brucellosis dr. satti new

BRUCELLOSISBRUCELLOSIS

DR. SATTI MOHD SALLEH

Overview

Overview

OrganismHistoryEpidemiologyTransmissionDisease in HumansDisease in AnimalsPrevention and ControlActions to Take

Center for Food Security and Public Health, Iowa State University, 2008

THE ORGANISMTHE ORGANISM

Brucella spp.Gram negative, coccobacilli bacteria

Facultative, intracellular organismEnvironmental persistence

Temperature, pH, humidityFrozen and aborted materials

Multiple species


The Many Names of Brucellosis

Human DiseaseMalta FeverUndulant FeverMediterranean FeverRock Fever of GibraltarGastric Fever

Animal DiseaseBang’s DiseaseEnzootic AbortionEpizootic AbortionSlinking of CalvesRam EpididymitisContagious Abortion


Transmission to Humans

Conjunctiva or broken skin contacting infected tissues

Blood, urine, vaginal discharges, aborted fetuses, placentas

Ingestion Raw milk & unpasteurized dairy products

Rarely through undercooked meat


Transmission to Humans

Inhalation of infectious aerosolsPens, stables, slaughter houses

Inoculation with vaccinesB. abortus strain 19, RB-51

B. melitensis Rev-1 Conjunctival splashes, injection

Person-to-person transmission is very rareIncubation varies

5-21 days to three months


EPIDEMIOLOGYEPIDEMIOLOGY

DISEASE IN HUMANS

DISEASE IN HUMANS

Human Disease

Can affect any organ or organ systemAll patients have a cyclical fever

Variability in clinical signsHeadache, weakness,

arthralgia, depression, weight loss, fatigue, liver dysfunction


Human Disease

20-60% of casesOsteoarticular complications

○Arthritis, spondylitis, osteomyelitis

Hepatomegaly may occurGastrointestinal complications

2-20% of casesGenitourinary involvement

○Orchitis and epididymitis most common


Human DiseaseNeurological

Depression, mental fatigue Cardiovascular

Endocarditis resulting in deathChronic brucellosis is hard to define

Length, type and response to treatment variableLocalized infection

Blood donations of infected persons should not be accepted


Human DiseaseCongenitally infected infants

Low birth weightFailure to thrive

JaundiceHepatomegalySplenomegaly

Respiratory difficultyGeneral signs of sepsis (fever, vomiting)

Asymptomatic


Differentials

TuberculosisToxoplasmosis

CMVHIV infection

Brucella spp.Gram negative, coccobacilli bacteria

Facultative, intracellular organismEnvironmental persistence

Temperature, pH, humidityFrozen and aborted materials

Multiple species


MOST HUMAN INFECTION CAUSED BY:

BRUCELLA MELIENTESIS ( 3 bio Types) Sheep, Goat, Camel-

Brucella Abortus ( Cattle ) 9Bio Types- BRUCELLA SUIS– Pigs ( 5Bio types )-

Brucella CANIS – Dogs ( Rare )

B. melitensis Latin America, Middle East,

Mediterranean, eastern Europe, Asia, and parts of Africa

Accounts for most human casesIn the Mediterranean and Middle East

○Up to 78 cases/100,000 people/year○Arabic Peninsula 20% seroprevalenceRecent emergence in cattle on

Middle Eastern intensive dairy farms


B. abortusWorldwide

Some countries have eradicated it

Notifiable diseasein many countries

Poor surveillance and reporting due to lack of recognition

Fever of Unknown Origin (FUO)


