Lecture 16: LRTI Infections

(LRTI Infections) Lecture 16 · Infections of the lower respiratory tract tend to be more severe because alveoli function is impacted Infections of the LRT are caused by: · choice of antimicrobial therapy may be life saving Mycobacterium Tuberculosis (TB) · bacillus, non-motile, acid fast, strict aerobe Consumption · Bacteria · Viruses · Fungi · Parasites · no toxin produced, inflammation is major pathogenic mechanism · capable of intracellular survival & growth in macrophages (facultatively intracellular) · many latent infections but only some become active ↳ CMI usually controls infection but is also responsible for pathology of disease -CMI: cell mediated immunity (adaptive system) · after TB exposure three things could happen: ① Latent infection: where few TB organisms enter macrophages and remain latent there ② Primary tubercle forms: immune system stops replication by forming a granuloma around bacterium and prevent access to oxygen ③ Spread of active infection: this happens in immunocompromised individuals Primary Infection often in Lung · Host walls off the infection in a "tubercle" (granuloma) · Tubercle/granuloma ↳ macrophage, B and T cells surround TB and they cannot replicate because of the low pH and low oxygen concentration · Disseminated infection ↳ occurs if tubercle does not form or ruptures and bacteria spreads ↳ this is called miliary tuberculosis Second Stage Infection · "miliary" infection · directly spread from primary infection OR reactivation of a latent infection · characterized by a spread of tubercles/granulomas ↳ You can get it anywhere in the body · symptoms: weight loss, fever, night sweats, chronic cough, coughing up blood, lethargic TB infection (latent) · MTB present · Tuberculin skin test positive · Chest X-ray normal · Sputum smears and cultures negative · No symptoms · Not infectious · Not defined as a case of TB TB disease (active in lungs) · MTB present · Tuberculin skin test positive · Chest x-ray reveals lesions · Sputum smears and cultures positive · Symptoms: cough, fever, weight loss · Often infectious before treatment · Defined as a case of TB Pathogenicity · mycolic acid forms an impermeable barrier to entry of molecules into the bacillus ↳ survive long periods on dry surfaces ↳ b/c of mycolic acid Z-Neelson (acid fast stain) is required · cord factor: causes bacteria to clump together and inhibit phagocytosis ↳ also toxic to host cells Risk Factors for TB: · presence of another infection eg. HIV · physiological and environmental stress ↳ malnutrition etc. · depressions of the immune system due to older age Laboratory Diagnosis · acid-fast rods in sputum · culture takes a long time to grow · QuantiFERON Gold: blood sample tests if T lymphocytes are activated and measures interferon levels produced ↳ can differentiate between latent and active · Skin tests for TB: test for cell mediated/acquired immunity by detection of memory cells (only shows exposure) · Tuberculin Test: used as a screening test Vaccine · BCG: bacillus calmette-guerin · live culture of Mycobacterium bovis · only given to children at high risk · vaccine doesn't last very long · adults have almost no effect, children some effect ↳ PPD (purified protein derivative)infracutaneously ↳ measure diameter of injection ↳ delayed hypersensitivity reaction measured · Mantoux test: a quantitative tuberculin test Treatment and Antibiotic Resistance · multiple drug regimens used to prevent development of drug resistance · treatment lasts 6mo-1yr b/c bacterium slow growth · MDR-TB and XDR-TB is a growing problem · MDR-TB resistant to isoniazid and rifampicin (first line drugs) · XDR-TB resistant to first and second line drugs · isolation and quarantine Pneumonia (or pneumonitis) · Typical: classically caused by S. pneumoniae, responds to penicillin treatment · Atypical: caused by other organisms, penicillin resistant, includes virus, bacteria, and fungi · most common cause of infection-related death globally · causes of pneumonia in adults and children different ↳ adults: mainly bacterial ↳ children: mainly viral "Pneumococcal" Pneumonia · encapsulated facultatively anaerobic G+ diplococci · most common cause of pneumonia, involves alveoli and bronchi · symptoms: fever, rust coloured sputum (blood), breathing