e learning mycobacteria 15.pdf

7/26/2019 E learning mycobacteria 15.pdf

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Mycobacteria


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Introduction

Order: Actinomycetales

Family: Mycobacteriaceae

Genus: Mycobacterium

> 100 species


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Classification

1. Mycobacteriumtuberculosis

complex(MTBC)

M.tuberculosis

M.bovis

M.africanum

M.pinnnipedii

M.microti

M.caprae

M.canettii

2. Mycobacterium le3. Atypical mycobact

M.avium avium

M.avium intracel

M. kansasiiM. fortuitum

M. chelonae

M.abscessus


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General characteristics

Cell wall rich in lipids(mycolic acids)- comprise 60% owall weight

Slow growers: > 7 days to form colonies

Acid-fast: do not decolourise in acid and alcohol


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Virulence factors

Virulence attributed to ability to survive within macr


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Mycobacteriumtuberculosis


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Epidemiology

In 2013, 9M infected, 1.5M deaths- 360,000 HIV-pos Leading killer of HIV-positive individuals- of all HIV

deaths

480,000 developed MDR-TB

2 billion latently Mtb-infected(LTBI) reservoirs The 2015 MDG of halting and reversing TB incidence

been achieved

Kenya among 22 high burden countries


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Modes of transmission

Droplet infection Person to person by inhalation aerosols

Mycobacterium tuberculosis (Pulmonary tuberculosis

Ingestion of milk

Infected cattle

Mycobacterium bovis (Intestinal tuberculosis)

Contamination of abrasions

Laboratory workers (Skin infection)


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Pathogenesis

Penetrate the alveoli Phagocytosis by resident alveolar macrophages & de

cells

Prevent fusion of the phagosome with lysosomes

Alveolar macrophages produce cytokines and chem Circulating macrophages and lymphocytes are attra

infectious focus


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Pathogenesis

Macrophages may fuse to form multinucleated giancells(MGCs=Langhans cells)

May also differentiate to form lipid-rich foamy macr

Results in granuloma formation

Infected macrophages can also spread to local lymphblood

Subsequent spread to other tissues, BM, spleen, kid


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Pathogenesis

1. Primary infection 10% of immune competent individuals

Bacilli grow unimpeded in host macrophages

2. Latent infection

90% of immune competent individuals

Controlled bacillary growth

Bacilli either killed or survive within cellular granua non-replicating state

Can persist for decades


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Pathogenesis

3. Post-primary infection May develop directly from a primary lesion= progres

primary tuberculosis

OR

Endogenous reactivation of latent infectionOR

Infection or exogenous reinfection


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Pathogenesis

Post-primary lesions often develop in the upper regi Immune-mediated control of bacillary growth fails

Tuberculoma formation- granuloma formation but wtissue destruction and caseation

Liquefication of caseous material Erosion into a bronchus


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Pathogenesis

Cavity is formed= characteristic feature of post-primpulmonary TB

*Granuloma formation= central event in the immunresponse against M.tb

Spread of bacilli from cavities

Though bronchus- other areas of the lung, trache

Swallowed-intestinal tract, anal fistulas

Through bloodstream to other organs


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Factors affecting susceptibility to

Age Immune status

Medical conditions

Genetic factors e.g. HLA-DR allele

Environmental factors- exposure to populations ofenvironmental mycobacteria

Mycobacterial factors- strain variation in virulence


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Clinical manifestations

Weight loss 10% PTB

Low grade fever, malaise, night sweats, chest paincough(>2 weeks), haemoptysis

EPTB

Depends on the site: skeletal, genital tract, urinarCNS, GIT, adrenal, cardiac


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Laboratory diagnosis

Specimen:sputum, gastric washings, urine, aspiratespathological material, etc

Staining of specimen using

Ziehl Neelsen (ZN) stainacid-fast bacilli (AFBs)-bacilli on a blue or green background

Kinyoun staining

Fluorescence stains -auramine O or rhodamine stfluorescent microscopy


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Culture Gold standard in TB diagnosis Require incubation for 6 8 weeks before declari

negative

Solid culture (Lowenstein Jensen(LJ), Middlebroo& 7H11

Liquid culture -Middlebrook 7H12, Bactec, MGITmycobacterial growth indicator tube


