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1、1CholeraCAI DACHUAN Ph.DDepartment of Infectious diseases 2nd Clinical College CQMU2Cholera is an acute diarrhoeal disease that can kill victim within hours if left untreated. Up to 80% of cases can be successfully treated with oral rehydration salts口服补液盐. Key facts3456HistoryCholera likely has its

2、origins in the Indian subcontinent being prevalent流行的 in the Ganges delta since ancient times. The disease first spread by trade routes to Russia in 1817, then to Western Europe, and from Europe to North America.7General Characteristics of V.choleraeGram-negative, curved rod革兰氏阴性,弯曲杆状Motile运动, singl

3、e polar flagellum单极鞭毛 They tolerate alkaline media that kill most intestinal commensals肠道共生菌, but they are sensitive to acid. 8Vibrio Cholerae tadpoles 9O1Atypical O1O2O200O139Vibrio Cholerae : biotypeUntil 1992, cholera was caused by only two serotypes, Inaba (AC) and Ogawa (AB), and two biotypes,

4、classical and El Tor, of toxigenic O group 1 V cholerae.10Cholera can be spread as an endemic地方性, epidemic流行性, or pandemic 大流行disease.Previously, the disease swept the world in 6 great pandemics and later receded into its ancestral home in the Indo-Pakistani subcontinent and Africa. Epidemiology 11E

5、pidemiology 121314In 1961, the El Tor biotype of V cholerae emerged from the Sulawesi, causing the 7th great cholera pandemic. In 1992, with the emergence of O139 in India and Bangladesh. It might be the 8th pandemic.Epidemiology 15Epidemiology symptomatic cases & asymptomatically infected individua

6、lsHumans apparently are the only natural host for the cholera vibrios.Reservoir: shellfish and planktonCase:Infections = 1:3 to 1:10016Key factsEvery year, there are an estimated 35 million cholera cases and 100 000120 000 deaths due to cholera.The short incubation period of two hours to five days,

7、enhances the potentially explosive pattern of outbreaks爆发流行. 17Cholera appears to exhibit three major epidemiologic patterns: heavily endemic neoepidemic 新发流行 occasional limited outbreaks偶然的局地爆发Epidemiology 18Periodicity周期性: The epidemic may vary from year to year Seasonally季节性: depending partly on

8、the amount of rain and degree of flooding. Epidemiology 19Pathogenesis Up to 1011 living cholera vibrios not be recovered from stools of the volunteers After the gastric acidity neutralized, however, cholera diarrhea developed in most volunteers given 104 cholera vibrios.20Pathogenesis Attachment粘附S

9、mall intestine is normally relatively free of bacteria because of the effective clearance mechanisms of peristalsis蠕动 and mucus secretion.21adherence factorsHemagglutinins血凝素toxin-coregulated pilimotility运动性 of the vibriosmucinolytic enzymes粘蛋白溶酶Neuraminidase神经氨酸苷酶proteases22Choleragen霍乱肠毒素23Monomer

10、ic enzymatic moietypentameric binding moiety24Pathogenesis25Pathogenesis osmolality26Pathophysiology Na K Cl HCO3 Stool:adult 135 15 100 45 child 105 25 90 Serum: 136 3.8 98 24 148 5.0 106 32Voluminous大量 watery diarrhea and vomiting result in hypovolemic shock ,electrolyte turbulance and acidosis .2

11、7Clinical Manifestations 28Step 1: Diarrhea and Vomiting Abrupt onset of diarrhea “Quiet” diarrhea Vomiting after diarrhea29V cholerae does not elicit an inflammatory response. (few leukocytes and no erythrocytes in stool)Because of the large volume of diarrhea, patients with cholera have frequent a

12、nd often uncontrolled bowel movements. ( abdominal cramps腹部痛性痉挛).30DiarrheaProfuse watery diarrhea is a hallmark of cholera. a acute, severe, watery diarrheaMaybe more than that of any other infectious diarrhea. 250 mL/kg in 24h The stool may contain fecal material early in the course of clinical il

13、lness. a rice water appearance 31Cholera hospital with several empty beds, made up with plastic sheets and a hole for drainage .32“rice water”33Step 2: Dehydration脱水Loss of electrolyte :Muscle cramps Metabolic acidosisHypovolemic shockLoss of skin turgor皮肤弹性下降, scaphoid abdomen舟状腹 , and weak pulse34

14、3536losses of normal body weight35% thirst develops58%postural hypotension体位性低血压, weakness, tachycardia, and decreased skin turgor10%oliguria少尿, weak or absent pulses脉弱或无脉, sunken eyes ,wrinkled skin皮肤褶皱, coma37Assessment of Dehydration ConditionEyesTearsMouth and TongueThirstSkin Pinch皮肤挤压DecisionW

15、ell, alert警觉NormalPresentMoist潮湿Drinks normally, notthirstyGoes back quicklyMild*Restless, irritableSunkenAbsentDry*Thirsty, drinks eagerly*Goes back slowlyModerate*Lethargic昏睡 or unconscious无意识, floppy身软Very sunken and dryAbsentVery dry*very thirsty*Goes back very slowlySevere38Step 3:Convalescence

16、恢复期39Other signs for severe dehydration include absent radial pulse桡动脉脉搏 and low blood pressure.Tears are relevant signs only for infants and young children.Decreased intravascular volume is manifested by tachycardia, absent or barely palpable peripheral pulses, and hypotension.40cholera sicca干性霍乱 T

17、his is an mon, severe form of cholera. In this form of cholera there is massive outpouring of fluid and electrolytes into dilated intestinal loops. There is no diarrhoea and vomiting. Often the condition is not recognised as a form of cholera.41SymptomsCholera is an extremely virulent disease. It af

