Brucellosis

BRUCELLOSIS

Synonyms

  • In animals: Bang's disease, Contagious abortion, Epizootic abortion, ‘Kandruveechu noiy’ (Tamil)
  • In humans: Melitococcosis (Brucella melitensis), Malta fever (Brucella melitensis), Mediterranean fever (Brucella melitensis), Undulant fever (Brucella abortus) 

Type of zoonosis

  • Direct anthropozoonosis
  • Occupational zoonosis

Definition

  • It is an infectious disease in humans, causes acute or chronic brucellosis and is clinically characterized by chills, profuse sweating, weakness and fatigue, insomnia, sexual impotence, headache, arthralgia and generalized malaise, which last for weeks and months; commonly shows remissions (hence also known as undulant fever). It is an acute or chronic contagious disease of domestic animals that causes placentitis and abortion in farm animals, especially at last trimester of pregnancy (at about 6th month of pregnancy in cattle).

Brief history

  • It is an emerging disease since the discovery of Brucella melitensis by Bruce in 1887. ‘Brucellosis’ is named after its researcher David Bruce. Danish veterinarian Bernard Bang isolated Brucella abortus as the agent and the additional name Bang's disease was assigned in 1897.
  • In 1905, Maltese doctor and archaeologist Sir Temi Zammit identified unpasteurized milk as the major source of the pathogen and it has since become known as Malta fever.

Etiology

  • The "classic Brucella" are Brucella abortus in cattle, B. melitensis in goats and B. suis in swine. Other zoonotic Brucella are B. canis in dogs, B. ovis in sheep and B. neotomae in rats, particularly in desert rat. B. ovis and B. neotomae are nonzoonotic agents. Recently B. maris has been identified from marine animals.
  • Biovars of Brucella spp.
    • Brucella melitensis - Biovars 1 to 3
    • Brucella abortus - Biovars 1 to 7
    • Brucella suis - Biovars 1 to 5
  • Brucella spp. are Gram negative, facultative intracellular pathogen, non motile, aerobic and coccobacilli.

 Brucella_colonies

Growth of Brucella organisms on selective medium 

Reservoir and incidence 

  • The disease is widely prevalent in all the countries of the world. Brucellosis is still a serious problem facing the Veterinary and Medical professions.
  • In India, the disease is widely prevalent in all the States. 
  • Human brucellosis due to B.canis is uncommon but can be acquired from dogs; most cases resulted from contact with aborting bitches.
  • Each year about a half million cases of brucellosis occur around the world (WHO, 1975).
  • It has been eradicated from Finland, Norway, Sweden, Denmark, the Netherlands, Belgium, Switzerland, Germany, Australia, Hungary, the former Czechoslovakia, Rumania and Bulgaria.
  • Swine brucellosis is never had this problem in Muslim countries as a result of religious beliefs that have limited swine rising.
  • The natural reservoirs are cattle (Brucella abortus), goats (Brucella melitensis) and swine (Brucella suis).

Socio economic impact

  • Biological warfare: The United States biological warfare program focused on three agents of the Brucella group: Porcine Brucellosis (agent US), Bovine Brucellosis (agent AB) and Caprine Brucellosis (agent AM). Agents US and AB had a median infective dose of 500 organisms/person and AM was 300 organisms/person. The rate-of-action was believed to be 2 weeks, with duration of action of several months. AM was always believed to be a more virulent disease and a 3% fatality rate was expected.
  • Permanent sterility in male
  • Monetary loss
  • Reduced export on international trade
  • Loss of man-hours and man-days
  • Abortions in both animals and human beings

Source of infection

  • Raw milk, fresh cheese and raw vegetables contaminated with the excreta of infected animal and/or carrier animals
  • Faeces of infected animal and/or carrier animals
  • Uterine and vaginal discharges
  • Placenta and foetal membranes
  • Aborted foetus and its contents
  • Contaminated environment, water, feed, utensils, farm equipment
  • Semen from infected bulls

