Brucellosis
Brucellosis is a zoonosis spread primarily via ingestion of unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever.
The bacteria causing this disease, Brucella, are small, Gram-negative, nonmotile, nonspore-forming, rod-shaped bacteria. They function as facultative intracellular parasites, causing chronic disease, which usually persists for life. Four species infect humans: B. abortus, B. canis, B. melitensis, and B. suis. B. abortus is less virulent than B. melitensis and is primarily a disease of cattle. B. canis affects dogs. B. melitensis is the most virulent and invasive species; it usually infects goats and occasionally sheep. B. suis is of intermediate virulence and chiefly infects pigs. Symptoms include profuse sweating and joint and muscle pain. Brucellosis has been recognized in animals and humans since the early 20th century.
Signs and symptoms
The symptoms are like those associated with many other febrile diseases, but with emphasis on muscular pain and night sweats. The duration of the disease can vary from a few weeks to many months or even years.In the first stage of the disease, bacteremia occurs and leads to the classic triad of undulant fevers, sweating, and migratory arthralgia and myalgia. Blood tests characteristically reveal a low number of white blood cells and red blood cells, show some elevation of liver enzymes such as aspartate aminotransferase and alanine aminotransferase, and demonstrate positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms occur in 70% of cases and include nausea, vomiting, decreased appetite, unintentional weight loss, abdominal pain, constipation, diarrhea, an enlarged liver, liver inflammation, liver abscess, and an enlarged spleen.
This complex is, at least in Portugal, Israel, Palestine, Syria, Iran, and Jordan, known as Malta fever. During episodes of Malta fever, melitococcemia can usually be demonstrated using blood culture in tryptose medium or Albini medium. If untreated, the disease can give rise to focalizations or become chronic. The focalizations of brucellosis usually occur in bones and joints, and osteomyelitis or spondylodiscitis of the lumbar spine, accompanied by sacroiliitis, is very characteristic of this disease. Orchitis is also common in men.
The consequences of Brucella infection are highly variable and may include arthritis, spondylitis, thrombocytopenia, meningitis, uveitis, optic neuritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.
Cause
Brucellosis in humans is usually associated with consumption of unpasteurized milk and soft cheeses made from the milk of infected animals—often goats—infected with B. melitensis, and with occupational exposure of laboratory workers, veterinarians, and slaughterhouse workers. These infected animals may be healthy and asymptomatic. Some vaccines used in livestock, most notably B. abortus strain 19, also cause disease in humans if accidentally injected. Brucellosis induces inconstant fevers, miscarriage, sweating, weakness, anemia, headaches, depression, and muscular and bodily pain. The other strains, B. suis and B. canis, cause infection in pigs and dogs, respectively.Overall findings support that brucellosis poses an occupational risk to goat farmers with specific areas of concern including weak awareness of disease transmission to humans and lack of knowledge on specific safe farm practices such as quarantine practices.
Wildlife reservoirs and zoonotic transmission
Brucellosis affects both domestic and wildlife species, with the latter serving as significant reservoirs that contribute to disease persistence and transmission. Notably, bison, elk, wild boars, and deer have been identified as carriers, particularly in North America and Europe Humans can contract the disease through direct handling of infected animals, aerosol exposure, or consumption of undercooked game meat. Additionally, the wildlife trade has been implicated in the geographical spread of brucellosis, as the movement and sale of infected animals, particularly in unregulated markets, introduce the bacteria into new ecosystems, increasing disease risks for both humans and animals. Reports from Central Asia and sub-Saharan Africa highlight cases where wildlife trafficking has facilitated brucellosis outbreaks in non-endemic regions.Transmission through hunting and game meat consumption
Hunters and individuals who consume wild game face an elevated risk of brucellosis exposure due to direct contact with infected animals and inadequate meat preparation. Transmission can occur during field-dressing or handling of infected carcasses, as Brucella bacteria can enter the body through skin abrasions, mucous membranes, or inhalation of aerosolized pathogens. Additionally, the consumption of undercooked or improperly handled wild game meat remains a significant risk factor, particularly in regions where game animals constitute a primary food source. Implementing protective measures, such as the use of personal protective equipment during handling and ensuring thorough cooking of game meat, is essential to mitigating the risk of brucellosis transmission within hunting communities.Diagnosis
The diagnosis of brucellosis relies on:- Demonstration of the agent: blood cultures in tryptose broth, bone marrow cultures. The growth of brucellae is extremely slow, and the culture poses a risk to laboratory personnel due to the high infectivity of brucellae.
- Demonstration of antibodies against the agent, either with the classic Huddleson, Wright, and/or Bengal Rose reactions, either with ELISA or the 2-mercaptoethanol assay for IgM antibodies associated with chronic disease
- Histologic evidence of granulomatous hepatitis on hepatic biopsy
- Radiologic alterations in infected vertebrae: the Pedro Pons sign and marked osteophytosis are suspicious of brucellic spondylitis.
Due to the similarity of the O polysaccharide of Brucella to that of various other Gram-negative bacteria, the appearance of cross-reactions of class M immunoglobulins may occur. The inability to diagnose B. canis by SAT due to lack of cross-reaction is another drawback. False-negative SAT may be caused by the presence of blocking antibodies in the α2-globulin and in the α-globulin fractions.
Dipstick assays are new and promising, based on the binding of Brucella IgM antibodies, and are simple, accurate, and rapid. ELISA typically uses cytoplasmic proteins as antigens. It measures IgM, IgG, and IgA with better sensitivity and specificity than the SAT in most recent comparative studies. The commercial Brucellacapt test, a single-step immunocapture assay for the detection of total anti-Brucella antibodies, is an increasingly used adjunctive test when resources permit. PCR is fast and should be specific. Many varieties of PCR have been developed and found to have superior specificity and sensitivity in detecting both primary infection and relapse after treatment. Unfortunately, these are not standardized for routine use, and some centres have reported persistent PCR positivity after clinically successful treatment, fuelling the controversy about the existence of prolonged chronic brucellosis.
Other laboratory findings include normal peripheral white cell count, and occasional leucopenia with relative lymphocytosis. The serum biochemical profiles are commonly normal.