1. .
MYCOBACTERIA

2. 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

3. 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

4. Classification

5. 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

6. 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)

7. 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.

8. MYCOBACTERIUM TUBERCULOSIS cont..
Properties:
Grows slowly doubling time of 18hours
Culturing of clinical specimen should be held for 6-8wks 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

9. 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

10. 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

11. 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.

12. MYCOBACTERIUM TUBERCULOSIS cont..
Pathogenesis:
Two types of lesions:
Exudate
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

13. 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

14. 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

15. 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.

16. 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
Atypical Mycobacteria
M.avium-intracellulare(MAC)
Disseminated disease,PTB,sub acute lymphadenitis
Disseminated disease among AIDS patients
M.kansasii
TB like disease,osteomyelitis,lymphoadenopathies
Those with lung disease,immunocompromised
M.scrofulaceum
Cx Lymphadenitis(scrofula)
Young children

17. MYCOBACTERIUM TUBERCULOSIS cont..
Clinical features of important Mycobacteria:
Organism
Main site of infection
Skin Test in Common Use
Multiple drug therapy used
Vaccine Availability
M.tuberculosis
Lungs
Yes
M.avium -intracellulare No
M.leprae
Skin,Nerve

18. 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

19. 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

20. 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

21. 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.

22. 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)

23. 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

24. 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:
TH1 response(DTH,IFNϒ,macrophages) leads to milder tuberculoid leprosy
TH2response (humoral antibody) leads severe lepromatous leprosy

25. 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

26. Mycobacterium leprae(Hansen’s Disease)
Clinical Presentations cont…..:
Why disfigurement? There several factors:
Skin anaesthesia resulting to burns and trauma
Resorption of bone leading to loss of features eg; nose and finger tips
Infiltration of the skin and nerves leading to thickening and folding of the skin

27. 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

28. 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

29. HAEMOPHILUS
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30. 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

31. 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.

32. HAEMOPHILUS Scientific classification: Kingdom: Bacteria
Phylum: Proteobacteria
Class: Gammaproteobacteria
Order: Pasteurellales
Family: Pasteurellaceae
Genus :Haemophilus
Species: H. influenzae
H.ducreyi

33. HAEMOPHILUS .

34. 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.

35. HAEMOPHILUS
Haemophilus influenzae type b(Hib)

36. 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

37. 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

38. 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

39. 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

40. HAEMOPHILUS
. Haemophilus ducreyi image: