2. microbial diseases of respiratory system AO rev3.pdf

Chapter 24 Microbial Diseases of the Respiratory System Pharmacy Upper respiratory tract: nose, pharynx and auditory tubes Lower respiratory tract: larynx, trachea, bronchial tubes, and alveoli Microbiology II : 1 Dr. Mohammad Al-Najjar and Dr. Amin Omar : Respiratory System Anatomy 2 Structure and...

Chapter 24 Microbial Diseases of the Respiratory System Pharmacy Upper respiratory tract: nose, pharynx and auditory tubes Lower respiratory tract: larynx, trachea, bronchial tubes, and alveoli Microbiology II : 1 Dr. Mohammad Al-Najjar and Dr. Amin Omar : Respiratory System Anatomy 2 Structure and function of the Respiratory System 1. The upper respiratory system consists of the nose, pharynx and auditory (eustachian) tubes. Defense structures: – Coarse hairs in the nose filter large particles from air entering the respiratory tract. – The ciliated mucous membranes of the nose and throat trap airborne particles and remove then from the body – Lymphoid tissue, tonsils, and adenoids provide immunity 3 2. The lower respiratory system consists of the larynx, trachea, bronchial tubes, and alveoli. Defenses structures: – The ciliary escalator of the lower respiratory system helps prevent microorganisms from reaching the lungs. – Macrophages in alveoli phagocytose microbes in the lungs – Respiratory mucus contains IgA antibodies. 4 Normal microbiota of the Respiratory System 1. 2. The normal microbiota of the nasal cavity and throat can include pathogenic microorganisms. The lower respiratory system is usually sterile because of the action of the ciliary escalator. 5 Upper Respiratory System Diseases Pharyngitis Caused by: S. pneumoniae Laryngitis S. pyogenes viruses Tonsillitis Sinusitis : caused by bacteria viruses and fungi Epiglottitis: H. influenzae type b Most respiratory tract infections are self-limiting. – An illness or condition which will either resolve on its own or which has no long-term harmful effect on a person’s health. 6 Bacterial Diseases of the upper respiratory system 1.Streptococcal pharyngitis (strep throat): – This infection is caused by group A -hemolytic streptococci, the group that consists of Streptococcus pyogenes. – Symptoms of this infection are inflammation of the mucous membrane and fever; tonsilitis and otitis media may also occur. – Preliminary rapid diagnosis is made by indirect agglutination tests. – Definitive diagnosis is based on a rise in IgM antibodies. – Penicillin is used to treat streptococcal pharyngitis. – Immunity to streptococcal infections is type-specific. – Strep throat is usually transmitted by droplets but at one time was commonly associated with unpasteurized milk. 7 Streptococcal Pharyngitis Also called strep throat Streptococcus pyogenes Resistant to phagocytosis Cause disease by: – Streptokinases lyse clots – Streptolysin is cytotoxic (exotoxin) Diagnosis by enzyme immunoassay (EIA) tests Complications of Strep Throat as: – rheumatic fever – Glomerulonephritis (kidney infection) 8 Scarlet fever (‫)حمى قرمزية‬: – Strep throat, caused by an erythrogenic toxinproducing S. pyogens, results in scarlet fever. – Symptoms include a red rash, high fever, and enlarged tongue. 9 2. Diphtheria Caused by Corynebacterium diphtheriae: Gram-positive rod Diphtheria toxin produced by lysogenized C. diphtheriae – A membrane, containing fibrin and dead human and bacterial cells, forms in the throat and can block the passage of air. – The exotoxin inhibits protein synthesis, and heart, kidney, or nerve damage may result. – Antitoxin must be administered to neutralize the toxin, and antibodies can stop growth of the bacteria. Prevented by DTaP vaccine (combined vaccine against Diphtheria, Tetanus, and Pertussis) – Diphtheria toxoid 10 Corynebacterium diphtheriae 11 3.Otitis Media Caused by: Streptococcus pneumoniae (35%) Haemophilus influenzae (20–30%) Moraxella catarrhalis (10–15%) Streptococcus pyogenes (8–10%) Staphylococcus aureus (1–2%) Incidence of S. pneumoniae reduced by vaccine 12 Viral Disease of the Upper Respiratory System The The Common Cold Any one of approximately 200 different viruses can cause the common cold; Symptoms include sneezing, nasal secretions, and congestion, Sinus infections, lower respiratory tract infections, laryngitis, and otitis media can occur as complications of a cold. Colds are most often transmitted by indirect contact. Rhinoviruses (30–50%) – Coronaviruses (10–15%) – Rhinoviruses prefer temperatures slightly lower than body temperature. The incidence of colds increases during cold weather, possibly because of increased interpersonal indoor contact or physiological changes. Antibodies are produced against the specific viruses. 