MICR 201 Microbiology for Health Related Sciences

1. MICR 201 Microbiology for Health Related Sciences Microbiology- a clinical approach by Anthony Strelkauskas et al. 2010 Chapter 21: Infections of the respiratory system

2. Why is this chapter important? • The respiratory system is the most commonly infected system. • Health care providers will see more respiratory infections.

3. Map for chapter 21

4. The respiratory system • A major portal of entry for infectious organisms • It is divided into two tracts – upper and lower. • The division is based on structures and functions in each part. • The two parts have different types of infection.

5. The respiratory system • The upper respiratory tract (URT): • Nasal cavity, sinuses, pharynx, and larynx • Exposed to microbes and abundant normal microbiota • Infections fairly common • Usually nothing more than an irritation • The lower respiratory tract (LRT): • Lungs and bronchi • Fewer particles and microbes reach LRT • Greatly reduced normal microbiota • Infections more dangerous • Gas exchange takes place here • Easy access to blood stream • Can be very difficult to treat

6. Physical and innate defenses of the respiratory system

7. Pathogens of the respiratory system

8. Pathogens of the respiratory system • Respiratory pathogens are easily transmitted from human to human. • They circulate within a community such as Mycoplasma pneumoniae. • Infections spread easily. • Some respiratory pathogens exist as part of the normal flora such as Streptococcus pyogenes, Streptococcus pneumoniaeand Haemophilus influenzae • Others are acquired from animal sources – zoonotic infections. • Q fever from farm animals caused by Coxiella burnetii • Psittacosis from parrots and other birds caused by Chlamydia psittaci

9. Pathogens of the respiratory system • Water can be a source of respiratory infections. • Legionellosis caused by Legionella pneumophila • Contaminated water can be aerosolized. • Droplets can be inhaled and infection can result.

10. Pathogens of the respiratory system • Fungi are also a source of respiratory infection. • Usually in immunocompromised patients • Most dangerous are Aspergillusand Pneumocystis.

11. Pathogens of the respiratory system • Some pathogens are restricted to certain sites. • Legionella only infects the lung. • Other pathogens cause infection in multiple sites. • Streptococcus pneumoniaecan cause: • Middle ear infections. • Sinusitis. • Pneumonia.

12. Bacteria infecting the respiratory system • Can be divided into groups depending on the infections they cause • Otitis media, sinusitis, and mastoiditis • Pharyngitis • Typical and atypical community-acquired pneumonia • Hospital-acquired (nosocomial) pneumonia

13. Bacteria infecting the respiratory system Obligate intracellular Life cycle with elementary bodies and reticulate bodies No cell wall Require cholesterol

14. Otitis media, sinusitis, masteoiditis • Middle ear, mastoid cavity, and sinuses are connected to the nasopharynx. • Sinuses and eustachian tubes have ciliated epithelial cells. • A virus initially invades the ciliated epithelium. • This destroys the ciliated cells, allowing bacteria to invade. • Mastoiditis is uncommon but very dangerous. • Mastoid cavity is close to the nervous system and large blood vessels.

15. Pharyngitis • A variety of bacteria can cause infection in the pharynx. • A classic infection is strep throat. • Caused by Streptococcus pyogenes(same as Group A streptococci) • Contains M proteins which inhibits phagocytosis • Produces pyrogenic toxins which cause the symptoms seen with pharyngitis • S. pyogenes can also cause scarlet fever when infected with certain phages that code for erythrogenic toxin and toxic shock syndrome.

