Chapter 19: Diseases that affect the Respiratory System

Signs and Symptoms (Tuberculosis)

Humans easily infected but quite resistant to disease development 85% TB cases contained in the lungs Clinical tuberculosis forms: Primary Secondary Disseminated/extrapulmonary

Prevention (Acute Otitis Media)

Prevnar Hib

Antigenic shift (Influenza)

RNA exchange between different viruses Occurs during coinfection of a host cell More likely to produce pandemic strains

Culture and Diagnosis (Pharyngitis:Streptococcus pyogenes)

Rapid diagnostic tests: on pharyngeal swab specimens Use antibodies to detect group A streptococci High rate of false-negative results (confirm with culturing) Culturing: of pharyngeal swab specimens Plated on sheep blood agar S. pyogenes causes beta-hemolysis Distinguish from beta-hemolytic group B streptococci and enterococci Bacitracin disc test

Signs and Symptoms (Influenza)

Begin in upper respiratory tract, Can progress to lower tract Headache, chills, dry cough, body Aches, fever, stuffy nose, Sore throat Extreme fatigue Secondary infections

Multidrug-Resistant Tuberculosis (MDR-TB)

Defined as being resistant to at least isoniazid and rifampin: Requires treatment of 18 - 24 months with four to six drugs Common in people who have been previously treated with tuberculosis 20% of cases are MDR-TB. In some parts of the world, 50 - 60% of cases are MDR-TB. People with MDR-TB are sicker and have higher mortality rates than those infected with non-MDR-TB

Pneumocystitis (carinii) jiroveci (Community-Acquired Pneumonia)

Discovered in 1909 Agent of pneumocystitis pneumonia One of the most frequent opportunistic infections in AIDS patients Likely transmitted through the inhalation of spores Traditional antifungal drugs are ineffective against Pneumocystitis pneumonia because of the chemical makeup of the organism's cell wall.

Transmission (Common Cold)

Indirect contact, droplet contact

Extrapulmonary Tuberculosis

Infection outside of the lungs: Regional lymph nodes Kidneys (renal tuberculosis) Long bones Genital tract (genital tuberculosis) Brain and meninges (tubercular meningitis) Immunosuppressed patients, young children Untreated tubercular meningitis has a 30 - 50% mortality rate.

Extensively Drug-Resistant Tuberculosis (XDR-TB)

MDR-TB strains with resistance to two additional drugs: Reported in 84 countries 9% of MDR-TB cases worldwide Few treatment options Estimated 70% mortality rate within months of diagnosis India and China have the highest burden of XDR-TB

Signs and Symptoms (Pharyngitis)

Pain Inflammation of the throat Reddened and/or swollen mucosa Swollen tonsils Foul-smelling breath White packets visible on the walls of the throat (streptococcal disease)

Treatment (Pharyngitis:Streptococcus pyogenes)

Penicillin is the antibiotic of choice. Cephalexin used for patients with penicillin allergy. Antibiotic treatment needed to prevent serious sequelae

Symptoms (Common Cold)

Sneezing Scratchy throat Runny nose Fever in children

Virulence Factors (Pharyngitis:Streptococcus pyogenes)

Specialized polysaccharides protect the bacterium from being dissolved by lysozyme. Lipoteichoic acid: contributes to the adherence of the cell wall to the epithelial cells of the pharynx M protein: resists phagocytosis, contributes to adherence Hyaluronic acid capsule: contributes to adhesiveness

Extracellular toxins (Pharyngitis:Streptococcus pyogenes)

Streptolysin O and streptolysin S: Cause beta-hemolysis of sheep blood agar Injure cells and tissues Erythrogenic toxin: Responsible for the bright red rash Induces fever Only lysogenic strains of S. pyogenes that contain genes from a temperate bacteriophage can synthesize this toxin.

Causative Agents (Pharyngitis)

The same viruses causing the common cold Result of mechanical irritation from prolonged shouting or drainage from the sinus cavity Most serious cases of pharyngitis caused by: Streptococcus pyogenes Fusobacterium necrophorum

Transmission and Epidemiology (Tuberculosis)

Transmitted via droplets of respiratory mucus suspended in air Can survive for 8 months in fine aerosol particles Susceptibility influenced by: Inadequate nutrition Debilitation of the immune system Poor access to medical care Lung damage Genetics Infection of poverty: 1.3 million people died from tuberculosis in 2013 60% of U.S. cases are among foreign-born persons People who work in nursing homes, hospitals, or jails are at higher risk.

