eMedicine Specialties > Pediatrics: General Medicine > Infectious Disease
Brucellosis
Updated: Jan 25, 2008
Introduction
Background
The first clinical case compatible with brucellosis was credited to JA Maston, an assistant surgeon in the Royal Army Medical Corps. Brucellosis in an alphaproteobacteria that was discovered in 1887 by David Bruce, an English doctor working with British soldiers in Malta, by microscopic examination of a spleen from a fatal case.
Brucellosis is primarily a zoonotic infectious disease found in both domestic and wild animals. Humans are accidental hosts, but brucellosis continues to be a major public health concern worldwide and is the most common zoonotic infection. Brucellosis has been known by various names, including Mediterranean fever, Malta fever, gastric remittent fever, and undulant fever.
Brucellosis can be acquired via exposure to infected animals or infected food. The primary means of prevention is the pasteurization of dairy products, but slaughter campaigns of infected cattle have also been used to control the infection at its source in some countries.
Pathophysiology
Brucella species are facultative intracellular pathogens that are capable of surviving and replicating within phagocytic cells of the host. Shortly after gaining entry to the body, brucellae are ingested by polymorphonuclear leukocytes (PMLs), which are attracted to the site of inoculation. The principal virulence factor is cell wall lipopolysaccharide (LPS). Normal serum factors, including complement, are involved in opsonization of the organisms to allow phagocytosis, but PMLs have limited ability to kill bacteria within phagocytes. A copper-zinc superoxide dismutase, o- polysaccharide, and nucleotidelike substances are among the factors that protect brucellae from being killed by PMLs.
Brucellae that are not killed by PMLs are ingested by macrophages, where they become localized within organs of the reticuloendothelial system (ie, liver, spleen, bone marrow) and multiply in macrophages and monocytes. However, any organ system can be involved in brucellosis (ie, CNS, heart, joints, genitourinary system, pulmonary system, and skin), and localization of the process may cause focal symptoms or findings.
Shortly after infection, humoral antibodies directed against LPS and other cell wall antigens are produced. However, development of cell-mediated immunity is the principle mechanism of recovery. The host response to infection with Brucella abortus is characterized by the development of tissue granulomas indistinguishable from those of sarcoidosis. In contrast, infection with the more virulent species (Brucella melitensis, Brucella suis) more commonly results in visceral microabscesses.
Frequency
United States
Brucellosis is still a reportable disease in the United States, although the Centers for Disease Control and Prevention (CDC) has received reports of only 100-200 cases annually (a rate of 0.4 per one million population) in the last several years. Texas has the highest incidence of cases (1.38 per one million population). Nationally, the infection is due to 2 main sources: importation of disease (from infected food products or international travel) and cross-border spread1 (mostly B melitensis) from Mexico into neighboring states (mostly affecting Hispanics).
International
The geographic distribution of brucellosis is limited by effective public and animal health programs, and prevalence of the disease widely varies from country to country.2 Brucellosis is still endemic in the Mediterranean countries, the Arabian Peninsula, Western Asia, Eastern Europe, and parts of Africa and Latin America. Control campaigns have effectively removed it from countries like the United Kingdom and Ireland. Early vaccination attempts were problematic; the vaccine controlled symptoms of the disease but did not actually prevent infection.
A clear (although nonlinear) association between gross domestic product (GDP) and rates of brucellosis is evident according to European Union (EU) data. No countries with a GDP above 90% of the mean had an incidence above 10 annual cases per million population.
In very resource-poor countries (such as some African countries) in which brucellosis is endemic, control through animal slaughter is a poor option because of the fragile nature of the food supply.
Mortality/Morbidity
Duration of symptoms for more than 30 days before diagnosis is the major risk factor for developing focal disease. Mortality is low (<2%) and is most frequently found in those with endocarditis due to brucellosis.
- The most common focal complications are as follows:
- Osteoarticular complications - Especially, sacroiliitis (20-30% - but rarer in children)
- Genitourinary tract complications - Especially, epididymoorchitis in males (2-49%)
- Neurobrucellosis3 - Meningitis4 (1-2%) and, less commonly, papilledema, optic neuropathy, radiculopathy, stroke, and intracranial hemorrhage
- Endocarditis (1%) - Responsible for most mortality associated with the disease
- Hepatic abscess (1%)
- Other less common complications include the following:
- Splenic abscess
- Thyroid abscess
- Epidural abscess
- Pneumonitis
- Pleural empyema
- Uveitis
- Aneurysm of the aorta
- Aneurysm of the cerebral vessels
- Peritonitis
Race
No racial predilection is known (however, see United States for information about cross-border cases).
Sex
Food-borne brucellosis is not limited according to age or sex and is found in women and men in equal numbers.
Age
Farmers, ranchers, veterinarians, and meat inspectors have the highest risk; however, people of all ages are susceptible. Childhood brucellosis is more common in countries where B melitensis is the prevalent species; in the United States, only about 10% of cases occur in people younger than 19 years.
Clinical
History
In children, brucellosis is frequently a mild self-limiting illness and is less chronic than in adults. A key element in the history is exposure to an infected animal or food. Symptoms are nonspecific, usually occurring within 2-4 weeks of inoculation.
- Symptoms include weakness, excessive sweating, lethargy, anorexia, weight loss, arthralgia, myalgia, abdominal pain, and headache.5
- Symptoms in young children include refusal to eat, lassitude, refusal to bear weight, and failure to thrive.
- Brucellosis can present as a fever of unknown origin,6 and the fever may undulate, repeatedly coming and going (hence, the term "undulant fever").
- In the chronic form, with longer than 1 year of illness (undiagnosed and untreated brucellosis), an afebrile pattern is typical, with a history of myalgia, fatigue, depression, and arthralgias (chronic fatigue syndrome is the most important disease in the differential diagnosis). The chronic form is primarily caused by B melitensis and usually affects adults older than 30 years. The chronic form is rare in children.
Physical
Physical abnormalities can be minimal. Fever and minimal lymphadenopathy are the most common physical findings. Occasionally, hepatosplenomegaly may be present. Disease is infrequently localized; physical findings are predominately related to a single organ.
- Physical examination reveals hot swollen tender joints, with limited movement in patients with arthritis (most commonly knees, ankles, and hips).
- A point of tenderness and limited movement is present in patients with osteomyelitis.
- Sacroiliitis is rare in children.
- Nuchal rigidity, Kerning sign, and Brudzinski sign are seen if meningitis is the focal point.
- Papilledema, cranial nerve palsy, and focal neurologic deficits may be present in patients with increased intracranial pressure or brain abscess.
- Generalized tenderness, rebound tenderness, and sluggish or absent bowel sounds can be expected in patients with peritonitis.
- A tender swollen scrotum with erythema is present in patients with epididymoorchitis.
- A new or changing murmur may be detected in patients with infective endocarditis.
- A pericardial rub is present in patients with pericarditis.
Causes
Brucella species are small, fastidious, non–spore-forming, gram-negative coccobacilli. They lack flagella, endospores, capsules, and naturally occurring plasmids. Their metabolism is oxidative, and all strains are aerobic, although some species require carbon dioxide for primary isolation.
Brucellae have catalase activity, but oxidase activity varies. Most strains reduce nitrate to nitrite. Hydrogen sulfide production and urase activity also vary. The bacteria can be grown on various laboratory media, including serum dextrose, blood, and chocolate agar. Four species are pathogenic to humans: B abortus, B melitensis, B suis, and Brucella canis.
Table 1. Animal Hosts for Brucella Species
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Table
| Nomina Species | Biovars | Preferred Host |
| B abortus | 1-6, 9 | Cattle |
| B melitensis | 1-3 | Goats, sheep |
| B suis | 1-3 | Swine |
| 4 | Reindeer | |
| 5 | Rodents | |
| B canis | None | Dogs |
| Nomina Species | Biovars | Preferred Host |
| B abortus | 1-6, 9 | Cattle |
| B melitensis | 1-3 | Goats, sheep |
| B suis | 1-3 | Swine |
| 4 | Reindeer | |
| 5 | Rodents | |
| B canis | None | Dogs |
More on Brucellosis |
 Overview: Brucellosis |
| Differential Diagnoses & Workup: Brucellosis |
| Treatment & Medication: Brucellosis |
| Follow-up: Brucellosis |
| References |
| Next Page » |
References
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Further Reading
Keywords
brucellosis, Brucella abortus, Brucella melitensis, Brucella suis, Brucella canis, Brucella infection, zoonosis, Mediterranean fever, Malta fever, gastric remittent fever, undulant fever, sarcoidosis, endocarditis, sacroiliitis, epididymoorchitis, meningitis, papilledema, optic neuropathy, radiculopathy, stroke, intracranial hemorrhage, neurobrucellosis, hepatic abscess, splenic abscess, thyroid abscess, epidural abscess, pneumonitis, pleural empyema, uveitis, peritonitis, food-borne brucellosis, failure to thrive, chronic fatigue syndrome, hepatosplenomegaly, lymphadenopathy, arthritis, osteomyelitis
