1、Typhoid fever Catalog 1、Summary 2、Etiology3、Epidemiology4、Pathogenesis and Pathology5、Clinical Manifestations6、Complication7、Laboratory Examinations8、Diagnosis and Differential Diagnosis9、Treatment10、Prophylaxis S Summaryummarysalmonella typhi fecal-oral route summer and autumn Post-infection immuni
2、ty can last decades Key signs and symptoms:constant fever, relative bradycardia, mental status changes, diarrhea or constipation, “rose spots”, hepatosplenomegaly, and leucopenia. Etiology Salmonella typhigermnegative, short-rod, aerobic, non-capsulated, non-spore-formingbelong to the salmonella spe
3、cies “D” groupO body or somatic antigen, the H antigen on the flagellar, and the Vi or virulence antigen Nonfastidious Enterobacteriaceae endotoxinElectron microscope 22500 Figure The Typhoid BacillusEpidemiologysource of infectionPatients and pathogeny carriers Chronic carriers, which have typhi or
4、ganisms persisting in stools or urine for 3 months Chronic carriers are public health threats, because they may substantially contaminate local water supplies, particularly in areas lacking appropriate treatment facilities.Typhoid MaryTyphoid MaryMary Mallon, better known as Typhoid Mary, was the fi
5、rst person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever. She was presumed to have infected 51 people, three of whom died, over the course of her career as a cook. She was twice forcibly isolated by public health authorities and died after a
6、 total of nearly three decades in isolation. Route of TransmissionRoute of Transmission Infection occurs through ingestion of the organisms in food (shellfish, fruit, vegetables) contaminated at the source or during handling (hands or instruments soiled by faeces/urine of infected person). Flies may
7、 infect the food in which the organism then multiplies to attain an infective dose. Either the contaminated water or food can bring epidemics.Susceptible PopulationAny age and either sex may contract typhoid fever, but children and young adults are most commonly affected.Epidemiologic Feature These
8、often occur as point-source epidemics, from healthy carriers to food. Outbreaks may occur through person-to-person contamination. Direct faecal contamination of untreated water supplies may cause extensive outbreaks.The Indian subcontinent and parts of Africa, Asia, and Central and South America tha
9、t are economically poor countries are endemic for typhoid fever. In developed countries, clean drinking water and adequate waste disposal have dramatically diminished the prevalence of typhoid fever, and most cases of typhoid fever are imported from endemic areas.Pathogenesis and PathologyWhen the b
10、acterium passes down to the bowel, it penetrates through the intestinal mucosa to the underlying tissue. The organisms are phagocytosed by mononuclear phagocytesthe bacterium will multiply and/or are drained by terminal lacteals and thoracic lymph duct to the bloodstream, named the first bacteremia.
11、 In the second phase of the disease the bacterium replicated in mononuclear phagocyte system, and the often violent symptoms such as hyperphrexia, malaise, and myalgia begin. If the immune system is unable to stop the infection here, the bacterium penetrates further to the bone marrow, liver and bil
12、e ducts, from which bacteria are excreted into the bowel contents, named the second bacteremia. At the same time, organisms excreted in the bile either reinvade the intestinal wall or are excreted in the feces. Salmonella typhi(PH2; 105) stomach （achlorhydria ） intestinal mucosa to the underlying ti
13、ssue thoracic lymph duct bloodstream（ the first bacteremia ） bone marrow, liver and bile ducts bloodstream（ the second bacteremia） endotoxin signs and symptoms（ constant fever,relative bradycardia, “rose spots”, hepatosplenomegaly, and leucopenia organisms excreted in the bile either reinvade the in
14、testinal wall necrosis and ulceration at the intestinal tract （Enterorrhagia and Intestinal Perforation)PathologyPathology ：monocyte phagocyte system proliferative reaction The first week: Lymphoid hyperplasia swellingThe second week: Necrosis of lymphoid tissueThe third week: The necrotic tissue sl
15、oughs off, leaving an ulcerThe fouth week: Ulcer healingtyphoid noduletyphoid noduleClinical Manifestations incubation ： 10 to 14 days The clinical cause of classical typhoid fever may be separated into four phases Early stage 、Acme stage 、Catabasis stage 、Convalescence stage （1week）（）（2-3week）（）（3-
16、4week）（）（5week）Early stage ：( 1week )fever, chills, weakness, headache, malaise, and myalgia Initially the fever is low grade, but it rises progressively, and by the second week it is often high and sustained (3940)Acme stage ：(23week)1. Pyrexia(sustainedfever)2. Central nervous system(lethargic fac
17、e ) 3. Gastrointestinal system (diarrhea or constipation)4. Cardiovascular system (relative bradycardia )5. Skin (Rose spot ) 6. hepatosplenomegalysustained feverThe classical temperature chart has a plateau at 3940 Typical pattern is present only in the untreated and uncomplicated case, and other p
