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MEDICAL BIOLOGY: ON BRUCELLOSIS

The following points are made by G. Pappas et al (New Engl. J. Med. 2005 352:2325):

1) Brucellosis, like tuberculosis, is a chronic granulomatous infection caused by intracellular bacteria and requires combined, protracted antibiotic treatment. The disease causes much clinical morbidity as well as a considerable loss of productivity in animal husbandry in the developing world. In this era of international tourism, brucellosis has become a common imported disease in the developed world.

2) Brucellosis has been present for millennia[1] and has managed to elude eradication, even in most developed countries.[2,3] A high prevalence in certain geographic areas is well recognized, although largely underestimated. The relationship between the disease and individual socioeconomic status is exemplified in the United States, where programs to eradicate brucellosis have successfully limited the annual incidence of the disease, which now occurs predominantly in California and Texas (which account for more than half of the US cases), with relatively high rates of incidence in North Carolina, Illinois, Florida, Wyoming, Iowa, and Arizona. The disease usually presents in Hispanic populations and is probably related to the illegal importation of unpasteurized dairy products from neighboring Mexico, where the disease is endemic.[4,5]

3) The bacterium brucella belongs to the {alpha}2 subdivision of the proteobacteria, along with ochrobactrum, rhizobium, rhodobacter, agrobacterium, bartonella, and rickettsia. The traditional classification of brucella species is largely based on its preferred hosts. There are six classic pathogens, of which four are recognized human zoonoses. The presence of rough or smooth lipopolysaccharide correlates with the virulence of the disease in humans. Two new brucella species, provisionally called Brucella pinnipediae and B. cetaceae, have been isolated from marine hosts within the past few years.

4) Brucella is a monospecific genus that should be termed B. melitensis, and all other species are subtypes, with an interspecies homology above 87 percent. The phenotypic difference and host preference can be attributed to various proteomes, as exemplified by specific outer-membrane protein markers. All brucella species seem to have arisen from a common ancestor to which B. suis biotype 3 shares particular similarity. Although the scientific accuracy of this classification cannot be disputed, its practicality has been under scrutiny. The complete sequencing of the B. melitensis genome was achieved in 2002. The complete sequencing of B. abortus and B. suis has recently been accomplished as well.

References (abridged):

1. Capasso L. Bacteria in two-millennia-old cheese, and related epizoonoses in Roman populations. J Infect 2002;45:122-127

2. Corbel MJ. Brucellosis: an overview. Emerg Infect Dis 1997;3:213-221

3. Young EJ. An overview of human brucellosis. Clin Infect Dis 1995;21:283-289

4. Fosgate GT, Carpenter TE, Chomel BB, Case JT, DeBess EE, Reilly KF. Time-space clustering of human brucellosis, California, 1973-1992. Emerg Infect Dis 2002;8:672-678. [Erratum, Emerg Infect Dis 2002;8:877.]

5. Chang MH, Glynn MK, Groseclose SL. Endemic, notifiable bioterrorism-related diseases, United States, 1992-1999. Emerg Infect Dis 2003;9:556-564

New Engl. J. Med. http://www.nejm.org

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Related Material:

ON BRUCELLOSIS AND THE BRUCELLA GENOME

The following points are made by V.G. DelVecchio et al (Proc. Nat. Acad. Sci. 2002 99:443):

1) Brucellosis is a major zoonotic disease that causes abortion in wild and domestic animals and Malta or undulant fever in humans. Although the spread of the disease is controlled in developed countries by livestock testing, vaccination, and slaughter programs, brucellosis is a major problem in the Mediterranean region and parts of Asia, Africa, and Latin America, where it causes severe economic losses (1).

2) The disease is transmitted to humans by consumption of nonpasteurized milk and milk products or by direct contact with infected animals or carcasses (2, 3). On contact, Brucellae penetrate the skin or mucosal membranes and enter the lymph nodes, which become hemorrhagic, resulting in bacteremia, which facilitates dissemination throughout the body. During the early phase of infection, Brucellae invade macrophages, adapt to the acidic environment, and multiply in the vacuolar compartments (4). Like Salmonella, Mycobacterium, and Legionella, Brucella prevents phagosome/lysosome fusion (5). The infection involves many tissue types and organs. Symptoms, which may include fever, chills, headache, pain, fatigue, dementia, and arthritis, are nonspecific. The infection can be treated with combinations of antibiotics such as doxycycline and streptomycin or doxycycline and rifampin. Vaccines against Brucellae have varying degrees of success in controlling the disease; however, human vaccines are not available, and the animal vaccines currently in use are pathogenic to humans.

3) The authors report that the genome of B. melitensis (strain 16M) was sequenced and found to contain 3,294,935 base pairs distributed over two circular chromosomes of 2,117,144 bp and 1,177,787 base pairs encoding 3,197 open reading frames.

4) In a commentary on this work, E. Moreno and I. Moriyon (Proc. Nat. Acad. Sci. 2002 99:1) make the following points:

a) On September 23, 1905, a cargo carrying 60 goats from Malta arrived in New York. The herd was kept in quarantine because of several deaths that occurred during the journey. Crewmen, an agent from the U.S. Bureau of Animal Industry, which was responsible for the shipment, and a woman who drank milk that "escaped" from the quarantine station displayed the characteristic symptoms of "Mediterranean fever." Lieutenant Colonel David Bruce, a physician of the Royal Army, who discovered "Micrococcus melitensis " in 1887 in infected British soldiers residing in Malta, had forewarned the U.S. sanitary authorities about the risk of "Mediterranean fever" by importing goats from Malta. In November 1906, after isolation of "M. melitensis," the goats were destroyed.

b) Almost 100 years after this episode, the genome sequence of Brucella melitensis (renamed after David Bruce) has been resolved by DelVecchio et al. (2002), bringing new light to the understanding of the biology of this pathogen. The disease, known as brucellosis, is found in all continents, affecting mainly low-income countries; in addition, it constitutes a contemporary concern because Brucella strains are potential agents of biological warfare.

References (abridged):

1. Corbel, M. J. (1997) Emerg. Infect. Dis. 3, 213-221

2. Young, E. J. (1983) Rev. Infect. Dis. 5, 821-842

3. Young, E. J. (1995) Clin. Infect. Dis. 21, 283-289

4. Porte, F. , Liautard, J. P. & Kohler, S. (1999) Infect. Immun. 67, 4041-4047

5. Baldwin, C. L. & Winter, A. J. (1994) Immunol. Ser. 60, 363-380

Proc. Nat. Acad. Sci. http://www.pnas.org

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