Lymphoreticular and Hematopoietic Infections
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BRUCELLOSIS

General Goal: To know the major cause(s) of this disease, how it is transmitted, and the major manifestations of the disease.

Specific Educational Objectives: The student should be able to:

1. recite the most common causes of brucellosis (shape and gram stain?). Is this an intracellular (if so what cells does it dwell in) or extracellular pathogen?

2. describe the common means of transmission.

3. describe the major manifestations. Since this disease is called undulant fever determine what the fever is like (high/low), the periodicity of the fever (daily, every other week), and how long the fever lasts. Other diseases have similar presentations and it will help to know the information requested above.

4. describe how you treat and prevent this infection.

Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 6th Edition. pp.361-363.

Lecture: Dr. Neal R. Chamberlain

Overview

Brucellosis, also called undulant or Malta fever, is a prolonged febrile disease involving the reticuloendothelial system and is transmitted to man from a genitourinary infection of sheep, cattle, and pigs.

Etiology

Brucella abortus, B melitensis, B suis, and B canis are gram-negative coccobacilli.

Manifestations

There are three types of brucellosis: inapparent, acute (lasting < 1 month), and chronic (lasting > 1 month). The incubation period is about 7–21 days after contact, inhalation, or ingestion of the organisms. Symptoms include malaise, chills, daily fevers (39–40°C), weakness, headache, backache, and anorexia and weight loss. Especially in cases of infection due to B melitensis, the fever and drenching sweats recur in late afternoon or evening. Brucellosis can continue for weeks to years. Other symptoms include splenomegaly with lymphadenopathy and hepatomegaly. This recurring febrile disease can be confused with other recurring febrile illnesses (e.g., malaria and relapsing fever). Table P-3 lists the differences in the length of the fever and fever periodicity.

Table P-3. Disease, Causative Agent, Periodicity of fever and Length of Fever in Diseases with Recurring Fevers
Disease	Causative Agent	Periodicity of the fever	Length of fever
Malaria	Plasmodium	Every 2 to 3 days (except P falciparum where fever can be continuous)	Fever lasts 24 hours with the fever ending in a drenching sweat
Brucellosis (undulant fever, or Malta fever)	Brucella	Every day	Fever recurs in the evening and is gone by morning following a drenching sweat
Relapsing fever	Borrelia	Every 7-10 days	Fever lasts 7-10 days

Epidemiology

There are around 120 cases of brucellosis cases per year in the U.S., with 50–60% occurring in handlers of livestock or meat products.
Patients range in age from 20 to 50 years; the disease is five times more common in men than in women.
The disease has been reported in every state in the U.S.; however, more cases occur in states that are heavily involved in the livestock industry.
Infection results from occupational exposure to infected animals (e.g., feral swine) or consumption of unpasteurized products (e.g., milk or cheese). Organisms gain entry by contact through mucous membranes or broken skin or by inhalation or ingestion.

Pathogenesis

The Brucella organisms penetrate the skin or mucous membranes, are engulfed by polymorphonuclear leukocytes, and then enter the lymphatics and the bloodstream. Brucella multiplies within the polymorphonuclear leukocytes and lyses them (facultative intracellular parasite). Brucella can also multiply within the macrophages of the reticuloendothelial system inducing small granulomas and abscesses. Periodic release of Brucella into the blood induces recurrent chills and fever. Antigen-specific activated macrophages are able to kill Brucella with T lymphocytes. B melitensis infections are usually the most severe. B abortus is associated with less frequent infection and a greater proportion of subclinical cases. The virulence of B suis strains for humans varies but is generally intermediate in severity.

Diagnosis

Brucellosis should be suspected in patients with typical manifestations and a history of exposure. Definitive diagnosis requires isolation of Brucella from the blood or from reticuloendothelial tissue biopsies (bone marrow). The gram-negative coccobacilli require 2–3 days of incubation at 37°C and 5–10% carbon dioxide to produce visible colonies on blood agar. A positive tube agglutinin assay using B abortus antigen has a titer of 160–640.

Therapy and Prevention

Treatment of brucellosis includes tetracycline plus gentamicin or streptomycin for 4–6 weeks; fever may persist 2–7 days after the start of therapy. About 10% of cases relapse within 3 months of therapy. Infections can be prevented by minimizing occupational exposure, pasteurizing dairy products, immunizing livestock, and destroying infected stock.

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