16. Pharyngitis (strep throat)

17. Streptococcus pyogenes

18. Diphtheria • Caused by the toxin produced by Corynebacterium diphtheriae • Diphteria toxin is a potent inhibitor of protein synthesis • It is a localized infection. • Presents as severe pharyngitis • Can be accompanied by plaque-like pseudomembrane in the throat • Can obliterate airways • Toxinemia causes life threatening systemic symptoms • Multiple organs can be affected • Myocarditis

19. Diphtheria • Therapy • Toxin neutralization most important • Done quickly as possible • Antitoxin only neutralize free toxin • Antibiotics - Erythromycin • Transmission: • Droplet aerosol • Direct contact with skin • Fomites (to a lesser degree) • Vaccination against diphtheria is part of the DTaP protocol. • Diphtheria, Tetanus, acellular Pertussis • Infection is rare when vaccination is in place. • Diphtheria still occurs frequently in some parts of the world. • Particularly where conditions do not permit vaccination.

20. Viral infections of the upper respiratory tract • Rhinovirus infection (the common cold) • Parainfluenza

21. Rhinovirus infection • There are several hundred serotypes of rhinovirus. • Fewer than half have been characterized. • 50% are picornaviruses • Extremely small, non-enveloped, single-stranded RNA viruses • Optimum temperature for picornavirus growth is 33˚C (temperature in the nasopharynx) • Short incubation time, illness lasts about 1 week • There is no specific therapy • ~ 7 days

22. Parainfluenza infections • Belongs to paramyxovirus group • 4 serotypes with varying disease pattern • Single-stranded nonfragmented enveloped RNA virus • Contains hemagglutinin and neuraminidase • Transmission and pathology similar to influenza virus • Parainfluenza virus replicates in the cytoplasm. • Influenza virus replicates in the nucleus. • Parainfluenza is genetically more stable than influenza. • Parainfluenza serious problem in infants and small children. • Cause laryngotracheitisis with croup (barking spastic cough) • Infection becomes milder as the child ages • No specific treatment available

23. Bacterial infections of the lower respiratory tract • Bacterial pneumonia • Tuberculosis • Pertussis • Inhalation anthrax • Legionella pneumonia (Legionnaire’s disease) • Q fever • Psittacosis (Ornithosis)

24. Bacterial pneumonia Lobular Productive cough with purulent sputum Crackling Interstitial Unproductive cough Highly antibiotic- resistant bacteria (MRSA, ESBL-producing gram negative rods)

25. Breath sounds • Normal breath sound: http://jan.ucc.nau.edu/~daa/heartlung/breathsounds/WINAUS/Audio/AEND.WAV • Fine crackles: http://jan.ucc.nau.edu/~daa/heartlung/breathsounds/WINAUS/Audio/FINERALES.WAV • Coarse crackles http://jan.ucc.nau.edu/~daa/heartlung/breathsounds/WINAUS/Audio/COURSERALES.WAV

26. Mycoplasma pneumonia • Mild form of pneumonia • Accounts for about 10% of all pneumonias • Referred to as walking pneumonia • No need for hospitalization. • Most common age for infections between 5 and 15 years. • Causes approximately 30% of all teenage pneumonias • Caused by Mycoplasma pneumoniae • Lacks a cell wall • Acquired by droplet transmission • Infectious dose fewer than 100 pathogens • Found throughout the world, especially in temperate climates

27. Mycoplasma pneumonia • Organism can be shed in upper respiratory secretions for: • 2 to 8 days before symptoms appear. • Up to 14 weeks after symptoms subside. • Usual treatment is erythromycin or tetracycline

28. Nosocomial pneumonia:Pathogenesis • Acquired in the hospital. • Patients who require admittance to hospital typically have conditions associated with local or systemic immunosuppression. • Hospital harbors highly resistant bacteria.

29. Tuberculosis • An estimated 1.7 billion people are infected. • 3 million deaths each year due to Tb. • AIDS and HIV infection have had a significant role in the increase of tuberculosis. • They increase the efficiency of the tuberculosis transmission cycle. • Poverty and poor socioeconomic conditions are breeding grounds for tuberculosis.

