Mycobacteria Flashcards
Mycobacterium are neither gram positive or gram negative; __________ are used instead/
-Acid fast stains
3 groups of mycobacteria
- M. tuberculosis complex
- nontuberculosis mycobacteria
- M. leprae
Physiology and structure of mycobacteria
- slow rate of replication
- lipid-rich outer layer of mycolic acids
- resistant to desiccation
- acid-fast stains, not gram stains
- nonspore forming, non-motile bacilli
- obligate aerobes
3 several important properties due to myobacteria’s outer layer of mycolic acids
- resistance to gram staining
- resistance against dessication which is important in airborne transmission
- myocolic acid biosynthesis is target for INH drug
Mycobacteria are facultative _______ pathogens
-intracellular
M. tuberculosis niche and mechanism for survival
- replication within macrophages
- stays within vesicle and prevents its fusion with lysosomes
Because M. tuberculosis is spread by an airborne route, it usually first encounters ________ and then is carried to a __________.
- alveolar macrophage
- regional lymph node
At the level of histopathology, the immune response to mycobacterial infections is dominated by __________.
- granulomas
- inflammatory aggregates of macrophages and T cells
- may contain multinucleated giant cells
Caseous necrosis often develops at the centers of _______ granulomas.
-tuberculosis
What type of immune response is required to combat tuberculosis?
- cell-mediated rather than humoral response, as expected in an intracellular pathogen
- Th1 response is most effective
While M. tuberculosis replicated well in resting macrophages, it can be killed by _______.
-activated macrophages
Why do HIV patients suffer from a high rate of tuberculosis?
-they lack their CD4+ T cell responses which are crucial in the cell mediated response necessary to combat TB
CD4+ T cells which recognize M. TB and become activated produce ________. What does this do?
- interferon-gamma
- this in turn activates macrophages to produce TNF-alpha and to kill bacteria within their phagosomes
TB is one of the leading infectious causes of death worldwide. About ______ of the world’s population are infected. Most of these infections are asymptomatic and fall into the category of LTBI. These people however have about a _______ lifetime risk of developing active TB.
- 1/3 (2 billion)
- 10%
T/F: TB is a relatively new disease of humanity.
-false; been with humans from the beginning
TB was also known as _____ in Europe.
-consumption
Rates of TB continued to fall until the mid 1980s when the _______ spurred a rise in the incidence again.
-AIDS epidemic
Blocks/defects in what 3 things increase susceptibility to mycobacteria
- CD4+ T cell responses
- TNF blockage
- IFN-gamma receptor defects
Current problems with TB
- still many latent infections
- increasing drug resistance
- global levels of disease remain high, partly due to HIV
Risk factors for TB
- homelessness, urban poverty, malnutrition, crowding, alcoholism
- increases in inmates, healthcare workers, and immigrants from regions with high endemic TB
Transmission of TB
- airborne transmission by aerosol droplet nuclei
- can remain suspended in air for hours
Protection from TB requires what kind of mask?
-N95 respiratory mask
T/F: Having HIV doesnt increase risk of getting TB
-true, just makes it worse
Clinical diseas of primary TB infection
- aerosol deposition of bacilli into alveoli
- replication in macrophages and migration to regional LN
- control of infection with development of cellular immunity
- often no evidence of primary infection beyond position TST
- Lymphohematogenous seeding of lungs and extrapulmonary sites
Latent TB infection (LTBI)
- controlled primary infection without clinical disease
- no evidence of active TB on chest x-ray
- chest x-ray may show calcification at pulmonary site of initial infection (Ghon focus) or in mediastinal nodes (Ranke complex)
- NOT CONTAGIOUS
Reactivation of TB
- may occur after initial control of infection by immune system
- risk of reactivation if issue developed in cell-mediated immunity
In pulmonary TB, reactivation is most common where?
-apex of lung
Histologic Characteristics of pulmonary TB
-caseous necrosis and formation of cavities
-rupture of cavities into bronchi and spread to other areas of lung
-
Symptoms of Pulmonary TB
- local symptoms: cough and sputum production, shortness of breath
- Prominent systemic symptoms: fever, chills, night sweats, fatigue, weight loss
- highly contagious
3 other forms of TB outside of pulmonary TB
- primary progressive TB pneumonia
- Miliary TB
- extrapulmonary TB
Primary progressive TB pneumonia
-local disease following initial infection
Miliary TB
- progressive, disseminated hematogenous tuberculosis
- when M. tb overwhelms the immune system
Extrapulmonary TB
- direct spread along mucosal surfaces: GI tb, laryngeal TB
- direct extension form lungs to pleural space
- lymphohematogenous spread
What can extrapulmonary TB via lymphohematogenous spread cause?