13 Lower Respiratory System Diseases Many of the same microorganisms that infect the upper respiratory system also infect the lower respiratory system. Caused by Bacteria, viruses, and fungi Diseases of the lower respiratory system include – Bronchitis – Bronchiolitis – Pneumonia 14 Bacterial diseases 1. Pertussis (Whooping Cough) Caused by Bordetella pertussis Gram-negative coccobacilli Cytotoxin is Pertussis toxin Tracheal cytotoxin of cell wall damages ciliated cells Prevented by DTaP vaccine (acellular Pertussis cell fragments) The disease symptoms; Stage 1: catarrhal stage, like common cold Stage 2: paroxysmal stage—violent coughing sieges Stage 3: convalescence stage Treatment of pertussis with antibiotics, most commonly erythromycin or other macrolides, is not effective after onset of the paroxysmal coughing stage but may reduce transmission. 15 2. Tuberculosis Caused by Mycobacterium tuberculosis – Acid-fast rod; – transmitted human-to-human Other types; – M. bovis: not transmitted from human to human – M. avium-intracellulare complex infects people with late-stage HIV infection Treatment: prolonged treatment with multiple four antibiotics, isoniazid, ethambutol, pyrazinamide, and rifampin. Vaccines: BCG vaccine, live culture of avirulent M. bovis; not widely used in United States ❑ Diagnosis of Tuberculosis Tuberculin skin test screening – Positive reaction means current or previous infection – Followed by X-ray or CT exam, acid-fast staining of sputum, culturing of bacteria 16 Figure 14.10c Epidemiological graphs. BCG vaccine Reported cases per 100,000 people 120 100 80 60 40 20 0 1948 1958 1968 1978 1988 1998 2008 Year Reported tuberculosis cases, 1948–2010 17 Stages of Tuberculosis 18 19 Stages of Tuberculosis 20 21 22 3. Pneumococcal Pneumonia Caused by Streptococcus pneumoniae: – encapsulated diplococci Symptoms: infected alveoli of lung fill with fluids; interferes with oxygen uptake, fever, breathing difficulty chest pain, rust-colored sputum. Diagnosis: The bacteria can be identified by: – the production of alpha-hemolysins, – inhibition by optochin (derivative of hydroquinine( – bile solubility – capsule serological tests. Treatment: macrolides, fluoroquinolones Prevention: pneumococcal vaccine. A vaccine consists of purified capsular material from serotypes of S. pneumoniae. 23 4.Haemophilus influenzae Pneumonia Gram-negative coccobacillus Predisposing factors: alcoholism, poor nutrition, cancer, or diabetes Symptoms: resemble those of pneumococcal pneumonia Diagnosis: isolation; special media for nutritional requirements (hemoglobin components V and X factors ( hemin and Nicotinamide adenine dinucleotides) Treatment: third generation cephalosporins 24 5. Mycoplasmal Pneumonia Primary atypical pneumonia; walking pneumonia Caused by Mycoplasma pneumoniae – Pleomorphic, wall-less bacteria Common in children and young adults Symptoms: mild but persistent respiratory symptoms; low fever, cough, headache (3 weeks of longer) Diagnosis: PCR and serological testing Treatment: tetracyclines (eliminate the symptoms but doesn’t eliminate the bacteria) 25 6. Legionellosis Caused by Legionella pneumophila – Gram-negative rod – which is capable of replication within macrophages. Found in water Transmitted by inhaling aerosols; not transmitted from human to human Symptoms: potentially fatal pneumonia that tends to affect older men who drink or smoke heavily, high fever of 40.5°C, cough Diagnosis: culture on selective media, DNA probe Treatment: erythromycin 26 7. Chlamydial Pneumonia Caused by Chlamydophila pneumoniae Obligate intracellular Transmitted from human to human Symptoms: mild respiratory illness common in young people; resembles mycoplasmal pneumonia Diagnosis: serological tests Treatment: tetracyclines 27 8. Psittacosis (Ornithosis) Derived from the disease’s association with psittacine birds, such as parakeets and other parrots The causative agent is Chlamydia psittaci (Gram negative obligate intracellular) inhalation of dried particles from infected birds droppings. Psittacosis is a form of pneumonia that usually causes fever, coughing, headache, and chills (inflammation of liver brain and heart 3-4 weeks). Tetracycline is a treatment option Psittacosis is diagnosed by isolating the bacterium in embryonated eggs or by cell culture. 28 PCR can be used to identify the Chlamydia species. 9. Q Fever The causative agent is the obligately parasitic, intracellular bacterium Coxiella burnetii Cases of acute Q fever usually feature symptoms of high fever, headaches, muscle aches, and coughing C. burnetii is a parasite of several arthropods, especially cattle ticks. Cattle ticks spread the disease among dairy herds, and the microbes are shed in the feces, milk, and urine of infected cattle The disease is spread to humans by ingesting unpasteurized milk and by inhaling aerosols of microbes generated in dairy barns. 