Case

1. *

2. *
*Definition and organism
*History
*Epidemiology
*Transmission
*Disease in Humans
*Differential diagnosis
*Prevention and treatment
*Take home msg

3. Definition:
Human brucellosis, a chronic granulomatous
zoonosis caused by intracellular facultative
bacteria of the genus Brucella , involves many
organs and tissues.
The disease usually affects young and middle age
adults.
According to the WHO, brucellosis is classified
among the top world neglected zoonotic diseases
and has social, economic, and public health impact
on tropical and subtropical regions of the world.

4. Causes: Brucellosis affects many wild and domestic animals,
including:
Cattle, Goats, Sheep, Pigs ,Dogs, especially those used in
hunting, Deer,
Elk, Bison, Moose, Camels
A form of brucellosis also affects harbor seals, porpoises and
certain whales.

5. *Organism
Gram-negative intracellular cocobacilli

6. *

7. History:
This disease was first diagnosed
in the Mediterranean area, where
it received its initial name “Malta
fever”. Thousands of new cases of
brucellosis are reported annually
worldwide.

8. Other names for brucellosis:
*Malta Fever
*Undulant Fever
*Mediterranean Fever
*Rock Fever of Gibraltar

9. Incidence:
more than 500,000 infections per year worldwide
The high incidence rates of brucellosis were seen
in countries as Kenya (203.07 cases / 100 000),
Yemen (89.96), Syria (47.26), Greece (42.96) and
Eritrea (21.82).
 Compared with "The global map of human
brucellosis "written by Georgios Pappas, et al. in
2006, the situation of brucellosis in many epidemic
areas has improved. However, new hot spots of this
disease continue to appear, especially in Africa and
the Middle East countries with incidence of the
disease fluctuating

10. The geographic origin of Brucella melitensis isolates from
Egypt. In this map, the isolates in the associated
governorates are shown

11. • Age
more prevalent in the young population, with 60% of
cases in persons aged 13-40 years, 16% in those aged
40-60 years, and 2.5% in 60 years and older.
 Brucellosis may be more common in children in
developing countries because of a lack of
pasteurization.
• Sex
Brucellosis is more common in males as compared to
females. Occupational exposure to animals is the most
likely cause of this gender vulnerability.

12. *Populations at Risk

13. *Transmission in Humans
•Eating raw dairy products of infected animals: unpasteurized
milk, ice cream, butter, cheeses and raw or undercooked meat
of infected animals.
•Inhaling contaminated air: Farmers, hunters, laboratory
technicians and slaughterhouse workers.
•Touching blood and body fluids of infected animals: blood,
semen or placenta can enter bloodstream through a cut or
other wound. Because normal contact with animals — touching,
brushing or playing — doesn't cause infection, people rarely get
brucellosis from their pets. Even so, people who have
weakened immune systems should avoid handling dogs that are
known to have the disease.
Brucellosis normally doesn't spread from person to person,
but in a few cases, women have passed the disease to their
children during birth or through their breast milk. Rarely,
brucellosis may spread through sexual activity or through
contaminated blood or bone marrow transfusions.

15. Pathophysiology
The incubation period : three days or several weeks.
Symptoms frequently last for several months, and chronic
infections with brucellosis may last for years.

16. Clinical forms:
Brucella could escape from the host immune system, infect any
organs in the body, and survive in the intracellular organisms,
thereby inducing prolonged relapses, morbidity, and chronic
condition.
 Acute brucellosis usually include weight loss, chills, sweating,
fever, headache, back pain, arthralgia, anorexia, and fatigue.
Subacute brucellosis cases typically present less severe
symptoms compared to the acute form.
Chronic infections also cause generalized musculoskeletal
pain
 The relapse of brucellosis is very commonly reported because
of partial, incomplete, or inappropriate antibiotic treatment as
well as deficient immunologic response that is sometimes
difficult to diagnose
The disease often becomes chronic, and clinical manifestation
could persist for more than16 months, and the majority of
patients experience relapse, even after appropriate treatments

18. *OSTEOARTICULAR MANIFESTATIONS
Osteoarticular involvement is the most frequent
complication, occurs in up to 85% of the patients.
Including sacroiliitis, spondylitis, osteomyelitis, peripheral
arthritis, bursitis and tenosynovitis.
The type of skeletal involvement mainly depends on a
patient’s age. The sacroiliac joints and knee arthritis
predominate in children and young adults, whereas the spine is
the most common site of involved in elderly patients.
This range of manifestations can lead patients to initially
visit rheumatologist.
Variable clinical features and lack of specific symptoms
often cause a delay in diagnosis of osteoarticular brucellosis.
Diagnosis of musculoskeletal brucellosis may be difficult due
to nonspecific clinical symptoms.

