1. RESPIRATORY TRACT INFECTIONS Department of Microbiology Faculty of Medicine Brawijaya University

2. The Respiratory tract Most common entry point for infections Pathogens that enter the respiratory system can infect other parts of the body Upper respiratory tract :  nose, nasal cavity, sinuses, throat and associated structures such as the middle ear and auditory tube Lower respiratory tract  Trachea, bronchi, bronchioles, and alveoli in the lungs

5. Protective Mechanisms Normal flora: Commensal organisms Limited to the upper tract can include pathogenic microorganisms Mostly Gram positive or anaerobic Microbial antagonist (competition) The lower respiratory system is usually sterile because of the action the ciliary escalator

6. Clearance of particles and organisms from the respiratory tract Cilia and microvilli move particles up to the throat  where they are swallowed. Alveolar macrophages migrate and engulf particles and bacteria in the alveoli deep in the lungs. Protective Mechanisms

7. Other Protective Mechanisms Nasal hair, nasal turbinates Mucus Involuntary responses (coughing) Secretory IgA Immunocompetent cells

8. Microbial Diseases of The Upper Respiratory System Specific areas of the upper respiratory system can become infected to produce pharyngitis, laryngitis, tonsilitis, sinusitis and epiglottitis These infections may be caused by several bacteria and viruses, often in combination

9. Bacterial Diseases of The Upper Respiratory System Streptococcal Pharyngitis (Strep Throat) Scarlet Fever Otitis Media Diphteria

10. Streptococcal Pharyngitis (Strep Throat) This infection is caused by group A beta- hemolytic streptococci (Streptococcus pyogenes) Gram positive cocci, katalase : negative

11. Streptococcus pyogenes Capsule -resistant to phagocytosis Enzymes damage host cells M protein adhesin The M protein has many antigenic varieties and thus, different strain of S.pyogenes cause repeat infections

12. Strep Throat Fever Tonsillitis Enlarged lymph nodes Middle-ear infection Treatment : Antibiotic  Penicillin

13. Scarlet Fever Strep throat, caused by an erythrogenic toxin-producing S.pyogenes, result in Scarlet Fever S.pyogenes produces erythrogenic toxin when lysogenized by a phage Symptoms include a red rash, high fever, and a red, enlarge tongue (strawberry tongue)

14. Scarlet Fever Caused by Erythrogenic Toxin secreted by S. pyogenes

15. Scarlet Fever The erythrogenic toxin is coded by a gene lysogenic bacteriophage within the genome of S. pyogenes Rash is an inflammatory reaction to the toxin

16. Infected Middle Ear (otitis media)

17. Otitis Media Can occur as a complication of nose and throat infections Pus accumulation causes pressure on the eardrum Bacterial causes include : Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, and Staphylococcus aureus

18. Diphtheria

19. Caused by Corynebacterium diphtheriae Transmitted by droplets or fomites Infects the upper respiratory tract Begins with severe sore throat, low-grade fever and swollen lymph nodes or with skin rash, 1-6 days after infection

20. Corynebacterium diphtheriae Aerobic Gram + bacillus, club-shaped morphology, metachromatic granules, form V and Y-shaped figures Exotoxin inhibits protein synthesis of cells to which it binds, and heart, kidney, or nerve damage may result Destroyed cells and WBC form "pseudomembrane" which blocks airways

21. Corynebacterium diphtheriae To produce exotoxin, C. diphtheriae must be infected with a bacteriophage carrying the toxin gene

22. An “AB” toxin B = binding subunit A = active subunit which binds to and inhibits a eucaryotic ribosomal translation factor Vaccine is diphtheria toxoid

23. Diphtheria

24. Laboratory diagnosis : isolation of the bacteria and the appearance of growth on differential media, ELEK test, PCR for detection tox gene Antitoxin must be administered to neutralize the toxin, and antibiotics can stop growth of bacteria Routine immunization  diphtheria toxoid in the DTaP vaccine Slow –healing skin ulcerations are characteristic of cutaneous diphtheria

25. Viral Diseases of The Upper Respiratory System THE COMMON COLD Any one of approximately 200 different viruses can cause the common cold; Rhinoviruses cause about 50% of all, Coronaviruses 15 – 20 %. In about 40% of cases no causative agent can be identified Symptoms include sneezing, nasal secretions, and congestion Sinus infections, lower respiratory tract infections, laryngitis, and otitis media can occur as complication

26. THE COMMON COLD Colds are most often transmitted by indirect contact Rhinovirus grow best slightly below body temperature The incidence of colds increases during cold weather, possibly because increased interpersonal indoor contact or physiological changes Antibodies are produced against the specific viruses

27. Microbial Diseases of The Lower Respiratory Tract Many of the same microorganisms that infect the upper respiratory system also infect the lower respiratory system Diseases of the lower respiratory include bronchitis and pneumonia Bacterial, viral and fungal infection can cause Inflammation of the lung with fluid filled alveoli

