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1、TYPHOID FEVER AND PARATYPHOID FEVERGuoliGuoli Lin Lin Department of Infectious Diseases Department of Infectious Diseases The Third Affiliated Hospital of SYSU The Third Affiliated Hospital of SYSU Typhoid and Paratyphoid n nDefinitionDefinitionn nEtiologyEtiologyn nPathogenesis n nEpidemiologyEpide
2、miologyn nClinical manifestationsn nThe laboratory and The laboratory and other examinationsother examinationsn nComplicationsComplicationsn nDiagnosis and Diagnosis and differential differential diagnosisdiagnosisn nPrognosisPrognosisn nTreatmentTreatmentn nPreventionsPreventionsn nParatyphoid Feve
3、rParatyphoid FeverDefinition of Typhoid fevern nAcute enteric infectious diseaseAcute enteric infectious diseasen ncaused by Salmonella caused by Salmonella typhityphi ( (S.TyphiS.Typhi). ).n nprolonged fever, Relative prolonged fever, Relative bradycardiabradycardia, apathetic , apathetic facial ex
4、pressions,facial expressions, roseolaroseola, , splenomegalysplenomegaly, , hepatomegalyhepatomegaly, , leukopenialeukopenia. .n nintestinal perforation, intestinal hemorrhageintestinal perforation, intestinal hemorrhage Etiology Serotype: D group of Salmonella Gram-negative rod non-spore flagella C
5、ulture characteristics n nAntigens: located in the cell capsule Antigens: located in the cell capsule H ( H (flagellarflagellar antigen). antigen). O (Somatic or cell wall antigen). O (Somatic or cell wall antigen). Vi (polysaccharide virulence) Vi (polysaccharide virulence) “ “widelwidel test” test
6、”A schematic diagram of a single A schematic diagram of a single Salmonella Salmonella typhityphi cell cell showing the locations of the H (showing the locations of the H (flagellarflagellar), 0 (somatic), and ), 0 (somatic), and Vi (K envelope) antigens.Vi (K envelope) antigens.n nEndotoxinEndotoxi
7、n n nA variety of plasmidsA variety of plasmidsn nResistance: Live 2-3 weeks in water. Resistance: Live 2-3 weeks in water. 1-2 months in stool. Die out quickly in 1-2 months in stool. Die out quickly in summersummer Resistance to drying and cooling Resistance to drying and coolingEpidemiologyn ncon
8、tinues to be a global health problemcontinues to be a global health problemn n areas with a high incidence include Asia, areas with a high incidence include Asia, Africa and Latin AmericaAfrica and Latin American n affects about 6000000 people with more affects about 6000000 people with more than 60
9、0000 deaths a year. 80% in Asia .than 600000 deaths a year. 80% in Asia .n n sporadic occur usually, sometimes have sporadic occur usually, sometimes have epidemic outbreaks.epidemic outbreaks.Source of infectionCases and chronic carriersCases discharge from incubation, more in Cases discharge from
10、incubation, more in 24 weeks after onset, a few (about 25%) 24 weeks after onset, a few (about 25%) last longer than 3 months last longer than 3 months chronic carrier chronic carrier Typhoid MaryTyphoid MaryTransmission fecal-oral route close contact with patients or carriers contaminated water and
11、 food flies and cockroaches.Susceptibility and immunityn nall people equally susceptible to infectionn nacquired immunity can keep longer, reinfection are raren nimmunity is not associated with antibody level of “H”, “O”and “VI”.n nNo cross immunity between typhoid and paratyphoid.Susceptibility and
12、 immunityn nAll seasons, usually in summer and autumn.n nMost cases in school-age children and young adults.n nboth sexes equally susceptible.Pathogenesisngastrointestinal tract host-pathogen interactionsnThe amount of bacilli infection (105baeteria). ingested orallyingested orally Stomach barrier (
13、some Eliminated) Stomach barrier (some Eliminated) enters the small intestineenters the small intestinePenetrate the mucus layer Penetrate the mucus layer enter mononuclear phagocytes of enter mononuclear phagocytes of ilealileal peyerspeyers patches and mesenteric lymph nodespatches and mesenteric
