Microbial Diseases Respiratory System.pptx

Powerpoint

1. Diseases of the Respiratory System Dr R.S. MKAKOSYA microbiology

2. Intended learning outcomes Recall anatomy The Normal flora Aetiology Pathogenesis Diagnosis Management Prevention respiratory

3. Microbial diseases of the respiratory system Structures of the Respiratory System Respiratory system exchanges gases between the atmosphere and the blood Divided into two main parts Upper respiratory system ( Nose, Nasal cavity, Pharynx, Tonsils, Mucus - Lower respiratory system ( Larynx, Trachea, Bronchi , Alveoli, Diaphragm ), and Various protective components Ciliated mucous membrane, alveolar macrophages, and secretory antibodies respiratory

4. Figure 22.1 Structures of the respiratory system-overview

5. Normal Microbiota of the Respiratory System Lower respiratory system Typically microorganisms are not present Upper respiratory system Colonized by many microorganisms Normal microbiota limit growth of pathogens Normal microbiota may be opportunistic pathogens respiratory

6. Bacterial Diseases of the Upper Respiratory System, Sinuses, and Ears Streptococcal Respiratory Diseases Signs and symptoms Sore throat and difficulty swallowing May progress to scarlet or rheumatic fever Pathogen and virulence factors Caused by group A streptococci ( S. pyogenes ) Variety of virulence factors M proteins, hyaluronic acid capsule, streptokinases , C5a peptidase, pyrogenic toxins, streptolysins respiratory

7. Streptococcal Respiratory Diseases Pathogenesis Occurs when normal microbiota are depleted, large inoculum is introduced, or adaptive immunity is impaired Epidemiology Spread via respiratory droplets Occurs most often in cold weather Diagnosis, treatment, and prevention Often confused with viral pharyngitis Penicillin is an effective treatment respiratory

8. Diphtheria Signs and symptoms Presence of a pseudomembrane that can obstruct airways Pathogen and virulence factors Caused by Corynebacterium diphtheriae Virulence factors C. diptheriae produces diphtheria toxin Prevents polypeptide synthesis and causes cell death respiratory

9. Figure 22.2 A pseudomembrane, characteristic of diphtheria Pseudomembrane

10. Diphtheria Pathogenesis and epidemiology Spread via respiratory droplets or skin contact Symptomatic in immunocompromised or nonimmune individuals Diagnosis, treatment, and prevention Diagnosis based on presence of a pseudomembrane Treat with antitoxin and antibiotics Immunization is an effective prevention respiratory

11. Sinusitis and Otitis Media Signs and symptoms Sinusitis causes pain and pressure of the affected sinus accompanied by malaise Otitis media results in severe pain in the ears Pathogen and virulence factors Caused by various respiratory microbiota May be due to upper respiratory system and auditory tube damage respiratory

12. Sinusitis and Otitis Media Pathogenesis and epidemiology Bacteria in the pharynx spread to the sinuses via the throat Sinusitis is more common in adults Otitis media is more common in children Diagnosis, treatment, and prevention Symptoms often diagnostic No known way to prevent sinusitis respiratory

13. Infections of the lower respiratory system ( pneumonia) Definition of pneumonia Classifications of pneumonia Risk factors for pneumonia Management of pneumonia Assessment for severity of pneumonia Complications Prevention respiratory

14. DEFINITION PATHOLOGICAL: Inflammation of the lung parenchyma Polymorphonuclear leukocyte exudate in and around alveoli, terminal bronchioles Develops in 3 stages: Engorgement : lung is wet, edematous & congested Red hepatization : lung is red, dry, friable & solid Grey hepatization : softened lung & exudation of yellow purulent fluid respiratory

15. Clinical presentation CLINICAL: Acute illness consisting of a syndrome of Fever, cough, sputum production and Clinical signs of consolidation and Typical chest radiograph (CXR) changes respiratory

16. pathogenesis Microbes can access the lower respiratory tract by: Inhalation of aerosolized material Aspiration of normal flora of the upper respiratory tract Seeding from other infected sites via bloodstream Only microbes of < 5µm diameter reach the alveoli to cause inflammation respiratory

17. CLASSIFICATION SITE Lobar vs. bronchopneumonia AETIOLOGY Community acquired vs. nosocomial pneumnia MICROBIOLOGY Causative organism: bacteria, virus, fungi TYPICAL VS. ATYPICAL respiratory

18. Involvement of a distinct region of the lung Polymorph exudate clots in the alveoli rendering them solid Classically seen in previously healthy young people Usually caused by S. pneumoniae 1. SITE: lobar/segmental respiratory