problems and chest pain · often spreads to the blood by alveoli close to blood stream ↳ bacteremia → septicemia → sepsis · vaccines: polysaccharide and conjugate · pathogenicity: many virulence factors ↳ capsule (main virulence factor) ↳ cell wall: lipoteichoic acids and peptidoglycan ↳ autolysins: self-destruction, release chemicals that aid inflammation ↳ pneumolysins: damage pneumocytes in lungs ↳ production of hydrogen peroxide, neuraminidase, and IgA protease Pneumonia Risk Factors · Asthma · Cystic Fibrosis · Chronic Obstructive Pulmonary Disease (COPD) · Weakened immune system (HIV, cancer... ) · Young children and elderly Bronchiolitis in Infants · usually after an upper respiratory tract infection · disease restricted to children <2 years · bronchioles in children are very small so if they are inflamed and swollen the passage of air to and from alveoli is reduced · necrosis of epithelial cells and interstitial pneumonia · 75% of cases caused by RSV RSV (Respiratory Syncytial Virus) · enveloped RNA virus transmitted by direct contact and sometimes droplet · most susceptible are infants and children under 5, and elderly in nursing homes · seasonal epidemics: late winter and early spring · life threatening pneumonia and bronchiolitis in infants · symptoms: coughing and wheezing · premature babies highest risk for serious disease b/c lungs aren't as well developed · treatment: no effective antiviral or vaccine · prophylaxis: synagis used for extremely at risk babies and is very expensive Croup (children) · parainfluenza virus (PIV)(enveloped RNA) · swelling of mucous membranes in the respiratory tract · larynx and trachea have non-expandable rings of cartilage and since children have narrow tubes so obstruction can occur · typical seal-like barking cough · no treatment or vaccine Covid-19 · new enveloped RNA virus probably from bat reservoir · four subtypes: alpha and beta (human pathogens), gamma and theta (animal) ↳ beta is the serious group · symptoms: fever, conjunctivitis, pharyngitis, coryza, headache, dizziness, generalized weakness, vomiting, diarrhea, dry cough, shortness of breath, lack of taste and smell, fatigue · severe disease usually presents after 9 days of infection ↳ lymphopenia, especially in the peripheral blood T cells ↳ increased plasma concentration of inflammatory cytokines and chemokines ↳ elevated D-dimer and fibrinogen increased clotting (hypercoagulable) How does this Corona Virus affect Humans? · glycoprotein spikes: responsible for tropism and attachment to host cell ↳ two functional units: - S1 used to bind to receptors on host cells - S2 used to fuse host cell and virus envelope · main receptor for Covid-19: Angiotensin converting enzyme 2 (ACE2) ↳ highly expressed in lung, heart, ileum, kidney, bladder, epithelial and endothelial cells ACE2 · normally it breaks down proteins (angiotensin II) which can increase inflammation and the death of cells in the alveoli · harmful effects of ANG II are reduced by ACE2 · When COVID-19 is bound to ACE2 then it cannot prevent the damaging effects of ANG II Vaccines and Antivirals · few antiviral substances found that can shorten duration of disease but not prevent · a common cortisone derivative dexamethazone has been found to improve survival Influenza A · Influenza A, B, C are enveloped orthomyxoviridae, segmented RNA viruses · Influenza A + B have 8 RNA segments, C has 7 Helps new viruses leave host cells · Only Influenza A has subtypes Glycoprotein for attachment Symptoms: · Malaise · Fever · Headache · Myalgia Incubation Period and Infectious Dose · small infections dose · Sore throat · virus viable on hard surfaces 1-2 days · Cough more severe in smokers · incubation 1-5 days · droplet transmission Antigenic Drift · point mutations in the viral genome encoding for H or N antigens · these strains cause the yearly infections (some cross immunity from year before) Antigenic Shift · recombination of the viral RNA segments with those from another human or an animal · significant changes in the H and N surface antigens · leads to pandemics b/c no immunity to "new" viruses Fungal Diseases: Histoplasmosis, Coccidiodomycosis, Aspergillosis, Pneumocystis jiroveci (especially in AIDS and other immune-suppressed individuals like transplant patients, opportunistic yeast)