Anda di halaman 1dari 49

Mycobacteria

Introduction
Order: Actinomycetales
Family: Mycobacteriaceae
Genus: Mycobacterium
> 100 species

Classification
1. Mycobacterium
tuberculosis
complex(MTBC)
M.tuberculosis
M.bovis
M.africanum
M.pinnnipedii
M.microti
M.caprae
M.canettii

2. Mycobacterium leprae
3. Atypical mycobacteria
M.avium avium
M.avium intracellulare
M. kansasii
M. fortuitum
M. chelonae
M.abscessus

General characteristics
Slightly curved or straight rods which may curve
Non-motile
Non-spore forming
Non-capsulated
Obligate aerobes
M.bovis requires reduced O2 tension

Sensitive to UV light, sunlight, heat at 60-80OC for 30-60 min,


boiling

General characteristics
Cell wall rich in lipids(mycolic acids)- comprise 60% of cell
wall weight
Slow growers: > 7 days to form colonies
Acid-fast: do not decolourise in acid and alcohol

Virulence factors
Virulence attributed to ability to survive within macrophages

Mycobacterium tuberculosis

Epidemiology
In 2013, 9M infected, 1.5M deaths- 360,000 HIV-positive
Leading killer of HIV-positive individuals- of all HIV-related
deaths
480,000 developed MDR-TB
2 billion latently Mtb-infected(LTBI) reservoirs
The 2015 MDG of halting and reversing TB incidence has
been achieved
Kenya among 22 high burden countries

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)
10

Pathogenesis
Penetrate the alveoli
Phagocytosis by resident alveolar macrophages & dendritic
cells
Prevent fusion of the phagosome with lysosomes
Alveolar macrophages produce cytokines and chemokines
Circulating macrophages and lymphocytes are attracted to
infectious focus

Pathogenesis
Macrophages may fuse to form multinucleated giant
cells(MGCs=Langhans cells)
May also differentiate to form lipid-rich foamy macrophages
Results in granuloma formation
Infected macrophages can also spread to local lymphnodes,
blood
Subsequent spread to other tissues, BM, spleen, kidneys

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 granulomas in
a non-replicating state
Can persist for decades

Pathogenesis
3. Post-primary infection
May develop directly from a primary lesion= progressive
primary tuberculosis
OR
Endogenous reactivation of latent infection
OR
Infection or exogenous reinfection

Pathogenesis
Post-primary lesions often develop in the upper regions
Immune-mediated control of bacillary growth fails
Tuberculoma formation- granuloma formation but with
tissue destruction and caseation
Liquefication of caseous material
Erosion into a bronchus

Pathogenesis
Cavity is formed= characteristic feature of post-primary
pulmonary TB
*Granuloma formation= central event in the immune
response against M.tb
Spread of bacilli from cavities
Though bronchus- other areas of the lung, trachea, larynx
Swallowed-intestinal tract, anal fistulas
Through bloodstream to other organs

Factors affecting susceptibility to TB


Age
Immune status
Medical conditions
Genetic factors e.g. HLA-DR allele
Environmental factors- exposure to populations of
environmental mycobacteria
Mycobacterial factors- strain variation in virulence

Clinical manifestations
Weight loss 10%
PTB
Low grade fever, malaise, night sweats, chest pain, chronic
cough(>2 weeks), haemoptysis
EPTB
Depends on the site: skeletal, genital tract, urinary tract,
CNS, GIT, adrenal, cardiac

Laboratory diagnosis
Specimen:sputum, gastric washings, urine, aspirates, CSF,
pathological material, etc
Staining of specimen using
Ziehl Neelsen (ZN) stain acid-fast bacilli (AFBs)- red
bacilli on a blue or green background
Kinyoun staining
Fluorescence stains -auramine O or rhodamine stain for
fluorescent microscopy

