Paratyphoid

Introduction to paratyphoid Paratyphoid fever is an acute infectious disease caused by paratyphoid bacillus. There are three pathogens, M. parahaemolyticus, E. parahaemolyticus and C. parahaemolyticus. The symptoms of paratyphoid fever are similar to those of typhoid fever, but the symptoms of paratyphoid fever are quite different. The incubation period is shorter than typhoid fever, usually 8 to 10 days, sometimes only 3 to 6 days. basic knowledge The proportion of illness: 0.0025% Susceptible people: no special people Mode of infection: respiratory transmission Complications: osteomyelitis endocarditis pericarditis

Cause of paratyphoid fever

Pathogen infection (75%):

There are three pathogens of paratyphoid fever:

The pathogen of a pair of typhoid A is A. paratyphi A, or Salmonella paratyphimurium;

The pathogen of 2 typhoid fever B is Escherichia coli, or Salmonella paratyphimurium;

The pathogen of the three typhoid fever C is C. parahaemolyticus, or Salmonella paratyphimurium. The above three bacilli belong to the A, B, and C groups of Salmonella, and can be classified according to the phage typing method. Both parahaemolyticus have "O" and "H" antigens, of which C. parahaemolyticus also has "Vi" antigen. Under natural conditions, paratyphoid bacillus can only infect humans.

Low immunity (15%)

When the body's immunity is low and the resistance is reduced, the body is infected by the bacteria after passing through the environment or after contacting the patient, causing symptoms of paratyphoid fever.

Paratyphoid prevention

The prevention of this disease should take comprehensive preventive measures with a focus on cutting off the transmission route, and adapt to local conditions.

1. Control the source of infection to isolate and treat patients early. The isolation period should be until the clinical symptoms disappear. 15 days after the body temperature returns to normal, the stool culture test can also be performed once, /5 to 7 days, and 2 consecutive times are negative. Dissolution, patient's toilet, toilet, utensils, clothing, daily necessities must be properly disinfected, the management of chronic carriers should be strictly implemented, food, conservation, water supply and other industries should be regularly checked, early detection of bacteria Those with chronic carriers should be transferred from the above-mentioned jobs, treated, and regularly supervised and managed. Close contacts should be medically observed for 23 days. Patients with suspected typhoid fever with fever should be treated early.

2. Protection of susceptible typhoid vaccination can play a certain protective role for susceptible populations, typhoid fever, paratyphoid A, B triple vaccine prevention effect is not ideal, the response is also large, not used as a routine immune prevention application, in outbreaks There are different opinions on the emergency immunization problem in epidemic areas, which may have a certain effect on the control epidemic. Ty21a strain oral attenuated live vaccine, approved in the United States in 1989, has fewer adverse reactions and has certain protective effects.

Paratyphoid complications Complications osteomyelitis endocarditis pericarditis

Complications include arthritis, joint abscess, osteomyelitis, pneumonia, endocarditis, pericarditis and so on.

Paratyphoid symptoms common symptoms abdominal pain high fever diarrhea cold warfare reaction positive

Paratyphoid A, the symptoms of B and typhoid are very similar, but the symptoms of paratyphoid C are quite different, the incubation period is shorter than typhoid, usually 8 to 10 days, sometimes only 3 to 6 days.

1. Paratyphoid A, B is slow onset, but it is not uncommon for sudden rise. At the beginning, there may be acute gastroenteritis symptoms such as abdominal pain, vomiting, diarrhea, etc. After about 2 to 3 days, the symptoms are relieved, and then the body temperature rises. Symptoms of typhoid fever appear, and there are also significant symptoms of gastrointestinal inflammation, and those who last longer are more common with paratyphoid fever. They have been called "gastrointestinal gastroduodenal typhoid fever", and fever often peaks within 3 to 4 days. Larger, missed heat type is rare, heat cycle is shorter (average paratyphoid A 3 weeks, paratyphoid B 2 weeks), toxic blood symptoms are mild, but intestinal symptoms are more significant, can appear relatively slow pulse and liver, spleen Swelling, the same as typhoid, rash often appears earlier, can be spread throughout the body and is slightly larger than the typhoid rash and darker (paratyphoid A), but sometimes papular (paratyphoid B), recurrence and re-ignition in paratyphoid B, more common, especially with paratyphoid A, intestinal bleeding, intestinal perforation are less common, the mortality rate is lower.

