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1、TYPHOID FEVER AND PARATYPHOID FEVER,Guoli Lin Department of Infectious Diseases The Third Affiliated Hospital of SYSU,Typhoid and Paratyphoid,DefinitionEtiologyPathogenesis EpidemiologyClinical manifestationsThe laboratory and other examinations,ComplicationsDiagnosis and differential diagnosisProgn
2、osisTreatmentPreventionsParatyphoid Fever,Definition of Typhoid fever,Acute enteric infectious diseasecaused by Salmonella typhi(S.Typhi).prolonged fever,Relative bradycardia,apathetic facial expressions,roseola,splenomegaly,hepatomegaly,leukopenia.intestinal perforation,intestinal hemorrhage,Etiolo
3、gy,Serotype:D group of Salmonella Gram-negative rod non-spore flagella Culture characteristics,Antigens:located in the cell capsule H(flagellar antigen).O(Somatic or cell wall antigen).Vi(polysaccharide virulence)“widel test”,A schematic diagram of a single Salmonella typhi cell showing the location
4、s of the H(flagellar),0(somatic),and Vi(K envelope)antigens.,Endotoxin A variety of plasmidsResistance:Live 2-3 weeks in water.1-2 months in stool.Die out quickly in summer Resistance to drying and cooling,Epidemiology,continues to be a global health problem areas with a high incidence include Asia,
5、Africa and Latin America affects about 6000000 people with more than 600000 deaths a year.80%in Asia.sporadic occur usually,sometimes have epidemic outbreaks.,Source of infection,Cases and chronic carriersCases discharge from incubation,more in 24 weeks after onset,a few(about 25%)last longer than 3
6、 months chronic carrier Typhoid Mary,Transmission,fecal-oral route close contact with patients or carriers contaminated water and food flies and cockroaches.,Susceptibility and immunity,all people equally susceptible to infectionacquired immunity can keep longer,reinfection are rareimmunity is not a
7、ssociated with antibody level of“H”,“O”and“VI”.No cross immunity between typhoid and paratyphoid.,Susceptibility and immunity,All seasons,usually in summer and autumn.Most cases in school-age children and young adults.both sexes equally susceptible.,Pathogenesis,gastrointestinal tract host-pathogen
8、interactionsThe amount of bacilli infection(105baeteria).,ingested orally Stomach barrier(some Eliminated)enters the small intestinePenetrate the mucus layer enter mononuclear phagocytes of ileal peyers patches and mesenteric lymph nodes proliferate in mononuclear phagocytes spread to blood.initial
9、bacteremia(Incubation period).,Pathogenesis,Pathogenesis,enter spleen,liver and bone marrow(reticulo-endothelial system)further proliferation occurs A lot of bacteria enter blood again.(second bacteremia).Recovery,S.Typhi.,stomach,Lower ileum,thoracic duct,1st bacteremia(Incubation stage)10-14d,(mon
10、onuclear phagocytes),2nd bacteremia,liver、spleen、gall、BM,ectearly stage&acme stage(1-3W）,LN Proliferate,swell necrosis defervescence stage（3-4w）,Enterorrhagia,intestinal perforation,Pathologyessential lesion:proliferation of RES(reticuloendothelial system)specific changes in lymphoid tissues and mes
11、enteric lymph nodes.typhoid nodules“Most characteristic lesion:ulceration of mucous in the region of the Peyers patches of the small intestine,回肠：集合淋巴结(PEYERSPATCHES)增生,伤寒小结(TYPHOID NODULE),Major findings in lower ileum,Hyperplasia stage(1st week):swelling lymphoid tissue and proliferation of macrop
12、hages.Necrosis stage(2nd week):necrosis of swelling lymph nodes or solitary follicles.,Major findings in lower ileum,Ulceration stage(3rd week):shedding of necrosis tissue and formation of ulcer-intestinal hemorrhage,perforation.Stage of healing(from 4th week):healing of ulcer,no cicatrices and no c
13、ontraction,Clinical manifestationsIncubation period:360 days(714).The initial period(early stage)First week.Insidious onset.Fever up to 39400C in 57 dayschills、ailment、tired、sore throat、cough,abdominal discomfort and constipation et al.,The fastigium satgesecond and third weeks.Sustained high fever、
14、partly remittent fever or irregular fever.Last 1014 days.Gastro-intestinal symptoms:anorexia、abdominal distension or pain、diarrhea or constipationNeuropsychiatric manifestations:confusion、blunt respond even delirium and coma or meningism,Circulation system:relative bradycardia or dicrotic pulse.sple
15、nomegaly、hepatomegaly toxic hepatitis.roseola:30%,maculopapular rash 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.,fatal complications:intestinal hemorrhage intestinal perforation severe toxemia,de
16、fervescence stagefever and most symptoms resolve by the forth week of infection.Fever come down,gradual improvement in all symptoms and signs,but still danger.convalescence stagethe fifth week.disappearance of all symptoms,but can relapse,图 典型伤寒自然病程示意图,Clinical forms:Mild infection:very common seen
17、recently symptom and signs mild good 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 misdiagnose,Persistent infection:diseases continue than 5 weeksAmbulatory infection:mild symptoms,early i
18、ntestinal bleeding or perforation.,Fulminate infection:rapid onset,severe toxemia and septicemia.High fever,chill,circulation failure,shock,delirium,coma,myocarditis,bleeding and other complications,DIC et all.,Special manifestationsIn children Often atypical sudden onset with high fever.Respiratory
