Brucellosis Genus And Species

[Lupita Calvi]

Althoughdomesticated animals are of particular importance, brucellosis is also found in wild animals that exist in herds (eg, bison or elk in North America and wild boar in Germany). [4] Humans have only a limited risk from wild animals, mainly because of lack of proximity or intimate contact and infrequent use of milk and meat products from these animals. Concerns have been voiced that interaction of wild animals with domesticated ones may lead to infection of agricultural herds, though supportive evidence is quite limited.

The global burden of human brucellosis remains enormous. The organism causes more than 500,000 infections per year worldwide. The annual number of reported cases in United States (about 100) has dropped significantly because of aggressive animal vaccination programs and milk pasteurization. Most US cases are now due to the consumption of imported unpasteurized dairy products from Mexico. Approximately 60% of human brucellosis cases in the United States now occur in California, Texas, Arizona, and Florida.

Interest in brucellosis has been increasing because of the growing phenomena of international tourism and migration, in addition to the potential use of Brucella as a biological weapon. [5] Familiarity with the manifestations of brucellosis and knowledge of the optimal laboratory studies are essential for the recognition of this reemerging zoonosis. B melitensis, B abortus, and B suis have been completely sequenced, and these sequencing data will help improve our understanding of the pathogenesis and the manifestations of this complex disease.

Definitive diagnosis of brucellosis is based on culture, serologic techniques, or both. Clinically, identification to the genus level is sufficient to warrant initiation of therapy. The particular Brucella species involved does not affect the choice of therapeutic agents; however, speciation is necessary for epidemiologic surveillance and requires more detailed biochemical, metabolic, and immunologic testing.

Brucellae are aerobic gram-negative coccobacilli that possess a unique ability to invade both phagocytic and nonphagocytic cells and to survive in the intracellular environment by finding ways to avoid the immune system. This ability helps explain why brucellosis is a systemic disease and can involve almost every organ system.

Brucella can gain entry into the human body through breaks in the skin, mucous membranes, conjunctivae, and respiratory and gastrointestinal (GI) tracts. Sexual transmission has not been convincingly documented. Ingestion usually occurs by way of unpasteurized milk; meat products often have a low bacterial load. In the United States, percutaneous needlestick exposure, conjunctival exposure through eye splash, and inhalation are the most common routes of entry.

Once within the bloodstream, the organisms quickly become intracellular pathogens contained within circulating polymorphonuclear cells (PMNs) and macrophages, making use of numerous mechanisms to avoid or suppress bactericidal responses. Animal data suggest that the lipopolysaccharide (LPS) coat (smooth in B melitensis, B abortus, and B suis; rough in B canis) is likely to play a role in intracellular survival, perhaps because of adenine and guanine monophosphate production, which inhibits phagosomal fusion and oxidative burst activity.

In addition, Brucella species have relatively low virulence, toxicity, and pyrogenicity, making them poor inducers of some inflammatory cytokines, such as tumor necrosis factor (TNF) and interferons. Furthermore, the bacteria do not activate the alternative complement system. Finally, they are thought to inhibit programmed cell death.

After ingestion by phagocytes, about 15-30% of brucellae survive. Susceptibility to intracellular killing differs among species, with B abortus readily killed and B melitensis rarely affected; these differences might explain the differences in pathogenicity and clinical manifestations in human cases of brucellosis. [6]

Brucellae that survive are transported into the lymphatic system and may replicate there locally; they also may replicate in the kidney, liver, spleen, breast tissue, or joints, causing both localized and systemic infection. Any organ system can be involved (eg, central nervous system [CNS], heart, joints, genitourinary system, pulmonary system, and skin); localization of the process may cause focal symptoms or findings. After replication in the endoplasmic reticulum, the brucellae are released with the help of hemolysins and induced cell necrosis.

Development of cell-mediated immunity is the principal mechanism of recovery. The host response to infection with B abortus is characterized by the development of tissue granulomas indistinguishable from those of sarcoidosis. In contrast, infection with the more virulent species (B melitensis and B suis) more commonly results in visceral microabscesses.