19. Usually bilateral Consolidation is scattered throughout the lung fields Mainly seen in Elderly Debilitating or chronic respiratory disease, e.g. chronic bronchitis 2 . SITE: bronchopneumonia respiratory

20. INTERSTITIAL Involves invasion of the lung interstitium Characteristic of viral infections of the lungs LUNG ABSCESS a.k.a. necrotizing pneumonia Cavitation & destruction of the lung parenchyma 3 . SITE: interstitial vs. abscess respiratory

21. COMMUNITY ACQUIRED Common type of pneumonia Occur in people who haven’t been recently hospitalized Caused by most bacteria & viruses Organisms are usually sensitive to empiric antibiotics respiratory

22. RISK FACTORS Immune deficiency: Primary, e.g. complement deficiency Secondary, e.g. HIV infection, malnutrition Extremes of age, Prior viral & other respiratory tract infections Asthma, bronciectasis, chronic bronchitis, COPD, cystic fibrosis Disturbed consciousness in association with General anaethesia, convulsions, alcoholism, epilepsy, head trauma Predisposing disease states: heart/liver/renal failure, diabetes, bronchogenic & metastatic malignancy respiratory

23. Bacterial Diseases of the Lower Respiratory System Bacterial Pneumonias Lung inflammation accompanied by fluid–filled alveoli and bronchioles Described by affected region or organism causing the disease Bacterial pneumonias are the most serious and the most frequent in adults respiratory

24. Pneumoccocal Pneumonia Signs and symptoms Short, rapid breathing; rust-colored sputum Pathogen and virulence factors Caused by Streptococcus pneumoniae Virulence factors include adhesins , capsule, pneumolysin Pathogenesis and epidemiology Infection occurs by inhalation of bacteria Bacterial replication causes damage to the lungs Diagnosis, treatment, and prevention Penicillin is the drug of choice for treatment Vaccination is method of prevention respiratory

25. Accounts for 30-50% of CAP Gram positive diplococci Virulence factors: IgA1 protease, polysaccharide capsule, pneumolysin causes lobar pneumonia Isolated from sputum (rusty colored) Rx: penicillin/ erythromicin Complications: meningitis, endocarditis, septic arthritis Strep. pneumoniae respiratory

26. Primary Atypical ( Mycoplasmal ) Pneumonia Signs and symptoms Include fever, malaise, sore throat, excessive sweating Pathogen and virulence factors Caused by Mycoplasma pneumoniae Virulence factors include an adhesion protein Epidemiology Bacteria spread by nasal secretions Diagnosis, treatment, and prevention Treated with tetracycline and erythromycin Prevention difficult since infected individuals may be asymptomatic respiratory

27. Klebsiella Pneumonia Signs and symptoms Pneumonia symptoms combined with a thick, bloody sputum Pathogen and virulence factors Caused by Klebsiella pneumoniae Virulence factors include a capsule Pathogenesis and epidemiology Immunocompromised individuals at greatest risk for infection Diagnosis, treatment, and prevention Treated with antimicrobials Prevention involves good aseptic technique by health care workers respiratory

28. The prominent capsule of Klebsiella pneumoniae Capsules

29. Other Bacterial Pneumonias Haemophilus influenzae and Staphylococcus aureus Disease similar to pneumococcal pneumonia Yersinia pestis Causes pneumonia called pneumonic plague Chlamydophila psittaci Causative agent of ornithosis Disease of birds that can be transmitted to humans Chlamydophila pneumoniae Causes pneumonia, bronchitis, and sinusitis respiratory

30. TUBERCULOSIS R.S. Mkakosya

31. LEARNING OUTCOMES By successful completion of this lesson learners must: give a brief description of tuberculosis explain the aetiology of tuberculosis narrate the clinical presentation of tuberculosis list the drugs used for TB treatment describe the administration route of each drug explain the mechanism of action of the first line antituberculous drugs explain the development of resistant to antituberculous drugs explain the importance of adherence to TB treatment demonstrate an understanding on the results of treatment adherence test respiratory

32. Tuberculosis Slow progressive, chronic granulomatous infection which often affect the lungs; other organs and tissues may be involved It is characterized by chronic productive cough, low grade fever, night sweats and weight loss The aetiologic agent is highly contagious but very few infected people develop tuberculosis Persistent infection may reactivate after decades following deterioration of immune status Infection can also be through exogenous route AETIOLOGY Genus mycobacterium introduced to include causative agents of tuberculosis and leprosy Mycobacteria are aerobic, asporogenous, nonmotile, nonencapsulated, straight or slightly curved acid fast bacilli occurring singly and in occasional threads each cell measuring 0.3-0.6 m X 1-4m Tuberculosis caused by the Mycobacterium tuberculosis complex (M. tuberculosis, M. bovis, M. africanum, and M. microti) Mycobacterium tuberculosis complex are obligate pathogens but can survive in other organic materials respiratory

