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Brucellosis
Professor AbdelRahman A Mokhtar
Internal Medicine Dept
Mansoura University
2014
Center for Food Security and Public Health, Iowa State University, 2008
Human brucellosis
María Pía Franco, Maximilian Mulder, Robert H Gilman, Henk L Smits
A renewed scientific interest in human brucellosis has
been fuelled by its recent re-emergence and enhanced surveillance in many
areas of the world, and from its status as a class B bioterrorist agent.
The disease remains the world’s most common bacterial zoonosis, with over half
a million new cases annually and prevalence rates in some countries exceeding
ten cases per 100 000 population.
Despite being endemic in many developing countries,brucellosis remains
underdiagnosed and under-reported.
Furthermore, since brucellosis is an important cause of veterinary morbidity and
mortality,the disease can also cause important economic losses indeveloping
countries
Lancet Infect Dis 2007; 7: 775–86
Center for Food Security and Public Health, Iowa State University, 2008
Endemicity :
Endemicity :
Aseroprevalence
rate of 20% was
identified on the
Arabic Peninsula,
with greater than
2% having active
brucellosis.
In the Middle East,
B. melitensis may
exceed the
prevalence of B.
abortus in cattle in
some areas as it
has emerged on
some intensive
dairy farm
Expansion of animal industries and urbanization, and the lack of hygienic
measures in animal husbandry and in food handling, as well as consumers‟
preference for fresh dairy goods which may be contaminated, partly account for
Brucellosis remaining a public health hazard.
The Organism
Center for Food Security and Public Health, Iowa State University, 2008
Brucella spp.
• Gram negative, coccobacilli bacteria
• Facultative, intracellular organism
• Environmental persistence
− Temperature, pH, humidity
− Frozen and aborted materials
− It is a facultative, intracellular
pathogen and thus requires prolonged
treatment with clinically effective
antibiotics.
• Multiple species
Susceptibility
 Killed at 600 C in 10
minutes
 Pasteurization of milk .
 Survival is long in
refrigerated milk,
ice creams and cheese.
Center for Food Security and Public Health, Iowa State University, 2008
Species Biovar/
Serovar
Natural Host Human
Pathogen
B. abortus 1-6, 9 cattle yes
B.melitensis 1-3 goats, sheep yes
B. suis 1, 3 swine yes
2 hares yes
4 reindeer, caribou yes
5 rodents yes
B. canis none dogs, other
canids
yes
B. ovis none sheep no
B. neotomae none Desert wood rat no
B. maris (?) marine mammals ?
Center for Food Security and Public Health, Iowa State University, 2008
Order of pathogenicity to humans:
B. melitensis,
B. suis
B. abortus,
Rarely
B. canis,
and
marine mammal Brucella.
Center for Food Security and Public Health, Iowa State University, 2008
The Many Names of Brucellosis
Human Disease
• Malta Fever
• Undulant Fever
• Mediterranean Fever
• Rock Fever of
Gibraltar
• Gastric Fever
Animal Disease
• Bang’s Disease
• Enzootic Abortion
• Epizootic Abortion
• Slinking of Calves
• Ram Epididymitis
• Contagious Abortion
Center for Food Security and Public Health, Iowa State University, 2008
History
Center for Food Security and Public Health, Iowa State University, 2008
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases
•Contracted Malta
fever
•Described his own
case in great detail
Jeffery Allen
Marston
Center for Food Security and Public Health, Iowa State University, 2008
Sir David Bruce
(1855-1931)
•British Army
physician and
microbiologist
•Discovered
Micrococcus
melitensis
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases
Center for Food Security and Public Health, Iowa State University, 2008
Bernhard Bang
(1848-1932)
•Danish physician
and veterinarian
•Discovered
Bacterium abortus
could infect cattle,
horses, sheep,
and goats
Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases
Center for Food Security and Public Health, Iowa State University, 2008
History
• Alice Evans, American bacteriologist
− Credited with linking the organisms
− Similar morphology and pathology
between:
 Bang’s Bacterium abortus
 Bruce’s Micrococcus melitensis
• Nomenclature today credited to
Sir David Bruce
− Brucella abortus and Brucella melitensis
Transmission
Center for Food Security and Public Health, Iowa State University, 2008
Transmission to Humans
• Conjunctiva or broken skin
contacting infected tissues
( Brucella abortus and B. suis infections often )
− Blood, urine, vaginal discharges, aborted
fetuses, placentas
• Ingestion ( Brucella melitensis infection is primarily foodborne )
− Raw milk & unpasteurized dairy
products
− Rarely through undercooked meat
Center for Food Security and Public Health, Iowa State University, 2008
Transmission to Humans
• Inhalation of infectious aerosols
− Pens, stables, slaughter houses
• Inoculation with vaccines
− B. abortus strain 19, RB-51
− B. melitensis Rev-1
− Conjunctival splashes, injection
• Person-to-person transmission is very rare
(blood transfusions, bone marrow transplants, and sexual
contact between lab workers and their spouse)
• Incubation varies
− 5-21 days to three months
Center for Food Security and Public Health, Iowa State University, 2008
Who is at Risk?
• Occupational Disease
− Cattle ranchers/dairy farmers
− Veterinarians
− Abattoir workers
− Meat inspectors
− Lab workers
• Hunters
• Travelers
• Consumers of unpasteurized dairy
products
Center for Food Security and Public Health, Iowa State University, 2008
Disease in Humans
Pathophysiooogy
After infecting the host, the pathogen becomes sequestered within cells of the
reticuloendothelial system. The mechanisms by which brucella enters cells and
evades intracellular killing and the host immune system are the subject of much
research and debate.
In depth analysis of the complete Brucella spp genomes has failed
to identify any of the classic virulence factors such as toxins, fimbriae, and capsules,
which raises the possibility that these organisms use unique and subtle mechanisms
to evade host defences, penetrate host cells, alter intracellular trafficking to avoid
degradation and killing in lysosomes, and modulate the intracellular environment to
allow long-term intracellular survival and replication.
Research suggests that the smooth, non-endotoxic lipopolysaccharides help block the
development of innate and specifi c immunity during the early stage of infection, and
protect the pathogen from the microbicidal activities
of the immune system.
Additionally, smooth lipopolysaccharide in brucella may be involved in the inhibition of
apoptosis (ie, programmed cell death) of infected cells, since
resistance to apoptosis of infected cells has been observed in patients with acute and
chronic disease
The organism can gain entry through abraded skin, mucous membranes and
conjunctiva[ .
Entry of the organism through any of these surfaces invites phagocytic neutrophil cells
to the site of entry and the organism is phagocytosed by neutrophils and tissue
macrophages.
They carry the ingested organism to the regional lymph nodes.
If the organism escapes host defense mechanisms in the regional lymph node, spread
to the circulation occurs resulting in bacteremia.
These free organisms in circulation are phagocytosed by the neutrophils and localization
occurs primarily to the liver, spleen and bone marrow with formation of granulomas
Complications like endocarditis,
osteomyelitis, neurobrucellosis
are rare if appropriate
antimicrobial therapy is started
during the first few weeks of the
illness
Malta Fever
The one common sign in all patients is an intermittent
irregular fever of variable duration, thus the term undulant
fever.
