BrucellosisBrucellosis

Brucellosis is an Brucellosis is an enzooticenzootic infection (i.e. endemic in infection (i.e. endemic in animals). animals).

Although six species of Although six species of BrucellaBrucella Gram-negative bacilli Gram-negative bacilli are known, only four are important to humans: are known, only four are important to humans:

1.1. B. melitensisB. melitensis (goats, sheep and camels in Europe, the (goats, sheep and camels in Europe, the Middle East, Africa, India, Central Asia and South Middle East, Africa, India, Central Asia and South America). causes the most severe disease.America). causes the most severe disease.

2.2. B. abortusB. abortus (cattle, mainly in Africa, Asia and South (cattle, mainly in Africa, Asia and South America).America).

3.3. B. suisB. suis (pigs in South Asia) is often associated with (pigs in South Asia) is often associated with abscess formation. abscess formation.

4.4. B. canisB. canis (dogs). (dogs). an insidious onset, frequent relapse, an insidious onset, frequent relapse, and a chronic course and a chronic course

BrucellaBrucella spp spp..

This organism is an aerobic, small, Gram-This organism is an aerobic, small, Gram-negative coccobacillus that can persist in the negative coccobacillus that can persist in the environment invariably depending on environment invariably depending on temperature, pH, and humidity. temperature, pH, and humidity.

BrucellaBrucella spp. can persist indefinitely if frozen or spp. can persist indefinitely if frozen or protected in aborted fetuses or placentas. protected in aborted fetuses or placentas.

It is a facultative, intracellular pathogen and thus It is a facultative, intracellular pathogen and thus requires prolonged treatment with clinically requires prolonged treatment with clinically effective antibiotics. effective antibiotics.

Sir David Bruce (1855-1931)

The microorganism responsible for Malta fever was discovered by a British Army physician, Sir David Bruce, on July 9, 1887, which he called Micrococcus melitensis.

Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases

Bernhard Bang (1848-1932)

•Danish physician and veterinarian

•Discovered Bacterium abortus in 1897 could infect cattle, horses, sheep, and goats. And the disease known as Bangs disease

Professor FEG Cox. The Wellcome Trust, Illustrated History of Tropical Diseases

Infected animals may excrete Infected animals may excrete BrucellaBrucella spp. in their milk spp. in their milk for prolonged periods and human infection is acquired by for prolonged periods and human infection is acquired by ingesting contaminated dairy products, uncooked meat ingesting contaminated dairy products, uncooked meat or offal.or offal.

Animal urine, faeces, vaginal discharge and uterine Animal urine, faeces, vaginal discharge and uterine products may act as sources of infection through products may act as sources of infection through abraded skin and aerosols to the respiratory tract and abraded skin and aerosols to the respiratory tract and conjunctiva. conjunctiva.

Transmission to HumansTransmission to Humans

Conjunctiva or broken skin contacting infected Conjunctiva or broken skin contacting infected tissuestissues– Blood, urine, vaginal discharges, aborted fetuses, Blood, urine, vaginal discharges, aborted fetuses,

placentasplacentas

Ingestion Ingestion – Raw milk & unpasteurized dairy productsRaw milk & unpasteurized dairy products– Rarely through undercooked meatRarely through undercooked meat

Inhalation of infectious aerosols can also occur Inhalation of infectious aerosols can also occur while cleaning out an infected animal’s pen, or in while cleaning out an infected animal’s pen, or in a slaughter house.a slaughter house.Person-to-person transmission is very rarePerson-to-person transmission is very rare

Who is at RiskWho is at Risk??

Occupational DiseaseOccupational Disease– Cattle ranchers/dairy farmersCattle ranchers/dairy farmers– Veterinarians Veterinarians – Abattoir workersAbattoir workers– Meat inspectorsMeat inspectors– Lab workersLab workers

HuntersHunters

TravelersTravelers

Consumers of unpasteurized dairy Consumers of unpasteurized dairy productsproducts

Clinical featuresClinical features

BrucellaBrucella spp. are intracellular organisms that survive for spp. are intracellular organisms that survive for long periods within the reticulo-endothelial system. long periods within the reticulo-endothelial system.

