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45 21/11/2017

number 15+16

Done by

Corrected by

Doctor Dr Hamed Al-Zoubi

Mycobacterium

Dr Hamed Al-Zoubi

Mycobacterium tuberculosis

• 2billions cases

• 3million deaths

• HIV, MDR

Mycobacterium Tuberculosis Complex

Major human pathogens :

1.Mycobacterium tuberculosis (M. tuberculosis (

2.M. Africanum

3.M. Bovis

4.M. Canettii: smooth

Aerobic acid fast rods.

UV, Alcohol, aldehydes S

Alkaline acid and ammonia R

Mycobacterium Tuberculosis Complex

MYCOBACTERIUM / structure

MYCOBACTERIUM

Growth medium :

Lowenstein–Jensen medium (LJ):

Egg-glycerol with malachite green :

Liquid medium :

MYCOBACTERIUM

Pathogenesis: Caused by immune response

Lung

Primary TB:

Macrophages 1 in alveoli > Ghon’s focus

> To hilar lymph nodes > primary TB complex

> PTB attacked by Macrophages 2 (O2 consumption) > surrounding the lesion in granuloma (caseation) > latent

Tuberculosis (TB) in other places: Skin, intestine and lymph nodes

MYCOBACTERIUM• 90 % of primary infections infections > latent <

reactivation or reinfection > post primary TB

• Reactivation of primary TB > Post primary TB (Also dueto REinfection :(

• Same as in primary but tuberculoma instead of granuloma

• Spread to LLL, upper airways, bladder, skin (Lopusvulgaris) and bladder (more spread and infectivity (

• 10 % of primary > secondary TB > meningitis, pott’s disease, urogenital and skin involvement (s.t milliary TB if opened into a blood vessel > disseminated (

MYCOBACTERIUM

Clinically :

• The following factors increase the likelihood that a patient will have tuberculosis (TB :(

• HIV infection

• History of prior TB treatment

• TB exposure, Travel to or emigration from a TBendemic area

• Homelessness, shelter-dwelling, incarceration

MYCOBACTERIUM

• Classic features associated with active TBare as follows :

• Cough

• Weight loss/anorexia

• Fever

• Night sweats

• Hemoptysis

• Chest pain

MYCOBACTERIUM

Diagnosis :

History and Examination

CXR <<<

PPD test

Lab :

Acid fast stain (Ziehl–Neelsen stain (Culture 6-8 Weeks on L J , shorter in liquid medium

Interferon Gamma interferon

PCR

MYCOBACTERIUM

PPD test (Mantoux test):

2-12 Weeks post infection

Given intradermally

Read within 2-3 days

Delayed HS reaction in the skin

Active infection, vaccine, environmental TB

IGRT?interferon gamma release test

MYCOBACTERIUM / PPD test results

MYCOBACTERIUM

Management:

Isolation:?

Combination, DOTs

(1st line anti TB)

RIFINA 6months +Ethambutol and Pyrazinamide first 2months

2nd line treatment in MDR:

Macrolides, Fluroquinilones, aminoglycosides, cycloserine...

3rd line treatment:

Linezolid, rifabutin, arginine, vitamin D..

Prevention: BCG life attenuated vaccine : ?

• BCG vaccine has a documented protectiveeffect against meningitis and disseminatedTB in children .

Mycobacterium leprae

• Acid fast, aerobic, intracellular bacilli similar to M. Tuberculosis (fat in cell wall (

• It causes leprosy (Hansen’s disease (

• Leprosy: chronic granulomatous disease principally affectingthe skin, mucous membrane, peripheral nervous system andanterior chamber of eyes .

• Approximately 2 million cases worldwide; Africa, Asia andsouth America (India, Nepal, Tanzania, Brazil, Madagascar,Mozambique (

Mycobacterium leprae

• MOT :

• Inhalation (respiratory droplets (

• Incubation period on average is 4-8 years (1-30 years (

• Pathogenesis: (determined by the immune response (• Brief bacteraemic phase

• Binds to macrophages and Schwann cells

• immune response

Mycobacterium leprae

• Clinically :

• Thickened lesions of skin / nodules

• Nerve thickening and Loss of sensation (muscle weakness, tissue /organ and nasal septum destruction, ulcers (...

