Transcript Mycobacteria

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MYCOBACTERIA
Mycobacteria cont…..
• Objectives:
 Introduction:
 Scientific classification
 Mycobacterium tuberculosis
 Shared Mycobacterial Properties
 Transmission and Epidemiology
 Pathogenesis
 Clinical course of Tuberculosis
 Disease transmission and incidences
 Treatment of active TB
 Prevention
 Mycobacterium leprae(Hansen’s Disease
Mycobacteria
Introduction:
They are aerobic acid- fast bacilli(rods)
They are neither gram –ve nor +ve stain poorly by dyes
used in Gram stain so acid fast bacilli(ability to retain
carbolfuchsin stain despite treatment with ethanol
hydrochloric acid mixture
Have high lipid content on cell wall hence acid-fast
Major pathogens are Mycobacterium tuberculosis and
Mycobacterium leprae
Atypical mycobacteria are :
M.avium –intracellular are complex and
Mycobacterium kansasii- cause tuberculosis like disease
Classification
Introduction cont…
• Mycobacterium chelonei occassionally causes
disease in immunocompromised patient or
patients with prosthetic devices
MYCOBACTERIUM TUBERCULOSIS
• Causative bacterium for Tuberculosis disease the
bacterium infects one third of World population
• Causes 3mil. Deaths / Year
• Causes 8 million new cases / year
Introduction cont…
• Shared Mycobacterial Properties:
 Mycobacteria are slow growing
aerobes,fucultative intracellular rods with lipid
rich cell wall hence acid fast
 Cell wall composed of three layers:
Hydrophobic layer
- Mycosides-acid fastness (Acid fastness)
- Wax D(Immunoadjuvant)
- Cord factor(virulence)
- Antigenic proteins(DTH response)
MYCOBACTERIUM TUBERCULOSIS
• Shared Mycobacterial Properties:
 Cell wall composed of….
Arabinogalactan-mycolic acid layer( convalently
attached to peptidoglycan)
Thick peptidoglycan layer
 Diseases caused:
• Diseases caused by Mycobacteria often are
chronic with prolonged latent period with periods
of remission alternating with active disease
manifestations.
MYCOBACTERIUM TUBERCULOSIS cont..
Properties:
 Grows slowly doubling time of 18hours
 Culturing of clinical specimen should be held for 68wks before recorded negative
 Can be cultured on bacteriologic media
 Medium contains complex nutrients(eg.egg yolk) and
dyes which limit unwanted flora present in sputum
samples.
 M.tuberculosis is obligate aerobe that is why likely to
cause disease in highly oxygenated tissue – lung
upper lobe and kidney
 The Cell wall contains several complex lipids(Mycolic
acids) which contribute in acid fastness
MYCOBACTERIUM TUBERCULOSIS cont..
Properties cont..:
 Phosphatides help in caseation necrosis
 Wax D active component enhancing immune
response
 The organism contains various proteins when
combined with waxes elicits delayed
hypersensitivity these proteins are antigens in the
Purified Protein Derivatives(PPD)skin test or
tuberculin skin test.
 M. tuberculosis is relatively resistant to acids and
alkalis
MYCOBACTERIUM TUBERCULOSIS cont..
Properties cont..:
 M.tuberculosis is resistant to dehydration so
survives in dried sputum hence transmission by
aerosol.
 Nowadays shows multiple drug resistance(MDR)
due to chromosomal mutations
MYCOBACTERIUM TUBERCULOSIS cont..
Transmission and Epidemiology:
 Transmission is by respiratory aerosol mainly by
coughing from smear positive source to initial site
which is lung but this does not completely exclude
smear negative sources.
 Drinking unpasteurized cow milk from infected
cow leads to gastrointestinal tuberculosis –
Causative agent is Mycobacterium bovis
 The disease is common in socioeconomically
disadvantaged people with poor nutrition and
housing.
MYCOBACTERIUM TUBERCULOSIS cont..
Pathogenesis:
Two types of lesions:
a. Exudate
b. Granulomatous
Exudate lesions: Consist of a acute inflammatory
response occurs in the lungs at the initial and
common sites of infection. Inhaled mycobacteria
are engulfed by alveolar macrophages and living
in phagosomes replicate produces exported
repetitive protein which prevent fusing of
phagosomes and lysosomes hence prevents
bacterial destruction
MYCOBACTERIUM TUBERCULOSIS cont..
Intracellular growth: Protects mycobacteria from
antibody mediated elimination
Other macrophages are attracted to the site and
destroy the infected cells releasing mycobacteria
that can spread through blood stream.