14、lymph nodes proliferate in mononuclear phagocytes proliferate in mononuclear phagocytes spread to blood. initial spread to blood. initial bacteremiabacteremia (Incubation (Incubation period).period).PathogenesisPathogenesis enter spleen, liver and bone marrow enter spleen, liver and bone marrow ( (r
15、eticuloreticulo-endothelial system) -endothelial system) further proliferation occursfurther proliferation occurs A lot of bacteria enter blood again. A lot of bacteria enter blood again. (second (second bacteremiabacteremia). ). Recovery RecoveryS.Typhi.stomachLower ileumpeyers patches &mesenteric
16、lymph nodesthoracic duct 1st bacteremia(Incubation stage)10-14d(mononmononuclear uclear phagocphagocytesytes )2nd bacteremialiver、spleen、gall、BM ,ectearly stage&acme stage(1-3W）LN Proliferate,swell necrosis defervescence stage（3-4w）Bac. In gallBac. In fecesS.Typhi eliminatedconvalvescence stage(4-5w
17、)Enterorrhagia,intestinal perforation Pathologyn nessential lesion: proliferation of RES (reticuloendothelial system ) specific changes in lymphoid tissues and mesenteric lymph nodes.typhoid nodules“n n Most characteristic lesion: ulceration of mucous in the region of the Peyers patches of the small
18、 intestine回肠：回肠：集合淋巴结集合淋巴结(PEYERSPATCHES)增生增生伤寒小结(TYPHOID NODULE)Major findings in lower ileumnHyperplasia stage(1st week): swelling lymphoid tissue and proliferation of macrophages.nNecrosis stage(2nd week): necrosis of swelling lymph nodes or solitary follicles.Major findings in lower ileumn nUlce
19、ration stage(3rd week): shedding of necrosis tissue and formation of ulcer - intestinal hemorrhage, perforation .n nStage of healing (from 4th week): healing of ulcer, no cicatrices and no contraction Clinical manifestationsIncubation period: 360 days(714).The initial period (early stage)n n First w
20、eek. n nInsidious onset. n nFever up to 39400C in 57 daysn nchills、ailment、tired、sore throat、cough ,abdominal discomfort and constipation et al. The fastigium satgen nsecond and third weeks.n nSustained high fever、partly remittent fever or irregular fever. Last 1014 days. n nGastro-intestinal sympto
21、ms: anorexia、abdominal distension or pain、diarrhea or constipationn nNeuropsychiatric manifestations: confusion、blunt respond even delirium and coma or meningismn nCirculation system: relative bradycardia or dicrotic pulse.n nsplenomegaly、hepatomegaly toxic hepatitis.n nroseola :30%, maculopapular r
22、ash a faint pale color, slightly raised round or lenticular, fade on pressure2-4 mm in diameter, less than 10 in number on the trunk, disappear in 2-3 days.nfatal complications: intestinal hemorrhage intestinal perforation severe toxemiadefervescence stagen nfever and most symptoms resolve by the fo
23、rth week of infection.n nFever come down, gradual improvement in all symptoms and signs, but still danger.convalescence stagen nthe fifth week. disappearance of all symptoms, but can relapse图图 典型伤寒自然病程示意图典型伤寒自然病程示意图Clinical forms: n nMild infection: very common seen recently symptom and signs mild g
24、ood general condition temperature is 380C short period of diseases recovery expected in 13 weeks seen in early antibiotics users young children mild more easy to misdiagnosen nPersistent infection: diseases continue than 5 weeksn nAmbulatory infection: mild symptoms,early intestinal bleeding mild sy
25、mptoms,early intestinal bleeding or perforation.or perforation. n nFulminate infection: rapid onset, severe toxemia and septicemia. High fever,chill,circulation failure, shock, delirium, coma, myocarditis, bleeding and other complications, DIC et all.Special manifestationsn nIn children Often atypic
26、alOften atypical sudden onset with high fever. sudden onset with high fever. Respiratory symptoms and diarrhea, dominant. Respiratory symptoms and diarrhea, dominant. Convulsion common in below 3. Convulsion common in below 3. relative bradycardia rare. relative bradycardia rare. SplenomegalySplenom
27、egaly, , roseolaroseola and leucopenia less common. and leucopenia less common.nIn the agedtemperature not high, weakness common.More complications.high mortality.n nclinical manifestations reappear clinical manifestations reappear n nless severe than initial episode less severe than initial episode
28、 n nIts temperature recrudesce when temperature Its temperature recrudesce when temperature start to step down but abnormal in the period of start to step down but abnormal in the period of 2-3 weeks and persist 57 days then back to 2-3 weeks and persist 57 days then back to normal.normal.n nseen in
29、 patients with short therapy of seen in patients with short therapy of antibiotics.antibiotics.Recrudescencerelapsen nserum positive of S.typhi after 13 weeks of temperature down to normal.n nSymptom and signs reappearn nthe bacilli have not been completely removedn nSome cases relapse more than onc
30、eLaboratory findingsRoutine examinations:Routine examinations: white blood cell count is normal or decreased. Leukocytopenia(specially eosinophilic leukocytopenia). recovery with improvement of diseases decreased in relapseBacteriological examinations:Bacteriological examinations: n nBlood culture:
31、Blood culture: the most common use the most common use8090% positive during the first 2 weeks of illness8090% positive during the first 2 weeks of illness 50% in 3rd week 50% in 3rd week not easy in 4th week not easy in 4th weekre-positive when relapse and recrudescere-positive when relapse and recr
32、udesce attention to the use of antibiotics attention to the use of antibioticsn nThe bone marrow culture The bone marrow culture the most sensitive testthe most sensitive testspecially in patients pretreated with antibiotics.specially in patients pretreated with antibiotics.n nUrine and stool cultur
33、esUrine and stool culturesincrease the diagnostic yieldincrease the diagnostic yieldpositive less frequentlypositive less frequentlystool culture better in 34 weeks stool culture better in 34 weeks n nThe duodenal string test to culture bile The duodenal string test to culture bile useful for the di
34、agnosis of carriers.useful for the diagnosis of carriers.n nRose spots: Not use routinelyRose spots: Not use routinelySerological tests(Vidal test):Serological tests(Vidal test): five types of antigens:five types of antigens:somatic antigen(O),flagella(H) antigen, and paratyphoid fever somatic antig
35、en(O),flagella(H) antigen, and paratyphoid fever flagella(A,B,C) antigen.flagella(A,B,C) antigen.n nAntibody reaction appear during first weekAntibody reaction appear during first weekn n70% positive in 34 weeks and can prolong to 70% positive in 34 weeks and can prolong to several monthsseveral mon
36、thsn nin some cases, antibodies appear slowly, or in some cases, antibodies appear slowly, or remain at a low level, remain at a low level, n nsome(1030%) not appear at all.some(1030%) not appear at all.n nO agglutinin antibody titer 1:80 and H O agglutinin antibody titer 1:80 and H 1:160 or O 4 tim
37、es higher supports a 1:160 or O 4 times higher supports a diagnosis of typhoid feverdiagnosis of typhoid fevern nO rises alone, not H, early of the O rises alone, not H, early of the disease.Only H positive, but O negative, often disease.Only H positive, but O negative, often nonspecifically elevate
38、d by immunization or nonspecifically elevated by immunization or previous infections or previous infections or anamnesticanamnestic reaction. reaction.n nAntibody level maybe lower when have used Antibody level maybe lower when have used antibiotics early.antibiotics early.n nSome cross reaction bet
