The genus Brucella and clinical manifestations of brucellosis

O gênero Brucella e as manifestações clínicas de brucelose

REVIEW

MICROBIOLOGY

The genus Brucella and clinical manifestations of brucellosis

O gênero Brucella e as manifestações clínicas de brucelose

Mariana Noyma Xavier^I; Érica Azevedo Costa^I; Tatiane Alves Paixão^I; Renato Lima Santos^I,1

^IDepartamento de Clínica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais (UFMG). Av. Antônio Carlos, 6627, 31270-901, Belo Horizonte, MG, Brasil. E-mail: [e-mail]

ABSTRACT

Infection with bacteria of the genus Brucella results in major economic and political impact by causing reproductive diseases in a significant number of domestic animal species. Moreover, it has a great social significance, since many species are capable of causing human infection, with severe consequences. Dissemination of knowledge on a specific disease is an essential step for its control. Considering that brucellosis is still the most prevalent zoonosis in the world, information about taxonomy, clinical signs in domestic animals and humans are crucial for attempting to reduce the prevalence of this disease. The recent isolation and characterization of non-classical species of Brucella indicates that a lot remains to be discovered about this genus. Nevertheless, due to the social-economic importance of brucellosis, this review aims to clarify points related to taxonomy of the genus and describe the clinical relevance of infection in humans and domestic animals.

Key word: Brucellosis, Brucella, taxonomy.

RESUMO

A infecção por bactérias do gênero Brucella apresenta grande importância econômica e política por causar doenças com impacto reprodutivo em um número significativo de espécies de animais domésticos. Além disso, possui grande importância social, já que várias espécies são capazes de causar infecção humana, com graves consequências. A difusão do conhecimento em relação a uma determinada doença é um passo essencial para o seu controle. Considerando-se que a brucelose ainda é a zoonose mais prevalente no mundo, informações sobre a taxonomia, os principais sinais clínicos nas diferentes espécies domésticas e os diferentes aspectos da doença humana são de importância crucial para a tentativa de diminuir a prevalência dessa enfermidade. O recente isolamento e a caracterização de espécies não clássicas de Brucella demonstram que ainda há muito a ser descoberto sobre esse gênero. Tendo em vista a importância socioeconômica da infecção por Brucella spp., esta revisão tem como objetivos esclarecer pontos relacionados à taxonomia do gênero, bem como descrever aspectos clínicos relevantes na infecção humana e nas diferentes espécies domésticas.

Palavras-chave: Brucelose, Brucella, taxonomia.

INTRODUCTION

Brucella spp. are Gram-negative, facultative intracellular pathogens. In nature, Brucella spp. are pathogens that do not multiply in the environment, but usually are transmitted directly from host to host. (GORVEL & MORENO, 2002). These organisms belong to the genus Brucella and cause brucellosis, which has variable clinical features that are strongly dependent on the bacterium and host species. Some of these organism can potentially cause human infections, resulting in one of the most important and widespread bacterial zoonosis in the world (SANTOS et al., 2005).

The genus Brucella was named after David Bruce, who first isolated the organism (then named Micrococcus melitensis) in 1887 from the spleen of a soldier suffering from a disease that was called Malta Fever (NICOLETTI, 2002; SANTOS et al., 2005). The zoonotic nature of brucellosis was demonstrated in 1905 by isolating Brucella from goat milk (NICOLLETI, 2002). Importantly, even as late as 1955, over 200 cases of brucellosis were caused by ingestion of a special cheese from Maltese goats (WYATT, 1999). In 1895, 1914, and 1966, Brucella species were isolated from aborted bovine, swine, and canine fetuses, respectively. In 1953, Brucella ovis was identified as a cause of epididymitis in rams (NICOLLETI, 2002). In the last 15 years 3 new non-classical species of Brucella has been identified (ROSS et al., 1994; FOSTER et al., 1996; SCHOLZ et al 2008a). The recent isolation and characterization of non-classical species of Brucella demonstrates that in spite of brucellosis being an old disease, there is still several aspects of these organisms and their associated diseases that remain unknown.

Taxonomy

Taxonomy is important to identify and classify in logical order the great diversity of living beings (MORENO et al., 2002). The genus Brucella belongs phylogenetically to the a-proteobacteria, a group that contains bacterial species with a wide variety of lifestyles, including symbionts of animals and plants (Wolbachia, Sinorhizobium), as well as obligate or facultative intracellular and extracellular pathogens, such as Rickettsia, Brucella and Agrobacterium (TSOLIS, 2002).

Six species are currently recognized within the genus Brucella: B. melitensis, B. abortus, B. suis, B. ovis, B. canis, and B. neotomae. This classification is mainly based on differences in biochemical characteristics, pathogenicity and host preferences (Table 1). Each of these species of Brucella is adapted to a specific host, but not exclusively (ALTON et al, 1975; ALTON 1990).

