BRUCELLOSIS

Brucellosis is disease of domestic and wild animals that is transmittable to humans (zoonosis). The array of nonspecific signs and symptoms of brucellosis led Simpson to remark "No disease, not excepting syphilis and tuberculosis, is more protean in its manifestations".

Historic reference

In 1859 Marston reported the first accurate description of ^brucellosis as a distinct entity. Marston, an assistant surgeon in the Royal Artillery, detailed his personal experience with "Mediterranian gastric remittent fever" while stationed in Malta during Crimean War. The causative agent remained unknown until 1886, when Bruce isolated Micrococcus (later Brucella) melitensis from the spleen of a fatal case of Malta fever. Zammit, a physician working with the Mediterranean Fever Commission (1904-1907) made observations that ultimately identified goats as the reservoir of brucellosis in Malta. Restrictions on the consumption of unpasteurized goats^milk led to a dramatic decline in the incidence of brucellosis among military personnel. Meanwhile in 1895, the Danish veterinarian Bernard Bang identified Bacillus (later Brucella) abortus as the cause of contagious abortions in cattle. The relationship between the agents of Malta fever and Bang's disease was not recognized until the 1920s from the work of American bacteriologist Alice Evans, who recommended renaming the genus Brucella to honor Bruce. In 1914 Traum isolated B. suis from aborting swine, and in 1966 Carmichael identified B. canis as the cause of contagious abortions in Beagle dogs. B. ovis (1953) and B. neotomae (1957) were isolated from sheep and wood rats, respectively, but neither is pathogenic for humans. In 1897, Wright first applied the serum agglutination test to the diagnosis of brucellosis; this test remains the standard against which other serologic methods are compared.

Etiology

Brucellae are small, gram-negative coccobacilli that are nonmotile and do not form spores. They grow aerobically, although B. abortus and B. ovis may require supplement for primary isolation. Nutritional requirements are relatively simple. Any high-quality peptone-based media enriched with blood or serum can be used; however,initial isolation may require prolonged (2-30 days) incubation. Brucella strains are always catalase-positive, but oxidase and urease activities and the production of H9S are variable. Traditionally, the major nomen species of Brucella have been differentiated by selective inhibition of growth on media containing dyes, such as thionin and basic fuchsin. A series of brucella-phages can also be used for typing smooth and nonsmooth brucellae.

45 Infectious diseases

Although six nomen species of Brucella are recognized, the results of DNA-DNA hybridization studies indicate that the genus comprises a single species (B. melitensis) with multiple biovars. Nevertheless, the nomen species designations are retained for taxonomic purposes and to avoid confusion. Phylogenetically, Brucella spp. appear to have a common origin with free-living, soil-dwelling organisms. Based on 16S rRNA sequences, Brucella spp. are classified in the a-2 group of the a-proteobacteria together with Agrohacterium tumefaciens and Bartonelta (Rochalimaea) henselae.

Chromosomal exchange among the brucellae by transformation, conjugation, or transduction is unknown, and no plasmids or temperate bacteriophages have been found. Studies using restriction endonuclease techniques indicate that B. melitensis contains two independent chromosomes. In addition, the genes for structural proteins, and functional enzymes have been cloned from B. abortus.

The major cell wall antigen of the brucellae is endotoxic lipo-polysaccharide (LPS), the structure of which accounts for serologic cross-reactions among smooth strains and with other gram-negative bacteria. The A and M antigens first described by Wilson and Miles have been characterized; the A chain consists of a homopolymer of l,2-linked-4-formamido-4,6-dideoxy-manno-pyranose residues, whereas the M chain is identical except that every fifth glycose residue is linked through the 1,3- rather than the 1,2-carbon atoms. Other outer membrane proteins resemble the OmpF and OmpA of Escherichia coli.

Epidemiology

Brucellosis is a zoonosis and virtually all infections derive directly or indirectly from animal exposure. The disease exists worldwide especially in the Mediterranean basin, the Arabian peninsula, the Indian subcontinent, and in parts of Mexico and Central and South America. Brucella abortus is found principally in cattle, but other species such as buffalo, camels, and yaks can be of local importance. Brucella melitensis occurs primarily in goats and sheep, although camels appear to be an important source in some countries. Brucella suis biovars 1-3 occur in domestic and feral swines and can cause abattoir-associated infections. Brucella suis biovar 4 is confined to reindeer and caribou or their predators in the tundra regions of subarctic. Brucella canis is found primarily in kennel-raised dogs; it is the least common cause of human brucellosis. In animals, brucellosis is a chronic infection that persists for the life of the animal. Localization of brucellae within the female and male reproductive organs accounts for the major clinical manifestations: abortion and sterility. Brucellae are shed in large numbers in milk, urine, and products of pregnancy from infected animals. The disease is transmitted to humans by direct contact with infected animals, their carcasses, or via ingestion of unpasteurized milk or milk products. Occupations associated with an increased risk of brucellosis include animal husbandry, veterinary medicine, abattoir work, meat inspection, and laboratory science. The ingestion of

