Transcript BRUCELLOSIS

BRUCELLOSIS
Dr. Indumathi
Consultant Microbiologist
Gokula Metropolis Clinical Laboratory
GRAM NEGATIVE COCCOBACILLI
(PARVO BACTERIA)
• BORDETELLA, BRUCELLA, YERSENIA,
PASTEURELLA, FRANCESELLA
• HAEMOPHILUS, MORAXELLA,
GARDENERELLA
• HACEK
Historical Background
• Malta Fever
– Major health problem to British troops in Malta in the 19th and early
20th centuries.
Cases(1901-07)
Deaths
Navy
1705
30
Army
1947
55
Civil services
4627
489
HISTORICAL BACKGROUND
• MEDITERRANEAN FEVER
• UNDULANT FEVER
• MALTA FEVER
Historical Background
• 1860 J.A. Maraston; assistant surgeon in
the British Army in Malta -- first accurate
description “Mediterranian Gastric Remittent
Fever”
• David Bruce (1855-1931)
-1883 sent to Malta to provide medical care
to the troops.
- 1887 isolated “micrococcus” from spleens
of 4 soldiers died of the disease.
Historical Background
What is the source?
“Mediterranean Fever Commission”
1904
Historical Background
• 1905 ZAMMIT; MALTESE PHYSICIAN
- GOATS: SOURCE OF INFECTION. : GOATS’
MILK
• 1897 E. BANG; DANISH VETERINARIAN
-INTRACELULAR PATHOGEN CAUSING
ABORTION IN CATTLE NAMED “BACILLUS
ABORTUS”.
• 1918 A.EVANS; AMERICAN MICROBIOLOGIST
BACILLUS ABORTUS AND MICROCOCCUS
MELITENSIS & NAMED IT BACTERIACEAE.
Historical Background
• 1920 Meyer and Shaw suggested
BRUCELLA
• 1914 Mohler isolated organism from
liver & spleen of Pigs--B.suis.
• 1957 B. neotome, 1963 B. ovis, 1966 B.
canis
Epidemiology
• Worldwide zoonosis
• Only 17 countries declared brucellosis
free1986
• Six species
1. B.abortus - mainly cattle
2. B.melitensis - sheeps & goats
3. B.suis - pigs
4. B. canis - dogs
5. B. ovis - sheep (not human pathogen)
6. B. neotomae - desert wood rat
(not human pathogen)
• B. melitensis -- most common worldwide
Epidemiology
• ENDEMIC DISEASE :Saudi Arabia, Iran, Iraq
• MOSTLY B. MELITENSIS & B. ABORTUS.
• NO CLEAR FIGURES ABOUT INCIDENCE &
PREVALENCE.
• INCIDENCE : 5.4 PER 1000 PER YEAR.
• PREVALENCE : 8.6 - 38 % - SOME REGIONS.
Bacteriology
• GRAM NEGATIVE COCCI, COCCOBACILLI,
• STRICT AEROBIC, NONMOTILE, NONSPORE
FORMING.
•
•
•
•
3 SPECIES:
B.MELITENSIS : GOATS
B.ABORTUS
: CATTLE
B.SUIS
: PIGS
BACTERIOLOGY
• FACULTATIVE INTRACELLULAR
• STRICT AEROBES/FASTIDIOUS
• 5-10% CARBONDIOXIDE : FOR B.ABORTUS
• SLOW GROWTH ON ORDINARY MEDIA
• ENRICHED MEDIUM : GLUCOSE/SERUM/
• TRYPTICASE SOY BROTH/AGAR
BIOCHEMICAL REACTIONS
• NO FERMENTATION OF SUGARS
• OXIDATIVE
• OXIDASE AND UREASE POSITIVE
• IMVIC : ----
SPECIES DIFFERENTIATION
TEST
DYE SEN
BASIC FUCH
THIONIN
HYDROGEN
SULPHIDE
CO2
REQUIREMENT
HOST
ABORTUS
MELITENSIS
SUIS
R
S
YES
R
R
NONE
S
R
YES
YES
nONE
NONE
CATTLE
SHEEP/GOAT
PIGS
Transmission
• ZOONOSIS AFFECTING DOMESTIC ANIMALS.
