Download NAME OF DISEASE HEALTH ALERT

[Insert Health Department Name]
[Insert Unit Name]
[Street]
[City, State and Zip Code]
[Insert Logo]
Phone: [insert number]Fax: [insert number]
[Email Address], [Website]
BRUCELLOSIS HEALTH ALERT
[INSERT DATE]
[Insert short description why Health Alert is being released (e.g., Two cases of brucellosis have been identified)]
This Health Alert and additional information on brucellosis is posted on the [insert website name] at [insert web
link].
ACTIONS REQUESTED OF ALL CLINICIANS:
1.
2.
3.
4.
5.
6.
Consider brucellosis in patients with unexplained flu-like symptoms.
Inquire about exposures.
Report suspected and confirmed cases to the [insert unit/department name] at [insert phone number].
As directed by [insert unit/department name], test suspected cases.
Provide treatment and chemoprophylaxis as described below.
Implement infection control measures.
INCIDENT SUMMARY
[Insert event-specific background information (e.g., Suspected aerosol release of Brucella).]
DESCRIPTION
Brucellosis is caused by bacteria of the genus Brucella. Human infection causes acute febrile illness and can
affect many organ systems, depending on how it is acquired. It is a highly transmissible zoonosis, which mainly
infects ruminant mammals, including cattle, sheep, goats, pigs, and camels. Human infections arise through
direct contact with infected animals or their milk. Fewer than 200 total human cases per year are reported in the
United States, and most of these cases are from Texas and California, where brucellosis is associated with the
ingestion of unpasteurized goat milk products (including “queso fresco”) imported from Mexico. During the
period 1994-2003, there were 275 total cases reported in California; of these, 2 occurred in San Francisco.
Disease incidence is much higher in the Middle East and Mediterranean regions, and in China, India, and Latin
America. The control of human disease is affected by control of animal disease through vaccination, test and
slaughter of infected herds, and by pasteurization of milk products. Human-to-human transmission is rare.
Brucellosis is considered to be a dangerous potential biological weapon because it is highly infectious by the
airborne route and could be used in an aerosolised form or as a contaminant of food, milk and water. The
organism survives well in the environment and widespread contamination is possible. Human infection is rarely
fatal but brucellosis can be a protracted debilitating illness often requiring prolonged antibiotic treatment. There
are no effective human vaccines.
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[Insert Health Department Name]
CASE DEFINITION
The following definitions should be used to identify exposed persons and cases. Testing, treatment, and
implementation of infection control measures should be based upon these definitions.
BRUCELLOSIS: CASE DEFINITION
Categorization
Definition
1. Potentially
History of one of the following:
 Being at [insert location of exposure] during [insert date range during which exposure was
possible (Note: Incubation period is usually within 4 weeks)]; OR
 Ingestion of unpasteurized milk or dairy products infected with Brucellosis (within 60 days
of onset of symptoms); OR
 Being a contact of a probable/confirmed case with a history of:
o Sexual contact (within past 60 days)
o Mother-to-child contact (breast-feeding, trans-placental) (within past 60 days); OR
 Occupational exposure (within past 60 days) including:
o Dermal contact with infected mammals through abrasions of the skin or inhalation of
aerosol from infected products of conception
Exposed person who develops a fever (>38.0ºC or 100.4 ºF) with or without other
characteristic symptoms.
1) Clinically compatible case of Brucellosis: characterized by acute or insidious onset of fever
(>38.0ºC or 100.4 ºF), night sweats, undue fatigue, anorexia, weight loss, headache, and
arthralgias; AND
Exposed Person
2. Suspect Case
3. Probable Case
2a) Epidemiologic link to a confirmed case; OR
2b) Supportive serology (i.e., Brucella agglutination titer of greater than or equal to 160 in one
or more serum specimens obtained after onset of symptoms).
4. Confirmed Case
1) Clinically compatible case of Brucellosis: characterized by acute or insidious onset of fever
(>38.0ºC or 100.4 ºF), night sweats, undue fatigue, anorexia, weight loss, headache, and
arthralgias, AND
2a) Isolation of Brucella sp. from a clinical specimen; OR
2b) Fourfold or greater rise in Brucella agglutination titer between acute- and convalescentphase serum specimens obtained greater than or equal to 2 weeks apart and studied at the same
laboratory; OR
2c) Demonstration by immunofluorescence of Brucella sp. in a clinical specimen.
CLINICAL FEATURES
Clinical manifestations of brucellosis are diverse and often non-specific, and the course of the disease is
variable. For most exposures, the clinical syndrome does not clearly relate to the route of entry of the organism;
however those exposed via the aerosol route may have increased frequency of respiratory symptoms. B.
melitensis tends to cause more severe, systemic illness than the other brucellae; B. suis is more likely to cause
localized, suppurative disease.
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[Insert Health Department Name]
BRUCELLOSIS: CLINICAL FEATURES
Incubation
Period
2-4 weeks (range 5 days – several months)

Transmission
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
Signs &
Symptoms
Laboratory
Findings

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
Inhalation of Brucella bacteria (intentional aerosol release, infected aerosols in laboratory,
infected products of conception from animals)
Ingestion of unpasteurized milk or dairy products infected with Brucella
Direct contact with a person infected with Brucella (sexual, transplacental and breast milk)
Direct skin contact with infected mammals through abrasions of the skin (usually related to
occupational exposure in veterinarians or farmers)
Fever (>38.0ºC or 100.4 ºF) always occurs; spiking or “undulant” pattern may be apparent
May have acute, subacute, or chronic presentation
Other consitutional symptoms: malaise, anorexia, back pain, myalgias, arthralgias,
headache
“Malodorous perspiration”
Mild lymphadenopathy (10-20%)
Hepatomegaly or splenomegaly (20-30%)
Nonspecific skin lesions (papules, ulcers, e. nodosum, petechiae) in 5%
Weight loss among chronically infected
Almost any organ system can be involved
Most affected persons recover in 3-12 months; however, a minority may develop one or
more of the complications below.
Complications
 Skeletal: osteomyelitis (most common); also sacroiliitis, spondylitis, peripheral arthritis
 Reproductive: spontaneous abortion; epididymo-orchitis
 GI: acute ileitis, hepatitis, liver abscess, liver granuloma
 CNS: meningitis, encephalitis, brain abscess, myelitis
 CV: endocarditis, pericarditis
 Pulmonary: bronchitis, pneumonia, lung nodules, abscess, hilar adenopathy, pleural
effusion/empyema, lung abscess
 Uveitis
 Mild leukopenia with relative lymphocytosis
 Mild anemia and thrombocytopenia may be present; DIC is rare
 Other abnormalities are related to the organ system involved
Although the illness can be protracted and debilitating, brucellosis is rarely fatal in humans, less than 2% even
without treatment. Those developing endocarditis are the only subgroup of patients with significant mortality.
REPORTING
Immediately report all cases of brucellosis (including suspect cases) to your facility’s infection control
practitioner AND to the [Insert Department/Unit Name]: [Insert Phone Number]. The health department can
authorize and facilitate testing and will initiate the public health response as needed. Please ask family members
and close contacts of patients for their telephone contact information, or ask these individuals to stay at the
hospital for public health interview and potential intervention.
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[Insert Health Department Name]
INFECTION CONTROL
For all cases including suspect cases in a healthcare setting (hospital, emergency department, nursing facility, or
outpatient clinic):
1. Immediately notify your infection control practitioner(s).
2. Immediately notify [Insert Department/Unit Name]: [Insert Phone Number].
3. Utilize the following infection control precautions:
Infection Control for Caregivers
Person-to-person transmission of brucellosis is extremely rare; therefore, Standard Precautions are considered
adequate for patients with brucellosis.
See http://www.sfcdcp.org/document.html?id=317 for key features of standard infection control
precautions.
Laboratory Workers
Brucella organisms present a significant hazard to laboratory personnel and any sub-culturing or growth should
be handled in containment level 3 facilities.
Decontamination
After exposure to aerosolized Brucella, patients should be instructed to shower using soap and water all over
and remove and launder clothing.
LABORATORY & DIAGNOSTIC TESTING
Consider testing symptomatic persons. Asymptomatic persons need not be tested.
If you are testing or considering testing for Brucella:
1. Immediately notify:
a. [Insert Department/Unit Name]: [Insert Phone Number]. The health department can authorize
and facilitate testing and will initiate the public health response as needed; AND
b. Your hospital laboratory and infection control practitioner that Brucella is under suspicion;
AND
2. If testing is deemed necessary:
a. Use appropriate precautions when obtaining diagnostic specimens.
b. Specimens to be obtained should include:
i. Serum: Collect acute phase serum (10-12 cc) as soon as possible after disease onset
followed by convalescent specimen 21 days later.
ii. Blood: At least two sets of blood cultures should be taken prior to the start of antibiotic
treatment.
iii. Bone marrow, spleen, or liver: Collect per institution’s surgical/pathology procedure.
iv. Other samples as indicated by clinical presentation per institution’s protocol.
c. Submit specimens to your hospital laboratory, and notify them to test for Brucella sp. If needed,
your lab will submit specimens to the public health laboratory for testing.
Tests for Brucella include serology (by Standard Agglutination test (SAT), microagglutination test (MAT), or
ELISA), isolation by culture, and immunoflorescence. The process to culture Brucella takes several weeks, and
is not useful for rapid identification. PCR tests are becoming available, but standardization is still lacking.
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[Insert Health Department Name]
TREATMENT AND CHEMOPROPHYLAXIS
Neither CDC nor the Working Group on Civilian Biodefense has issued bioterrorism-specific
treatment/prophylaxis recommendations for Brucellosis. [Insert Department/Unit Name] will provide
situational guidance in response to events [Insert website link where guidance will be posted].
