Brucellosis: Complete Clinical Approach to a Zoonotic Intracellular Infection

Clinical Medicine Year 3 • diagnosis, focal disease, treatment and One Health prevention

Laboratory safety: Tell the laboratory when brucellosis is suspected. Brucella can be aerosolised during processing and is a recognised laboratory-acquired infection. Handle cultures using appropriate biosafety procedures and involve public-health/veterinary services.

Why brucellosis is easy to miss

Brucellosis may be an acute febrile illness, an undulating fever lasting months, or a focal infection of the spine, sacroiliac joint, testis, brain or heart. It often resembles malaria, tuberculosis, enteric fever, endocarditis or inflammatory rheumatologic disease. A precise animal, food and occupational history is often the diagnostic turning point.

Learning outcomes

Identify the medically important Brucella species, reservoirs, routes of transmission and occupational risks.
Explain intracellular survival, reticuloendothelial dissemination and focal complications.
Recognise acute, subacute, chronic, relapsing and localised disease.
Select blood cultures, serology, PCR and site-specific specimens while protecting laboratory staff.
Construct combination treatment plans for uncomplicated and focal disease, including pregnancy and children.
Prevent infection through pasteurisation, protective equipment, animal control, safe abortion-material disposal and One Health collaboration.

1. Definition and causative species

Brucellosis is a zoonotic infection caused by small, gram-negative, non-motile, non-spore-forming coccobacilli of the genus Brucella. The bacteria are facultative intracellular organisms that survive within macrophages and cause prolonged bacteraemia and granulomatous inflammation.

Species	Main animal reservoir	Human exposure pattern
B. melitensis	Goats and sheep	Unpasteurised dairy, small-ruminant births; often severe human disease
B. abortus	Cattle and buffalo	Raw milk, abattoir and veterinary exposure
B. suis	Pigs and wild swine	Hunters, butchers, pig farmers; abscesses and focal disease
B. canis	Dogs	Breeders, kennel workers and contact with reproductive material
Other species	Marine mammals and wildlife	Rare, occupational or travel-associated disease

2. Reservoirs and transmission

2.1 Food-borne transmission

Unpasteurised milk, fresh cheese, yoghurt, ice cream and other dairy products can contain organisms. Meat is a less efficient route when thoroughly cooked, but handling raw meat or organs can inoculate broken skin.

2.2 Occupational and environmental exposure

Farmers, herders, veterinarians, animal-health workers, abattoir staff, butchers, slaughterhouse cleaners, laboratory workers, hunters and people assisting animal births have the highest risk. Placenta, aborted fetuses, lochia, vaginal secretions, milk and contaminated bedding may contain large numbers of bacteria. Aerosols can be generated in slaughter, necropsy, laboratory culture or cleaning.

2.3 Person-to-person transmission

Human transmission is uncommon, but has been reported through breastfeeding, sexual contact, blood transfusion, tissue transplantation and perinatal exposure. A patient with brucellosis does not usually require respiratory isolation, but standard precautions and safe handling of blood/secretions are essential.

3. Pathogenesis and immunology

Brucella enters through the gastrointestinal tract, conjunctiva, respiratory tract or skin breaks. It is taken up by macrophages and uses intracellular trafficking and stress-response mechanisms to avoid killing. It travels to lymph nodes, liver, spleen, bone marrow and reproductive organs. Cell-mediated immunity forms granulomas and may suppress but not eradicate the organism.

Bacteraemic phase: fever, chills, sweats, malaise and hepatosplenomegaly.
Reticuloendothelial persistence: organisms survive in macrophages, producing prolonged or relapsing fever.
Focal seeding: bacteria localise in osteoarticular tissues, testes, CNS, heart valves, liver, spleen and lungs.
Relapse: incomplete therapy, inadequate tissue penetration, undrained abscess or an unrecognised focus permits recurrence.

4. Clinical forms

4.1 Acute brucellosis

Sudden or gradual fever, chills, drenching sweats, severe fatigue, headache, anorexia, myalgia and arthralgia may follow exposure. The fever can rise and fall (“undulant fever”), but this classic pattern is not required.

4.2 Subacute and chronic disease

Patients may complain of months of fatigue, insomnia, irritability, poor concentration, low back pain, depression, weight loss and intermittent fever. Chronic disease can be disabling even when inflammatory markers are modest.

4.3 Osteoarticular brucellosis

Sacroiliitis, spondylitis, vertebral osteomyelitis, peripheral septic arthritis and bursitis are the commonest focal complications. Back pain, hip/buttock pain, restricted movement, night pain, radiculopathy or weakness warrants MRI or specialist imaging. A painful joint requires aspiration to distinguish Brucella, pyogenic infection, TB and crystal disease.