These marine mammal Brucella isolates have phenotypic and molecular features as well as host preferences that are clearly distinct from the six previously recognized species (JAHANS et al., 1997; CLAVAREAU et al., 1998; VERGER et al., 2000; WATSON et al., 2003; JACQUES et al., 2007). In 2000, a new species of the genus, with different features when compared to other known species, was isolated from the rodent Microtus arvalis, and named of B. microti (SCHOLZ et al., 2008a). Recently, a novel Brucella species has been isolated from post partum uteruses of pregnant baboons with history of stillbirth (SCHLABRITZ-LOUTSEVITCH et al., 2009).

In recent years, an important controversy has developed concerning the taxonomy of the genus Brucella. Although Brucella species can be differentiated by conventional phenotypic tests, theses species display a high degree of DNA homology in DNA-DNA hybridization assays (>90% identity), including the recently recognized marine mammal strains (VERGER et al., 1987, 1998, 2000). Therefore, it has been proposed that the genus Brucella should be a monospecific genus, with B. melitensis as the sole species and the other species should be considered as biovars (VERGER et al., 1985, 1987). Conversely, several molecular genotyping methods have been developed and applied to characterize Brucella species, indicating that significant DNA polymorphisms occur between species, which favor the current multi-species classification of Brucella (HALLING et al., 2005). Importantly, comparison of genome sequences of B. suis and B. melitensis demonstrated that exist clusters of genes that are unique in both species (designated genetic islands). It is reasonable to hypothesize that these unique genes may contribute to the differences in host specificity between Brucella species (TSOLIS, 2002). Furthermore, recent studies based on comparative whole genome analysis of several Brucella species indicate that there is limited divergence with a large number of pseudogenes. Interestingly, these genomic analyses do not clearly explain the host preferences of Brucella spp. (WATTAM et al., 2009; FOSTER et al., 2009). One of these studies indicates that at the B. ovis is the basal lineage to the rest of the Brucella spp., and that apparently most Brucella species diverged from their common B. ovis ancestor in the past 86,000 to 296,000 years (FOSTER et al., 2009).

It is noteworthy that the International Committee on Systematics of Prokaryotes, Subcommittee on the Taxonomy of Brucella has taken a clear position recommending a taxonomic classification that includes different species within the genus, either classical or new, which are still considered as individual species. Therefore, the genus currently group nine species, namely B. melitensis, B. abortus, B. suis, B. ovis, B. canis, B. neotomae, B. ceti, B. pinnipedialis, and B. microti (http://www.the-icsp.org/subcoms/Brucella.htm, Last modified 15 February 2008). The newly isolated Brucella species from baboons (SCHLABRITZ-LOUTSEVITCH et al., 2009) has not yet been classified nor included in the above mentioned list.

Brucella melitensis

B. melitensis is the most important etiologic agent of brucellosis in small ruminants, although cattle and other ruminants may also be infected. This species has three different biovars (BRICKER & HALLING, 1994) and it has the higher zoonotic potential within the genus, and thus it is recognized as the most important agent of human brucellosis (ALTON, 1990). This pathogen is widespread in several parts of the world, particularly the biovar 3 in Mediterranean and Middle Eastern countries (BANAI, 2002). Parts of Latin America are also seriously affected with biovar 1, especially Mexico, Peru and Northern Argentina (LUCERO et al., 2008). Importantly, B. melitensis have never been isolated in Brazil, where it is considered a foreign disease (POESTER et al., 2002).

In goats and sheep, B. melitensis infection causes abortion, reduced milk yield, and orchitis. Both sexually mature genders are equally susceptible. The predominant sign of acute infection is reproductive failure with abortion and birth of weak offspring. Abortions occur mostly during the last two months of gestation. Generally, transmission in sheep and goats occurs through materials excreted from the female genital tract (ALTON, 1990).

In goats, approximately two thirds of acute natural infections during pregnancy lead to infection of the udder and milk excretion of the bacteria during the subsequent lactation. Persistent infection of the udder is accompanied by intermittent shedding of the agent in milk. Inflammation of the mammary gland reduces milk production. However, clinical signs of mastitis are seldom detectable in naturally infected goats (ALTON, 1990).

B. melitensis is the most virulent Brucella for humans with a few organisms (10 to 100) being sufficient to cause a debilitating chronic infection (FUGIER et al., 2007). Humans acquire brucellosis mainly through ingestion of contaminated milk and unpasteurized dairy products. Contact of mucosas and skin abrasions with fluids and tissues from aborted fetuses of infected animals are also important sources of Brucella transmission (HARTIGAN 1997; FUGIER et al., 2007). Furthermore, people may be infected by inhalation of contaminated dust or aerosols. Thus, Brucella is one of the most common laboratory-acquired pathogens worldwide and is included in the potential biological weapon list (SANTOS et al., 2005).