28. Bacterial Diseases of The Lower Respiratory System Bacterial Pneumonias Pertussis (Whooping Cough) Tuberculosis  (module) Melioidosis

29. Bacterial Pneumonias Typical Pneumonia is caused by Streptococcus pneumoniae (= Diplococcus pneumoniae = Pneumococcus) Atypical Pneumonias are caused by other microorganisms

30. Pneumococcal Pneumonia

31. Is caused by encapsulated S.pneumoniae The bacteria can be identified by the production of alpha hemolysin, inhibition by optochin, bile solubility, and through serological test Symptoms are fever, breathing difficulty, chest pain, and rust-colored sputum Treatment : penicillin, fluoroquinolones Prevention : pneumococcal vaccine consist of 23 serotypes of S.pneumoniae

32. Haemophilus influenzae Pneumonia H.influenzae is a gram-negative coccobacil Alcoholism, poor nutrition, cancer, and diabetes are predisposing factors for H.influenzae Treatment : 2 nd generation of cephalosporins that are resistant to beta-lactamases produced by many H.influenza strains

33. Mycoplasmal Pneumonia Mycoplasma pneumoniae causes mycoplasmal pneumonia; it is an endemic disease The mycoplasmas, which do not have cell walls, do not grow under the condition normally used to recover most bacterial pathogens

34. M.pneumoniae produces small “fried egg” colonies after two weeks incubation on enriched media containing horse serum and yeast extract Diagnosis is by PCR or serological test Treatment : tetracycline

35. Legionellosis This disease is caused by aerobic gram- negative rod Legionella pneumophila The bacterium can grow in water, such as air- conditioning cooling towers, and then disseminated in the air This pneumonia does not appear to be transmitted from person to person Bacterial culture, FA test, and DNA probes are used for laboratory diagnosis Treatment : Erythromycin

36. Psittacosis (Ornithosis) The term “psittacosis” is applied to the human Chlamydia psittaci disease acquired from contact with birds and also the infection of psittacin birds (parrots,parakeets,etc) Elementary bodies allow the bacteria to survive outside a host Commercial bird handlers are most susceptible to this disease The bacteria are isolated in embryonated eggs, mice, or cell culture. Identification is based on FA staining Treatment : tetracyclines

38. Chlamydial Pneumonia Chlamydia pneumoniae, causes pneumonia; it is transmitted from person to person C.pneumoniae produces round,dense, glycogen-negative inclusion that are sulfonamide-resistant The elementary bodies some time have a pear- shaped appearance Suggesting that C.pneumoniae associated with atherosclerotic coronary artery and cvd Tetracycline is used for treatment

39. Chlamydia pneumoniae

40. Q Fever Obligately parasitic, intracellular Coxiella burnetii causes Q Fever The disease is usually transmitted to humans through unpasteurized milk or inhalation of aerosols in dairy barns Mild respiratory disease lasting 1 – 2 weeks; occasional complication such as endocarditis occur Treatment : doxycycline and chloroquin

41. Melioidosis Melioidosis is caused by Burkholderia pseudomallei, a gram-negative rod formerly placed in the genus of Pseudomonas Melioidosis is transmitted by inhalation, ingestion, or through puncture wounds Symptoms include pneumonia, sepsis, and encephalitis Most common in Southeast Asia and northern Australia Treatment : Ceftazidime

42. Pertussis (Whooping Cough) Pertussis is caused by Bordetella pertussis B.pertussis is a small, obligately aerobic gram- negative coccobacillus The virulent strain posses a capsule The bacteria attach specifically to ciliated cells in the trachea, first impeding their ciliary action and then progressively destroying the cells The filamentous hemagglutinin mediates adhesion to ciliated epithelial cells

43. Pertussis (Whooping Cough) B.pertussis produce several toxins. The tracheal toxin  damage to the ciliated cells, pertussis toxin  blood stream and associated with systemic symptoms of the disease The initial stage of pertussis resemble a cold and is called catarrhal stage The paroxismal (second) stage  deep cough The convalescence stage can last for months Regular immunization  decreases the incidence of pertussis (DTaP) Treatment : erythromycin

45. Viral diseases of The Lower Respiratory System VIRAL PNEUMONIA Viral pneumonia can occur as a complication of influenza, measles, or even chickenpox The etiologies are not usually identified in a clinical laboratory because of the difficulty in isolating an identifying viruses

46. Respiratory Syncytial Virus (RSV) Respiratory syncytial virus is probably the most common cause of viral respiratory disease in infants RSV is an RNA virus, member of Paramyxoviridae family, genus Pneumovirus RSV replication occur initially in epithelial cells of the nasopharynx  spread into the lower repiratory tract and cause bronchiolitis and pneumonia The symptoms are coughing and wheezing that last for more than a week The most recent approved treatment : humanized monoclonal antibody, Palivizumab (Synagis)