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To confirm M.tuberculosis from culture: Slow growth

Colonial morphology

Nitrate reductase test positive

Niacin test positive


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Molecular techniques

PCR from culture; some direct from sputum

Immunological tests

Tuberculin skin test does not distinguish betweevaccination and disease. Usually negative in patie

advanced AIDS QuantiFERON , T-SPOT TB Detect interferon . F

& latent TB


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Tuberculin skin test


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reatment

1

st

line: isoniazid,

rifampicin/ rifabutin,

ethambutol,

pyrazinamide, streptomycin

2nd line:

para-amino salicy

cycloserine,

fluoroquinolone(ofloxacin/ ciprof

levofloxacin/ etc) amikacin,

kanamycin,

capreomycin,

ethionamide


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Drug resistance

Multidrug resistant TB (MDR TB):

resistant to at least rifampicin & isoniazid

Extensively drug resistant TB (XDR TB):

MDR strains that are also resistant to a fluoroquiand at least one second-line injectable agent (amkanamycin or capreomycin)


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ontrol

Prompt detection of cases & effective Rx

Isolation of cases on Rx until non-infectious

Follow up contacts of cases

Reducing overcrowding

Vaccination with BCGvariable results contraindicated in patients with AIDS


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Mycobacteriumleprae


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Introduction

Obligate intracellular organism- can grow in the moor in the armadillo

=Hansens bacilli

Reservoir- infected humans, low infectivity

Transmission- skin to skin contact, respiratory route

Incubation: 3 5 years, can be as long as 30 years

Bacilli resemble tuberculous bacilli but are not so stracid fast


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Pathogenesis

Principal target is the schwann cell

Resulting nerve damage is responsible for the anaesand muscle paralysis

Repeated injuries lead to gradual destruction of ext

Infiltration of skin and cutaneous nerves leads to forof visible lesions with pigmentary changes


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Depends on patients immune reaction

Ranges from tuberculoid to lepromatous form

1. Tuberculoid leprosy(Paucibacillary)

Strong cellular immune reaction but a weak humoral res

Infected tissues- mainly lymphocytes and granulomas, re

few bacilli

2. Lepromatous leprosy(multibacillary)

Strong antibody response but a specific defect in the maand Schwann cells


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1. Intermediate forms

Borderline tuberculoid(BT)

Mid-borderline(BB)

Borderline lepromatous(BL)


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Tuberculoid leprosy
http://upload.wikimedia.org/wikipedia/commons/e/e2/Leprosy_thigh_demarcated_cutaneous_lesions.jpghttp://upload.wikimedia.org/wikipedia/commons/e/e2/Leprosy_thigh_demarcated_cutaneous_lesions.jpg


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Lepromatous leprosy


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Does not grow in cell-free cultures therefore histopafindings

Detection of acid fast bacilli in nasal discharges, scrafrom the nasal mucosa

PCR


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Treatment, prevention and contr

Multidrug therapy

Dapsone

Rifampicin

Clofazimine


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Environmental mycobacteria


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Introduction

= Atypical, opportunistic, MOTTs(mycobacterial othetuberculous), NTM(non-tuberculous mycobacteria)

Saprophytes of soil and water

Cause opportunistic disease

Low virulence

Cause disease in profound immunosuppression


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Clinical importance

Most prevalent= MAC

M.avium intracellulare

M.avium avium

Cause lymphadenitis and pulmonary lesions

Disseminated disease in profound immunosuppressi

M.ulcerans- causes Buruli ulcer

M.xenopi- pulmonary lesions in man

l l


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Clinical importance

M.chelonae; M.absessus; M.fortuitum; M.peregrinum

Responsible for post-injection abscesses and wouinfections including corneal ulcers

Opportunistic diseases caused b


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Opportunistic diseases caused b

MOTTs1. Localized lymphadenitis

2. Skin lesions following traumatic inoculation of bact

3. Tuberculosis-like pulmonary lesions

4. Tuberculosis-like non-pulmonary lesions

5. Disseminated disease

L b di i T


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Laboratory diagnosis, Treatment

Microscopy, culture

Resistant to many anti-TB drugs

Rifampicin + Ethambutol- 18-24 months

Macrolides

Fluoroquinolones


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