TB & Fungal Respiratory Infections Flashcards
mycobacterium tuberculosis - general overview
*M. tuberculosis complex (M. tuberculosis, M. africanum, M. bovis)
*acid-fast bacilli (aerobic, nonsporulating, rod)
*waxy cell envelope (mycolic acid + lipids):
-acid-fastness & impermeability to gram staining
-resistance to acid, alkali, drying, & germicides
-resistance to killing by antibody & complement
-slow growth
acid-fast bacilli
*acid-fast: retain color when stained, even after they have been washed in an acid solution
*sometimes referred to as a “red snapper”
mycobacterium tuberculosis virulence factor
*CORD FACTOR:
-aka TDM (trehalose-6,6’-dimycolate)
-most abundant cell wall lipid
-correlated with virulence
-causes organism to arrange into “serpentine cords”
TB epidemiology
*about 2 billion people worldwide have TB
*almost 1/3 of the world’s population
*in some countries, almost 80% have TB
*#1 cause of DEATH from INFECTIOUS DISESAE in the world
synergy between TB and HIV
*TB is the #1 cause of death due to infectious disease in people living with HIV (PLWH)
*risk of contracting TB DOUBLES within the first year of acquiring HIV and continues to increases as HIV progresses
*PLWH are at high risk of reactivating latent T and of becoming re-infected with TB after treatment
*TB often progresses at accelerated rate in PLWH
TB pathogenesis
*aerosolized respiratory droplets containing mycobacterium tuberculosis are inhaled (infectious dose = 10 bacilli)
*pulmonary macrophages phagocytose bacilli, but instead of being killed, the TB bacilli proliferate over next several weeks
*enough antigen has been produced to stimulate a cellular immune response (CD4 and CD8 T cells) attempt to contain the infection and/or kill infected cells
*macrophages and T cells wall off infection, forming GRANULOMAS
caseating granulomas and TB
*caseation:
-areas of necrosis, loss of tissue architecture
-caused by TNF, reactive oxygen species, cytotoxic agents (granzymes & perforin)
*granuloma:
-rim of healthy macrophages & T cells that are walling off infected macrophages, dead and dying infected cells, and free organisms
latent TB
*immune system successfully contains infection
*asymptomatic
*NOT contagious
*can advance to active TB
active TB
*TB is active and grows in body
*patients develop symptoms
*can spread from person to person
*progressive disease can result in death
symptoms of active TB
*fever
*night sweats
*weight loss
*cough
*hemoptysis (tissue destruction leads to erosion of a blood vessel)
*extrapulmonary TB: spine, joints, CNS, lymph nodes, pericardium, liver, intestines, other
diagnosis of latent TB
*no symptoms
*screening recommended for possible exposures and/or those with high risk of progression to active TB (HIV infection, etc)
*screening tests:
-tuberculin skin test
-interferon gamma release assay (IGRA)
diagnosis of active TB
*symptoms
*imaging (CXR, CT)
*sputum: AFB smear and culture; PCR
*biopsy:
-pathology
-AFB smear & culture
-PCR
tuberculin skin test (TST)
*TB antigens are injected into the skin
*if a person have memory cells from a prior TB exposure, those immune cells will react to the antigens by producing cytokines and inflammation
*48-72 hours later, the diameter of the induration (NOT the erythema) is measured:
-5mm is positive for: PLWH, organ transplant, other immunosuppressed people
-10mm is positive for: people have recently immigrated from areas with high TB incidence, experiencing homelessness, renal failure, diabetes, health care workers
-15mm is positive for: people with NO known risk factors
interferon gamma release assay
*a screening test used to assess for latent TB infection
*T cells in patient’s blood sample are stimulated with tuberculosis-specific peptides and the activity of the T cells is approximated by measuring interferon gamma
treatment for latent TB
*we treat to prevent progression of latent to active TB
*rifampin daily for 4 months OR INH or combination of both
active TB - isolation precautions
*place patients in special respiratory isolation (negative pressure room with use of N95 masks)
active TB treatment
- induction phase (4 drugs for 2 months): rifampin + INH + pyrazinamide + ethambutol
- continuation phase (2 drugs for 4 months): rifampin + INH
non-tuberculous mycobacteria (NTM) - overview
*>180 different species
*acid-fast bacilli
*saprophytic organisms that become pathogenic
*generally no person-to-person spread
*risk factors include: malignancy, organ transplantation, HIV infection, and structural lung disease
mycobacterium avium intracellulariae complex (MAI or MAC)
*non-tuberculous mycobacteria (NTM)
*2 presentations: 1) nodular bronchiectasis; and 2) fibrocavitary lung
*disseminated disease due to MAC: present with fever, weight loss, lymphadenopathy, diarrhea, particularly in persons with advanced HIV infection
important non-tuberculous mycobacteria (NTM) to be familiar with
*mycobacterium avium intracellulariae complex (MAI or MAC)
*mycobacterium marinum
*mycobacterium scrofulaceum
mycobacterium marinum - clinical presentation
*small, raised erythematous lesions, commonly involving the hand
*progressive spreading of nodular lesions up to elbow or farther
*no fever or other symptoms
*classic risk factor: water (ex. cleaning fish tanks without gloves)