18、atterns may lead to difficulty.sustained feverCentral nervous system dull expressionlesslethargic facecoated tongueslight deafness a musty odourSeverely agitated, delirious, complete stupor or coma dull expressionless lethargic faceGastrointestinal system Vague abdominal discomfort , Vomiting Consti
19、pation occurs more frequently than diarrhoea The liver and spleen is enlarged and soft, and there is often diffuse tenderness. Cardiovascular system relative bradycardia: A better description is that the pulse rate is relatively slow compared to the temperature during the first week of illness, and
20、it seldom exceeds 100 per minute.rose spotsCharacteristic skin rash:no larger than 1-2mm in diameter seldom number more than 10 to 12 in chest, up abdomen, and back The spots are rose-colored, slightly raised and fade on pressure. Catabasis stage : It is the third or fourth week that the fever drops
21、 and the general condition slowly improves. But there is a danger of complication. Intestinal perforation of profuse bleeding from the intestinal mucosa may occur if typhoid fever is left untreated.Clinical ManifestationsConvalescence stage :The fifth week of the disease that has the feature of norm
22、al temperature, good appetite.The two conceptsThe two conceptsrelapserelapse：Patients in recovery stage, stable cooling temperature rise again after a period of time, clinical symptoms appear again.recrudescencerecrudescence：The signs and symptoms of patients gradually reduced, the temperature does
23、not drop to normal once again increased, clinical symptoms appear plication1. Enterorrhagia 2. Intestinal Perforation3. heart valves (endocarditis )4. bones (osteomyelitis) 5. Pneumonia 6. kidneys (glomerulitis )EnterorrhagiaA common complication may be a very serious complication of typhoid fever;
24、it usually occurs 14 to 21 days after the onset of the illness and is often silent. In the majority of cases, the bleeding is slight and resolves without the need for blood transfusion, but in 2% of cases, bleeding is clinically significant and can be rapidly fatal if a large vessel is involved.Inte
25、stinal PerforationIt classically occurs during the third week of illness. In many cases the first indication of perforation may be the presence of free fluid in the abdomen. There will also be deterioration in the general condition of the patient, severe abdominal pain, absent bowel sounds, and vomi
26、ting. Laboratory Examinations Routine Detection white blood cell count : A low count with a relative lymphocytosis is commonly seen The count of eosinophilic cells may be low or zero.Culture of the Typhoid BacillusBlood cultures: positive in 60%80% of patientsbone marrow culture : positive in 80%95%
27、 of patientsStool and urine culture : positive in the third or fourth week ,so Clinic rarely usedSerologic Testing The role of the agglutination reaction of the serum, or the Widal test, is controversial, because the sensitivity, specificity, and predictive values of this widely used test vary consi
28、derably among geographic areas. The diagnostic titers are 1:80 for O antibody, 1:160 for H antibody, or the titers of post sample is at least 2 double of the former.H H antigen agglutination reaction agglutination reaction O antigen agglutination agglutination reactionreactionwidal test The O antige
29、n agglutination becomes positive at the early stage and decreases soon. But the case of H antigen agglutination is converse. widal testIn an un-immunised patient it does not become positive until after 7 to 10 days of illness. In an endemic area, or in patients who have had previous TAB vaccine inoc
30、ulations, the H antibody level can be raised by many non specific illnesses, and therefore-yield little specific data. widal testwidal testAn O antigen agglutination of 1:200 in a patient with a rising titer is much more value. TO TH TA TB TC TO TH TA TB TC meaning early in the disease Not long ago
31、had been infected typhoid typhoid fever paratyphoid fever A paratyphoid fever B paratyphoid fever C DiagnosisThe diagnosis must be made mainly on epidemiology finding, clinical examination and laboratory investigations. Some tests such as a low blood cell count and positive of Widal reaction may ind
32、icate the diagnosis. In the appropriate clinical setting, the definitive diagnosis of typhoid fever requires isolation and biochemical characterization of etiologic agent. Early in the course of disease, blood and bone marrow cultures yield the highest recovery of organisms, while later in the cours
33、e of disease, stool and sometimes urine cultures are more likely to become positive. Differential DiagnosisParatyphoids A, B and C： The laboratory is usually required as the final authority. Geographic distribution sometimes simplifies the matter; the paratyphoids are rare in East Africa, but paraty
