Brucellosis

What is Brucellosis?

Brucellosis is a zoonotic infectious-allergic disease, prone to chronicity, occurring with a primary lesion of the musculoskeletal system, cardiovascular, nervous and reproductive systems.

Brief historical information
The disease has been known since the days of Hippocrates, but its scientific study began only in the 60s of the XIX century (J. Marston, 1859). At that time, it was called the “Mediterranean or Maltese fever.” The causative agent of brucellosis was first discovered by D. Bruce (1886), who gave the bacteria the name Micrococcus melitensis. Later, Bang and B. Stribold identified similar microorganisms (B. abortus) for infectious abortions in cows (1897), and J. Traum in pigs (B. suis, 1914). In 1920, the bacteria were combined into one genus, named after D. Bruce Brucella, and the disease they caused was called brucellosis. Later, new types of Brucella were identified – B. neotomae (1957), B. ovis and B. canis (1970).

Serological tests for brucellosis were started by A. Wright and D. Semplom (1897). Agglutination Reaction (RA) Wright later gained great importance in the laboratory diagnosis of the disease.

Causes of Brucellosis

Pathogens are aerobic and microaerophilic fixed Gram-negative bacteria of the genus Brucella. According to the international classification, the genus Brucella consists of 6 independent species, which are divided into a number of biovars. Brucella has a pronounced polymorphism: cocci and elongated sticks are observed in one preparation. B. melitensis is more often represented by coccoid forms, B. abortus and B. suis are rods with rounded ends. The most frequent lesions in humans are caused by B. melitensis, represented by 3 biovars (the main hosts are sheep and goats). More rarely, B. abortus, represented by 9 biovars (the main host is cattle), and B. suis, represented by 4 biovars (the main hosts are pigs, hares, reindeer). In rare cases, a person may be affected by B. canis (the main host is a dog).

Identifying Brucella species and biovars in specific areas and in the foci of infection has important epidemiological and epizootological importance in terms of classifying foci, assessing the degree of intensity of the epidemic and epizootological processes, establishing the facts of brucella migration from one species to another, identifying the pathways of the pathogen, and choosing tactics treatments, etc.

Brucella are highly invasive and can penetrate intact mucous membranes; they are referred to as intracellular parasites, but they can also be outside the cell. Brucella are quite stable in the environment. More than 2 months remain in water, 3 months in raw meat, up to 30 days in salted meat, 2 months in cheese, and 4 months in wool. Brucella die when heated to 60 ° C in 30 minutes, while boiling – instantly. Sensitive to the action of many disinfectants – a 2% solution of carbolic acid, a 3% solution of creolin and lysol, a 0.2-1% solution of bleach and chloramine kill them within a few minutes.

Epidemiology
The main source and reservoir of infection are sheep, goats, cattle and pigs. Reported cases of human infection with reindeer brucellosis. In rare cases, the source of infection can be horses, camels, yaks and some other animals that secrete the pathogen with milk, urine, feces, amniotic fluid. Most often, a person becomes infected with brucellosis from small livestock, the causative agent of which (V. melitensis) causes the majority of severe forms of the disease. It is also quite common for a person to become infected with B. abortus from cattle, however, a clinically expressed infection is recorded in isolated cases. The course of the disease is easy; a sick person is not dangerous to others.

The mechanism of transmission of the pathogen is diverse, most often fecal-oral; contact-aided use is also possible (if the pathogen enters the damaged skin and mucous membranes) and the aerogenic transmission mechanisms. The epidemiological significance of food products and raw materials of animal origin determine the massiveness of seeding, the type of pathogen, the duration of its preservation. The most dangerous are raw dairy products (milk, cheese, cheese, koumiss, etc.), meat and raw materials (wool, astrakhan and leather) from goats and sheep with brucellosis. Meat is a much lower epidemiological risk, as it is usually consumed after heat treatment. However, in some cases, with insufficient heat treatment (national cooking characteristics – sliced, blood shashlyk, raw minced meat, etc.), meat and meat products can be the cause of brucellosis infection.

Sick animals pollute the soil, litter, fodder, and water with Brucella, which in turn become factors that cause human infection. There have been cases of human infection during manure removal. The aspiration route of infection is possible when inhaling air-dust mixture containing infected fragments of wool, manure, earth. This way of infection is possible when shearing, sorting wool, combing down (development, knitting, etc.), as well as when cleaning premises and territories where animals are kept or raw materials are processed from them. In this case, Brucella can also penetrate the mucous membrane of the conjunctiva of the eye. There are cases of laboratory aerogenic infection when working with bacteria cultures. There are cases of human infection through water, but the epidemiological significance of this route of transmission is small. Possible intrauterine infection of the fetus and infection of children when feeding with breast milk.

The natural susceptibility of people is high. Post-infectious immunity usually lasts 6-9 months. Repeated diseases are observed in 2-7% of cases.

Major epidemiological signs. Brucellosis – a ubiquitous infection; foci of disease are found on all continents. Moreover, it is characterized by a pronounced professional nature of morbidity: it is most common in rural areas among livestock workers. The incidence of people is closely associated with epizootics among cattle, sheep and goats. A significant place in some cases is occupied by the possibility of the migration of brucella from a biologically adapted host to other animals. Migrations are most often facilitated by joint keeping or joint grazing of various animal species. The greatest danger is the migration of B. melitensis to cattle. Mainly people working with animals get sick: shepherds, shepherds, milkmaids, veterinary and zootechnical workers, employees of bacteriological laboratories, meat processing plants, slaughterhouses, and wool-processing factories. Infection can occur during the processing of raw meat, leather, animal hair, patients with brucellosis. In such cases, the penetration of Brucella into the human body occurs through the skin, mucous membranes of the eye, nose, mouth. In laboratory examinations of livestock breeders, 1.5-2% of individuals with antibodies to brucellosis pathogens are detected. The prevalence of brucellosis is not identical across regions, it is recorded mainly in livestock areas. Epizootics and a high incidence of brucellosis persist in the CIS countries, mainly in Kazakhstan and Central Asian countries, from which infectious raw materials are possible to enter Ukraine. The maximum number of goat-sheep type brucellosis occurs in the spring-summer period. When infected with brucellosis from cattle, seasonality is less pronounced, which is explained by a long lactation period and infection mainly through milk and dairy products.

Pathogenesis During Brucellosis

Brucella penetrate the human body through mucous membranes or damaged skin, leaving no changes in the area of ​​the entrance gate. By lymphogenous pathogens are brought into the regional lymph nodes and accumulate in them. This phase of the infection is called lymphogenous and corresponds to the incubation period of the disease. Its duration may be different and depends on the ratio of the activity of pathogens (infectious dose) and the body’s defenses. With long-term preservation of brucella in the lymph nodes, an immunological rearrangement of the body occurs, antibodies detected in serological reactions accumulate, a skin allergy test with brucellin becomes positive, but clinical manifestations do not develop (primary latency phase).

After it comes hematogenous phase (phase of hematogenous drift). Bacteremia and endotoxemia develop, and clinical symptoms of acute brucellosis appear. These manifestations are associated with functional disorders of the autonomic nervous system under the influence of endotoxin and toxic-allergic reactions.

With blood flow, pathogens are spread through organs rich in reticuloendothelium, and fixed in them (the phase of poly-focal localizations). The macrophage system is activated, diffuse changes develop in organs and tissues, and focal accumulations of macrophages are formed with intracellularly parasitic brucella in them. These processes, aimed at reducing the intensity of bacteremia, localization and fixation of pathogens, lead to the formation of secondary polyorgan foci of infection in the form of specific granulomas. In connection with the sensitization of the body, allergic manifestations develop – delayed-type hypersensitivity reactions, and sometimes immediate-type hypersensitivity.