Others develop an intermittent fever and other persistent
symptoms that typically wax and wane at 2- 14 day intervals.
Most people with this undulant form recover completely in
three to 12 months.
A few patients become chronically ill.
Relapses can occur months after the initial symptoms, even
in successfully treated cases.
In many patients, the symptoms last for two to four weeks
and are followed by spontaneous recovery.
Brucellosis remains a diagnostic puzzle due to
Ambiguous,
Non-specific manifestations
& increasingly unusual presentations.
 The disease is characterized by acute
bacteremic phase followed by a chronic stage
during which the bacteria localize in
reticuloendothelial tissues (LNs, liver, spleen,
bone marrow).
 Manifestations of the disease include:
1) Fever for 3-4 weeks followed by afebrile
period of similar duration, so it is called
undulant fever.
2) Weakness, bone pain, profuse sweating +
enlarged LNs, liver and spleen.
3) Brucella melitensis is the most severe
form.
Human brucellosis has a wide spectrum of clinical
manifestations, earning it a place alongside syphilis and
tuberculosis as one of the “great imitators
Thus to an unaware
physician, the clinical
diagnosis becomes a
challenging one.
Disease predominantly developing in one organ or organ
system is described as localized.
Human brucellosis usually manifests as an acute (< 2 months)
or subacute (2-12 months) febrile illness, which may persist
and progress to a chronically (> 1 year) incapacitating
disease with severe complications.
However, distinctions
between generalized and localized disease, or between acute
and chronic disease, are largely arbitrary, as the pathogenic
processes remain the same.
Unusual manifestations of brucellosis: a retrospective case series in a
tertiary care Greek university hospital
I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris
EMHJ • Vol. 16 No. 4 • 2010
Eastern Mediterranean Health Journal
La Revue de Santé de la Méditerranée orientale
Clinical Patterns
Subclinical form
• Subclinical or asymptomatic infection
• This clinical form is diagnosed by
positive serology.
• The patients have no history or
physical signs of acute or chronic
illness. It has been documented
more frequently in farmers, abattoir
workers, and veterinarians.6,39
Acute form
• This is the typical form of
brucellosis.
• Almost all patients have a history
of fever accompanied by
weakness, malaise, headache,
back-ache, anorexia, weight loss,
myalgia, and arthralgia.
• A temperature over 38.5”C is
measured in more than 85% of
patients.
• Splenomegaly and hepatomegaly
are found in about 6-35% of the
cases.
• Any organ involvement can be
seen, but arthritis is more
frequent (40-50%).
Subacute form
• This refers to a group of patients who have relapsed
because of incomplete or partial antibiotic treatment and
patients who have received inappropriate antibiotics
because of incorrect diagnosis.
• The clinical picture is more protean and may be an
important cause of fever of unknown origin.
• The symptoms are generally milder, and localized infection
can be seen.
Chronic brucellosis
• Chronic brucellosis is similar to chronic fatigue
syndrome.
It is extremely rare in children, but frequent in
older people. These patients generally suffer from
a psychoneurosis, sweating, and weight loss.
Fever is rare. Localized infection can be seen;
however, ocular manifestations, such as
episcleritis and uveitis, are frequent.
Chronic brucellosis can be extremely difficult to diagnose, if the serologic
results are equivocal and the organism cannot be cultured.
Localized infection
• Localized brucellosis refers to cases in which organisms
are not isolated from blood but are localized in specific
tissues, such as the bone, joints, cerebrospinal fluid, liver,
kidneys, spleen, or skin.
Localization may be the
principal manifestation of systemic infection, or may be
the only manifestation of a chronic infection. Localized
infection is sometimes named as a complication when it
occurs as a result of systemic infection.
Center for Food Security and Public Health, Iowa State University, 2008
The most common sites
• Involved are osteoarticular,
especially sacroiliitis (20%–30%)
with large joints most frequently
affected in children, and the
genitourinary system, especially
epididymo orchitis (2%–40% of
males).
• Osteoarticular disease is universally the most common
complication of brucellosis, and three distinct forms exist — peripheral
arthritis, sacroiliitis, and spondylitis.
• Osteoarticular complications are sometimes linked to a genetic predisposition,
• with recent data suggesting an association with HLA-B39.
• Peripheral arthritis
• Is the most common and is nonerosive, since it usually involves the knees,
hips, ankles, and wrists in the context of acute infection.
Prosthetic joints can also be affected in peripheral arthritis.
Brucellosis has also been proposed as a cause of reactive arthritis.
Sacroiliitis,
is readily diagnosed, also usually in the context of acute brucellosis.
• spondylitis,
remains notoriously difficult to treat and often seems to result in residual damage. The
lumbar spine is the usual site of involvement.
Spondylitis can be easily diagnosed with plain radiography, in which the characteristic Pons
sign (a steplike erosion of the anterosuperior vertebral margin) can be identified, or with
scintigraphy and magnetic resonance imaging.
Arthritis
Bursitis
Tenosynovitis
osteomyelitis
spondylitis sacroiliitis
Spondylitis typically affects men over the age of 40 years.
Areas of the spine that are involved include: lumbar (60%),
thoracic (19%) and cervical (12%).
Tenosynovitis
Reproductive system
• The reproductive system is the
second most common site of focal
brucellosis. Brucellosis can present
as epididymoorchitis in men and is
often difficult to differentiate from
other local disease.
• Hepatitis is common, usually manifesting as mild
transaminasemia.
• Liver abscess and jaundice are rare.
• Granulomas can be present in liver-biopsy
specimens in cases of both
B. Melitensis And B. abortus
• Ascites is often present, either as a temporary
exacerbation of preexisting hepatic disease or as
frank peritonitis.
Relatively Common
Gastrointestinal complications :
Unusual gastrointestinal manifestations of brucellosis include peritonitis,
pancreatitis, acute cholecystitis, and acute abdomen
Unusual manifestations of brucellosis,
• Neurobrucellosis (1%–2%) Neurological findings
can be diverse and could include peripheral
neuropathies, chorea, meningo encephalitis,
transient ischaemic attacks, psychiatric
manifestations, and cranial nerve compromise.
• Hepatic abscess (1%).
• Mucocutaneous manifestations
Include erythematous papular lesions, purpura,
dermal cysts, and Stevens-Johnson syndrome.
• Endocarditis—with the aortic valve being
the most commonly affected structure and
multiple valve involvement being common
within this subset of Patients.
It is the most serious complication, accounting for most of the
5% total mortality rate of human brucellosis.
• Pulmonary manifestations,
Pleural effusions and pneumonias, can
be found in up to 16% of
complicated cases of brucellosis.
• Leucocytosis is observed in about
9% of patients and if found, focal
complications should be excluded .
Leucopenia (11% of patients).
Thrombocytopenia (10% of patients)
Anaemia is seen more frequently,
affecting 26% of patients.
