1. RESPIRATORY TRACT DISEASES

3. General Goal: To know the major mechanisms of defense in the URT, the major mechanisms invaders use to avoid the defenses of the LRT, the common modes of transmission and the most common microbes that infect a particular location of the respiratory tract. Objectives: 1. defense mechanisms the body uses to protect itself from infections. 2. identify the microbes normally found in the respiratory tract (normal flora). 4. the mechanisms microbes use to infect the respiratory tract. 5. The common microbial pathogens and the locations they usually infect.

5. Respiratory Tract Pathogens Wide Ranges of Organisms 1)Viruses = Rhinoviruses, Respiratory syncitial virus (RSV), Adenoviruses, Influenza, Parainfluenza 2)Group A streptococci = pharyngitis 3)Other streptococci = S. pneumoniae = sinusitis, Group B = pneumonia of infants 4)Other microorganisms = C. diphtheriae, M. pneumoniae, Fungi Parasites

6. The respiratory tract is the most common site for infection by pathogens. Direct contact with the physical environment and is exposed to microorganisms in the air. The human respiratory tract is exposed to many potential pathogens via the smoke, soot, and dust that is inhaled from the air. It has been calculated that the average individual ingests about 8 microorganisms per minute or 10,000 per day.

7. The anatomy of the respiratory tract – elimination of particles and potential pathogens. Nasal cavity has a mucociliary lining. The inside of the nose is lined with hair. The turbinate bones ("baffle plates") are covered with mucus which collect particles not filtered by nasal hairs. The adenoids and tonsils are lymphoid organs in the upper respiratory tract that are quite important in developing an immune response to pathogens. Mucus is secreted by both single and subepithelial mucus-secreting cells. There are two main obstacles a bacterium or virus must overcome in order to initiate an infection in the respiratory tract. 1.The microorganism must avoid being caught up in the mucus layers of the upper respiratory tract, being transported to the back of the throat, and eventually being swallowed. 2.If the invader has avoided the physical defense mechanisms of the upper respiratory tract, and is deposited in the lower respiratory tract or lung, it must either avoid phagocytosis, or be able to survive and multiply in the phagocytic cell.

8. Normal Flora Organisms of the Nose, Nasopharynx, and Oropharynx I NOSE: 1.The most common bacteria found in the nose are staphylococci. These organisms are found just inside the nares and include Staphylococcus aureus and S. epidermidis. 2.In addition to the staphylococci, aerobic corynebacteria ("diphtheroids") can be cultured from the nasal surfaces. 3.Small numbers of Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae can also be found in the nasopharynx. However, most of these strains are not encapsulated or virulent. It should be noted that nonencapsulated, nontypable H. influenzae has been shown to play a significant role in the pathogenesis of otitis media.

9. Normal Flora Organisms of the Nose, Nasopharynx, and Oropharynx II OROPHARINX 1. The nose and the oropharynx contains large numbers of S. aureus and S. epidermidis. 1. The most important group of microorganisms native to this body niche are the alpha-hemolytic streptococci or viridans streptococci: S. mitis, S. mutans, S. milleri, and S. salivarius. 2. Additionally, cultures from this region usually show large numbers of diphtheroids, Moraxella catarrhalis, and small Gram-negative cocci related to Neisseria species.

10. Role of normal flora The normal flora of these areas have two main functions that play a role in maintaining the healthy state of the host. 1.The organisms compete with pathogenic organisms for potential attachment sites. 1.These organisms often produce substances (toxins or acids) which are bactericidal.

11. Mechanisms Used By Respiratory Tract Pathogens To Initiate Disease I ID - Sufficient number of infectious agent inhaled Airborne microbes. Alive and viable while in the air. The organism must be deposited on susceptible tissue in the host.

12. Mechanisms Used By Respiratory Tract Pathogens To Initiate Disease II 1.Colonize surfaces before it can cause obvious disease. 2.Mechanisms used especially by respiratory tract pathogens:  Bacterial adherence factors = F and M proteins of Strep. pyogenes, Hemagglutinins of B. pertussis.  Extracellular toxins = diphtheria toxin; pertussis toxin.  Growth in host tissue = viruses, chlamydia sp.  Evasion of host immunity = capsules of Strep. pyogenes (also M protein), S. pneumoniae and H. influenzae by inhibiting phagocytosis.

13. The Common Cold

14. ETIOLOGY EPIDEMIOLOGY The common cold is caused by a multitude of organisms. 90 percent of the cases of the common cold are due to viruses. The common cold is worldwide in it's distribution and is spread person-to-person. Most commonly the viruses are spread during hand- to-hand contact (shaking hands, etc.). The average child (less than 5 years of age) will get 5-7 colds per year and the average adult will get 1-2 colds per year. The common cold is seen mostly in the winter months. More infections in these months occur due to more person-to-person contact during this time of year. The most common cause of the common cold is the rhinoviruses (10 to 25%).

15. Nonbacterial Agents that Cause Upper Respiratory Tract Infections of Man Myxoviruses Influenza A, B, C Parainfluenza 1, 2, 3, 4 Respiratory Syncytial Virus 1 (maybe 2) Coronaviruses 1 Picornaviruses Rhinoviruses- most common cause, > 100 types Coxsackie virus A 24 (perhaps only A 21 causes respiratory illnesses ) Coxsackie virus B 6 (perhaps only B 4, B 5 cause respiratory illnesses) Echoviruses 31 (perhaps only types 11, 20, 25 cause respiratory illnesses) Adenoviruses 34 (types 1, 2, 3, 5, 7, 14, 21 are responsible for respiratory illnesses) Mycoplasma pneumoniae

16. Rhinoviruses These viruses are responsible for 25% of the colds seen in the U.S. There are at least 100 immunologically distinct rhinoviruses. This makes vaccine production virtually impossible. 80% of these bind to ICAM-1on the human epithelial cells. These viruses are picornaviruses labile to pH of 3 therefore they are not present in the gastrointestinal tract as one would see the poliovirus. These viruses also grow optimally at 33° C which is the temperature of the nasal mucosa of humans.

17. Coronaviruses These viruses are enveloped RNA viruses. More than 20 strains of coronaviruses have been obtained from humans. In adults coronaviruses can cause from 10 to 24% of common colds.

18. Coxsackieviruses and Echoviruses Both these viruses are picornaviruses which are placed in the enterovirus category due to their residence in the intestines. Coxsackieviruses are grouped into groups A and B. Each group consists of several serotypes. Echoviruses are not grouped but several types exist. Usually these viruses cause aseptic meningitis and pleurodynia (pain in the intercostal muscles due to irritation of pleural surfaces) but occasionally they have been found to cause the common cold.

19. Myxoviruses This group of viruses contains Influenza viruses, Parainfluenza viruses, and Respiratory Syncytial virus; all of which can cause the common cold. Influenza viruses (types A, B, and C) typically cause influenza, which we will discuss later, however it can also cause the common cold. In adults the four types of parainfluenza viruses can cause the common cold, however, in children these viruses can cause severe disease including croup, bronchitis, and pneumonia. Respiratory syncytial virus causes the common cold in adults. In children it is associated with severe lower respiratory tract infections.

20. Adenoviruses Only a few of the 34 types of adenoviruses cause the common cold. These infections are particularly a problem in military recruits.

21. Mycoplasma pneumoniae This organism is not a virus but rather a cell-wall deficient bacterium. This organism can cause respiratory infections that range from the common cold to bronchopneumonia.

22. PATHOGENESIS The suspectable person acquires the virus by direct contact or via inhalation of droplets. The cells lining the nasal passages and the pharynx are infected by the virus. Rhinovirus attaches itself to the cells lining the nasal region by binding to ICAM-1 (InterCellular Adhesion Molecule-1). Inflammatory changes occur with hyperemia, edema, and leukocyte inflammation. The ciliated columnar epithelial cells are destroyed and slough off. The destruction reaches its peak by day 2 to 5. Regeneration of the cells begins quite quickly with new cells formed by about the 14th day. The acute phase of the illness presents with a runny nose. Large amounts of material is produced that is clear and mucoid. After 1 to 2 days secondary bacterial infection by the normal flora causes the secretions to become mucopurulent. If severe blockage of the sinus ostia and the eustachian tube occurs it may lead to paranasal sinusitis or otitis media.

23. MANIFESTATIONS Initially, the patients experiences nasal stuffiness, sneezing, and headache. Rhinorrhea then occurs with increasing severity. General malaise, lacrimation (secretion and discharge of tears), sore throat, slight fever, and anorexia are common in moderate to severe cases. If the organisms get into the trachea and bronchi then a tracheobronchitis develops and the patients may start coughing and feeling substernal discomfort.

24. DIAGNOSIS This is largely dependent on the patients symptoms, the localization of the disease process, the time of year, and an afebrile course. Laboratory culture of the viruses has been done but is very impractical. Serology is also unnecessary but is available. Prognosis: Usually, the patient totally recovers in 1 week. Complications are usually related to extension of infection to the lower respiratory tract resulting in bronchitis, or inflammation of the nasal ostia/eustachian tube resulting in paranasal sinusitis/otitis media.

