传染病学：3霍乱（英文）

1、Cholera,cholera,Pathogen：vibrio cholera Eight pandemics over most of the globe A infectious disease international quarantine infection disease,etiology,vibrio cholerae,Gram-negative It is rapidly motile by means of a single polar flagellum. O139 serogroup with capsule Hanging drop test under microsc

2、ope Appearing school of fish in feces smear Generate rapidly in the alkalinity environment,antigen,Bacterial cell（） antigenhas high specificity, and is the basis for the classification and typing of vibrio cholera Flagellum （） antigencommon in vibrio cholera,Classification of vibrio cholera by WHO,O

3、1 vibrio cholera Non-O1 vibrio cholera Untypical-O1 vibrio cholera,O1 vibrio cholerae,According to the phenotype，two biotypes were typed： classical biotype El -Tor biotype According to the O antigen， V. cholerae O1 are further divided into the following subserotypes ： ogawa(小川） strains express A and

4、 B antigens inaba （稻叶） strains express A and C antigens hikojema 颜岛）strains express A, B and C antigens,non- O1 vibrio cholerae,No ability to agglutinate the multipartial serum of O1 vibrio cholerae Containing more than 200 serogroups such as O2,O3,O138 and so on， with no pathogenicity generally O13

5、9 serogroup has following specificities： A new serogroup detected in Bengal in 1992 With the same toxin gene with O1 serotype，and leading to epidemic diarrhea,untipical- O1 vibrio cholerae,With the ability to agglutinate the multipartial serum of O1 V.cholerae With no enterotoxin and pathogenicity,R

6、esistance of vibrio cholerae,Sensitive to heat, dry ,acid and common antiseptics Die after drying for 2 hours or heating to 55 for 10 minutes Die immediately after boiling Survive for 4 minutes in the normal gastric acid,Survive more longer in physical environment El Tor biotype can survive for 1-3

7、weeks in river and well water Survive time prolonged as adhere to algae or crustacean Even survive for more than one year, if external environment was suitable,Resistance of vibrio cholerae,Three types of toxin,type toxin endotoxin，the major component of bacterial vaccin type toxinepitoxin，is choler

8、a enterotocin， Product of metabolism in the generation of vibrio cholera Key substance leading to cholera diarrhea type toxin has no association with pathogeny,epidemiology,epidemic history,1st6th pandemic（18171923）：clssical biotype 7th pandemic（1961up to now）：El Tor biotype In 1992, cholera caused

9、by O139 serotype began in India and Bengal, and spread to surrounding countries（8th pandemic）,cases of vibrio cholerae in 1961-2000,year,cases,source of infection,Bacteria carrier Patients Bacterial eliminating time ：5 days，2 weeks at most Severe patients，with a great deal of bacterium eliminating，

10、107109 vibrio cholerae stains per milliliter of stool，are the important infection source,route of transmission,Water or food polluted by vibrio cholera Contact in daily life,susceptibility,Susceptible generally More with inapparent infection，less with apparent infection Acquired immunity after infec

11、tion，but persistent time is short and reinfection will occur.,epidemiologic character,Tropical zone：onset whole year China：epidemic in summer or autumn，crest-time is July to September Geographic characteristic: distribute along river or sea,pathogenic mechanism,pathogenic mechanism,Determinants： The

12、 level of gastric acid secretion Quantity and virulence of V.cholera,V. cholerae must survive passage through the gastric barrier of the stomach and reach the small intestine,Generate greatly in the alkalinity environment of the small intestin and release cholera enterotoxin,Pass though the slime la

13、yer of the intestinal mucosa,paghogenic mechanism,Choleragen,cholera enterotoxin （also named choleragen）plays the key role in pathogenesis,Figure The bacterium produces a toxin （left） that is the cause of the cholera. The toxin molecule is composed of several parts, one of which （coloured blue） pene

14、trates the cell membrane （yellow）,mechanism for excessive secretion of small intestine,Cholera Toxin is a prototype A/B subunit toxin, consisting of one A subunit and 5 B subunits. The B subunit binds the holotoxin to a eukaryotic cell surface receptor GM1,（A） Cholera toxin approaching target cell s

15、urface.,（B） Binding of B subunits to oligosaccharide of GM1 ganglioside.,（C） Conformational alteration of holotoxin presenting A subunit （black） to cell surface.,The mature A subunit is proteolytically cleaved to produce a 21.8kDa A1 polypeptide, and a 5.4kDa A2 polypeptide in cell. NAD is cleaved b

16、y A1 and yields ADP-ribose to act on G protein.,（E） Reduction of disulfide bond of A subunit by intracellular glutathione, freeing A1 and A2.,（F） Cleavage of NAD by A1 yielding ADP-ribose and nicotinamide.,（D） Entry of A subunit.,mechanism for excessive secretion of small intestine,ADPribosylation o