Human infections with B. melitensis may have variable clinical manifestations and can become life threatening (COLMENERO et al., 2002). Although the majority of patients present with general symptoms, such as fever, malaise, sweats and lymphadenopathy and/or hepatosplenomegaly, a more severe form of the disease can be accompanied with osteo-articular signs (spondylitis, arthritis and osteomyelitis) or genitourinary tract changes (orchitis, epididymitis, glomerulonephritis and kidney abscesses) (HARTIGAN, 1997; COLMENERO et al., 2002). More severe complications comprise, in descending order of frequency, neurobrucellosis, liver abscesses, and endocarditis (FUGIER et al., 2007).

Brucella abortus

B. abortus has seven different biovars, namely biovars 1-6 and 9. Cattle is the preferential host for B. abortus, but the organism can be transmitted to buffaloes, camels, deer, dogs, horses, goats, sheep, and man (KUDI et al., 1997). In Brazil, bovine brucellosis due to B. abortus is the most prevalent Brucella infection (POESTER et al., 2002).

B. abortus causes primarily a disease in cows, being isolated from the udder, uterus, and lymphoid organs (POESTER et al., 2006). Outbreaks of brucellosis in dairy herds result in decreased milk production, increase somatic cell count in milk, occurrence of abortions and post-partum metritis (MEADOR & DEYOE, 1989). Late abortion is associated with necro-hemorrhagic placentitis (Figure 1) and fetal lesions, particularly fibrinous pleuritis and pericarditis and pneumonia (XAVIER et al., 2009). Infected cows usually abort only once, and subsequent gestations may generate calves that may be born weak or healthy. Some infected cows will not exhibit any clinical symptoms of the disease and give birth to normal calves. Transmission occurs mainly after abortion or parturition of infected cows via contaminated fetus, fetal membranes, and uterine secretions (SILVA et al., 2005).

Bulls can be infected but they do not readily spread the disease. B. abortus is a common cause of orchitis that is often associated with a vesiculitis and epididymitis. Infection in males may result in either temporary or permanent infertility, depending on the intensity of the lesions (EAGLESOME & GARCIA, 1992).

Brucella suis

Porcine brucellosis is an emerging disease caused by B. suis biovars 1, 2 and 3. It is mainly a disease of domestic and wild pigs but it can also affects other species such as cattle, horses, rabbits, dogs, and humans (EWALT et al., 1997, FRETIN et al., 2008). Biovars 1 and 3, which have pathogenic potential for humans, occur in Europe, North, South and Central America, Southern Asia and Pacific islands (FRYE et al., 1991). In Brazil, only the biovar 1 has been isolated, and there are just a few reports of B. suis in the country, with a seroprevalence of 0.34% in recent surveys (BRAZIL, 2000). Prevalence is very low in industrial swine production systems (CARVALHO NETA et al., 2005), but it may be quite high among backyard pigs slaughtered without sanitary inspection in Brazil (FREITAS et al., 2001).

Porcine brucellosis is a herd problem. Pigs of all ages can acquire the infection, but the disease primarily occurs in adults. B. suis is excreted in large numbers, for long periods in the semen and urine as well as in uterine discharges and milk being transmitted by both venereal and oral routes (ALTON, 1990).

B. suis infection in pigs often does not result in clinical signs, and therefore clinical diagnosis is very difficult. B. suis causes primarily a genital disease with abortions, but it also affects other organs, especially bones and joints (FELDMAN & OLSON, 1933). Brucellosis is the only disease in which reproductive failure in sows is accompanied by orchitis in boars and osteo-articular disorders such as arthritis, osteomyelitis, spondylitis and paralysis. The most important clinical signs in sows are infertility, irregular estrus, abortion in any stage of gestation and birth of weak piglets with a high neonatal mortality rate (DEYOE, 1967). Although orchitis and epididimitis are the most common lesions in boars, in some cases the infection is restricted to sexual glands and may not result in impaired fertility but can be an important source for shedding the organism in the semen (VANDEPLASSCHE et al 1967).

Brucella ovis

B. ovis infection has been reported in Australia, New Zealand, North and South America, South Africa, and many countries in Europe. It occurs in most sheep-raising regions of the world (BURGUESS, 1982). In Brazil, serological surveys in the state of Rio Grande do Sul demonstrated an average seroprevalence in positive sheep flocks of 13.4% (ranging from 6.9 to 50%) (MAGALHAES NETO & GIL-TURNES, 1996), whereas a seroprevalence of 5.57% has been reported in the Northeastern part of the country (CLEMENTINO et al., 2007).