Brucellosis 49

contaminated dairy products such as fresh goat's milk cheese is the source most likely to involve the general population. Meat products are rarely a source of brucellosis because they are not usually eaten raw and the numbers of organisms in muscle tissue are low. Unusual food "delicacies" such as blood and bone marrow have also been implicated in the transmission of brucellosis. Human-to-human transmission of brucellosis is extremely rare. Reports of sexual transmission are circumstantial, but the potential exists because brucellae have been isolated from human spermatozoa. Accidental self-inoculation with live Brucella vaccines is a risk for infection among ranchers and veterinarians.

Brucellosis in children is not rare as once thought, especially in areas where B. melitensis is enzootic. The manifestations of brucellosis are similar in neonates, children, and adults. It is not uncommon to observe outbreaks of the disease within families especially when a common food source is involved.

The role of wildlife in the epidemiology of brucellosis remains controversial. Wild hares in Europe are a reservoir for B. suis biovar 2 and can sporadically transmit the disease to domestic and feral swines.

Pathogenesis

Brucella usually gain entry to the body through abrasious in the skin in the course of handling infected animals or their carcasses. Accidental inoculation of the conjunctival the eyes is another route of infection that is especially common to veterinarians using live Brucella vaccines. Infect the respiratory tract is a special risk for abattoir work engaged in the slaughter of infected animals. Brucella melitensis is generally transmitted via ingestion of unpasteurizel products and appears to be more resistant than B. abortus to inactivation by gastric juices. Antacids and other drugs that decrease gastric acidity have been implicated in brucellosis transmitted by the oral route. The incubation time from exposure to the onset of symptoms is generally 2-3 weeks, although this may vary according to the inoculum size and perhaps the route of inoculation. Subclinical infection is suggested by the finding of antibodies to Brucella in individuals lacking symptoms or signs of disease.

Spink compared brucellosis to typhoid fever, with bacteria entering the lymphatics and replicating in regional lymph nodes. Hematogenous dissemination is then followed by localization of bacteria in organs rich in elements of the reticuloendothelia system (RES), including the liver, spleen, lymph nodes, bone marrow, and kidneys. Normal human serum has bactericidal activity against some Brucella spp. and is able to opsonize organisms for phagocytosis by polymorphonuclear (PMN) leukocytes. Strains of B. melitensis ,are generally more resistant to bacteriolysis, which may help explain the greater virulence of this species.

The brucellae are facultative intracellular pathogens that have the ability to survive and even multiply within the phagocytic cells of the host. The mechanisms by which the brucellae evade intracellular killing by PMN leukocytes is incompletely

50 Infectious diseases

understood; however, properties of the bacterial surface appear to enable it to escape detection. Factors believed to contribute to the intracellular survival of brucellae include the production of adenine and 5-guanosine monophosphate, which suppress the loperoxidase-H202-halide system of neutrophils, substances that inhibit phagosome-lysosome fusion in macrophages, and enzymes, such as superoxide dismutase, that defend against oxidative destruction. Brucellae are also ingested by macrophages of the RES,in which they initially survive and multiply. Growth of the pathogen in the spleen appears to be important for the induction of cell-mediated immunity, and bacterial cell wall endotoxin is a potent spleen mitogen.

The major virulence factor of the brucellae is smooth LPS. Nonsmooth strains usually have reduced virulence and are more susceptible to killing by normal serum from a variety of potential host species. Naturally nonsmooth species (B. cams and B. ovis) have a greatly restricted host range and a limited capacity to infect other species. Growth of B. abortus in placental tissues of cattle is stimulated by the presence of erythritol, which may explain the localization of brucellae in the genital tract of ungulates. Differences in host responses to various Brucella spp. is suggested by experimental animal studies in which B.abortus induces granulomas, whereas B. melitensis and B. suis produce tissue abscesses.