The possibility of long-term persistence of pathogens inside macrophages is explained by the incompleteness of phagocytosis and the slow development of reactions of the immune response. Metastatic foci of brucella reproduce easily in organs with the development of localized infiltrates; The clinical picture shows signs of focal lesions on the part of the musculoskeletal, nervous, and other systems. Subsequent episodes of release of pathogens into the bloodstream support bacteremia and endotoxemia, give the disease a wave-like character. These mechanisms develop into the phase of subacute brucellosis, but in some cases focal lesions form early, even at the stage of acute brucellosis.

The disease is prone to long-term course and transition to a chronic condition. Long-term preservation of pathogens in metastatic foci with episodes of re-dissemination and the development of reactive-allergic changes underlies chronic brucellosis (the phase of exo-focal seeding and reactive-allergic changes). In the chronic process, the pathogenetic significance of bacteremia and endotoxemia, the activity of inflammatory and allergic organ focal reactions, weakens. The formation of new inflammatory foci is associated primarily with autoimmune mechanisms.

With chronic brucellosis in various organs and systems, functional and sometimes irreversible organic disorders are formed with the development of persistent cicatricial changes. They persist even after complete sanation of the organism and in these cases underlie the pathogenesis of the phase of the so-called residual metamorphosis (the phases of the outcome and residual effects). Functional disorders are distinguished by a paucity of objective symptoms with an abundance of subjective complaints.

Symptoms of Brucellosis

The incubation period is 1-4 weeks, but can be extended to 2-3 months with the development of latent infection. According to modern clinical classification based on the generally accepted classification of GP Rudnev, there are acute (up to 1.5 months), subacute (up to 4 months), chronic (more than 4 months) and residual (clinical consequences) form.

Acute Brucellosis. May develop gradually (more often in older persons) or quickly. With the gradual onset of the disease over various periods of time (from several days to several weeks), patients complain of indisposition, weakness, sleep disturbances, decreased performance, pain in joints, various muscle groups and lower back. When examining noted subfebrile, sometimes – an increase in peripheral lymph nodes of the type of micro-polyadenopathy. In the future, signs of intoxication gradually increase, the body temperature becomes high, chills and pouring sweats appear, the liver and spleen increase in size.

With the rapid development of acute brucellosis is manifested by a rise in body temperature to high numbers (39 ° C and above) during the first 1-2 days of the disease. Remittent, wavy or intermittent fever accompanies pronounced chills, resulting in profuse sweating. The febrile reaction usually lasts several days, but can lengthen to 3-4 weeks, taking a wave-like character. However, in most cases, the state of health of patients due to moderate intoxication remains relatively satisfactory, even against the background of high body temperature and fairly significant objective changes. This clinical feature of brucellosis is often the cause of difficulties in the differential diagnosis of the disease.

Patients complain of headache, emotional instability, irritability, sleep disturbances, pain in muscles and joints. When viewed at a height of fever, hyperemia of the face and neck, pallor of the skin of the trunk and extremities are noted. Peripheral lymph nodes, especially cervical and axillary, slightly increase in size, can be somewhat painful on palpation. Micropolyadenopathy, which is considered an early clinical sign of brucellosis, has been rarely encountered recently (no more than in 20-25% of cases). Sometimes in the subcutaneous tissue, but in the area of ​​the muscles and tendons, painful, dense nodules or nodes ranging from a pea to a small chicken egg can be palpated – fibrositis and cellulite, although their appearance in patients is more characteristic of the next, subacute form of brucellosis. The liver and spleen are enlarged, sensitive to palpation. In 10-15% of cases, organ diseases of the musculoskeletal system, the genital sphere, and the peripheral nervous system with corresponding focal symptoms develop in the acute period of the disease.

The severity of brucellosis depends largely on the type of pathogen (its virulence). Diseases caused by B. abortus are usually easier to treat than lesions caused by B. melitensis.

Subacute form. Characterized by a relapsing course. Feverish periods with a temperature reaction of varying severity and duration (usually several days) alternate with periods of apyrexia. During the ascent, the temperature curve becomes irregular, the temperature level is subject to significant fluctuations even during the day.

Patients present numerous various complaints. Concerned diffuse pain in muscles, bones and joints, paresthesia, depressed mood. Sleep and appetite worsen, muscular weakness develops, dry mouth, thirst, and constipation appear.

On examination, patients often reveal fibrositis and cellulite. On the part of the cardiovascular system, they note relative bradycardia at a height of fever and slight tachycardia during periods of normal body temperature, muffled heart sounds. In severe cases, signs of infectious-allergic myocarditis, endocarditis and pericarditis can be detected. Pathology of the respiratory system is rarely detected (catarrhal sore throat, pharyngitis, bronchitis, bronchopneumonia). Changes in the digestive organs are functional, which is reflected in the complaints of patients. In severe cases, it is possible to develop meningism and sluggish serous meningitis.

Much more often than with acute brucellosis, multiple organ lesions and allergic reactions develop (exanthema, dermatitis, reactions of the superficial vessels of the skin, etc.). First of all, there are lesions of the musculoskeletal system: arthritis and polyarthritis, synovitis, bursitis, tendovaginitis, etc. Sexual lesions are typical – in men, orchitis and epididymitis, in women, menstrual disorders, endometritis, spontaneous abortions. Damage to the nervous system can manifest itself in the form of plexites, isioradiculitis.

Chronic brucellosis. Characterized by variability of clinical manifestations and recurrent course. Temperature reaction and other manifestations of intoxication are weak or moderately pronounced. Periods of exacerbations replace remission, the duration of which can reach 1-2 months. The deterioration observed in the occurrence of fresh focal processes.

The clinical picture of chronic brucellosis is dominated by focal lesions from various organs and systems.

Signs of changes in the musculoskeletal system are characterized by the development of recurrent, long-lasting arthritis with frequent involvement of the periarticular fiber (periarthritis), bursitis, tendovaginitis, periostitis, perichondritis. Fibrositis and cellulite in the lumbosacral region and above the elbow joints are typical. Lesions of various parts of the spine are manifested by severe pain, restriction of movements, deformities, destructive changes.

Affections of the nervous system are expressed in the form of radiculitis, plexitis, intercostal neuralgia, neuritis of the auditory and optic nerves, and sensitivity disorders. In rare cases, the development of meningoencephalitis, diencephalic syndrome. Changes in the vegetative nervous system cause hyperhidrosis, the phenomena of vegetative-vascular dystonia. Neuroses and reactive states (the “difficult character” of patients) are often formed.

Urogenital pathology is manifested by orchitis and epididymitis in men, oophoritis, salpingitis, endometritis and menstrual disorders in women. Characterized by miscarriage, dysmenorrhea, infertility.

In chronic brucellosis, complex organ lesions develop most often (mixed form).

Chronic active brucellosis can last up to 2–3 years, and upon repeated infection, it can take much longer. Its transition to the chronic inactive form is characterized by the absence of the formation of fresh foci and intoxication, the predominance of functional disorders, the long-term preservation of serum antibodies and a positive skin-allergic test (Byrne test).

Consequences of brucellosis (residual brucellosis). Persist in the absence of the pathogen in the human body. Characteristic residual effects, mainly of a functional nature due to immunoallergic restructuring and disorders of the autonomic nervous system: sweating, irritability, changes in the neuropsychic sphere, arthralgia, and sometimes subfebrile.

However, more severe consequences of brucellosis may be associated with the development of irreversible fibro-cicatricial changes involving nerve trunks, plexuses, roots, which provokes the appearance of various neurological symptoms.

Organic changes in the musculoskeletal system, sometimes developing in patients with brucellosis (joint deformities, ankylosis, contracture, muscle atrophy, spondylosis), in some cases require surgical treatment and determination of the disability group.