Although Brucella infection is primarily controlled through cell-mediated immunity rather than antibody activity, some immunity to reinfection is provided by serum immunoglobulin (Ig). Initially, IgM levels rise, followed by IgG titers. IgM may remain in the serum in low levels for several months, whereas IgG eventually declines. Persistently elevated IgG titers or second rises in IgG usually indicate chronic or relapsed infection. IgA antibodies are elaborated late and also may persist for very long intervals.

Of the 4 Brucella species known to cause disease in humans (B abortus, B melitensis, B canis, B suis), B melitensis is thought to be the most virulent and causes the most severe and acute cases of brucellosis; it is also the most prevalent worldwide. B melitensis may be acquired via exposure to animals or animal products or, in the case of laboratory technicians, to specimens from animals (including humans) whose tissues are operated upon or submitted for culture or pathologic analysis. [7]

B abortus is more widely distributed throughout the world than B melitensis is, but it is less pathogenic for both animals and humans. It has, however, been the most common cause of brucellosis in North America. This species gives rise to mild-to-moderate sporadic disease that rarely causes complications.

B suis has been the second most common cause of brucellosis in North America. Infection with this species gives rise to a prolonged course of illness, often associated with suppurative destructive lesions.

B canis infection has a disease course that is indistinguishable from that of B abortus infection. It infection has an insidious onset, causes frequent relapses, and does not commonly cause chronic brucellosis.

Slaughterhouse workers, primarily those in the kill areas, become inoculated with brucellae through aerosolization of fluids, contamination of skin abrasions, and splashing of mucous membranes. Farmers and shepherds have similar exposure risks, and they also have exposure to aborted animals. Veterinarians are usually infected by inadvertent inoculation of animal vaccines against B abortus and B melitensis. Laboratory workers (microbiologists) are exposed by processing specimens (aerosols) without special precautions.

Although brucellosis is still a reportable disease, it has become rare as a result of the institution of veterinary control measures (eg, routine screening of domestic livestock and vaccination programs). Approximately 100 cases are reported annually to the Centers for Disease Control and Prevention (CDC), mostly from California, Florida, Texas, Arizona, and Virginia. Incidental cases arise as a result of relaxation of surveillance standards or because of the increasing international exchange of foodstuffs and animals that may harbor Brucella organisms.

Most human cases of brucellosis in the United States are due to B melitensis. The B abortus and B suis species that have accounted for most brucellosis in North America are less likely to engender clinical disease in humans than B melitensis is. When disease develops in North Americans, it often does so with greater latency to onset and milder manifestations.

Brucellosis causes more than 500,000 infections per year worldwide. Its geographic distribution is limited by effective public and animal health programs, and the prevalence of the disease varies widely from country to country. [1] Overall, the frequency of brucellosis is higher in more agrarian societies and in places where handling of animal products and dairy products is less stringent.

European Union (EU) data suggest that there is a clear (though nonlinear) association between gross domestic product (GDP) and rates of brucellosis. According to these data, no countries with a GDP above 90% of the mean had an annual incidence of brucellosis higher than 10 cases per million population.

The heaviest disease burden lies in countries of the Mediterranean basin and Arabian Peninsula, and the disease is also common in India, Mexico, and South and Central America. Although some countries (eg, the United Kingdom and Ireland) have effectively controlled brucellosis, new areas of human brucellosis have emerged in areas such as central and southwest Asia.

Because of variable reporting, true estimates in endemic areas are unknown. Incidence rates of 1.2-70 cases per 100,000 people are reported. In very resource-poor countries (such as some African countries) in which brucellosis is endemic, control through animal slaughter is a poor option because of the fragile nature of the food supply. Brucellosis was recently reported in a tick species in the Inner Mongolia region of China. [8]

In a systematic review commissioned by the World Health Organization (WHO) with the goal of determining a disability weight for clinical manifestations of human brucellosis, the investigators proposed a disability weight of 0.150 for chronic localized brucellosis and 0.190 for acute brucellosis. [9] These estimates were based on disability weights from the 2004 Global Burden of Disease Study. Further study is required before a consensus can be reached.

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