• CONCENTRATED IN MILK, URINE, GENITAL ORGANS.
ROUTES OF TRANSMISSION
• ORAL : UNPASTEURISED MILK & PRODUCTS
RAW MILK OR MEET.
• RESPIRATORY: LAB WORKERS.
• SKIN: ACCIDENTAL PENETRATION OR ABRASION
– - AT RISK FARMERS & VETERINARIANS.
• OTHER ROUTES:
CONJUNCTIVAL, BLOOD TRANSFUSION,
TRANSPLACENTAL, ? PERSON TO PERSON.
Pathogenesis
Entry to the body
Macrophage activation
Intracelluar multiplication
Lymphatics
RES organs
Blood
Any organ
Polymorph migration &
Phagocytosis
VIRULENCE FACTORS
• RESISTS PHAGOCYTOSIS :
• LOW M.W. MOLECULES INHIBIT
FUSION OF
LYSOSOMES/PHAGOSOMES
• ABILITY TO SURVIVE
INTRACELLULARLY : PROLONGED
PERSISTANCE
Pathogenesis
• CELL MEDIATED IMMUNITY ALSO ACTIVATED
WITH GRANULOMA FORMATION (MAINLY
WITH B. ABORTUS)
• HUMORAL ANTIBODY RESPONSE OF LITTLE
IMPORTANCE
• MAIN WAY OF BODY CONTROL OF THE
INFECTION IS THROUGH COMMITTED TLYMPHOCYTES PRODUCING LYMPHOKINES
(- INTERFERON) WHICH ACTIVATE
MACROPHAGE KILLING
Clinical Manifestations
•
•
•
•
•
INCUBATION PERIOD: VARIABLE 2- 8 WKS.
PRESENTATION: ACUTE 50% & INSIDIOUS 50%
SX & SIGNS NOT SPECIFIC.
CAN AFFECT ANY ORGAN.
COMMON NONSPECIFIC SX: - FEVER WITH
RIGORS.
SWEATS, MALAISE, ANOREXIA.
- HEADACHE, BACK PAIN.
Clinical Manifestations
Acute
(8wks)
Undulant
(<52 wks)
Chronic
(>52wks)
Young adults
> 40 yrs
Arthralgia
Children,
young adults
++
+++
+++
High fever
95%
50-70%
No
Hepatomegaly
66%
50%
Occasional
Splenomegaly
50-70%
< 40%
Rare
Psychiatric
No
Occasional
Frequent
Ocular
(uveitis)
No
1-2%
5-10%
Age
Clinical Manifestations
• GIT 70% : ANOREXIA, ABD. PAIN, VOMITING,
DIARRHEA,CONTIPATION,
HEPATOSPLENOMEGALY.
• LIVER : INVOLVED IN MOST CASES BUT LFTS
NORMAL OR MILDLY ABNORMAL.
– GRANULOMAS (B. ABORTUS).
– HEPATITIS (B.MELITENSIS).
– ABSCESSES (B.SUIS).
Clinical Manifestations
• SKELETAL 20-60% :
• ARTHRITIS, SPONDYLITIS, OSTEOMYELITIS.
• SACROILIITIS - MOST COMMON.
• ATHRITIS - OLIGOARTICULAR : HIP, KNEE &
ANKLES.
