Brucellosis

By: Dr. Hawine Bekele

 Objective
At the end of this lecture students should be
able to:
• know the epidemiology, microbiology,
pathogenesis of brucella infection
• Understand the transmission mode and
treatment of the infection
• be aware about the prevention methods
 Outline
• Introduction
• Epidemiology
• Microbiology
• Transmission
• Pathogenesis
• Clinical presentation
• DDX
• Diagnosis
• Treatment
• Prognosis
 Introduction
• Brucellosis is a bacterial zoonotic infection
caused by the bacterial genus Brucella.
• It is transmitted to humans by contact with fluids
from infected animals (sheep, cattle, goats, pigs,
or other animals) or derived food products such
as unpasteurized milk and cheese.
•  the disease is an old one that has been known
by various names, including meditranian fever,
Malta fever, gastric remittent fever.
• Humans are accidental hosts, but brucellosis
continues to be a major public health concern
world wide and is the most common zoonotic
infection.
• The global burden of human brucellosis
remains enormous: the infection cause more
than 500,000 infections per year world wide.
• Brucellosis has high morbidity both for humans
and animals; it is an important cause of
economic loss and public health problems in
many developing countries.
• The prevalence of brucellosis has been
increasing due to growing international tourism
and migration in addition to the potential use of
brucella as a biologic weapon.
• The organisms which are small aerobic
intracellular cocobacilli localize in the
reproductive organs of host animals, causing
abortions and sterility.
• They are shed in large numbers in the animal’s
urine, milk, placental fluid and other fluids.
• To date, 8 species have been identified, named
primarily for the source animal or features of
infection.
• Of these, the following 4 have moderate to
significant human pathogencity: Brucella
melitensis, Brucella suis, Brucella abortus and
Brucella canis.
• Familiarity with the manifestations of
brucellosis and knowledge of the optimal
laboratory studies are essential for the
recognition of this re-emerging zoonosis.
 Epidemiology
• Brucellosis causes more than 500,000 infections per
year worldwide.
• Its geographic distribution is limited by effective
public and animal health programs, and the
prevalence of the disease varies widely from country
to country.
• Overall, the frequency of brucellosis is higher in
more agrarian societies and in places where handling
of animal products and diary products is less
stringent.
• The heaviest disease burden lies in countries
of the Mediterranean basin and Arabian
peninsula, and is also common in India,
Mexico, south and central America.
• Because of variable reporting, true estimates
in endemic areas are unknown. Incidence
rates of 1.2-70 cases per 100,000 people are
reported.
• 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.
• Brucellosis in the meditrranaian chiefly due to
B.melitensis has the highest age/sex related
incidence in males in their mid 20s.
• For unknown reasons, men aged 13-40 years
are particularly vulnerable to the
manifestations of illness due to B. Melitensis.
• Brucellosis is generally uncommon in infants.
The international literatures suggests that
brucellosis may be more common in children
in developing countries because of lack of
pasteurization and working in an agrarian
society.
• Worldwide, brucellosis is more common in
males than in females. Young adult males
predominate in most series of patients with
brucellosis compiled in areas of endemic
disease.
• A report from northern Saudi Arabia found the
male to female ratio 1.7: 1 chiefly individuals
aged 13-40 years.
• No racial predilection is found.
 Pathophysiology
• Brucellae are aerobic gram- negative
cocobacilli that posses a unique ability to
invade both phagosyitic and nonphagocytic
cells and to survive in the intracellular
environment by finding ways to avoid the
immune system.
• It is a systemic illness and can involve almost
every organ system.
• Brucella can gain entry into the human body through
breaks in the skin mucous membranes, conjunctivae,
respiratory and GI tracts.
• Ingestion usually occur by way of unpasteurized milk
and meat products.
• Once within the blood stream , the organism quickly
become intracellular pathogens contained within
circulating PMN and macrophages making use of
numerous mechanisms to avoid or suppress
bactericidal responses.
• After ingestion by phagocytes, about 15-30%
of brucellae survive. Susuptability to
intracellular killing differs among specieces,
with B.abortus being radily killed and B.
Melitenesis rarely affected.
• Brucellae that survive are transported into the
lymphatic system and may replicate in the
kidney, spleen, liver, breast tissue or joints
causing both localized and systemic infection
• Any organ system can be involved (CNS, heart,
GUS, Pulmonary system, skin)
• Localization of the process may cause focal
symptoms or findings.
• After replication in the endoplastic reticulum ,
the brucellae are released with the help of
hemolysins and induce cell necrosis.
 Microbiology
 Small
 Non-motile
 Facultative intracellular aerobic rods
 0.5-0.7 micron in diameter
 0.6-1.5 micron in length
 Gram negative coco bacilli
 lacks capsule, spores and flagella
 Ethiology
• Brucellosis is caused by infection with brucella
species. The traditional classification of these
species is based primarily based on the
preferred hosts.
Organism Animal reservoir Geographic distribution

