Typhoid and Paratyphoid

Introduction to Typhoid and Paratyphoid Typhoid fever, paratyphoid fever is an acute digestive tract infection caused by typhoid fever and paratyphoid bacilli A, B. clinically with persistent high fever, relative pulse slowness, characteristic poisoning symptoms, splenomegaly, rose rash and leukopenia feature. Intestinal bleeding, intestinal perforation is the main complication. The main pathological feature of typhoid fever is the hyperplasia of the whole body reticuloendothelial system. The lesions in the lower ileal lymphoid tissue are most prominent, and paratyphoid fever is caused by paratyphoid A, B, and Bacillus. Its clinical manifestations, diagnosis, treatment and prevention are the same as typhoid fever. basic knowledge The proportion of illness: 0.001% Susceptible people: no special people Mode of infection: digestive tract spread Complications: Enterohemorrhagic Escherichia coli infection

Typhoid and paratyphoid fever

Typhoid fever, paratyphoid fever is an acute digestive tract infection caused by typhoid and paratyphoid bacillus A, B, C. It can be caused by water and food pollution. This disease is distributed throughout China and is distributed throughout the year, with the most summer and autumn. Children, young and middle-aged.

The pathogen of the disease is Salmonella typhimurium, belonging to the D group (group) of Salmonella, negative for Gram stain, short rod-shaped, 1 to 3.5 m long, 0.5 to 0.8 m wide, with flagella around, capable of activity, no spore generation , without capsule, can grow on ordinary medium, and grow better in medium containing bile.

Salmonella typhimurium has strong viability in nature. It can survive for 2 to 3 weeks in water and can last for 1 to 2 months in feces. It can not only survive in milk, but also can breed, can withstand low temperature, and can be used in freezing environment. It lasts for several months, but it is weak against light, heat, dryness and disinfectant. It is dead for several hours after direct sunlight. It is heated to 60 °C for 30 minutes or immediately after boiling. It is killed in 5% carbolic acid for 5 minutes. The residual chlorine in the disinfected drinking water can reach 0.2 to 0.4 mg/L and can be quickly killed.

Salmonella typhimurium only infects humans and does not infect animals under natural conditions. This bacterium can release strong endotoxin when it is lysed, which plays an important role in the occurrence and development of this disease. A small amount of endotoxin is injected into humans or Intravenous rabbits can cause chills, fever, discomfort and leukopenia. These phenomena are very similar to those of typhoid patients. The bacteria ("O") antigen, flagella ("H") antigen and surface of typhoid bacillus (" "Vi" antigens can produce corresponding antibodies, but these are not protective antibodies. Because "O" and "H" are highly antigenic, they are often used in serum agglutination test (fat reaction) to aid clinical diagnosis. To make typhoid vaccine for vaccination, the "Vi" antigen is found in the new isolate (especially from the patient's blood), can interfere with the bactericidal efficacy and phagocytosis in serum, is an important factor in determining the virulence of Salmonella typhi, but the antigen Sex is not strong, the agglutination titer of the resulting "Vi" antibody is generally low and very short; when the pathogen is cleared from the human body, the "Vi" antibody titer drops rapidly, and the "Vi" antibody is detected. The disease The diagnosis is not very helpful, but it helps to find carriers. The typhoid bacillus containing "Vi" antigen can be lysed by specific phage. The "Vi" type II phage can be used to divide typhoid bacillus into about 100 phage types. It is helpful to track the source of infection.

Typhoid and paratyphoid prevention

The focus of prevention of this disease is to strengthen drinking water, food hygiene and manure management, and cut off the route of transmission. The protective effect of the injected vaccine was not satisfactory. In recent years, the oral attenuated vaccine (Ty2la) has been promoted and has been tested in some countries in the Middle East and Latin America, but the effects are mostly limited.

1. Don't go to a stall with poor sanitation and a restaurant.

2, do not eat raw or half-life to eat seafood such as buttercups, oysters, and scorpions.

3, develop good hygiene habits, do not drink raw water, wash hands before and after meals.

4, patients with unexplained persistent fever, should go to the hospital for diagnosis and treatment in time, so as not to delay the disease.

5, when there are typhoid patients in and around the home, it is necessary to pay attention to self-protection. For potentially contaminated items, use boiling, disinfectant soaking, etc. to disinfect.

