Micro ii lecture 4,5

MYCOBACTERIA

MYCOBACTERIABacilli, non motile, non capsulated and

non spore formingStrict aerobes. Acid-fast bacilli (AFB).i.e. they are difficult to stain because of

their thick cell wall and its high lipid content, but once stained, they resist decolorization by acid or alcohol.

Members of Mycobacterium group:

Mycobacterium Atypical mycobacterium tuberculosis complex Tuberculosis leprae

Mycobacterium mycobacterium Tuberculosis bovis tuberculosis in cattleTuberculosis in man transmitted to man

Mycobacterium tuberculosisSlender, straight or curved rods

arranged singly or in pairs, Non motile, Non capsulated Non spore forming.

virulence factors1.Cord factors (glycolipid )→inhibit migration of PMN neutrophils→ immunogenic → protective immunity.→ growth in parallel groups.2. Cell wall mycolic acid → inhibit formation of

phagolysome→ intracellular survival of tubercle bacilli after ingestion by macrophages.

3. Resistance to anti-tuberculosis antimicrobials→ acquired by mutation.

Pathogenesis :

The organism is non toxigenic. It produces disease by its ability to

survive and multiply within the macrophages.

Transmission: Air borne droplet nuclei or contaminated

dust particles that arise from patients with open pulmonary tuberculosis.

The site of initial infection is usually the lung. The organisms are inhaled to the bronchi and

reach alveoli where they are engulfed by alveolar macrophages. The majority of these

bacilli are destroyed or inhibited.

The bacilli have 4 potential fates:

Multiply and cause primary TB

Killed by the immune system

Proliferate after a latency period

( reactivation or post primary disease)

latent TB (asymptomatic) or

progress to symptomatic disease

Primary TBAfter 3 days → slow multiplication of the

surviving organisms → initial lesion e.g. Ghon's focus in lung → Spread by lymphatics → lymph nodes → enlarged and caseate.

The initial lesion + enlarged draining lymph nodes → primary complex.

According to the immune status of the host, either the individual develops → latent infection.

Or → progresses to symptomatizing disease.

Latent TB infection (LTBI)After 3-4 weeks → cell mediated immunity →

formation of granuloma → limit the infection → establishing LTBI.

Patients with LTBI → have no symptoms. → don’t spread the infection to other people. → have positive tests for latent TB.Mycobacteria within the granuloma → remain

dormant. → viable. → can be reactivated later in life.

Progressive primaryIn a minority of cases, the organisms → carried by the thoracic duct → blood stream (bacteremia) → dissemination of infection → distant areas → e.g. meningitis, disease of the kidneys, etc.If a focus ruptures into a blood vessel→

dissemination throughout the body → formation of numerous granulomata (miliary tuberculosis).

Post-primary TBIt develops in 10% of people with tuberculous infection. Either by → reactivation of dormant tubercle

bacilli. Or → re-infection.Higher risk → persons in the first 2 years after

primary infection. Or → immunosuppressed patients e.g. HIV infection.

CLINICAL MANIFESTATIONS OF TUBERCULOSIS:

A. Systemic effects of tuberculosis (TB): Fevers, sweating with loss of weight. An increase in the peripheral blood leukocytic countB. Pulmonary TB: Productive cough is the most common symptom Rarely, hemoptysis may be a presenting symptom Abnormalities on the chest radiograph.C. Extrapulmonary TB: is more common in

Immunosuppressed and In young children e.g. disseminated, pleural, genitourinary, meningitis and

skeletal affection.

D- Oral manifestation oftuberculosis:Oral lesions → usually secondary to →

inoculation with infected sputum or → hematogenous spread.

Oral tuberculous lesions : → nonspecific in clinical presentation. → diagnosis requires a high degree of awareness.→ palate and dorsum of the tongue (frequently affected sites).

1 -Primary complex The primary complex involves the

oropharyngeal region. An oral ulcer may develop at the site of entry.

This ulcer is painless and progressing. Submaxillary and cervical lymph nodes are

enlarged and may caseate discharging through sinus tracts.

2-Oral ulceration secondary to pulmonary tuberculosis

Abrasions, ulcerations or traumatic lesion of the oral mucosa provides an ideal portal of entry of the bacilli coughed up.

The ulcers are seen in the lateral sides of the tongue.

It is very painful. The regional lymph nodes are not enlarged.

3 -Lupus vulgarisIt is a form of skin tuberculosis.It may be due to exogenous inoculation or

direct spread from the blood or lymphatics. It commonly affects the face, the cheeks, and

the nose. However, the oral mucosa may be affected in

the form of small nodules or as irregular papilli - nodular lesion.

Lupus vulgaris

4-Tuberculous periapical infection and osteomyelitis:

Secondary to pulmonary tuberculosis, the organism may colonize the periapical granuloma associated with various teeth and roots leading to cold dento- alveolar abscess with lack of pain and inflammation.