Poor semen quality associated with decreased sperm motility and concentration as well as sperm abnormalities is often associated with early infection (CAMERON & LAUERMAN, 1976). B. ovis causes primarily epididymitis in sexually mature rams, and occasionally abortion in ewes (LAWRENCE, 1961). Later on, palpable lesions may develop in the epididymis, which may be unilaterally (Figure 2) or, occasionally, bilaterally affected (LAWRENCE, 1961). Conversely, some infected rams not develop palpable lesions (CARDOSO et al., 1989). In addition, a considerable number of infected rams may shed B. ovis in the semen for long periods, without any clinical sign of infection. Asymptomatic rams may develop only a mild subfertility or retain normal fertility, thus increasing the risk of spreading the infection in the herd. The transmission can occur by direct contact between rams kept in the same premises for prolonged periods of time (HUGHES et al., 1972; BROWN et al., 1973).

In ewes, B. ovis can uncommonly cause abortion associated with placentitis beginning at 30 days of gestation. Infected ewes may give birth to weak lambs with a high neonatal mortality rate (MEINERSHAGEN et al., 1974).

Brucella canis

Canine brucellosis is caused by B. canis that infects domestic dogs, wild carnivores and rarely other domestic animals (CARMICHAEL, 1990). It is especially common in Central and South America (MIRANDA et al., 2005). Infection of dogs with B. canis is widespread in Brazil, with prevalence ranging between 0.84 to 58.3% and it is concentrated mostly in the Southeast and South regions of the country (AZEVEDO et al., 2003; KEID et al., 2004; MIRANDA et al., 2005). Humans are susceptible to B. canis, but infections are uncommon and they are usually mild. Most natural human infections have been acquired through close contact with infected dogs. Laboratory infections have also been reported (CARMICHAEL, 1990).

Natural infections occur most commonly after ingestion of contaminated placental tissues or aborted fetuses, vaginal secretions from infected bitches, and during breeding. The organism may be shed for long periods in vaginal secretion after abortion and semen (CARMICHAEL & KENNEY, 1970; GEORGE et al., 1979).

In females, the most prominent clinical sign is abortion after 45-55 days of gestation in about 75% of the cases. Early embryonic death and reabsorption, or abortion 10-20 days after mating, may occur in some cases (CARMICHAEL, 1990). In males, the main sign is epididymitis and orquitis, which may be unilateral or bilateral, and often results in infertility. Semen from infected males usually contains large numbers of abnormal sperm and inflammatory cells, especially during the first three months after infection. Chronically infected males may have no sperm, or reduced numbers of immature sperm (CARMICHAEL & JOUBERT, 1988).

A particularity of B. canis infection is a prolonged bacteremia. Therefore, blood culture is a valuable diagnostic approach in this case (CARMICHAEL & KENNEY, 1970).

Brucella ceti and Brucella pinnipedialis

Since 1990, Brucella strains have been isolate from a variety of marine mammal species, including seal (Phoca vitulina), dolphins (Tursiops truncates; Delphinus delphis; Lagenorhynchus acutus; Stenella coeruleoalba), whale (Balaenoptera acutorostrata), and other species (EWALT et al 1994.; ROSS et al., 1994; FOSTER et el., 1996; CLAVAREAU et al., 1998; WYATT, 1999). These isolates have been classified as B. ceti and B. pinnipedialis, referring to isolates from cetaceans and seals, respectively (FOSTER et al., 2007). Transmission may occurs by direct contact trough mucosas and injured skin, oral route due to ingestion of other infected marine mammals (FOSTER et al., 2002), or by vertical or horizontal transmission to fetus since Brucella has been isolated in fetal tissues and in milk from dolphins (HERNANDEZ-MORA et al., 2008).

Pathological changes include skin abscesses, hepatic and splenic necrosis or/and histiocytic inflammation, meningitis, discospondilitis and abortion (FOSTER et al., 1996). Non suppurated meningoencephalitis has been described as the most consistent histological change in dolphins with neurological signs and positive serology and immumohistochemistry to Brucella sp. (GONZÁLEZ et al., 2002; HERNANDEZ-MORA et al., 2008). These marine Brucella species are capable of infecting terrestrial mammal species as demonstrated by experimental infection of cattle (RHYAN et al., 2001).

Marine Brucella species are capable of infecting humans causing neurological disorders (SOHN et al., 2003; HERNANDEZ-MORA et al., 2008). Transmission to human occurs probably through direct contact with marine mammals, although there reports of human brucellosis caused by marine isolates in which there was no evidences of contact of the patient with marine animals (SOHN et al., 2003; McDONALD et al. 2006; HERNANDEZ-MORA et al., 2008).