Laboratory diagnosis
Culture Gold standard in TB diagnosis
Require incubation for 6 8 weeks before declaring
negative
Solid culture (Lowenstein Jensen(LJ), Middlebrook 7H10
& 7H11
Liquid culture -Middlebrook 7H12, Bactec, MGIT
mycobacterial growth indicator tube

Laboratory diagnosis
To confirm M.tuberculosis from culture:
Slow growth
Colonial morphology
Nitrate reductase test positive
Niacin test positive

Laboratory diagnosis
Molecular techniques
PCR from culture; some direct from sputum
Immunological tests
Tuberculin skin test does not distinguish between
vaccination and disease. Usually negative in patients with
advanced AIDS
QuantiFERON , T-SPOT TB Detect interferon . For active
& latent TB
28

Tuberculin skin test

29

Treatment
1st line:
isoniazid,
rifampicin/ rifabutin,
ethambutol,
pyrazinamide,
streptomycin

2nd line:
para-amino salicylic acid
cycloserine,
fluoroquinolones
(ofloxacin/ ciprofloxacin/
levofloxacin/ etc)
amikacin,
kanamycin,
capreomycin,
ethionamide

30

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 fluoroquinolone
and at least one second-line injectable agent (amikacin,
kanamycin or capreomycin)

31

Control
Prompt detection of cases & effective Rx
Isolation of cases on Rx until non-infectious
Follow up contacts of cases
Reducing overcrowding
Vaccination with BCG variable results
contraindicated in patients with AIDS

32

Mycobacterium leprae

Introduction
Obligate intracellular organism- can grow in the mouse pad
or 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 strongly
acid fast

Pathogenesis
Principal target is the schwann cell
Resulting nerve damage is responsible for the anaesthesia
and muscle paralysis
Repeated injuries lead to gradual destruction of extremities
Infiltration of skin and cutaneous nerves leads to formation
of visible lesions with pigmentary changes

Clinical manifestations
Depends on patients immune reaction
Ranges from tuberculoid to lepromatous form
1. Tuberculoid leprosy(Paucibacillary)
Strong cellular immune reaction but a weak humoral response
Infected tissues- mainly lymphocytes and granulomas, relatively
few bacilli

2. Lepromatous leprosy(multibacillary)
Strong antibody response but a specific defect in the macrophages
and Schwann cells

Clinical manifestations
1. Intermediate forms
Borderline tuberculoid(BT)
Mid-borderline(BB)
Borderline lepromatous(BL)

Tuberculoid leprosy

Lepromatous leprosy

Laboratory diagnosis
Does not grow in cell-free cultures therefore histopathologic
findings
Detection of acid fast bacilli in nasal discharges, scrapings
from the nasal mucosa
PCR

Treatment, prevention and control


Multidrug therapy
Dapsone
Rifampicin
Clofazimine

Environmental mycobacteria

Introduction
= Atypical, opportunistic, MOTTs(mycobacterial other than

tuberculous), NTM(non-tuberculous mycobacteria)


Saprophytes of soil and water
Cause opportunistic disease
Low virulence
Cause disease in profound immunosuppression

Clinical importance
Most prevalent= MAC
M.avium intracellulare
M.avium avium
Cause lymphadenitis and pulmonary lesions
Disseminated disease in profound immunosuppression
M.ulcerans- causes Buruli ulcer
M.xenopi- pulmonary lesions in man

Clinical importance
M.chelonae; M.absessus; M.fortuitum; M.peregrinum
Responsible for post-injection abscesses and wound
infections including corneal ulcers

Opportunistic diseases caused by


MOTTs
1.
2.
3.
4.
5.

Localized lymphadenitis
Skin lesions following traumatic inoculation of bacteria
Tuberculosis-like pulmonary lesions
Tuberculosis-like non-pulmonary lesions
Disseminated disease

Laboratory diagnosis, Treatment


Microscopy, culture
Resistant to many anti-TB drugs
Rifampicin + Ethambutol- 18-24 months
Macrolides
Fluoroquinolones