29 Viral diseases 1. Viral Pneumonia Viral pneumonia occurs as a complication of influenza, measles, or chickenpox. Viral etiology suspected if no other cause is determined SARS-associated coronavirus emerged in Asia 2003 In 2012-2017, Middle East respiratory syndrome coronavirus (MERS-CoV) was first reported in Saudi Arabia COVID-19 (SARS-Cov-2) has been reported as pandemic since Dec 2019 in China and spread worldwide. 30 2. Respiratory Syncytial Virus (RSV) Common in infants; 4,500 deaths annually Causes cell fusion (syncytium) in cell culture (virus-induced cell fusion facilitates the transfer of viral genomes to the neighboring cells). Symptoms: pneumonia in infants Diagnosis: serological test for viruses and antibodies Treatment: humanized monoclonal antibodies, (palivizumab), ribavirin (sever cases). 31 3. The Influenza Virus Is caused by Influenzae virus and is characterized by chills, fever, headache, and general muscular aches. No intestinal symptoms Hemagglutinin (H) spikes used for attachment to host cells and neuraminidase (N) spikes project from the outer lipid bilayer of the virus used to release virus from cell Viral strains are identified by antigenic differences in the H and N spikes; they are also divided by antigenic differences , their protein coats (A, B, and C). Antigenic Shifts that alter the antigenic nature of the H and N spikes make natural immunity and vaccination of questionable value. (Spanish flu 1918) 32 Antigenic drift – Point mutations in genes encoding HA or NA spikes – May involve only one amino acid – Allows virus to avoid mucosal IgA antibodies Deaths during an influenza epidemic are usually from secondary bacterial infections. 1% mortality, very young and very old Multivalent vaccines are available for the elderly and other high-risk groups. Treatment: zanamivir and oseltamivir inhibit neuraminidase Prophylaxis: multivalent vaccine 33 Influenza Serotypes Type Antigenic Year Severity Subtype A H3N2 H1N1 H2N2 H3N2 H1N1 1889 1918 1957 1968 1977 B None 1940 Moderate C None 1947 Very mild Moderate Severe Severe Moderate Low 34 Fungal Diseases of the Lower Respiratory System Fungi often produce spores that are disseminated through the air Opportunistic fungi are able to grow in – 1- immunosuppressed patients: transplant drugs, and anticancer drugs – 2- AIDS patients. Histoplasmosis Histoplasmosis superficially resembles tuberculosis The causative organism, Histoplasma capsulatum Dimorphic fungus: – it has a yeast-like morphology in tissue growth, – a filamentous mycelium carrying reproductive conidia in soil or artificial media The most effective chemotherapy is Amphotericin B or Itraconazole. Pneumocystis Pneumonia Pneumocystis pneumonia is caused by Pneumocystis jirovecii (fungus that behaves like protozoa) Persons with compromised immunity are the most susceptible to symptomatic Pneumocystis pneumonia The drug of choice for treatment is currently Trimethoprim/Sulfamethoxazole, but there are several alternatives, such as Clindamycin or intravenous Pentamidine. The fatality rate is 100% without treatment. Other Fungi Involved in Respiratory Disease Many opportunistic fungi may cause respiratory disease, particularly in hosts who are immunosuppressed or have been exposed to massive numbers of spores. Aspergillosis is an important example; it is airborne by the conidia of Aspergillus fumigatus. Similar pulmonary infections sometimes result when individuals are exposed to spores of other mold genera, such as Rhizopus and Mucor. Predisposing factors include an impaired immune system, cancer, and diabetes. As with most systemic fungal infections, there is only a limited arsenal of antifungal agents available; Amphotericin B has proved the most useful. Helminthic infection of respiratory system Paragonimus westermani: – – – – – – – – Platyhelminthes trematode Causes paragonimosis Eating raw crayfish It stimulates an inflammatory response that allows it to cover itself in granulation tissue forming a capsule. The eggs in the surrounding tissue become pseudotubercles. If the worm becomes disseminated and gets into the spinal cord, it can cause paralysis; Capsules in the heart can cause death. bad cough, bronchitis, and blood in sputum (hemoptysis) 39 ❖ 1. Intestinal nematodes (Egg infective) Ex. Ascaris lumbricoides Ex. Enterobius vermicularis (pinworm) Eggs, excreted with feces, accidentally ingested by another host. The eggs hatch in the small intestine of the host. The larvae then burrow out of the intestine and enter the blood. They are carried to the lungs, where they grow. The larvae will then be coughed up, swallowed, returned to the small intestine, where they mature into adults. ❖ 2. Tissue and blood dwelling nematodes (Larvae infective) Ex. Trichinella (under cooked meat) A few nematode larvae live in soil can enter a human host directly through the skin. Skin rash where the nematode entered, but the larvae can migrate to the intestine, causing abdominal pain, or to the lungs, causing a cough. It is coughed up in sputum, swallowed, finally carried to the small intestine 40