• Disfigurement and mutilation

• classification

1. Tuberculoid (Paucibacillary) leprosy

2. Lepromatous (Multibacillary) leprosy

3. Borderline leprosy

Mycobacterium leprae

• Tuberculoid :• Few skin lesions < 5

• Usually no acid fast bacilli seen in the lesions

• Lepromatous :

• skin lesions > 5

• Many acid fast bacilli seen in lesions

• More in cold areas (nose, ear, knees, elbow and buttocks (

• ‘Leonine facies ’

Mycobacterium leprae

Mycobacterium leprae

Mycobacterium leprae / diagnosis

• Full thickness skin biopsy, skin scrapings and nasal smears

• 1 . Acid fast staining and histological examination :

• Also for diseases classification and therapy monitoring

• 2 . Molecular techniques (probing and PCR which isPromising

• 3 . Culture :• not available in vitro

• Grown in mice footpads, athymic mice and in Armadillo

Armadillo

Mycobacterium leprae / treatment

Effective treatment is available :

1 . Paucibacillary

• Dapsone + Rifampicin

• 6months

2 . Multibcillary

• Dapsone+Rifampicin+Clofazamine

• 12months

Mycobacterium leprae / treatment

Effective treatment is available :

1 . Paucibacillary

• Dapsone + Rifampicin

• 6months

2 . Multibcillary

• Dapsone+Rifampicin+Clofazamine

• 12months

•The End

Spirochaetes

Dr Hamed Al Zoubi

• Treponema

)T. pallidum (

)T. pertenue (

)T.endemicum (

)T. carateum (

orher non pathogenic spp

T. pallidum• Syphilis :• Belongs to spirochetes which are thin – walled ,

flexible spiral rods

• Motile by flagella :

at both sides

wrap around the bacterial cell body .

In contrast to other motile bacteria, these flagella do not protrude into the surrounding medium but are enclosed within the bacterial outer membrane

• Has not been grown on bacteriologic media

Syphilis

• Transmission :1. Sexually2. Contact with skin lesions

3. Congenital (mother to baby (

4. Blood donation during primary and secondarystages

Syphilis• Pathogenesis :

• No toxins

• Multiplication at primary site of infectionleading to a painless ulcer called Chancre

• Widespread via blood to many tissues

• Primary, secondary, latent, late tertiary stages

• Human only

• Infectious dose less than 10 organisms

• Incubation period: 2-10 weeks, 3 wks usually

• Early (primary and secondary), latent andtertiary stages

• Overall and of the early diseases :

• 1/3 will heal without treatment

• 1/3will go into latent

• 1/3into tertiary

Syphilis / clinically1 . Primary :

• Painless Chancre on genitalia, cervix or anogenital area

• Usually single

• Disappear spontaneously in 3 – 6 weeks

• Infectious

• Inguinal LNE

• Exudates used for diagnosis

2 . Secondary syphilis (infectious :(

• 2 -12 weeks after chancre disappeared

• Non specific symptoms (e.g fever malaise, lethargy ,headache, lymph nodeenlargement (

• Maculopapular and pustular rash mainly on trunkand extremities

• Heals spontaneously

• There might be Multiplication and production of lesion in lymph nodes, liver, joints, muscles, skin and mucous membranes

3 . Latent :

• No lesion but serological evidence exists

• Early and late latent

• Early latent phase: may reactivate and manifest as asecondary lesion i.e infectious

4 . Tertiary (3-30 years :(

• Neurosyphilis: e.g Meningoencephalitis and paralysis

• Cardiovascular: aneurysm of ascending aorta, aortitis

• Skin and bone granulomatous lesions (Gummas (

• Congenital syphilis:

• Blood – placenta – fetus

• Intrauterine death, abortion, low birth weight

• Facial abnormalities e.g saddle shape nose

• Diagnosis:

1. Detection of the organism in the exudates and lesions using dark field E.M or phase contrast, Immunofluorescent antibodies

Low sensitivity

2. Serology:

A. Non-specific antibodies (1-2 weeks after the primary chancre appears):

• Rapid plasma regain test (VDRL test): detectinganticardiolipin antibodies

• Cardiolipin?

B. Specific antibody detection:

• These tests should be used to confirm that a positiveresult with a non-specific test is truly due to syphilis.

Syphilis / serology – specific antibody detection

1. FTA-Abs (fluorescent Treponema antibodies-absorption): patient's serum is first absorbed with non-pathogenic treponemes to remove cross-reacting antibodies before reaction with T. pallidum antigens

2.TPHA (Treponema pallidum Haemagglutinin antibodies (

• Treatment :• Penicillin G• If allergic, Doxycycline or erythromycin is a good

alternative• In neurosyphilis use penicillin and Doxycycline together

• Prevention :• No vaccine• Early diagnosis and treatment of case and contact is

important• Sexually transmitted :• Test for syphilis if any STD exists

• Borrelia Burgdorferi: Lyme Disease.. Common USA, Biting Insects (Ticks).. Wild Animals, Rodents, Birds ..Incub. Few Weeks-Months..Single/Multiple Skin Lesions.. Systemic Disease.. Arthritis, CNS.. Cardic Abnormalities..

• B. recurrentis: recurrent fever, can be fatal• Liptospiral diseases: Zoonosis, mild-severe

fatal systemic .. Weils’s disease ..high Fever,Jaundice, vasculitis, Bleeding.

