1. Typhoid fever

2. 历史 在 19 世纪 50 年代克里米亚战争爆发时，因伤寒而死亡的士兵是因战 伤而死亡的 10 倍。伤寒可引起高热和肠道出血，具有很高的传染性。 到了 1898 年，尽管这种疾病在当时仍然无法治愈，赖特却研制 出了伤寒疫苗。在次年爆发的布尔战争期间，士兵死于伤寒者仍然 要 5 倍于因战伤而死亡者。然而在第一次世界大战时，这种疫苗得到 了采用。数百万的士兵因战壕内恶劣的条件而死亡，但死于伤寒的 只有 100 人。 1907 年，厨师玛莉 · 马龙造成伤寒玛莉事件，可说是医学史上有 名的案例。伤寒玛莉 伤寒的症状包括高热、皮疹、寒战和出汗。 一个赖特未能预料到的问题是 “ 伤寒玛丽 ” 。玛丽这位妇女是位厨 师，她所到之处都引发了伤寒的蔓延，尽管她本人并未患病，但却 把所携带的病菌传染给了吃她食物的人。当最终被证实为传播病菌 的人后，她被扣留并 终身监禁。 伤寒玛丽

3. Definition Typhoid fever is an acute intestinal infectious disease caused by salmonella typhi and presents continuous fever, relatively slow pulse, neural toxic symptoms, symptoms in gastrointestinal tract, rose spots, hepatomegaly, splenomegaly, etc. Hemorrhage and perforation in intestines are mainly serious complications.

4. Pathogen 1. Salmonella typhi belongs to Salmonella D, stained by gram is negative. 2. H,O and Vi antigen of the bacillus can induce corresponding antibodies that can be detected in early stage(early diagnosis). 3. Endotoxin is the major cause of the disease. 4. resistance of Salmonella typhi is strong in natural environment, but sensitive to heat and common chemical drugs.

5. Epidemiology Distribution: There are about 33 millions cases of typhoid fever worldwide each year. Most cases occur in the developing world, especially in South and East Asia, Africa, Latin America and India.

6. Sources of infection 1. Both of patients and chronic carriers are Sources of infection. Patients can excrete bacillus during the course of the disease, especially from 2nd to 4th week after the disease occurs. 2. Patients who can excrete bacillus over 3 months are called chronic carriers, they are the main source of infection.(2~5 ％ )

7. Routes of transmission 1. The contaminated water and food 2. Routine contact with patients or carriers 3. Flies and cockroaches The contaminated water is thought as the main route to transmit the bacillus, and often cause fulminant epidemicity.

8. Groups at risk all people equally susceptible to infection acquired immunity can keep longer, reinfections are rare

9. Epidemic features all seasons, often in summer and autumn most cases in school-age children and young adults

10. Pathogenesis Ingested orally → Stomach barrier (some Eliminated) → enters the small intestine → Penetrate the mucus layer → enter macrophages of Peyer’ patches and mesenteric lymph nodes → thoracic lymph duct → spread to blood. ( Initial bacteremia, incubation period)

11. Pathogenesis →reproduce in mononuclear phagocyte system → A lot of bacteria enter into blood again and produce endotoxin (second bacteremia, 1-3weeks,typical clinical manifestation) →intestinal lymph node swell,proliferation,necrosis → enter liver spleen, gall bladder, kidney and bone marrow (farther proliferation occurs)

12. Pathogenesis → largely reproduce in gall bladder → invade intestinal lymphoid tissue (Defervescence stage,3-4 weeks,induce Intestinal hemorrhage and perforation) release chronic carrier → Recovery

13. Pathology essential lesion: Proliferation of monocyte macrophage system Special changes in aggregated lymphatic nodes and solitary lymphatic nodes of lower ileum.

14. Pathology Major findings in lower ileum Hyperplasia stage (1st week) Necrosis stage (2nd week) Ulceration stage (3 rd week) Stage of healing (from 4 th week)

15. Pathology Typhoid cell: Typhoid nodule(typhoid granuloma):

16. Clinical manifestations Incubation period: nearly 10 days The process of typical cases can be divided into 4 stages: 1. The initial period 2. The critical period (fastigium) 3. Defervescence stage (catabasis) 4. Convalescence stage

17. The initial period The first week Insidious onset Fever accompanied with general malaise, anorexia, angina, cough and so on.

18. The critical period The second and third weeks. 1.Sustained high fever, partly remittent fever or irregular fever. Last 10-14 days. 2.Gastro-intestinal symptoms: Anorexia, abdominal distension, constipation can be seen in most of the patients, seldom expressed by diarrhea. Slight tender in right lower quadrant

19. The critical period 3.Neuropsychiatric manifestations: Apathy, retardation, even express by toxic encephalopathy symptoms such as phrenitis, coma, pathologic reflex and so on. 4.Circulation system: Relative bradycardia or dicrotic pulse. 系副交感神经引起的，体温升 高与脉搏增加不成比例，即脉 搏不随体温的升高而加快。

20. The critical period 5.Splenomegaly, hepatomegaly, occasionally poisoned hepatitis can happende. 6.Rose spots: in 7-14 days of typhoid fever,there is rosiness macules or papules appear at chest, abdomen or back, limbs. fade on pressure, 2-4 mm in diameter, less than 10 in number. disappear in 2-4 days.

22. Defervescence stage the 4th weeks. Fever come down, gradual improvement in all symptoms and signs, but still danger.

23. Convalescence stage The 5th week complete recovery within 1 month.

24. Clinical forms: Mild infection Moderate infection Persistent infection Ambulatory infection: Mild symptoms, early intestinal bleeding or perforation. Fulminate infection Rapid onset, severe toxemia.

