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Brucellosis

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					                             Brucellosis
Microbiology and epidemiology
Brucellae are slow-growing, small, aerobic, nonmotile, nonencapsulated, non–spore-
forming, gram-negative coccobacilli
Brucellosis is an enzootic infection (i.e. endemic in animals). Although six species of
Brucella are known, only four are important to humans: B. melitensis (goats, sheep and
camels), B. abortus (cattle), B. suis (pigs) and B. canis (dogs).B. ovis, neotomae and
recent isolates from marine mammals, tentatively named maris

More than 500,000 cases of brucellosis are reported yearly to the World Health
Organization from 100 countries
Alternative na me for brucella include : malta f., andulant f., Gibraltar fever, and
Mediterranean fever.
B. melitensis is enzootic in the Middle East, Africa, India, Central Asia and South
America. B. abortus is found in Africa, Asia and South America, and B. suis in South
Asia.
B. melitensis causes the most severe disease; B. suis is often associated with abscess
formation.

Infected animals may excrete brucellae in their milk for long periods of time and human
infection is acquired by ingesting contaminated milk, cheese, yoghurt and butter.
Uncooked meat and offal may also spread infection. Animal urine, faeces, vaginal
discharge and uterine products may act as sources of infection through abraded skin or
via splashes and aerosols to the respiratory tract and conjunctiva.

Pathogenesis
    After penetrating the epithelial cells of human skin, conjunctiva, pharynx, or lung,
      Brucella organisms initially induce an exuberant polymorphonuclear neutrophil
      response in the submucosa.
    After ingestion of organisms by neutrophils and tissue macrophages, spread to
      regional lymph nodes occurs. If host defenses within the lymph nodes are
      overwhelmed, bacteremia follows.
    The usual incubation period between infection and bacteremia is 1½ to 3 weeks.
    Bacteremia is also accompanied by phagocytosis of free Brucella organisms by
      neutrophils and localization of bacteria primarily to the spleen, liver, and bone
      marrow, with the formation of granulomas.
    If the inoculum is large and the patient receives no treatment, large granulomas
      may form, suppurate, and serve as a source of persistent bacteremia with the
      potential for multiorgan spread. The primary virulence factor of Brucella appears
      to be cell wall lipopolysaccharide.
Clinical features
    Brucellae are intracellular organisms that can survive for long periods within the
       reticulo-endothelial system. This explains many of the features of clinical
       brucellosis, including the chronicity of the disease and the tendency to relapse
       even after adequate antimicrobial therapy.
    Clinically, human brucellosis may be divided into subclinical illness, acute or
       subacute disease, localized disease and complications, relapsing infection, and
       chronic disease .

1. Subclinical Illness
Detected only by serologic testing, asymptomatic or clinically unrecognized human
brucellosis often occurs in high-risk groups, including slaughterhouse workers, farmers,
and veterinarians. More than 50% of abattoir workers and up to 33% of veterinarians
have high anti-Brucella antibody titers but no history of recognized clinical infection.


2. Acute and Subacute Disease
     After an incubation period of several weeks or months, acute brucellosis may
       occur as a mild, transient illness (with B. abortus or B. canis) or as an explosive,
       toxic illness with the potential for multiple complications (with B. melitensis).
     Approximately 50% of patients have an abrupt onset over days, whereas the
       remainder has an insidious onset over weeks.
     Symptoms in brucellosis are protean and nonspecific. More than 90% of patients
       experience malaise, chills, sweats, fatigue, and weakness.
     More than 50% of patients have myalgias, anorexia, and weight loss.
     Fewer patients complain of arthralgias, cough, testicular pain, dysuria, ocular
       pain, or visual blurring. Likewise, few localizing physical signs are apparent.
     Fever, with temperatures often greater than 39.4° C (103° F), occurs in 95% of
       patients. An undulating or intermittent fever pattern is unusual. A relative pulse
       temperature deficit may occur.
     Splenomegaly is present in 10 to 15%, and lymphadenopathy occurs in up to 14%
       (axillary, cervical, and supraclavicular locations are most frequent, related to hand
       wound or oropharyngeal routes of infection); hepatomegaly is less frequent.
     Other laboratory findings in acute or subacute disease may include mild anemia,
       lymphopenia or neutropenia (especially with bacteremia), lymphocytosis,
       thrombocytopenia, or (rarely) pancytopenia. The majority of infected individuals
       recover completely without sequelae if the diagnosis is appropriately made and
       prompt therapy is initiated.

3. Localized Disease and Complications
     Brucella organisms may localize in almost any organ but most commonly localize
       in bone, joints, central nervous system (CNS), heart, lung, spleen, testes, liver,
       gallbladder, kidney, prostate, and skin. Localized disease may occur
       simultaneously at multiple sites. Localized complications most often appear in
       association with a more chronic course of illness, although complications may
       occur with acute disease caused by B. melitensis or B. suis.
4. Relapsing Infection
     Up to 10% of patients with brucellosis experience relapses after antimicrobial
       therapy. Relapses occur usually 3 to 6 months after completion of therapy but
       may be seen up to 2 years after treatment.
     Relapses are associated frequently with antimicrobial resistance as well as the
       intracellular location of the organisms, which protects the bacteria from certain
       antibiotics and host defense mechanisms.
     Relapsing infection is difficult to distinguish from reinfection in high-risk groups
       with continued exposure.