2. Paratyphoid C Clinical symptoms are complex, and the following three types are common.

(1) Typhoid type: Symptoms and paratyphoid A, B is similar, acute onset, rapid rise in body temperature, irregular heat type, more with chills, headache, body aches, etc., children with convulsions and irritability, In severe cases, there may be paralysis or coma. In the course of the disease, there is often liver, splenomegaly, jaundice and abnormal liver function. The heat course is about 1 to 2 weeks. After the heat is gradually receding, the condition tends to improve.

(2) acute gastroenteritis type: caused by eating food contaminated by this bacteria; mainly gastrointestinal symptoms, short course of disease, about 2 to 5 days to recover.

(3) sepsis type: common in frail children and patients with chronic depletion diseases, mainly manifested as sepsis symptoms, acute onset, chills, high fever, irregular, relaxation or intermittent heat type, heat range 1 ~ 3 weeks, if there are suppurative complications, longer course, often rash, liver, splenomegaly, and jaundice, more than half of the patients may have the following prolonged suppurative complications during the course of the disease: 1 often In the costal cartilage, ribs, clavicle and knee, ankle, foot, finger, lumbar vertebrae, humerus and other joints, and then a localized abscess, abscess only mild redness, pierced into the sinus in a few weeks, or spread nearby Osteoporosis causes osteomyelitis, and it also lasts for several months without breaking, so the appearance looks like tuberculous infection, but the culture of pus can be found in C. parahaemolyticus, 2 pulmonary infection and lung purulent lesions, most patients with bronchitis , pneumonia, pleural effusion, empyema, etc., sometimes sputum culture can detect this bacteria, 3 purulent meningitis, endocarditis, pericarditis, pyelonephritis, etc. also occasionally occur, such complications need to be longer Time treatment.

3. The recurrence of paratyphoid fever and reburning are quite common, especially with paratyphoid fever.

Paratyphoid examination

(1) routine inspection

Most of the white blood cells are 3×109/L4×109/L, with neutropenia and disappearance of eosinophils. The latter gradually rises with the improvement of the disease, and the extreme eosinophils are >2%, absolute counting. More than 4 × 108 / L can be basically excluded from typhoid fever, mild proteinuria in high fever, fecal occult blood test positive.

(two) bacteriological examination

1 blood culture is the evidence of diagnosis, the disease can be positive in the early stage, the positive rate of the 7th to 10th day can reach 90%, the third week is reduced to 30% to 40%, and the fourth week is often negative;

2 The positive rate of bone marrow culture is higher than that of blood culture, especially suitable for those who have been treated with antibiotics and those with negative blood culture;

3 fecal culture, from the incubation period can be positive, up to 80% in the third to fourth week, the positive rate of 6 weeks after the disease decreased rapidly, 3% of patients can be more than one year;

4 urine culture: the positive rate in the late stage of the disease can reach 25%, but the fecal contamination should be avoided;

5 Rose rash scraping or biopsy sections can also be positively cultured.

(3) Immunological examination

1. Feidashi test typhoid serum agglutination test, that is, the fat-reaction positive person has the auxiliary diagnostic value for typhoid fever and paratyphoid fever. The antigen used in the examination includes typhoid bacillus (O) antigen, flagellar (H) antigen, paratyphoid A There are 5 kinds of antigens of B, C and C flagella. The purpose is to determine the agglutination titer of various antibodies in the serum of patients by agglutination method. The positive reaction rate is not much in the first week of the disease course. Generally, the positive rate increases gradually from the 2nd week to the 4th. Weeks can reach 90%. After the recovery, the positive reaction can last for several months. In a few patients, the antibody is very late, and even the whole course of antibody titer is very low (14.4%) or negative (7.8% to 10%), so it cannot According to this, the disease is excluded.

The Widal test has been used for nearly 100 years. In the 1960s, some people objected to its specificity. The results showed that there was confusion and confusion. The Widal"s test of non-typhoid fever disease also showed positive results, such as various acute infections and tumors. , connective tissue disease, chronic ulcerative colitis, can have positive results, Perlnan et al believe that sterile colon cells and Enterobacter may have a common antigen, colonic mucosal damage produced by anti-colon antibodies and Salmonella cells The antigen should cross-react, so the judgment of the results of the fatda reaction should be cautious. It is necessary to closely combine the clinical data. It should also emphasize the comparison of serum antibody titers during the recovery period. It is suggested that the positive rate of the epidemic strain antigen compared with the international strain can be used. To improve, it is recommended to replace the international standard strain with local epidemic strains to increase the positive rate of typhoid diagnosis in endemic areas.

