brucellosis diagnosis and treatment UOD

1. Brucellosis
Muayad Aghali Merza
Infectious Diseases Specialist
School of Medicine
26st
November 2014

2. Objectives
Students should be able to:
• Define brucellosis.
• Describe the causative organism.
• Describe pathogenesis and clinical features of the disease.
• Mention diagnostic methods of brucellosis.
• State treatment of brucellosis.
• Describe prevention and control of the disease.

3. Definition

4. Brucellosis
o Brucellosis is a zoonosis primarily of
domestic animals, causing a chronic
debilitating septicemic disease leading to
abortion.
o The disease is prevalent worldwide and is
particularly common in the Mediterranean
and Middle Eastern countries, and in parts of
Africa and South America.

5. Other Names of Human
Brucellosis
o Malta Fever, Undulant Fever, Mediterranean
Fever, Gastric Fever.
o The causal Brucella species are named after
Sir David Bruce, who discovered the cause of
one form of the disease while serving in
Malta in 1887.

6. The Organism

7. Brucella spp.
o Gram negative, intracellular coccobacilli
bacteria.
o Non-motile, non-capsulated, non-spore
forming.

8. Brucella spp.
o Environmental persistence.
• Temperature, pH, humidity.
• Frozen and aborted materials.
o Multiple species.

9. Species Main animal
host
Human
Pathogen
Pathoge-
nicity
B. abortus cattle yes Moderate
B. melitensis goats, sheep yes Highest
B. suis pigs yes High
B. canis dogs yes Moderate
Main Causative Species of
Human Brucellosis

10. Antigenic Structure and Classification
o A and M antigens are common to 3 mains
Brucella spp.
o B. melitensis has the highest concentration of
M antigen and causes the most serious
infections.
o The difference between species is related to
the amount of the two main antigen:

11. • B. abortus : A:M=20:1
• B. melitensis: A:M=1:20
• B. suis : A:M=2:1
Antigenic Structure and Classification
AA MM
AA MM
MMAA

12. Pathogenesis

13. Pathogenesis
o Ingestion:
• Raw milk & unpasteurized dairy products.
• Rarely through undercooked meat.
o Inhalation:
o Inoculation:
o Person-to-person transmission is very rare.
of placental or uterine discharges, blood
and urine.

14. Pathogenesis
o Animal tissues and products, such as
placenta, uterus and milk, that are rich in
erythritol (a growth factor for brucellae) can
be heavily contaminated and highly
infectious.
o Spread in the body occurs via lymphatics,
replication within lymph nodes, and then wide
hematogenous spread to organs and tissues.

15. Pathogenesis
o Intracellular parasitism: brucellae have a
particular tendency to persist intracellularly,
notably in the reticuloendothelial system.

16. Who is at Risk?
o Occupational Disease:
• Cattle ranchers/dairy farmers.
• Veterinarians.
• Abattoir workers.
• Meat inspectors.
• Lab workers.
o Hunters.
o Travelers.
o Consumers of unpasteurized dairy products.

17. Clinical features

18. Clinical features
o Incubation period: 1-3 weeks,
occasionally several months.
o Can affect any organ or organ system.
o Fever may be intermittent or undulant.
Fever, often persists for months or
years. Undulant fever
39.5
37.0

19. Clinical features
o Non specific symptoms: sweating,
anorexia, constipation, rigor and
weakness.
o Depression.
o Osteoarticular complications e.g. arthritis,
osteomyelitis.

20. Clinical features
o Splenomegaly, lymphadenopathy and
hepatomegaly.
o Orchitis and epididymitis.
o A septicemic disease, abortion can occur.

21. Clinical features
o Classification: Acute (< 1 year) and Chronic
(>1 year).
o Low case fatality rate mostly due to
infective endocarditis.

22. Diagnosis

23. Diagnosis
1- Clinical features.
2- Serology: brucella agglutinins in the blood.
3- Blood or tissue culture.
4- Polymerase Chain Reaction (PCR).

24. Diagnosis in Humans
o Serology: brucella agglutination test.
• Four-fold or greater rise in titer.
• Samples 2 weeks apart.
o BAT detects antibody to B. abortus, B.
melitensis and B. suis but NOT to B. canis.
o Therefore, specific serologic tests for B.
Canis must be requested.
o Rose Bengal Test is useful for screening.

25. Positive
agglutination
Negative
agglutination

26. Diagnosis in Humans
o False positive: cross reactivity with
antibodies of F. tularensis,, E. coli and V.
cholerae.
o False negative: in prozone phenomenon.

27. Diagnosis in Humans
o Prozone phenomenon may occur secondarily
to hyperantigenemia, which might result in a
false-negative results.
o High levels of antigen may prevent the
formation of antigen-antibody complexes.
o To solve this problem, routine dilution of the
serum beyond 1:320 would help to prevent
such a problem.

28. o 2-ME-test (mercaptoethanol): more specific,
positive in chronic Brucellosis.
o ELISA test:
• High IgM in acute infection.
• High IgG in chronic infection.
Diagnosis in Humans

29. Diagnosis in Humans
o Culture of blood, bone marrow and tissue fluids.
• Blood culture: +ve in about 50 -70% of
cases.
• Bone marrow culture is the standard criterion,
since the reticuloendothelial system holds a
high concentration of the organism.
Sensitivity 80-90%.
• Blood or bone cultures should be incubated
for at least 6 weeks.

30. o PCR is a rapid and accurate method for
diagnosis of Brucella species.
o CBC: Non specific, (leucopenia, lymphocytosis,
anemia). Moderate elevation of ESR.
Diagnosis in Humans

31. Treatment, Prognosis and
Prevention & Control

32. Treatment of Choice
o Combination therapy has the best efficacy.
• Doxycycline for six weeks in
combination with streptomycin for 2-3
weeks or rifampicin for 6 weeks.
o CNS cases treat 6-9 months.
• Same for endocarditis cases plus
surgical replacement of valves.

33. Prognosis
o This disease is easily curable with a low
risk of relapse or chronicity.
o About 5% of treated cases relapse
• Failure to complete the treatment
regimen

34. Prevention and Control
o Education about risk of transmission.
• Farmer, veterinarian, abattoir worker,
butcher, etc.
o Wear proper attire if dealing with infected
animals/tissues.
• Gloves, masks, goggles.
o Avoid consumption of raw dairy products.

35. Prevention and Control
o Immunize animals in areas of high
prevalence.
• Effective attenuated live bacterial vaccines
exist against B. abortus (strain 19) and B.
melitesis (Rev-I), but as yet none exists
for B. suis or B. canis.
o No human vaccine.

36. Questions?