Brucella neotomae

B. neotomae was discovered by STOENNER & LACKMAN (1957) and approved as a new species of Brucella in 1980. B. neotomae is known to infect only the desert wood rat under natural conditions in the USA, and no other cases in addition to the original isolation have been reported.

Brucella microti

B. microti has been isolated from systemically infected common voles (Microtus arvalis) in South Moravia, Czech Republic in 2000 (SCHOLZ et al., 2008a). Later on, B. microti was isolated from mandibular lymph nodes of wild red foxes (Vulpes vulpes) hunted in Austria. SCHOLZ et al., 2008b). Furthermore, specific B. microti DNA sequences were recently detected in soil, but whether soil is the primary habitat of B. microti remains to be investigated (SCHOLZ et al., 2008c).

CONCLUSION

The genus Brucella includes several organisms, some of which with a very significant zoonotic potential, whereas some species poses significant risk for animal health and production. In the recent past years the there has been an increasing number of newly recognized species of Brucella.

Received 01.15.09

Approved 05.14.09

• ALTON, G.G. et al. Laboratory techniques in brucellosis 2.ed. Genebra: World Health Organization, 1975. 190p.
• ALTON, G.G. Brucella melitensis In: NIELSEN, K.H.; DUNCAN, J.R. Animal brucellosis Boca Raton: CRC 1990. p.383-422.
• AZEVEDO, S.S. et al. Inquérito sorológico e fatores de risco para a brucelose por Brucella canis em cães do município de Santana de Parnaíba, Estado de São Paulo. Pesquisa Veterinária Brasileira, v.23, n.4, p.156-160, 2003.
• BANAI, M. Control of small ruminant brucellosis by use of Brucella melitensis Rev.1 vaccine: laboratory aspects and field observations. Veterinary Microbiology, v.90, n.1-4, p.497-519, 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00231-6>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(02)00231-6.
• BRAZIL, MINISTÉRIO DA AGRICULTURA. Boletim de Defesa Sanitária Animal, v.30, p.39-50, 2000.
• BRICKER, B.J.; HALLING, S.M. Differentiation of Brucella abortus bv. 1, 2, and 4, Brucella melitensis, Brucella ovis, and Brucella suis bv. 1 by PCR. Journal of Clinical Microbiology, v.32, n.11, p.2660-2666, 1994.
• BROWN, G.M. et al. Studies on the transmission of Brucella ovis infection in rams. Cornell Veterinarian, v.61, p.265-280, 1973.
• BURGUESS, G.W. Ovine contagious epididymitis: a review. Veterinary Microbiology, v.7, p.551-575, 1982. Disponível em: <http://dx.doi.org/10.1016/0378-1135(82)990049-9>. Acesso em: 12 mai 2009. doi:10.1016/0378-1135(82)90049-9.
• CAMERON, R.D.A.; LAUERMAN, J.R. Characteristics of semen changes during Brucella ovis infection in rams. Veterinary Record, v.99, p.231-233, 1976
• CARDOSO, M.R.I. et al. Alterações da morfologia espermática em carneiros naturalmente infectados pela Brucella ovis Arquivo da Faculdade de Veterinária da UFRGS, v.17, p.39-48, 1989.
• CARMICHAEL, L.E. Brucella canis In: NIELSEN, K. et al. Animal brucelosis Boca Raton: CRC, 1990. p.335-350.
• CARMICHAEL, L.E.; KENNEY, R.M. Canine brucellosis: the clinical disease, pathogenesis and immune response. Journal of American Veterinary Medical Association, v.156, p.1726-1734, 1970.
• CARMICHAEL, L.E.; JOUBERT, J.C. Transmission of Brucella canis by contact exposure. Cornell Veterinarian, v.78, p.63-73, 1988.
• CARVALHO NETA, A.V. et al. Brucelose suína. Cadernos Técnicos de Veterinária e Zootecnia, n.47, p.57-65, 2005.
• CLAVAREAU, C. et al. Phenotypic and molecular characterization of a Brucella strain isolated from a minke whale (Balaenoptera acutorostrata). Microbiology, v.144, n.12, p.3267-3273, 1998.
• CLEMENTINO, I.J. et al. Inquérito soro-epidemiológico e fatores de risco associados à infecção por Brucella ovis em carneiros deslanados do semi-árido da Paraíba. Pesquisa Veterinária Brasileira, v.27, n.4, p.137-143, 2007.