18、fects both children and adults and can kill within hours. About 75% of people infected with V. cholerae do not develop any symptoms, although the bacteria are present in their faeces for 714 days after infection and are shed back into the environment, potentially infecting other people. 42Among peop

19、le who develop symptoms, 80% have mild or moderate symptoms, while around 20% develop acute watery diarrhoea with severe dehydration. This can lead to death if untreated. People with low immunity such as malnourished营养不良 children or people living with HIV are at a greater risk of death if infected.4

20、3Lab StudiesHematological tests血液学检查Hemoconcentration血液浓缩: Hematocrit血细胞压积, serum-specific gravity, and serum protein are elevated .First observed, they generally have a leucocytosis白细胞增多 without a left shift.44Serum electrolytesSodium: 130-135 mmol/LPotassium : normal.Bicarbonate碳酸氢盐 : less than 15

21、 mmol/L in severely dehydrated patients .Lab Studies45Renal profile肾功: Blood urea nitrogen血尿素氮 and serum creatinine血肌酐 are elevated, reflecting the decrease in glomerular filtration. Lab Studies46Direct microscopic examination: V cholerae is a gram-negative curved bacillus弯曲杆菌 .Dark field organism暗视

22、野观察: The characteristic motility can be examined easily by direct dark field examination of the stool. Moreover, it can be confirmed by adding Vibrio antisera, which results in cessation终止 of motility of only the homologous organism.Lab Studies474849Lab Studies : Culture Routine differential media:

23、Colonies are lactose-negative, like all other intestinal pathogens, but sucrose蔗糖-positive. Alkaline enrichment media: As Vibrio species has the ability to grow at a high pH or in bile salts, peptone water蛋白胨水 (pH 8.5-9) or selective media containing bile salts are mended to facilitate isolation隔离 a

24、nd lab diagnosis. 50Diagnosis in labRapid bacteriologic diagnosis offers relatively little clinical advantage to the patient with secretory diarrheaNevertheless, rapid identification of the agent can profoundly affect the subsequent course of a potential epidemic outbreak.51Complicationsacute renal

25、failureacute pulmonary edema52Principle: Strict quarantine严格检疫 Rehydration in time及时补液 Antibiotics adjuncts 辅用抗生素TREATMENT53Steps in the treatment of a patient with suspected choleraStep 1: Assess for dehydration. Step 2: Rehydrate the patient and monitor frequently. Then reassess hydration status.

26、Step 3: Maintain hydration. Step 4: Administer an oral antibioticStep 5: Feed the patient.54TREATMENTRapid correction of hypovolemia and metabolic acidosis and prevention of hypokalemia are important.Oral administration of a glucose-electrolyte solution is effective in replacing stool losses and may

27、 be used after initial IV rehydration. 5556Electrolyte and Glucose Concentration (mmol/L) Na+ Cl- K+ HCO3- GluCholera Stool Adults 130 100 20 44 Children 100 90 33 30 Intravenous Solutions Lactated Ringer solution 130 109 4 28 0 Dhaka 133 98 13 48 0 Isotonic sodium chloride 154 154 0 0 0 solutionPer

28、u polyelectrolyte 90 80 20 30 111 WHO ORS 90 80 20 30 111 57SOLUTION 541 with glucose:Sodium chloride 5g 0.9%NaCL 550mlSodium bicarbonate 4g 5%NaCO3 80mlPotassium chloride 1g 10%KCL 10mlGlucose 10g 5%GS 360mlTREATMENT58Severe dehydration Administer IV fluid immediately to replace fluid deficit. 8000

29、12000ml/dMonitor the patient very frequently. After the initial administration, the radial pulse should be strong and blood pressure should be normal. Reassess the patient after 3 hours.TREATMENT59Moderate dehydration :40008000ml in 24 hours2000ml in 2 hours2000ml +total loss in 12 hoursAdminister O

30、RS solution according to the condition of dehydration TREATMENTORS=oral rehydration salt口服补液盐60Age115 yWeight30 kg ORS in mL200-400400-600600-800800-12001200-22002200-4000Use the patients age only when weight is unknown. The approximate amount of ORS required (in mL) also can be calculated by multip

31、lying the patients weight (in kg) times 75. Approximate Amount of ORS Solution to Administer in the First 4 Hours61Mild dehydration:30004000ml in 24 hours35ml/minPatients who are first observed with no signs of dehydration can be treated with ORS packets . TREATMENT62TREATMENTThe oral solution mende

32、d by the WHO contains: 20 g glucose; 3.5 g sodium chloride2.9 g trisodium citrate dihydrate (or 2.5 g sodium bicarbonate)1.5 g potassium chloride per liter of water. 63ORS around the world 64Estimate of ORS Solution Packets to be Administered: AgeAmount of Solution After Each Loose StoolORS Packets

33、Needed10 yearsAs much as is wantedEnough for 200 mL/d65A simple way to prepare “ORS”66Use of oral antibiotics in patients with severe dehydration: An effective antibiotic can: reduce the volume of diarrhea shorten the period during which V cholerae O1 is excreted. shortening the period of hospitaliz

34、ation. 67Begin antibiotic therapy after the patient has been rehydrated (usually in 4-6 h) and vomiting has stopped. The choice of antibiotics is determined by the susceptibility patterns of the local strains of V cholerae O1 or O139. TREATMENT6869Cholera is an easily treatable disease. Up to 80% of

35、 people can be treated successfully through prompt administration of oral rehydration saltsTREATMENT70Very severely dehydrated patients require administration of intravenous fluids. Such patients also require appropriate antibiotics to diminish the duration of diarrhoea, reduce the volume of rehydration fluids needed, and shorten the duration o

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