Granulomatous lesions: Consist of giant
cells(Langhans’ giant cells) centrally containing
dormant but viable tubercle bacilli surrounded
by a zone of epithelioid cells-can be released
later in life
MYCOBACTERIUM TUBERCULOSIS cont..
Pathogenesis:
 No any Mycobacterium produces toxins
 They infect macrophages and other
reticuloendotherial cells
 M.tuberculosis survives and multiply in
phagosomes and prevents lysosome from
degradative function
 The bacterium presence and host response cause
two types of lesions
MYCOBACTERIUM TUBERCULOSIS cont..
• Pathogenesis cont…
• Langhan’s giant cells: Pathological findings in
tuberculous lession.
• Tubercle: A granuloma surrounded by fibrous
tissues that has undergone central caseation
necrosis.
MYCOBACTERIUM TUBERCULOSIS cont..
• Mycobacterial Diseases:
Species
Diseases
Distribution
M.tuberculosis
Pulmonary and
Extrapulmonary
tuberculosis
↑ incidence among young kids ,
elderly , chronic ill and
immunocompromised
M.bovis
Tuberculosis in cattle and
humans
Those who consume
contaminated milk
M.leprae
Leprosy(Hansen’s disease)
Common in Asia and Africa
M.avium-intracellulare(MAC)
Disseminated
disease,PTB,sub acute
lymphadenitis
Disseminated disease among
AIDS patients
M.kansasii
TB like
disease,osteomyelitis,lymp
hoadenopathies
Those with lung
disease,immunocompromised
M.scrofulaceum
Cx Lymphadenitis(scrofula)
Young children
Atypical Mycobacteria
MYCOBACTERIUM TUBERCULOSIS cont..
• Clinical features of important Mycobacteria:
Organism
Main site
of
infection
Vaccine
Availability
Lungs
Skin Test in Multiple
Common
drug
Use
therapy
used
Yes
Yes
M.tuberculosis
M.avium intracellulare
Lungs
No
Yes
No
M.leprae
Skin,Nerve No
Yes
No
Yes
MYCOBACTERIUM TUBERCULOSIS cont..
• Clinical course of Tuberculosis: Active disease occurs
within 2yrs of infection 5%-10%(Primary) and recurs
later in life
 Localized infection foci: Form within lung after
inhalation of M.tuberculosis-DTH response restricts
proliferation of bacteria with macrophages
 Clinical manifestations of active TB:
-Nonspecific symptoms: malaise , weight
loss,cough,night sweats and haemoptysis ,fatigue
-Active disease marked by pneumonitis,abscess
formation,cavitation one or both upper lobes of lungs
and Hilar lymphadenopathy. (nontender
lymphnodenopathy)- usually unilaterally
MYCOBACTERIUM TUBERCULOSIS cont..
 Clinical manifestations of active TB cont…:
-Calcification of healed primary lesions leaves
scar appearing as spots on the lungs in
radiographs(Ghon complex)
 Secondary pulmonary tuberculosis:
Recurrence of clinical manifestations due to
reactivation of dormant tubercle bacilli,
reinfection-common in immunocompromised pts
MYCOBACTERIUM TUBERCULOSIS cont
 Secondary pulmonary tuberculosis cont….:
Formation of fibrocaseous cavity lesions near apex
of upper lobes.
 Extra pulmonary (Miliary) tuberculosis:
- Meaning tissues other than lungs are attacked by
the M.tuberculosis(eg:Lymph nodes,GUT,CNS etc)
these is a consequence of haematogeneous spread
of tubercle bacilli
MYCOBACTERIUM TUBERCULOSIS cont
 Disease transmission and incidences:
- Human are only natural reservoir for
M.tuberculosis
-Spread is by respiratory droplets and promoted by
crowding and coughing.
- Young children , elderly and immunocopromised
ones at greater risk of infection.
MYCOBACTERIUM TUBERCULOSIS cont
 Treatment of active TB:
• Multidrug therapy:
(Isoniazid,rifampin,pyrazinamide)for successful
treatment.
• Multidrug therapy resistance(MDR) strains becoming
more common nowadays-esp.among
immunocompromised pts-are treated with a
combination of:
(isoniazid,rifampin,pyrazinamide,ethambutol and
streptomycin)
MYCOBACTERIUM TUBERCULOSIS cont
 Prevention:
 - Surveillance programs using PPD skin test
identify previously infected individuals then chest
X-rays or with positive response.
 -Prophylactic isoniazid may be given to those at
risk
 BCG- Bacillus Calmette–Guérin(Live attenuated
BCG vaccine)-risk for immunocompromised
individuals
Mycobacterium leprae(Hansen’s Disease)
• M.leprae causes leprosy a disease characterized
by skin lesions,nerve damage and extensive tissue
destruction.