4.4 Genitourinary disease

Epididymo-orchitis, testicular pain/swelling, prostatitis, infertility and pelvic inflammatory symptoms occur through direct or haematogenous seeding. Testicular torsion must be excluded urgently in acute scrotal pain.

4.5 Neurobrucellosis

Headache, meningism, confusion, cranial-nerve palsy, hearing loss, seizures, focal deficits, myelitis or psychiatric change may occur. CSF often shows lymphocytic inflammation and raised protein, but results can be atypical. Treatment is longer and requires agents with CNS penetration.

4.6 Endocarditis

Endocarditis is uncommon but accounts for a disproportionate number of deaths. Persistent bacteraemia, new murmur, heart failure, embolic stroke, splenic infarct or glomerulonephritis should prompt transthoracic and often transoesophageal echocardiography.

4.7 Hepatosplenic and pulmonary disease

Hepatitis, cholestasis, splenomegaly, hepatic/splenic abscesses, pneumonia and pleural disease are less common but important in severe infection.

4.8 Pregnancy and neonatal disease

Brucellosis in pregnancy has been associated with miscarriage, preterm birth, intrauterine infection and neonatal disease. Review unpasteurised dairy and animal-birth exposure, involve obstetrics and do not rely on a single negative test.

Urgent referral: new murmur/heart failure, neurological signs, severe back pain or weakness, acute scrotum, septic arthritis, shock, jaundice, splenic tenderness or pregnancy with systemic illness.

5. History and examination

5.1 Essential questions

Which animals are kept, slaughtered, hunted or handled? Are goats, sheep, cattle, pigs or dogs involved?
Was there contact with abortions, placenta, blood, milk, birthing fluid, carcasses or animal vaccination?
Does the patient drink raw milk, eat fresh cheese or handle unpasteurised dairy?
What is the occupation of the patient and household members? Any similar illness?
Travel to pastoral, livestock or known endemic areas; previous brucellosis; incomplete antibiotic courses.
Back/joint pain, testicular symptoms, headache, hearing/vision changes, cardiac symptoms, weight loss and night sweats.

5.2 Examination

Measure fever, pulse, blood pressure, weight and mental state. Examine lymph nodes, liver, spleen, spine, sacroiliac joints, peripheral joints, skin, testes, heart (murmur/heart failure), lungs and neurological function. Look for focal tenderness rather than waiting for obvious abscesses.

6. Diagnosis

6.1 Blood culture

Collect adequate blood cultures before antibiotics and warn the laboratory. Cultures may be negative after treatment or in chronic disease and may require prolonged incubation. A negative culture does not exclude brucellosis when exposure and serology are convincing.

6.2 Serology

Standard agglutination tests, ELISA and other validated assays detect antibodies. A four-fold rise in paired titres or a significant titre in the context of local background levels is more convincing than one isolated result. Antibodies may persist after cure, cross-react with other organisms or be absent early/immunosuppressed patients.

6.3 PCR and site-specific tests

PCR can assist when available, particularly after antibiotics or in focal disease. Aspirate a joint or abscess for culture/PCR; send CSF for cell count, protein, glucose, culture and PCR; biopsy bone, node or valve material when necessary.

Investigation	Purpose	Interpretive caution
Blood cultures	Direct confirmation and susceptibility	Slow; sensitivity falls after antibiotics
Standard agglutination/ELISA	Evidence of exposure/immune response	Cross-reactions, background titres and persistent antibodies
FBC/ESR/CRP	Inflammatory burden and cytopenias	May be normal in chronic disease
Liver/renal profile	Organ involvement and treatment baseline	Abnormal tests may be disease or drug-related
Echo	Endocarditis/pericardial assessment	Repeat/TEE if suspicion remains high
MRI spine/joint imaging	Spondylitis, sacroiliitis, abscess and cord risk	Differentiate TB, pyogenic infection and malignancy
CSF	Neurobrucellosis	CSF culture may be negative; interpret with clinical syndrome

7. Differential diagnosis

Malaria and enteric fever, especially in prolonged fever in Uganda.
Tuberculosis, HIV-associated infection, infective endocarditis and lymphoma.
Leptospirosis, Q fever, rickettsial disease and visceral leishmaniasis where epidemiologically relevant.
Pyogenic spondylodiscitis, septic arthritis, reactive arthritis and inflammatory rheumatologic disease.
Viral hepatitis, connective-tissue disease, occult abscess and malignancy.

8. Treatment principles

Brucella is intracellular and relapse is common with monotherapy or a short course. Use at least two active agents, ensure adequate duration and treat the focal site. Confirm the current Uganda/WHO regimen, contraindications, pregnancy status and organ function.