This explains many of the clinical features, including the This explains many of the clinical features, including the chronicity of disease and tendency to relapse even after chronicity of disease and tendency to relapse even after antimicrobial therapy. antimicrobial therapy.

Acute illness is characterised by Acute illness is characterised by 1.1. a high swinging temperature, rigors. a high swinging temperature, rigors. 2.2. Lethargy. Lethargy. 3.3. Headache. Headache. 4.4. joint and muscle pains.joint and muscle pains.5.5. scrotal pain.scrotal pain.6.6. delirium, abdominal pain and constipationdelirium, abdominal pain and constipation

Physical signs are non-specific, e.g. enlarged lymph Physical signs are non-specific, e.g. enlarged lymph nodes. nodes. Enlargement of the spleen may lead to hypersplenism Enlargement of the spleen may lead to hypersplenism and thrombocytopenia. and thrombocytopenia.

Clinical featuresClinical features

Localised infection , which occurs in about 30% of Localised infection , which occurs in about 30% of patients, is more likely if diagnosis and treatment are patients, is more likely if diagnosis and treatment are delayed. delayed.

BrucellaBrucella organisms may localize in almost any organ but organisms may localize in almost any organ but most commonly localize in bone, joints, central nervous most commonly localize in bone, joints, central nervous system (CNS), heart, lung, spleen, testes, liver, system (CNS), heart, lung, spleen, testes, liver, gallbladder, kidney, prostate, and skin. gallbladder, kidney, prostate, and skin.

Human DiseaseHuman Disease

Can affect any organ or organ systemCan affect any organ or organ system

All patients have a cyclical feverAll patients have a cyclical fever

Variability in clinical signsVariability in clinical signs– Headache, weakness, Headache, weakness,

arthralgia, depression, arthralgia, depression, weight loss, fatigue, weight loss, fatigue, liver dysfunctionliver dysfunction

Human DiseaseHuman Disease

20-60% of cases20-60% of cases– Osteoarticular complicationsOsteoarticular complications

Arthritis, spondylitis, osteomyelitisArthritis, spondylitis, osteomyelitis

Hepatomegaly may occurHepatomegaly may occur

Gastrointestinal complicationsGastrointestinal complications

2-20% of cases2-20% of cases– Genitourinary involvementGenitourinary involvement

Orchitis and epididymitis most commonOrchitis and epididymitis most common

FOCAL MANIFESTATIONS OF FOCAL MANIFESTATIONS OF BRUCELLOSISBRUCELLOSIS

MusculoskeletalMusculoskeletalSuppurative arthritis; synovitis, bursitis Suppurative arthritis; synovitis, bursitis Osteomyelitis Osteomyelitis Spinal spondylitis Spinal spondylitis Paravertebral or psoas abscess Paravertebral or psoas abscess

Central nervous systemCentral nervous systemMeningitis Meningitis Cranial nerve palsies Cranial nerve palsies Intracranial or subarachnoid haemorrhage Intracranial or subarachnoid haemorrhage Stroke Stroke Myelopathy Myelopathy Radiculopathy Radiculopathy

OcularOcularUveitis Uveitis Retinal thrombophlebitis Retinal thrombophlebitis

FOCAL MANIFESTATIONS OF BRUCELLOSISFOCAL MANIFESTATIONS OF BRUCELLOSIS

CardiacCardiacMyocarditis Myocarditis Endocarditis Endocarditis

RespiratoryRespiratoryPneumonitis or abscesses Pneumonitis or abscesses Hilar adenopathyHilar adenopathy

AbdominalAbdominalSplenic abscesses or calcification Splenic abscesses or calcification Hepatitis Hepatitis

GenitourinaryGenitourinaryEpididymo-orchitis Epididymo-orchitis

HaematologicalHaematologicalPancytopenia Pancytopenia

RELAPSING INFECTION.RELAPSING INFECTION.

Up to 10% of patients with brucellosis relapse after Up to 10% of patients with brucellosis relapse after antimicrobial therapy. antimicrobial therapy.

This probably results from the intracellular location of the This probably results from the intracellular location of the organisms.organisms.