39、ween group “D” and Some cross reaction between group “D” and “A”.“A”.n nFalse positive in some infectious diseases.False positive in some infectious diseases.n nSome positive in blood culture ,but negative in Some positive in blood culture ,but negative in vidalvidal test. test.n nVi often useful fo
40、r carrier (1:40) Vi often useful for carrier (1:40) molecular biological tests: molecular biological tests: DNA probe or polymerase chain reaction DNA probe or polymerase chain reaction (PCR)(PCR)ComplicationsIntestinal hemorrhageCommonly appear during the second-third week of Commonly appear during
41、 the second-third week of illnessillnessdifference between mild and greater bleedingdifference between mild and greater bleedingoften caused by unsuitable food, diarrhea et al often caused by unsuitable food, diarrhea et al serious bleeding in about 28% serious bleeding in about 28%a sudden drop in
42、temperaturea sudden drop in temperature、 rise in pulserise in pulse、and and signs of shock followed by dark or fresh blood in the signs of shock followed by dark or fresh blood in the stool.stool. Intestinal perforation: n nThe more serious .Incidence,1-4%The more serious .Incidence,1-4%n nCommonly
43、appear during 2-3 weeks. Commonly appear during 2-3 weeks. n nTake place at the lower end of ileum.Take place at the lower end of ileum.n nBefore perforation,abdominal pain orBefore perforation,abdominal pain or diarrhea,intestinal bleeding . diarrhea,intestinal bleeding . n nWhen perforation, abdom
44、inal pain, sweating, drop in When perforation, abdominal pain, sweating, drop in temperature, and increase in pulse rate, then, rebound temperature, and increase in pulse rate, then, rebound tenderness when press abdomen,tenderness when press abdomen, abdomen muscle abdomen muscle entasiaentasia, re
45、duce or disappear in the , reduce or disappear in the sonant extent of liver, sonant extent of liver, leukocytosisleukocytosis . . n nTemperature rise .peritonitis appear.Temperature rise .peritonitis appear.n nceliac free air under x-ray. celiac free air under x-ray. n nToxic hepatitisToxic hepatit
46、is: : common,1-3 weeks common,1-3 weeks hepatomegalyhepatomegaly, ALT elevated, ALT elevated get better with improvement of diseases in 23 get better with improvement of diseases in 23 weeksweeksn nToxic Toxic myocarditismyocarditis. . seen in 2-3 weeks, usually severe toxemia. seen in 2-3 weeks, us
47、ually severe toxemia. n nBronchitis, bronchopneumonia.Bronchitis, bronchopneumonia. seen in early stageseen in early stageOther complicationsOther complications: :n ntoxic encephalopathy. toxic encephalopathy. n nHemolytic uremic syndrome. Hemolytic uremic syndrome. n nacute cholecystitisacute chole
48、cystitis、n nmeningitismeningitis、n nnephritis et al.nephritis et al.图图 典型伤寒自然病程示意图典型伤寒自然病程示意图Diagnosis n n Epidemiology datan nTypical symptoms and signsn nLaboratory findings.Differential diagnosisnViral infections: such as upper respiratory tract infection. such as upper respiratory tract infectio
49、n. abrupt onset with fever, headache, leucopenia, abrupt onset with fever, headache, leucopenia, sore throat, cough, sore throat, cough, coryzacoryza. . no rose spots, no enlargement of liver & spleen. no rose spots, no enlargement of liver & spleen. The course of illness no more than 2 wks.The cour
50、se of illness no more than 2 wks. differential diagnosis depends on typical differential diagnosis depends on typical manifestations and blood culture.manifestations and blood culture.Malariahistory of exposure to malaria.history of exposure to malaria.Paroxysms(often periodic) of sequential Paroxys
51、ms(often periodic) of sequential chill,high fever and sweating.chill,high fever and sweating.Headache, anorexia, Headache, anorexia, splenomegalysplenomegaly, anemia, , anemia, leukopenialeukopeniaCharacteristic parasites in Characteristic parasites in erythrocytes,identified in thick or thin blood