5. Chronic Disease
     Disease with a duration of more than 1 year has been called chronic brucellosis.
     A majority of patients classified as having chronic brucellosis really have
       persistent disease caused by inadequate treatment of the initial episode, or they
       have focal disease in bone, liver, or spleen.
     About 20% of patients diagnosed as having chronic brucellosis complain of
       persistent fatigue, malaise, and depression; in many aspects this condition
       resembles the chronic fatigue syndrome.
     These symptoms frequently are not associated with clinical, microbiologic, or
       serologic evidence of active infection and may represent a preexisting
       psychoneurosis.


FOCAL complication OF BRUCELLOSIS

Musculoskeletal

      Suppurative arthritis; synovitis, bursitis
      Osteomyelitis
      Spinal spondylitis
      Paravertebral or psoas abscess


Central nervous system

      Meningitis
      Cranial nerve palsies
      Intracranial or subarachnoid haemorrhage
      Stroke
      Myelopathy
      Radiculopathy
Ocular

      Uveitis
      Retinal thrombophlebitis
      Cardiac
      Myocarditis
      Endocarditis

Diagnosis
   Definitive diagnosis of brucellosis depends on the isolation of the organism. Blood
cultures are positive in 75-80% of infections caused by B. melitensis and 50% of those
caused by B. abortus.
 The non-radiometric 'Bactec' system gives a good isolation rate, but if brucellosis is
suspected, prolonged incubation and blind subcultures are recommended.
Bone marrow culture should not be used routinely but may increase the diagnostic yield,
particularly if antibiotics have been given before specimens are taken.
 CSF culture in neurobrucellosis is positive in about 30% of cases.

World-wide, the serum agglutination test is the serological technique most commonly
employed to detect brucellosis.
 Agglutination should be carried out to a high dilution (at least 1/640) to avoid the
prozone phenomenon whereby non-agglutinating IgG and IgA molecules completely
block the agglutinating reaction.
Significant agglutination titres may persist for months or years after recovery and in
endemic areas a single titre of 1/320 or a fourfold rise in titre is needed to support a
diagnosis of acute infection.
The test usually takes several weeks to become positive but should eventually detect 95%
of acute infections. The pre-treatment of serum with 2-mercaptoethanol helps to
distinguish between IgG and IgM responses.
The enzyme-linked immunosorbent assay (ELISA) also identifies IgM and IgG
antibodies; IgM decreases rapidly within the first few months of illness.

Specialist laboratory techniques including the use of the anti-human globulin (Coombs)
test may be necessary to distinguish chronic disease from past inactive infection.


Management
    Aminoglycosides show synergistic activity with tetracyclines when used against
     brucellae. Standard therapy therefore consists of doxycycline 100 mg 12-hourly
     for 6 weeks, with streptomycin 1 g i.m(or new regimen that include gentamycine
     3-5mg /kg) . daily for the first 2 weeks. The relapse rate with this treatment is
     about 5%.
    An alternative oral regimen consists of doxycycline 100 mg 12-hourly plus
     rifampicin 900 mg (15 mg/kg) daily for 6 weeks, but failure and relapse rates are
     higher, particularly with spondylitis. Rifampicin may antagonise doxycycline
     activity by reducing serum levels through enzyme induction.
   Chronic illness should be treated for a minimum of 3 months and many
    authorities would extend this to 6 months, depending upon the condition of the
    patient and the result of sequential serological tests.
   The optimum therapy for neurobrucellosis is unknown, and there is no current
    agreement on the combination or number of drugs to use. Treatment should
    continue for at least 3 months, and longer if CSF pleocytosis persists.
   the usual drug that is used is 3ed generation cephalosporine or doxicycline +
    refampicn + cotrimoxazole


Prevention
   The control of human brucellosis is related directly to prevention programs in
    domestic animals and avoiding unpasteurized milk and milk products. In
    slaughterhouses, important means of prevention include careful wound dressing,
    protective glasses and clothing, prohibition of raw meat ingestion, and the use of
    previously infected (immune) individuals in high-risk areas.
Prognosis
   Brucellosis appropriately treated within the first month of symptom onset is
    curable. Acute brucellosis often produces severe weakness and fatigue, and
    patients are frequently unable to work for up to 2 months.
   Immunity to reinfection follows initial Brucella infection in the majority of
    individuals.
   With early antimicrobial therapy, cases of chronic brucellosis or localized disease
    and complications are rare.
   Of patients who die of brucellosis, 84% have endocarditis involving a previously
    abnormal aortic valve, often associated with severe congestive heart failure.


With best luck

				
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posted:11/19/2011
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