17、f G protein inhibits the activity of GTPase Since AC is activated, ATP is changed to cAMP persistently cAMP stimulates pit cells to produce H2O, chloridate and bicarbonate, and inhibits the absorption of chloridate by chorionic villi cell.,（G） ADP-ribosylation of G protein, inhibiting action of GTPa

18、se and “locking” adenylate cyclase in “on” mode.,Second messenger,mechanism for excessive secretion of small intestine,pathophysiology,The feces of cholera patients is isosmotic. The concentrations of potassium and bicarbonate in feces are 25 times higher than those in blood. See Table： Severe vomit

19、ing and diarrhea lead to dehydration, electrolyte disturbances, and acid-base imbalance.,pathologic anatomy,Dry skin, contraction of parenchymatous organs Dry gastrointestinal placenta percreta，mild inflammation of intestinal mucosa，full of “rice water stool” in intestine Renal megaly，angiotelectasi

20、s of glomcrulus and interstitium，cloudy swelling, degeneration and necrosis of renal tubule epithelium,clinical manifestation,clinical manifestation,Incubation period：1-3 days Onset abruptly Clinical manifestation is associated with the type of V.cholera Infections with clssical biotype and O139 V.c

21、holera are relatively severe Infections with El Tor biotype V.cholera are mild,course of diseases,Diarrhea and vomit period Dehydration and prostration period Recovery and response period,diarrhea and vomit period,Persist for several hours or 12 days Vomit following diarrhea Afebrile commonly（except

22、 O139）,diarrhea and vomit period,Diarrhea character： profuse and frequent yellow water stool rice water stool blood water stool No fecal foul smell Scare abdominal pain,diarrhea and vomit period,Vomiting character： Without nausea Projectile vomiting Vomit gastric contents initially, but shortly vomi

23、t watery liquid.,dehydration and prostration period,1. dehydration poor skin turgor sunken eyes hoarse voice hypourocrinia,agitation, hoarse voice, thirsty,Sunken eyes and cheeks,dehydration and prostration period,Scaphoid abdomen,“washer-womans hands”,Tabescent , cold and clammy skin with poor turg

24、or,dehydration and prostration period,2.Circulatory failure Degression of blood pressure Conscious disturbance,dehydration and prostration period,3. Metabolic acidosis deep breath, conscious disturbance sometimes 4. Muscle convulsion spasmus region pain and muscle rigidity 5. hypopotassemia hypomyot

25、onia, tendon reflex disappear meteorism arhythmia,dehydration and prostration period,complication,Renal failure Acute pulmonary edema and congestive heat failure,recovery and response period,A few patients have responsive low-grade fever,clinical character of O-139 vibrio cholerae,Severe symptoms Ab

26、dominal pain Complications: extra-intestinal infections such as bacteremia,clinical types,“cholera sicca”,sudden onset of cholera with no diarrhea and vomiting toxic shock immediately High mortality,diagnosis,confirmed diagnosis,Correspond with one or more than one of the following items： with sympt

27、oms of diarrhea and vomiting, positive results of stool culture in epidemic region，with typical symptoms，4 times increase of serum agglutinating antibody without diarrhea and vomiting，positive results of stool culture，with diarrhea symptom 5 days pre- or post-stool test，close contact history,uncerta

28、inable diagnosis,Correspond with one or more than one of the following items: with typical symptoms，but uncertain results of etiology test obvious contact history in epidemic period，with diarrhea and vomiting symptoms, without other reasons,differential diagnosis,Infections with other Vibrions Infec

29、tions with E.coli producing toxin Saimonella enteritis Viral enteritis Acute bacillary dysentery,laboratory test,blood routine,Increase of RBC and Hb WBC 10109/L，neutrophilc leukocytosis and mononuclear leukocytosis,biochemistry test,Decrease of serum sodium, potassium, and chlorine Decrease of HCO3

30、,stool test,Stool routine：mucago and several RBC and WBC are seen Gram stain：gram-negative Vibrion，appearing school of fish arrangement,stool test,Dynamic test：Vibrion is observed shuttling by hanging drop on glass under microscope Immobilization test：To aggulate the antiserum of O1 or O139 serogrou

31、p Bacterial culture：To ascertain the type of pathogenic bacteria,serology test,It is significant for diagnosis that paired serum titres of antiagglutinin antibody more than 4 times increase than normal. Used to the following purposes： Diagnosis of epidemiology Diagnosis of the uncertainable cases wi

32、th negative stool culture results,treatment,treatmental principle,Strict isolation Prompt fluid infusion Antibacterial and symtomatic treatment,serious isolation,Submit the epidemic status Isolation according to the criteria of A infectious disease After disappearance of symptoms，stool are cultured

