2. BRUCELLOSIS (MALTA FEVER, ROCK FEVER)
• Is one of the classical zoonoses (infections of animals
transmitted to humans). It is an important cause of fever in
many parts of the world and is often underdiagnosed because
of lack of laboratory facilities. This is increasingly recognized in
India and neighboring countries, and in some Pacific settings.
• Brucellae are Gram-negative coccobacilli. At least six species
infect a wide variety of land-based mammals and new species
have recently been described in marine mammals such as
whales and seals. Three species are responsible for most
human infections:
3. EPIDEMIOLOGY
1- Brucella abortus: prevalent in cattles, usually a in Africa, the
Indian Subcontinent and temperate zones. (More insidious onset, are
more likely to affect the axial skeleton and to become chronic)
2- Brucella melitensis: whose normal ruminant host is sheep and
goats but is also found in camels, is particularly prevalent in
countries around the Mediterranean, the Middle East and Central and
South America. (More acute onset and is more likely to affect
peripheral joints as well as the vertebrae).
3- Brucella suis: whose natural host is pigs, is still a problem in the
USA. ( Acute presentation complicated by focal deep tissue
abscesses).
4. MODE OF INFECTION
• Humans acquire infection from ingesting milk or dairy products
such as laban, buttermilk and cheeses that have not been
pasteurized.
• The products of abortion and placentae from infected animals are
highly infectious and farmers and veterinarians can easily become
infected by aerosol transmission from the products of conception.
• Rarely, human brucellosis can be acquired via breast milk, sexual
transmission or transfusion of blood products.
• Veterinarians and farmers sometimes have localized skin disease
caused by direct contact with infected animal products.
• Brucellosis is not transmitted by eating the meat of infected
animals unless it is eaten raw and has been externally
5. CLINICAL MANIFESTATIONS
• The organisms are intracellular and can remain hidden in the
reticuloendothelial system so that clinical incubation periods after
infection range from several weeks to months.
• The incubation period is usually one to four weeks; occasionally, it
may be as long as several months.
• In animals, they are important causes of epididymitis, abortion and
infertility, but host animals may appear symptomless.
• Brucellosis is a systemic infection with a broad clinical spectrum,
ranging from asymptomatic disease to severe and/or fatal illness.
6. SYMPTOMS:
• The symptoms of brucellosis are of recurrent prolonged bouts of
fever. If specific treatment is not given, undulating patterns of fever
may last for several weeks, followed by an afebrile period and then
relapse.
• Approximately half of all cases are associated with focal
musculoskeletal symptoms, which may be the only clinical clue that
differentiates brucellosis from other causes of fever such as
typhoid, Q fever, malaria, etc.
• Fever is worse at night and may be associated with profuse
sweating.
• Patients are depressed, anorexic and lethargic, although the onset
7. • A small proportion present with more pronounced
neuropsychiatric disorder or low-grade meningoencephalitis
(neurobrocellosis)
• 5–10% of men have orchitis which must be distinguished from
mumps.
• Patients often have a dry cough, mimicking the presentation of
typhoid.
• Epistaxis is an unusual but well-recognized presentation
because of associated thrombocytopenia, but other features of
8. BY EXAMINATION:
• Patients look unwell and are lethargic but do not look as toxic as those
with enteric fever.
• The temperature is almost invariably raised but often returns to normal
during a 24-h cycle.
• Up to 10% have cervical or other lymphadenopathy, which must be
differentiated from glandular fever, HIV or tuberculous (TB) adenitis.
• One-quarter have mild to moderate splenomegaly.
• The chest is usually clear, even if the patient has a cough.
• Individual joints may show signs typical of septic arthritis with swelling,
heat, tenderness and effusions. There may be local tenderness, especially
on movement of vertebrae or sacroiliac joints, but deformity of the back
or long tract neurological signs are very unusual and suggest TB rather
9. • Brucellosis is rarely fatal unless complicated by endocarditis
(∼1% of cases).