Relapses occur most frequently within months after initial Relapses occur most frequently within months after initial infection but may occur as long as 2 years after infection but may occur as long as 2 years after apparently successful treatment.apparently successful treatment.

Diagnosis in HumansDiagnosis in Humans

Isolation of organismIsolation of organism– Blood, bone marrow, other tissuesBlood, bone marrow, other tissues

Serum agglutination testSerum agglutination test– Four-fold or greater rise in titerFour-fold or greater rise in titer– Samples 2 weeks apartSamples 2 weeks apart

ImmunofluorescenceImmunofluorescence– Organism in clinical specimensOrganism in clinical specimens

PCRPCR

DiagnosisDiagnosis

Definitive diagnosis of brucellosis depends on the Definitive diagnosis of brucellosis depends on the isolation of the organism. isolation of the organism.

Blood cultures are positive in 75-80% of infections Blood cultures are positive in 75-80% of infections caused by caused by B. melitensisB. melitensis and 50% of those caused by and 50% of those caused by B. B. abortusabortus. .

Bone marrow culture should not be used routinely but Bone marrow culture should not be used routinely but may increase the diagnostic yield, particularly if may increase the diagnostic yield, particularly if antibiotics have been given before specimens are taken. antibiotics have been given before specimens are taken.

CSF culture in neurobrucellosis is positive in about 30% CSF culture in neurobrucellosis is positive in about 30% of cases. of cases.

Brucella agglutination testBrucella agglutination test

Serum tests are also used to detect brucellosis antibodies. Serum tests are also used to detect brucellosis antibodies.

standerd brucella agg. Test detect both IgG & IgM standerd brucella agg. Test detect both IgG & IgM

In endemic areas a single high titre of In endemic areas a single high titre of > 1/320> 1/320 or a or a fourfold fourfold riserise in titre is needed to support a diagnosis of acute in titre is needed to support a diagnosis of acute infection. infection.

2- mercapto-etanol (2-ME)2- mercapto-etanol (2-ME)

This detect Ig G ab & indicate either active brucellosis or This detect Ig G ab & indicate either active brucellosis or re-infectionre-infection

ELISA testELISA test

The test usually takes several weeks to become positive The test usually takes several weeks to become positive but should eventually detect 95% of acute infections. but should eventually detect 95% of acute infections.

Serological testSerological test

ManagementManagement ManagementManagement

standard therapy in acute infection consists of standard therapy in acute infection consists of

doxycycline 100 mg 12-hourly for 6 weeks plusdoxycycline 100 mg 12-hourly for 6 weeks plus

streptomycin 1 g i.m. daily for the first 2 weeks. streptomycin 1 g i.m. daily for the first 2 weeks.

The relapse rate with this treatment is about 5%. The relapse rate with this treatment is about 5%.

An alternative oral regimen consists of:An alternative oral regimen consists of:

doxycycline doxycycline 100 mg 12-hourly plus 100 mg 12-hourly plus rifampicinrifampicin 900 mg 900 mg (15 mg/kg) daily for 6 weeks, (15 mg/kg) daily for 6 weeks,

but failure and relapse rates are higher, particularly with but failure and relapse rates are higher, particularly with spondylitis. spondylitis.

Rifampicin and co-trimoxazoleRifampicin and co-trimoxazole are potential agents to are potential agents to use in pregnancy. use in pregnancy.

ManagementManagement

Endocarditis Endocarditis is often treated with three active drugs, is often treated with three active drugs, usually usually doxycycline, rifampicin and streptomycindoxycycline, rifampicin and streptomycin, but , but surgery is often required. surgery is often required.

Chronic illness or neurobrucellosisChronic illness or neurobrucellosis should be treated should be treated for a minimum of 3 months and many authorities would for a minimum of 3 months and many authorities would extend this to 6 months, depending upon the response. extend this to 6 months, depending upon the response.