6, emergency prevention medication, you can use compound sulfamethoxazole 2 tablets, twice a day, take 3-5 days.

7. Emergency vaccination: Prevention and treatment of typhoid vaccines for key populations in outbreak areas and adjacent areas.

Typhoid and paratyphoid complications Complications Enterohaemorrhagic Escherichia coli infection

Intestinal bleeding, intestinal perforation.

Symptoms of typhoid and paratyphoid fever common symptoms, missed fever, irregular heat, intestinal bleeding, nasal discharge, constipation, expression, apathy, fatigue, sluggish reaction, dull abdominal discomfort

symptom

The typical natural course of typhoid fever lasts about 4 weeks and can be divided into 4 phases:

(1) The initial period is equivalent to the first week of the disease course, and the onset is mostly slow (75% to 90%). Fever is the earliest symptom, often accompanied by general malaise, fatigue, loss of appetite, sore throat and cough, etc. The temperature is stepped up, reaching 39 to 40 °C in 5 to 7 days. There may be chills and less chills before fever, and sweating during fever is not significant.

(B) The extreme period is equivalent to the second to third week of the disease course, often with typical symptoms of typhoid fever, which is helpful for diagnosis.

1. High heat and high heat continue to retreat, most (50% to 75%) are in the form of heat retention, and a few are in the form of relaxation or irregular heat, lasting about 10 to 14 days.

2. Digestive system symptoms Loss of appetite is more obvious than before, the tongue and tongue are red, the moss is thick and greasy (so-called typhoid tongue), abdominal discomfort, abdominal distension, and more constipation, a few are mainly diarrhea, due to the intestine Most of the disease is in the terminal ileum and ileocecal area, and there may be mild tenderness in the right lower abdomen.

3. The symptoms of the nervous system are directly proportional to the severity of the disease. It is caused by the central nervous system of endotoxin in typhoid bacillus. The patient has mental paralysis, apathy, sluggishness, slow response, hearing loss, severe convulsions or coma. Meningeal irritation (viral meningitis), these neurological symptoms often decline with body temperature to gradually recover.

4. Symptoms of the circulatory system often have relatively slow pulse (20% to 73%) or sometimes severe vein is one of the clinical features of this disease, but in the case of toxic myocarditis, the relative slow pulse is not obvious.

5. The splenomegaly begins on the 6th day, and the glandular enlargement (60%-80%) can often be reached under the left rib. The soft or tenderness may occur in a few patients (30%-40%). , soft or with tenderness, severe jaundice, abnormal liver function, suggesting the presence of toxic hepatitis.

6. The rash has a course of 7 to 13 days. Some patients (20% to 40%) have pale red maculopapular rash (rose rash) with a diameter of about 2 to 4 mm. The color is faded, and the number is below 12, which appears in batches. It is mainly distributed in the chest and abdomen, and can also be found in the back and limbs. It disappears within 2 to 4 days. Crystal-shaped sweat rash (or white sputum) is not uncommon, and it occurs mostly in sweating.

(3) The remission period is equivalent to the third to fourth week of the disease course. The body's resistance to typhoid bacilli gradually increases, the body temperature fluctuates and begins to decline, the appetite gradually improves, the abdominal distension gradually disappears, and the splenomegaly begins to retract, but there are The risk of intestinal bleeding or intestinal perforation requires special vigilance.

(4) The recovery period is equivalent to the fourth weekend of the disease course, the body temperature returns to normal, the appetite is improved, and the health is generally restored in about 1 month.

Other clinical types

In addition to the above-mentioned typical typhoid, according to the age of onset, the immune status of the human body, the virulence and quantity of the pathogenic bacteria, the irregular application of antibacterial drugs in the early stage of the disease, and the presence or absence of complications, typhoid can be divided into the following types.

(1) The symptoms of mild systemic toxic blood are mild, the course of disease is short, and it is cured within 1 to 2 weeks. It is more common in patients who have received typhoid vaccine injection before the onset of illness or have applied effective antibiotics in the early stage of the disease. It is not uncommon in children. Due to the mild condition, the symptoms are not typical, which may lead to missed diagnosis or misdiagnosis.