19、 symptoms and diarrhea,dominant.Convulsion common in below 3.relative bradycardia rare.Splenomegaly,roseola and leucopenia less common.,In the agedtemperature not high,weakness common.More complications.high mortality.,clinical manifestations reappear less severe than initial episode Its temperature
20、 recrudesce when temperature start to step down but abnormal in the period of 2-3 weeks and persist 57 days then back to normal.seen in patients with short therapy of antibiotics.,Recrudescence,relapse,serum positive of S.typhi after 13 weeks of temperature down to normal.Symptom and signs reappeart
21、he bacilli have not been completely removedSome cases relapse more than once,Laboratory findingsRoutine examinations:white blood cell count is normal or decreased.Leukocytopenia(specially eosinophilic leukocytopenia).recovery with improvement of diseases decreased in relapse,Bacteriological examinat
22、ions:Blood culture:the most common use8090%positive during the first 2 weeks of illness 50%in 3rd week not easy in 4th weekre-positive when relapse and recrudesce attention to the use of antibiotics,The bone marrow culture the most sensitive testspecially in patients pretreated with antibiotics.Urin
23、e and stool culturesincrease the diagnostic yieldpositive less frequentlystool culture better in 34 weeks The duodenal string test to culture bile useful for the diagnosis of carriers.Rose spots:Not use routinely,Serological tests(Vidal test):five types of antigens:somatic antigen(O),flagella(H)anti
24、gen,and paratyphoid fever flagella(A,B,C)antigen.Antibody reaction appear during first week70%positive in 34 weeks and can prolong to several monthsin some cases,antibodies appear slowly,or remain at a low level,some(1030%)not appear at all.,O agglutinin antibody titer 1:80 and H 1:160 or O 4 times
25、higher supports a diagnosis of typhoid feverO rises alone,not H,early of the disease.Only H positive,but O negative,often nonspecifically elevated by immunization or previous infections or anamnestic reaction.Antibody level maybe lower when have used antibiotics early.,Some cross reaction between gr
26、oup“D”and“A”.False positive in some infectious diseases.Some positive in blood culture,but negative in vidal test.Vi often useful for carrier(1:40)molecular biological tests:DNA probe or polymerase chain reaction(PCR),ComplicationsIntestinal hemorrhageCommonly appear during the second-third week of
27、illnessdifference between mild and greater bleedingoften caused by unsuitable food,diarrhea et al serious bleeding in about 28%a sudden drop in temperature、rise in pulse、and signs of shock followed by dark or fresh blood in the stool.,Intestinal perforation:The more serious.Incidence,1-4%Commonly ap
28、pear during 2-3 weeks.Take place at the lower end of ileum.Before perforation,abdominal pain or diarrhea,intestinal bleeding.When perforation,abdominal pain,sweating,drop in temperature,and increase in pulse rate,then,rebound tenderness when press abdomen,abdomen muscle entasia,reduce or disappear i
29、n the sonant extent of liver,leukocytosis.Temperature rise.peritonitis appear.celiac free air under x-ray.,Toxic hepatitis:common,1-3 weeks hepatomegaly,ALT elevated get better with improvement of diseases in 23 weeksToxic myocarditis.seen in 2-3 weeks,usually severe toxemia.Bronchitis,bronchopneumo
30、nia.seen in early stage,Other complications:toxic encephalopathy.Hemolytic uremic syndrome.acute cholecystitis、meningitis、nephritis et al.,图 典型伤寒自然病程示意图,Diagnosis Epidemiology dataTypical symptoms and signsLaboratory findings.,Differential diagnosisViral infections:such as upper respiratory tract in
31、fection.abrupt onset with fever,headache,leucopenia,sore throat,cough,coryza.no rose spots,no enlargement of liver&spleen.The course of illness no more than 2 wks.differential diagnosis depends on typical manifestations and blood culture.,Malaria,history of exposure to malaria.Paroxysms(often period
32、ic)of sequential chill,high fever and sweating.Headache,anorexia,splenomegaly,anemia,leukopeniaCharacteristic parasites in erythrocytes,identified in thick or thin blood smears.,LeptospirosisEndemic area,contacted with urine of mice.Abrupt fever,chills,severe headache,and myalgias,especially of the
33、calf muscles.Leptospires can be isolated from blood,cerebrospinal fluid.Special agglutination titers develop after 7 days and may persist at high levels for many years.,Epidemic Louse-Borne typhusprodromal of malaise and headache followed by abrupt chills and fever.headaches,prostration,persisting h
34、igh fever.Maculopapular rash appears on the forth to seventh days on the trunk and in the axillas,spreading to the rest of the body but sparing the face,palms,and soles.Laboratory confirmation by proteins OX19 agglutination and specific serologic tests.,Tuberculosiscontinuous high or low fever,fatig
35、ue,weight loss,night sweats.Mild coughpulmonary infiltration on chest radiographpositive tuberculin skin test reaction(most cases)acid-fast bacilli on smear of sputumsputum culture positive for mycobacterium tuberculosis.,Septicemia of Gram-negative bacilliabrupt onset,high fever,symptom of toxemia.