33. Can survive in sputum for 3 months, 2-6 months in the soil, 6 months in the laboratory Sensitive to UV light, heat (destroyed during pasteurization) Susceptible to alcohol, formaldehyde and gluteraldehyde Resistant to acids, alkali and quaternary ammonium compounds Rabbits are more sensitive to M. bovis than to M. tuberculosis Guinea pigs sensitive to both M. tuberculosis and M. bovis respiratory

34. PATHOGENESIS Inhalation of droplets with viable bacilli or ingestion of contaminated food/drink Bacilli deposited into the alveolar space where they are engulfed by alveolar macrophages Infectious inoculum resists intracellular destruction and persists, eventually multiplying and killing the macrophages Virulence due to the ability of surviving in macrophages Accumulating mycobacteria stimulate an inflammatory focus which matures into a granulomatous lesion characterized by a mononuclear cell infiltrate surrounding a core of degenerating epitheloid and multinucleated giant cells Lesions become enveloped in fibrin and the center progresses to caseous necrosis Erosion of caseous tubercles into adjacent airways result in cavitation and release of bacilli into sputum respiratory

35. CLINICAL MANIFESTATIONS Primary TB Generally subclinical but positive to PPD; Fever, non-productive cough, shortness of breath X-ray of the chest may show patchy or lobular infiltrate in the anterior segment of the upper, middle and lower lobes Pleurisy without parenchyma infiltrate, pleuritic chest pain, fever, chills, sweats and dyspnea Progressive TB Low grade fever, night sweats, fatigability, loss of appetite, weight loss, cough and occasional haemoptysis Sputum smear positive Post Primary Reactivation Night sweats, chills, fatigue, fever, haemoptysis, physical examination reveals dullness and rales in the upper lung fields. PPD and culture positive Extra-pulmonary TB Clinical manifestation general e.g. fever or typical of the organ involved e.g. dysuria in genitourinary TB, back pain in vertebral TB (1) Lymphatic TB (2) genitourinary TB (3) vertebral and articular TB (4) meningeal TB (5) Peritoneal TB (6) perirdial TB (7) milliary TB respiratory

36. CLINICAL MANIFESTATIONS respiratory

37. Diagnosis of tuberculosis-overview

38. TREATMENT 1 ST Line drugs: Isoniazid (INH; isonicotinic acid hydrazide), rifampicin, pyrazinamide (PZA)and/or ethambutol (EMB) for the first 2 months then continue with isoniazid and rifampicin Antituberculous drugs Isoniazid: Most active against M. tuberculosis where it exerts bactericidal effect. Well absorbed when given orally and eliminated through urine. May cause peripheral neuropathy and mental disturbance which can be prevented by giving pyridoxine (vit. B6) Rifampicin: One of the rifamycins. Broad spectrum antibiotic active against M. leprae, M. marinum, M.kansasii and M. haemophilum. Together with rifabutin are semisynthetic derivative of the naturally occurring antibiotic rifamycin B. Rifabutin is active against M. avium complex. Rifamycin act by binding to the  subunit of the DNA dependent RNA polymerase and prevent initiation of protein synthesis. Causes flu-like syndrome especially when given intermittently. Contraindicated in administration of steroids, oral contraceptives and antiepleptic drugs Pyrazinamide: Synthetic derivative of nicotinamide. Bactericidal only in acidic environment and after intracellular conversion by a bacterial amidase to pyrazinoic acid All the three are hepatotoxic Ethambutol: Generally mycobacteristatic but has a wider spectra activity over the mycobacteria. Causes ocular damage respiratory

39. respiratory Second-line drugs (SLDs) used for the treatment of TB Aminoglycosides e.g. kanamycin, amikacin Polypeptides e.g. capreomycin, viomycin, enviomycin Fluoroquinolones e.g. ciprofloxacin, levofloxacin, moxilofloxacin Thioamides e.g. prothionamide, ethionamide Cycloserine and P-aminosalicylic acid Other drugs in the second line treatment or Third line Rifabutin, linezolid, thioacetazone, macrolides (e.g. clarithromycin), thiolidazine, vitamin D and arginine