34、phoid B is not uncommon in Britain.Differential DiagnosisSalmonella Infection and Gastroenteritis Salmonella, the dysentery group, and staphylococci may occasionally cause an invasive illness resembling typhoid fever with bacteremia. Usually, however, the gastrointestinal symptoms are more acute tha
35、n the general manifestations and the pyrexia much lower and of shorter duration. Differential DiagnosisMalaria This may be mistaken for typhoid in countries where both are endemic. A history of previous attacks, the more rapid onset in malaria, the shivering and sweating, the high early pyrexia, the
36、 relative infrequency of abdominal symptoms and signs, and a positive blood slide all point to a diagnosis of malaria.Differential DiagnosisInfluenza Influenza may also be confused with typhoid, but is usually of much more rapid onset with high temperature, severe sore throat, cough, and the absence
37、 of a palpable spleen and rose spots.Differential DiagnosisBacillary Dysentery The onset is usually acute, with severe blood diarrhoea. Diarrhoea with blood is rare in early typhoid. The signs and symptoms in dysentery are usually abdominal and remain so, the mental state and chest being clear.Diffe
38、rential DiagnosisPulmonary Tuberculosis and Atypical Abdominal Tuberculosis These are probably the most difficult diagnoses to differentiate from typhoid in economically poor countries. The pyrexia and vague symptoms and signs may be very similar. A chest X-ray, or laboratory confirmation of typhoid
39、, may be the only sure method of diagnosis. General Management Feeding of the patient must include an adequate fluid and mineral intake, and a low roughage diet . Constipation should be only treated with liquid paraffin and hypopiesis coloclyster with normal sodium. Cathartic, such as neostigmine, s
40、enna leaf is prohibited. Retention of urine may be silent in the toxic patient and will require catheterisation. Hyperpyrexia will require tepid sponging mental disturbance may require sedation The general observation of the patient is important. This is with particular regard to pulse, blood pressu
41、re, respiration, severe toxaemia, blood in the stools, and any evidence of intestinal haemorrhage or perforation.Antimicrobial TherapyChloramphenicol, TMP/SMX, ampicillin, third-generation cephalosporins, and quinolones have been used successfully for the treatment of typhoid fever. Unfortunately, a
42、ntimicrobial resistance has emerged to each of these agents. Some Salmonella isolates are multidrug resistant. For this reason, whenever possible, antimicrobial therapy should be based on an individual isolates susceptibility profile, obtained by standard methods. Chloramphenicol was the first drug
43、used for the treatment of typhoid fever. However, increasing resistance, high relapse rates, bone marrow toxicity, and the promotion of a chronic carrier state have limited its usefulness. advantages include its high efficacy, low cost, and oral administration.Ampicillin and TMP/SMX were used to tre
44、at typhoid fever after chloramphenicol resistance emerged. For susceptible isolates, these drugs are effective, easily administered, and do not have the high rate of relapse associated with chloramphenicol.The third-generation cephalosporin, ceftriaxone, is highly effective for the treatment of the
45、treatment of typhoid fever in adults and children. Third-generation cephalosporins are especially useful as empiric therapy in areas in which multiple-drug resistance has been reported. Currently, ciprofloxacin is the drug of choice for adults from India, Asia, or the Middle East. Chromosomally medi
46、ated quinolone resistance has emerged .In addition the relapse rates appeared to be much higher in the inadequately treated patients. It is therefore recommended that treatment of the initial infection with antibiotics should be continued for at least 14 days Complication Therapy Enterorrhagia:For e
47、nterorrhagia ,treatment should be by early blood transfusion, nothing by mouth for 24 hours, adequate dosages of suitable analgesics by injection, and very careful nursing and medical supervision. Complication Therapygastrointestinal perforation:Patients with gastrointestinal perforation during typh
48、oid require resuscitation with fluids, blood, and oxygen, as appropriate, followed by surgery. ProphylaxisIn typhoid fever prevention is mainly by ensuring pure water supplies and sewage disposal, raw food such as vegetables and shellfish. On the other hand, the accent is on improvement of personal
49、hygiene.Prophylactic measures should be directed toward prevention and the treatment of every suspected carrier, as well as the improvement of hygienic standards of food handlers and the public generally.It has been shown that typhoid inoculation of typhoid, paratyphoid a, and paratyphoid b vaccine
50、(TAB), is of limited value in the prevention of typhoid fever. It is also of practically no value in affecting the course of the disease once typhoid has been contracted. A few vaccines have had more success and or should presently be ready for licensure. Question and AnswerClinical manifestations a
