Brucellosis

Brucellosis is a zoonotic bacterial infection caused by Brucella species, predominantly Brucella melitensis, associated with sheep and goats, and Brucella abortus, associated with cattle.

It is transmitted through consumption of unpasteurised dairy products or direct contact with infected livestock and their birth products. It produces a characteristic undulant febrile illness capable of affecting virtually any organ system.

There is a tendency toward chronic, relapsing disease if inadequately treated, given the organism's facultative intracellular survival within host macrophages. This necessitates prolonged combination antibiotic therapy to achieve durable cure.

Pathophysiology and epidemiology

• The organism survives and replicates within host macrophages, evading humoral immune clearance and explaining both the characteristic chronic, relapsing nature of inadequately treated infection and the requirement for antibiotic agents with good intracellular penetration as the basis of effective combination treatment regimens.
• Occupational exposure (farmers, veterinarians, abattoir workers) and consumption of unpasteurised dairy products (particularly soft cheese) in endemic regions (Mediterranean, Middle East, parts of Latin America, Central Asia) represent the principal transmission routes.
• The disease remains an important consideration in travellers returning from or residents of these endemic areas.

• Fever, characteristically undulant (waxing and waning over days to weeks, though this classical pattern is inconsistently observed in practice), together with drenching night sweats, malaise, arthralgia and weight loss, characterises the typical presentation, developing after an incubation period of one to several weeks.
• Osteoarticular involvement is the commonest focal complication, including peripheral arthritis, sacroiliitis (a particularly characteristic manifestation) and, less commonly, spondylitis, which can mimic tuberculous spinal infection both clinically and radiologically.
• Hepatosplenomegaly is common, and other focal manifestations include epididymo-orchitis, endocarditis (uncommon but disproportionately responsible for most brucellosis related mortality given the destructive valvular involvement), and, rarely, central nervous system involvement (neurobrucellosis) with meningitis or other neurological manifestations.
• A relevant dietary or occupational exposure history to unpasteurised dairy products or livestock should be actively sought in any patient with a compatible prolonged febrile illness, particularly with relevant travel or residence history in an endemic region.

• Blood culture, ideally with prolonged incubation given the fastidious, slow growing nature of this organism, can confirm the diagnosis, particularly during the acute febrile phase.
• Laboratory notification of suspected brucellosis is important both to optimise culture conditions and given the significant laboratory acquired infection risk associated with handling this organism.
• Serological testing (standard agglutination test, with a significant titre or, ideally, a fourfold rise between acute and convalescent samples supporting the diagnosis) is the mainstay of diagnosis in most clinical settings given the practical challenges of reliable culture confirmation.
• Polymerase chain reaction testing on blood offers an increasingly available, more rapid diagnostic alternative where accessible.
• Full blood count frequently shows a normal or mildly reduced white cell count with relative lymphocytosis, and imaging (magnetic resonance imaging for suspected spondylitis, echocardiography for suspected endocarditis) is directed according to any specific focal complication suggested by the clinical presentation.

• Combination antibiotic therapy is required given the high relapse rate with monotherapy, with doxycycline 100 mg twice daily for six weeks combined with rifampicin 600 to 900 mg once daily for six weeks representing a standard, widely used regimen.
• Doxycycline combined with streptomycin (1 g intramuscularly once daily for two to three weeks) or gentamicin represents an alternative combination with evidence of somewhat lower relapse rates compared with the doxycycline rifampicin combination. It requires the practical consideration of injectable aminoglycoside administration for the initial treatment period.
• Complicated disease, including spondylitis, neurobrucellosis or endocarditis, requires more prolonged combination therapy (often three drugs, and extended duration of several months, with endocarditis frequently additionally requiring surgical valve replacement given the destructive nature of brucella endocarditis and its poor response to antibiotic therapy alone.
• Children under eight years and pregnant women, in whom doxycycline is generally avoided, are treated with alternative regimens (such as rifampicin combined with co trimoxazole). Treatment is guided by specialist paediatric or obstetric infectious disease input given the complexity of balancing effective treatment against relevant drug safety considerations in these populations.
• Prevention through pasteurisation of dairy products, appropriate protective equipment for at risk occupational groups, and livestock vaccination programmes in endemic regions represents the primary public health preventive strategy, given the absence of an approved human vaccine.