Other exceptionally rare
manifestations
• Including thyroid, splenic and
epidural abscess, pneumonitis,
pleurisy or empyema and uveitis.
Unusual manifestations of brucellosis: a retrospective case series in a
tertiary care Greek university hospital
I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris 1
EMHJ • Vol. 16 No. 4 • 2010
Eastern Mediterranean Health Journal
• Brucella pelvic tubo-ovarian abscess
mimicking a pelvic malignancy.
• Seoud MA1, Kanj SS, Habli M, Araj GF,
Khalil AM.
•
• A 57-y-old woman presented with recurrent abdominal and pelvic
pain of 6 months' duration with low-grade fever. A computed
tomographic scan indicated an ovarian tumor. Laparotomy
revealed a pelvic abscess. Her symptoms resolved following
surgery and antibiotic therapy. Pathology revealed an extensive
inflammatory process. Tissue culture grew Brucella sp. The
diagnosis and management of this previously undescribed pelvic
tubo-ovarian abscess present a particular challenge
Scand J Infect Dis.
2003;35(4):277-8
In sum,
practically every organ and system
of the
human body can be affected in brucellosis — a
fact that underscores the importance of including
brucellosis in the differential diagnosis in areas of
endemic disease, even if clinical features are not
entirely compatible.
Unusual manifestations of brucellosis: a retrospective case series in a tertiary care Greek
university hospital
I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris 1
EMHJ • Vol. 16 No. 4 • 2010
Eastern Mediterranean Health Journal
Center for Food Security and Public Health, Iowa State University, 2008
DIAGNOSIS
• Human brucellosis is a
multisystem disease that may present with a broad spectrum
of clinical manifestations and its complications can affect
almost all organs and systems with varying incidence
(Andres Morist et al., 2003; Cesur et al., 2003; Gur et al.,
2003).
Its clinical manifestations and focal complications
are often troublesome in making a clinical diagnosis.
Its diagnosis therefore requires microbiological confirmation
by means of isolation from blood culture or demonstration
of the presence of specific antibodies by serological tests.
Diagnosis
Detailed history
• Because of the protean clinical manifestations of
brucellosis, the cornerstone of clinical diagnosis
lies in taking a detailed history and paying careful
attention to epidemiological information.
Detailed patient interviews are crucial for the
diagnosis of human brucellosis, especially in
urban and non-endemic areas, and in cases of
imported brucella, in which travellers acquire the
disease abroad and become ill in non-endemic
settings.
Physical examination may
reveal:
• Physical examination
may reveal: swelling of joints,
tenderness over joints and the lower
back, splenomegaly, hepatomegaly,
external lymphadenopathy, jaundice,
mouth ulcerations, scrotal swelling
and a variety of cutaneous eruptions
Center for Food Security and Public Health, Iowa State University, 2008
Laboratory Diagnosis
• Laboratory testing is indispensable
for diagnosis and should always be
combined with a high index of clinical
suspicion.
Laboratory Diagnosis
• At present, laboratory diagnosis of
human brucellosis is based on :
• 1)Isolation of the bacteria ( microbiologic culture).
• 2) Detection of anti-Brucella antibodies ( Serology )
• 3) The use of molecular methods for the detection of
Brucella DNA.
Each of these tests has advantages and
limitations and, thus, requires careful
interpretation.
Brucella culture 1
• The number of bacteria in clinical samples may vary widely,
with the isolation of Brucella being highly dependent on the
• stage of disease (acute versus chronic),
• antibiotic pre-treatment, the existence of an appropriate
• clinical specimen and the culturing methods used .
• The number of viable bacteria circulating in the blood of
patients with brucellosis is assumed to be low and therefore
the sample volume is critical.
• Bacteraemia usually occurs early in the course of the
disease, and patients with bacteraemia are more likely to
suffer fever and chills than those without .
• Consequently, isolation rates are much higher during the
first two weeks of symptomatic disease and in blood
cultures taken during the pyrexial phase
• In acute cases, sensitivity can vary
from 80% to 90%.
• In contrast, isolation rates are much
lower in chronic cases, ranging
between 30% and 70%.
• The likelihood of isolation in patients
with chronic disease and focal
complications can be improved by
using sampling material from
affected sites.
Brucella culture 2
New culture types
Bone marrow cultures have proven to be more
sensitive than blood cultures for the detection of Brucella
spp. at any stage of disease, and the mean time to detection
is significantly reduced .
This method has also proven its usefulness in patients
treated with antibiotics.
As bone marrow aspiration and biopsy can be painful,
the procedure should be restricted to specific cases, i.e.
serologically negative patients in whom there is a strong
clinical suspicion of brucellosis .
Brucella culture 3
• During the first week of infection, IgM
antibodies against lipopolysaccharide
antigens appear in the serum, followed by
IgG antibodies as early as the second
week.
• Both antibody isotypes peak during the
fourth week, and the use of antibiotics
was associated with a decline of both IgM
and IgG class antibodies.
SEROLOGIC Diagnosis
• The first agglutination test for the detection of
antibody to Brucella infection was reported by
Wright and Smith over 100 years ago (Nielsen,
2002; Pabuccuoglu et al., 2011).
• In this test, a mixture of bacterial cell antigens
and human patient serum was incubated in a
glass tube.
• If a “mantle” pattern of cell sediment was
observed, it was considered positive, while a
“button” pattern was considered as negative.
• The test which is still in use today is based on a
similar concept, except that only Brucella abortus
cells are used as the antigen (Nielsen and Yu,
2010).
SEROLOGIC Diagnosis
o Standard tube agglutination
test (STAT)
o We use a wide range of dilutions of the patient’s
serum (1/20 to 1/5120) to avoid prozone phenomenon.
o A titer of 1/160 or more is diagnostic.
o However, interpretation of the titer is done in light of
endemicity of the disease and occupation of the patient.
SEROLOGIC Diagnosis
The standard tube agglutination test (SAT) is the most widely used serologic test for
the confirmation of human brucellosis.
The detection of seroconversion or high antibody titers (> or = 1/160) are
considered diagnostic together with a compatible clinical presentation.
The lack of seropositivity in patients with strongly suspected clinical picture may be
attributed to the performance of tests early in the course of infection, the presence
of blocking antibodies (non-agglutinating, incomplete) or the so-called "prezone"
phenomenon.
Enzyme immunoassays (ELISA) which measure specific IgM, IgG and IgA
antibodies, allow for a better interpretation of the clinical situation and overcome the
false negativities/positivities which may arise in SAT.
In contrast to bacterial culture, serological testing is fast, non-hazardous and more
sensitive and therefore preferred in routine clinical practice.
SEROLOGIC Diagnosis
SEROLOGIC Diagnosis
Agglutination titres ≥ 1:160 or
a fourfold rise of titres in follow-up sera are considered to be indicative of active
infection.
For the serological diagnosis of human brucellosis, the serum agglutination test
(SAT) is still considered to be the reference method
The level of sensitivity of the serological tests differs for the different stages of
the disease and in particular a lower sensitivity applies very early in the infection
and in patients with chronic disease or experiencing a relapse.