B. suisBiovars 1 and 3

Worldwide problems where swine are raised Free

United Kingdom, Canada Eradicated

Holland, Denmark Low Incidence

○Middle East, North Africa


B. canis

Poorly understood 1-19% prevalence in

United StatesRarely causes disease in

humans


intracellular Organisms–

Incubation ; Weeks to Months

Human Acquire Infections from

Ingesting Milk– Dairy Products ( Not Pasteurized )-

Products of Abortion & Placenta (Infected Animals, Farmers, Veterinarian

Breast Milk ( Rare )-Sexual Transmission ( Rare )-

Transfusion of Blood (Rare)-Only Raw Meat

---CLINICAL---

Recurrent Prolonged Fever-Undulating Patterns-

A febrile Period-Relapse-

Musculoskeletal Symptoms– Fever Mostly at Night-

Profuse sweating- Anorexia, Lethargy ,Depressions-

Neuropsychiatric Manifestations

MeningoEncephalitis-5-10 % Orchitis-

Dry cough-Epistaxis-

Meletenesis more acute Onset

Children (Fever,Joint pain

single joint– Rule out RH -fever

Suis ( Deep tissue Abscess )-10 % Lymphodenephathy)25 % Spleenomegally-Endocarditis less 1%

DIAGNOSIS

GENERAL Low WBC w/ Lymphophenia- Low

platelets-Low Hag-

Low Alkaline Phosphates-Low Transeminates-

ESR-

CULTURE Blood Culture 2/3 Meletenesis-1 Week to 3 Weeks to 6 Weeks-

( Risk of Aerosol-) Bone marrow culture-

Synovial fluid

SEROLOGY

Standard Agglutination Test– Prozone Phenomenon ( False

Negative )-Increase Dilution – 1/640–

Fourfold Rise on Titer ( Acute & Convalescent Sample )-

Previous Exposure ( Low Titer )-

SEROLOGY Negative result does rule out-

Antigen Used is Important-Mercaptoethanol (Dissociate 1gm.)

Cross react -ve-Bacilli (Yersenia, Cholera)-EL Dipsticks-

PCR ( DNA ) sensitive- Tissues ( Non Calcified Granuloma-

Radiology ( differentiate from TB )ISA –Specific IgG ,IGM Immuno essay-

ImagingPatients with spine symptoms MRI

examination to rule out spinal cord compromise .

Plain radiographs, radionuclide bone scintigraphy, CT scanning, and joint

sonography .

Radiology of SpineBrucellosis Tuberculosis

Site Lumbar Dorso lumbar

Vertebrae Multiple,contigous Contigous

Disctis Late Early

Body Intact until late Morphology lost early

Canal compression Rare common

Epiphysitis

Osteophyte

Antero Superior (Pedro-

Pons’ –Sign )

Parrot beak Anterolateral

General + Lower Disc region,Centre,subperiostrialunusual

Deformity Wedging uncommon Anterior wedging

Recovery Of whole body Sclerosis Variable

Paravertebral abscess Small well localized Common discrete loss,transverse process

Psoas Abscess Rare More likely

Localized snowflake calcification in chronic hepatosplenic brucellosis only specific radiographic finding.

TREATMENT

3 Questions Guide Management once

Diagnosis has been made -#Is the disease acute less than 1

month or Relapsing or Chronic more than 6 months ###- Is there disease of

bone or joints-? -?Has TB or other been Excluded -?

MANAGEMENT

Adults =acute non focal disease,

treatment 6 weeks-.Patients with focal disease and or

chronic disease. Treat for 3 months-No mono therapy ,early relapse,

Increase 30% Endocarditis 6 months

ANTIBIOTICS

At least 2 antibiotics Suspicious of TB

Treat bothDo not take REFAMPICINE OR STREPTOMYCINE if

TB not excluded 3 .Gold Standard

Doxycline (6 – 12 weeks 100 mg / BIDStripmycine 1G (2-3 weeks)

4 .Gentamycin 8 mg / kg may be substituted for streptomycin

Optimum duration?? WHO – 14 days

5 .AlternativeDoxycycline 6 weeks + orRifampicin 3 months

(relapse is 10 % compared to 5 % with doxystriptomycin)

6 .Co-trimoxazoleHigh dose (3 tabs / BID) S/E drug rash &anemia,

supplement with folic acidFor adults (cotrimoxazole + doxycycline better than

dcotrimoxazole + rifampicin)Children (3 weeks rather than 6 weeks)

Pregnant women

Rifampicin alone or + Co – trimoxazole (avoid or add folic acid in 1st trimester

PregnancyPremature labour and fetal wastage

Rifampin — 900 mg once daily for six weeks

Rifampin — 900 mg once daily plus trimethoprim-sulfamethoxazole(TMP-SMX; 5 mg/kg of the trimethoprim component twice daily) for four weeks

8 .Triple TheraphyDoxy + Rifampicin + gentamycine

Superior to double treatmentUse for all infection with complication ex.