40. respiratory Acceptable abbreviations: Antituberculous drugs can abbreviated as below: First line tuberculosis drugs Isoniazid INH H Rifampicin RMP R Pyrazinamide PZA Z Ethambutol EMB E Streptomycin STM S Second line tuberculosis drugs Ciprofloxacin CIP P-aminosalicylic acid PAS P Moxifloxacin MXF

41. respiratory Resistance to antituberculous drugs Non compliance Single drug use Mutation Species resistance (e.g. M. bovis naturally resistant to PZA) Resistant to INH MDR (multi-drug resistant) resistant to at least INH and RMP Extensively drug-resistant tuberculosis" ( XDR-TB ) MDR-TB that is resistant to quinolones

42. respiratory Resistance cont’ Patient with suspected MDR-TB, the patient should be started on SHREZ + MXF+ cycolserine pending the result of laboratory sensitivity testing Confirmed as resistant to both INH and RMP, five drugs should be chosen PZA, EMB An aminoglycoside (e.g. amikacin or kanamycin) or polypeptide (e.g. capreomycin) A fluoroquinolone (preferably MXF) Rifabutin cycloserine a thioanide (e.g. prothionamide or ethionamide) PAS A macrolide (e.g. clarithhromycin) Linezolid high-dose INH (if low-level resistance)

43. respiratory Compliance Vital for full treatment Non compliance may lead to emergency of resistance Reasons for non compliance Bulky drugs Requirement for an empty stomach

44. respiratory Compliance Testing Test urine for isoniazid and rifampicin levels The interpretation of urine analysis is based on the fact that isoniazid has a longer half-life than rifampicin: urine positive for isoniazid and rifampicin patient probably fully compliant urine positive for isoniazid only patient has taken his medication in the last few days preceding the clinic appointment, but had not yet taken a dose that day. urine positive for rifampicin only patient has omitted to take his medication the preceding few days, but did take it just before coming to clinic. urine negative for both isoniazid and rifampicin patient has not taken either medicine for a number of days In the absence of urine testing; RMP colours the urine and all bodily secretions (tears, sweat, etc.) an orange-pink colour (colour fades 6-8 hours after each dose).

45. respiratory Adverse effects associated with the drugs peripheral neuropathy (seen with INH) can be stopped by pyridoxine Thrombocytopaenia with RMP Itching RMP commonly causes itching without a rash in the first two weeks Rifampicin makes hormonal contraception less effective Hepatitis : PZA, RMP, INH Rash : PZA, RMP, EMB Fever due to drug allergy PZA is a common cause of rash, hepatitis and of painful arthralgia Capreomycin and amikacin may cause deafness in the unborn child

46. respiratory A model prescription 2HREZ/4HR 3 A prefix (2 and 4) denotes the number of months the treatment should be given for A subscript (3) denotes intermittent dosing (so 3 means three times a week) and No subscript means daily dosing

47. Mycobacteria in Immunocmpromised MAC Others include; M. kansasii, M. xenopi, M. gordonae, M. malmonese Greater surveillance and increased survival of Immunocompromised Minimal pulmonary invasion M. avium>M. intracellulare Common port of entry gastrointestinal MAC found in all organs M. kansasii commonly implicated respiratory

48. Pertussis (Whooping Cough) Signs and symptoms Initially cold-like, then characteristic cough develops Pathogen and virulence factors Bordetella pertussis is the causative agent Produces numerous virulence factors Includes adhesins and several toxins Pathogenesis Pertussis progresses through four phases Incubation, catarrhal, paroxysmal, and convalescent respiratory

49. Pertussis (Whooping Cough) Epidemiology Highly contagious Bacteria spread through the air in airborne droplets Diagnosis, treatment, and prevention Symptoms are usually diagnostic Treatment is primarily supportive Prevention is with the DTaP vaccine respiratory

50. Inhalational Anthrax Signs and symptoms Initially resembles a cold or flu Progresses to severe coughing, lethargy, shock, and death Pathogen and virulence factors Bacillus anthracis is the causative agent Virulence factors include a capsule and anthrax toxin Pathogenesis and epidemiology Anthrax not spread from person to person Acquired by contact or inhalation of endospores respiratory

51. Inhalation Anthrax Diagnosis , treatment, and prevention Diagnosis based on identification of bacteria in sputum Early and aggressive antimicrobial treatment necessary Anthrax vaccine available to selected individuals respiratory

52. Mycoses of the Lower Respiratory System Coccidioidomycosis Signs and symptoms Resembles pneumonia or tuberculosis Can become systemic in immunocompromised persons Pathogen and virulence factors Caused by Coccidioides immitis Pathogen assumes yeast form at human body temperature Pathogenesis Arthroconidia from the soil enter the body through inhalation respiratory