In general, the likelihood of a true-positive serological test result in suspected
cases can be increased by a high pretest probability based on clinical signs and
symptoms of thedisease
• Coomb’s antiglobulin test
• Used to detect non agglutinating IgA
antibodies which interfere with
agglutination by IgG or IgM in STAT.
A variety of serological tests has been applied, but at least two
serological tests have to be combined to avoid false negative results.
Lateral flow assay (LFA)
The LFA is a simplified ELISA for the qualitative detection of antigen specific
antibodies in serum, or whole blood samples (Christopher et al., 2010). The
assay is based on the binding of specific antibodies to antigen immobilised
on a test strip (cellulose membrane matrix). It allows the detection of specific
IgM as well as specific IgG antibodies and that a high sensitivity is assured
for all stages of the disease (Nielsen and Yu, 2010).
• Application of the assay does not require specific
expertise, equipment or electricity, and test kits
may be kept in stock without the need for
refrigeration, thus, making the assay a very
useful one for poor resource countries including
most African countries and migratory herds/flocks
(Abdoel et al., 2008, Baddour, 2012).
• However, its interpretation is subjective,
depending on the formation of a visible coloured
line of reaction, and the assay it self tends to be
expensive because of the multiple
ingredients/components involved (Nielsen and Yu,
2010).
Two patients that showed a SAT of 1/80 had a positive blood culture and tested
positive in the PCR and for specific IgM antibodies in the lateral flow assay.
These data highlight the importance of using more than one test in diagnosis of
brucellosis especially in endemic areas where
active brucellosis cannot be excluded in a patient with SAT lower than
1/160
In addition, SAT suffers from high false negative rates in complicated and chronic
cases
SEROLOGIC Diagnosis
Moreover, SAT false negative results may occur in patients with very recent
infection or those who have blocking antibodies in their serum. The flow assays
detected five out of six individuals that were hemoculture-positive. Of these five
patients, two serum samples showed SAT of 1/80.
SEROLOGIC Diagnosis
The antibodies tend to persist in patients long after recovery; therefore, in
endemic areas, high background values could occur that may affect the
diagnostic value of the test.
Molecular Diagnosis
• Molecular biology as a diagnostic tool is
advancing and will soon be at the point of
replacing actual bacterial isolation.
• It is rapid, safe and cost effective, the only real
problems being some uncertainties regarding
specificity.
• However, PCR requires a sophisticated laboratory
and highly skilled staff. Therefore, the use of the
RB, the flow assay, or a combination of the two
tests appears a good choice for countries such as
Egypt where brucellosis is endemic but laboratory
support is not readily available
TREATMENT
Treatment is given to shorten the duration of symptoms, prevent relapse, and avert
complications such as arthritis, sacroiliitis, spondylitis, encephalitis,
endocarditis, epididymoorchitis, and abortion.
Because monotherapies were historically characterised
by high rates of relapse, a combination of two drugs is
currently used
Recommendations for specific regimens in reference sources are inconsistent.
Guidelines of the World Health Organization, last published in
1986, recommended doxycycline with rifampicin for six weeks in place of their
previously recommended regimen of tetracycline for six weeks in combination
with streptomycin for the first two to three weeks.4 The relative merits of these two
regimens are still being discussed
Alternative treatments include other antibiotics,such as fluoroquinolones and co-
trimoxazole and their combinations with rifampicin.
DRUGS Used
ttt
• Appropriate therapy for neuroBrucellosis requires: the use
of 2 or 3 antimicrobials that cross blood brain barrier
(BBB), supportive care and symptomatic treatment in
addition to treatment of specific complications such as
convulsions. The antimicrobials that are commonly used in
the treatment
• t of neuroBrucellosis include: ceftriaxone: 2 grams
intravenously (IV) twice daily, rifampicin: 600 mg per day,
doxycycline 100mg twice daily, trimethoprim-
sulfamethoxazole 960 mg twice daily in addition to
ciprofloxacin and streptomycin.
• Treatment of neuroBrucellosis can range from 1to19
months, although it is advisable to give antimicrobials for at
least 4 to 6 months
Center for Food Security and Public Health, Iowa State University, 2008
Prognosis
• May last days, months, or years
• Recovery is common
• Disability is often pronounced
• About 5% of treated cases relapse
 Failure to complete the treatment regimen
 Sequestered infection requiring surgical
drainage
• Case-fatality rate: <2% ( untreated)
− Endocarditis caused by B. melitensis
Prevention and
Control
Center for Food Security and Public Health, Iowa State University, 2008
Prevention and Control
• Education about risk of transmission
− Farmer, veterinarian, abattoir worker,
butcher, consumer, hunter, public
• Wear proper attire if dealing with
infected animals/ tissues
− Gloves, masks, goggles
• Avoid consumption of raw dairy
products
Center for Food Security and Public Health, Iowa State University, 2008
Prevention and Control
• Immunize in areas of
high prevalence
− Young goats and sheep with Rev-1
− Calves with RB51
− No human vaccine
• Eradicate reservoir
− Identify, segregate, and/or cull
infected animals
Q.1 The re interest in Brucellosis has emerged in
the last decade because all of the following except :
• A) The disease remains the world’s most
common bacterial zoonosis .
• B) Its status as a class A bioterrorist agent.
• C) Despite being endemic in many developing
countries, brucellosis remains under diagnosed
and under-reported.
• D) Brucellosis is an important cause of veterinary
morbidity and mortality, causing important
economic losses in developing countries
Q. Transmission of brucella to human
can occur through any of the following
routes except :
• A) Ingestion of raw milk & unpasteurized dairy
products and rarely through undercooked meat.
• B) Inhalation of infectious aerosols .
• C) Conjunctiva or intact skin contacting infected
tissues.
• D) Person-to-person transmission is
very rare (blood transfusions, bone marrow
transplants, and sexual contact between lab
workers and their spouse)
Q.3) Regarding localisation (
complication) of brucellosis all is true
except :
• A) Endocarditis is the most grave .
• B) Genitourinary , oophoritis is more
frequent than epidedimoorchitis and
can be misdiagnosed as ovarian
tumor.
• C) Osteoarticular localisation is the
most common.
• D) Hepatic abscess is rare.
Q.4 Regarding the laboratory diagnosis of
brucellosis select the most appropriate answer :
• A) Bone marrow cultures have proven to be more sensitive than
blood cultures for the detection of Brucella spp. at any stage of
disease.
• B) The number of viable bacteria circulating in the blood of
patients with brucellosis is assumed to be good and so the sample
volume has no much influence on the result of blood culture.
C) The level of sensitivity of the serological tests differs for the
different stages of the disease and in particular a higher sensitivity
applies very early in the infection and in patients with chronic
disease or experiencing a relapse.
• D) Active brucellosis can be excluded in a patient with SAT
lower than 1/160.
Q5.Regarding neurobrucellosis select
the most appropriate answer :
• A) Neurological findings can be diverse
and could include chorea, meningo
encephalitis, and transient ischaemic
attacks.