 Pathogenesis:
 Immune response initiated by patient determines
the outcomes of infection:
a. TH1 response(DTH,IFNϒ,macrophages) leads to
milder tuberculoid leprosy
b. TH2response (humoral antibody) leads severe
lepromatous leprosy
Mycobacterium leprae(Hansen’s Disease)
• Clinical Presentations:
• IP: Several years onset of disease is gradual
• Tuberculoid leprosy – Hypopigmented macular or
plague like skin lesions, thickened superficial nerves
and anaesthesia.
• Lepromatous leprosy:- Multiple nodular skin lesions
resulting to lionlike facies but after treatment
patients develop erythema nodosum
leprosum(ENL)-sign of CMI restoration
• ENL-Normally are painful nodules
Mycobacterium leprae(Hansen’s Disease)
• Clinical Presentations cont…..:
• Why disfigurement? There several factors:
a. Skin anaesthesia resulting to burns and
trauma
b. Resorption of bone leading to loss of features
eg; nose and finger tips
c. Infiltration of the skin and nerves leading to
thickening and folding of the skin
Mycobacterium leprae(Hansen’s Disease)
• Laboratory Diagnosis
• Demonstration of Acid fast bacilli on the skin
lesion or nasal scrapings
• Noticing of lipid-laden macrophages(foam cells)
containing acid fast bacilli
• For tuberculoid form – few organisms are notice
granulomas are diagnostic
• Culturing normally are negative as organisms do
not glow on artificial media
• Serological tests- not useful
Mycobacterium leprae(Hansen’s Disease)
• Treatment: Mainstay of therapy is
Dapsone(diaminodiphenyl-sulfone)
• Combination therapy:dapsone,clofazimine for
lepromatous and dapsone & rifampin for
tuberculoid form.
• Prevention: Isolation of all lepromatous patients
in combination with chemoprophylaxis
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• HAEMOPHILUS
HAEMOPHILUS
• Haemophilus is the name of a group of bacteria.
There are several types of Haemophilus
• They can cause different types of illnesses
involving breathing, bones , joints, and the
nervous system.
• One common type, Hib (Haemophilus influenzae
type b), causes serious disease. It usually strikes
children under 5 years old.
• They are Gram-negative coccobacilli bacteria
HAEMOPHILUS
• They are obligate parasites found on mucous
membranes of humans and some animals
• H.influenze and H.ducreyi are the most medically
important species
• They are categorized as pleomorphic bacteria
because of the wide range of shapes they
occasionally assume.
HAEMOPHILUS
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Scientific classification:
Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Pasteurellales
Family: Pasteurellaceae
Genus :Haemophilus
Species: H. influenzae
H.ducreyi
HAEMOPHILUS
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HAEMOPHILUS
• Haemophilus influenzae:
• Pathogenesis:
- It has antiphagocytic capsule which is critical
virulence factor
-H.influenza type b(Hib) most virulent of 6 types
invades the mucosa enters blood to causes
systemic disease
Non capsulated H.influenza: Normal flora of upper
respiratory tract but may cause localized
opportunistic infections.
HAEMOPHILUS
Haemophilus influenzae type b(Hib)
HAEMOPHILUS
• Diseases caused by H.influenzae:
-Systemic infection primarily affects unimmunized
young children and spread by respiratory droplets
 Meningitis in infants:( 3-18months of age)
Mild respiratory disease of short duration
followed by bacteremia then miningitis
 Epiglottitis in children:(2-4years of age)
Cellulitis and swelling of supraglottic tissues can
block breathing
HAEMOPHILUS
 Cellulitis in cheek of very young
Begins in buccal mucosal spreads to face and neck
causing swelling bluish –red patches on skin and
fever.
 Arthritis affecting single large joints in children
less than 2years of age
 Otitis,sinusitis & bronchitis caused by
noncapsulated strains of H.influenzae in both
adult and children
 Pulmonary disease- Common in elderly with
immunodeficiency and asplenic patients
HAEMOPHILUS
• Treatment and Prevention:
 Prompt treatment with broad
spectrum(Ceftriaxone for severe infection)
 Hib vaccine consists of type b capsular material
conjugated to diphtheria toxoid proteins-part of
childhood immunization schedule
 Rifampin prophylaxis- for close contact
HAEMOPHILUS
• Haemophilus ducreyi: Causative agent of
Chancroid- Sexually transmittable disease
symptomatic in males and asymptomatic in
females
 Characterized by painful ulcer that develops on
genitalia or perianal region and accompanied with
Inguinal lymphadenopathy
 IP:5-7 days after exposure
HAEMOPHILUS
• . Haemophilus ducreyi image: