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Brucellosis

Brucellosis, also known as undulant fever, Mediterranean fever, and Malta fever, is a zoonotic infection caused by the bacterium Brucella. The primary transmission routes to humans include ingestion of unpasteurized dairy products and direct contact with infected animals or their secretions. This disease has been recognised in both animals and humans since the early 20th century.

Signs and Symptoms

The symptoms of brucellosis are varied and often resemble those of other febrile illnesses. Key symptoms include fever, chills, loss of appetite, night sweats, muscle and joint pain, and headache. The disease can last from a few weeks to several months or even years. In the initial stage, bacteraemia occurs, leading to undulant fevers, sweating, and migratory arthralgia and myalgia. Blood tests typically show a low count of white and red blood cells, elevated liver enzymes, and positive Bengal rose and Huddleston reactions. Gastrointestinal symptoms are present in about 70% of cases, manifesting as nausea, vomiting, weight loss, abdominal pain, and liver issues.

A graph of the cases of brucellosis in humans in the United States from the years 1993–2010 surveyed by the Centres for Disease Control and Prevention through the National Notifiable Diseases Surveillance System.
A graph of the cases of brucellosis in humans in the United States from the years 1993–2010 surveyed by the Centres for Disease Control and Prevention through the National Notifiable Diseases Surveillance System.

Complications

Brucellosis can lead to several severe complications if left untreated. These include central nervous system infections, inflammation and infection of the spleen and liver, epididymo-orchitis in men, arthritis, endocarditis, and various neurological disorders collectively known as neurobrucellosis.

Cause

Brucellosis is caused by Brucella, a small, Gramme-negative, rod-shaped bacterium that functions as a facultative intracellular parasite. Four species infect humans: B. abortus (primarily cattle), B. canis (dogs), B. melitensis (goats and sheep), and B. suis (pigs). B. melitensis is the most virulent and invasive species.

Granuloma and necrosis in the liver of a guinea pig infected with Brucella suis.
Granuloma and necrosis in the liver of a guinea pig infected with Brucella suis.

Diagnosis

Diagnosis relies on several methods, including blood cultures, serological tests, and imaging studies. Blood cultures can take up to two months to grow and pose a risk to laboratory personnel. Serological tests such as the Huddleson, Wright, and Bengal Rose reactions, ELISA, and the 2-mercaptoethanol assay for IgM antibodies are commonly used. Radiologic alterations in infected vertebrae, such as the Pedro Pons sign, are also indicative of brucellosis.

Brucella Coombs Gel Test. Seropositivity detected to GN177.
Brucella Coombs Gel Test. Seropositivity detected to GN177.
Rose Bengal Plate Test.
Rose Bengal Plate Test.

Prevention

Preventive measures include avoiding unpasteurized dairy products, thoroughly cooking meat, wearing gloves, and taking safety precautions in high-risk workplaces. Vaccination of domestic animals is also recommended. Public awareness and education about the disease and its transmission are very important, especially in endemic areas.

Treatment

Brucellosis is treated with antibiotics, typically a combination therapy to prevent relapse and ensure eradication of the bacteria. The gold standard treatment involves daily intramuscular injections of streptomycin for 14 days and oral doxycycline for 45 days. Alternative regimens include doxycycline plus rifampicin and triple therapy with doxycycline, rifampicin, and co-trimoxazole for neurobrucellosis. Despite treatment, relapses occur in 5 to 10% of patients.

Prognosis

Mortality from brucellosis in the early 20th century was around 2%, mainly due to endocarditis. Advances in antibiotics and surgery have reduced mortality rates. Prevention of human brucellosis largely depends on eradicating the disease in animals and adopting safe food practices, such as pasteurising milk and avoiding raw meat.

Epidemiology

Europe

Disease incidence map of B. melitensis infections in animals in Europe during the first half of 2006.
Disease incidence map of B. melitensis infections in animals in Europe during the first half of 2006.

UK

Mainland Britain has been free of brucellosis since 1979, with the last outbreak in cattle occurring in Cornwall in 2004. Northern Ireland was declared officially brucellosis-free in 2015.

United States

The US has a rigorous testing and vaccination programme to control brucellosis. Dairy herds are certified brucellosis-free through annual testing, and infected cows are often culled to prevent disease spread.

History

David Bruce (centre), with members of the Mediterranean Fever Commission (Brucellosis).
David Bruce (centre), with members of the Mediterranean Fever Commission (Brucellosis).

Brucellosis was first noted in the 1850s in Malta and was extensively studied by David Bruce in 1887. Maltese scientist Themistocles Zammit identified unpasteurized goat milk as a significant source of the disease in 1905. Subsequent research by Alice C. Evans in the 1920s helped establish the need for pasteurisation to prevent the disease.

The lab in which Sir Themistocles Zammit and the Mediterranean Fever Commission carried out research about brucellosis from 1904 to 1906 is located within the Castellania in Valletta, Malta.
The lab in which Sir Themistocles Zammit and the Mediterranean Fever Commission carried out research about brucellosis from 1904 to 1906 is located within the Castellania in Valletta, Malta.

Biological Warfare

Brucella species were weaponized by several countries during the mid-20th century. The US developed brucellosis as a biological weapon, but all such weapons were destroyed by 1972 following President Nixon's order to discontinue the biological warfare programme.

Other Animals

Brucellosis affects various domestic and wild animals. In cattle, B. abortus is the principal cause, leading to abortions and arthritic joints. Dogs infected with B. canis can transmit the disease through breeding. Marine mammals are also susceptible to B. ceti, which impacts reproductive health. Wildlife management and vaccination programmes aim to control the spread of brucellosis among animals.


Self-assessment MCQs (single best answer)

What is another name for brucellosis?



What is the primary transmission route of brucellosis to humans?



Which species of Brucella is most virulent and invasive to humans?



What are common symptoms of brucellosis?



What is the gold standard treatment regimen for brucellosis?



Which serological test is commonly used to diagnose brucellosis?



What percentage of brucellosis patients typically experience relapses despite treatment?



Which preventive measure is recommended to avoid brucellosis?



Where was brucellosis first extensively studied in the 1880s?



What is a significant complication of untreated brucellosis?



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