Tuberculous osteomyelitis of the jaw is a rare form and is associated with systemic tuberculosis.

Dentoalveolar abcess and tuberculous osteomyelitis

5- tuberculous parotitis:

It is either: → 2ry to 1 ry focus in the lung as a result of hematogenous or lymphatic spread.

Or → 1 ry disease due to autoinfection from the oral cavity

Laboratory diagnosis

Treatment: I- TB disease :

Treatment is usually combined and prolonged (6-9 months). Why………?

Bacilli are intracellular metabolically inactive This prolongation may emerge resistant stains

(due to chromosomal mutation) and produce toxicity.

So, usually a combination of more than 2 drugs is given to avoid toxicity and prevent emergence of resistant strains.

First line treatment drugs: isoniazid (INH), rifampin (RIF), ethambutol (EMB) and pyrazinamide (PZA). Second line treatment drugs: They are used when resistance or toxicity occurs; they include streptomycin, fluoroquinolones, amikacin, ethionamide, cycloserine & p-aminosalicylic acid (PAS).

II. Latent TB:Treatment reduces the risk of progression to disease. INH daily or twice weekly dosing for 6-9 months.

III. Resistant strains:

Multi drug resistant TB (MDR-TB): strains resistant to at least INH and RIF.

Extensive Drug resistant TB (XDR-TB): This is resistant to isoniazid and rifampin + any fluoroquinolone + at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).

Treatment of such strains is based on results of drug susceptibility testing.

Prophylaxis: Vaccines:

Bacille Calmette Guerin (BCG) vaccine The human and bovine strains are almost antigenically similar; BCG vaccine is a live-attenuated vaccine prepared from bovine strain. It is given to children intradermally in the first 3 months of life. The immunity after the vaccine depends on creating a controlled focus.

-Gram positive bacilli tend to form chains or filaments.

- Most are saprophytic in soil .

Actinomycetes

• Pathogenic members responsible for actinomycosis.

• It is a chronic infection produced by • Actinomyces israelii.• It normally colonize mouth, upper

respiratory tract, GIT and female genital tract.

• . Cause disease: barrier is disrupted.

. The organisms grow in anaerobic niche forming multiple abscesses connected by sinus tracts that contain microscopic colonies of organisms called sulphur granules

. Sulphur granules are yellow or orange , formed of filamentous organisms bound together by calcium phosphate.

Infection may be cervicofacial, thoracic abdominal or pelvic.

Oral cervicofacial actinomycosis: The infection develops inside the tissue of the neck, jaw or mouth. Most cases are a complication of dental problems, poor oral hygiene, gum disease, dental abscess, tonsillitis, dental or jaw surgery. This is the most common type of actinomycosis and accounts for an estimated half of all cases.

Specimen: crushed sulphur granules. Gram stained film: gram positive branched

bacilli. IF for tissue section. Isolation & identification: culture on

thioglycolate broth or brain heart under anaerobic conditions. Slowly growing need 2 weeks. identification by biochemical reaction.

Treatment

Laboratory diagnosis

TreatmentPenicillin is the drug of choiceTetracycline, clindamycin can be used.

Anaerobic Gram negative bacilli: Bacteroides fragilis: is the predominant

normal intestinal flora.Prevotella melaninogenica: normal flora

of the upper respiratory tract and female genital tract

Porphyromonas: part of normal oral flora, can be cultured from gingival and periapical tooth infections

MorphologyPleomorphic Gram negative bacilli,

capsulated.

CultureStrict anaerobes grow on enriched culture

media as blood agar.

Virulence factorsCapsule

Bacteroides fragilis

With other anaerobes (peptococci, peptostreptococci, fusiform bacteria) they cause pelvic, abdominal, lung and brain abscesses. Also they cause peritonitis, empyema. Such infections are characterised by foul odour

Pathogenesis

Specimen: discharge or exudate from deep part of the wound or lesion.

Gram stained smear: pleomorphic gram negative bacilli.

Culture: on blood agar or special media under anaerobic condition.

Laboratory diagnosis

Treatment

Clindamycin and Metronidazole

Fusobacterium (Fusiform bacilli)

Pleomorphic Gram-negative rods. They are isolated from mixed bacterial

infection. They cause ulcerative gingivostomatitis

or trench mouth together with normal spirochaetes of the mouth ( Borrelia vencentii).

When massive tissue involvement occurs, especially on tonsils, it is termed Vincent’s angina.

Pseudomembrane.

Trench mouth

specimen.Film.Culture. Ascetic fluied

Treatment.

Lab. Diagnosis:

Anaerobic Gram positive bacilli:Lactobacilli:

They are Gram-positive bacilli, present in pairs or chains,

Anaerobic or facultative anaerobes. Lactobacilli are major members of

normal flora of the vagina, mouth, stomach and small intestine.

They cause dental caries and rarely subacute bacterial endocarditis.

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