25. Relapse and recrudescence Relapse and recrudescence can be found in typhoid fever Relapse: clinical manifestation appear and blood culture is positive again after decrease of temperature due to decrease of immunity. Recrudescence: before convalescence stage, temperature increase again before it decrease to normal, last for 5-7 days, due to uncontrolled bacterimia.

26. Chronic carrier state A chronic intestinal carrier state, defined as documented fecal excretion of S typhi, is observed in 2% to 5% of typhoid fever patients. The gallbladder is the site of persistent intestinal infection.

27. Complications 1. Intestinal hemorrhage 2. Intestinal perforation(most serious) 3. Other complications poisonal hepatitis: poisonal mycarditis bronchitis, bronchopneumonia. poisonal encephalopathy. hemolytic uremic syndrome. acute cholecystitis. DIC.

28. Complications Intestinal hemorrhage Commonly appear during the second to the third week of illness Difference form mild to severe bleeding (occult blood in fecal—large amount of hemorrhage) Often caused by unsuitable food, motivation and so on. Serious bleeding: a sudden drop in temperature, rise in pulse, blood pressure decrease and signs of shock followed by dark or fresh blood in the stool.

29. Complications Intestinal perforation: The most serious complication. Commonly appear during the second--third week. Take place at the lower end of ileum. Express by sudden acute right lower abdominal pain, nausea, vomiting, drop in temperature and blood pressure, increase in pulse rate, then symptoms of peritonitis appear such as abdomen muscle entasia, reduce or disappear in the sonant extent of liver, leukocytosis, temperature rise, celiac free air under x-ray.

30. Laboratory findings Routine examinations: blood routine: WBC 3-5×109/L, neutrophilic granulocyte decrease, eosinophils decrease or disappear (significant to the degree of disease) urine routine:mild proteinuria fecal routine:blood

31. Laboratory findings Bacteriological examinations: blood culture The earliest positive cultural examination Re-positive when relapse and recrudescence. the bone marrow culture The most sensitive test Specially in patients pretreated with antibiotics. urine and stool cultures Stool culture is better in 3-4 weeks(75%) urine culture is 25% in 3-4 weeks rose spots: Not use routinely

32. Laboratory findings Widal test Five types antigen: Somatic antigen (O), flagella (H) antigen, and paratyphoid fever flagella (A,B,C) antigen. 1. OAb≥1:80 and HAb≥1:160 ----positive 2. OAb increase without increase of HAb: early stage of the disease. HAb increase without increase of OAb: immunization or previous infections or anamnestic reaction. 3. Examined once a week to dynamic detection

33. Laboratory findings Widal test 4. Antibody level may be lower or even not appear at all due to mild infection, use of antibiotics early and so on. 5. False positive in some infectious disease such as schistosomiasis, TB and so on. 6. “Vi” often useful for chronic carrier.

34. Laboratory findings Molecular biological tests: DNA probe or PCR.

35. Diagnosis epidemiologic data typical symptoms and signs laboratory findings

36. Diagnosis Standard: according to one of below positive culture of blood, bone marrow, urine, stool or rose pox. OAb≥1:80 HAb≥1:160 or dose of OAb increase more than 4 times.

37. Differential diagnosis i nfluenza: fever,headache,WBC↓ 1) No sustained fever 2) No hepatomegaly and splenomegaly 3) Wedal’s reaction and culture of blood are negative

38. Differential diagnosis fever, Malaria: fever, Splenomegaly, hepatomegaly,WBC↓ 1) Fever with chill; temperature drops with sweat and no symptoms of toxicity. 2) Splenomegaly is obviously seen and is felt rigidity. 3) Anemia of S. typhi and 4) Malaria can be detected in blood, but culture of S. typhi and Widal’s reaction is negative.

39. Differential diagnosis TB ： persistant fever,WBC ↓ 1) Fever: Irregular fever 2) Night sweat, quick pulse and breath and other symptoms of toxicity. 3) Culture of blood is tuberculomyces and tuberculocide (INH+RFP+SM) is effective. 4) X-ray detection can provide assistant differential diagnosis.

40. Differential diagnosis Septicemia: fever, Septicemia: fever, Splenomegaly, hepatomegaly,WBC↓ 1) Primarily infected focus 2) Shock often occurs and last for a long time ( several days) 3) Positive results of bacterial blood culture.

41. Treantment 1. General treatment isolation and rest good nursing care diet: easy to digest, abundance in vitamin and little with fibrin. Impropriety diet can induce occurrences of intestinal hemorrhage and perforation.

42. Treantment 2. Expectant treatment For high fever: physical measures firstly, antipyretic drugs should be administrated with caution Dexamethasone in addition to antibiotics reduces mortality.

43. Treantment 3. Etiologic treatment Quinotones( first choice): Norfloxacin, Ofloxacin, ciprofloxacin Caution: not in children and pregnant Ⅲ Cephalosporin: Ceftriaxone and Ceftazidime. Others: chloromycetin, ampicillin and so on.

44. Treantment Treatment of complication. Intestinal bleeding: bed rest, fast, close observation of vital signs. keep banlance of acid-base, water-electrolyte. use of hemostat. according to the condition of the patients, blood transfusion, ataractic, even surgery treatment can be given. Intestinal perforation: early diagnosis, fast, gastro-intestinal decompress, surgery treatment and use of antibiotics.

45. Treatment Chronic carriers are usually treated with oral ampicillin, 4 to 6 days.

46. Prevention Control the source of infection: Isolate the patients until temperature drop to normal for 15 days or give fecal culture per 5 days, negative for 2 times. Chronic carriers should be transfered from diet-service occupation. Cut the route of transmission: Public and individual sanitation. Improve immunity

47. The end