Uncomplicated adult disease

A commonly used teaching regimen is doxycycline for at least six weeks plus rifampicin for at least six weeks. Some protocols add streptomycin or gentamicin during the first 1–2 weeks to reduce relapse. Follow the national protocol and susceptibility information rather than combining medicines independently.

Osteoarticular disease

Use combination therapy for a longer course with imaging follow-up. Drain septic joints or abscesses and involve orthopaedics for instability, cord compression, extensive bone destruction or failure of medical treatment.

Neurobrucellosis

Use prolonged combination therapy with CNS-penetrating agents, guided by infectious-disease/neurology specialists and CSF response. Manage raised intracranial pressure, seizures, hearing loss and hydrocephalus.

Endocarditis

Use prolonged multidrug therapy, repeat cultures and early cardiology/cardiothoracic review. Valve surgery may be required for heart failure, uncontrolled infection, abscess or embolic risk.

Pregnancy and children

Avoid tetracyclines when contraindicated in pregnancy and young children. Use a guideline-approved alternative combination and coordinate obstetric/paediatric monitoring.

9. Monitoring treatment

Review fever, sweats, weight, appetite, focal pain, neurological symptoms and adherence at every visit.
Monitor liver enzymes and renal function; rifampicin interactions; aminoglycoside hearing/vestibular and renal toxicity; doxycycline gastrointestinal/photosensitivity effects.
Repeat cultures or serology only when clinically indicated; antibody titres may decline slowly and do not alone prove cure.
Document the focal site, planned duration and end-of-treatment review. Relapse usually requires a new culture and search for an undrained focus.

10. Complications and prognosis

Complication	Clinical clues	Management priority
Endocarditis	Murmur, HF, emboli, persistent bacteraemia	Echo, prolonged combination therapy, surgical review
Spondylitis/sacroiliitis	Back/hip pain, fever, neurological deficit	MRI, prolonged therapy, spinal/orthopaedic care
Septic arthritis	Hot swollen joint and restricted movement	Aspiration, drainage and targeted therapy
Neurobrucellosis	Meningism, seizures, cranial palsy, confusion	CSF/imaging, CNS-penetrating regimen and neurological care
Epididymo-orchitis	Scrotal pain/swelling	Ultrasound, torsion exclusion and prolonged therapy
Hepatic/splenic abscess	RUQ/LUQ pain, persistent fever, organ enlargement	Imaging, drainage and specialist treatment
Relapse	Recurrent fever months after therapy	Repeat cultures/serology and search for focal disease

11. Prevention and One Health control

11.1 Individual protection

Pasteurise milk and avoid fresh cheese or dairy of uncertain origin.
Wear gloves, waterproof apron, eye protection and a mask when assisting animal births, handling placentas, carcasses or aborted fetuses.
Cover skin breaks and wash hands; do not eat, drink or smoke in animal-handling areas.
Use biosafety precautions for laboratory specimens and report exposures immediately.

11.2 Veterinary and community control

Vaccinate cattle, sheep and goats through veterinary programmes; test, isolate and control infected herds.
Separate animals during birthing and dispose of placenta, fetus and bedding safely by trained personnel.
Educate farmers, herders, veterinarians, butchers, hunters, laboratory workers and consumers about risk.
Notify clusters and link human cases with veterinary investigation; human treatment alone cannot eliminate the reservoir.

12. Clinical reasoning examples

Example A: undulating fever and back pain

A herder has three months of fever, night sweats, weight loss and sacroiliac pain. Malaria tests are repeatedly negative. Ask about raw milk, collect blood cultures and serology, request MRI and do not label the back pain as mechanical without assessing spondylitis.

Example B: culture-negative endocarditis

A patient has fever, a new murmur, anaemia and negative routine cultures after receiving antibiotics. Brucellosis belongs in the differential if there is livestock/raw-dairy exposure. Contact the laboratory, send specialised serology/PCR and obtain echocardiography.

Example C: occupational exposure

An abattoir worker splashes birth fluid into the eye. Irrigate promptly, report the exposure, involve occupational/public health services and arrange risk-based follow-up. Do not wait for fever before seeking advice.

13. Examination pearls

Think brucellosis when prolonged fever is accompanied by sweats, arthralgia and raw-dairy/animal exposure.
Intracellular organisms require combination therapy and adequate duration.
Endocarditis, neurobrucellosis and spinal disease determine prognosis and treatment length.
A negative culture after antibiotics does not exclude disease.
Human treatment without animal-source control allows continued transmission.

14. References

SlideShare: Brucellosis — transmission, occupational risk, animal reservoirs, clinical consequences, treatment/prognosis and prevention.
WHO/CDC brucellosis clinical and laboratory guidance.
Uganda Clinical Guidelines and One Health/veterinary brucellosis-control guidance.