(B) fulminant onset of fulminant, severe toxic symptoms, chills, high fever, abdominal pain, diarrhea, toxic encephalopathy, myocarditis, hepatitis, intestinal paralysis, shock and other performance, often have a significant rash, but also complicated by DIC.

(3) The protracted onset is similar to the typical typhoid. Due to the low immune function of the human body, the fever persists, which can reach 45 to 60 days. The typhoid fever patients with chronic schistosomiasis often belong to this type.

When typhoid fever is combined with schistosomiasis, the onset is more urgent. The fever is often relaxation or intermittent. The hepatosplenomegaly is more obvious. The eosinophils are significantly reduced or disappeared during the febrile phase and the extreme phase. Normal value, the heat can be extended from January to February.

(D) The typhoid fever in children is generally older, the clinical manifestations are more like adults, the younger the age, the more abnormal the symptoms.

The symptoms of school-age children are similar to those of adults, but they are mostly mild, often acute onset, with persistent fever, loss of appetite, abdominal pain, constipation, apathy, lethargy, irritability, thick tongue, abdominal distension and hepatosplenomegaly. Slow pulse and rose rash are rare, white blood cell count is often not reduced, the course of disease is short, sometimes only 2 to 3 weeks, that is, natural recovery, due to intestinal lesions, intestinal bleeding, intestinal perforation and other complications are also less.

Infants and typhoids are often not typical, the course of disease is also mild, acute onset, accompanied by vomiting, convulsions, irregular high fever, fast pulse, abdominal distension, diarrhea, etc., rare rose, white blood cell count is often increased, and bronchitis or pneumonia is quite common .

(5) The temperature of senile typhoid fever is not high, the symptoms are atypical, and the phenomenon of weakness is obvious; bronchial pneumonia and heart dysfunction are easy to occur, often persistent intestinal dysfunction and memory loss, prolonged disease course, recovery is not easy, and the mortality rate is high.

Recurrence and reburning: 1 to 2 weeks after the disappearance of symptoms, the clinical manifestations are similar to those of the first episode, and the blood culture is converted to recurrence. The symptoms of recurrence are mild, the course of disease is short, and the latent pathogens in the gallbladder or reticuloendothelial system multiply. Re-invasion of blood circulation; insufficient course of treatment, easy to see when the body's resistance is low, even recurrence 2 to 3 times, re-ignition refers to the course of the disease, the body temperature gradually rises in the process of gradual decline, 5 to 7 days after the normal, blood The culture is often positive, and the mechanism is similar to that of the initial one.

Typhoid and 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. Fertility test typhoid serum agglutination test

That is to say, the fat-reaction positive person has the auxiliary diagnostic value for typhoid fever and paratyphoid fever. The antigens used in the examination include typhoid bacillus (O) antigen, flagellar (H) antigen, paratyphoid A, B, and c flagella antigens. The purpose is to determine the agglutination titer of various antibodies in the patient's serum 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 second week to 90% in the fourth week. After the recovery, the positive reaction can be positive. For several months, a small number of patients had antibodies that rose very late, and even the entire course of antibody titer was low (14.4%) or negative (7.8% to 10%), so the disease could not be ruled out accordingly.

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.

Diagnosis of typhoid fever and paratyphoid fever

diagnosis

According to the local typhoid epidemic situation, my past medical history, history of exposure to typhoid bacterin, presence or absence of contact with typhoid patients, and high fever, special symptoms of poisoning, and laboratory tests, decreased white blood cell count during the course of disease, classification of neutral lymphocytes Relative increase, while eosinophils decreased or disappeared, the fatda reaction (+) increased more than 4 times, anti-"O">1:80, anti-"H">1:160 meaningful, bacteriological examination, onset The positive rate of blood culture was the highest in 1~2 weeks, and the chance of positive urine culture was high in 3~4 weeks. The positive rate of bone marrow culture was higher than that of blood culture and lasted for a long time.

Differential diagnosis

1. Chronic enteritis: clinical manifestations of fever, mucus, similar to dysentery, the disease is more common in young children and the elderly.

2. Septicemia: caused by Salmonella choleraesuis, patients with high fever, chills, anorexia and anemia, often accompanied by local lesions (such as cholecystitis, etc.), generally can be isolated from the blood pathogens.

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