BRUCELLOSIS

Case identification and management in humans

Esayas Kebede Gudina, MD, DTM&H, PhD
Associate Professor of Medicine
Jimma University
May 2019
LEARNING OBJECTIVES
 Define Brucellosis

 Describe the epidemiology of brucellosis in human

 Explain how Brucella affect the body

 Describe clinical manifestation and case definition of

brucellosis in human

 Explain diagnosis and management of brucellosis

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What is one health?

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BRUCELLOSIS
= Bang's disease
= Crimean fever
= Gibraltar fever
= Malta fever
= Maltese fever
= Mediterranean fever
= Rock fever
= Undulant fever

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BRUCELLOSIS
 It is a highly contagious zoonotic infection

 Mainly disease of livestock:

 Cattles, goat, sheep and pigs are main reservoirs

 Humans almost always get the infection from

animals

 Affects all age and both sexes

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TRANSMISSION
 Oral entry - most common route
 Ingestion of contaminated animal products: raw milk, cheese or
meat
 Contact with contaminated fingers

 Percutaneous
 Close contact with secretions

 Aerosols
 Inhalation
of dried secretions
 Contamination of the conjunctiva

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 Human to human transmission is very rare
 ETIOLOGY
 Brucellosis is caused by different Brucella Spp.
 Gram negative bacteria
 Strict aerobic, nonmotile, nonspore forming

B. melitensis B. abortus B. suis B. canis

Disease in Most common Less common very rare Infrequent
human
Severity of Severe Subclinical/mild Severe mild
disease
Source Sheep, goats, Cattle or buffalo Swine Dog
and camels
Clinical Acute and More insidious in onset Focal -
syndrome aggressive and more likely to abscess
presentation become chronic
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EPIDEMIOLOGY
 The disease exists worldwide

 The true global prevalence of human brucellosis is unknown

 Misdiagnosis of cases
 Inadequacy of reporting
 Lack of disease surveillance

 Major endemic areas include:

 Countries of the Mediterranean basin
 Arabian Gulf
 The Indian subcontinent
 Parts of Mexico
 Central and South America

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 It causes more than 500,000 infections per year worldwide
BRUCELLOSIS IN ETHIOPIA

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GROUP DISCUSSION
Group 1 – Who are at risk for brucellosis infection?

Group 2 – How is brucellosis transmitted?

Group 3 – What are determinants of disease (brucellosis) in

humans?

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PREVALENCE IN ETHIOPIA
Brucellosis Seropositivity in Animals and Humans in
Ethiopia: A Meta-analysis

 The overall true prevalence estimated – 6.7%

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Getachew Tadesse. PLoS Negl Trop Dis. 2016

HUMAN BRUCELLOSIS IN ETHIOPIA
Seroepidemiology of Human Brucellosis Among Blood Donors in
Southern Ethiopia: Calling Attention to a Neglected Zoonotic Disease

The seroprevalence of human brucellosis in this

study was found to be 10.6%

Possessionof domestic ruminant animals, contact

with ruminant animals, and husbandry practices at
home were associated with seropositivity.

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Workalemahu B et all. 2017. ASTMH
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CLINICAL PRESENTATION
 The presentation of brucellosis is characteristically
variable and non-specific:
 Fever • Arthralgia
 Night sweats • Fatigue
 Malaise • Weight loss
 Anorexia • Depression

 Fever is the most common symptom

 The onset may be abrupt or insidious

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CLINICAL PRESENTATION
 The incubation period varies from 1 week to several
months

 Presentation of brucellosis often fits one of three

patterns:
1. Febrile illness that resembles typhoid but is less severe
2. Fever and acute monoarthritis, typically of the hip or knee
(in a young child)
3. Long-lasting fever and low-back or hip pain (in older
people)

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FEVER IN BRUCELLOSIS
 Brucellosis almost invariably causes fever and presents
commonly as acute febrile illness

 Two features that distinguish brucellosis from other

tropical fevers:
1. Left untreated, the fever of brucellosis shows an
undulating pattern that persists for weeks before the
commencement of an afebrile period
2. Presence of musculoskeletal symptoms and signs in about
one-half of all patients

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PHYSICAL FINDINGS
 Fever – 38 to 40oC

 Hepatosplenomegaly (or isolated hepatomegaly or

splenomegaly)

 Osteoarticular findings can include tenderness and

swelling over affected joints, bursitis, decreased range of
motion, and joint effusion (rare).

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SYSTEMIC INFECTIONS WITH
BRUCELLOSIS
 Osteoarticular disease, especially sacroileitis — 20 to 30
% percent and vertebral spondylitis.
 Large joints are affected most commonly in children

 Genitourinary disease, especially epididymo-orchitis – 2

to 40 % of males

 Neurobrucellosis, usually presenting as meningitis —1

to 2 %

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COMPLICATIONS OF BRUCELLOSIS
 Endocarditis

 Hepatic abscess

 Damage of prosthetic devices

 Prosthetic heart valves
 Pacemakers
 Prosthetic joint

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DIFFERENTIAL DIAGNOSIS
 Typhoid Fever
 Tuberculosis

 Malaria

 Ankylosing Spondylitis and Undifferentiated

Spondyloarthropathy
 Influenza

 Infective Endocarditis

 Infectious Mononucleosis

 Viral Hepatitis

 Cryptococcosis

 Histoplasmosis
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 Leptospirosis
LABORATORY FINDINGS
 Leucocyte count – Normal/reduced
 Thrombocytopenia

 ESR/CRP-Normal/Increased

 CSF/Body fluid analysis – Lymphocytosis, low glucose levels

 Biopsied samples of lymph node, liver – non-caveating

granuloma without acid fast bacilli

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DIAGNOSIS
 History of exposure
 Isolation of Brucella spp. from blood, BM, joint or body
fluid
 Bloodculture - 60% sensitivity
 Bone marrow culture – 80-90% sensitive

 Serological tests - main method of diagnosis

 Serum agglutination test
 ELISA Rose Bengal test – not validated for human
diagnostic
 PCR
 Imaging of bones and joints

 Biopsy of affected organs 23

CASE DEFINITION OF BRUCELLOSIS
Clinical Description
An illness characterized by acute or insidious onset of fever and
one or more of the following:
 Night sweats, arthralgia, headache, fatigue, anorexia, myalgia,
weight loss, arthritis/spondylitis, meningitis, or focal organ
involvement (endocarditis, orchitis/epididymitis,
hepatomegaly, splenomegaly) 

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2010
LABORATORY CRITERIA FOR
DIAGNOSIS
Definitive 
 Culture and identification of Brucella spp. from clinical specimens
 Evidence of a fourfold or greater rise in Brucella antibody titer
between acute- and convalescent-phase serum specimens obtained
greater than or equal to 2 weeks apart
Presumptive
 Brucella total antibody titer of greater than or equal to 160 by
standard tube agglutination test (SAT) or Brucella
microagglutination test (BMAT) in one or more serum specimens
obtained after onset of symptoms
 Detection of Brucella DNA in a clinical specimen by PCR assay 25
CASE CLASSIFICATION
Probable
 A clinically compatible illness with at least one of the
following:
 Epidemiologically linked to a confirmed human or animal
brucellosis case
 Presumptive laboratory evidence, but without definitive laboratory
evidence of Brucella infection

Confirmed
 A clinically compatible illness with definitive laboratory
evidence of Brucella infection
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CASE -1
 A 29-year-old woman who worked as a research assistant in a
veterinary microbiology laboratory complainsed of
intermittent fever, anorexia, profuse sweating, malaise,
headache, normotensive (110/60 mm Hg) and muscle pain
especially of the neck and shoulder, and arthralgia for 3 d.

 She was one of the 9 laboratory workers who were involved

in a research on isolation of B. melitensis from goats for the
past 3 months.

 How do you approach?

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CONT…..
 The next day, she was admitted to a clinic for blood tests
against dengue and malaria but was found negative.

 Therefore, a common flu was suspected and she was

prescribed vitamin C, paracetamol and cough syrup.

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CONT…..
 The complaints, however, persisted on and off for the
next one month and the conditions were getting worse.
 Anemia and hypotension (90/50 mm Hg) were
eventually developed and she started to show reduced
body weight from 50 kg to 43 kg.
 Abdominal palpations revealed hepatomegaly and
splenomegaly with pain.
 The hemoglobin, hematocrit and neutrophil were low
while the lymphocytes and erythrocyte sedimentation
rate were high during the first month of infection.
 What is next step? 29
CASE 2
 A 19-year-old man presented with a 2-week history of fever,
sweating, low back and leg pain, lassitude, loss appetite, nausea and
vomiting.
 He gave a history of raw milk ingestion and animal contact.

 Physical examination showed signs of icteric skin and sclera,

tenderness in the right hypochondriac region and
hepatosplenomegaly.
 On admission to hospital, laboratory tests showed WBC 3500/mmc
(polymorphs 63% and lymphocytes 33%), haemoglobin 13.8 g/dL,
platelet 89000/mmc, erythrocyte sedimentation rate 19 mm/h, and C-
reactive protein 21.7 mg/dL (N<0.8 mg/dL).
 Biochemical tests were as follows: AST 771 U/L, ALT 471 U/L, ALP
355 U/L, GGT 432 U/L, total bilirubin 2.61 mg/dL, direct bilirubin
1.45 mg/dL and albumin 3.7 g/dL. 30
CONT
 Viral hepatitis markers were found to be negative (HBsAg,
anti-HBc total, anti-HBc IgM, anti-HAV IgM, and anti-
HCV).
 Blood culture grew Brucella melitensis.

 Leukopenia and thrombocytopenia returned to normal levels

at the 7th and 14th day of his admission, respectively.
 Liver function tests improved at the 28th day.

 Treatment of the brucellosis was performed with antibiotics

(tetracycline 500 mg orally four times daily for 6 weeks and
streptomycin 1 g IM once daily for 21 days).
 Finally, a case of brucellosis with acute hepatitis and
bicytopenia was treated with a successful outcome. 31
CASE 3
 A 39-year-old lady having unusually chronic
asymmetric, additive, peripheral polyarthritis.

 The patient had a history of contact with an aborted goat.

 The patient has also contact with sheep

 How do you approach this patient?

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CONT…..
 Isolation was confirmed by Bruce-Ladder polymerase
chain reaction (PCR) from synovial fluid.

 Rose Bengal Plate Agglutination Test (RBPT) and

Standard Tube Agglutination Test (SAT) were positive
for Brucella-specific antibodies both for patient and in
contact with sheep and goats.

 The patient was treated with doxycycline and rifampicin

for 16 weeks and was recovered fully
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TREATMENT
 Antimicrobial treatment

 Aim of treatment
 Relieves symptoms
 Shortens the duration of illness
 Reduces the incidence of complications and relapse

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TREATMENT OF BRUCELLOSIS
Adult
 IM streptomycin (0.75–1 g daily for 14–21 days)
together with doxycycline (100 mg twice daily for 6
weeks) This regimen is believed to be more effective, mainly
in preventing relapse.

 Rifampin (600–900 mg/d) plus doxycycline (100 mg

twice daily) for 6 weeks More convenient but probably
increases the risk of relapse.

Children and pregnant women

 IM streptomycin and TMP-SMX
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TREATMENT OF COMPLICATION
 Brucella endocarditis
IM streptomycin with a tetracycline and rifampin for 6 months

 Neurobrucellosis
IM streptomycin with doxycycline and ceftriaxone

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PREGNANCY AND BRUCELLOSIS
 Premature labor and fetal wastage

 Treatment options
 Rifampin — 900 mg once daily for six weeks

 Rifampin— 900 mg once daily plus trimethoprim-

Sulphmethoxazole (TMPSMX; 5 mg/kg of the trimethoprim
component twice daily) for four weeks

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PREVENTION
 National commitment to testing and slaughter of infected
herds/flocks, control of animal movement, and active
immunization of animals

 Pasteurization of all milk products before consumption

 Reporting all cases of brucellosis in animals and humans

to the appropriate public health authorities

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POST EXPOSURE PROPHYLAXIS (PEP)
AND VACCINATION IN HUMAN
 Following accidental injury, Doxycycline for 6 weeks is
advised

 No safe, effective vaccine exists to immunize humans

against brucellosis.

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PROGNOSIS
 Relapse occurs in up to 30% of poorly compliant
patients

 Mortality is low

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BIO-TERRORISM
 B. melitensis and B.suis have been developed experimentally
as biological weapons by state sponsored programmes

 Their relative stability in aerosol form, combined with low

infectious dose make them suitable agents for this purpose.

 Brucella could be used to attack human and/or animal

populations.

 The impact is likely to be greatest in those areas in which the

disease is not endemic.

 The organism can be obtained from natural sources in many 41

parts of the world.
SUMMARY
 Cattles, goat, sheep and pigs are main reservoirs
 Most cases are caused by B. melitensis

 Transmission to human occurs through environmental or

occupational contact with infected animal, foodborne
and rarely person to person

 Common presentation is acute febrile illness

 Complication may affect any organ system

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SUMMARY…
 Definite diagnosis is made by isolation of brucella from clinical
specimen

 Essential element of treatment of brucellosis is providing effective

antibiotic for adequate length of time

 Treatment in uncomplicated brucellosis in adults is with streptomycin

and doxycycline

 Prevention of human brucellosis is based on occupational hygiene and

food hygiene
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 Prognosis is good with treatment
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