-

Anatomic pathology

The main factors of pathomorphology disorders are allergic reactions, which occur in places of brucella localization, and cause considerable focal changes. The most vulnerable are connective tissue, vessels, neurologic and lymphatic systems. Brucellosis granulomas form in acute period, gradually they are exposed to fibrous transition or sclerosis, though some granulomas can even suppurate. Such morphologic changes causes stable functional lesions of affected organs.

Clinical manifestations

The onset of symptoms of brucellosis is acute in approximately one-half of cases and insidious in the remainder. They usually begin from 2 to 8 weeks after inoculation. Symptoms are nonspecific (fever, sweats, malaise, anorexia, headache) and patients are sometimes misdiagnosed as suffering from "the flu". An "undulant" fever pattern is observed if go untreated for long periods of time. Some patients complain of malodorous sweat and a peculiar taste in their mouth. Depression is common, and often in excess of the seventy symptoms. In comparison to the myriad of somatic complaints, physical abnormalities may be few. Mild lymphadenopathy occurs in 10-20 % and splenomegaly in 20-30 % of cases. Hepatomegaly is reported in 20-60 %, but may vary with the species of brucellae or the presence of concomitant parasitic and protozoal infections in some populations.

Brucellosis is a systemic infection that can involve many organs and tissues. When patients present with manifestations involving a specific organ, some authors refer to this as "focal" or localized disease. However, there is little compelling

Brucellosis 51

evidence to suggest that such complications necessarily represent a distinct subset of patients. Nevertheless, when the infection involves the central nervous system or cardiovascular structures, such cases are difficult to treat and the outcome can be affected.

With appropriate treatment most patients recover within weeks to months, although a minority will experience a more delayed recovery. Since it is necessary to treat for prolonged periods of time, relapses are not uncommon, especially if therapy is discontinued prematurely. Relapse is not due to antibiotic resistance, since strains of brucellae isolated during relapse have been shown to have antimicrobial sensitivity patterns identical to the original infecting organism.

Since the onset of symptoms of brucellosis can be insidious, it is often difficult to distinguish acute from chronic forms of the disease. Spink defined chronic brucellosis as symptoms persisting for more than 12 months after the diagnosis was made. Most patients with chronic brucellosis have persisting foci of infection, such as suppurative lesions in bones, liver, or spleen. Some patients who have had brucellosis will continue to complain of nonspecific symptoms, such as fatigue, malaise, and depression, in the absence of objective evidence of infection. Although low levels of brucella antibodies may be present in their serum, they lack the elevated titers of IgG antibodies seen in chronic or relapsing brucellosis. Symptoms in such patients resemble the "chronic fatigue syndrome" and most likely represent a preexisting psychoneurosis.

Veterinarians using B. abortus strain 19 vaccine for immunizing cattle are at risk of accidental self-inoculation by needle stick or conjunctival splash. Although the vaccine has attenuated virulence for animals, it is capable of producing brucellosis in man. Inoculation of strain 19 into individuals with preexisting brucella antibodies generally causes localized inflammation at the injection site and transient fever and chills. This response is self-limited, lasting 24-48 hours, and is thought to represent hypersensitivity to brucella antigens. In contrast, individuals without preexisting antibodies are at risk of developing brucellosis if the inoculum of vaccine is sufficient.

Gastrointestinal tract. Brucellosis, like typhoid fever, is an enteric fever in which systemic symptoms generally predominate over complaints localized to the gastrointestinal tract. Nevertheless, when sought, alimentary tract complaints are elicited in up to 70 % of patients. These include anorexia, abdominal pain, vomiting, diarrhea, or constipation. Hyperemia of the intestinal mucosa with inflammation of Peyer's patches has been reported. Inflammation of the ileum has been documented radiographically and histologically in patients presenting with colitis caused by B. melitensis.

Because it is the largest organ of the RES, the liver is probably always involved in brucellosis; however, liver function tests are usually only slightly elevated. The spectrum of pathologic findings in brucella hepatitis is varied. Infection with B. abortus is characterized by granulomatous hepatitis

52 Infectious diseases

indistinguishable from sarcoidosis. The range of hepatic lesions caused by B. melitensis includes small aggregates of mononuclear cells within portal triads and larger aggregates extending into the parenchyma resembling viral hepatitis. Occasionally one finds collections of mononuclear cells including histiocytes forming loose granulomas. Brucella suis can cause suppurative abscesses involving the liver and spleen. Hepatic lesions resolve with anti-microbial therapy and, in the absence of other toxins, cirrhosis does not occur. Brucellosis is also a rare cause of cholecystitis, pancreatitis, and spontaneous bacterial peritonitis.