Pathogenesis (Pharyngitis:Streptococcus pyogenes)

Untreated result in serious complications. Scarlet fever: S. pyogenes infected with a bacteriophage Produces erythrogenic toxin Sandpaper-like rash with high fever Fatality rate up to 95% Rheumatic fever: due to an immunologic cross-reaction between streptococcal M proteins and the heart muscle

Causative Agents (Sinusitis)

Various viruses Various bacteria, often a mixed infection Various fungi Allergies, structural abnormalities are common noninfectious causes

Causative Agent (Common Cold)

over 200 different viruses Rhinoviruses: 99 serotypes Coronavirus Adenovirus Respiratory syncytial virus

Treatment (Acute Otitis Media)

"Watchful waiting" Antibiotics Tympanic membrane tubes

Prevention and Treatment (Healthcare-Associated Pneumonia)

-Elevation of patients' heads to a 45-degree angle helps reduce aspiration of secretions. -Good preoperative education of patients about the importance of deep breathing; and frequent coughing can reduce postoperative infection rates. -Proper care of mechanical ventilators and respiratory therapy equipment -Empiric therapy should begin as soon as hospital-associated pneumonia is suspected.

Hantavirus (Community-Acquired Pneumonia)

-1993: cluster of unusual cases of severe lung edema among healthy young adults in the Four Corners area -Bunyaviridae family: enveloped virus -Associated with the presence of mice in close proximity with humans Transmitted via airborne dust contaminated with urine, feces, or saliva of infected rodents -Localized outbreak in 2012 in Yosemite

Transmission and Epidemiology (Healthcare-Associated Pneumonia)

-Abnormal breathing and aspiration of normal upper respiratory tract biota (and occasionally the stomach) into the lungs -Mechanical ventilation: Organisms take advantage of lowered immune response

Diphtheria

-Causative Agent: Corynebacterium diphtheriae Non-spore-forming, gram-positive, club-shaped -Transmission: Droplet contact, direct contact, fomites -Virulence factor: Diphtheria exotoxin encoded by a bacteriophage -Culture/Diagnosis: Tellurite medium (gray/black colonies) -Prevention: Diphtheria toxoid vaccine (DTaP) -Treatment: Antitoxin plus penicillin or erythromycin

Respiratory Syncytial Virus

-Causative Agent: Respiratory syncytial virus (RSV) -Transmission: Droplet and indirect contact via fomite Peak incidence in the winter and early spring Premature babies and children 6 months or younger are susceptible 100,000 children hospitalized each year -Virulence factor: "Giant cell" (syncytia) formation -Prevention: Passive antibody for high-risk children

Whooping Cough (Pertussis)

-Causative Agent: Bordetella pertussis -Transmission: Droplet contact -Signs and Symptoms: Incubation phase: 3 - 21 days Catarrhal stage: characterized by runny nose, 1-2 weeks Paroxysmal stage: bouts of severe coughing (paroxysm) Recovery phase: susceptible to other respiratory infection -Prevention: DTaP vaccine, antibiotic treatment for contacts Vaccine does not provide lifelong immunity Many outbreaks today due to lack of vaccination, booster

Histoplasma capsulatum (Community-Acquired Pneumonia)

-Endemically distributed in all continents except Australia -Highest incidence in eastern and central U.S. -Grows most abundantly in moist soils high in nitrogen content, especially those supplemented with bird droppings -Extremely widespread distribution measured by injecting fungal extract under the skin

Atypical pneumonias (Community-Acquired Pneumonia)

-Mycoplasma and Chlamydophila Transmitted by aerosol droplets among people in confined to close living quarters. Family, students, the military -"Walking pneumonia" Lack of acute illness in most patients

Normal Biota of the Respiratory Tract

-Normal biota that can cause serious disease: Streptococcus pyogenes Haemophilus influenzae Streptococcus pneumonia Neisseria meningitidis -Normal biota performs the function of microbial antagonism: Reduces the chances of pathogens establishing themselves Lactobacillus sakei suppresses Corynebacterium tuberculostearicum in the sinuses.