36、Chill,sweats.Shock.Positive of gram-negative bacilli from blood culture.,Prognosis:Case fatality 0.51%.but high in old ages、infant、and serious complicationsHave immunity for ever after diseasesAbout 3%of patients become fecal carriers.,TREATMENTGeneral treatmentisolation and restgood nursing care an
37、d supportive treatment close observation T,P,R,BP,abdominal condition and stool.suitable diet include easy digested food or half-liquid food.drink more water intravenous injection to maintain water and acid-base and electrolyte balance,Symptomatic treatment:for high fever:physical measures firstlyan
38、tipyretic drugs such as aspirin should be administrated with cautiondelirium,coma or shock,2-4mg dexamethasone in addition to antibiotics reduces mortality.,Etiologic and special treatment1.Quinolones:first choice its highly against S.typhi penetrate well into macrophages,and achieve high concentrat
39、ions in the bowel and bile lumens Norfloxacin(0.10.2 tidqid/1014 days).Ofloxacin(0.2 tid 1014days).ciprofloxacin(0.25 tid)caution:not in children and pregnant,2.Chloramphenicol:For cases without multiresistant S.typhi.Children in dose of 5060mg/kg/per day.adult 1.52g/day.tid.Unable to take oral medi
40、cation,the same dosage given introvenously after defervescence reduced to a plete a 1014 day course.But,drug resistance,a high relapse rate,bone marrow toxicity.,3.Cephalosporines:Only third generation effective Cefoperazone and Ceftazidime.24g/day.1014 days.4.Treatment of complication.Intestinal bl
41、eeding:bed rest,stop diet,close observation T,P,R,BP.intravenous saline and blood transfusion,and attention to acid-base balances.sometimes,operative.,Perforation:early diagnosis.stop diet.decrease down the stomach pressure.intravenous injection to maintain electrolyte and acid-base balances.use of
42、antibiotics.sometimes operative.,Toxic myocarditis:bed rest,cardiac muscle protection drugs,dexamethasone,digoxin.5.Chronic carrier:Ofloxacin 0.2 bid or ciprofloxacin 0.5 bid,46 weeks.Ampicillin 36g/day tid plus probenecid 11.5g/day.46 weeks.TMP+SMZ2 tabs.Bid.13 months.Cholecystitis may require chol
43、ecystectomy.,Prophylaxis1.control source of infection Isolation and treatment of patients stool culture one time per 5 days.if negative continued two times,without isolation.Control of carriers.observation of 25 days(15 days in paratyphoid)when close contact,2.Cut of course of transmission key way a
44、void drinking untreated water and food.3.Vaccination side-effect more,less use,Paratyphoid fever A,B,CCaused by Salmonella paratyphoid A,B,C.respectively.in no way different from typhoid fever in epidemiology,pathogenesis,pathology,clinical manifestations,diagnosis,treatment and Prophylaxis,Paratyph
45、oid A,B:incubation period 215days,in genaral,810 days.milder in severityfewer in complications.Better in prognosis,relapse more common in Paratyphoid A.Treatment same as in typhoid fever.,Paratyphoid C:Always sudden onset.Rapid rise of temperature.Presented in different forms-Septicemia,Gastroenteritis and Enteric feverComplications-arthritis,abscess formation,cholecystitis,pulmonary complications are commonly seen.Intestinal hemorrhage and perforation not as common as in typhoid fever.,