Skeletal. Osteoarticular manifestations of brucellosis are reported in 20-60 % of patients. The spectrum of bone and joint lesions includes arthritis, spondylitis, osteomyelitis, tenosynovitis, and bursitis. Sacroiliitis is the most commonly reported complication. Peripheral joints most often involved are hips, knees, and ankles. Brucella are a rare cause of sternoclavicular arthritis. Spondylitis is more common in elderly patients, and may result in paraspinal abscesses.

Radiographic abnormalities are late findings, whereas bone scans may detect inflammation early in the disease. Bone scan may be useful to differentiate hip from sacroiliac involvement. In cases of spondylitis, the earliest radiographic findings are straightening of the spine and disk space narrowing, followed by epiphysitis as the main sign of bone destruction. Computed tomography may reveal early signs of joint destruction and is especially useful to detect paraspinal abscess formation.

Analysis of synovial fluid from peripheral joint effusions reveals a predominance of mononuclear cells, and brucellae are isolated in about 50 % of cases. A reactive spondyloarthropathy has been described in some patients with brucellosis that is believed to be caused by circulating immune complexes; however, no association with a specific human leukocyte antigen (HLA) phenotype has been found.

Neurologic. Neurologic manifestations of brucellosis include meningitis, encephalitis, meningovascular complications, parenchymatous dysfunctions, peripheral neuropathy/radiculopathy, and psychosis. Rare cases of intracerebral and epidural abscesses have also been reported. Central nervous system involvement occurs in less than 5 % of patients and usually presents as acute or chronic meningitis. Meningitis can be the presenting manifestation or it can occur late in the course of brucellosis. There is little to distinguish it from other causes of meningitis except that nuchal rigidity occurs in less than one-half of cases. Cerebrospinal fluid (CSF) analysis reveals a lymphocytic pleocytosis, elevated protein content, and low to normal glucose level. Cultures of CSF are positive in less than one-half of cases, but the diagnosis is made by finding specific antibodies in the CSF.

Cardiovascular. Endocarditis occurs in less than 2 % of cases, but it accounts for the majority of brucellosis-related deaths. Before effective antimicrobial therapy, and surgery to replace infected heart valves, brucella endocarditis was nearly always fatal. The aortic valve is involved more often than the mitral valve, and aneurysms of the Valsalva sinus are especially common. Mycotic aneurysms of

Brucellosis 53

Mycotic aneurysms of the ventricles, brain, aorta, and other arteries have been reported. Rapid techniques to recover brucellae from blood, combined with echocardiography, have improved our ability to make a diagnosis. Although some cases have been treated successfully with antibiotics alone, combined medical and surgical treatment is usually required. Other cardiovascular complications include myocarditis and pericarditis.

Pulmonary. Respiratory symptoms are reported in up to 25 % of patients with brucellosis, after inhalation of contaminated aerosols or via bacteremic spread to the lungs. Respiratory involvement in brucellosis ranges from flulike symptoms with a normal radiograph, to bronchitis, bronchopneumonia, solitary or multiple nodules, lung abscesses, miliary lesions, hilar lymphadenopathy, and pleural effusions. Rarely are brucelle identified in stains or cultures of expectorated sputum.

Genitourinary. Although brucellae can be recovered from the urine of patients with brucellosis, genitourinary complications are rare. In men, unilateral epididymo-orchitis is the usual manifestation. Interstitial nephritis, exudative glomerulonephritis, and IgA nephropathy have also been reported. Pyelonephritis and abscess are rare complications and may resemble renal tuberculosis.

The principal manifestation of brucellosis in animals is abortion, and the presence of erythritol in placental tissues of susceptible animals is believed to play a role in the localizatiol of brucellae in the genital tract. Although brucellosis can cause abortion in women, there is little evidence that the incident higher than with other bacteremic infections.

Hematologic. The hematologic manifestations of brucellosis are variable, including anemia, leukopenia, or thrombocytopenia. Pancytopenia is rare, but may be associated with evidence of bone marrow erythrophagocytosis.

Cutaneous. Cutaneous manifestations of brucellosis have been reporte about 5 % of cases. Many transient, nonspecific lesions are described, including erythema nodosum, papules, rashes and ulcers. Petechiae, purpura, and cutaneous vasculitis have also been reported.