• Risk factors → occupational disease, common in
1. Farmers
2. Meat handlers
3. Veterinary services
10. THE PATTERN OF PRESENTATION
• Varies with the age of the patient and the infecting species;
• Brucella abortus
More insidious onset
More likely to become chronic
More likely to affect the axial skeleton
- B. melitensis
More acute onset
More severe disease
More likely to affect peripheral joints as well as the vertebrae
- B. suis
Acute presentation complicated by focal deep tissue abscesses
11. PRESENTATION
1- Acute brucellosis:
Outcome
Acute disease lasts for weeks, leading to chronic, relapsing infection that
may last for years
A substantial minority will only have self-limiting disease
Children Often present with fever and a single affected joint typically
the hip or knee (may be mistaken for rheumatic fever or septic arthritis)
12. 2- Chronic brucellosis
- Onset is insidious
- There is a story of recurrent flu with lassitude, malaise, headache, sweating,
low backache and depression
- Temperature may be normal
- The appearance may reflect a serious disease or may be normal
- Moderate splenomegaly may be present
13. COMPLICATIONS
• [May occur with acute or chronic disease and may be the presenting feature]
1. Bone and joints:
Osteoarticular complications are the most common focal forms of the disease
Reported in 10-80% of cases depending on the ages of the patients & Brucella spp.
- Sacroiliitis occurs in young patients → local tenderness on movement of the sacroiliac
joints
- Spondylitis
Occurring in old persons (average age is 40 yr), May affect single or multiple sites
Usually in the lumbar spine (L 4) → local tenderness
Causing bone necrosis with new bone formation (sclerosis), and can destruct vertebra
and disc.
- Paravertebral, epidural, or psoas abscesses may occur
14. - Arthritis
Usually involves large weight-bearing joints (hips and knees), may be acute or chronic
Reactive → commonly polyarticular, migratory resembles rheumatic fever or
Septic → usually monoarticular
Signs of arthritis include swelling, hotness, tenderness and effusions of the affected joint
- Osteomyelitis: rare, affecting long bones as femur, tibia and humorous
- Deformity of the back or long tract neurological signs are very unusual and suggest TB rather
than brucellosis .
15. 2- NEURO-PSYCHIATRIC:
- Depression and mental inattention are common symptoms ± psychosis.
- Neurologic syndromes in brucellosis (Neurobrucellosis) occurs in about 5% of
cases and include:
Meningitis, meningoencephalitis
Myelitis, radiculoneuronitis
Brain abscess, epidural abscess
Granuloma
Demyelinating and meningovascular syndromes.
- Acute or chronic meningitis is the most frequent nervous system complication.
16. 3- CARDIOVASCULAR:
- Endocarditis occurs in 1- 2% of cases esp. with B. melitensis, but it
accounts for the majority of brucellosis-related deaths (valve destruction and
heart failure).
- Pericarditis, myocarditis are also reported.
17. 4- GENITOURINARY:
- Interstitial nephritis, pyelonephritis, glomerulonephritis & IgA nephropathy
have been reported.
- Epididymoorchitis occurs in 5-10% of men with brucellosis (must be
distinguished from mumps).
- Unilateral or bilateral epididymoorchitis common in children
- Prostatitis and seminal vesiculitis common in adults
18. 5- GASTROINTESTINAL:
- Hepatitis with mild jaundice (non-specific or granulomatous disease)
- Hepatosplenic abscesses are rare
- Mesenteric lymphadenitis with abscess formation
- Ulceration, bleeding & perforation.
- Acute ileitis, colitis and spontaneous peritonitis
- Lesions ranging from small, almost insignificant aggregates of mononuclear cells
surrounding foci of necrosis, to a diffuse nonspecific inflammation resembling viral
hepatitis.
- Acute cholecystitis or Gall stones.
19. OTHER COMPLICATIONS
Cutaneous
- Petechiae, purpura, and vasculitis are reported in 5% of patients.
Pulmonary: rare
- Airborne transmission of brucellosis is a problem in abattoirs and laboratories.
- Complications range from flu-like symptoms to bronchitis, pneumonia, lung nodules,
abscess, military lesions, hilar adenopathy, pleural effusion or empyema.
Hematologic:
- Anemia, leukopenia, thrombocytopenia, and clotting disorders.
- Granulomas are found in the bone marrow in as many as 75% of cases.
20. Ocular:
- Iridocyclitis, nummular keratitis, multifocal choroiditis & optic neuritis and uveitis have been reportd.
Pregnancy → abortion.