Brucella Melitenisis Goats, sheep, camels Mediterranean, Asia,

Latin America, parts of
Africa and some southern
European countries
Brucella Abortus Cows, buffalo, camels, Worldwide
yaks
Brucella suis Pigs (biotype 1-3) South America, Southeast
Asia, USA
Brucella Canis Canines Cosmopolitan

Brucella ovis Sheep No known human case

Brucella neotomae Rodents No known human case

Brucella pinnipediae and Marine animals, dolphins, Human reports with

brucella cetaceae seals neurobrucellosis
• Of the 4 brucella species known to cause
disease in humans B.melitenisis is thought to
the most virulent and causes the most sever
and acute cases of brucellosis, it also the most
prevalent worldwide.
• B. Abortus is more widely distributed
thorough out the world but is less pathogenic
for both humans and animals.
• Slaughterhouse workers, primarily those in the
kill area become inoculated with brucellae
through aerozolization of fluids, contamination
of skin abrasions and splashing of mucus
membrane. Farmers and shepherds have
similar risk.
• Veteranians are usually infected by inadvertent
inoculation of animal vaccine against B.
Melitenisis and B.abortus
 Clinical presentation
• A careful history is most helpful tool in the
diagnosis of brucellosis, since every case of
brucellosis involves exposure to an affected animal
either directly or indirectly.
• Fever is the most common symptom and sign of
brucellosis occurring in 80-100% of cases.
• Fever can be associated with a relative bradycardia
• FUO is a common initial diagnosis in patients with
low endemicity
• Constitutional symptoms of brucellosis include
anorexia, asthenia, fatigue, weakness, malaise
and weight loss are very common (>90%)
• Bone and joint symptoms include arthalgias,
low back pain, spine and joint pain and rarely
joint swelling
• Neuropsychiatric symptoms of brucellosis are
common despite the rare involvement of the
CNS.
• Headache, depression and fatigue are the frequently
reported symptoms.
• 50% of patients have GI complaints primarily dyspepsia.
• Genitourinary infections 2ndry to brucellosis include
orchitis, UTI and glomerulonephritis
• Neurologic symptoms include weakness, dizziness, gait
disturbance
• Cough and dyspnea develop in up to 19% of patients
• Endocarditis is also reported
• The incubation period ranges from one to four
weeks.
• Acute illness usually consists of the insidious
onset of fever, night sweats, atralgia, myalgia,
low back pain, weight loss, fatigue, malaise,
headache and diziness
• Physical findings are variable and non specific
may include hepatosplenomegally and/or
lymphadenopathy
• Localized infection: focal infection occur in about
30% of the cases
• Brucellosis can affect any organ system
• Chronic brucellosis refers to patients with clinical
manifestations for more than one year after the
diagnosis of brucellosis is established
• it is carachterized by localized infection and/or
relapse in patients with objective evidence of
infection
• Physical examination findings:
 Complications
 Osteo articular
 Hepatobiliary and GI
 Genetourinary
 Cardiovascular
 Pulmonary
 Hematolgic
 Diagnosis
• For the diagnosis of brucellosis the laboratory
finding together with the exposure history,
clinical manifestation, occupation is important.
• Laboratory tools for the diagnosis of brucellosis
include culture, serology and PCR
• Ideally the diagnosis is made by culture of the
organism from blood or other sites such as
bone marrow or liver biopsy specimen
• Results of routine labratory studies are usually
non specifc. White blood cell count are usually
normal to low, pancytopenia can occur.
• Minor abnormalities in hepatic enzymes are
relatively common
• The standard test for the diagnosis of
brucellosis is the isolation of organism from
blood or tissues .
• The sensitivity of blood culture with improved
techniques is approximately 60%
 Differential diagnosis
TB
Bacterial pneumonia
 FUO
 Lymphoma
GU TB
 acute epididimitis
 bronchitis
Infectious mononucleosis
Meningitis
 osteomylitis
Typhoid fever
 Treatment
• The goal of medical therapy in brucellosis is to
control symptoms as quickly as possible in
order to prevent complication and relapse.
• Initial care for brucellosis is supportive. Given
the non-specific symptoms the patient
complains it is difficult to diagnose in the ED.
• Although multiple antibiotics display in vitro
activity against brucella species, clinical
respones has been demonstrated with only a
limited number of agents.
• The following drugs display clinical activity
with low relapse rate
• Doxycycline, gentamycin, streptomycin,
rifampin, cotrimoxazole