ManagementManagement

PrognosisPrognosis

May last days, months, or yearsMay last days, months, or years

Recovery is commonRecovery is common

Disability is often pronounced Disability is often pronounced

About 5% of treated cases relapseAbout 5% of treated cases relapseFailure to complete the treatment regimenFailure to complete the treatment regimen

Sequestered infection requiring surgical drainageSequestered infection requiring surgical drainage

Case-fatality rate: <2% ( untreated)Case-fatality rate: <2% ( untreated)– Endocarditis caused by Endocarditis caused by B. melitensisB. melitensis

Lyme diseaseLyme disease

The causative agent of Lyme disease is a flagellated The causative agent of Lyme disease is a flagellated spirochaetal bacterium of the genus spirochaetal bacterium of the genus Borrelia. Borrelia.

B. burgdorferiB. burgdorferi is the type species found in the northern is the type species found in the northern hemisphere. hemisphere.

The reservoir of infection is maintained in ixodid (hard) The reservoir of infection is maintained in ixodid (hard) ticks that feed on a variety of large mammals, particularly ticks that feed on a variety of large mammals, particularly deer. deer.

The organism is transmitted to humans, who are The organism is transmitted to humans, who are incidental hosts, via the bite of infected ticks; larval, incidental hosts, via the bite of infected ticks; larval, nymphal and adult forms are all capable of spreading nymphal and adult forms are all capable of spreading infection. infection.

Clinical featuresClinical features

Early localised diseaseEarly localised disease

The characteristic feature is a skin reaction The characteristic feature is a skin reaction around the site of the tick bite, known as around the site of the tick bite, known as erythema migrans.erythema migrans. Initially, a red macule or Initially, a red macule or papule appears 2-30 days after the bite. It papule appears 2-30 days after the bite. It then enlarges peripherally with central then enlarges peripherally with central clearing, and may persist for months. clearing, and may persist for months.

Early disseminated diseaseEarly disseminated disease

During this stage the organism seeds to other During this stage the organism seeds to other organs via the blood stream and lymphatics. organs via the blood stream and lymphatics. There may be a pronounced systemic reaction .There may be a pronounced systemic reaction . Neurological involvement may follow weeks or Neurological involvement may follow weeks or months after infection. months after infection. Common features include lymphocytic Common features include lymphocytic meningitis, cranial nerve palsies and peripheral meningitis, cranial nerve palsies and peripheral neuropathy. neuropathy. Carditis, sometimes accompanied by Carditis, sometimes accompanied by atrioventricular conduction defectsatrioventricular conduction defects

Late diseaseLate disease

Late manifestations include Late manifestations include

arthritis, arthritis,

polyneuritis polyneuritis

encephalopathy. encephalopathy.

Brain parenchymal involvement causing Brain parenchymal involvement causing neuropsychiatric abnormalitiesneuropsychiatric abnormalities

DiagnosisDiagnosis

The diagnosis of Lyme borreliosis is primarily clinical.The diagnosis of Lyme borreliosis is primarily clinical.

Culture from biopsy material is not generally available, Culture from biopsy material is not generally available, has a low yield, and may take longer than 6 weeks.has a low yield, and may take longer than 6 weeks.

Antibody detection is the best means of confirming the Antibody detection is the best means of confirming the diagnosis. diagnosis.

DNA detection by PCR has been applied to blood, urine, DNA detection by PCR has been applied to blood, urine, and biopsies of skin and synovium. and biopsies of skin and synovium.

PCR positivity in CSF is useful in confirming the PCR positivity in CSF is useful in confirming the diagnosis of neuroborreliosis.diagnosis of neuroborreliosis.

TreatmentTreatment

Erythema migrans always requires therapy because of Erythema migrans always requires therapy because of the risk of progressive disease. the risk of progressive disease. Standard therapy consists of a Standard therapy consists of a 14-day course of 14-day course of doxycycline (200 mg daily) or amoxicillin (500 mg 8-doxycycline (200 mg daily) or amoxicillin (500 mg 8-hourly). hourly).

Disseminated disease and arthritis require prolonged Disseminated disease and arthritis require prolonged therapy; a minimum of therapy; a minimum of 30 days' treatment with either 30 days' treatment with either doxycycline or amoxicillin plus probenecid is required.doxycycline or amoxicillin plus probenecid is required.

Neuroborreliosis is treated with Neuroborreliosis is treated with parenteral β-lactam parenteral β-lactam antibiotics for 3-4 weeks. antibiotics for 3-4 weeks.