Diagnosis

Because the symptoms of brucellosis are nonspecific, it is imperative that the clinician obtain a detailed history, including occupation, exposure to animals, travel to enzootic areas, and ingestion of high-risk foods (unpasteurized dairy products). Somatic complaints (weakness, fatigue, malaise, anorexia, body aches, mental inattention, and depression) predominate over objective physical findings ([ever, malodorous sweats, lymphadenopathy, and hepatosplenomegaly).

Routine laboratory tests, such as the white blood cell (WBC) count may not suggest an infectious process. The WBC count is usually normal or depressed, rarely exceeding 10,000 cells/mm3. Anemia, leukopenia, and thrombocytopenia are common. The erythrocyte sedimentation rate (ESR) is variable and of little diagnostic value. The diagnosis of brucellosis is made with certainty when brucellae are recovered from blood, bone marrow, or other tissues. The rate of isolation

Infectious diseases

from blood varies from 15 to 70 % depending on the methods and the duration of incubation. Because brucellae are facultative intracellular pathogens, cultures of bone marrow may have a higher yield than blood. The Castaneda bi phasic technique is said to improve the yield while avoiding the need for I subcultures. Most clinical laboratories now employ rapid isolation methods (Bactec, DuPont Isolator, etc.), which are satisfactory for isolating brucellae from blood when they are maintained for a sufficient time (=30 days). The isolation time for Brucellae may be reduced by lysis-concentration techniques and other systems capable of detecting low concentrations of bacteria. Although preliminary studies with the polymerase chain reaction (PCR) using rRNA sequences show promise, further studies are needed to determine its role as a rapid diagnostic test for brucellosis. Once a microorganism is isolated, many clinical laboratories employ rapid identification systems based on the pattern of biochemical reactions. Biochemical profiles for Brucella are not included in all corn-Rial computerized data bases and brucellae have been identified as Moraxella.

In the absence of bacteriologic confirmation, serologic tests are used to make a presumptive diagnosis. Although a number of techniques have been developed to measure Brucella antibodies, the serum agglutination test (SAT) is the simplest and most widely used. The SAT measures the total quantity of agglutinating antibodies. Treatment of the serum with agents that reduce disulfide bonds (2-mercaptoethanol or dithiothreitol) permits the differentiation of immunoglobulin classes, since they destroy the agglutinability of IgM but do not alter IgG. No single titer of Brucella antibodies is always "diagnostic"; however, most cases of active infection will have titers 1:160 or greater, with IgG antibodies being present. A decline in IgG antibodies over time is prognostic of a good response to therapy, whereas a second rise in Ig G presages bacteriologic relapse. The antigen used in the SAT is prepared from B. abortus 1119, which reacts with other smooth brucellae (B. melitensis and B. suis). Since B. cants is a rough species lacking smooth O-polysaccharide, it is necessary to use antigen prepared from B. canis or B. ovis for serodiagnosis of canine brucellosis.

The use of standardized reagents and procedures in the performance and interpretation of Brucella serologic tests cannot overemphasized. Although enzyme-linked immunosorbent assay (ELISA) is reportedly more sensitive than the SAT, the lack of a standardized antigen makes it difficult to compare results from different laboratories. Reliable Brucella antigens for the SAT are commercially available; however, the antigen used in the "febrile agglutinins" screening test is insensitive unreliable for diagnosing brucellosis. False-negative reactions can occur if serum is not diluted beyond 1:320 owing to a prozone, and false positive reactions can occur with serum containing antibodies to the organisms of cholera, tularemia, and yersiniosis. In very rare instances, false-negative reactions result from the presence of serum-blocking substances. When so-called "blocking antibodies" are suspected, they can be detected using other serologic techniques,such as the Coombs test or a blocking antibody assay.

Brucellosis 55

Differential diagnosis

Polyorganic lesions and multiple clinical manifestations complicate diagnostics of brucellosis, especially on early stages (acute brucellosis). Acute beginning, triad of clinical signs (chill,fever,sweat),hepatosplenomegaly require differentiation with malaria, the same manifestations can be caused by sepsis. Continuous fever, hepatosplenomegaly, bradycardia, l^ucopenia also are characteristic signs of abdominal typhus. Diferential diagnosis with generalized form of tularemia, Q-fever, infectious mononucleosis, rheumatism, lymphogranulematosis also should be considered. Anyway, the final confirmation of diagnosis is possible only after

obtaining of results of laboratory methods of diagnostics.