• B)Cranial nerves are never affected.
• C) Treatment of neuro Brucellosis can range
from 1 to 3months, although it is advisable to
give antimicrobials for at least 4 to 6 weeks.
• D) Neurobrucellosis has been reported in
up to 10% of cases.

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Brucellosis lecture.pptx

  • 1. Brucellosis Professor AbdelRahman A Mokhtar Internal Medicine Dept Mansoura University 2014
  • 2. Center for Food Security and Public Health, Iowa State University, 2008
  • 3. Human brucellosis María Pía Franco, Maximilian Mulder, Robert H Gilman, Henk L Smits A renewed scientific interest in human brucellosis has been fuelled by its recent re-emergence and enhanced surveillance in many areas of the world, and from its status as a class B bioterrorist agent. The disease remains the world’s most common bacterial zoonosis, with over half a million new cases annually and prevalence rates in some countries exceeding ten cases per 100 000 population. Despite being endemic in many developing countries,brucellosis remains underdiagnosed and under-reported. Furthermore, since brucellosis is an important cause of veterinary morbidity and mortality,the disease can also cause important economic losses indeveloping countries Lancet Infect Dis 2007; 7: 775–86
  • 4. Center for Food Security and Public Health, Iowa State University, 2008 Endemicity :
  • 5. Endemicity : Aseroprevalence rate of 20% was identified on the Arabic Peninsula, with greater than 2% having active brucellosis. In the Middle East, B. melitensis may exceed the prevalence of B. abortus in cattle in some areas as it has emerged on some intensive dairy farm
  • 6. Expansion of animal industries and urbanization, and the lack of hygienic measures in animal husbandry and in food handling, as well as consumers‟ preference for fresh dairy goods which may be contaminated, partly account for Brucellosis remaining a public health hazard.
  • 8. Center for Food Security and Public Health, Iowa State University, 2008 Brucella spp. • Gram negative, coccobacilli bacteria • Facultative, intracellular organism • Environmental persistence − Temperature, pH, humidity − Frozen and aborted materials − It is a facultative, intracellular pathogen and thus requires prolonged treatment with clinically effective antibiotics. • Multiple species
  • 9. Susceptibility  Killed at 600 C in 10 minutes  Pasteurization of milk .  Survival is long in refrigerated milk, ice creams and cheese.
  • 10. Center for Food Security and Public Health, Iowa State University, 2008 Species Biovar/ Serovar Natural Host Human Pathogen B. abortus 1-6, 9 cattle yes B.melitensis 1-3 goats, sheep yes B. suis 1, 3 swine yes 2 hares yes 4 reindeer, caribou yes 5 rodents yes B. canis none dogs, other canids yes B. ovis none sheep no B. neotomae none Desert wood rat no B. maris (?) marine mammals ?
  • 11. Center for Food Security and Public Health, Iowa State University, 2008 Order of pathogenicity to humans: B. melitensis, B. suis B. abortus, Rarely B. canis, and marine mammal Brucella.
  • 12. Center for Food Security and Public Health, Iowa State University, 2008 The Many Names of Brucellosis Human Disease • Malta Fever • Undulant Fever • Mediterranean Fever • Rock Fever of Gibraltar • Gastric Fever Animal Disease • Bang’s Disease • Enzootic Abortion • Epizootic Abortion • Slinking of Calves • Ram Epididymitis • Contagious Abortion
  • 13. Center for Food Security and Public Health, Iowa State University, 2008
  • 15. Center for Food Security and Public Health, Iowa State University, 2008 Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases •Contracted Malta fever •Described his own case in great detail Jeffery Allen Marston
  • 16. Center for Food Security and Public Health, Iowa State University, 2008 Sir David Bruce (1855-1931) •British Army physician and microbiologist •Discovered Micrococcus melitensis Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases
  • 17. Center for Food Security and Public Health, Iowa State University, 2008 Bernhard Bang (1848-1932) •Danish physician and veterinarian •Discovered Bacterium abortus could infect cattle, horses, sheep, and goats Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases
  • 18. Center for Food Security and Public Health, Iowa State University, 2008 History • Alice Evans, American bacteriologist − Credited with linking the organisms − Similar morphology and pathology between:  Bang’s Bacterium abortus  Bruce’s Micrococcus melitensis • Nomenclature today credited to Sir David Bruce − Brucella abortus and Brucella melitensis
  • 20. Center for Food Security and Public Health, Iowa State University, 2008 Transmission to Humans • Conjunctiva or broken skin contacting infected tissues ( Brucella abortus and B. suis infections often ) − Blood, urine, vaginal discharges, aborted fetuses, placentas • Ingestion ( Brucella melitensis infection is primarily foodborne ) − Raw milk & unpasteurized dairy products − Rarely through undercooked meat
  • 21. Center for Food Security and Public Health, Iowa State University, 2008 Transmission to Humans • Inhalation of infectious aerosols − Pens, stables, slaughter houses • Inoculation with vaccines − B. abortus strain 19, RB-51 − B. melitensis Rev-1 − Conjunctival splashes, injection • Person-to-person transmission is very rare (blood transfusions, bone marrow transplants, and sexual contact between lab workers and their spouse) • Incubation varies − 5-21 days to three months
  • 22. Center for Food Security and Public Health, Iowa State University, 2008 Who is at Risk? • Occupational Disease − Cattle ranchers/dairy farmers − Veterinarians − Abattoir workers − Meat inspectors − Lab workers • Hunters • Travelers • Consumers of unpasteurized dairy products
  • 23. Center for Food Security and Public Health, Iowa State University, 2008
  • 25. Pathophysiooogy After infecting the host, the pathogen becomes sequestered within cells of the reticuloendothelial system. The mechanisms by which brucella enters cells and evades intracellular killing and the host immune system are the subject of much research and debate. In depth analysis of the complete Brucella spp genomes has failed to identify any of the classic virulence factors such as toxins, fimbriae, and capsules, which raises the possibility that these organisms use unique and subtle mechanisms to evade host defences, penetrate host cells, alter intracellular trafficking to avoid degradation and killing in lysosomes, and modulate the intracellular environment to allow long-term intracellular survival and replication. Research suggests that the smooth, non-endotoxic lipopolysaccharides help block the development of innate and specifi c immunity during the early stage of infection, and protect the pathogen from the microbicidal activities of the immune system. Additionally, smooth lipopolysaccharide in brucella may be involved in the inhibition of apoptosis (ie, programmed cell death) of infected cells, since resistance to apoptosis of infected cells has been observed in patients with acute and chronic disease
  • 26. The organism can gain entry through abraded skin, mucous membranes and conjunctiva[ . Entry of the organism through any of these surfaces invites phagocytic neutrophil cells to the site of entry and the organism is phagocytosed by neutrophils and tissue macrophages. They carry the ingested organism to the regional lymph nodes. If the organism escapes host defense mechanisms in the regional lymph node, spread to the circulation occurs resulting in bacteremia. These free organisms in circulation are phagocytosed by the neutrophils and localization occurs primarily to the liver, spleen and bone marrow with formation of granulomas Complications like endocarditis, osteomyelitis, neurobrucellosis are rare if appropriate antimicrobial therapy is started during the first few weeks of the illness
  • 27.
