Typhoid fever

Introduction to enteric typhoid Enteric typhoid, also known as typhoid fever, is an acute systemic infection caused by typhoid bacillus, which is mainly transmitted by water and food. Patients and carriers are sterilized from the urination. The recovery period of patients can last for about 2 to 6 weeks, and a small number of patients can be sterilized for more than one year, which is a great threat to healthy people. If the water source or food is contaminated, people who drink the same source of water or food with the same source may have an outbreak, regardless of age. If the mother has typhoid fever, it can also be transmitted to the newborn through contact. There are fewer diseases under 2 years old, and more cases occur in summer and autumn. basic knowledge Sickness ratio: 0.0012% Susceptible people: no special people Mode of infection: digestive tract spread, contact spread Complications: bronchitis pneumonia

Cause of intestinal typhoid fever

The typhoid bacillus enters the digestive tract from the mouth and is usually killed by gastric acid. However, if the amount of invading bacteria is large, or the gastric acid is secreted, the defense function of the intestinal flora is destroyed, and the typhoid bacillus can enter the small intestine and invade the intestinal mucosa. .

Salmonella typhimurium proliferates in the small intestine and passes through the intestinal mucosal epithelial cells to reach the lamina propria of the intestinal wall. Some pathogens are engulfed by macrophages and multiply in their cytoplasm, and some enter the ileum to collect lymph nodes, isolated lymphoid follicles and mesentery. The lymph nodes grow and multiply, and then enter the bloodstream through the thoracic duct, causing transient bacteremia, that is, the primary bacteremia period. After 1 to 3 days after ingesting the pathogen, the pathogen that enters the bloodstream is quickly taken by the liver and spleen. The mononuclear-macrophage system in the bone marrow and lymph nodes phagocytose, the primary bacteremia period is short, the patient is still asymptomatic, and is in clinical incubation period.

After being phagocytosed by mononuclear-macrophages, typhoid bacilli still multiply in the cells and then enter the blood circulation again, causing a second severe bacteremia, which lasts for several days to several weeks. Patients have successive clinical manifestations, typhoid fever The bacilli spread to the whole body, invade the liver, gallbladder, spleen, kidney, bone marrow and other organ tissues, release endotoxin, clinical fever, general malaise, obvious toxic symptoms, hepatosplenomegaly, skin rose rash, etc. When the disease is equivalent to the first to second weeks of the disease, blood and bone marrow culture can often obtain positive results. The typhoid bacillus is multiplied in the biliary tract, discharged to the intestine with the bile, and partially excreted with the feces, spreading the pathogen to the outside, and partially passing the intestinal mucosa. Invade the intestinal lymphatic tissue again, causing severe inflammatory reaction in the lymphatic tissue of the intestinal wall that has been sensitized, mononuclear cell infiltration, lymphoid tissue swelling, necrosis, and shedding to form ulcers. If the lesion involves blood vessels, it may cause intestinal bleeding. Invasion of the muscular layer and the serosal layer can cause intestinal perforation, which are clinically serious complications. This pathological process generally corresponds to the second to third weeks of the disease course.

Whether it is infected after infection with typhoid bacillus, it is closely related to the amount of bacteria infected, the virulence of the strain, the immune status of the organism, etc. The larger the amount of live infection, the greater the chance of onset; the strain with Vi antigen is more virulent. The same amount of infection, the incidence rate is higher, the body's immune defense function is low, it is more susceptible to infection.

Enteric cold prevention

The focus is on strengthening diet, drinking water hygiene and manure management, and cutting off the route of transmission. Patients and carriers are isolated according to intestinal infectious diseases until one week after drug withdrawal, once a week for fecal culture, two consecutive negatives, long-lasting dead vaccine The protective effect is not satisfactory, and the oral attenuated vaccine is in trial use.