30. Tuberculosis • Drug resistance becoming increasingly dangerous. • Major reason for resistance is noncompliance. • Combination therapy for many months • Drugs have pronounced side effects • Early detection is vital. • Initial symptoms are similar to those seen in other respiratory infections – it is important to look for: • Fever, fatigue, weight loss, night sweat, chest pain, shortness of breath, congestion with coughing, thick sputum • X ray shows typical shadows primarily in the upper lobes (aerobic organism)

31. Tuberculosis • Caused by Mycobacterium tuberculosis • Rod-shaped bacillus • Aerobic • Acid-fast • Produces mycolic acid • Makes it difficult to Gram stain • Protects the pathogen from antibiotic therapy and host defenses

32. Tuberculosis: Pathogenesis • For healthy people, tuberculosis is a self-limiting disease. • Host defenses deal with it effectively. • Tuberculosis serious if cell-mediated immunity is compromised or inefficient. • Macrophages ingest bacteria but cannot kill them properly. • If immune response functional macrophages initiate adaptive immune response with granuloma formation (macrophages with Mycobacteria, peripheral lymphocyte wall) • Macrophages become activated by INF gamma secreted by Th cells and can kill bacteria, some bacteria become dormant but can reactivate later in life. • If immune response insufficient, macrophages die, release enzymes, inflammation, liquefaction (caseous necrosis), rupture, release into airway lumen, expectoration.

33. Tuberculosis and tuberculin reaction • Once infected patients show positive tuberculin reaction. • A positive test does not mean active tuberculosis. • If patient is severely immunocompromised, the tuberculin test may become negative. Positive tuberculin test ~ 72 h after injection

34. Tuberculosis: Treatment • Usually a triple therapy containing: • Isoniazid (INH) • Rifampicin (RFP) • Pyrazinamide (PZA) • All three are taken once a day for two months. • INH and RFP are taken for nine more months. • If the strain is drug-resistant, initial treatment includes ethambutol. • Compliance with the drug therapy is very important. • Compliance can be difficult because of side effects. • The drugs are very toxic. • Most serious is liver toxicity. • Major threats: multidrug resistant (MDR) and extremely drug resistant (XDR) strains

35. Tuberculosis: Treatment • Directly observed therapy (DOT) is used to prevent multi-drug-resistant tuberculosis. • DOT involves delivery of scheduled doses of medication by a health care worker. • Patient’s ingestion or injection of drugs is directly administered, observed, and documented. • Ensures that patients receive medication. • DOT helps prevent: • Spread of tuberculosis. • Occurrence of MDR and XDR

36. Pertussis(Whooping cough) • Spread by airborne droplets from patients in the early stages. • Highly contagious • Infects 80-100% of exposed susceptible individuals. • Spreads rapidly in schools, hospitals, offices, and homes – just about anywhere.

37. Pertussis • Caused by Bordetella pertussis • Gram-negative coccobacillus • Does not survive in the environment • Reservoir is humans. • Attaches to ciliated respiratory epithelial cells • Symptoms similar to those of a cold. • Infected adults often spread the infection to schools and nurseries. • However, can produce large quantities of numerous toxins and virulence factors (pertussis toxin, tracheal cytotoxin, and many more) that cause severe damage.

38. Pertussis • Mortality is highest in infants and children under 1 year old. • Immunization against pertussis started in the 1940s. • Continues today as part of DTaP vaccination • Pertussis appears to be making a comeback. • Epidemics are occurring every 3-5 years. • Greatest numbers of infections are among 10-20 year-olds. • People who were not immunized • Shows a relationship between lack of vaccination and infection • Recently, even immunized became infected probably due to waning immunity.

39. Pertussis:Infection has three stages • Catarrhal stage – 1-2 weeks • Persistent profuse and mucoid rhinorrhea (runny nose) • May have sneezing, malaise, and anorexia • Most communicable during this stage • Paroxysmal stage • Persistent coughing • Up to 50 times a day for 2 to 4 weeks • Characteristic whooping sound is heard. • Patient’s trying to catch his/her breath • Apnea may follow the coughing, especially in infants. • Significant increase in lymphocytes. • Convalescent stage • Frequency and severity of coughing and other symptoms gradually decrease.