33、every other day. When results of continuous twice stool cultures are negative, isolation can be released.,veinal fluid infusion,Principle of fluid infusion Earlier, prompt, adequate Drip of NS-GS, drip of fast-slow，correct acidosis and supply calcium， Correct acidosis and supply calcium，supply potas

34、sium as soon as urine appears.,which fluid?,fluid categories： 541 fluid（most suitable） diarrhea treatment solution 21 solution Ringers natrium lacticum solution,Feces of patients are isosmotic，in which the concentrations of potassium and bicarbonates are 2-5 times of those in blood. Severe vomiting

35、and diarrhea can lead to dehydration, electrolyte disturbances and acid-base imbalance,which fluid?,Fluid dosage ：according to the degree of dehydration, dosage in the initial 24 hours：,which fluid?,velocity?,Correct in shock phase：4080ml/min Maintain in blood pressure phase：2030ml/min Correct in de

36、hydration phase： 510ml/min Maintain in transfusion phase： 35ml/min,take orally,compoundings of ORS： Glycose 20g NaCL 3.5g NaHCO3 2.5g KCL 1.5g Dissolved in drinking water with the volume of 1000ml,take orally,Principle： No damage to the absorption of glycose in intestinal tract Leading to the absorp

37、tion of water Leading to the absorption of electrolytes Especially suitable for： Old and weak patients Patients with cardiorespiratory dysfunctional Patients necessary for supplying potassium promptly,antibacterial treatment,Antibacterial agents： doxycycline quinolones SMZ （O139 insensitive） （purpos

38、eto reduce the quantity of diarrhea，to shortern the diarrhea and vomit stage and excreting bacteria stage）,assistant treatment,Drugs to inhibit the secretion of intestinal mucosa： chlorderazin berberine antifani Adrenocortical hormone,symptomatic treatment,Correct acidosis Correct hypopotassemia Cor

39、rect shock Treat pulmonary edema,prevention,contaminator control,Establish and perfect the out-patient clinic of the diarrhea disease Isolate patients,break off transmission route,Improve the environment sanitation Strengthen the disinfection of drinking water and the administration of food,immunity

40、 improvement,Innoculate bacterial vaccin in epidemic,influencing complication?,Answer：the main factors which effect the liability of cholera are： Gastric acid, such as hypoacidity or absence Hygienic habit, such as eating raw marine products, drinking raw water, no washing hands before meal and afte

41、r toilet, and so on Age. In the endemicity of cholera，children are liable to infect and onset because of low or no immunity. Adolescents are more liable to infect in the cholera emerging district, because they are all sensitive, and have broad action range and more opportunities to contact V.cholera

42、. Population fluxion. Fluid population are liable to affect cholera.,main pathogenic mechanism,Answer：the main pathogenic mechanisms are： Onset of cholera is determined by the following two aspects: a. Level of gastric acid b. Amount and virulence of V.cholera. When the secretion of gastric acid dec

43、reases or the amounts of V.cholera increase，V.cholera will pass though the barrier of gastric acid and into the small intestine. With the help of flagellar movement and protease， V.cholera pass though the slime layer of intestinal mucosa and adhere to the brush border of epithelial cell. V.cholera g

44、enerate greatly in the alkalinity environment in the small intestine and produce cholera enterotoxin (also named choleragen）。 Cholera enterotoxin acts on the intestinal mucosa and glandular epithelium, provokes intestinal juice secreted excessively, and water diarrhea is seen.,typical clinical cours

45、e,Answer：The typical clinical course is ： Diarrhea and vomit period：Vomit following diarrhea；profuse and frequent stool，appearing “rice water stool”, yellow water stool, blood water stool，no feces foul smell；abdominal pain and fever scarely. Dehydration and prostration period：Skin kraurosis；Hoarse s

46、ound and thirsty；Sunken eyes； Scaphoid abdomen ；Muscle convulsion；Serious patients show blood pressure decrease, breathlessness and consciousness. Recovery and response period：Scare patients have responsive low-grade fever.,character of pathogeny，clinic，treatment,Answer： Caracters of pathogeny, clin

47、ic, and treatment of O139 cholera are： Caracters of pathogeny are：having capsule and specific bacterial antigen，no difference with O1 serogroup on the aspects of morphology, cultivate character, biochemisty and so on；no agglutination with routine diagnostic serum but specific O139 antiserum. Clinic

48、characters：serious symptom；abdominal pain commonly；with the complications of extra-intestinal infections such as bacteremia. Main points of treatment：Principles of fluid fusion are the same with cholera by O1 serogoup；It is resistant to SMZ and streptomycin，and suitable drugs should be selected according to the results of susceptibility.,tr