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: early isolation, treatment of patients, isolation period should be until the clinical symptoms disappear, 15 days after the body temperature returns to normal, can also be used for fecal culture examination, 1 / 5 ~ 7 days, 2 consecutive negative Can be quarantined, the patient's urine, toilet, utensils, clothing, daily necessities must be properly disinfected, the management of chronic carriers should be strictly enforced, the diet, conservation, water supply and other industry practitioners should be regularly checked, early detection Carriers, chronic carriers should be transferred from the above jobs, treatment, regular supervision and management, close contacts should be medical observation for 23 days, suspected typhoid fever with fever, should be treated early.

2, cut off the route of transmission: in order to prevent the key measures of this disease, do a good job in health education, do a good job of manure, water and food hygiene management, eliminate flies, develop good hygiene habits, wash hands before and after meals, do not eat or not Clean food, no drinking raw water, raw milk, etc., improve water supply sanitation, and strictly implement water sanitation supervision. It is the most important link to control the epidemic of typhoid fever. The epidemic of typhoid fever is the most important position in many areas. The incidence can be significantly reduced.

3, protection of susceptible: typhoid vaccination can play a certain protective role for susceptible population, typhoid fever, paratyphoid A, B triple vaccine prevention effect is not ideal, the response is also large, not as a routine immune prevention application, in There are different opinions on the emergency immunization problem in outbreak 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 a certain protective effect.

Enteric complication Complications bronchitis pneumonia

The complications of typhoid fever are complex and diverse, and the incidence is different. The same patient may have multiple complications at the same time or in succession.

1, intestinal bleeding : a common serious complication, the incidence of about 2.4% to 15%, more common in the second to third week of the disease, from fecal occult blood to a large number of bloody stools, a small amount of bleeding can be asymptomatic or only mild dizziness, pulse Fast; a large number of bleeding when the heat plummeted, pulse speed, body temperature and pulse curve crossover phenomenon, and dizziness, pale, irritability, cold sweat, blood pressure and other shock performance, there are more chances of diarrhea complicated with intestinal bleeding, during the course of the disease Excessive activities, improper diet, too rough, excessive diet, excessive exertion during defecation, and inappropriate therapeutic enema can all be causes of intestinal bleeding.

2, intestinal perforation : the most serious complication, the incidence of about 1.4% to 4%, more common in the second to third week of the disease, intestinal perforation often occurs in the end of the ileum, but also in the colon or other intestinal segments; perforation The number is mostly one, a few are 1 or 2, and there are reports of up to 13 people. The performance of intestinal perforation is sudden severe pain in the right lower quadrant, accompanied by nausea, vomiting, cold sweat, fine pulse, respiratory promotion, body temperature and blood pressure drop. (shock period), after 1~2h, abdominal pain and other symptoms are temporarily relieved (quiet period), and soon the body temperature rises rapidly and signs of peritonitis appear, manifested as abdominal distension, persistent abdominal pain, abdominal wall tension, extensive tenderness and rebound pain, intestine The sound is weakened to disappear, there is free fluid in the abdominal cavity, X-ray examination has free gas under the armpit, the number of white blood cells is higher than the original one with the left shift of the nucleus (peritonitis), the cause of intestinal perforation is roughly the same as intestinal bleeding, and some cases are complicated with intestinal tract. Intestinal perforation occurs simultaneously with bleeding.

3, bronchitis and pneumonia : bronchitis is more common in the early stage of the disease; pneumonia (bronchial pneumonia or lobar pneumonia) often occurs in the extreme stage and late stage of the disease, mostly secondary infection, rarely caused by typhoid bacillus, toxemia In severe cases, there may be shortness of breath, pulse rate and cyanosis, but coughing is not obvious. Physical examination may reveal pulmonary voice and/or lung consolidation.