• Diagnosis: Serological Tests, Special culture

Chlamydia

Family: Chlamydiaceae

• Genus: Chlamydia– C. trachomatis - Urogenital infections,

trachoma, conjunctivitis, pneumonia and lymphogranuloma venerium (LGV (

• Genus: Chlamydophilia– C. psittaci - Pneumonia (psittacosis (

– C. pneumoniae - Bronchitis, sinusitis ,pneumonia and possibly atherosclerosis

N.B. New taxonomy, previously three species in one genus - Chlamydia

Chlamydia- Microbiology

• Small obligate intracellular parasites

• Inner and outer membrane

• LPS but no peptidoglycan– Cell wall not well characterized

• Energy parasites– Can’t make ATP

Physiology and Structure

• Elementary bodies (EB (– Extracellular form

– Rigid outer membrane• Disulfide linked proteins

– Resistant to harsh conditions

– Non-replicating, non-metabolically active form

– Infectious form• Bind to columnar epithelial cells (macrophages (

Physiology and Structure

• Reticulate bodies (RB(– Intracellular form

– Fragile membrane• Fewer disulfide bonds

– Metabolically active form

– Replicating form

– Non-infectious

Developmental Cycle of Chlamydia

• EB bind to host cells– Epithelial

– Macrophage

• Internalization– Endocytosis

– Phagocytosis

• Inhibition of phagosome-lysosome fusion

• Reorganization into RB– Breakdown of disulfide

bonds

• Growth of RB

Chlamydia trachomatis

• Trachoma

• Inclusion conjunctivitis

• Infant pneumonia

• Ocular lymphogranuloma venerium

• Urogenital infections

• Lymphogranuloma venerium

C. trachomatis

• Ocular infections– Worldwide

– Poverty and overcrowding

– Endemic in Africa, Middle East, India, SE Asia

– United States - American Indians

– Infection of children

– Transmission: droplets, hands, contaminatedclothing, flies, contaminated birth canal

Clinical Syndrome -Trachoma

From: G. Wistreich, Microbiology Perspectives, Prentice Hall

Clinical Syndrome -Trachoma )C.trachomatis biovar: trachoma (

• Chronic or repeated infection– Follicle formation on conjunctiva

– Scarring of the conjunctiva

Clinical Syndrome -Trachoma

• Eyelids turn in and abrade cornea– Ulceration

– Scarring

– Blood vessel formation

Clinical Syndrome -Trachoma

• Flow of tears impeded–Secondary infections

Clinical Syndrome - Ocular Lymphogranuloma Venereum

(C.trachomatis biovar: LGV)

• Conjunctivitis and associated lymphadenopathy

Clinical Syndrome - LymphogranulomaVenereum

C. trachomatis (biovar: LGV (• First stage

– Small painless vesicular lesion at infection site

– Fever, headache and myalgia

• Second stage– Inflammation of draining lymph nodes

– Fever, headache and myalgia

– Buboes (rupture and drain (

– Proctitis

– Ulcers or Elephantiasis

Patient with LGV

Bilateral inguinal buboes (arrows (

C. trachomatis - Diagnosis

• Histo Cytology– Iodine-staining

inclusions

– Not sensitive

• Culture– Iodine staining

inclusions

– Most specific

Iodine-stained inclusion bodies

C. trachomatis - Diagnosis

• Antigen detection (ELISA or IF(– Group specific LPS

– Strain specific outer membrane proteins

• Serology– Can’t distinguish between current or past infection

– Detection of high titer IgM antibodies can be helpful

• Nucleic acid probes– Several kits available

– May eventually replace culture

C. trachomatis - Treatment and Prevention

• Tetracycline, erythromycin and sulfonamides

• Vaccines are of little value

• Treatment coupled with improved sanitation

• Safe sexual practices

• Treatment of patients and their sexual partners

Chlamydophilia (Chlamydia) psittaci

• Psittacosis (Parrot fever (

• Ornithosis

Pathogenesis - C. psittaci

• Inhalation of organisms in bird droppings– Person to person transmission is rare

• Hematogenous spread to spleen and liver– Local necrosis of tissue

• Hematogenous spread to lungs and other organs

• Lymphocytic inflammatory response– Edema, infiltration of macrophages, necrosis and

occasionally hemorrhage

– Mucus plugs may develop in alveoli

• Cyanosis and anoxia

Laboratory Diagnosis - C. psittaci

• Serology (Complement fixation test ( –Fourfold rise in titer

Treatment and Prevention - C. psittaci

• Tetracycline or erythromycin

• Quarantine of imported birds

• Control of bird infection– Antibiotic supplementation of food

Chlamydophilia (Chlamydia) pneumoniae

• Atypical pneumonia

• Atherosclerosis?

Pathogenesis - C. pneumoniae

• Person to person spread –Respiratory droplets

• Bronchitis, sinusitis and pneumonia

Laboratory Diagnosis - C. pneumoniae• Serology

–Fourfold rise in titer

Treatment and Prevention - C. pneumoniae

• Tetracycline or erythromycin

• Difficult to prevent transmission

• No vaccine

The End