Treatment

Treatment is carried out according to clinical period and gravity of disease course. At acute brucellosis, relapses of subacute and chronic forms the antibiotics are used, mainly: tetracyclin, aminoglygoside, tienamicines, levomycetin, rifampicin, which often are administered in combination for better effect. For example: streptomycin, gentamicin or kanamycin are used in combination with tetracyclin, doxycycline or rifampicin. The course of the combined antibiotic therapy lasts for 10 - 20 days and more. Then during 10 days inject levomycetin 0.5-1 (IM) or (IV) twice per day, levomycetin 0.5 4 times per day or tienam 0.5-0.75 every 12 hours in a muscle. One of schemes of treatment provides using of medicines of prolonged action - doxycycline 0.2 per day or 0.1 every 12 hours (PO) during 20 days, and then 0.1 daily during 10 days.

Antibiotics must be injected during all feverish period and during 10 - 12 days after normalization of body temperature. They act selectively only on the brucellas, freely circulating in blood and lymph. Taking into account, that brucellas are localized intracellularly, and also in connection with probability of relapses, through 7-10 days antibiotic therapy will be repeated by preparation which was not prescribed yet, during 10-12 days.

Preparation of a choice may be bactrim (trimetoprim sulfamethaxazol) which component "trimethoprim" influences on intracellularly posed brucellas. One of the approved circuits provides indication of bactrim ( 2 tablets per day during 20 days then carry out 10-day course of treatment by tetracyclinum). The best results are received at a combination of biseptole with rifampicin.

Antibacterial therapy is expedient for combining with an antibrucella immunoglobulin in ampoules on 1.5 mL by two or three courses with an interval of 20 days. Each course consists of Ç (²Ì) injections of immunoglobulin 2-4-6 ml, 2-3 days.

The basic method of treatment of chronic brucellosis, which manifests with focal disorders, is the vaccinotherapy. It consists of the medical polyvalent brucellous inactivated vaccine. Two courses of accine intravenous injection are most effective. Instead of a medical vaccine it is possible to use a brucellin.

56 Infectious diseases

Among nonspecific medicines prescibe butadion, acetylsalicylic acid, ibufrofen, indomethacin, mefenemic acid.

In an exudative-proliferative stage of inflammation indicate rheopyrinum, in proliferative-sclerotic ortophen (voltaren). Glucocorticoids are indicated at disorders of central and perepheric nervous system, at myocarditis, orchitis and at other expressed focal changes. Prednisolone is indicated in dose 20-30 mg per day during 2-3 weeks. Among antihistaminics use dimedrole, suprastin, tavegil etc. In complex treatment prescribe an acid ascorbic, vitamin preparations of group B, rutin.

At calming infectious process, chronic and residual brucellosis - methyluracil, natry nucleinic, prodigiosan, polybiolin, polyoxydony immuno-and biostimulators timogen or T- activin are indicated. For a resorption of proliferation of a connecting tissue and acceleration of neogenesis use lydasa, ronidas, gumisole, rumalone, an extract of aloe. A pharmacotherapy is widely combined with physiotherapeutic methods.

Prophylaxis

Prevention of brucellosis in men depends on the control or eradication of the disease in domestic animals. In addition, calfhood immunization using B. abortus strain 19 vaccine and routine pasteurization of milk have resulted in a dramatic decline in the incidence of human brucellosis. The use of B. melitensis strain Rev-1 vaccine in countries where caprine brucellosis is enzootic has resulted in a decrease in human brucellosis due to this species. Although no effective vaccine exists for B. suis, improved swine husbandry practices have lowered the incidence of porcine brucellosis. In the past, live-attenuated brucella vaccines were used for human immunization in some countries; however, they were restricted to high-risk personnel in areas of high endemicity. No vaccine is coursely available for human use. Laboratory-acquired brucellosis can be prevented by adherence to biosafety level 3 precautions.

Control questions:

1. Etiology of brucellosis.

2. Epidemiology of brucellosis.

3. Pathogenesis of brucellosis.

4. Anatomic pathology of disease.

5. Main clinical symptoms and signs of brucellosis.

6. Laboratory methods of brucellosis diagnostics.

7. Criteria of brucellosis diagnosis.

8. Differential diagnosis of brucellosis.

9. Treatment of brucellosis.

10. Prevention of brucellosis.

Shigellosis

Date: 2014-12-21; view: 1743