52、erythrocytes,identified in thick or thin blood smears.smears.n nLeptospirosisEndemic area,contacted with urine of mice.Endemic area,contacted with urine of mice.Abrupt fever,chills,severe headache,and Abrupt fever,chills,severe headache,and myalgiasmyalgias, , especially of the calf muscles.especial
53、ly of the calf muscles.LeptospiresLeptospires can be isolated from can be isolated from blood,cerebrospinal fluid.blood,cerebrospinal fluid.Special agglutination titers develop after 7 days Special agglutination titers develop after 7 days and may persist at high levels for many years.and may persis
54、t at high levels for many years.Epidemic Louse-Borne typhusEpidemic Louse-Borne typhusn nprodromalprodromal of malaise and headache followed by of malaise and headache followed by abrupt chills and fever.abrupt chills and fever.n nheadaches,prostration,persisting high fever.headaches,prostration,per
55、sisting high fever.n nMaculopapularMaculopapular rash appears on the forth to rash appears on the forth to seventh days on the trunk and in the seventh days on the trunk and in the axillasaxillas, , spreading to the rest of the body but sparing the spreading to the rest of the body but sparing the f
56、ace,palms,and soles.face,palms,and soles.n nLaboratory confirmation by proteins OX19 Laboratory confirmation by proteins OX19 agglutination and specific serologic tests. agglutination and specific serologic tests. Tuberculosisn ncontinuous high or low fever,fatigue,weight continuous high or low feve
57、r,fatigue,weight loss,night sweats.loss,night sweats.n nMild coughMild coughn npulmonary infiltration on chest radiographpulmonary infiltration on chest radiographn npositive tuberculin skin test reaction(most positive tuberculin skin test reaction(most cases)cases)n nacid-fast bacilli on smear of s
58、putumacid-fast bacilli on smear of sputumn nsputum culture positive for mycobacterium sputum culture positive for mycobacterium tuberculosistuberculosis. .Septicemia of Gram-negative bacillin nabrupt onset,high fever,symptom of toxemia.n nChill,sweats.n nShock.n nPositive of gram-negative bacilli fr
59、om blood culture.Prognosis:n nCase fatality 0.51%. n nbut high in old ages、infant、and serious complicationsn nHave immunity for ever after diseasesn nAbout 3% of patients become fecal carriers .TREATMENTTREATMENTGeneral treatmentGeneral treatmentn nisolation and restn ngood nursing care and supporti
60、ve treatment close observation T,P,R,BP,abdominal close observation T,P,R,BP,abdominal condition and stool .condition and stool . suitable diet include easy digested food or suitable diet include easy digested food or half-liquid food.drink more waterhalf-liquid food.drink more water intravenous inj
61、ection to maintain water and intravenous injection to maintain water and acid-base and electrolyte balanceacid-base and electrolyte balancen nSymptomatic treatment: for high fever:n nphysical measures firstlyphysical measures firstlyn nantipyretic drugs such as aspirin should be antipyretic drugs su
62、ch as aspirin should be administrated with cautionadministrated with cautionn ndelirium,coma or shock,2-4mg delirium,coma or shock,2-4mg dexamethasone in addition to antibiotics dexamethasone in addition to antibiotics reduces mortality.reduces mortality. Etiologic and special treatmentEtiologic and
63、 special treatment1.Quinolones: 1.Quinolones: first choice first choice its highly against its highly against S.typhiS.typhi penetrate well into macrophages,and achieve high penetrate well into macrophages,and achieve high concentrations in the bowel and bile lumens concentrations in the bowel and b
64、ile lumens n nNorfloxacin (0.1Norfloxacin (0.10.2 0.2 tidtidqid/10qid/1014 days).14 days).n nOfloxacin (0.2 Ofloxacin (0.2 tidtid 10 1014days). 14days). n nciprofloxacin (0.25 ciprofloxacin (0.25 tidtid) )caution: not in children and pregnantcaution: not in children and pregnant2.Chloramphenicol: 2.