*needle aspiration and AFB cultures reveal mycobacterium marinum
mycobacterium scrofulaceum
*mycobacteria causing cervical lymphadenitis
*requires biopsy and culture for diagnosis
nocardia spp. - overview
*aerobic, gram positive rod
*weakly acid-fast
*long, branching filaments
*found in the environment
nocardia spp - clinical syndromes
*pulmonary syndrome can mimic TB
*skin and soft tissue infection
*CNS infection (brain abscess)
nocardia spp - treatment
TMP-SMX plus a combination of other antibiotics
actinomyces spp. - overview
*ANAEROBIC, gram positive rod
*NOT acid-fast
*long, branching filaments
*normal flora of oropharynx, GI tract, vagina
actinomyces spp. - clinical syndromes
*cervicofacial infections, odontogenic abscesses with draining sinus tracts
*lung abscesses
*pelvic infections
nocardia spp - treatment
penicilin
important endemic (dimorphic) fungi to know
*recall: dimorphic fungi are in different forms (in body, yeast form; in environment, mold form)
*blastomyces
*coccidioides
*histoplasma
coccidioidomycosis - geographic distribution
*southwest US
blastomycosis - geographic distribution
*eastern US
histoplasmosis - geographic distribution
*eastern US/midwest
endemic (dimorphic) fungi - concepts
*exist as mold in soil and yeast in tissue
*can all cause acute or chronic pneumonia
*can all disseminate, especially in immunocompromised hosts
*acquired primarily via inhalation of spores during outdoor activities near soil, decaying vegetation, or body of water
*are NOT transmitted person-to-person
*can form granulomas
histoplasma capsulatum
*dimorphic (endemic) fungi
*smears & histopath show ovoid 3-5 micrometer yeasts with NARROW-BASED BUDDING; often within macrophages
*association with bird droppings or bat guano in caves
*90% of infections are subclinical; invasive and disseminated disease more likely in immunocompromised hosts
*clinical features:
-hilar lymphadenopathy
-oral ulcerations
-bone marrow involvement (pancytopenia)
-splenomegaly
blastomycosis
*dimorphic (endemic) fungi
*smears & histopath show 8-15 micrometer multinucleate BROAD-BASED BUDDING YEASTS
*associated with clearing wood, beaver dams
*over 1/2 of patients manifest clinical disease:
-pneumonia
-disseminated disease: skin, bone, CNS, GU tract (prostatis in men)
coccidioidomycosis
*dimorphic (endemic) fungi
*smears & histopath show spherules with endospores
*association with exposure to desert soil, dust storms, etc (more common in SOUTHWEST US - Cali, etc)
*“Valley Fever”: fever, cough, fatigue
*erythema nodosum
*dissemination: CNS (meningitis), bones/joints, skin
endemic (dimorphic) fungi - diagnosis
*imaging
*biopsy with histopath: FUNGAL SMEARS & CULTURES
*urine histo antigen
*urine or serum blasto antigen
*Coccidioides serolgy
endemic (dimorphic) fungi - treatment
*itraconazole
*if severe disease: Amphotericin B
aspergillus spp. - overview
*mold with ACUTE-ANGLE BRANCHING, septated hyphae
*ubiquitous in environment
*many different species
*opportunistic pathogen (neutropenia, impaired CMI)
*sites of infection: pulmonary, sinus, CNS
aspergillus spp. - 4 types of disease
- allergic bronchopulmonary aspergillosis (ABPA)
- aspergilloma
- chronic necrotizing pulmonary aspergillosis
- invasive aspergillosis
aspergillus spp. disease: allergic bronchopulmonary aspergillosis (ABPA)
*hypersensitivity to aspergillus spores, causing inflammation of bronchioles and eosinophilia
aspergillus spp. disease - aspergilloma
*fungus ball inside an old lung cavity (usually from TB)
*can be benign, or cause angio-invasion and need to be surgically removed
aspergillus spp. disease - chronic necrotizing pulmonary aspergillosis
*“semi-invasive” disease
*typically in those with underlying lung disease and/or immunocompromising conditions
aspergillus spp. disease - invasive aspergillosis
*a feared infection for immunocompromised hosts
*usually in the lungs, but can cause severe disease in the sinuses, CNS, eyes, or elsewhere
aspergillus spp. - diagnosis
*imaging
*culture
*biopsy with histopathology
*aspergillus galactomannan assay (serum or BAL)
aspergillus spp. - treatment
voriconazole
mucormycosis - overview
*refers to infections from several different molds, otherwise called “zygomycosis” (mucor, rhizopus, and others)
*broad, aseptate, “ribbon-like”, RIGHT-ANGLE branching hyphae
*ubiquitous in nature; become airborne and inhaled
*risk factors: poorly controlled diabetes (esp. DKA), neutropenia
*an enzyme called ketone reductase allows mucor to thrive in high-glucose, low pH environments
mucormycosis - pathogenesis
*inhalation of spores → proliferation in blood vessels → penetrate cribriform plate or lung parenchyma
mucormycosis - clinical syndromes
*rhino-orbital-cerebral mucormycosis (headache, facial pain, black necrotic eschar)
*pulmonary mucormycosis
mucormycosis - treatment
surgical debridement + amphotericin B
pneumocystis jirovecii pneumonia (PCP)
*opportunistic fungal infection
*worldwide distribution
*risk factor: cell mediated immunity defects, particularly HIV (CD4 < 200)
*subacute presentation (cough, fever, dyspnea on exertion)
*diffuse bilateral infiltrates on CXR
*serum LDH & B-D-glucan often elevated
*diagnosis: demonstration of organism in respiratory secretions/lung tissue by GMS staining, IMF staining, or PCR
*treatment: TMP-SMX
