Brucella Species (Brucellosis)

Pathogen and Pathogenesis

Brucellae are small, gram-negative coccobacilli that lack endospores, capsules, or native plasmids. Their metabolism is oxidative, and all strains are aerobic, although some strains can require added carbon dioxide for primary isolation. Various media support the growth of brucellae in vitro; however, prolonged incubation (≥21 days) may be required. Rapid isolation techniques such as Bactec (Becton, Dickinson, Franklin Lakes, NJ) systems have shortened the time for primary isolation. Culture of bone marrow may have a higher yield than routine cultures of blood. Brucella strains are always catalase positive, but production of oxidase, urease, and hydrogen sulfide is variable. Rapid identification systems have misidentified Brucella as Moraxella spp., Haemophilus spp., and Ochrobactrum spp. Because of the risk of laboratory-acquired infection, biosafety level 3 practices, containment equipment, and facilities are recommended for the handling of suspected Brucella cultures. ^,

Brucella spp. contain an unconventional cell wall lipopolysaccharide that differs from classical enterobacterial endotoxin such as Escherichia coli . For example, B. abortus lipopolysaccharide possesses a diaminoglucose backbone (rather than glucosamine); acyl groups are longer (C18–C19, C28 rather than C12 and C14) and are linked to the core by amide bonds (rather than ester and amide bonds). These properties result in a lipid A with low endotoxic activity, resistance to degradation within macrophages, and protection against the host’s toll-like receptor 4–mediated innate immune response. ^,

Brucella spp. are facultative intracellular pathogens that can survive and replicate within host phagocytic cells. Innate and acquired humoral immunity plays some role in resistance to infection; however, cell-mediated immunity is the major mechanism of recovery from brucellosis. Coincident with acquired cellular resistance, hypersensitivity to brucella antigens develops, and this may contribute to some of the clinical manifestations of the disease.

Epidemiology

Brucellosis exists worldwide but is especially prevalent in the Mediterranean basin, the Arabian peninsula, the Indian subcontinent, and in parts of Mexico, Central America, and South America. It also has reemerged in Eastern Europe following a decline in veterinary and human health services. ^, Although brucellosis was once common in the US, eradication of bovine brucellosis has reduced the incidence of human infection to <0.5 cases per 100,000 population. In states bordering Mexico, where B. melitensis remains enzootic in goats, brucellosis is 8 times more prevalent than elsewhere in the country, and childhood brucellosis has become an imported disease.

Humans are accidental hosts, contracting the disease by direct contact with infected animals, their carcasses, or their milk. Farmers, veterinarians, abattoir workers, and laboratory personnel are at increased risk of infection. Increasingly, cases of brucellosis are linked to ingestion of fresh goat milk cheese imported from countries where the disease is enzootic. In some countries, brucellosis has been linked to the ingestion of raw camel milk or cheese. Consequently, people of all ages can be infected, and they may have no history of direct animal contact. In the evaluation of patients with unexplained fever, clinicians should obtain a thorough history of travel, food consumption, occupation, and avocations.

The usual routes of transmission of brucellosis from animals to humans are listed in Table 161.2 . Human-to-human transmission is rare, but cases of apparent venereal transfer have been reported. ^, Brucellosis during pregnancy poses a risk of spontaneous abortion ^, and rarely may present a risk to hospital personnel involved in delivery. ^, Although rare, neonatal brucellosis has been reported, and transmission could occur through the placenta of an infected mother or by breast milk following delivery. ^, Once considered rare in children, brucellosis now is recognized commonly in countries where B. melitensis is enzootic. In such areas, fresh milk from goats and camels is fed to children, and newborn animals often share family living space, thus providing conditions favorable to transmission. In countries where brucellosis is no longer common, failure of physicians to consider the diagnosis may contribute to the low reported incidence of childhood infection.

Clinical Manifestations

Brucellosis is a systemic illness characterized by nonspecific complaints with a paucity of abnormal physical findings. The onset can be insidious or acute, with symptoms generally beginning 2–4 weeks after exposure. Series of childhood brucellosis from countries where B. melitensis is endemic indicate that fever, malaise, lethargy, and joint pains are the most common complaints, and a typical presentation is a child with fever who refuses to bear weight on an extremity ( Table 161.3 ). Compared with adults, the lower proportion of reported general symptoms (e.g., sweats, chills, headache) in children could reflect the difficulty in obtaining accurate histories from this age group.