Overview
- Definition
- A zoonotic disease caused by the gram-negative Brucella species transmitted to humans from livestock, causing a flu-like illness with potentially lethal complications of endocarditis or neurobrucellosis
Reservoirs include cattle, sheep, goats, and pigs
High-risk occupations: abattoirs, veterinarians, animal handlers, and microbiology laboratory workers
Uveitis (80%) is the most common ocular manifestation, usually occurring during acute brucellosis
- Symptoms
Blurry vision
Floaters
Photopsia
- Laterality
Unilateral or bilateral
- Course
Ocular disease occurs in chronic brucellosis and typically resolves after an appropriate course of antimicrobial therapy
- Age of onset
All age groups
- Gender/race
No gender predilection
Common in the Mediterranean, Arab gulf, India, Central America and South America, Asia, and sub-Saharan Africa
- Systemic association
Council of State and Territorial Epidemiologists (CSTE) definition: “An illness characterized by acute or insidious onset of fever and one or more of the following: night sweats, arthralgia, headache, fatigue, anorexia, myalgia, weight loss, arthritis/spondylitis, meningitis, or focal organ involvement (endocarditis, orchitis/epididymitis, hepatomegaly, splenomegaly)”
- Acute brucellosis
Average incubation: 1–4 weeks (but highly variable, ranging from 5 days to 6 months)
Often subclinical with mild flu-like illness with no sequelae
- Symptomatic disease presents with fever, anorexia, weight loss, headache, arthralgia, and malaise, with focal organ involvements
Musculoskeletal: spondylitis and arthritis, especially of the sacroiliac joints and large joints of the lower extremities, osteomyelitis of the vertebrae, tibia, and especially knee
Heart: endocarditis (most common cause of death)
Central nervous system (CNS): meningoencephalitis (change in mental status, seizure, coma, neurologic deficits, nuchal rigidity)
Gastrointestinal (GI): hepatic abscess, hepatomegaly, splenomegaly
Genitourinary: orchitis/epididymitis
Pulmonary: multiple syndromes
Hematologic: cytopenia, disseminated intravascular coagulation
Dermatologic: variable morphologies of rashes
- Chronic brucellosis (defined as >1 year of symptoms following diagnosis)
Can be persistent localized infection (e.g., bone or eye disease) or relapse following treatment
Some patients attribute symptoms to chronic brucellosis without objective evidence of infection
Exam: Ocular
Anterior Segment
Episcleritis
Diffuse or nodular scleritis
Nummular keratitis
Chronic granulomatous or non-granulomatous iridocyclitis
Posterior Segment
Multifocal choroiditis, either in geographic pattern or in circumscribed nodules, is most characteristic of posterior segment disease
Vitritis of varying severity
- Optic disc edema or hyperemia
Retrobulbar optic neuritis, chiasmal arachnoiditis
Cystoid macular edema
Retinal vasculitis
Retinitis with edema and hemorrhage
Exudative retinal detachment
Exam: Systemic
Hepatosplenomegaly (most common physical finding), lymphadenopathy
Right upper quadrant abdominal tenderness
Knee swelling, sacroiliac tenderness
New or changing murmur (endocarditis), pericardial rub (pericarditis)
Nuchal rigidity, Kerning sign, and Brudzinski sign (meningitis)
Tender, swollen and erythematous scrotum (orchitis)
Imaging
- FA
Optic nerve staining or leakage
Multiple hyperfluorescent lesions with late leakage
- ICG
Multiple hypofluorescent and hyperfluorescent lesions, early
Multiple hyperfluorescent spots with associated large areas of hypofluorescence, late
- Visual field
Bilateral blind spot enlargement or visual field constriction
Laboratory and Radiographic Testing
Fluid culture for identification of Brucella species (e.g., blood, aqueous, vitreous)
- Standard agglutination test (SAT)—most commonly used
“Gold standard” test that uses an antigen derived from B. abortus to detect both Immunoglobulin G (IgG) and Immunoglobulin M (IgM) agglutinating antibodies
Titers exceeding 1:160 are considered significant for brucellosis in endemic areas (1:80 in non-endemic areas)
Interpretation of serologies can be challenging in endemic areas and in patients who have been treated previously
This test does not detect antibodies to B. canis, which requires B. canis serology for diagnosis
- Enzyme-linked immunosorbent assay (ELISA)
ELISA and SAT both cross-react with other bacteria
ELISA and SAT can both give false-negative results early in infection and in immunocompromised patients
Polymerase chain reaction (PCR)
Anterior chamber tap or vitreous tap with Goldmann-Witmer coefficient analysis
Differential Diagnosis
Tuberculosis
Syphilis
Sarcoidosis
White dot syndromes
Lyme disease
Outer retinal toxoplasmosis
Diffuse unilateral subacute neuroretinitis (DUSN)
Septic choroiditis
Viral retinitis
Presumed ocular histoplasmosis syndrome (POHS)
Vogt-Koyanagi-Harada (VKH) syndrome
Sympathetic ophthalmia
Treatment
- Adults and children >8 years
Oral doxycycline 2–4 mg/kg/day (maximum 200 mg/day) in two divided doses or oral tetracycline 30–40 mg/kg/day (maximum 2000 mg/day) in four divided doses, PLUS
Rifampin 15–20 mg/kg/day (max 600–900 mg/day) in one or two divided doses
This combination is given for a minimum of 6 weeks
- Pregnancy patients and children <8 years
Oral TMP-SMZ (trimethoprim, 10 mg/kg per day, maximum 480 mg/day; and sulfamethoxazole, 50 mg/kg per day, maximum 2400 mg/day) divided in two doses for 4–6 weeks, OR
Rifampin with ceftriaxone
TMP-SMZ should be avoided during the last week of pregnancy before delivery due to risk for kernicterus
- Cases complicated by endocarditis or meningitis
Add streptomycin (20–40 mg/kg per day, maximum 1 g/day divided in two doses) or gentamicin (5 mg/kg per day divided in one–three doses) to the above regimen for the first 2 weeks, then extend the regimen for 4–6 months
Surgical intervention for deep-tissue abscesses
About 10% of patients have relapsing infection despite systemic antimicrobial therapy, due to evasion by intracellular organisms
Topical and systemic corticosteroids are appropriate once antimicrobial therapy has been commenced
Referral/Co-management
Infectious disease
Cardiology
Neurology