19. *Spinal brucellosis
*The spine is one of the most common organs involved up to 54%
* Lumbar vertebrae are the most frequently affected.
* Presents as spondylitis, spondylodiscitis and/or discitis.
*Back pain is the most common complaint, reported by 1/2 of the
patients.
* patients with spinal brucellosis with back pain and sciatica some
times misdiagnosed as intervertebral disc and undergo surgery. Given
the high prevalence of backache, brucellosis should be considered as
a differential diagnosis for sciatic and back pain, especially in the
patients who are at occupational risk of brucellosis in endemic areas.
* Serological screening tests need to be conducted in all such
patients, although serology may not be positive in all cases. MRI may
be the best method to diagnosis and localize the cause of
spondylodiscitis, epidural abscess, or compression on the spine and
spinal nerves related to brucellosis. Epidural abscess is a rare
complication of spinal brucellosis but can lead to severe outcomes,
such as permanent neurological deficits, or even death if not treated
timely.

20. Spondylitis (vertebral osteomyelitis)
High prevalence rate up to 60%
mostly observed in men aged > 40 years old.
 Lumbar (60%), sacral (19%) and cervical (12%) vertebrae are the most
common affected sites.
 Back pain may be gradual or sudden onset with pain radiating to the leg.
Patients experience difficulty in walking and night-pain.
Severe pain can make patients bed-ridden. Spinous processes of affected
vertebrae are tender. The ‘straight leg-raising’ test may be positive. Spinal
deformities are rare (this is possibly due to delay in the diagnosis).
Neurological deficit (paraplegia), which is reportedly rare, was noticed in
few patients

21. There are two types of spinal brucellosis, focal and
diffuse.
 In focal involvement, osteomyelitis is localized in the
anterior aspect of an endplate at the disco-vertebral
junction, but in the diffuse type, osteomyelitis affects the
entire vertebral endplate or the whole vertebral body.
Spondylitis is the dangerous complication of brucellosis
due to its association with epidural, paravertebral and
psoas abscess and potential resultant nerve compression.
Plain X-ray of the lumbar spine may be normal in about
30–40% of brucella spondylitis patients in the first 3–6
months.
 MRI is the most valuable method to diagnose spinal
brucellosis or spinal epidural abscess. MRI is also helpful to
differentiate between pyogenic spondylitis and brucellar
spondylitis.

22. Spondylodiscitis
This is simultaneous inflammation of
vertebrae and disc, and usually occurs via
hematogenous spread.
Up to 85% of osteoarticular involvements are
related to brucellar spondylodiscitis. Lumbar
(60%-69%), thoracic (19%) and cervical
segments (6%-12%).single-focal or multi-focal
involvements.( 3%-14% )
It is the most severe form of osteoarticular
involvement, due to high rate of skeletal and
neurological sequels despite therapy.

23. *Radionuclide bone scintigraphy is an important technique in
determination of musculoskeletal region of brucellosis. Increased
uptake of the involved region on bone scintigraphy is more in favor
of brucellar spondylodiscitis than tuberculous spondylodiscitis.
*MRI is the choice for diagnosis of spondylodiscitis, epidural abscess
and cord or root compression relevant to brucellosis. In MRI, the
lesion is found as destructive appearance (Pedro Pons’ sign) at
antero-superior corner of vertebrae accompanied by prominent
osteosclerosis, which is a pathognomonic finding.

25. Brucellar spondylodiscitis. a. Sagittal STIR image shows hyperintense lesions
contiguous spinal involvement. b. Sagittal T1-weighted image shows hypointense
signal in the vertebral bodies and endplates. c. Contrast enhanced T1-weighted
sagittal image shows formation of spondylitis and involvement of intervertebral disc
space between T10-S1 vertebral levels. d. Contrast enhanced T1-weighted axial

26. *

27. Discitis
The intervertebral disc can be infected without
spondylitis,
In addition to back pain, disc herniation and
sciatica can be described by the patient with
discitis
simultaneous existence of spondylolysis and
spondylolisthesis with brucellar discitis caused
misdiagnosis.