JOINT ASP. - MONOCYTOSIS, CULTURE +VE IN 50
%
CLINICAL MANIFESTATIONS
• NEUROLOGIC
– MENINGITIS, ENCEPHALITIS,
RADICULOPATHY & PERIPHERAL
NEUROPATHY, INTRACEREBRAL
ABSCESSES
– MENINGITIS
» ACUTE OR CHRONIC
» NECK RIGIDITY < 50%
» CSF
• LYMPHOCYTIC PLEOCYTOSIS
• (N) OR LOW SUGAR
• INCREASE PROTEIN
• CULTURE +VE < 50%
• AGGLUTINATION +VE IN >95%
CLINICAL MANIFESTATIONS
• CARDIOVASCULAR
– ENDOCARDITIS 2% (MAJOR CAUSE OF
MORTALITY)
– RX: VALVE REPLACEMENT AND
ANTIBIOTICS
– PERICARDITIS & MYOCARDITIS
• PULMONARY
– INHALATION OR HEMATOGENOUS
– CAUSE ANY CHEST SYNDROME
– RARELY BRUCELLA ISOLATED FROM
SPUTUM
Clinical Manifestations
• GENITOURINARY
– EPIDYDEMOORCHITIS
– PYONEPHROSIS (RARE)
• CUTANEOUS
– NONSPECIFIC
• HEMATOLOGIC
– ANEMIA
– LEUKOPENIA
– THROMBOCYTOPENIA
DIAGNOSIS
• HISTORY OF ANIMAL CONTACT IS
PIVOTAL
• IN ENDEMIC AREA, IT SHOULD BE
IN THE DD OF ANY NONSPECIFIC
FEBRILE ILLNESS
Diagnosis
• LABORATORY
–WBC (N) OR
. MONOCYTOSIS
–SPECIMENS: BLOOD
–
BONE MARROW
–BLOOD CULTURES : CASTANEDA’S
»SLOW GROWTH = 4 WEEKS
»NEW AUTOMATED SYSTEM BATEC
IDENTIFIES HE ORGANISM 4-8
DAYS
Diagnosis
• SEROLOGY
– STANDARD AGGLUTINATION TEST – (SAT
DIAGNOSTIC ??
1 : 160 - NON ENDEMIC
1 : 320 - ENDEMIC AREA
» SAT - FALSE NEGATIVE
• PROZONE
• BLOCKING ANTIBODIES
–OTHER TESTS: COOMBS,
ELISA, CFT,
Brucella Antibodies
• AGG = IgG + IgM
• 2ME = IgG
• DETECTING INFECTED ANIMALS:
• MILK RING TEST ; MILK + BACTERIAL
SUSPENSION (STAINED) : BLUE RING
ABOVE CREAM LINE
Prognosis
• Preantibiotic era
– Mortality 2% mainly endocarditis
• Morbidity
– High with B. melitensis
– Nerve deafness
– Spinal cord damage
Prevention
–CONTROL OF DISEASE IN DOMESTIC
ANIMALS
»IMMUNIZATION USING
»B. ABORTUS STRAIN S19
»ROUTINE PASTEURIZATION OF
MILK
–IN LABS STRICT BIOSAFETY
PRECAUTIONS
Treatment
DRUGS AGAINST BRUCELLA
• TETRACYCLINES
• AMINOGLYCOSIDES
– STREPTOMYCIN SINCE 1947
– GENTAMICIN
– NETILMICIN
• RIFAMPICIN
• QUINOLONES - CIPROFLOXACIN
Treatment
Drugs against Brucella
• Treatment for uncomplicated Brucellosis
– Stremptomycin + Doxycycline for 6 weeks
» ? TMP/SMX + Doxycycline for 6 weeks
– WHO recommendation 1986
» Rifampicin + Doxycycline for 6 weeks
• Treatment of complicated Brucellosis
– Endocarditis, meningitis
– No uniform agreement
– Usually 3 antibrucella drugs for 3 months
Untreated Brucellosis
10000
Titer
1000
IgG
IgM
100
10
1
2
3
4
Weeks
5
6
Treated Brucellosis
10000
Treatment
Titer
1000
IgG
IgM
100
10
1
2
3
4
Months
5
6
7
Relapse
PREDICTORS OF RELAPSE
MALE SEX
INADEQUATE ANTIBIOTIC
THERAPY.
POSITIVE CULTURE ON INITIAL
DISEASE
THROMBOCYTOPENIA
Ariza, et al: CID 20:1241, 1995