Intestinal typhoid symptoms common symptoms intestinal bleeding intestinal perforation plaque rash response dull abdominal discomfort toxemia stagnant irregular heat

The typhoid bacillus enters the digestive tract from the mouth, invades the lymphoid tissue of the small intestine mucosa, multiplies in the lymph nodes, and then enters the bloodstream to cause fever, drowsiness, headache, general malaise and nausea, vomiting, diarrhea and other symptoms. If you do blood culture, you can see the growth of Salmonella typhi. Bacteria are carried to various organs with blood flow, but the main lesions are in the intestines. In the first week of onset, the lymph nodes in the small intestine wall are swollen. On the second and third weeks, on the basis of swelling, local necrosis and crusting, and the scars form a ulcer, and the ulcer reaches a certain depth and size, which can cause bleeding and perforation. .

Enteric typhoid examination

First, routine inspection

Including blood, urine and feces, blood: the total number of white blood cells is often reduced, about (3 ~ 5) × 10 ^ 9 / L, the classification count see neutropen reduction with nuclear left shift, lymph, monocytes relatively increased, Eosinophils decrease or disappear, such as differential count eosinophils more than 2% or absolute counts higher than 0.04 × 10 ^ 9 / L, and no parasitic diseases (schistosomiasis, hookworm, etc.), typhoid The diagnosis should be very careful. After entering the recovery period, the total number of white blood cells gradually returns to normal, and eosinophils appear again. When the disease recurs, eosinophils decrease or disappear again, which has certain hints on the disease process, red blood cells and hemoglobin. Generally no major changes, severe patients with longer course, or complicated with intestinal bleeding, anemia can occur, such as acute intravascular hemolysis, hemolytic uremic syndrome or DIC, etc., should be the corresponding special examination.

Urine: Patients with high fever may have mild proteinuria and occasionally a few casts.

Manure: In the case of intestinal bleeding, there may be fecal occult blood or bloody stools.

Second, bacteriological examination

1. Blood culture is the evidence for diagnosis. It can be positive in the early stage of the disease. The positive rate of the 7th to 10th day is up to 90%, and the third week is 30% to 40%. 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 weeks, 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. Scrapping or biopsy sections of rose rash can also be positively cultured.

Third, immunological examination

1. Feidashi test typhoid serum agglutination test, ie, fat-positive reaction, has diagnostic value for typhoid fever and paratyphoid fever. The antigen used in the examination includes typhoid bacillus (O) antigen, flagellar (H) antigen, paratyphoid 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 Widals test of non-typhoid fever disease also showed positive results, such as various acute infections, tumors, and connective tissue. Hepatic diseases and chronic ulcerative colitis can all have positive results. Perlnan et al believe that sterile colon cells and Enterobacteriaceae may have common antigens, and anti-colon antibodies and Salmonella bacterial antigens produced by colonic mucosal damage Cross-reaction, therefore the judgment of the results of the fatda reaction should be prudent, must be closely combined with clinical data, should also emphasize the comparison of serum antibody titers during the recovery period, it has been suggested that the positive rate can be improved compared with the international strains using the epidemic strain antigen. 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, which is easy to operate, convenient for grassroots promotion and high specificity. However, the sensitivity is low, and the authors report that it is 24% to 92%, which is mainly affected by the time of collecting serum. It 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 test (IFT): Indirect immunofluorescent antibody detection was carried out by Doshi et al. using Salmonella typhimurium Vi suspension as antigen, and 134 (95.7%) of 140 cases of blood culture-positive typhoid fever were positive. Only 394 (1%) of the 394 controls were false positives. There are still 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. .

Fourth, molecular biology diagnostic methods

1. DNA Probe DNA probe is a diagnostic reagent prepared by DNA for detecting or identifying a specific bacterium by using a labeled specific DNA fragment (probe) and denatured in the specimen. The hybridization of bacterial DNA is carried out 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. Sensitivity requires up to 1000 bacteria in the specimen to be detected. DNA Probe has high specificity and low sensitivity, and is generally used for strain identification and isolation.

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 JAE HS uses PCR to amplify the flagellar antigen-encoding 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 use. Product contamination occurs, so controlling the false positives and false negatives of the PCR method is the key to improving accuracy.