28. Sacroiliitis
Observed in nearly 80% of patients especially who are
infected with B. melitensis spp., with focal complications and
more frequently in adults.
Sacroilitis is acute, unilateral to start with, but if the disease
is left untreated bilateral sacroilitis occurs
 Sacroiliitis may be associated dactylitis, olecranon bursitis,
humerus osteomyelitis and iliac muscle abscess, and with other
systemic diseases, like endocarditis, pyelonephritis and
thyroiditis.
X-ray SI joint showing unilateral (in acute stage) or bilateral
(chronic or advanced disease) sacroilitis. This is likely to be
mistaken for ankylosing spondylitis.
 High-resolution MRI has a higher sensitivity than scintigraphy
in the diagnosis of brucellar sacroiliitis

29. *

30. Limbs
 peripheral skeleton involvement is less prevalent compared with
vertebral features. Arthralgia, enthesopathy, osteomyelitis, arthritis,
bursitis, tendonitis and tenosynovitis are frequent findings
Arthritis occurs in 14%-26% of the patients suffering from acute,
sub-acute or chronic brucellosis.
 Knee, hip and ankle joints are among the most common peripheral
regions affected.
 Shoulders, wrists, elbows, interphalangeal and sternoclavicular
joints may also be involved.
In children, monoarthritis is the most common type of
musculoskeletal brucellosis that mostly involves hip and knee joints.
 Brucellosis can involve the peripheral joints through septic (with
presence of pathogen) and reactive (lack of the pathogen)
mechanisms.

31. Septic arthritis in brucellosis progresses slowly and starts with
small pericapsular erosions. Onset of joint pain may be severe,
sudden onset or mild and gradual onset.
arthritis may last for a few days to few months. Synovial fluid
from the affected joint is usually straw-coloured, cloudy with
raised white blood cell count. The synovial membrane biopsy may
reveal granulomas. Synovial fluid culture may grow brucellae
 Blood culture is positive in 20%–70% of such patients. Although
synovial fluid assessment is the most useful diagnostic method,
the isolation of the pathogen from synovial fluid is not easy. In
relation to the diagnosis of purulent arthritis, it may be necessary
to rely on bone marrow culture in those patients with negative
serology.
Plain X-ray of the joint may be normal.
 Brucellosis should be considered in the differential diagnosis for
a patient presenting with knee or hip arthritis symptoms in
endemic regions to prevent misdiagnosis and serious
complications.

32. Bursitis, tenosynovitis are rare in
brucellosis. There are occasional reports of
subacromion, greater trochanteric bursitis
and inflammation of tendons at the wrist or
ankle.
Osteomyelitis at extra spinal sites is rare;
when present it produces local signs of
inflammation with an overlying sinus

33. *Other system involvement:
Hepatic abscesses and granulomas occur in some cases.
 Spontaneous bacterial peritonitis
Respiratory symptoms, including a cough, dyspnea, and pleurisy,
may occur; however, in most cases, chest radiography is normal,
although focal abscesses, effusions, granulomas may exist.
 Neurologic symptoms: GBS, subarachnoid hge, myelitis
associated with acute neurobrucellosis
Immune thrombocytopenic purpura
lymphadenopathy, splenomegaly, and hepatomegaly.
 Epididymo-orchitis
Endocarditis with new or changing murmurs, and a pericardial
rub
Skin lesions: maculopapular eruptions, EN, abscesses
 Ocular findings: uveitis, keratoconjunctivitis, iridocyclitis,
optic neuritis, and cataracts.

34. Investigations

35. Laboratory tests:
*Serology is often positive in the patients.
 In the acute infection, IgM antibody firstly appears, followed by
IgG and IgA. serological tests [the Wright and 2-
Mercaptoethanol (2-ME) tests]
culture(organism isolation from blood, bone marrow, wounds,
purulent discharge or other body tissues and fluids, with
culture or molecular/histological assessment) (the slow-
growing nature of Brucella > the cultures may take a week or
more to become positive. Bone marrow culture has a higher
yield than blood cultures because the reticuloendothelial
system holds a high concentration of brucellae.
*The Wright test, which is a standard agglutination test (SAT),
measures the total amount of IgM and IgG antibodies, and the 2-ME
test measures IgG antibody.

36. *In the endemic regions, a SAT titer ≥ 1:160 and 2-ME
titer ≥ 1:80 is in favor of brucellosis diagnosis.
*Repeated serologic testing is recommended if the
initial titer is low.
* ELISA is another type of serological test, but has less
sensitivity and specificity.
*PCR is a molecular method which can be very useful
due to its quick procedure and high sensitivity and
specificity, if it is available.
* Direct aspiration or tissue biopsy is usually
necessary to identify the causative organism.
Analysis of liver biopsy specimens may reveal
granulomatous hepatitis and hepatic microabscesses

37. CBC: neutropenia and anemia.
Thrombocytopenia secondary to
hepatosplenomegaly or from immune
thrombocytopenia.
Inflammatory Markers: elevated C-reactive
protein, erythrocyte sedimentation rate, serum
lactate dehydrogenase, and alkaline
phosphatase.
Liver Enzymes: Elevation is very common &
may reflect severity of hepatic involvement &
correlate clinically with hepatomegaly.