In conclusion, it should be noted that the course of the disease at the present stage is distinguished by a number of features:

  • febrile reaction of the wrong type is often limited to subfebrile condition;
  • lesions of the musculoskeletal system are manifested primarily by pain reactions, less often – by focal inflammatory processes;
  • lymphadenopathy and an enlarged spleen develop in no more than 25% of cases;
  • focal lesions develop earlier, in 12-15% of cases already in the period of acute brucellosis;
  • organic lesions of the central nervous system are rarely observed;
  • lesions of the visceral organs in chronic brucellosis are usually manifested by disorders of the cardiovascular system;
  • residual brucellosis occurs mainly with functional rather than organic disorders.

Diagnosis of Brucellosis

Acute brucellosis is differentiated from diseases accompanied by prolonged fever (typhoid-paratyphoid diseases, malaria, tuberculosis, nonspecific systemic diseases, HIV infection, sepsis, lymphogranulomatosis, etc.). In acute brucellosis, the wrong nature of the temperature curve, the emergence of micro-polyadenopathy, chills, sweating, an increase in the size of the liver and spleen are noted. In some cases, fibrositis and cellulite are found in this period of the disease. Characteristic severity of clinical symptoms (especially high body temperature) with a fairly satisfactory state of health. In subacute and chronic brucellosis, rheumatism and rheumatoid arthritis, tuberculosis focal lesions, syphilitic and gonorrheal arthritis should be excluded. In these forms of brucellosis, periods of increased body temperature are replaced by epireksii episodes, the patients’ complaints are many and varied (pains in the joints, muscles, bones, paresthesias, etc.); focal multiorgan manifestations and allergic reactions, fibrositis and cellulitis are characteristic.

Laboratory diagnosis of brucellosis
To isolate the pathogen, blood cultures, punctates of lymph nodes, cerebrospinal fluid, and bone marrow are cultured. Due to the high contagiousness of Brucella, bacteriological diagnostics can be performed only in specially equipped (“regime”) laboratories. Isolation of pathogens is rarely carried out due to the duration and complexity of cultivation of the pathogen, as well as the relatively low seeding rate.

Recently, aggregate hemagglutination, RCA and RLA, ELISA, detecting Brucella antigens in biological media (primarily in the blood), have been introduced into practice.

Serological reactions are widely used (Wright’s RA, RSK, RNGA, RIF), which reveal an increase in the titers of specific antibodies in paired sera, the value of which increases in the presence of clinical signs of brucellosis. In chronic brucellosis, incomplete antibodies are detected in the Coombs reaction. Wright’s reaction is most informative in acute brucellosis. Recently, the reaction of lysis of Brucella under the influence of the patient’s serum has been successfully applied.

To obtain adequate results, the recommended simultaneous use of 3-4 serological methods of research (complex serodiagnosis).

Widespread intradermal allergy test Byurne with the introduction of brucellin (protein extract broth culture of brucella). Given the time required for the growth of specific body sensitization to Brucella antigens, its formulation is recommended no earlier than 20-25 days from the onset of the disease. The sample is considered positive if the diameter of the edema is more than 3 cm; the development of hyperemia and soreness at the injection site of brucellin are optional. A positive Byrne test is observed in all forms of brucellosis, including the latent course of the infectious process; she persists for years after reconvalescence. The sample can also be positive in individuals vaccinated with a live anti-brutal vaccine, and in laboratory workers who have been in contact with Brucella antigens for a long time.

With the introduction of brucellin, an additional sensitization of the organism occurs, and a pronounced local reaction (necrosis) may occur. In order to avoid these phenomena, neutrophil damage and leukocytolysis reactions are being introduced into practice. They are placed with the patient’s blood in a test tube without introducing an allergen into the body.

Brucellosis Treatment

The outpatient mode in the lungs and stationary in severe cases of the disease. Etiotropic therapy is effective in acute brucellosis; a smaller effect is observed when the process is activated in patients with subacute and chronic forms. Optimal consider the appointment of two antibiotics, one of which must penetrate the cell membrane. Apply one of the following combinations, taking into account contraindications (children under 15 years of age, pregnancy, lactation, epilepsy).