• COLMENERO, J.D. et al. Chronic hepatosplenic abscesses in Brucellosis. Clinico-therapeutic features and molecular diagnostic approach. Diagnostic Microbiology and Infectious Disease, v.42, n.3, p.159-167, 2002. Disponível em: <http://dx.doi.org/10.1016/S0732-8893(01)00344-3>. Acesso em: 10 mai 2009. doi:10.1016/S0732-8893(01)00344-3.
• DEYOE, B.I. Pathogenesis of three strains of Brucella suis in swine. American Journal of Veterinary Research, v.28, n. 125, 951-957, 1967.
• EAGLESOME, M.D.; GARCIA, M.M. Microbial agents associated with bovine genital tract infection and semen. Part I. Brucella abortus, Leptospira, Campylobacter fetus and Tritrichomonas foetus Veterinay Bulletin, v.62, p.743-775, 1992.
• EWALT, D.R. et al. Brucella suis biovar 1 in naturally infected cattle: A bacteriological, serological and histological study. Journal of Veterinary Diagnostic Investigation, v.9, p.417-420, 1997.
• EWALT, D.R. et al. Characteristics of a Brucella species from a bottlenose dolphin (Tursiops truncates). Journal of Veterinary Diagnostic Investigation, v.6, p.448-452, 1994.
• FELDMAN, W.H.; OLSON, C. Spondylitis of swine associated with bacteria of the Brucella group. Archives of Pathology, v.16, p.195-210, 1933.
• FOSTER, G. et al. Brucella ceti sp. nov. and Brucella pinnipedialis sp. nov. for Brucella strains with cetaceans and seals as their preferred hosts. International Journal of Systematic and Evolutionary Microbiology, v.57, n.11, p.2688-2693, 2007. Disponível em: <http://dx.doi.org/10.1099/ijs.0.65269-0>. Acesso em: 12 mai 2009. doi:10.1099/ijs.0.65269-0.
• FOSTER, G. et al. Isolation of Brucella species from cetaceans, seals and an otter. Veterinary Record, v.138, n.24, p.583-586, 1996.
• FOSTER, G. et al. A review of Brucella sp. infection of sea mammals with particular emphasis on isolates from Scotland. Veterinary Microbiology, v.90, n.1-4, p.563-580, 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00236-5>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(02)00236-5.
• FREITAS, J.A. et al. Risco de brucelose zoonótica associado a suínos de abate clandestino. Revista de Saúde Pública, v.35, n.1, p.101-102, 2001.
• FRETIN D. et al. Brucella suis identification and biovar typing by real-time PCR. Veterinary Microbiology, v.131, n.3-4, p.376-85, 2008.
• FRYE, G.H. et al. Cooperative State Federal Brucellosis Erradication Program. Proceeding Annual Meeting of the United States Animal Health Association, v.97,p.138-154,1991.
• FUGIER, E. et al. Virulence factors in brucellosis: implications for aetiopathogenesis and treatment. Expert Reviews in Molecular Medicine, v.9, n.35, p.1-10, 2007. Disponível em: <http://journals.cambridge.org/action/displayAbstract?fromPage=online&aid=1595120>. Acesso em: 11 mai 2009. doi: 10.1017/S1462399407000543.
• FOSTER, J.T. et al. Whole-genome-based phylogeny and divergence of the genus Brucella Journal of Bacteriology, v.191, n.8, p.2864-2870, 2009. Disponível em: <http://dx.doi.org/10.1128/JB.01581-08>. Acesso em: 12 mai 2009. doi:10.1128/JB.01581-08.
• GEORGE, L.W. et al. Semen examination in dogs with canine brucellosis. American Journal of Veterinary Research, v. 40, p.1589-1595, 1979.
• GONZÁLEZ, L. et al. Chronic meningoencephalitis associated with Brucella sp. infection in live-stranded striped dolphins (Stenella coeruleoalba). Journal of Comparative Pathology, v.126, n.2-3, p.147-152, 2002. Disponível em: <http://dx.doi.org/10.1053/jcpa.2001.0535>. Acesso em: 11 mai 2009. doi:10.1053/jcpa.2001.0535.
• GORVEL JP, MORENO, E. Brucella intracellular life: from invasion to intracellular replication. Veterinary Microbiology, v. 90, n.1-4, p.281-297. 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00214-6>. Acesso em: 12 mai 2009. doi:10.1016/S0378-1135(02)00214-6.
• HALLING, S.M. et al. Completion of the genome sequence of Brucella abortus and comparison to the highly similar genomes of Brucella melitensis and Brucella suis Journal of Bacteriology, v.187, n.8, p.2715-2726, 2005. Disponível em: <http://dx.doi.org/10.1128/JB.187.8.2715-2726.2005>. Acesso em: 11 mai 2009. doi:10.1128/JB.187.8.2715-2726.2005.