Diagnosis and identification of intestinal typhoid

diagnosis

Diagnosis can be performed based on clinical manifestations and examinations.

Differential diagnosis

1, viral infection: upper respiratory tract virus infection can also have persistent fever, headache, white blood cell count, similar to early typhoid, but these patients are more acute onset, more with upper respiratory symptoms, often no slow pulse, no splenomegaly Large or rose rash, blood and other bacterial cultures and serum fat darner reaction are negative, the general course of disease is short, can also self-heal without antibiotics.

2, malaria: all types of malaria, especially falciparum malaria is easy to be confused with typhoid fever, but malaria fluctuates daily with large body temperature, with chills or chills before fever, sweating when hot retreat, spleen is slightly harder, anemia is more obvious, peripheral Blood and bone marrow smears can be found in Plasmodium, and rapid antipyretic treatment with effective antimalarial drugs is not effective.

3, leptospirosis: the influenza typhoid type of this disease is very common during the summer and autumn epidemic, acute onset, accompanied by chills and fever, fever is persistent or relaxation type, similar to typhoid, patients have a history of contact with infected water, Conjunctival congestion, body aches, especially pain and tenderness of the gastrocnemius, inguinal lymphadenopathy, peripheral blood leukocyte count increased, erythrocyte sedimentation rate, urine output decreased, serum immunology test was positive.

4, acute viral hepatitis: acute jaundice hepatitis in the early stage of jaundice fever, general malaise, digestive tract symptoms, leukopenia or normal, not easy to distinguish from typhoid, but this patient has jaundice every 5 to 7 days of the disease, The body temperature also returned to normal, the liver was tender and the liver function was abnormal. It can be diagnosed by serological markers of viral hepatitis. In addition, typhoid fever complicated with toxic hepatitis is also confused with viral hepatitis, but the liver function damage of the former. Relatively light, those with jaundice still have fever after the appearance of jaundice, and have other characteristic manifestations of typhoid fever.

5, sepsis: some Gram-negative bacilli must be differentiated from typhoid fever, this disease may have biliary, urinary tract, intestinal and other primary infections, fever often accompanied by chills, sweating, bleeding tendency, many patients In the early stage, shock can occur and the duration is longer. Although the white blood cells can be normal or slightly lower, but often with the left side of the nucleus, the diagnosis must rely on bacterial culture.

6, miliary tuberculosis: fever is more irregular, often accompanied by night sweats, pulse faster, 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: There is a history of contact with sick animals or drinking unsterilized cattle, goat milk or dairy products, long-term irregular fever, wave-hot type on the attack, joints, muscle pain and sweating, serum cloth Brucella agglutination test is positive, blood and bone marrow culture can be isolated to Brucella.

8, endemic typhus: onset 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, 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, and the blood is inoculated into the abdominal cavity of guinea pig to isolate the rickettsia.

9, tuberculous meningitis: some patients with typhoid can have severe headache, sputum, lethargy, neck resistance and other manifestations of vaginal meningitis, easily confused with tuberculous meningitis, but many patients with tuberculous meningitis With 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., without the anti-tuberculosis effect treatment gradually worsened, cerebrospinal fluid examination In line with tuberculous meningitis changes, cerebrospinal fluid smear, culture, animal inoculation can be found in tuberculosis.

10. Malignant histiocytosis: The pathological feature of this disease is that the tissue cells in the mononuclear-macrophage system are abnormally proliferated and infiltrated, and the clinical manifestations are complex and variable, sometimes mainly characterized by fever, liver, splenomegaly and leukopenia. In addition, there may be tissue cell enlargement and phagocytosis in the typhoid bone marrow tablets, 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) multinucleated giant tissue cells, hyperplastic tissue cells of different shapes, and can phagocytose red, white blood cells and platelets, peripheral blood picture showed significant whole blood cell reduction, antibacterial drug treatment is invalid.

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