47. BRONCHIOLITIS RSV

48. Influenza (Flu) History of influenza 412 BC - first mentioned by Hippocrates 1580 - first pandemic described 1580-1900 - 28 pandemics

49. Pandemic influenza in the 20 th Century 19201940196019802000 H1N1 H2N2H3N2 1918 “Spanish Flu”1957 “Asian Flu”1968 “Hong Kong Flu” 20-40 million deaths1 million deaths

50. Influenza Virus Family Orthomyxoviridae Three main types  Type A Multiple species  Type B Humans  Type C Humans and swine 15 HA and 9 NA for influenza A  All in aquatic birds Hemagglutinin (HA)  Function: Sites for attachment to infect host cells Neuraminidase (NA)  Function: Remove neuraminic acid from mucin and release from cell

51. Antigenic drift  Changes in proteins by genetic point mutation & selection  Immune response no longer protects fully  Ongoing and basis for change in vaccine each year Antigenic shift  Changes in proteins through genetic reassortment  Produces different viruses not covered by annual vaccine  pre-existing antibodies do not protect  may get pandemics Influenza A Virus

53. AGE SHIFTS IN MORTALITY Concept of “The Doctrine of Original Antigenic Sin,” by Thomas Francis (1960) - immune response is greatest to antigens to which first exposure occurred in childhood. Persons born before 1957 who were exposed in childhood to influenza A (H1N1) viruses might be better protected against this viral subtype than those who were first exposed to other influenza A subtypes, H2N2 and H3N2, at a later date.

54. Ecology of Influenza Virus A

55. Avian Influenza  Avian Influenza is an infection caused by avian (bird) influenza (flu) viruses  Flu viruses occur naturally among birds worldwide  Wild birds carry the viruses in their intestines, but usually do not get sick  Easily transmitted to domesticated birds like chickens, ducks, and turkeys and usually acquire them by coming in contact with contaminated excretions—they usually die.  May be transmitted to other species  May mutate to cause human to human infections  >300 million domestic poultry culled  186 human cases/ 105 fatalities 24 March 06

56. REASSORTMENT

57. α2-3 α2-6 Sebaran reseptor α2-3 atau α2-6 sialic acids pada saluran pernafasan manusia Influenza virus Receptors in Human air way, Nature vol. 440, 23 March 2006 f. Bronchiole g. Alveolus c. Pharynx e. Bronchus d. Trachea b. Paranasal sinus a b c d e f g

58. Novel Influenza A (H1N1) 2009 Virus  SWINE FLU New strain of A (H1N1) Not previously detected in swine or human Unusual mix of genetic segments including of swine, avian and human influenza viruses Originated from pigs and at some point of time transmitted to human Cases began to appear from 17 th March’09 in Mexico with human – to – human transmission No cases in swine population and no infections from pork. Pigs are responsible only for mutation of virus.

59. PIG THE CREATOR

60. Treatment & Prevention Amantadine and rimantadine are effective prophylactic and curative drugs against Influenza virus A The NA inhibitors zanamivir and oseltamivir were approved in 1999 for tx both influenza A and B Multivalent vaccines are available for the eldery and other high-risk group

61. Fungal Diseases of The Lower Respiratory System Fungal spores are easily inhale ; they may germinate in the lower respiratory tract The incidence of fungal diseases has been increaseing in recent years

62. Histoplasmosis Histoplasma capsulatum causes a subclinical respiratory infection that only occasionally progresses to severe, generalized disease The disease is acquired by inhalation of airborne conidia Isolation of the fungus or identification in tissues sample is necessasry for diagnosis Treatment : Ampotericin B

63. Coccidioidomycosis Inhalation of the airborne arthroconidia of Coccidioides immitis can result Coccidioidomycosis Most cases are subclinical, but when there are predisposing factors such as fatigue and poor nutrition, a progressive disease resembling tuberculosis can result  fever, coughing, weight loss; occasionally fatal Treatment : Ampotericicn B

64. Pneumocystis Pneumonia Pneumocystis jeroveci (formerly P.carinii) is sometimes found in healthy human lung Pneumonia; a common serious complication of AIDS Treatment : Co- trimoxazole

65. Blastomycosis (North American Blastomycosis) Blastomyces dermatitidis is the causative agent of blastomycosis The infection begins in the lungs and can spread to cause extensive abcesses Treatment : Amphotericin B

66. Aspergillosis Many other opportunistic fungi may cause respiratory disease Aspergillus fumigatus can cause: Allergic bronchopulmonary aspergillosis Aspergilloma: in patients with pre-existing lung disease  mass of hyphae produce fungus ball Disseminated aspergillosis

67. Aspergillosis