• HERNANDEZ-MORA, G. et al. Neurobrucellosis in stranded dolphins, Costa Rica. Emerging Infectious Diseases, v.14, n.9, p.1430-1433, 2008. Disponível em: <http://dx.doi.org/10.3201/eid1409.071056>. Acesso em: 12 mai 2009. doi:10.3201/eid1409.071056.
• HUGHES, K.L. et al. Experimental Brucella ovis infection in ewe. Breeding performance of infected ewes. Australian Veterinary Journal, v.48, p.12-17, 1972.
• JACQUES I, et al. Oxidative metabolic profiles of Brucella strains isolated from marine mammals: contribution to their species classification. FEMS Microbiology Letter, v.270, n.2, p.245-249, 2007. Disponível em: <http://dx.doi.org/10.1111/j.1574-6968.2007.00675.x>. Acesso em: 12 mai 2009. doi:10.1111/j.1574-6968.2007.00675.x.
• JAHANS, K.L. et al. The characterisation of Brucella strains isolated from marine mammals. Veterinary Microbiology, v.57, n.4, p.373-382, 1997. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(97)00118-1>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(97)00118-1.
• KEID, L.B. et al. Brucella spp. isolation from dogs from commercial breeding kennels in São Paulo State, Brazil. Brazilian Journal of Microbiology, v.35, p.161-166, 2004.
• KUDI A.C. et al. Brucellosis in camels. Journal of Arid Environments, v.37, p.413-417, 1997. Disponível em: <http://dx.doi.org/10.1006/jare.1997.0277>. Acesso em: 12 mai 2009. doi:10.1006/jare.1997.0277.
• LAWRENCE, W.E. Ovine brucellosis. A review of the disease in sheep manifested by epididymitis and abortion. British Veterinary Journal, v.117, p.435-446, 1961.
• LUCERO, N.E. Brucella isolated in humans and animals in Latin America from 1968 to 2006. Epidemiology and Infection, v.136, n.4,p.6-503, 2008.
• MAGALHAES NETO, A.; GIL-TURNES, C. Brucelose ovina no Rio Grande do Sul. Pesquisa Veterinária Brasileira, v.16, p.75-79, 1996.
• McDONALD, W.L. et al. Characterization of a Brucella sp. strain as a marine-mammal type despite isolation from a patient with spinal osteomyelitis in New Zealand. Journal of Clinical Microbiology, v.44, n.12, p.4363-4370, 2006. Disponível em: <http://dx.doi.org/10.1128/JCM.00680-06>. Acesso em: 11 mai 2009. doi:10.1128/JCM.00680-06.
• MEADOR, V.P.; DEYOE, B.L. Intracellular localization of Brucella abortus in bovine placenta. Veterinary Pathology, v.26, n.6, p.513-515, 1989.
• MEINERSHAGEN, W.A. et al. Brucella ovis as a cause of abortion in ewes. American Journal of Veterinary Research, v.35, n.5, p.723-724, 1974.
• MIRANDA, K.L. et al. Brucelose canina. Cadernos Técnicos de Veterinária e Zootecnia, n.47, p.66-82, 2005.
• MORENO, E. et al. Brucella evolution and taxonomy. Veterinary Microbiology, v.90, n.1-4, p.209-227, 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00210-9>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(02)00210-9.
• NICOLETTI, P. A short history of brucellosis. Veterinary Microbiology, v.90, n.1-4, p.5-9, 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00209-2>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(02)00209-2.
• POESTER, F.P. et al. Brucellosis in Brazil. Veterinary Microbiology, v.90, n.1-4, p.55-62, 2002. Disponível em: <http://dx.doi.org/10.1016/S0378-1135(02)00245-6>. Acesso em: 11 mai 2009. doi:10.1016/S0378-1135(02)00245-6.
• POESTER, F.P. et al. Efficacy of strain RB51 vaccine in heifers against experimental brucellosis. Vaccine, v.24, n.25, p.5327-5334, 2006. Disponível em: <http://dx.doi.org/10.1016/j.vaccine.2006.04.020>. Acesso em: 12 mai 2009. doi:10.1016/j.vaccine.2006.04.020.
• RHYAN, J.C. et al. Seroconversion and abortion in cattle experimentally infected with Brucella sp. isolated from a Pacific harbor seal (Phoca vitulina richardsi). Journal of Veterinary Diagnostic Investigation, v.13, n.5, p.379-382, 2001.
• ROSS, H.M. et al. Brucella species infection in sea-mammals. Veterinary Record, v.134, n.14, p.359, 1994.
• SANTOS, R.L. et al. Brucelose:zoonose e bioterrorismo. Cadernos Técnicos de Veterinária e Zootecnia, v.47, p.83-98, 2005.