Treatment
Generally accepted principles of brucellosis treatment are that the antibiotics used must penetrate macrophages,
and that monotherapy has a higher rate of relapse compared with combined therapy regimens. BICHAT, the
European Commission’s Task Force on Biological and Chemical Agent Threats, has recommended as first-line
therapy: Doxycline 100 mg IV/PO twice daily, combined with either streptomycin 1 gm IM once or twice daily
for up to 2 weeks; OR rifampin 600-900 mg PO daily for 6 weeks; OR gentamicin 5 mg/kg/day IV in 2 divided
doses for up to 2 weeks. This regimen, dosage-adjusted to body weight, is also first-line treatment for children
>8 years old. Treatment with trimethoprim-sulfamethoxazole (TMP-SMX) plus rifampin is recommended for
pregnant women and for children <8 years of age. Quinolones have been used with success against Brucellae,
while macrolide antibiotics are not effective. Complications of brucellosis are also treated with 2-drug regimens,
while neurobrucellosis has generally been treated with 3 agents. Relapses occur in about 10% of cases, usually
during the first year after infection, and are often milder in severity than the initial disease. Relapse has been
managed with a repeated course of the usual antibiotic regimens. Most cases of relapse are felt to be caused by
inadequate treatment.
Post-Exposure Prophylaxis
There is no evidence base in human practice to support the use of PEP, but there is some supportive
experimental evidence from animal and laboratory-acquired exposures. The usual combination is rifampin 600
mg daily and doxycycline 200 mg daily. In the event of outbreak, [Insert Department/Unit Name] will
provide updated, situational guidelines for prophylaxis [Insert website link where guidance will be
posted].
Exposed persons should be made aware that development of fever, malaise, unexpected loss of weight or
joint/bone pain may be due to brucellosis and that they should mention this possibility if they attend any
physician for care. Clinical incubation could be prolonged for up to six months.
Possible recommended prophylaxis after exposure to Brucella (from WHO and British health authorities)
Antimicrobial agent
Adults
Children over 121
Children under 12
Doxycycline 100 mg PO twice daily
plus
Rifampin 600 mg PO daily
Doxycycline 2mg/kg PO twice daily
plus
Rifampin 10-15 mg/kg PO daily
Co-trimoxazole (sulfamethoxazole 40mg/kg
and trimethoprim 8mg/kg) PO daily
plus
Rifampin 10-15 mg/kg PO daily
Duration
3-6 weeks
3-6 weeks
3-6 weeks
Women who are
Rifampin2 600 mg PO daily
3-6 weeks
pregnant or breastfeeding
1
WHO recommends this treatment for children >8 years old. However, it is recognized that doxycycline should
not be given to children less than 12 years of age, or to pregnant or breastfeeding women. Doxycyline
combination treatment is only recommended for children over 12 years old.
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[Insert Health Department Name]
2
In pregnancy, rifampicin alone is conventionally used, although experience in the Middle East suggests that
combination with cotrimoxazole (2 tablets bd) is safe and effective. Fluoroquinolones may be used as an adjunct
in complicated cases or as a substitute for doxycycline in pregnant women. Expert advice should be obtained.
Persons directly exposed should have a baseline serum sample stored for possible later comparative serology in
the event of their developing symptoms.
Vaccine
There is currently no licensed vaccine available for brucellosis. Some limited clinical data exist on a live,
attenuated vaccine candidate, but licensing and production of this vaccine are not anticipated.
ADDITIONAL RESOURCES
 [Add your health department name and link.]
 CDC Emergency Preparedness & Response Bioterrorism Site: www.bt.cdc.gov/bioterrorism
 Health Protection Agency Deliberate Release:
www.hpa.org.uk/infections/topics_az/deliberate_release/menu.htm
REFERENCES
HPA (Health Protection Agency) Interim Guidelines for Action in the Event of a Deliberate Release:
Brucellosishttp://www.hpa.org.uk/infections/topics_az/deliberate_release/Brucellosis/brucellosis_guidelines.pdf
Accessed November 14, 2006.
CDC. Case definitions for infectious conditions under public health surveillance. MMWR 1997;46(RR10):1-55
http://www.bt.cdc.gov/Agent/Brucellosis/CaseDef.asp Accessed November 14, 2006.
CDC. Brucellosis technical information. Division on bacterial and mycotic diseases.
http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_t.htm Accessed November 14, 2006.
Bossi P et al. Bichat Guidelines for the Clinical Management of Brucellosis and Bioterrorism-related
Brucellosis. Eurosurveillance 2004; 9(12):1-5.
WHO. Brucellosis. World Health Organization Essential Medicines Library EMLib
http://mednet3.who.int/eml/disease_factsheet.asp?diseaseId=274 Accessed November 14, 2006.
Noriello S. Laboratory-acquired brucellosis. Emerg Infect Dis 2004; 10: 1848-1850.
Robichaud S, Libman M, Behr M, Rubin E. Prevention of laboratory-acquired brucellosis. Clin
Infect Dis 2004; 38:119-122.
Pappas G et al. Brucellosis. N Engl J Med 2005;352:2325-36.
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