40. Lung damage in pertussis Fig 1. A bronchus contains sloughed debris (B); its accompanying artery (A) is occluded by a fresh thrombus. Adjacent lung parenchyma is consolidated by hemorrhage (H) Halasa, N. B. et al. Pediatrics 2003;112:1274-1278

41. Pertussis • Most common complications of pertussis are: • Superinfection with Streptococcus pneumonia. • Convulsions. • Subconjunctival and cerebral bleeding and anoxia. • Antibiotics can be used in the early stages. • Limits the spread of infection. • Once the paroxysmal stage is reached, therapy is only supportive. • Vaccination is the best option.

42. Viral infections of the lower respiratory tract • Majority of acute viral infections in the lower respiratory tract are caused by: • Influenza virus. • Respiratory syncytial virus. • Common characteristics of infection are: • Short incubation period of 1 to 4 days. • Transmission from person to person. • Transmission can be direct or indirect. • Direct – through droplets • Indirect – through hand transfer of contaminated secretions

43. Influenza virus • Influenza virus is an orthomyxovirus. • Virions are surrounded by an envelope. • Genome is single-stranded RNA in eight segments. • Allows a high rate of mutation • Antigenic drift • Antigenic shift • Three major serotypes of virus: A, B, and C. • Differences are based on antigens associated with the nucleoprotein • A is best documented serotype • Transmission is primarily via droplet

44. Influenza:Pathogenesis • Virus multiplies in the ciliated cells of lower respiratory tract. • Results in functional and structural abnormalities • Cellular synthesis of nucleic acids and proteins is shut down. • Ciliated and mucus-producing epithelial cells are shed. • Substantial interference with clearance mechanisms • Localized inflammation

45. Influenza:Pathogenesis • Recovery from influenza starts with interferon. • Limits the spread of infection • Next step in defense is mediated by natural killer cells. • Reverses the infection • Finally, cytotoxic T cells and specific antibodies appear in large numbers. • Control the infection • Strong immune response can actually damage the host.

46. Influenza:Pathogenesis • Acute influenzal syndrome can develop. • Short incubation time – about 2 days • Symptoms appear in a few hours. • Fever, myalgia, headache, and occasional shaking chills • Maximum severity appears in 6 to 12 hours and lasts several days followed by gradual improvement. • Nonproductive cough develops • Lethal pneumonia may develop

47. Influenza:Pathogenesis • Bacterial superinfections are a serious complication of influenza. • Haemophilus influenzae • Streptococcus pneumoniae • Staphylococcus aureus • Usually involves the lungs • Can develop during the convalescent stage • Patient is debilitated. • Superinfection is identified by an abrupt worsening of the patient’s condition after initial stability.

48. Influenza:Pathogenesis • Influenza can cause death in three ways: • Underlying disease • People with limited cardiovascular activity or pulmonary function • Superinfection • Bacterial pneumonia and disseminated bacterial disease • Direct rapid progression • Overwhelming viral pneumonia and asphyxia

49. Influenza:Treatment • Two basic approaches • Symptomatic care • Anticipation of potential complications • The best treatments are: • Rest and fluid intake • Conservative use of analgesics for myalgia and headache • Cough suppressants. • Amantadine and rimantadine : block uncoating • Zanamivir and Oseltamivir: block neuraminidase

50. Influenza: Vaccination • Need a new vaccine every year because of shift and drift of the virus • Whole inactivated virus - flu shot • Live, attenuated cold adapted virus (LAIV or FluMist) • Made by combining the HA and NA genes of the targeted virus strain with the six other gene segments from mutant viruses known to have restricted growth at 370C • Nasal-spray inoculation • The reassortment viruses cannot replicate in the lung at core body temperature, but grow well in the cooler nasal mucosa where they stimulate an excellent immune response.