• SCHLABRITZ-LOUTSEVITCH, N.E. et al. A novel Brucella isolate in association with two cases of stillbirth in non-human primates - first report. Journal of Medical Primatology, v.38, p.70-73, 2009. Disponível em: <http://dx.doi.org/10.1111/j.1600-0684.2008.00314.x> . Acesso em: 12 mai 2009. doi:10.1111/j.1600-0684.2008.00314.x.
• SCHOLZ, H.C. et al. Brucella microti sp. nov., isolated from the common vole Microtus arvalis International Journal of Systematic and Evolutionary Microbiology, v.58, p.375-382, 2008a. Disponível em: <http://dx.doi.org/10.1099/ijs.0.65356-0>. Acesso em: 11 mai 2009. doi:10.1099/ijs.0.65356-0.
• SCHOLZ HC, et al. Isolation of Brucella microti from mandibular Lymph Nodes of Red Foxes, Vulpes vulpes, in Lower Austria. Vector Borne Zoonotic Disease 2008b, in press. Disponível em: <http://www.liebertonline.com/doi/pdfplus/10.1089/vbz.2008.0036?cookieSet=1>. Acesso em: 12 mai 2009. doi: 10.1089/vbz.2008.0036.
• SCHOLZ, H.C. et al. Isolation of Brucella microti from soil. Emerging Infectious Disease, v.14, n.8, p.1316-1317, 2008c. Disponível em: <http://dx.doi.org/10.3201/eid1408.080286>. Acesso em 11 mai 2009. doi:10.3201/eid1408.080286.
• SILVA, et al. Brucelose bovina. Cadernos Técnicos de Veterinária e Zootecnia, v.47, p.1-12, 2005.
• SOHN, A.H. Human neurobrucellosis with intracerebral granuloma caused by a marine mammal Brucella spp. Emerging Infectious Disease, v.9, n.4, p. 485-488, 2003. Disponível em: <http://www.cdc.gov/ncidod/EID/vol9no4/02-0576.htm>. Acesso em: 11 mai 2008.
• STOENNER, H.G.; LACKMAN, D.B. A new species of Brucella isolated from the wood rat, Neotomae lepida American Journal of Veterinary Research, v.18, p.947-951, 1957.
• TSOLIS, R.M. Comparative genome analysis of the alpha -proteobacteria: relationships between plant and animal pathogens and host specificity. Proceedings of the National Academy of Sciences of the United States of America, v,99, n.20, p.12503-12505, 2002. Disponível em: <http://dx.doi.org/10.1073/pnas.212508599>. Acesso em: 12 mai 2009. doi:10.1073/pnas.212508599.
• VANDEPLASSCHE, M. e al. Brucella suis infection and infertility in swine. Meded Veeartsenijsch Rijksuniv Gent, v.1,p.40, 1967.
• VERGER, J.M. et al. Classification of Brucella strains isolated from marine mammals using DNA-DNA hybridization and ribotyping. Research in Microbiology, v.151, n.9, p.797-799, 2000. Disponível em: <http://dx.doi.org/10.1016/S0923-2508(00)01145-1>. Acesso em: 11 mai 2009. doi:10.1016/S0923-2508(00)01145-1.
• VERGER, J.M. et al. Differentiation of Brucella melitensis, B. ovis and B. suis biovar 2 strains by use of membrane protein- or cytoplasmic protein-specific gene probes. Research in Microbiology, v.149, n.7, p.509-517, 1998.
• VERGER, J.M. et al. Taxonomy of the genus Brucella Annales de L'Institut Pasteur/ Microbiologie, v.138, n.2, p.235-238, 1987.
• VERGER, J.M. et al. Brucella, a monospecific genus as shown by deoxyribonucleic acid hybridization. International Journal of Systematic Bacteriology, v.35,p.292-295,1985.
• WATSON, C.R. et al. Isolation of Brucella species from common seals in Northern Ireland. Veterinary Record, v.153, n.5, p.155-156, 2003.
• WATTAM, A.R. et al. Analysis of ten Brucella genomes reveals evidence for horizontal gene transfer despite a preferred intracellular lifestyle. Journal of Bacteriology, 2009, in press. doi:10.1128/JB.01767-08.
• WYATT, H.V. Royal Navy surgeons and the transmission of brucellosis by goats' milk. Journal of Royal Naval Medical Service, v.85, n.2, p.112-117, 1999.
• XAVIER, M.N. et al. Pathology, immunohistochemistry and bacteriology of tissues and milk of cows and fetuses experimentally infected with Brucella abortus Journal of Comparative Pathology, v.140, n.2-3, p.149-157, 2009. Disponível em: <http://dx.doi.org/10.1016/j.jcpa.2008.10.004>. Acesso em: 11 mai 2009. doi:10.1016/j.jcpa.2008.10.004.

1

Autor para correspondência.

Publication Dates

• Publication in this collection
  21 Aug 2009
• Date of issue
  Oct 2009

History

• Received
  15 Jan 2009
• Accepted
  14 May 2009