Etiology
Brucellosis is caused by a bacterium from the genus Brucella. Brucellae are gram-negative aerobic coccobacilli.[1] They lack a capsule, plasmids, and flagella, and are intracellular pathogens. Several species have been isolated. [Figure caption and citation for the preceding image starts]: Brucella organisms and hostsCreated by Dr Nicholas J. Beeching, Dr Sherine Thomas, and Dr Alessandro Gerada [Citation ends].
Brucellosis tends to be an occupational disease, with farmers, animal handlers, abattoir workers, veterinarians, and laboratory personnel at greatest risk.[39][40] In humans, disease is mainly caused by B melitensis, B abortus, B suis, and occasionally by B canis. B melitensis has been associated with more aggressive and acute presentations, and worldwide is the most common species to infect humans. B abortus is usually associated with mild to moderate disease, and rarely causes complications outside the musculoskeletal system. B suis has been associated with focal abscesses.[41][42] B canis tends to cause frequent relapses, but is not commonly associated with chronic brucellosis. Human illness due to marine species of brucellosis (B cetaceae and B pinnipediae) has been recognized, and cases are rare. Other new species are being recognized in animals and in sporadic human cases, including B inopinata BO1, which has been reported in association with breast implants.[8][43][44][45]
The organisms can survive for variable periods of time in milk, cheese, and cream, and have been cultured from dairy products up to 11 weeks after production.[46][47][48][49][50] The organisms are also shed in animal excretions including urine and feces, and in products of conception. They can survive for long periods of time in the soil (up to 2 years), especially if moist, and, therefore, continue to infect humans and animals.[51]
Humans are end-hosts for infection and can acquire brucellosis in a variety of ways, including by ingestion of contaminated foods, especially unpasteurized milk and other dairy products such as soft cheeses, buttermilk, and laban, and, rarely, from raw meat. Infection on farms occurs by direct contact with infected animal products, especially related to parturition or by inhalation of infected aerosols from dried animal products of conception, and in the laboratory from aerosols or splashes onto conjunctivae from infected material. Veterinarians can acquire brucellosis by accidental inoculation of live animal vaccines. Less commonly, brucellosis is transmitted to humans by direct inoculation through cuts and abrasions. In addition, sexual, transplacental, and breast-milk transmission has been reported. Although rare, infection as a result of organ or tissue transplantation and/or blood transfusion can also occur.[52][53][54][55]
Pathophysiology
After ingestion or inoculation, Brucella species invade the mucosa, where polymorphonuclear leukocytes and activated macrophages mediate immune responses to eradicate the bacteria. However, brucellae can multiply and survive intracellularly by inhibiting and counteracting bactericidal effects within the phagosome.[2][56][57] They are then transported intracellularly via the lymphatics to organs rich in reticuloendothelial cells, and from there travel to other organs and tissues, where they can cause inflammation, granuloma formation, necrosis, and abscess formation. In animals, the infection localizes in the erythritol-rich placenta; this effect is less marked in humans, but can still result in abortion or miscarriage.[58][59] Immunity following exposure is not solid, and people may experience reinfection as well as relapse. There is no increase in the frequency or severity of brucellosis in people with HIV infection.[60][61]
The minimum infective dose and the incubation period of the disease depend on the infecting species and its route of entry into the body.[52] The incubation period can vary from 5 days to 7 months.[62][63]
Classification
Clinical classification
Subclinical: asymptomatic disease with an incidental diagnosis following serologic screening of high-risk people.
Acute: symptoms for 2-3 months prior to diagnosis.
Subacute: symptoms for 3-12 months prior to diagnosis.
Chronic: symptoms that persist for ≥1 year.
Relapsing disease: symptoms develop 2- 3 months following completion of therapy.
Formal classification systems for brucellosis vary widely. They are relatively subjective and of limited clinical use. It is more useful to consider whether or not the illness is active and therefore requires treatment, and if or where the disease is localized, which may influence the type and duration of antimicrobial therapy required.[1]
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