2. Other immunological examinations

(1) Passive hemagglutination test (PHA): sensitized red blood cells with typhoid bacillus antigen to react with the tested serum, and judge whether there is typhoid-specific antibody according to the red blood cell agglutination status. The positive rate at home and abroad is 90%~ 98.35%, the false positive rate is about 5%. Bao Xinghao et al reported that the detection rate of LSP-PHA for typhoid blood culture patients was 89.66%, early patients were 90.02%, and clinically diagnosed were 82.5%. The main detection was specific IgM antibody. Therefore, it can be used for early diagnosis.

(2) Convective immunoelectrophoresis (CIE): This method can be used for the detection of soluble typhoid antigen or antibody in serum. It is easy to operate, easy to promote at the grassroots level, and has high specificity. However, the sensitivity is low. The authors report that it is 24%-92. % is mainly affected by the time of collecting serum, and is most easily detected at the early stage of the disease, so it can be used for early diagnosis of typhoid fever.

(3) Cooperative agglutination test (COA): using Staphylococcus aureus strain A protein (SPA) to bind to the Fc segment of antibody IgG, first sensitizing the S. aureus with SPA with typhoid antibody, and then with antigen The reaction rate, the positive rate of this test is 81% ~ 92.5%, the specificity is 94% ~ 98%, in general, its sensitivity is higher than CIE, and the specificity is worse than CIE.

(4) Immunofluorescence assay (IFT): Indirect immunofluorescent antibody assay was performed by Doshi et al. using Salmonella typhimurium Vi suspension as antigen. 140 positive blood culture-positive typhoid fever patients (95.7%) were positive; 394 control subjects only Four cases (1%) were false positives. At present, there are few reports on this method. Whether typhoid vaccine vaccination and other Salmonella infections will affect the specificity of this test, further research is needed.

(5) Enzyme-linked immunosorbent assay (ELISA): The basic principle of ELISA is to use the amplification of enzymatic reaction to show the primary immunological reaction, which can detect both antigen and antibody, and detect Vi antigen in typhoid patients by ELISA. The sensitivity is up to 1ng/ml, which is higher than the CoA method of 9100ng/ml, and the Vi antigen in urine can be detected after 1:1024 dilution. Domestic, external ELISA has detected Vi antigen, V9 antigen, LPS, H in clinical specimens. The sensitivity of antigens is 62.5%-93.1%, which varies with the detection of antigens, and most of them are more than 80%. Hangzhou Baoxinghao and other ELISAs simultaneously detect IgM and IgG antibodies, and the sensitivity of LPS-IgM-ELISA is 91.38%. The specificity is 99.02%, and the LPS-IgG-ELISA is 93.1% and 98.02%, respectively. In the serum immunological diagnosis method of typhoid fever, the ELISA method is simple, rapid, sensitive and specific, and is a well-recognized diagnostic method. .

(4) Molecular biological diagnostic methods

1. DNA probe DNA probe is a diagnostic reagent prepared by DNA for detecting or identifying a specific bacteria by using a labeled specific DNA fragment (probe) and a denatured bacteria in the specimen. DNA hybridization is achieved by measuring whether a hybridization reaction occurs. Since the probe is prepared by a specific gene fragment specific to bacteria, the specificity is high, and the typhoid bacillus obtained by the culture is detected by a DNA probe, and is sensitive. Up to 1000 bacteria can be detected in sexually demanded specimens. DNAProbe has high specificity and low sensitivity, and is generally used for identification and isolation of strains.

2. Polymerase chain reaction (PCR) PCR method is a molecular biology method developed in the middle and late 1980s. It can amplify target genes or DNA fragments to millions of times in vitro within a few hours. Compared with DNA probes, it is 100-10000 times higher than that of DNA probes. The foreign JAEHS uses PCR to amplify the flagellar antigen coding gene of typhoid fever. The sensitivity can detect 10 typhoid bacteria with a specificity of 100%. The PCR method is highly sensitive and easy to appear. Product contamination, so controlling false positives and false negatives in PCR methods is the key to improving accuracy.

Paratyphoid diagnosis

Diagnostic criteria

Sometimes it is not easy to identify with typhoid, it must rely on bacterial culture and typhoid agglutination test to confirm the diagnosis.

1. The positive rate of blood and bone marrow culture is higher during bacterial culture, and the fecal culture is prone to be positive in patients with gastroenteritis. In patients with localized suppuration, pathogens can be detected from the extracted pus.

2. Typhoid agglutination test Paratyphoid A, B agglutination titer is higher, but the titer of paratyphoid C is lower, a small number of patients in the course of typhoid agglutination test is always negative.