25. THERAPY and PREVENTION Supportive therapy to ease the patients discomforts. WASH your hands and disinfect contaminated objects. Avoiding hand contact with other people during the cold season.

26. Pharyngitis

27. ETIOLOGY and EPIDEMIOLOGY Pharyngitis is common all over the world. In temperate climates it is most common during the winter and early spring. Acute pharyngitis is a very common patient complaint in office-based primary care practices (Family/General practice, pediatrics). Many different microbes can cause pharyngitis as a single manifestation or as part of a more generalized illness (see table below). The sore throat, malaise and fever is quite distressing to patients however, with few exceptions (ex. diphtheria), this illness is benign and self-limiting.

28. Approximately, 90 percent of sore throats in adults and 60 to 75% of sore throats in children are caused by viral agents. The beta hemolytic group A streptococcus (Streptococcus pyogenes) is the most common bacterial cause of acute pharyngitis accounting for 15-30% of cases in children and 5-10% of cases in adults. The use of an antimicrobial agent is indicated in therapy for "strep throat" Not treating "strep throat" can result in peritonsillar abscess, mastoiditis, rheumatic fever. Treatment of viral pharyngitis with antimicrobial agents is useless.

31. PATHOGENESIS I Viral pharyngitis The viruses gain access to the mucosal cells lining the nasopharynx and replicate in these cells. Damage to the host is often due to damage to cell in which the virus is replicating.

32. PATHOGENESIS II Bacterial pharyngitis Streptococcus pyogenes - person to person spread, The bacterial cell attaches to the mucosal epithelial cells via F and M proteins. Cellular and extracellular products appear to aid the bacterial invasion of the mucosa and its ensuing clinical manifestations. Direct extension to other sites can occur but is now quite rare. Nonsuppurative lesions resulting in rheumatic fever and glomerulonephritis still occur following strep throat infections.

33. PATHOGENESIS III Corynebacterium diphtheria- The bacterium is not very invasive and remains localized on the mucosal surfaces of the upper respiratory tract. Only Corynebacterium diphtheriae lysogenic for the bacteriophage carrying the toxin gene causes diphtheria. Disease is spread person to person by droplets in the colder months of the year. Healthy carriers, convalescent patients, and patients incubating the disease are the best transmitters of infection to others. Damage to the pharynx is caused by the diphtheria toxin which kills the mucosal cells by ADP-ribosylating elongation Factor II. The toxin can also cause damage to the heart and nerves Chlamydia pneumoniae- causes about 5% of the infections. Subacute onset and pharyngitis are common. Often a biphasic pattern is observed, with pharyngitis resolving before bronchitis or pneumonia develops.

34. Sinusitis

35. ETIOLOGY and EPIDEMIOLOGY The most common agents responsible for acute sinusitis are: Streptococcus pneumoniae, Haemophilus influenzae, Chlamydia pneumoniae Less common causes of sinusitis are: Staphylococcus aureus Streptococcus pyogenes, Gram-negative bacilli, respiratory viruses Chronic sinusitis is usually caused by a combined anaerobic and aerobic bacterial infection. Infection of the sinuses may follow the common cold, dental extractions, rhinitis due to allergies, and jumping into water forcing infected water into the sinuses. Infections of the sinuses occur mostly in the winter months.

36. PATHOGENESIS Obstruction of the paranasal sinusal ostia impedes drainage of mucus secretions. Bacteria can grow in these secretions irritating the underlying mucosa producing more secretions. Death and sloughing off of the mucosal cells occurs but cells will regenerate after the infection has cleared. Chronic sinusitis can result in irreversible damage to the mucosa and may cause polyps and mucoceles (mucous polyp, dilatation of a cavity with an accumulation of mucous) to form.

37. Respiratory airway infections

38. Epiglottitis, Laryngitis and Laryngotracheobronchitis

39. Overview Epiglottitis, laryngitis and laryngotracheo bronchitis are acute inflammatory diseases that involve the upper airway. These diseases are often collectively called croup. The most common and serious hazard of these diseases is obstruction of the airway. This is particularly important for the very young since their airways are much more narrow.

40. ETIOLOGY and EPIDEMIOLOGY The following organisms infect the upper airway: Haemophilus influenzae type b (capsular type), causes a very severe epiglottitis. Corynebacterium diphtheriae can also extend to the larynx from the pharynx.