  • 28. Malta Fever The one common sign in all patients is an intermittent irregular fever of variable duration, thus the term undulant fever. Others develop an intermittent fever and other persistent symptoms that typically wax and wane at 2- 14 day intervals. Most people with this undulant form recover completely in three to 12 months. A few patients become chronically ill. Relapses can occur months after the initial symptoms, even in successfully treated cases. In many patients, the symptoms last for two to four weeks and are followed by spontaneous recovery.
  • 29. Brucellosis remains a diagnostic puzzle due to Ambiguous, Non-specific manifestations & increasingly unusual presentations.
  • 30.  The disease is characterized by acute bacteremic phase followed by a chronic stage during which the bacteria localize in reticuloendothelial tissues (LNs, liver, spleen, bone marrow).  Manifestations of the disease include: 1) Fever for 3-4 weeks followed by afebrile period of similar duration, so it is called undulant fever. 2) Weakness, bone pain, profuse sweating + enlarged LNs, liver and spleen. 3) Brucella melitensis is the most severe form.
  • 31. Human brucellosis has a wide spectrum of clinical manifestations, earning it a place alongside syphilis and tuberculosis as one of the “great imitators Thus to an unaware physician, the clinical diagnosis becomes a challenging one.
  • 32. Disease predominantly developing in one organ or organ system is described as localized. Human brucellosis usually manifests as an acute (< 2 months) or subacute (2-12 months) febrile illness, which may persist and progress to a chronically (> 1 year) incapacitating disease with severe complications. However, distinctions between generalized and localized disease, or between acute and chronic disease, are largely arbitrary, as the pathogenic processes remain the same. Unusual manifestations of brucellosis: a retrospective case series in a tertiary care Greek university hospital I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris EMHJ • Vol. 16 No. 4 • 2010 Eastern Mediterranean Health Journal La Revue de Santé de la Méditerranée orientale Clinical Patterns
  • 33. Subclinical form • Subclinical or asymptomatic infection • This clinical form is diagnosed by positive serology. • The patients have no history or physical signs of acute or chronic illness. It has been documented more frequently in farmers, abattoir workers, and veterinarians.6,39
  • 34. Acute form • This is the typical form of brucellosis. • Almost all patients have a history of fever accompanied by weakness, malaise, headache, back-ache, anorexia, weight loss, myalgia, and arthralgia. • A temperature over 38.5”C is measured in more than 85% of patients. • Splenomegaly and hepatomegaly are found in about 6-35% of the cases. • Any organ involvement can be seen, but arthritis is more frequent (40-50%).
  • 35. Subacute form • This refers to a group of patients who have relapsed because of incomplete or partial antibiotic treatment and patients who have received inappropriate antibiotics because of incorrect diagnosis. • The clinical picture is more protean and may be an important cause of fever of unknown origin. • The symptoms are generally milder, and localized infection can be seen.
  • 36. Chronic brucellosis • Chronic brucellosis is similar to chronic fatigue syndrome. It is extremely rare in children, but frequent in older people. These patients generally suffer from a psychoneurosis, sweating, and weight loss. Fever is rare. Localized infection can be seen; however, ocular manifestations, such as episcleritis and uveitis, are frequent. Chronic brucellosis can be extremely difficult to diagnose, if the serologic results are equivocal and the organism cannot be cultured.
  • 37. Localized infection • Localized brucellosis refers to cases in which organisms are not isolated from blood but are localized in specific tissues, such as the bone, joints, cerebrospinal fluid, liver, kidneys, spleen, or skin. Localization may be the principal manifestation of systemic infection, or may be the only manifestation of a chronic infection. Localized infection is sometimes named as a complication when it occurs as a result of systemic infection.
  • 38. Center for Food Security and Public Health, Iowa State University, 2008
  • 39. The most common sites • Involved are osteoarticular, especially sacroiliitis (20%–30%) with large joints most frequently affected in children, and the genitourinary system, especially epididymo orchitis (2%–40% of males).
  • 40. • Osteoarticular disease is universally the most common complication of brucellosis, and three distinct forms exist — peripheral arthritis, sacroiliitis, and spondylitis. • Osteoarticular complications are sometimes linked to a genetic predisposition, • with recent data suggesting an association with HLA-B39. • Peripheral arthritis • Is the most common and is nonerosive, since it usually involves the knees, hips, ankles, and wrists in the context of acute infection. Prosthetic joints can also be affected in peripheral arthritis. Brucellosis has also been proposed as a cause of reactive arthritis. Sacroiliitis, is readily diagnosed, also usually in the context of acute brucellosis. • spondylitis, remains notoriously difficult to treat and often seems to result in residual damage. The lumbar spine is the usual site of involvement. Spondylitis can be easily diagnosed with plain radiography, in which the characteristic Pons sign (a steplike erosion of the anterosuperior vertebral margin) can be identified, or with scintigraphy and magnetic resonance imaging.
  • 41. Arthritis Bursitis Tenosynovitis osteomyelitis spondylitis sacroiliitis Spondylitis typically affects men over the age of 40 years. Areas of the spine that are involved include: lumbar (60%), thoracic (19%) and cervical (12%). Tenosynovitis
  • 42. Reproductive system • The reproductive system is the second most common site of focal brucellosis. Brucellosis can present as epididymoorchitis in men and is often difficult to differentiate from other local disease.
  • 43. • Hepatitis is common, usually manifesting as mild transaminasemia. • Liver abscess and jaundice are rare. • Granulomas can be present in liver-biopsy specimens in cases of both B. Melitensis And B. abortus • Ascites is often present, either as a temporary exacerbation of preexisting hepatic disease or as frank peritonitis. Relatively Common Gastrointestinal complications : Unusual gastrointestinal manifestations of brucellosis include peritonitis, pancreatitis, acute cholecystitis, and acute abdomen
  • 44. Unusual manifestations of brucellosis, • Neurobrucellosis (1%–2%) Neurological findings can be diverse and could include peripheral neuropathies, chorea, meningo encephalitis, transient ischaemic attacks, psychiatric manifestations, and cranial nerve compromise. • Hepatic abscess (1%). • Mucocutaneous manifestations Include erythematous papular lesions, purpura, dermal cysts, and Stevens-Johnson syndrome.
  • 45. • Endocarditis—with the aortic valve being the most commonly affected structure and multiple valve involvement being common within this subset of Patients. It is the most serious complication, accounting for most of the 5% total mortality rate of human brucellosis. • Pulmonary manifestations, Pleural effusions and pneumonias, can be found in up to 16% of complicated cases of brucellosis.
  • 46. • Leucocytosis is observed in about 9% of patients and if found, focal complications should be excluded . Leucopenia (11% of patients). Thrombocytopenia (10% of patients) Anaemia is seen more frequently, affecting 26% of patients.