38. Imaging methods
radiography, CT, MRI and bone scintigraphy).
Pedro Pons sign, erosion of the anterior
superior aspect of lumbar vertebrae with
osteophytosis, is associated with
spondylodiscitis caused by Brucella. Disc space
narrowing, bone destruction, and sclerosis
may be seen on imaging in patients with
spondylitis
 Analysis of imaging of musculoskeletal
brucellosis may be helpful in the diagnosis of
the disease and in prevention of delayed
manifestation of brucellosis with abscess
which requires invasive treatment methods.

39. Treatment

40. *The main purpose: treat the disease and its symptoms and signs,
and to prevent the relapse.
*Antimicrobials: Combinations of doxycycline, streptomycin,
gentamicin, ciprofloxacin, ofloxacin, co-trimoxazole (trimethoprim
plus sulfamethoxazole) and rifampicin are used.
* No standard therapy exists for osteoarticular brucellosis and
physicians prescribe drugs based on their experiences and
conditions of the disease (the involved site, and being
complicated/uncomplicated). Triple regimen containing
streptomycin (1 g daily) plus doxycycline (100 mg twice daily) plus
rifampin (15 mg/kg daily) over 6 months had 100% efficacy on
brucella. In contrast, double therapy with doxycycline and rifampin
was associated with relapses.
*Failure of antibiotic therapy or progressive neurological deficit,
recurrent infection, unstable spinal segment or marked kyphosis
need surgical intervention.
* The rate of surgical drainage in spinal brucellosis 7.6%-33%.
* In case of abscess in those patients with spondylodiscitis,
treatment duration will be prolonged and surgery may be needed.

43. *

46. *Role of hyberbaric O2 therapy:
•HBOT plays an important role in stimulation of the
bactericidal action of white blood cells which is substantially
impaired at the low oxygen tension observed in wounds.
• HBOT increases the oxygen tension in infected tissues,
resulting in direct bactericidal effects on some organisms
and inhibition of the growth of aerobic and facultative
anaerobic bacteria. ( oxygen-based free radicals oxidize
proteins & membrane lipids, damage DNA, inhibit metabolic
functions essential for microbial growth.
• HBOT also stimulates neovascularization, thus decreasing
tissue ischemia. These angiogenic effects are dose-dependent
and can result in 8- to 9-fold increases in the vascular density
of tissues . Improved vascularity not only improves tissue
oxygen tension and host defenses but also facilitates entry of
leukocytes, antibodies, and antibiotics into the infected
lesion.

47. Prevention:
• Avoid unpasteurized dairy ,all raw dairy foods.
• Cook meat thoroughly until it reaches an int. temp. (63 C) and let it
rest for at least 3 min. (a medium done) and to (71 C) ( well done).
poultry to (74 C).
• Wear rubber gloves when handling sick or dead animals or animal
tissue or when assisting an animal giving birth.
• Take safety precautions in high-risk workplaces:
 laboratory: handle all specimens under biosafety conditions.
Slaughterhouses: separating the killing floor from other processing
areas and use of protective clothing.
• Vaccinate domestic animals. In the United States, an aggressive
vaccination program has nearly eliminated brucellosis in livestock
herds. Because the brucellosis vaccine is live, it can cause disease in
people. Anyone who has an accidental needle stick while vaccinating
an animal should be treated.

48. Differential diagnosis

49. Infectious
Tuberculous is
 Syphilis
S. aureus, E. coli
and Salmonella
variety of fungi
including Aspergillus
spp., Candida spp.
and Cryptococcus
neoformans .
Non infectious
 Rheumatic diseases such
as axial spondyloarthritis ,
sarcoidosis.
Prolapsed intervertebral
disc
Degenerative disease of
the spine
Oncological diseases such
as Hodgkin lymphoma,
metastasis.
Myofascial pain syndrome

50. -Axial SPa Sacroiliitis condensans
sarcoidosis Infection (Brcella&Tb)
Sacroiliitis
(inflammatory)
*

52. Due to the wide range of clinical symptoms,
brucellosis may mimic other infectious and
noninfectious conditions
S. aureus, E. coli and Salmonella can also cause
sacroiliac infection, with musculoskeletal symptoms
with findings in imaging as thinning of the
periarticular fatty tissue layer, increased size of the
adjacent muscles, appearance of abscesses and
presence of destructive bone changes. This is
extremely rare with risk factors such as: being an IV
drug user or immunocompromised.