Streptococcus pneumonia (Community-Acquired Pneumonia)

-Pneumococcus Small, encapsulated gram-positive flattened coccus, often appearing in pairs (important!!) -Factors that favor the ability of the bacterium to cause disease: Old age The season Underlying viral respiratory disease Diabetes Chronic abuse of alcohol or narcotics -Vaccination encouraged with PPSV23

Culture and Diagnosis (Healthcare-Associated Pneumonia)

-Sputum and tracheal swabs are not useful -Endotracheal tube or bronchoalveolar lavage cultures provide better information but are invasive -Patients already on antibiotics may have an effect on results

Community-Acquired Pneumonia

-Streptococcus pneumonia: 40% of community-acquired bacterial cases -Legionella: Less common Causes serious disease -Haemophilus influenza: Once a major cause HIB vaccine reduced its incidence -Mycoplasma pneumoniae and Chlamydophila pneumoniae: Walking pneumonia -Histoplasma capsulatum: fungus -Hantavirus -Pneumonia can be a secondary effect of influenza.

Treatment (Tuberculosis)

-Treatment of latent TB: Rifampin and rifapentine: 4 and 3 months respectively Isoniazid: 9 months -Treatment of active TB: Rifampin, isoniazid, ethambutol, and pyrazinamide: 2 months Rifampin and isoniazid: either 4 or 7 months, depending on the case -One of the biggest problems with TB therapy is noncompliance -Failure to adhere to the antibiotic regimen results in MDR-TB.

Prevention (Influenza)

-Vaccination -Four types of influenza vaccine: Inactivated vaccine designed for intramuscular injection Inactivated vaccine designed for intradermal injection Live attenuated vaccine administered intranasally Recombinant vaccine: not grown in chicken eggs, designed for intramuscular injection CDC recommends every one over the age of 6 months receive one of these vaccinations. -New vaccine prospects: Target ion-channel proteins to eliminate all strains.

Legionella pneumophila (Community-Acquired Pneumonia)

-Weakly gram-negative bacterium that ranges from coccus to filaments -Able to survive and persist in natural habitats -Widely distributed in tap water, cooling towers, spas, ponds, and other fresh water Resistant to chlorine Can live in association with free-living amoebas -Released during aerosol formation and carried long distances

Pharyngitis:Fusobacterium necrophorum

10 - 30% of all cases in adolescents and young adults. Can invade the bloodstream and other organs, causing Lemierre's syndrome. "Strep" screening may miss infection. Sensitive to penicillin but not azithromycin: Clindamycin is the first-choice drug. No rapid test available

Transmission and Epidemiology (Pharyngitis:Streptococcus pyogenes)

30% of sore throats may be caused by S. pyogenes Transmission via respiratory droplets or direct contact with mucus secretions Carried as "normal" biota by 15% of the population More than 80 serotypes of S. pyogenes exist; immunity is serotype specific

Treatment (Sinusitis)

Broad-spectrum antibiotics for bacterial infection Antifungals and/or surgery for fungal infection

Tuberculosis

Called, "Capitan of the Men of Death" and "White Plague" Has reemerged as a serious threat 2 billion infected

Culture and Diagnosis (Tuberculosis)

Clinical diagnosis of disease relies on these techniques: Tuberculin testing Mantoux Test Chest X rays Generally used after a positive test Blood testing: IGRA Culture Acid-fast staining PCR for identification and susceptibility testing

Pneumonia

Disease characterized by an anatomical diagnosis: Inflammatory condition of the lungs in which fluid fills the alveoli A wide variety of microorganisms can cause pneumonia: Have appropriate characteristics that allow them to penetrate and survive in the lower respiratory tract Avoid phagocytosis or avoid being killed once inside phagocytes More children die of pneumonia than any other infectious disease. U.S.: 2 - 3 million cases, 45,000 deaths per year

Pharyngitis:Streptococcus pyogenes

Gram-positive coccus that grows in chains Does not form endospores Nonmotile Does not form capsules Facultative anaerobe that ferments a variety of sugars Does not produce catalase: Peroxidase system allows for its survival in the presence of oxygen.