21. DIAGNOSIS
1- CBC
- Shows low WBCs with lymphopenia and mild thrombocytopenia and anemia
2- ALT, AST, ALP → mild elevation is common
3- Culture [the most reliable method for confirming diagnosis]
- Blood culture
+ ve in 2/3 of cases of B. melitensis & < 1/3 of B. abortus cases
Most of the positives ocuuring between days 7 and 21, but may take up to 6 weeks if modern
culture systems not used
Laboratory staff must be told that brucellosis is a possibility, both to be aware of the hazard
of aerosol spread and to prolong the culture period
- Single bone marrow culture
Has a better yield than 3 sets of blood cultures
Occasionally useful in case of –ve blood culture (preceding antibiotics)
22. • Serological tests are still based on the old (Wright’s) standard
agglutination test (SAT). Brucella antigen supplied with the kit is
added to successive dilutions of patient serum, and if visible
agglutination occurs the test is positive. These tests are notoriously
affected by the ‘prozone phenomenon’, which causes false-negative
results. This occurs because patients with brucellosis have
immunoglobulin A (IgA) antibodies, which interfere with
agglutination at low dilutions, and the blocking effect is only
overcome at increasing serum dilutions. Thus, the result might be
negative at dilutions of 1/40, 1/80, 1/160 and 1/320 and positive
only at 1/640. Many inexperienced laboratories will only dilute serum
to 1/160 and therefore miss the true positives.
23. • As with all serological tests, a fourfold rise in titre between acute and
convalescent samples (10–14 days later) is strongly suggestive of
brucellosis, but this result is too delayed to guide the immediate
management of patients with fever.
• In endemic areas, many patients have had previous exposure to brucellosis
and have low titres of antibodies already, so the diagnostic ‘cut-offs’ for a
single sample to be positive have to be set higher, typically at 1/160 or
1/320. In a non-endemic area, or for an expatriate who has recently been
exposed for the first time in an endemic area, a titre of 1/80 would be
strongly predictive of brucellosis. About 10% of blood culture-positive
patients have negative serological results at first presentation, so a negative
result does not entirely rule out brucellosis.
25. TREATMENT
• Three questions guide management, once a presumptive or definite
diagnosis has been made.
1 Is the disease acute (duration <1 month) or relapsing or chronic (>6
months)?
2 Is there focal disease of bone or joints?
3 Has tuberculosis definitely been excluded?
• Adults with acute non-focal disease should be treated for a minimum
of 6 weeks. Patients with focal disease and/or chronic disease require
3 months of treatment.
26. - Combination of 2 antibiotics is the preferred regimen
- Triple therapy is indicated in complicated cases
- In patients in whom TB has not been excluded Use antimicrobials to which
only brucellosis responds (i.e. don't use streptomycin or rifampicin)
27. THE GOLD STANDARD REGIMEN
• oral tetracycline for 6–12 weeks plus 1g/day streptomycin
intramuscularly for 2–3 weeks is the gold standard.
• The preferred form of tetracycline is now 100 mg doxycycline
twice daily as it is easier to take and less likely to cause renal
toxicity.
• Modern aminoglycosides such as gentamicin (5 mg/kg/day for
10–14 days) can be substituted for streptomycin.
• Relapse rate after this regimen only 5%
28. ALTERNATIVE REGIMENS
- Doxycycline 100 mg twice daily + rifampicin 600 mg once daily before breakfast [Relapse rate after
this regimen > 10%]
- Doxycycline 100 mg twice daily + Co-trimoxazole 3 tab. Twice daily + folic acid daily [can cause
anemia and drug rashes]
- Rifampicin can interact with the contraceptive pill and therefore other forms of contraception may be
necessary.
- Children < 12 yrs
- Rifampicin + Co-trimoxazole
29. Pregnancy
- Rifampicin alone or
- Rifampicin + Co-trimoxazole 2 tab. Twice daily [in the 1st trimester, avoid co-trimoxazole
or add folic acid supplements]
- Doxycycline is contraindicated in pregnancy and lactation
Complicated cases [spondylitis, endocarditis, meningitis]
- Doxycycline + rifampicin + gentamicin
- Ceftriaxone may be added
- Patients with endocarditis often need valve replacement
30. - Acute cases → 2 drugs for 6 weeks
- Chronic or relapsing cases → 2 drugs for 3 months
- Complicated cases → 3 drugs for 3 months