53. Coccidioidomycosis lesions in subcutaneous tissue

54. Spherules of Coccidioides immitis Spherule Spores

55. Coccidioidomycosis Epidemiology Almost exclusively in southwestern U.S. and northern Mexico Diagnosis, treatment, and prevention Diagnosed by presence of spherules in clinical specimens Treat with amphotericin B Protective masks can prevent exposure to arthroconidia respiratory

56. Mycoses of the Lower Respiratory System cont’ Blastomycosis Signs and symptoms Flulike symptoms Systemic infections can produce lesions on the face and upper body or purulent lesions on various organs Pathogen Caused by Blastomyces dermatitidis Pathogenic yeast form at human body temperature respiratory

57. Cutaneous blastomycosis in an American woman

58. Blastomycosis Pathogenesis and epidemiology Enters body through inhalation of dust carrying fungal spores Incidence of human infection is increasing Diagnosis, treatment, and prevention Diagnosis based on fungus identification in clinical samples Treated with amphotericin B Relapse common in AIDS patients respiratory

59. Mycoses of the Lower Respiratory System cont’ Histoplasmosis Signs and symptoms Asymptomatic in most cases Symptomatic infection causes coughing with bloody sputum or skin lesions Pathogen Caused by Histoplasmosis capsulatum Pathogenic yeast form at human body temperature respiratory

60. Histoplasmosis Pathogenesis and epidemiology Humans inhale airborne spores from the soil Prevalent in the eastern U.S. Diagnosis, treatment, and prevention Diagnosis based on fungus identification in clinical samples Infections in immunocompetent individuals typically resolve without treatment respiratory

61. Mycoses of the Lower Respiratory System Pneumocystis Pneumonia (PCP) Signs and symptoms Difficulty breathing, anemia, hypoxia, and fever Pathogen Caused by Pneumocystis jirovecii Pathogenesis and epidemiology Transmitted by inhalation of droplets containing the fungus Common disease in AIDS patients Diagnosis, treatment, and prevention Diagnosis based on clinical and microscopic findings Treat with trimethoprim and sulfamethoxazole Impossible to prevent infection with P. jirovecii respiratory

62. Viral Diseases of the Upper Respiratory System Common Cold Signs and symptoms Sneezing, runny nose, congestion, sore throat, malaise, and cough Pathogens and virulence factors Enteroviruses (rhinoviruses) are the most common cause Numerous other viruses cause colds Pathogenesis Cold viruses replicate in and then kill infected cells respiratory

63. Rhinoviruses, the most common cause of colds

64. Common Cold Epidemiology Rhinoviruses are highly infective Spread by coughing/sneezing, fomites , or person-to-person contact Diagnosis, treatment, and prevention Signs and symptoms are usually diagnostic Pleconaril can reduce duration of symptoms Hand antisepsis is important preventive measure respiratory

65. Influenza Signs and symptoms Sudden fever, pharyngitis , congestion, cough, myalgia Pathogens and virulence factors Influenza virus types A and B are the causative agents Mutations in hemagglutinin and neuraminidase produce new strains respiratory

66. Influenza Pathogenesis Symptoms produced by the immune response to the virus Flu patients are susceptible to secondary bacterial infections Virus causes damage to the lung epithelium Epidemiology Transmitted via inhalation of viruses or by self-inoculation Complications occur most often in the elderly, children, and individuals with chronic diseases respiratory

67. Viral Diseases of the Lower Respiratory System Influenza Diagnosis, treatment, and prevention Signs and symptoms during a community-wide outbreak are often diagnostic Treatment involves supportive care to relieve symptoms Oseltamivir and zanamivir can be administered early in infection Prevent by immunization with a multivalent vaccine © 2012 Pearson Education Inc. respiratory

68. Viral Diseases of the Lower Respiratory System Severe Acute Respiratory Syndrome (SARS) Signs and symptoms High fever, shortness of breath, and difficulty breathing Later develop dry cough and pneumonia Pathogen and virulence factors Caused by a coronavirus called SARS virus Pathogenesis and epidemiology SARS virus spreads via respiratory droplets Diagnosis, treatment, and prevention Diagnosis based on signs and symptoms of SARS Treatment is supportive respiratory

69. Viral Diseases of the Lower Respiratory System Other Viral Respiratory Diseases Other viruses cause respiratory disease in children, the elderly, or immunocompromised individuals Cytomegalovirus Metapneumovirus Estimated to be the second most common cause of viral respiratory disease Parainfluenza viruses Three strains cause croup and viral pneumonia Occur primarily in young children respiratory