Transmission

  • In humans
    • Drinking of infected raw milk or unpasteurized milk.
    • Ingestion of cheese, raw vegetables and water contaminated with excreta of infected animals.
    • Handling of aborted foetus, fluids and foetal membranes.
    • Occupational exposure: Stockyard workers, slaughter house workers and butchers contract infection while handling foetuses, after births or by contact with vaginal secretions, excreta and carcasses of infected animals.
    • Veterinarian gets infection during rectal examination without wearing gloves and while conducting post mortem examination.
    • Through skin abrasions and conjunctiva.
    • Possibly airborne.
  • In animals
    • Ingestion of feed and water that are contaminated with aborted materials.
    • Mechanical transmission through flies, ticks, rats
    • Artificial insemination with frozen semen from infected bulls and dogs.

Disease in animals

  • The incubation period is ranged from 1 to 3 weeks, but some rare instances may take several months.
  • Abortions (at third trimester of pregnancy) are followed by immunity
  • Carrier state persists especially with secretions from the udder. 
  • Infertility, testicular abnormalities and poor semen quality.
  • Mastitis.
  • Inapparent infection may be common, as indicated by seropositivity.

Aborted_fetus_from_LAC-OG_ward

Aborted foetus by Brucella abortus

Disease in man

  • The incubation period ranges from 1 to 3 weeks.
  • It is a septicemic disease with sudden or insidious onset and is accompanied by continued intermittent or irregular fever.
  • It can be of acute or chronic form.
  • In acute brucellosis
    • Chills and profuse sweating (peculiar odour at night)
    • Weakness and fatigue
    • Normal temperature in the morning and rise at after noon.
    • Insomnia, nausea, headache, anorexia, arthralgia, muscular and body pain, weight loss, sexual impotence and orchitis in males.
    • Lymphadenopathy.
    • Neurological symptoms: Irritation, nervousness and depression. 
  • In chronic brucellosis
    • Symptoms are undulant nature, with periods of normal temperature between acute attacks; symptoms may persist for years, either continuously or intermittently.
    • Symptoms are associated with hypersensitivity and it is very difficult to diagnose.
  • Antibiotics can effect a cure within one year in about 80% of cases.
  • Case fatality may be less than 2% if untreated.
  • Neurobrucellosis can be developed in 1-3% of cases
  • The disease's sequelae are highly variable and may include granulomatous hepatitis, arthritis, spondylitis, anemia, leukopenia, thrombocytopenia, meningitis, uveitis, optic neuritis and endocarditis.

Diagnosis 

In human beings 

  • Based on the history and clinical signs. The clinical picture is not pathognomonic, although the herd history may be helpful.
  • Increased ESR and lymphocytosis are suggestive.
  • Isolation, identification and typing of Brucella agents from blood, bone marrow, from the sternum or ileal crest, lymph nodes and CSF.
  • Serology
    • Standard plate agglutination test (SPAT) for qualitative diagnosis
    • Standard tube agglutination test (STAT) for quantitative diagnosis. 100 IU is considered as positive titre in human beings. 
    • Rose Bengal plate agglutination test (RBPT) for qualitative diagnosis
    • Serological tests may have cross reaction with Cholera, Tularemia, Yersinia enterocolitica O:9, E.coli O:157 and O:116, Salmonella subtypes Kauffmann-White group N and Pseudomonas maltophila.
    • To detect the IgG antibody (IgM antibody present in the earlier stage of the infection, but IgG antibody always present), 2-mercaptoethanol and compliment fixation test can be performed.
    • ELISA
    • Lateral flow based Spot test for qualitative diagnosis
  • PCR

Serological tests for animals

  • Rapid slide agglutination test.
  • Milk ring test (MRT) or Abortus Bang ring test (ABRT): Dairy herds should be screened every 6 months by testing a bulk tank milk sample for antibodies against Brucella. If the ABRT is positive, all cows on the farm has to be tested individually (card test, plate or tube agglutination tests) and any "positive reactor" animals must be slaughtered. A positive test results will lead to a trace back and testing of other cattle at the farm of origin.
  • The reactivity of samples that are positive in screening tests should be retested using established confirmatory tests such as the complement fixation test or enzyme-linked immunosorbent assay.
  • Brucellin skin test, which can be used as a screening or as a confirmatory herd test when positive serological reactors occur in the absence of obvious risk factors in unvaccinated herds.
  • Diagnosis of B.melitensis and B.ovis is usually accomplished by bacterial isolation or demonstration of the organism in tissue or by serology.
  • AGID is more specific and sensitive than agglutination tests for B.canis.

