Brucellosis

Introduction to brucellosis It is widely used in many countries in the world. The high-incidence areas are the Mediterranean region, Asia, Central and South America, etc., and the annual new cases in the world are about 500,000. Before the founding of New China, the disease was very prevalent. After the founding of New China, a special prevention and treatment institution was established. The incidence rate has been significantly reduced. However, since 1994, the brucellosis of humans and animals in China has rebounded, and many areas that have been basically controlled have new ones. The prevalence of brucellosis in humans and animals, such as Binzhou in Shandong Province, Cixian County in Hebei Province, and Shanxi Province and Liaoning Province. The main reason for the rebound in the epidemic is free trade, exchange and movement of quarantine livestock. In addition, the supervision, management and disinfection of livestock products such as milk and meat are relaxed, livestock cannot be promptly and widely immunized, and the prevention and treatment team is scattered. It is an important reason for the prevention and treatment of brucellosis. Therefore, we must strengthen the prevention and control of brucellosis in order to achieve the goal of long-term basic control throughout the country. basic knowledge The proportion of the disease: the probability of the population is 2.1% Susceptible people: no specific people Mode of infection: contact spread Complications: anemia optic neuritis meningitis

Cause of brucellosis

Cause:

It is generally believed that after invading the human body through the skin mucosa, Brucella mainly invades the local lymph nodes through the lymphatic vessels to grow and multiply and is swallowed by macrophages. If it is not destroyed, it forms a infection foci, which breaks through the lymph node barrier after a large number of growth and reproduction. Into the blood circulation, in the blood circulation, Brucella continues to grow, breed, die, release endotoxin, sputum bacteremia, toxemia, endotoxin plays an important role in the occurrence of acute symptoms, 1mg endotoxin can make body temperature It rises to 40.5 °C and causes severe systemic symptoms. At this time, if the body's immune function is normal, the bacteria can be cleared and cured by the combination of T cells, macrophages and specific antibodies. If the specific immune function cannot remove the bacteria, The bacteria can enter the various organs and tissues to form infected or migratory lesions with the blood, especially macrophages. The bacteria in the lesion can enter the blood circulation multiple times to form recurrence and various allergic manifestations, to the chronic phase. Then the bacteria are mainly confined to various organ tissues, forming local lesions, or the bacteria have been cleared, but caused by allergies. In the lesions, Brucella is mainly parasitic in cells, and antibacterial drugs are not easy to enter and play a role. This may be one of the reasons why it is difficult to cure. The pathological changes of this disease are extremely extensive, and almost all organ tissues can be invaded. Nuclear phagocytic system is the most common, with diffuse cell proliferation in the acute phase, and granulomas composed of epithelial cells, macrophages, plasma cells and lymphocytes in the chronic phase. This granulomatosis and human sarcoidosis The lesions are similar, without cheese-like necrosis, which is a typical lesion of the disease. The rest, such as the cardiovascular system, the motor system, the reproductive system, and the nervous system, often have different lesions.

Brucellosis prevention

Comprehensive measures centered on livestock vaccination should be adopted.

1. Controlling the source of infection For livestock, regular quarantine, slaughtering of sick animals, sick and grazing of sick and healthy animals and immunization of vaccines can be adopted. The effect of vaccine immunization is very good, and there are various methods of immunization. Among them, the injection of bovine type 19 (S19) vaccine has a good preventive effect on preventing sheep and cattle, but the pregnant animal can cause abortion after injection, so it should be injected before breeding, and attention should be paid to prevent infection, pig type. No. 2 (S2) vaccine is also very effective in drinking water immunity. It is effective for preventing sheep, cattle and pigs, and it is simple and easy to operate. It saves labor and medical equipment and does not cause miscarriage of pregnant animals. The disadvantage is that in water source In many places, livestock are not used to drinking water in the sink, and they need to take the sheep to do the quantitative feeding. In addition, if the animals drink water by themselves, the amount of inoculation will be more or less, which will also affect the immune effect. In recent years, some people think that, for example, to the lamb Immunization with yak (oral or injection), the immune effect can last for a long time, can reduce the number of vaccination, save a lot of bacterin, in addition, some people try the sheep 5 (M5) bacterin immunization, think immune Good effect, fast speed, save people It is especially suitable for areas where water is abundant and it is difficult to promote drinking water immunity. Personal protection should be paid attention to when immunizing livestock. One problem in vaccine immunization is that the serological reaction of vaccine immunization is not easy to be serologically reactive with natural infection. Distinguish, making the diagnosis of brucellosis difficult. Recently, it has been reported that the rifampin-resistant Br. abortus mutant (RB5) does not interfere with serological diagnosis. In further research, the patients significance as a source of infection is not Large, but still need isolation treatment, the patient's excretion (mainly urine) should be disinfected.