  • Rifampicin (600-900 mg/day) and doxycycline (200 mg/day) by mouth in a continuous course of at least 6 weeks. With relapse, repeat the treatment.
  • Doxycycline (100 mg 2 times a day) course for 3-6 weeks and streptomycin (1 g intramuscularly 2 times a day) for 2 weeks. This combination is more effective than the previous one, especially with spondylitis, but the drugs used are highly toxic.
  • Oflaksatsatsin (200-300 mg 2 times a day) by mouth and rifampicin in the above doses.

The duration of the use of drugs explains the advisability of controlling their intake by patients.

In the complex therapy of brucellosis, detoxifying agents are used according to the general principles of their use, ATP, methionine, and mild immunostimulants (dibazol, pentoxyl, thymalin, etc.). Anti-inflammatory drugs are widely used – non-steroidal anti-inflammatory drugs (indomethacin, Brufen, etc.). For pain (neuritis, neuralgia, vegetative pain), symptomatic therapy in the form of novocaine blockades is carried out with a 1% novocaine solution, intravenous administration of a 0.25% novocaine solution in increasing doses.

Use of glucocorticoids should be carried out with great care. Their purpose is forced in case of damage to the central nervous system (meningitis, meningoencephalitis), as well as in marked inflammatory changes (orchitis, neuritis, etc.) and the absence of the effect of other anti-inflammatory drugs.

The treatment (killed) brucellosis vaccine in recent years for the treatment of patients is used less and less because of its ability to cause immunity suppression, increase the possibility of relapse, cause autoimmune reactions and reactions to the ballast substances contained in it.

During the period of stable remission in case of chronic form and residual brucellosis, physical therapy, physiotherapy and spa treatment (UHF, quartz, paraffin baths, radon baths) are prescribed.

Brucellosis Prevention

Epidemiological surveillance is based on the results of an assessment of the epizootic and epidemic situation. In this regard, the timely exchange of information and joint activities of the veterinary and sanitary-epidemiological services for the identification of diseases among animals and people and the assessment of risk factors for their occurrence play an important role in the organization and conduct of anti-brutal measures.

Prevention and control of brucellosis are based on a set of veterinary-sanitary and medical-sanitary measures aimed at reducing and eliminating the incidence of brucellosis in farm animals. The livestock of animals in disadvantaged areas should be systematically examined for brucellosis using serological and allergological tests for the timely detection and elimination of sick animals. As an auxiliary measure in regions endemic for brucellosis, active immunization of brucellosis in animals is carried out by administering a live vaccine. Permanent and temporary livestock workers, as well as meat processing plants, are also subject to vaccination. Of great importance are the neutralization of raw materials and animal products, boiling and pasteurization of milk and dairy products, and other activities. Special attention should be paid to the premises where livestock are kept. After the removal of manure or removal of aborted fruits and the latter, the room should be disinfected with a 20% bleach solution, a 2% formaldehyde solution or a 5% solution of a soap-creosol mixture. Adolescents, pregnant women and people suffering from chronic diseases are not allowed to take care of animals. All persons allowed to work with animals must be provided with special clothing, the ability to use disinfectants is also necessary. Great importance is the strict observance of the rules of personal hygiene. At the same time, systematic preventive examination of personnel engaged in working with animals is carried out (at least once a year). An important role is played by the explanatory work on the danger of eating raw milk and uncooked cheeses and sheep cheese, the use of animal fur from brucellosis-unfriendly farms.

Activities in the epidemic focus
Hospitalization of patients is carried out only according to clinical indications, as a sick person is not an epidemiological hazard. Clinical supervision of the patient is carried out within 2 years after clinical recovery. Persons in contact with sick animals are subject to clinical and laboratory examination, repeated after 3 months. As an emergency prophylaxis, rifampicin (0.3 g 2 times a day), doxycycline (0.2 g 1 time a day), tetracycline (0.5 g 3 times a day) are prescribed orally for 10 days.

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