation and loss of consciousness and they die. and this case we call it gravis cholera, (in outbreaks populations get infected so 2-5% would be very high number of severe cases) 14. Prevention is for : - People who expose to the pathogen: get vaccine. - People in the outbreak: has to take safe drinking water. 15. we have two types of Vaccine A. Dead one which is characterized by having less symptoms but less immunogenicity B. Life attenuated which is characterized by having symptoms but with longer immunity (no need to take it every year) ○ Who take the vaccine? Not for everybody, only for People who travel there eg.campaigns People exposed to sewage. MCQs Q1 - Name the type of diarrheal infection associated with V.cholerae? A) Acute watery bloody B) Acute watery rice water diarrhea diarrhea C) Acute watery diarrhea D) None with no blood Q2 - Which blood group is most susceptible to get cholera? A) AB B) A C) B D) O Q3 - What is the mode of transmission of V. cholera? A) Oral - oral transmission B) Fecal - oral transmission C) Oral- oral transmission D) Fecal - oral transmission through contaminated through contaminated through contaminated food through contaminated food Animal & water Animal & water & water & water Q4 - A watery stool sample was collected f rom the 5 year old boy who is suffering f rom diarrhea for 2 days. After the incubation in high pH media containing NaCl, smooth and round colonies appeared. Gram-negative, motile, comma-shaped bacteria were observed after the microscopic examination. Name the possible bacteria? A) Aeromonas spp B) E.coli C) H.pylori D) Vibrio cholerae Q5 - All the following statements about vibrio cholerae are true EXCEPT: A) Multiple flagella B) Motile C) Comma shaped rods D) Gram negative C) Alkalosis D) Renal failure Q6 - Which of the following is NOT a symptom of cholera gravis? A) Hypoglycemia B) Shock Q7 -Which of the following medium are used to differentiate the colonies of Vibrio cholerae? A) Alkaline bile salt B) MacConkey C) Thiosulphate-citrat e-bile-sucrose Answers: 1.B 2.D 3. D 4. D 5.A 6.C 7.C D) XLD SAQ Case 1 A 25 year old man presented in emergency department (ER) complaining of severe watery diarrhea, muscle cramps and dehydration after eating uncooked shellfish Q1: What is the most likely causative organism ? Q2: what are the points(factors) that indicate to the cause ? Q3: Describe the culture in TCBS media Q4: what is the pathogenesis ? Q5: describe the microbiology characteristic Q6: how do we treat it ? Q7: what are the clinical features ? Answers A1: Vibrio cholera A2: Shellfish, watery diarrhea and dehydration A3: A yellow colonies A4: by enterotoxin (cholera toxin (CT) ) A5: Gram-negative, curved or comma-shaped rods/bacilli A6: Mainly by Rehydration Antibiotics in severe cases A7 : Vomiting, watery diarrhea ,abdominal cramps Thanks to 441 Q bank team! TEAM 443 MICROBIOLOGY Team leaders Aishah Boureggah Aroub Almahmoud Maryam Alghannam Nazmi M Alqutub Team Members Mohammd Alqutub Raghad Almuslih Khalid Alsobei Afnan Alahmari Lama Alotabi Wajd Almutairi Sultan Albaqami Zahra Alhazmi Nourah Alarifi Moath Alhudaif Almas Almutari Sarah Alajaji Aban Basfar Reema Almotairi Alhawraa Alawami Mohammed Alarfaj Reema Algarni Shahad Alzaid Faris Alzahrani Farah Abukhalaf Danah Almuhaisen Abdulrahman Almusallam Remaz Almahmoud Areej Alquraini Zeyad Alotaibi Aleen Alkulyah Layan Al-Ruwaili Luay Alhudaithy Rafan Alhazzani Haya Alzeer Nazmi A Alqutub Reuf Alahmari Raseel Almutairi Rahaf Alshowihi Reena Alsadoni