Cholera 2024 PDF

Vibrio cholerae Prof. Abdulaziz Zorgani Dip-Bact, MSc, PhD, FIBS, Dip-HAI Vibrionaeceae V. cholerae and V. parahaemolyticus The genus include > 100 species that are commonly found in aquatic environments - The genus can be divided into non-halophilic (V. cholera) and halophilic (V. algaino...

Vibrio cholerae Prof. Abdulaziz Zorgani Dip-Bact, MSc, PhD, FIBS, Dip-HAI Vibrionaeceae V. cholerae and V. parahaemolyticus The genus include > 100 species that are commonly found in aquatic environments - The genus can be divided into non-halophilic (V. cholera) and halophilic (V. algainolyticus) Since 1817, there have been 7 cholera pandemics. The first 6 occurred from 1817-1923 and were caused by V. cholerae, the classical biotype. The pandemics originated in Asia The 7th pandemic began in Indonesia in 1961 and affected more countries and continents than the previous 6 pandemics. Caused by V. cholerae El Tor In Oct. 1992, an epidemic of cholera emerged from Madras, India as a result of a new serogroup (0139) Nearly 1.8 M people worldwide obtain their drinking water from sources contaminated with human feces (act as reservoir) Cholera is known to be endemic in ~ 50 nations (Asia and Africa) Vibrio cholerae Gram-negative Curved rod (comma shaped) Facultative anaerobe Single polar flagellum (motile) Optimal growth 30°C Oxidase positive, produce indole Slow LF Growth is rapid in the pH 7.4-9.6 On blood agar vibrios show haemodigesion Divisions of V. cholerae Has 200 different serogroups (O antigen), only two of which cause epidemic disease. All strains share the same flagellar (H) antigen, not involved in protection of susceptible host Hikojima possess determinants of both serotypes 01 antigen is divided into 3 types: A, B, C Strains may be further subdivided on the basis of their O antigens into the serotype Inaba and Ogawa. Some strains possess determinants of both of these subtypes and are known as serotype Hikojima A new strain did not agglutinate with antisera to any of the O serogroups and was assigned to a new serogroup O139 Bengal. It express capsule  Classification Biotype Oxidase VP Haemolysin (sheep Phage Polymyxin B or goat) Molecular techniques Classic + - - IV S can be used El Tor + + + V R - El Tor infection is relatively mild, or at least rarely fatal BUT - El Tor vibrio is highly infective but less virulent - Able to survive in the body longer than classical Cholerae - Patients are asymptomatic for about a week (carrier) - Carriers infect a greater population of people than classical Cholerae VP = Voges-Proskauer  Virulence factors Cycle of transmission Risk factors Decreased sanitation Ingestion of certain contaminated foods (rice) Age and Blood group O patients Decreased gastric acidity At the right time signal transduction pathway turns off the Vibrio polysaccharide synthesis (vps) operons that make the sticky matrix for biofilms (1000 more) resistant to acid shock QS also triggers a protease known to detach cells, perhaps both from the epithelial lining of the intestine and from biofilm aggregations (twice) ToxR, ToxS, ToxT gene system regulation “senses” environmental pH, osmolality, and temperature to turn on pili and choleragen production Vibrios attach to mature epithelium at the tips of intestinal villi via Tcp pili (Toxin co-regulated pili) Cholerae toxin acts at level crypts to disrupt electrolyte balance Incubation Period and Infectious Dose Ingestion of contaminated food/water V. cholerae survives on chitinous plankton Cholera is NOT transmissible person-to-person, but can easily be spread through contaminated food and water (fecal oral route) IP ranging from a few hours to 5 days Most cases presenting within 1-3 days Infectious dose ranges from 106 - 1011 colonizing units, to survive the gastric acid barrier About 75% of infected people do not develop symptoms 25% of those showing watery diarrhea symptoms and dehydration (2% sever hospitalized; 5% moderate illness outpatient; 18% mild illness)  Symptoms (Cholera Gravis) Abdominal cramping Weak and lethargic Sunken eyes and cheeks Dry mucous membranes (loss of skin turgor) Anuria (renal failure) Fever is infrequent since cholera is not invasive Vomiting, frequently watery, is common and may begin before or after diarrhea Diarrhea may be sudden or gradual Rapid onset of water associated with stool (flecks of mucus and a distinctive fishy odor – rice water stools - which contains little protein) There are NO RBCs or WBCs in the stool Up to 4M cholera cases annually – causes 100,000 – 120,000 death  Pathogenesis of V. cholerae (Cholera Gravis) Severest form of cholera in 2% of infected individuals The cholerae toxin (CT) (choleragen) is responsible for the severe diarrhea characteristic of the disease The binding of CT-A to G protein resulting in high intracellular cAMP level causes massive secretion of electrolytes and water through CFTR into the intestinal lumen Characterized by expulsion of electrolyte-rich fluid in patient’s stool (10% of body weight) (high concentrations of sodium, V. cholerae interaction with intestinal epithelial chloride, potassium, and bicarbonate) cells after ingestion. Bacterial secretion of CT upon High-volume fluid loss with electrolyte derangements that can binding to the GM1 ganglioside receptor leads to progress to hypovolemic shock and ultimately death the endocytosis of CT. CT-A subunits dissociate characterizes this gastrointestinal disease from CT-B after attachment to the ER, which 10-20 liters/day (107 vibrios/ml) causes CT-A to bind to G proteins and activate adenylate cyclase because of ATP cleavage. cAMP Responds well to rehydration therapies levels increase, resulting in the