  • 47. Other exceptionally rare manifestations • Including thyroid, splenic and epidural abscess, pneumonitis, pleurisy or empyema and uveitis. Unusual manifestations of brucellosis: a retrospective case series in a tertiary care Greek university hospital I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris 1 EMHJ • Vol. 16 No. 4 • 2010 Eastern Mediterranean Health Journal
  • 48.
  • 49.
  • 50.
  • 51.
  • 52.
  • 53. • Brucella pelvic tubo-ovarian abscess mimicking a pelvic malignancy. • Seoud MA1, Kanj SS, Habli M, Araj GF, Khalil AM. • • A 57-y-old woman presented with recurrent abdominal and pelvic pain of 6 months' duration with low-grade fever. A computed tomographic scan indicated an ovarian tumor. Laparotomy revealed a pelvic abscess. Her symptoms resolved following surgery and antibiotic therapy. Pathology revealed an extensive inflammatory process. Tissue culture grew Brucella sp. The diagnosis and management of this previously undescribed pelvic tubo-ovarian abscess present a particular challenge Scand J Infect Dis. 2003;35(4):277-8
  • 54. In sum, practically every organ and system of the human body can be affected in brucellosis — a fact that underscores the importance of including brucellosis in the differential diagnosis in areas of endemic disease, even if clinical features are not entirely compatible. Unusual manifestations of brucellosis: a retrospective case series in a tertiary care Greek university hospital I. Starakis,1 E.E. Mazokopakis 2 and H. Bassaris 1 EMHJ • Vol. 16 No. 4 • 2010 Eastern Mediterranean Health Journal
  • 55.
  • 56. Center for Food Security and Public Health, Iowa State University, 2008
  • 57. DIAGNOSIS • Human brucellosis is a multisystem disease that may present with a broad spectrum of clinical manifestations and its complications can affect almost all organs and systems with varying incidence (Andres Morist et al., 2003; Cesur et al., 2003; Gur et al., 2003). Its clinical manifestations and focal complications are often troublesome in making a clinical diagnosis. Its diagnosis therefore requires microbiological confirmation by means of isolation from blood culture or demonstration of the presence of specific antibodies by serological tests.
  • 59. Detailed history • Because of the protean clinical manifestations of brucellosis, the cornerstone of clinical diagnosis lies in taking a detailed history and paying careful attention to epidemiological information. Detailed patient interviews are crucial for the diagnosis of human brucellosis, especially in urban and non-endemic areas, and in cases of imported brucella, in which travellers acquire the disease abroad and become ill in non-endemic settings.
  • 60. Physical examination may reveal: • Physical examination may reveal: swelling of joints, tenderness over joints and the lower back, splenomegaly, hepatomegaly, external lymphadenopathy, jaundice, mouth ulcerations, scrotal swelling and a variety of cutaneous eruptions
  • 61. Center for Food Security and Public Health, Iowa State University, 2008
  • 62. Laboratory Diagnosis • Laboratory testing is indispensable for diagnosis and should always be combined with a high index of clinical suspicion.
  • 63. Laboratory Diagnosis • At present, laboratory diagnosis of human brucellosis is based on : • 1)Isolation of the bacteria ( microbiologic culture). • 2) Detection of anti-Brucella antibodies ( Serology ) • 3) The use of molecular methods for the detection of Brucella DNA. Each of these tests has advantages and limitations and, thus, requires careful interpretation.
  • 64. Brucella culture 1 • The number of bacteria in clinical samples may vary widely, with the isolation of Brucella being highly dependent on the • stage of disease (acute versus chronic), • antibiotic pre-treatment, the existence of an appropriate • clinical specimen and the culturing methods used . • The number of viable bacteria circulating in the blood of patients with brucellosis is assumed to be low and therefore the sample volume is critical. • Bacteraemia usually occurs early in the course of the disease, and patients with bacteraemia are more likely to suffer fever and chills than those without . • Consequently, isolation rates are much higher during the first two weeks of symptomatic disease and in blood cultures taken during the pyrexial phase
  • 65. • In acute cases, sensitivity can vary from 80% to 90%. • In contrast, isolation rates are much lower in chronic cases, ranging between 30% and 70%. • The likelihood of isolation in patients with chronic disease and focal complications can be improved by using sampling material from affected sites. Brucella culture 2
  • 67. Bone marrow cultures have proven to be more sensitive than blood cultures for the detection of Brucella spp. at any stage of disease, and the mean time to detection is significantly reduced . This method has also proven its usefulness in patients treated with antibiotics. As bone marrow aspiration and biopsy can be painful, the procedure should be restricted to specific cases, i.e. serologically negative patients in whom there is a strong clinical suspicion of brucellosis . Brucella culture 3
  • 68. • During the first week of infection, IgM antibodies against lipopolysaccharide antigens appear in the serum, followed by IgG antibodies as early as the second week. • Both antibody isotypes peak during the fourth week, and the use of antibiotics was associated with a decline of both IgM and IgG class antibodies. SEROLOGIC Diagnosis
  • 69. • The first agglutination test for the detection of antibody to Brucella infection was reported by Wright and Smith over 100 years ago (Nielsen, 2002; Pabuccuoglu et al., 2011). • In this test, a mixture of bacterial cell antigens and human patient serum was incubated in a glass tube. • If a “mantle” pattern of cell sediment was observed, it was considered positive, while a “button” pattern was considered as negative. • The test which is still in use today is based on a similar concept, except that only Brucella abortus cells are used as the antigen (Nielsen and Yu, 2010). SEROLOGIC Diagnosis
  • 70. o Standard tube agglutination test (STAT) o We use a wide range of dilutions of the patient’s serum (1/20 to 1/5120) to avoid prozone phenomenon. o A titer of 1/160 or more is diagnostic. o However, interpretation of the titer is done in light of endemicity of the disease and occupation of the patient. SEROLOGIC Diagnosis
  • 71. The standard tube agglutination test (SAT) is the most widely used serologic test for the confirmation of human brucellosis. The detection of seroconversion or high antibody titers (> or = 1/160) are considered diagnostic together with a compatible clinical presentation. The lack of seropositivity in patients with strongly suspected clinical picture may be attributed to the performance of tests early in the course of infection, the presence of blocking antibodies (non-agglutinating, incomplete) or the so-called "prezone" phenomenon. Enzyme immunoassays (ELISA) which measure specific IgM, IgG and IgA antibodies, allow for a better interpretation of the clinical situation and overcome the false negativities/positivities which may arise in SAT. In contrast to bacterial culture, serological testing is fast, non-hazardous and more sensitive and therefore preferred in routine clinical practice. SEROLOGIC Diagnosis
  • 72. SEROLOGIC Diagnosis Agglutination titres ≥ 1:160 or a fourfold rise of titres in follow-up sera are considered to be indicative of active infection. For the serological diagnosis of human brucellosis, the serum agglutination test (SAT) is still considered to be the reference method The level of sensitivity of the serological tests differs for the different stages of the disease and in particular a lower sensitivity applies very early in the infection and in patients with chronic disease or experiencing a relapse. In general, the likelihood of a true-positive serological test result in suspected cases can be increased by a high pretest probability based on clinical signs and symptoms of thedisease
  • 73. • Coomb’s antiglobulin test • Used to detect non agglutinating IgA antibodies which interfere with agglutination by IgG or IgM in STAT. A variety of serological tests has been applied, but at least two serological tests have to be combined to avoid false negative results.