2. Cutting off the route of transmission is also one of the important measures

(1) Treatment of livestock stream products: The stream products should be buried deeply and the contaminated sites should be strictly disinfected.

(2) Treatment of animal products: disinfection of dairy and dairy products (Pasteurization or boiling), fur disinfection (natural storage for 1 to 5 months, sun exposure, chemical disinfection, 60Co irradiation, etc.), meat should be cooked.

(3) Livestock manure should be used as fertilizer and fuel after harmless treatment, and the water source should be protected from being contaminated by the excrement of patients and sick animals.

(4) Personal protection, especially for occupational groups: When contacting sick animals, protective equipment: work clothes, masks, hats, aprons, latex or line gloves and rubber shoes, etc., use disinfectant or soapy water after work. Wash your hands, do not eat during work, wash your hands before meals, etc.

Brucellosis complications Complications anemia optic neuritis meningitis

1. Anemia of the blood system, leukopenia, thrombocytopenia is more common, severe whole blood reduction is mainly caused by cytophagocytosis, granuloma in the bone marrow may also play a role, the incidence of thrombocytopenic purpura is about 1% ~4%, sometimes very severe and lasting for a long time, requiring corticosteroids or spleen treatment.

2. Eye uveitis, optic neuritis, optic disc edema and corneal damage have been reported, immune complex may be the cause of uveitis, more common in chronic brucellosis.

3. The incidence of nervous system is about 3% to 5%. Meningitis, meningoencephalitis, myelitis, polyradiculoneuropathy, etc., and changes in cerebrospinal fluid in meningitis are similar to tuberculous meningitis: lymphocytes in cerebrospinal fluid. Increased, increased protein, mildly reduced glucose; positive for both bacterial culture and antibody testing.

4. The cardiovascular system is mainly endocarditis, which mainly invades the active membrane flap. 50% of the patients have active membrane flaps, and the mortality rate is high. In addition, there are occasional myocarditis, pericarditis, aortitis, etc. Pregnant women suffering from brucellosis will not terminate the pregnancy naturally, and there are different opinions, but most people think that if antibacterial treatment is not carried out, it will cause, abortion, premature birth, stillbirth can occur, in addition, liver abscess, Spleen abscess, pneumonia, glomerulonephritis, pleurisy, etc. have been reported, changes in pleural effusion similar to tuberculous pleurisy, including elevated adenosine deaminase (ADA).

Brucellosis symptoms Common symptoms Irregular fever Unexplained fever Lymph node enlargement

The clinical manifestations of this disease are very complicated, so the classification is difficult. According to the Testing Standard for the Diagnosis and Treatment of Human Brucellosis issued by the Office of the Leading Group for Prevention and Treatment of Endemic Diseases in Northern China in 1977, the clinical classification is acute and chronic. The active type and the chronic phase are relatively stable, the incubation period is 7 to 60 days, with an average of 2 weeks, and a few patients can reach several months to more than one year.

1. The acute phase of the disease is slowed down. The main symptoms are fever, hyperhidrosis, joint pain, testicular swelling and pain, etc. The fever is mostly low heat and irregular heat, and the typical wave shape appears in 5% to 20%. After 2 to 3 weeks, intermittent several days to 2 weeks, fever recurrence, repeated many times, the symptoms of poisoning during fever are not obvious, sometimes the symptoms after antipyretic are more serious than fever, so it has been called undulant fever ), sweating is also one of the prominent symptoms of this disease, often sweating at night or in the early morning heat, joint pain is often more intense, similar to rheumatic fever, is migratory, mainly involving large joints, testicular swelling and pain The most characteristic, accounting for 20% to 40% of male patients, is caused by orchitis and epididymitis, mostly unilateral, hepatosplenomegaly is also very common, other can still have headache, neuralgia, lymphadenopathy , rash, etc.