Brucella-Milk_ring_test

Milk ring test

Antigen identification

  • Smears of placental cotyledon, vaginal discharge and foetal lung, liver and abomasal contents should be fixed with heat or ethanol and stained by the modified Ziehl Neelsen (Stamp’s), Kosters’ staining, Gram's staining or Macchiavello staining methods
  • The presence of large aggregates of intracellular, weakly acid-fast organisms of Brucella morphology is presumptive evidence of brucellosis. Care must be taken in the interpretation of results as other infectious agents may have similar morphology (e.g. Coxiella burnetii, Chlamydophila psittaci) 
  • Polymerase chain reaction (PCR) methods.
  • Culture of blood, placental cotyledon, vaginal discharge, fetal tissues or abomasal contents or hygroma fluid should be made on Brucella selective media. 
  • Cultures can also be made from milk or colostrum, and from samples of tissues collected at post-mortem, such as mammary gland, uterus, supramammary, and internal iliac lymph nodes from females and testes, epididymis, seminal vesicles, accessory glands, external inguinal and internal iliac lymph nodes from males. The parotid, mandibular and retropharyngeal lymph nodes, from either males or females, are good sources of the organism.

Treatment

  • Antibiotics like tetracycline, chloramphenicol, rifampicin and the aminoglycosides streptomycin and gentamicin are effective against Brucella bacteria. However, the use of more than one antibiotic is needed for several weeks, due to the fact that the bacteria incubate within cells.
  • Combination regimens of two or three drugs are more effective.
    • Either (1) doxycycline plus rifampicin or streptomycin (or both); (2) trimethoprim-sulfamethoxazole plus rifampicin or streptomycin (or both) are effective in doses for 21 days.
    • Longer courses of therapy may be required to cure relapses, osteomyelitis or meningitis.
  • The gold standard treatment for adults is daily intramuscular injections of streptomycin 1 g for 14 days and oral doxycycline 100 mg twice daily for 45 days (concurrently). Gentamicin 5 mg/kg by intramuscular injection once daily for 7 days is an acceptable substitute when streptomycin is not available or difficult to obtain.

Prevention and control

  • Human brucellosis can be prevented by controlling and eradicating animal brucellosis.
  • Quarantine and testing.
  • Screening the herds and remove the reactors.
  • Test and slaughter method will be the most rational approach.
  • Hygienic disposal of aborted uterine discharges, foetus and foetal membranes.
  • Vaccination of all calves between 4 and 8 months of age with strain-19 vaccine (Dose is 5 ml in s/c route).
  • The main way of preventing brucellosis is by using fastidious hygiene in producing raw milk products or by pasteurization of all milk that is to be ingested by human beings, either in its pure form or as a derivate, such as cheese.

Vaccination

  • Strain 19 vaccine: Live-attenuated vaccine strain.
  • RB51 vaccine: Newer live-attenuated vaccine strain that is used  at present.
  • "Calfhood vaccination": Vaccination should be done during calfhood (4 to 8 months for S19; 4 to 12 months for RB51) so as to minimize the induction of antibodies that might be interpreted as evidence of actual infection.
  • Vaccination should not be conducted in pregnant animals because of the risk of vaccine-induced abortion.
  • S19 vaccine will induce brucellosis in humans who are inadvertently stuck. If this happens, person should receive doxycycline for 3 weeks and rifampicin antibiotics prophylactically. The potential for human disease due to RB51 remains unclear, but prophylaxis with doxycycline is prudent.
Last modified: Saturday, 17 September 2011, 5:57 AM