Brucellosis of the nervous system

Katelyn Bird (Ms. Bird of Indiana University School of Medicine has no relevant financial relationships to disclose.)
Karen L Roos MD FAAN (Dr. Roos of Indiana University School of Medicine has no relevant financial relationships to disclose.)
Originally released April 10, 1998; last updated April 2, 2018; expires April 2, 2021

This article includes discussion of brucellosis of the nervous system, Crimean fever, Malta fever, Mediterranean fever, micrococcus melitensis, remittent fever, and undulant fever. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.


Brucellosis is a multisystem bacterial illness and is 1 of the most common zoonotic diseases worldwide, endemic in many Mediterranean and Middle Eastern countries. Globally, more than 500,000 new cases occur each year. The disease is transmitted to humans through consumption of infected, unpasteurized animal milk or through direct contact with infected animals. Nonspecific complaints include irregular fevers, malaise, arthralgia, myalgia, weight loss, and night sweats. Infection of the nervous system, known as neurobrucellosis, occurs in 4% of patients. The neuropathology involves direct bacterial invasion, complicated by an inflammatory response. Isolation of Brucella remains the gold standard for diagnosis, but serological tests, including point-of-care assays and polymerase chain reaction, aid in establishing the diagnosis. Forty-five percent of patients will have abnormal neuroimaging findings. Parenteral ceftriaxone in combination with doxycycline and rifampin is now recommended as first-line therapy to achieve eradication and reduce the risk of relapse.

Key points


• Brucellosis is an acute, subacute, or chronic zoonotic illness caused by nonmotile, unencapsulated, intracellular, gram-negative coccobacilli that involves the central and peripheral nervous systems in approximately 4% of patients.


• Neurologic disease is caused by infection of the bacterium, as well as the inflammatory response elicited by the infection.


• The diagnosis of neurobrucellosis is made definitively by isolation of the bacteria in the CNS or presumptively in the context of a systemic infection with a neurologic syndrome.


• Forty-five percent of neurobrucellosis patients have abnormal neuroimaging findings, including inflammatory findings in the dura, leptomeninges, cranial nerve and/or spinal nerve roots, white matter involvement, vascular involvement, or hydrocephalus/cerebral edema.


• Treatment of neurobrucellosis using combined antibiotics regimens with a minimum of 1 month of parenteral ceftriaxone is recommended to achieve eradication and reduce the risk of relapse.

Historical note and terminology

Brucellosis has been present for millennia (Capasso 2002). In 1859, JA Marston gave the first clinical account of the disease that he named “Mediterranean fever” (Dalrymple-Champneys 1950). At that time, the condition was also known as “undulant,” “remittent,” “Malta,” or “Crimean fever.” Surgeon David Bruce was the first to isolate a “micrococcus” bacterium and identify it as the causative agent of Malta fever (Bruce 1889). This gram-negative coccobacilli was later renamed “Brucella” in his honor (Tan and Davis 2011).

Some medical historians have proposed that the chronic headaches and severe weakness suffered by Florence Nightingale may be attributable to neurobrucellosis contracted while serving during the Crimean War (Young 1995).

Brucellosis was 1 of 5 infectious agents (including anthrax, tularemia, Q fever, and Venezuelan equine encephalitis) developed by the United States during the Cold War as a potential biologic weapon (Hart and Ketai 2015). The U.S. National Institutes of Health have classified Brucella melitensis as a category B priority pathogen and possible bioterrorist agent due to its potential for infection via aerosol (Yagupsky and Baron 2005).

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