2. The chronic disease course is more than one year, which is called chronic phase. It can be developed from the acute phase, or it can be directly manifested as chronic without acute history. Anyone with chronic inflammation is characterized by low fever, symptoms and signs recurring or aggravated. Active type, those who have no chronic inflammation: normal body temperature, symptoms and signs or dysfunction are fixed, only in the case of climate change, only when the overwork is overweight, the relatively stable type, the performance in this period is more diverse, basically There are two types: one is systemic non-specific symptoms, similar to neurosis and chronic fatigue syndrome; the other is organic damage, among which the skeletal-muscle system is the most common, such as large joint damage, muscle contracture, etc. Systemic lesions are also more common, such as peripheral neuritis, meningitis, etc., genitourinary system lesions can also be seen, such as orchitis, epididymitis, ovarian inflammation.

Brucellosis examination

1. Peripheral blood leukocyte counts are normal or low, lymphocytes are relatively or absolutely increased, sometimes a small number of atypical lymphocytes may appear, erythrocyte sedimentation rate increases in the acute phase, and the chronic phase is normal or high, and the continuous growth rate suggests activity.

2. The pathogen separation can be separated from blood, bone marrow, cerebrospinal fluid, urine, pus, etc., the bovine Brucella is not easy to grow when it is initially separated, and it needs a proper carbon dioxide environment, because Brucella grows slowly, so various Culture can be judged to be negative after 2 to 4 weeks of incubation, but it has been reported that 93% (90/97) can be in 5 days or 97.6% (41/42) if BACTEC9240 blood culture system is used. Can be detected within 2 to 6 days, the recent report also confirmed this: blood culture can be obtained within 7 days, bone marrow culture in 4 days to obtain a positive result, generally considered that the blood culture positive rate is high, the chronic phase is low, The positive rate of bone marrow culture is higher than that of blood culture. If necessary, the specimen can be inoculated into guinea pigs to isolate Brucella. It is suggested that the specimen, especially the blood of chronic brucellosis, be injected into the egg yolk of the egg, and cultured at 37 ° C for 5 days. Then, the egg yolk solution was transferred to the agar slants, and observed at 37 ° C for 2 to 3 days, which was considered to increase the positive rate.

3. Immunological examination

(1) Serum agglutination test: There are many methods. The commonly used ones are test tube method and flat plate method. The former is more sensitive, the operation is simpler, and the specificity is better. Therefore, it is commonly used in laboratories; the latter is simpler in operation and high in sensitivity. However, there may be false positives, so it is suitable for screening. There are also many kinds of plate methods. Among them, the tiger red buffer slide agglutination test (RBPT) works best, and the agglutination test can appear in the first week of the disease course, the second ~ It is strongly positive in 3 weeks, and the test tube method is more than 1:100. The increase in titer in the course of disease is more than 4 times, but it is more significant, but it has been inoculated with cholera vaccine, rabbit fever vaccine, Brucella vaccine or Both brucellin and intradermal testers can increase the agglutination titer. It should be noted that the other agglutination reaction may have a prozone phenomenon (negative at low dilution and anti-positive at high dilution), so the dilution should be at least 1 : 100 or more, the cause of the phenomenon of anterior banding, some people think that due to the presence of IgA antibodies, some people think that it is related to: the ratio of IgA, IgG, IgM, when the IgA antibody is the main phenomenon, the agglutination reaction is acute The positive rate is very high, up to 80% to 90%, slow Period were lower, only about 30%.

