Write a short note on brucellosis.

Aetiology

Brucellosis is a zoonosis caused by small, Gram-negative, facultative intracellular coccobacilli of the genus *Brucella*. Species differ in virulence:

• *B. melitensis* — goats and sheep; the most virulent and the commonest cause of human disease in India
• *B. abortus* — cattle and buffalo
• *B. suis* — pigs
• *B. canis* — dogs

Transmission:

• Ingestion of unpasteurised milk and milk products — raw milk, fresh soft cheese, paneer and khoa — the commonest route in India
• Direct contact with infected animals, their placenta, birth products, blood or urine through skin abrasions or conjunctiva — an occupational disease of farmers, shepherds, veterinarians, abattoir workers and dairy workers
• Inhalation of aerosols — a recognised laboratory-acquired infection, so the laboratory must be alerted when brucellosis is suspected
• Rarely person-to-person

Incubation is variable — 1–4 weeks, but may be months.

Pathogenesis

*Brucella* is an intracellular pathogen that survives and multiplies within macrophages, evading humoral immunity. It disseminates through the reticuloendothelial system, forming non-caseating granulomas in liver, spleen, marrow and lymph nodes. This intracellular, granulomatous behaviour explains three clinical facts: the chronic relapsing course, the requirement for prolonged combination therapy with intracellularly active drugs, and the frequent misdiagnosis as tuberculosis.

Clinical Features

Brucellosis is called "the disease of mistakes" because it mimics so many other illnesses.

• Fever — classically UNDULANT: rising in the evening and falling with drenching sweats, in waves lasting days to weeks with afebrile intervals.
• Drenching night sweats with a characteristic mouldy or wet-hay odour (a classical description).
• Profound fatigue, malaise, anorexia and weight loss.
• Arthralgia, myalgia and low back pain — prominent and often the presenting complaint.
• Hepatosplenomegaly and lymphadenopathy.
• Depression and neuropsychiatric symptoms out of proportion to the physical findings — a well-described feature.

Focal (localised) complications — in up to 30%:

Chronic brucellosis — symptoms persisting beyond a year, with fatigue, arthralgia and depression, often without positive cultures; overlaps clinically with chronic fatigue syndrome and is difficult to distinguish from relapse.

Investigations

• Blood culture — the definitive test. *Brucella* grows slowly; the laboratory MUST be informed so that cultures are held for a prolonged period (modern automated systems detect it within a week, but classical methods required 4–6 weeks). Alert the laboratory also because of the aerosol risk to technicians. Bone marrow culture has a higher yield and remains positive after antibiotics.
• Serology:
• Standard tube agglutination test (SAT) — a titre of ≥ 1:160 with compatible illness is significant in non-endemic areas; higher cut-offs are used in endemic regions because of background seropositivity. Paired sera showing a fourfold rise are more reliable.
• Rose Bengal plate test — a rapid, cheap screening test used widely in India.
• ELISA for IgM and IgG — IgM indicates acute infection, persistent IgG suggests chronic or relapsed disease.
• Beware the prozone phenomenon — very high antibody levels can give a false-negative agglutination result unless the serum is diluted.
• PCR — sensitive and rapid, useful in focal disease and for monitoring.
• Supporting: normal or low white cell count with relative lymphocytosis (leucocytosis is unusual and suggests another diagnosis), anaemia, thrombocytopenia, mildly raised transaminases, raised ESR and CRP.
• Imaging for focal disease: MRI spine and sacroiliac joints (the investigation of choice for spondylitis and sacroiliitis), echocardiography if endocarditis is suspected, and MRI brain and CSF examination for neurobrucellosis.

Management

Principles: *Brucella* is intracellular, so treatment requires a combination of at least two drugs with good intracellular penetration, given for a prolonged period. Monotherapy and short courses cause relapse, which is the commonest reason for treatment failure.

• Uncomplicated adult disease: doxycycline combined with rifampicin, or doxycycline with an aminoglycoside (streptomycin or gentamicin) — the latter combination has lower relapse rates. Treatment lasts at least 6 weeks.
• Focal disease — spondylitis, neurobrucellosis, endocarditis: triple therapy for a prolonged period (3 months or more); neurobrucellosis requires drugs that cross the blood-brain barrier (ceftriaxone, co-trimoxazole, rifampicin); endocarditis usually requires valve replacement in addition to prolonged antibiotics.
• Children under 8 and pregnancy: doxycycline is contraindicated — use co-trimoxazole with rifampicin.
• Monitor for relapse clinically and serologically for at least 2 years; relapse usually occurs within 6 months and responds to a repeat course.

Prevention

• Pasteurisation or boiling of milk — the single most effective public health measure
• avoidance of raw milk products
• animal vaccination and test-and-slaughter programmes
• protective clothing, gloves and eye protection for occupational groups handling animals and birth products
• safe disposal of placentas and aborted material
• laboratory biosafety precautions.