secretion of In areas where not available, death rates are astronomical chloride and bicarbonate ions through CFTR protein channels (CFTR cystic fibrosis transmembrane conductance regulator) (ER endoplasmic reticulum) 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  Laboratory Diagnosis Vibrios often detected by dark field or phase contrast microscopy of stool, actively motile (not reliable) Rapid test (dipstick) Stool specimens are inoculated (3-6h) into alkaline peptone water, vibrios grow rapidly and accumulate on the surface When plated on (Thiosulfate Citrate Bile Salts Sucrose) TCBS plates (pH 8.6), yellow colonies appear V. cholera serogroup O1 antisera Confirm presence of cholera toxin PCR and monoclonal antibody-based stool tests Nationally Notifiable Diseases That Are Water-Related or Waterborne Oxidase +ve String test  Management ORS have shown 1 reduced mortality from cholera from over 50% to < 1 IV therapy Ringer’s ORS Lactate Used in Due to short duration of patients who lost illness, antibiotics not 3 more than 10% of highly recommended: – High cost body weight from 2 – Limited value – Resistance dehydration or are unable to drink due to vomiting The course of treatment is decided by the degree of dehydration Prevention Prevention depends upon the interruption of fecal-oral transmission 1- Sari cloth filtration 2- The WHO recommends prophylaxis if 1 household member in a family becomes ill. Mass administration of antibiotics to a whole community is not effective nor recommended 3- vaccines Vaccines Cholera vaccines offer incomplete protection Vaccination should never take the place of standard prevention and control measures 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: genetically engineered Provides >90% protection against classical biovar and 65-80% against ElTor biovar Vaxchora: a single-dose live oral cholera vaccine for adults 18 – 64 years old who are traveling to an area of active cholera transmission Three other oral inactivated, or non-live cholera vaccines approved by WHO https://www.who.int/teams/immunization-vaccines-and-biologicals/diseases/cholera Non-O1 V. cholerae Cause mild, sometimes bloody diarrhea, often accompanied by abdominal cramps Symptoms may occasionally be sever, in which case the disease resemble cholera All express capsule, and a few strains produce cholera toxin May elaborate a wide range of virulence factors, including enterotoxins, cytotoxins, haemolysins and colonizing factors V. parahaemolyticus This disease is most often associated with eating raw or inadequately cooked seafood or any food contaminated by handling raw seafood or contaminated water. Primarily associated with the consumption of raw oysters especially during summer Found abundantly floating free along the coastal waters all over the world and in fish and shellfish This disease is self-limiting and best treated with plenty of water replenishment Antibiotics are usually not necessary but in very sever cases tetracycline, ampicillin or ciprofloxacin could be used Not communicable from person to person Grow at 42˚C Diseases caused by V. parahaemolyticus The incubation period is usually between 12 – 24 h Is an intestinal infection that is characterized by lower gastrointestinal distress such as diarrhea and cramps In some cases, nausea, vomiting, fever and headache may also be present Occasionally, this disease may manifest itself as a dysentery-like illness with bloody or mucoid stools, high fever and a high white blood cell count Normally the disease has a duration of only two to three days  Diagnosis (V. parahaemolyticus) Diagnosed by isolating the Kanagawa Vibrio, when grown on high salt blood agar (NaCl 3.5%), produce the hemolytic reaction known as the “Kanagawa phenomenon” Diagnosis can be determined by the presence of the heat-stable cytotoxin in the patient’s stool culture or in implicated food V. parahaemolyticus will not grow CLED Helicobacter pylori Prof. Abdulaziz Zorgani Dip-Bact, MSc, PhD, FIBS, Dip-HAI  Characteristics Slender, curved Gram negative bacilli, motile Microaerophilic atmosphere, slow Urease positive 32 species (H. pylori, H. cinaedi and H. fennelliae), wide animal reservoir except H. pylori only in human The World Health Organization has classified HP as a class I carcinogen since 1994 Over 1 M new cases of gastric cancer and nearly 800 000 deaths occurred in 2020 making H. pylori-related disease the third leading cause of global cancer deaths  H. pylori Stomach is a glandular organ lined with epithelial cells Epithelium cells secret mucus while parietal cells secret acid and stem cells in between secret both HP able to live in hostile gastric environment, the acidity eht fo stomach dna duodenum Associated with over 95% of duodenal ulcers and 85% of gastric ulcers Associated with common gastritis (inflammatory response = infiltration of neutrophils and mononuclear cells into the gastric mucosa) Symptoms: nausea, vomiting (blood), feeling full after a small meal, lack of appetite, epigastric pain, belching are clinical indicators, black stool  Humans respond in various ways with H. pylori Multiple factors contribute to the gastric colonization, inflammation, alteration of gastric acid production, and tissue destruction that are characteristic of H. pylori disease HP is very persistence once established; acute and chronic inflammation of epithelium and lamina propria with cell destruction (peptic ulcer) The leading cause of peptic ulcers (1 in 6 individuals) Only a minority may develop gastric cancer Asymptomatic (>75%) Ulcer disease (10%) [peptic ulcer or duodenal ulcer] H. pylori Chronic atrophic gastritis Gastric adenocarcinoma (1%) MALT lymphoma (