41. Laryngitis: Parainfluenza viruses there are 4 types of virus. Types 1,3, and 4 are associated with the common cold and pharyngitis; types 1 and 3 are associated with croup; and types 1 and 3 are associated with bronchitis and bronchopneumonia. Adenovirus, Echovirus Influenza viruses typically cause lower respiratory tract infections but may infect the upper airway. Respiratory Syncytial viruses can cause croup but is usually associated with bronchiolitis or bronchopneumonia in infants. These infections are worldwide in distribution.

42. Mycoplasma pneumoniae Person-to-person contact is the usual means of spread. Young children are most susceptible to croup. H. influenzae causes infection most commonly in children ages 6 months to 2 years. By 6 to 10 years of age children have immunity to the parainfluenza viruses. Parainfluenza infections can occur anytime in the year.

43. Acute Bronchitis

44. ETIOLOGY and EPIDEMIOLOGY The following agents can cause bronchitis: Respiratory viruses that infect the upper respiratory tract Mycoplasma pneumoniae, Chlamydia pneumoniae, The following four organisms cause other symptoms which are characteristic of infection however bronchitis may be part of the symptoms observed Bordetella pertussis, Salmonella typhi, Measles virus, Streptococcus pyogenes,

45. Bronchitis usually occurs after some previous upper respiratory tract with extension of the infection to the bronchial tree. The predisposing factors for the development of bronchitis in children include poor nutrition, allergy, deficiencies in certain IgG subclasses, and rickets. Older predisposed individuals have emphysema or chronic respiratory diseases such as tuberculosis.

46. Bronchiolitis

47. This is an acute viral infection with a favorable outcome. The infection is usually self-limiting and is normally occurs in infants (less than one year old). The following agents cause bronchiolitis: Respiratory Syncytial virus (RSV is the most common) Influenza viruses Adenoviruses Rhinoviruses Parainfluenza viruses = type 3 Mycoplasma pneumoniae

48. Influenza

49. Although, it is a self-limiting disease severe complications leading to fatalities are seen in the very young, the elderly, those with underlying cardiovascular and pulmonary diseases, and women in their third trimester of pregnancy.

50. ETIOLOGY and EPIDEMIOLOGY The causative agent of the flu or influenza is the Influenza virus.

51. Whooping Cough (Pertussis) Bordetella pertussis, is a Gram-negative small bacillus. The pertussis toxin is believed responsible for most of the tissue damage. The toxin ADP-ribosylates guanine nucleotide-binding proteins affecting regulatory mechanisms in the cells. Other products of importance are the tracheal cytotoxin, a hemolysin, and a filamentous hemagglutinin.

52. Pertussis occurs worldwide and results in one million deaths a year. Up to 50% of the children getting pertussis can be traced to adults with chronic cough, a minority of cases are traced to children passing on the disease, and a significant number have no obvious source. Most of the severe cases are in children less than 1 year old.

53. INTRODUCTION TO LOWER RESPIRATORY TRACT INFECTIONS

54. Enumeration of organisms capable of causing pneumonia

55. Bacteria Streptococcus pneumoniae, Streptococcus pyogenes (Grp A) Streptococcus agalactiae (Grp B), Staphylococcus aureus, Bacillus anthracis, Other Bacillus sp., Nocardia sp., Enterobacteriaceae Pseudomonas aeruginosa, Acinetobacter sp., Burkholderia pseudomallei, Burkholderia mallei, Yersinia pestis, Francisella tularensis, Hemophilus influenzae, Bordetella pertussis Neisseria meningitidis, Legionella pneumophila, Legionella-like bacteria, Bacteroides melaninogenicus, Fusobacterium nucleatum Peptostreptococcus sp., Peptococcus sp., Actinomyces sp. Mycobacterium tuberculosis, Other Mycobacterium sp., Mycoplasma pneumoniae, Branhamella catarrhalis, Chlamydia trachomatis Chlamydia psittaci, Chlamydia pneumoniae, Coxiella burnetii (Q- fever)

56. Viruses Influenza Parainfluenza Cytomegalovirus Adenovirus Epstein-Barr Virus Herpes Simplex Virus Varicella-Zoster Coxsackievirus Measles Rhinovirus Respiratory Syncytial Virus

57. Fungi Aspergillus sp. Mucorales sp Candida sp. Histoplasma capsulatum Blastomyces dermatitidis Cryptococcus neoformans Coccidioides immitis Paracoccidioides brasiliensis Pneumocystis carinii

58. Parasites-Protozoa Plasmodium falciparum Entamoeba histolytica Toxoplasma gondii Leishmania donovani Parasites-Nematodes Ascaris lumbricoides Toxocara sp. Ancyclostoma duodenale Parasites-Cestodes Echinococcus granulosus