(2) Enzyme-linked immunosorbent assay (ELISA): 1:320 is positive, sensitivity is higher than agglutination test, specificity is also very good, and IgM, IgG, IgA antibodies can be determined separately, and IgM antibodies appear earlier. It reached a peak about 1 month after infection, and then began to decline. The IgG antibody was produced later, reached a peak at 6 months, and began to decline after 10 months. The growth and decline of IgA antibody was similar to that of IgG, and it was not easily destroyed by sulfhydryl compounds. Different antibodies were used to determine the recurrence. The IgG antibody increased again during relapse, while IgM and IgA antibodies often continued to decrease. This method can also measure anti-cytoplasmic (CP) antibodies and anti-LSP antibodies, respectively. Good, but it appears later, and early antibacterial treatment can affect its appearance. The latter appears earlier and is not affected by antibacterial drugs, but the specificity is slightly worse, so if the two are detected at the same time, the effect is best.

(3) Complement binding test: 1:16 is positive, the positive rate in acute phase and chronic phase is higher, the specificity is also strong, but the positive appearance time is later, the disease is only positive in the third week, and the operation is complicated. Therefore, it is only used for the diagnosis of patients, especially chronic patients.

(4) Anti-injection globulin test: 1:160 is positive for the determination of incomplete antibodies, positive for late appearance, slower disappearance, more sensitive than agglutination test and complement fixation test, positive rate in acute phase and chronic phase Higher and more specific, but the operation is more complicated, so it is only used for difficult cases, especially chronic patients.

(5) Other serological tests: passive hemagglutination test, agar diffusion test, indirect immunofluorescence test, immunoelectrophoresis and spot immunoassay (using silver-labeled Clostridium-specific antigen) can be applied. Some use of 2-mercaptoethanol Experiments to identify natural infections and vaccine immunizations, but yet to be studied.

(6) Intradermal test is a delayed hypersensitivity reaction, which starts to appear positive 2 to 3 weeks after onset, and can still last for several years to 20 years after recovery. Therefore, it is not possible to identify whether it is a current patient or a previous infection when it is positive. Used for epidemiological investigations, but negative for the diagnosis of this disease.

4. Molecular biological examination In recent years, primers capable of amplifying a 223 bp gene fragment encoding Mr. 31×103 Brucella antigen have been used for PCR to diagnose the disease, and the specificity and sensitivity are considered to be good except Ochrobactrum spp. In addition, other microbes related to bryogenes and bryogenes were negative, and 31 patients with brucellosis and 45 healthy people were tested for 100% specificity. The positive rate was 97%, and the positive rate of serum was found to be higher than that of whole blood. Recently, nested PCR was used, and it was considered that 30 bacteria could be detected without cross-reaction.

Histopathology can produce epithelioid cell granuloma in the reticuloendothelial system such as lymph nodes, spleen and liver. The histological changes of skin lesions are often non-specific, there is a strong inflammatory reaction around the blood vessels, the vascular endothelium is obviously proliferated, and granuloma is formed.

Diagnosis and identification of brucellosis

In the epidemic areas, there is a history of contact with sick animals, fever of unknown origin, headache and lymph nodes, spleen and hepatomegaly. The disease should be suspected. Epidemiological data is of great significance in assisting in the diagnosis of this disease. If you are infected with this disease, you can basically rule out the disease. Conversely, if you have the possibility of being infected with this disease, and the clinical recurrence of fever, significant sweating, joint pain, testicular swelling and pain, the incubation period is also consistent. The diagnosis can basically be established, blood, bone marrow, urine, cerebrospinal fluid, pus and other culture positive is the main basis for the diagnosis of the disease, should be sent multiple times, if necessary, PCR can also be used to detect specific antibody serum agglutination test It also has a large diagnostic value, especially in the course of the disease, the titer is more than 4 times higher, the enzyme-linked immunosorbent assay (ELISA) is more sensitive, the serum titer can be 100 times higher than the tube agglutination test, and the specificity is also It is better to be widely used. The complement binding test and the anti-human globulin test (Coombs test) are only used for agglutination and ELISA test negative cases, especially in chronic cases. Within the meaning of the diagnostic test for patients not now, but if negative skin test helps rule out the disease.

The acute phase of the disease should be differentiated from the longer-term febrile diseases in which the white blood cells are not high, especially those who have excessive sweating, joint pain, and major liver and spleen, such as typhoid fever, tuberculosis, rheumatoid arthritis, lymphoma, collagen disease, etc. In the chronic phase, it is necessary to distinguish from chronic osteoarthrosis, neurosis, and chronic fatigue syndrome.

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