Causative Agents (Influenza)

Influenza A, B and C viruses Orthomyxoviridae Lipoprotein envelope Glycoprotein spikes Hemagglutinin (H) Neuraminidase (N) Ion channels ssRNA genome 10 genes on 8 RNA strands

Transmission and Epidemiology (Influenza)

Inhalation of virus-laden aerosols and droplets Indirect contact with fomites Transmission aided by crowding, poor ventilation Drier air of winter facilitates spread of the virus Approximately 36,000 U.S. influenza deaths annually Mainly affects the very young and the very old

Prevention (Tuberculosis)

Limiting exposure to infectious airborne particles Patient isolation in negative-pressure rooms Other extensive precautions Live attenuated vaccine (BCG) Not used in U.S. Bovine tuberculosis bacterium Vaccinated individuals will respond positively to tuberculin test

Secondary (Reactivation) Tuberculosis

Live bacteria can remain dormant, then reactivate Chronic tuberculosis: tubercles expand Severe symptoms develop: "consumption" Violent coughing with greenish or bloody sputum Low-grade fever Anorexia, weight loss Extreme fatigue, night sweats Chest pain Untreated secondary disease has a 60% mortality rate.

Primary Tuberculosis

Minimum infectious dose is about 10 bacterial cells Bacteria multiply inside macrophages Escape leads to cell-mediated attack on bacteria Tubercle formation in lungs Neutrophils release enzymes causing necrotic caseous lesions that heal by calcification T cell action seen in tuberculin reaction

Causative agents (Acute Otitis Media)

Mixed infection of viruses and bacteria Mixed biofilm of bacteria in chronic otitis media

Antigenic drift (Influenza)

Mutation of glycoprotein (H, N) genes Reduced host immune response to virus Produces most seasonal influenza strain

Causative Agents (Tuberculosis)

Mycobacterium tuberculosis Acid-fast bacillus, strict aerobe, slow-growing Mycolic acids, waxes in cell walls Resistant to drying and disinfectants Cord factor linked to virulence M. avium infection in AIDS patients M. bovis infection from unpasteurized milk

Prevention (Pharyngitis:Streptococcus pyogenes)

No vaccine exists Prevention through good hand washing, especially after coughing, sneezing, and before preparing foods and eating

Culture and Diagnosis (Influenza)

Often diagnosed based on symptoms alone Culture and non-culture based tests to identify virus subtype causing infections Rapid influenza tests (immunofluorescence, PCR, ELISA) provide results in 24 hours. Viral culture provides results in 3 to 10 days.

Treatment (Influenza)

One of the first viral diseases for which effective antiviral drugs became available Must be taken early in the infection Amantadine and rimantadine Treat and prevent influenza type A Do not work against influenza type B Zanamivir (Relenza) Inhaled drug Works against influenza A and B Oseltamivir (Tamiflu) Resistance seen in 2007 - 2009

Healthcare-Associated Pneumonia

Up to 1% of hospitalized or institutionalized people experience pneumonia: -Mortality rate: 30 - 50% -Most frequent causes: Pseudomonas aeruginosa Acinetobacter baumanii Streptococcus pneumoniae Klebsiella pneumoniae S. aureus: HAP caused by MRSA Many are polymicrobial in origin

Respiratory viruses (Community-Acquired Pneumonia)

Very common causes of community-acquired pneumonia Either residents of the upper respiratory tract or acquired through daily activities Viral pneumonias are generally mild

Acute Otitis Media

Viral infections of the upper ear lead to inflammation of eustachian tubes, buildup of fluid, and bacterial multiplication in the fluid.

Pathogenesis and Virulence Factors (Influenza)

Virus binds ciliated cells of the respiratory mucosa Severe inflammation, irritation in lungs due to "cytokine storm" Hemagglutinin (H) binding to host cell receptors Neuraminidase (N) breaks down mucous of the respiratory tract, assists in viral budding/release 2009 H1N1 variants bound lower, more efficiently, in respiratory tract causing massive cytokine storm

Pathogenesis and Virulence Factors (Tuberculosis)

Waxy cell wall enhances survival in environment and within macrophages Stimulates strong cell-mediated immune response enhancing disease pathology