65、Chloramphenicol: n nFor cases without For cases without multiresistantmultiresistant S.typhiS.typhi. . n nChildren in dose of 50Children in dose of 5060mg/kg/per day. 60mg/kg/per day. n nadult 1.5adult 1.52g/day. 2g/day. tidtid. . n nUnable to take oral medication, the same dosage Unable to take ora
66、l medication, the same dosage given given introvenouslyintrovenously n nafter after defervescencedefervescence reduced to a half. complete a reduced to a half. complete a 101014 day course.14 day course.n nBut ,drug resistance, a high relapse rate,bone But ,drug resistance, a high relapse rate,bone
67、marrow toxicity.marrow toxicity. 3.Cephalosporines: Only third generation effective Only third generation effective CefoperazoneCefoperazone and and CeftazidimeCeftazidime. . 2 24g/day .1014 days.4g/day .1014 days.4.Treatment of complication.n nIntestinal bleeding:Intestinal bleeding: bed rest, stop
68、 diet,close observation T,P,R,BP. bed rest, stop diet,close observation T,P,R,BP. intravenous saline and blood transfusion,and intravenous saline and blood transfusion,and attention to acid-base balances.attention to acid-base balances. sometimes,operative. sometimes,operative.n nPerforation: Perfor
69、ation: early diagnosis. early diagnosis. stop diet. stop diet. decrease down the stomach pressure. decrease down the stomach pressure. intravenous injection to maintain electrolyte intravenous injection to maintain electrolyte and acid-base balances.and acid-base balances. use of antibiotics. use of
70、 antibiotics. sometimes operative. sometimes operative. n nToxic Toxic myocarditismyocarditis: : bed rest, cardiac muscle protection drugs, bed rest, cardiac muscle protection drugs, dexamethasonedexamethasone, , digoxindigoxin. .5.Chronic carrier:5.Chronic carrier: n nOfloxacinOfloxacin 0.2 bid or
71、0.2 bid or ciprofloxacinciprofloxacin 0.5 bid, 4 0.5 bid, 46 6 weeks.weeks.n nAmpicillinAmpicillin 3 36g/day 6g/day tidtid plus plus probenecidprobenecid 1 11.5g/day. 41.5g/day. 46 weeks.6 weeks.n nTMP+SMZTMP+SMZ2 tabs. Bid. 12 tabs. Bid. 13 months.3 months.n nCholecystitisCholecystitis may require
72、may require cholecystectomycholecystectomy. .n nProphylaxis1.control source of infection1.control source of infection Isolation and treatment of patients Isolation and treatment of patients stool culture one time per 5 days. stool culture one time per 5 days. if negative continued two times ,without
73、 if negative continued two times ,without isolation.isolation. Control of carriers. Control of carriers. observation of 25 days(15 days in paratyphoid) observation of 25 days(15 days in paratyphoid) when close contactwhen close contact2. Cut of course of transmission key way avoid drinking untreated
74、 water and food. 3.Vaccination side-effect more, less useParatyphoid fever A,B,Cn nCaused by Salmonella paratyphoid Caused by Salmonella paratyphoid A,B,C.respectively.A,B,C.respectively.n nin no way different from typhoid fever in in no way different from typhoid fever in epidemiology, pathogenesis
75、,epidemiology, pathogenesis, pathology,clinical manifestations, pathology,clinical manifestations, diagnosis, treatment and diagnosis, treatment and Prophylaxis ProphylaxisParatyphoid A,B:Paratyphoid A,B:n nincubation period 215days, in genaral,810 days.incubation period 215days, in genaral,810 days
76、.n nmilder in severitymilder in severityn nfewer in complications.fewer in complications.n nBetter in prognosis, Better in prognosis, n nrelapse more common in Paratyphoid A.relapse more common in Paratyphoid A.n nTreatment same as in typhoid fever.Treatment same as in typhoid fever.Paratyphoid C:n
77、nAlways sudden onset.Always sudden onset.n nRapid rise of temperature.Rapid rise of temperature.n nPresented in different forms- Septicemia, Presented in different forms- Septicemia, Gastroenteritis and Enteric fever Gastroenteritis and Enteric fevern nComplications-arthritis, abscess formation, Complications-arthritis, abscess formation, cholecystitischolecystitis, pulmonary complications are , pulmonary complications are commonly monly seen.n nIntestinal hemorrhage and perforation not as Intestinal hemorrhage and perforation not as common as in typhoid mon as in typhoid