  • 74.
  • 75. Lateral flow assay (LFA) The LFA is a simplified ELISA for the qualitative detection of antigen specific antibodies in serum, or whole blood samples (Christopher et al., 2010). The assay is based on the binding of specific antibodies to antigen immobilised on a test strip (cellulose membrane matrix). It allows the detection of specific IgM as well as specific IgG antibodies and that a high sensitivity is assured for all stages of the disease (Nielsen and Yu, 2010).
  • 76. • Application of the assay does not require specific expertise, equipment or electricity, and test kits may be kept in stock without the need for refrigeration, thus, making the assay a very useful one for poor resource countries including most African countries and migratory herds/flocks (Abdoel et al., 2008, Baddour, 2012). • However, its interpretation is subjective, depending on the formation of a visible coloured line of reaction, and the assay it self tends to be expensive because of the multiple ingredients/components involved (Nielsen and Yu, 2010).
  • 77. Two patients that showed a SAT of 1/80 had a positive blood culture and tested positive in the PCR and for specific IgM antibodies in the lateral flow assay. These data highlight the importance of using more than one test in diagnosis of brucellosis especially in endemic areas where active brucellosis cannot be excluded in a patient with SAT lower than 1/160 In addition, SAT suffers from high false negative rates in complicated and chronic cases SEROLOGIC Diagnosis Moreover, SAT false negative results may occur in patients with very recent infection or those who have blocking antibodies in their serum. The flow assays detected five out of six individuals that were hemoculture-positive. Of these five patients, two serum samples showed SAT of 1/80.
  • 78. SEROLOGIC Diagnosis The antibodies tend to persist in patients long after recovery; therefore, in endemic areas, high background values could occur that may affect the diagnostic value of the test.
  • 79. Molecular Diagnosis • Molecular biology as a diagnostic tool is advancing and will soon be at the point of replacing actual bacterial isolation. • It is rapid, safe and cost effective, the only real problems being some uncertainties regarding specificity. • However, PCR requires a sophisticated laboratory and highly skilled staff. Therefore, the use of the RB, the flow assay, or a combination of the two tests appears a good choice for countries such as Egypt where brucellosis is endemic but laboratory support is not readily available
  • 81. Treatment is given to shorten the duration of symptoms, prevent relapse, and avert complications such as arthritis, sacroiliitis, spondylitis, encephalitis, endocarditis, epididymoorchitis, and abortion. Because monotherapies were historically characterised by high rates of relapse, a combination of two drugs is currently used Recommendations for specific regimens in reference sources are inconsistent. Guidelines of the World Health Organization, last published in 1986, recommended doxycycline with rifampicin for six weeks in place of their previously recommended regimen of tetracycline for six weeks in combination with streptomycin for the first two to three weeks.4 The relative merits of these two regimens are still being discussed Alternative treatments include other antibiotics,such as fluoroquinolones and co- trimoxazole and their combinations with rifampicin.
  • 83. ttt • Appropriate therapy for neuroBrucellosis requires: the use of 2 or 3 antimicrobials that cross blood brain barrier (BBB), supportive care and symptomatic treatment in addition to treatment of specific complications such as convulsions. The antimicrobials that are commonly used in the treatment • t of neuroBrucellosis include: ceftriaxone: 2 grams intravenously (IV) twice daily, rifampicin: 600 mg per day, doxycycline 100mg twice daily, trimethoprim- sulfamethoxazole 960 mg twice daily in addition to ciprofloxacin and streptomycin. • Treatment of neuroBrucellosis can range from 1to19 months, although it is advisable to give antimicrobials for at least 4 to 6 months
  • 84. Center for Food Security and Public Health, Iowa State University, 2008 Prognosis • May last days, months, or years • Recovery is common • Disability is often pronounced • About 5% of treated cases relapse  Failure to complete the treatment regimen  Sequestered infection requiring surgical drainage • Case-fatality rate: <2% ( untreated) − Endocarditis caused by B. melitensis
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  • 87. Center for Food Security and Public Health, Iowa State University, 2008 Prevention and Control • Education about risk of transmission − Farmer, veterinarian, abattoir worker, butcher, consumer, hunter, public • Wear proper attire if dealing with infected animals/ tissues − Gloves, masks, goggles • Avoid consumption of raw dairy products
  • 88. Center for Food Security and Public Health, Iowa State University, 2008 Prevention and Control • Immunize in areas of high prevalence − Young goats and sheep with Rev-1 − Calves with RB51 − No human vaccine • Eradicate reservoir − Identify, segregate, and/or cull infected animals
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  • 90. Q.1 The re interest in Brucellosis has emerged in the last decade because all of the following except : • A) The disease remains the world’s most common bacterial zoonosis . • B) Its status as a class A bioterrorist agent. • C) Despite being endemic in many developing countries, brucellosis remains under diagnosed and under-reported. • D) Brucellosis is an important cause of veterinary morbidity and mortality, causing important economic losses in developing countries
  • 91. Q. Transmission of brucella to human can occur through any of the following routes except : • A) Ingestion of raw milk & unpasteurized dairy products and rarely through undercooked meat. • B) Inhalation of infectious aerosols . • C) Conjunctiva or intact skin contacting infected tissues. • D) Person-to-person transmission is very rare (blood transfusions, bone marrow transplants, and sexual contact between lab workers and their spouse)
  • 92. Q.3) Regarding localisation ( complication) of brucellosis all is true except : • A) Endocarditis is the most grave . • B) Genitourinary , oophoritis is more frequent than epidedimoorchitis and can be misdiagnosed as ovarian tumor. • C) Osteoarticular localisation is the most common. • D) Hepatic abscess is rare.
  • 93. Q.4 Regarding the laboratory diagnosis of brucellosis select the most appropriate answer : • A) Bone marrow cultures have proven to be more sensitive than blood cultures for the detection of Brucella spp. at any stage of disease. • B) The number of viable bacteria circulating in the blood of patients with brucellosis is assumed to be good and so the sample volume has no much influence on the result of blood culture. C) The level of sensitivity of the serological tests differs for the different stages of the disease and in particular a higher sensitivity applies very early in the infection and in patients with chronic disease or experiencing a relapse. • D) Active brucellosis can be excluded in a patient with SAT lower than 1/160.
  • 94. Q5.Regarding neurobrucellosis select the most appropriate answer : • A) Neurological findings can be diverse and could include chorea, meningo encephalitis, and transient ischaemic attacks. • B)Cranial nerves are never affected. • C) Treatment of neuro Brucellosis can range from 1 to 3months, although it is advisable to give antimicrobials for at least 4 to 6 weeks. • D) Neurobrucellosis has been reported in up to 10% of cases.