Typhoid fever

Introduction to Typhoid Typhoidfever is an acute intestinal infectious disease caused by typhoid bacillus, with persistent bacteremia and toxemia, a proliferative response of the mononuclear phagocytic system, and hyperplasia, swelling, and necrosis of the lower ileum lymphoid tissue. Formed with ulcers as the basic pathological features, typical clinical manifestations include persistent high fever, systemic toxic symptoms and gastrointestinal symptoms, relatively slow pulse, rose rash, hepatosplenomegaly, leukopenia, this disease is also known as enteric fever (entericfever ). However, the clinical manifestations of this disease are mainly caused by the spread of pathogens through the blood to the whole body of the body, but not caused by local intestinal lesions. Intestinal hemorrhage and intestinal perforation are the most serious serious complications. basic knowledge Sickness ratio: 0.0012% Susceptible people: no special people Mode of infection: digestive tract spread Complications: Myocarditis, hepatitis, bronchitis, pneumonia, uremia, hemolytic anemia

Typhoid fever

Salmonella typhimurium infection (35%):

Salmonella typhi (Salmonella typhi) is the pathogen of this disease. It was isolated from the spleen of Gaffkey in Germany in 1884. It belongs to the D group of Salmonella. It is short rod-shaped, Gram-negative bacilli, and has flagellum. , no capsule, no spore formation, 2 ~ 3m long, 0.4 ~ 0.6m wide, typhoid bacillus can grow in ordinary medium, forming medium size, colorless and translucent, smooth surface, neatly arranged colonies; Glucose, does not decompose lactose, sucrose and rhamnose, produces acid and does not produce gas. In bile-containing medium, typhoid bacillus is more likely to grow. Salmonella typhimurium has strong vitality in the natural environment. It can survive for 2 to 3 weeks in the feces. It can reach low temperature for 1~2 months. It can be kept for several months in a frozen environment. It is weak against sunlight, dryness, heat and disinfectant. It is killed when exposed to direct sunlight for several hours. Heating up to 60 °C for 30 minutes. Or boil immediately died; 3% phenol, 5min was also killed; disinfection residual chlorine in 0.2 ~ 0.4mg / L water can be quickly killed, in food (such as milk) can survive, and even can breed, typhoid bacillus only infected Humanity Under natural conditions, animals are not infected. Salmonella typhimurium does not produce exotoxin. When the cells are lysed, endotoxin is released, which plays an important role in the pathogenesis of this disease. Salmonella typhi has bacterial ("O") antigen and flagella ( "H") antigen, and surface ("Vi") antigen, etc., after infecting humans, can induce the corresponding antibodies, these antibodies are not protective antibodies, "O" and "H" are more antigenic, The typhoid serum agglutination test (fat reaction) can be used to detect the "O" and "H" antibodies in serum samples, which is helpful for the clinical diagnosis of this disease. The newly isolated typhoid bacillus from typhoid fever has Vi antigen. Vi antigen can interfere with the bactericidal efficacy in serum and prevent phagocytosis, and enhance the invasiveness of bacteria. It is an important factor determining the virulence of Salmonella typhimurium. Due to the weak antigenicity of Vi antigen, it induces a low agglutination titer of Vi antibody. The time is also short, and the clinical diagnosis of the patient is of little value. After the pathogen is removed from the human body, the Vi antibody also disappears; thus, it helps the detection of the bacillus bacillus, and the Salmonella typhimurium containing the Vi antigen can be specific. Phage cleavage, which can be divided into more than 100 phage types, phage typing helps epidemiological investigation and tracking of infectious sources.

The amount of bacteria infected (25%):

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.

Virulence of the strain (20%):

The endotoxin released by Salmonella typhimurium plays an important role in the pathological process of typhoid fever. However, studies have shown that the clinical symptoms of persistent fever and toxic symptoms in typhoid fever are not directly caused by endotoxemia. The actual cause is much simpler than that of simple Endotoxemia is much more complicated. Endotoxin enhances the inflammatory response of local lesions, activates monocyte-macrophages and neutrophils, and produces and releases various cytokines, plus toxic substances produced by necrotic tissue. It may be closely related to the clinical manifestations of typhoid fever. In addition, typhoid bacillus endotoxin can also induce DIC or hemolytic uremic syndrome, which is a clinical syndrome caused by microvascular coagulation confined to the kidney.

The immune status of the body (15%):

After the fourth week of the disease, the body's various immunitys gradually strengthened, especially the cellular immunity. The typhoid bacilli gradually disappeared from the blood and organs, the ulcer lesions in the intestinal wall gradually healed, the clinical manifestations gradually recovered, and the disease finally recovered. A few patients Probably because of insufficient immunity, the pathogens that have not been eliminated in the latent lesions can reproduce and invade the blood circulation to cause recurrence. The main pathological features of typhoid fever are systemic mononuclear-macrophage system (including liver, spleen, bone marrow, lymphoid tissue, etc.). ), the proliferative response of mononuclear-macrophages forms a "typhoid nodule", and the lesion is most prominent in the intestine, especially in the end of the ileum. The pathological process includes four stages: hyperplasia, necrosis, ulcer formation, and ulcer healing. During the first to second weeks of the disease, the lymphatic tissue of the intestine was swollen and bulged, showing a button-like protrusion. The collecting lymph nodes and isolated lymphoid follicles were most prominent at the end of the ileum. The mesenteric lymph nodes were also significantly proliferated and swollen. Lymph nodes and spleen in other parts. Bone marrow, hepatic sinusoidal cells also have different degrees of hyperplasia, intestinal lymphoid tissue lesions intensify, local camp Obstruction and necrosis, the formation of yellow scars, the third week of the disease, the formation of ulcers, the ulcer is oval or round, along the long axis of the intestine, necrosis if the blood vessels can cause bleeding, invasion of the muscle layer and The serosal layer can cause intestinal perforation, because the lesions at the end of the ileum are the most serious, and the perforation is more common in this part. The disease is cured from the 4th to 5th week, the ulcer is healed, no scar is left, and the intestinal stenosis is not caused. Under the light microscope The prominent feature of the above lesions is the infiltration of inflammatory cells mainly composed of macrophages, which are abundantly found at the bottom and periphery of the ulcer. The phagocytic ability of macrophages is strong, and the cytoplasm contains phagocytic lymphocytes, erythrocytes, typhoid bacillus and necrosis. Tissue debris, it is also known as "typhoid cells", is a characteristic feature of this disease, such cells aggregated into a group, constitutes the so-called typhoid granuloma or typhoid nodules, intestinal lesions are not necessarily serious with clinical symptoms The degree is positively correlated, especially in infants with severe toxemia. Intestinal lesions may not be obvious. Conversely, patients with mild or absent symptoms may have intestinal bleeding or intestinal perforation.

In the organs outside the intestine, the lesions of the spleen and liver are most prominent, the splenomegaly, the spleen and sinus expand and congestion, the medulla is obviously proliferated, the macrophage infiltrates, and the typhoid nodules are visible, the liver is obviously swollen, and the liver cells are turbid. Degeneration, focal necrosis, sinusoidal dilatation, typhoid nodules, mild inflammation of the gallbladder, severe toxemia, myocardial and kidney turbidity, rose rash is superficial capillary congestion, dilatation, mononuclear cell infiltration Can be found in typhoid bacillus, respiratory system is more common with bronchitis, there may be secondary bronchial pneumonia or lobar pneumonia, occasionally there may be kidney, meninges, bone marrow, pericardium, lung, middle ear and other migratory suppurative lesions.

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.

Typhoid 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 to 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 in manure, water source 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 persons: 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, 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.

Typhoid fever Complications Myocarditis, hepatitis, bronchitis, pneumonia, uremia, hemolytic anemia

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 hemorrhage : a common serious complication, the incidence rate is 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 rate is 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. Toxic myocarditis : the incidence rate is 3.5% to 5%, which is common in the second to third week of the disease with severe toxemia. The clinical features are increased heart rate, first heart sounds weakened, arrhythmia, pre-contraction, Diastolic galloping, low blood pressure, ECG showed prolonged PR interval, T wave changes, ST segment shift, etc. These symptoms, signs and ECG changes generally returned to normal as the condition improved.

4. Toxic hepatitis: the incidence rate is about 10% to 68.5% (mostly 40% to 50%), usually in the first to third weeks of the disease, mainly characterized by large liver, may be accompanied by tenderness, mildly elevated transaminase activity Even mild jaundice, clinically easy to be confused with viral hepatitis, as the condition improves, liver and liver function can return to normal soon, only occasionally liver failure can be life-threatening.

5. 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.

6. Acute cholecystitis : about 0.6% to 3%, characterized by fever, upper right abdominal pain and tenderness, often vomiting, jaundice, white blood cell count is higher than the original, typhoid fever and cholecystitis help gallstone formation, It is easy to cause bacterial status. It is also considered that patients with chronic cholecystitis and cholelithiasis are prone to typhoid fever.

7. Hemolytic uremic syndrome: The number of cases reported abroad is as high as 12.5% to 13.9%. There are also intrinsic reports in China. It is generally seen in the first to third weeks of the disease, and about half of them occur in the first week, mainly due to hemolysis. Anemia and renal failure, with increased fibrin degradation products, thrombocytopenia and red blood cell fragmentation, which may be caused by glomerular microvascular coagulation induced by typhoid bacillus endotoxin.

8. Hemolytic anemia : typhoid fever can be complicated by acute intravascular hemolysis, manifested as acute anemia, reticulocyte increase, white blood cell count increased with nuclear left shift, some cases have hemoglobinuria, a few cases of jaundice, uremia can also occur, patients Most of them are associated with erythrocyte glucose-6-phosphate dehydrogenase (G6PD) deficiency, and a few are associated with hemoglobin disease. The occurrence of hemolysis is often associated with typhoid infection itself and/or chloramphenicol application.

9.DIC : Foreign reports that some patients with typhoid fever may have thrombocytopenia, prothrombin reduction and hypofibrinogenemia during the course of the disease. According to DIC's laboratory, these coagulopathy can often return to normal as the condition improves. The typhoid combined with DIC can be manifested as severe systemic extensive bleeding, which can be life-threatening if not treated in time.

10. Psychiatric diseases: Most of them are seen in the febrile period. They can also occur before or after fever. Some patients present with infectious psychosis, have varying degrees of disturbance of consciousness, accompanied by illusions, hallucinations and emotions, and behavioral disorders. Some are characterized by toxic encephalopathy, in addition to mental and conscious disturbances, accompanied by tonic spasm, hemiplegia, cranial nerve palsy, pathological reflex positive and Parkinson's syndrome, individual multiple acute radiculitis can occur, after the ball Optic neuritis, typhoid and vaginal meningitis account for about 5% to 8% of typhoid cases, but typhoid meningitis is rare (0.1% to 0.2%), typhoid fever and neurological diseases generally improve with typhoid fever. Often recovered in a short period of time, it has been reported that typhoid fever can be accompanied by acute disseminated encephalomyelitis (acute disseminated encephalomyelitis), the pathogenesis may be similar to other causes of post-infection encephalitis.

Symptoms of typhoid common symptoms porcine papillary intestinal bleeding intestinal perforation response dull expression apathy fatigue abdominal discomfort irregular heat toxemia detoxification state

Typhoid fever can be diagnosed according to epidemiological data, clinical and immunological examination results, but the diagnosis of typhoid fever is based on the detection of pathogenic bacteria, the incubation period is 5 to 21 days, and the incubation period is related to the amount of infection.

1. Clinical manifestations The natural course of typical typhoid fever is about 4 weeks and can be divided into 4 phases.

(1) Initial stage: equivalent to the first week of the disease course, the onset is mostly slow, fever is the earliest symptoms, often accompanied by general malaise, fatigue, loss of appetite, headache, abdominal discomfort, etc., the condition gradually worsens, the body temperature rises step by step, It can reach 39 to 40 °C within 5 to 7 days. There may be chills before fever, less chills, and less sweating. At the end of the period, it can often reach the swollen spleen and liver.

(2) Extreme period: The second to third weeks of the disease course, often accompanied by the typical manifestations of typhoid fever, intestinal bleeding and intestinal perforation and other complications occurred in this period, the disease performance has been fully demonstrated during the period.

1 high heat: the heat of quenching is a typical heat type, a few can be relaxation type or irregular heat type, high heat often lasts about 2 weeks, the peak can reach 39 ~ 40 ° C, and there are more than 40 ° C.

2 digestive tract symptoms: lack of appetite, abdominal distension, abdominal discomfort or hidden pain, the right lower abdomen is obvious, there may be mild tenderness, more constipation, a few may have diarrhea.

3 neuropsychiatric symptoms: generally related to the severity of the disease, patients with weakness, mental paralysis, apathy, sluggish, slow response, hearing loss, severe cases may appear paralyzed, coma, can also present with virtual meningitis performance, these performance Both are associated with severe toxic symptoms, and as the body temperature drops, the condition is gradually reduced and restored.

4 circulatory system symptoms: often have relatively slow pulse (pulse acceleration is not commensurate with the rise in body temperature) or severe veins, such as complicated myocarditis, the relative slow pulse is not obvious.

5 hepatosplenomegaly: in this period can often touch the swollen spleen, soft, mild tenderness, can also be found in the liver, soft, tender, hepatosplenomegaly is usually mild, gradually return to normal with the recovery of the disease If the toxic hepatitis is invented, it can be seen that the liver function is abnormal such as jaundice and alanine aminotransferase.

6 rash: on the 7th to 12th day of the disease, some patients have a small red papule (rose rash) with a reddish skin. The diameter is about 2~4mm, the color is faded, slightly higher than the leather surface, not many, usually in 10 Left and right, appear in batches, distributed in the chest and abdomen, can also be seen in the back and limbs, most of them will disappear after 2 to 4 days, in addition, patients with more sweating can see crystal type of sweat (white peony).

(3) Remission period: During the third to fourth week of the disease, the body temperature began to fluctuate and gradually decreased. The patient still felt weak, the appetite began to recover, the abdominal distension was relieved, the swollen spleen retracted, and the tenderness subsided. Serious complications such as intestinal bleeding and intestinal perforation can still occur.

(4) Recovery period: At the 5th week of the disease, the body temperature returned to normal, the appetite improved, and the symptoms and signs returned to normal. It usually took about 1 month to fully recover.

The above-mentioned process is a natural course of typical typhoid fever (Fig. 1). Due to the immune status of the patient, the virulence, quantity, treatment measures, timely and appropriate treatment, complications, and whether or not the original chronic disease is affected, clinical manifestations Light and heavy.

2. Clinical types In addition to the typical process, the disease can have the following types.

(1) Light type: fever is about 38 °C, the symptoms of systemic toxic blood are light, the course of disease is short, and it can be recovered in 1 to 3 weeks. The symptoms are not many, and the typical typhoid fever is lacking. It is easy to cause misdiagnosis and missed diagnosis. Children's cases are not uncommon. Those who have received typhoid vaccine vaccination before the disease, or those who have been treated with effective antibiotics in the early stage of the disease.

(2) fulminant (heavy): acute onset, severe toxic symptoms, dangerous condition, rapid development, chills, high fever or hyperthermia, abdominal pain, diarrhea, shock, toxic encephalopathy, toxic myocarditis, toxic hepatitis, Toxic sputum, can also be complicated by DIC, etc., if early diagnosis, timely treatment and rescue, it is still possible to cure.

(3) Prolonged type: The initial performance of the onset is the same as that of the common type (typical). Due to the low immunity of the body, the fever persists and can last for several months. Relaxation or intermittent heat type, the hepatosplenomegaly is also significant. The typhoid fever with chronic schistosomiasis often has this type of performance. This patient's antibiotic treatment is not satisfactory, and sometimes it is necessary to cooperate with anti-schistosomiasis treatment to control the disease.

(4) Xiaoyao type: The symptoms of systemic toxic blood are light, the patient often lives as usual, works, does not notice the disease, and some patients may suddenly have intestinal bleeding or intestinal perforation and seek medical treatment.

(5) Frustration type: The onset is more urgent, which is similar to the typical typhoid performance, but the symptoms such as fever quickly subsided and healed in about 1 week.

(6) Pediatric typhoid fever: The clinical course of typhoid fever is not typical. The younger the age, the more atypical; the older the patient, the closer it is to adult disease, the typhoid fever, the onset of illness, the severity of illness, vomiting, abdominal pain, diarrhea Common gastrointestinal symptoms are common, often with irregular high fever, accompanied by convulsions, fast pulse, less common rose rash, increased peripheral blood leukocyte count, often accompanied by bronchitis or pneumonia, school-age children are mostly light or frustrated, with adults The performance is similar, the condition is mild, the course of disease is shorter, the relative slow pulse is rare, the number of white blood cells is not reduced, the intestinal lesions are also mild, and complications of intestinal bleeding and intestinal perforation are less.

(7) senile typhoid: symptoms are not typical, fever is not high, weakness is obvious, easy to complicated with bronchial pneumonia and cardiac insufficiency, persistent gastrointestinal dysfunction, memory loss, prolonged course, slow recovery, high mortality.

3. Recurrence and reburning

(1) Recurrence: The disease is prone to recurrence, the recurrence rate is generally about 10%. In early years, chloramphenicol was used as a special treatment. The recurrence rate has been reported to increase by 20%. The patient has 1 to 3 weeks after the retreat, and the clinical symptoms are again. Appear, but often lighter (occasionally more serious than the initial), the course of disease is about 1 to 3 weeks, blood culture can be re-acquired positive results, recurrence is more than 1 time, 2 times are rare, occasionally recurrence 3 to 4 times or In the above cases, the cause of recurrence is related to the low immune function of the body. The typhoid bacillus lurking in the macrophages of the body re-emerges and invades the blood circulation, causing bacteremia again. The recurrence is more common in patients with inadequate antibacterial therapy.

(2) Reburning: In the course of 2 to 3 weeks of the disease course, the process of body temperature begins to fluctuate and falls, but it has not reached normal. It lasts for 5 to 7 days, and the fever rises again. The symptoms can be slightly obvious when reburning, blood culture can be positive again, and reburning The mechanism is similar to recurrence.

Typhoid test

(1) 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.

(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 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. 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 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.

Typhoid diagnosis

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, etc.; 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, there are jaundice in the presence of jaundice still fever, and other characteristic manifestations of typhoid, blood culture typhoid can be positive, with the disease improved, liver and liver function return to normal, typhoid fever After the extreme period (week 2), it must be differentiated from the following diseases.

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 of proteobacteria is positive. The blood is inoculated into the abdominal cavity of guinea pigs 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 Comply with tuberculous meningitis changes; cerebrospinal fluid smear, culture, animal vaccination 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, 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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