- meningitis
- lymphadenitis (scrofula)
- renal TB
- Skeletal TB “pott’s disease”
Lab diagnosis of TB
- Tuberculin skin test (TST or Mantoux test): intracutaneous injection of purified protein derivative (PPD)
- interferon-gamma release assays
Limits to Tuberculin skin test
- false positive TST reactions: other mycobacterium in environment, recent BCG vaccination
- false negative TST reactions: weakened cellular immune response, malnutrition or chronic disease, AIDS patients
- criteria for interpretation of TST reflect patient risk factors
T/F: it is the redness of a TST, not the induration that is diagnostic of TB
- false; it is the induration
- 15 mm in everyone, lower if in higher risk population
How does a IGRA work?
- stimulates patient T cells with 2 peptides secreted by M. tb
- tests production of INF-gamma by patient T cells
- not affected by vaccination with BCG because uses 2 peptides not included in that vaccine
Culture and staining of M. tb
- smear and culture of sputum: culture may take 2-3 weeks or more to grow, DNA probes often used to rapidly ID isolate
- Acid-fast staining
- Fluorochrome stains
Molecular detection of TB
- PCR assays
- Xpert MTB/RIF assay: automated, rapid detection of Mtb, heminested real-time PCR of rpoB, detection of rifampin resistance
First line drugs for active TB
- Isoniazid (INH)
- Rifampin
- Pyrazinamide
- Ethambutol
- *Add Streptomycin for TB meningitis
Isoniazid (INH)
- inhibits mycolic acid synthesis
- strong, early bactericidal activity againt replication M. tb
- toxicity issues
Toxicity and Isoniazid
- hepatitis
- peripheral neuropathy: competitively inhibits activity of pyridoxine as cofactor, so give P supplement for patients with nutritional deficiencies and chronic diseases
Rifampin and side effects
- inhibits RNA polymerase
- Side effects: orange body fluids, hepatitis, interactions with other drugs
Pyrazinamide function and toxicity
- targets 30S ribosomal protein RpsA
- inhibits trans-translation and recycling of stall ribosomes
- may act against semi-dormant organisms
- toxicity: hepatitis and polyarthralgia
Ethambutol
- inhibits synthesis of cell wall arabinogalactan
- toxicity: retrobulbar neuritis: decreased red-green color discrimination or decreased visual acuity
Treatment of active TB
- use at least 3, usually 4, first line drugs
- treat for 6 months at least: 2 months on all 4, followed by 4 months of INH and RIF
- directly observe therapy to monitor adherence
How does one monitor TB while on medication?
- obtain sputum at least monthly
- 90-95% should be negative sputum by 3 months-
- considered not contagious if 3 consecutive AFB smears are negative
Treatment of LTBI
- 9 months of INH or 6 months of rifampin
- hepatic toxicity from INH increases over age 35
What type of vaccine is BCG vaccine?
- live, attenuated
- limited efficacy
- can cause disease in immunocompromised
What are the NTM?
- mycobacteria except M. tuberculosis and M. leprae
- divided into slow and rapid growers
- also classified by pigment production
Epidemiology of NTM
-frequently found in the environment
Clinical diseases from NTM
- Pulmonary diseases: chronic cough, fatigue, weight loss, NO fever
- Disseminated MAC: in HIV patients with Cd4+ <50, fever, weight loss, anemia, diarrhea, hepatosplenomegaly, no respiratory symptoms
- hypersensitivity pneumonitis: hot tub lung
- cervical lymphadenitis: in young children, usually from MAC, swollen but limited signs of inflammation
- Skin and soft tissue infections: rapid growers
Testing and laboratory diagnosis of NTM
- usually need culture of organism
- may be found as non-pathogens in cultures from non-sterile sites
Treatment of NTM
- multiple drug regimens
- prolonged courses of treatment
- antibiotic prophylaxis for HIV patients to prevent disseminated MAC
Leprosy is also called ________.
-Hansen’s disease
T/F: Leprosy is easy to culture in vitro
- false; still cannot be
- infects wild armadillos and can be cultured in mouse footpads
How is leprosy spread?
- contact with nasal secretions or droplet spread
- perhaps biting insects?
Clinical manifestations of leprosy
- grows as lower temperatures found within skin and extremities
- peripheral sensory nerve damage
- infiltrative skin lesions
- 2 categories of disease: multibacillary or paucibacillary
How is Leprosy diagnosed?
- history, exam, and biopsy
- NO CULTURE bc it cannot be grown in vitro
Treatment of leprosy
- multidrug regimens
- rifampin, dapsone, clofazimine
- 5 years of treatment