Differential diagnosis

In the early stage of typhoid fever (within the first week), the characteristic performance has not been revealed and should be differentiated from the following diseases:

1. Viral infections Upper respiratory tract infections may also have persistent fever, headache, and decreased white blood cell counts, similar to early typhoid fever, but such patients are more acute onset, often accompanied by upper respiratory symptoms, often without slow pulse, splenomegaly or rose The pathogens and serological tests of rash and typhoid are negative, and they often heal within 1 week.

2. Malaria Malaria, especially falciparum malaria is easily confused with typhoid fever, but malaria fluctuates greatly every day, with chills or chills before fever, sweating when hot retreat, spleen is slightly harder, anemia is more obvious, peripheral blood Plasmodium can be found in bone marrow smears, and rapid antipyretic treatment with effective antimalarial drugs is effective.

3. Leptospira disease The influenza typhoid type is very common during the summer and autumn epidemics, with acute onset, with chills and fever, and fever is persistent or relaxation type, similar to typhoid fever, patients have history of exposure to water, eye Conjunctival congestion, body aches, especially pain and tenderness of the gastrocnemius, inguinal lymphadenopathy, etc.; peripheral blood leukocyte count increased, erythrocyte sedimentation rate accelerated, relevant pathogens, serological examination can be confirmed.

4. Acute viral hepatitis Acute jaundice hepatitis has jaundice in the early stage, fever, general malaise, digestive tract symptoms, leukopenia or normal, not easy to distinguish from typhoid, but this patient has jaundice on the 5th to 7th day of the disease, body temperature It also returned to normal, liver tenderness, abnormal liver function, can be confirmed by viral hepatitis serological markers, in addition, typhoid fever and toxic hepatitis is also easily confused with viral hepatitis, but the former liver function damage relative Lighter, there are jaundice in the presence of jaundice still fever, and other characteristic manifestations of typhoid, blood culture typhoid can be positive, as the condition improves, liver and liver function return to normal, typhoid fever After the extreme period (week 2), it must be differentiated from the following diseases.

5. Septicemia Part of Gram-negative bacilli must be differentiated from typhoid fever. This disease can have biliary, urinary tract, intestinal and other primary infections. Fever is often accompanied by chills, sweating, bleeding tendency, many patients early Shock can occur and last for a long time, although white blood cells can be normal or slightly lower, but often with nuclear left shift, the diagnosis must rely on bacterial culture.

6. Miliary tuberculosis fever is more irregular, often accompanied by night sweats, rapid pulse, shortness of breath, cyanosis, etc., history of tuberculosis or close contact with tuberculosis patients, X-ray film shows miliary shadows in the lungs.

7. Brucellosis has contact with sick animals or drinking unsterilized cows, goat milk or dairy products, long-term irregular fever, wave-hot type on the attack, joints, muscle pain and sweating, serum blue The bacteria agglutination test is positive, and blood and bone marrow culture can be isolated to Brucella.

8. Endemic typhus onset is more urgent, high fever often accompanied by chills, fast pulse, conjunctival congestion and rash, rash appeared earlier (3rd to 5th day), the number is more, the distribution is wider, the color is dark red, pressure There is no retreat, there is pigmentation after rash, the course of disease is about 2 weeks, the number of white blood cells is mostly normal, and the agglutination reaction of proteus is abnormal. The blood is inoculated into the abdominal cavity of guinea pig to isolate the rickettsia.

9. Tuberculous meningitis Some patients with typhoid fever can have severe headache, sputum, lethargy, neck resistance and other manifestations of vaginal meningitis, which is easily confused with tuberculous meningitis, but patients with tuberculous meningitis There are other organ tuberculosis, although there is persistent fever but no rose rash and splenomegaly, headache and neck resistance are more significant, may be accompanied by nystagmus, cranial nerve spasm, etc., the course of treatment without TB is gradually worsened, cerebrospinal fluid examination is consistent Tuberculous meningitis changes; cerebrospinal fluid smear, culture, animal inoculation can find Mycobacterium tuberculosis.

10. Malignant histiocytosis The pathological features of this disease are abnormal proliferation and infiltration of tissue cells in the mononuclear-macrophage system. The clinical manifestations are complex and variable, sometimes mainly characterized by fever, liver, splenomegaly and leukopenia. In the typhoid bone marrow tablets, there may be tissue cell enlargement and phagocytosis, so it is easy to be confused, but the disease progresses rapidly, there is obvious anemia, bleeding symptoms; blood tablets and (or) bone marrow slices have specific malignant tissue cells And (or) multinuclear giant tissue cells, proliferating tissue cells of different shapes, and can phagocytose red, white blood cells and platelets; peripheral blood seems to have significant whole blood cell reduction, antibacterial therapy is ineffective.

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