Spondylitis, meningitis,endocarditis (may need volume replacement)

9 ? .Ceftriaxone

Follow – up at 3 weeksEncourage adherence to therapy

Return of appetite

Return of weight Investigation WBC, HB, ESR,

PLATELETES

Serology not very useful (variable pattern for months or year)

Relapse – define as further episode as further episode 6months

Failure to adequate treatmentTreatment for 3 months – include

streptomycin (to ensure compliance)

Chronic Brucellosis difficult to define serologically

Exclude chronic fatigue syndromeDepressionMalignancy

Immunity not solid (repeated infection)

Indications for SurgeryEndocarditis where valve replacement or

valve debridement is required Drainage or excision of abscesses,

especially those that have not responded to antimicrobials

Spinal epidural abscessRemoval of infected foreign bodies, eg,

pacemaker wires, prosthetic joints

Resection of mycotic aneurysmsProcurement of tissue for diagnostic

purposesChronic hepatosplenic suppurative

brucellosis may require surgery in addition to antibiotics to achieve cure

Osteoarticular Disease

Patients with Brucella spondylitis appear to respond better to doxycycline-streptomycin or a three-drug regimen (doxycycline-streptomycin-rifampin) than to doxycycline-rifampin.

NeurobrucellosisDoxycycline ,

RifampinTrimethoprim-sulfamethoxazole .

The duration of therapy is generally prolonged individualized according to clinical signs and symptoms

Continued until cerebrospinal fluid parameters have returned to normal

Public health aspectsEducation to people

Commitment of all related deportationControl of infected hands flucks

Animal vaccinationFor infected animal test & slaughter

Financial compliment

PREVENTION AND CONTROL

PREVENTION AND CONTROL

Prevention and Control

Education about risk of transmissionFarmer, veterinarian, abattoir worker,

butcher, consumer, hunter, publicWear proper attire if dealing with

infected animals/ tissuesGloves, masks, goggles

Avoid consumption of raw dairy products



Immunize in areas of high prevalence

Young goats and sheep with Rev-1Calves with RB51 No human vaccine

Eradicate reservoir Identify, segregate, and/or cull

infected animals



B. suis, B. ovis, and B. canis Venereal transmission

Separate females at birthing to reduce transmission on the farm or in kennel


RB51Approved for use February 1996 for calves

Able to differentiate “wild type” exposure from immunization

Lacks LPS-O antigen that causes antibody response on serologic or milk tests

Infectious to humansSerologically negative upon testing post-

exposureCDC registry of human exposures

32 documented exposures as of 1998


U.S. Eradication Program

U.S. Department of Agriculture1934 :Cooperative State-Federal Brucellosis

Eradication Program○Removal of diseased cattle due to drought

1951 :APHIS became involved1957 :124,000 positive herds

ApproachTest, slaughter, trace back,

investigate, and vaccinate



Target date for eradication was December 31, 1998

SurveillanceBrucellosis ring test

○Pooled milk

Market Cattle Identification○Blood test, individual

Indemnity for whole herd depopulation250$ nonregistered cattle/bison

750$ or 95% of value minus salvage value for registered cattle



Fiscal Year 20014.7 million calves vaccinated

9.9 million cattle tested under the Market Cattle Identification program

3 brucellosis herds depopulated○Indemnity paid = $211,153

○An additional $47,700 for purchase of animals or diagnostic purposes



http://www.aphis.usda.gov/vs/nahps/brucellosis/status_rpt/figure11.jpg


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Brucella as a Biological Weapon

Aerosolized B. melitensisCity of 100,000 people

Inhale 1,000 cells (2% decay per min)Case-fatality rate of 0.5%

50% hospitalized for 7 days○Outpatients required 14 visits

○5% relapsed

Results82,500 cases requiring extended therapy

413 deaths477.7$ million economic impact


brucellosis dr. satti new

Education

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iowa state university

infected tissuesblood

infected animals pen

person transmission

aborted fetuses

brucella abortus