53. Spondyloarthropathies: Sacroiliitis is a major criterion for its
diagnosis, associated with minor criteria such as arthritis,
dactylitis and enthesitis.
 In ankylosing spondylitis, bilateral sacroiliitis and the presence
of syndesmophytes are common
 in psoriatic arthritis and reactive arthritis, manifestations of
asymmetric and paravertebral sacroiliitis are more frequent. In
these pathologies, it is necessary to look for extraarticular,
mucocutaneous, ocular, and gastrointestinal and genitourinary
tract manifestations, among others, to support their diagnosis
poor response of pain to treatment with NSAIDs and negative
HLA B27, in addition to the asymmetric involvement seen on
MRI with a very acute time of evolution of the disease

54. Spinal tuberculosis, or Pott's disease:
can occur at any age. In areas of high endemicity such as Africa
infection is common in the paediatric age group, whereas in North
America and Europe, tuberculous spondylodiscitis is more
commonly seen in adult patients with a mean age of 40 years.
Two distinct patterns of vertebral tuberculosis may be seen:
1. Spondylodiscitis characterised by destruction of two or more
contiguous vertebrae and opposed end plates, with disc infection
and commonly a paraspinal mass or collection
2. Atypical form of spondylitis without disc involvement.
 20% of patients may have evidence of active pulmonary infection.
Positive tuberculin skin testing (PPD test) ( negative PPD should
not exclude the diagnosis)
backache is the predominant clinical feature, associated with
spine stiffness and spasm of the paravertebral muscles
.

56. Fungal infections
Bone or joint symptoms in patients with fungaemia raise the
suspicion for a focal complication at the time of presentation.
In fungal spondylodiscitis, back pain is the most frequent
complaint, while neurological impairment => infrequent
Kyphosis is uncommon due to the indolent nature of the
infection. Involvement of the vertebral bodies can lead to
vertebral compression fractures and deformity of the spine. In
addition, spread of infection along the anterior longitudinal
ligament can lead to psoas muscle or paravertebral abscesses
Metastatic disease
is usually seen in elderly patients but may be difficult to
differentiate from infection without a biopsy.

57. Prognosis
 The prognosis for most patients with brucellosis is
excellent.
The overall risk of relapse is low.
However, in patients with comorbid disorders like heart or
lung disease, the condition can be disabling.
Unlike many other infection disorders, the condition tends
to improve with physical activity rather than bed rest.
 The recovery usually takes 3-6 months. When recurrence
does occur, it may be either local or systemic.
Overall mortality in acute or chronic cases of brucellosis is
very low, certainly less than 5% and probably less than 2%.

58. Complications
 Rare if the patient is treated timely and appropriately, though
relapse of infection may occur. The risk for the development of
focal complications increases if symptom duration is greater than
one month before diagnosis.
Cardiovascular: Endocarditis, Myocarditis, Pericarditis
Genitourinary: Orchitis, Epididymo-orchitis, Glomerulonephritis,
Pyelonephritis
CNS: Meningitis, Meningoencephalitis, Papilledema, Radiculopathy,
Stroke, Optic neuropathy
Hematologic: Disseminated intravascular coagulation;
Hemophagocytic syndrome
Musculoskeletal: Spondylitis, Sacroiliitis, Arthritis, Osteomyelitis,
Bursitis, Tenosynovitis
Gastrointestinal or hepatobiliary: Hepatitis, Hepatic abscess, Acute
cholecystitis, Ileitis, Colitis
Spontaneous peritonitis
Abscess in the spinal cord, spleen, or thyroid

59. Take home Msg
1. Brucellosis has variable clinical features and osteoarticular
manifestations are the most common. Sacroiliac and spinal
joints are the most frequently involved regions.
Monoarthritis (knee/hip), sacroiliitis and spondylitis
predominate in children, adults and the elderly, respectively.
2. In order to diagnose the disease, history taking, physical
examinations, laboratory tests and imaging techniques are
needed.
3. Brucellosis should be considered as a differential diagnosis
for sciatic and back pain, especially in the endemic regions.
4. Radiological assessments would be very helpful in such cases.
Patients whose big joints, bone and artificial joints are
involved, may be referred to a rheumatology center.
5. Early and appropriate diagnosis and treatment of the disease
is the key of success in management of the patients with the
osteoarticular manifestation of brucellosis.