Respiratory Infections Flashcards
1
Q
What is the upper respiratory tract comprised of?
A
Nose, mouth, nasal cavity, throat and voice box
2
Q
What is the lower respiratory tract comprised of?
A
Windpipe, lungs and bronchus
3
Q
Name some tiers of defence which are used to protect the respiratory tract against infection.
A
Anatomical barriers such as cilia and mucous.
Tight network of dendritic cells within the respiratory mucousa.
Alveolar macrophages
Inflammatory cells, specifically neutrophils which are rapidly recruited.
Memory T-cells found in the interstitium around the bronchi, alveoli and vessels
4
Q
What reflex are cilia of the respiratory tract associated with and what do they use.
A
The cilia are associated with the cough reflex and use mucociliary apparatus with immunoglobulin A.
5
Q
Describe the cilia of smokers and how this affects risk of respiratory infection.
A
Smokers have slower moving cilia so movement of mucus is slowed. This increases risk of respiratory infections.
6
Q
Describe the purpose of mucus in the respiratory tract.
A
Any foreign particles are entrapped in mucus and travel to the back of the throat by ciliary action.
7
Q
Describe the purpose of dendritic cells within the respiratory mucosa.
A
Detect and catch any invading organisms and bring them to the draining lymph nodes. This generates an adaptive immune response.
8
Q
What are the purpose of alveolar macrophages in the respiratory tract ?
A
o Catch particles that reach the alveoli.
o These are environments rich in defence elements; IgG, complement, surfactant and fibronectin.
9
Q
Describe the purpose of rapidly recruiting inflammatory cells in the respiratory trac.
A
o Depending on the load of pathogens and the innate immune processes locally involved.
10
Q
When will memory T-cells be found in the intersitium around the bronchi and vessels ?
A
Once adaptive immunity is involved.
11
Q
Is the respiratory tract a sterile environment? Explain.
A
The respiratory tract is not a sterile environment.
Many microbiome are present, with many bacterial species.
12
Q
How can the flora of the respiratory tract help diagnose respiratory tract infections.
A
Healthy microbiome can allow prediction of the likely causative pathogen as species tend to grow in specific niches.
13
Q
Describe when a nasal swab may be the best method of sample collection and what diagnostic methods will be used.
A
Swabs can be used to collect samples when an upper respiratory tract infection is suspected. They will then be used in culture-based or molecular diagnostic methods.
14
Q
Describe when a throat swab may be the best method of sample collection and what diagnostic methods will be used.
A
Swabs can be used to collect samples when an upper respiratory tract infection is suspected. They will then be used in culture-based or molecular diagnostic methods.
15
Q
Where is sputum secreted from and found?
A
o Sputum is secreted from goblet cells found in the surface epithelium lining the respiratory tract and from seromucous glands in the connective tissue layer beneath the mucosal epithelium
16
Q
What is sputum used to diagnose?
A
Lower respiratory tract infections.
17
Q
Outline the features used to describe sputum and what each of them mean.
A
o Mucoid – containing or resembling mucous Purulent – containing pus Mucopurulent – containing pus and mucous Frothy – visible froth Viscous – thick and sticky Blood-stained – visible blood present
18
Q
What is a bronchoalveolar lavage and what are they used to diagnose?
A
o A bronchoalveolar lavage is when a measured amount of fluid is introduced to the respiratory tract using a bronchoscope and then collected for examination. They are used in the diagnosis of lower respiratory tract infections.
19
Q
Outline some diagnostic methods for respiratory infections.
A
Culture Microscopy Serology Antigen detection assays PCR
20
Q
What does serology detect.
A
o Serology is based around the detection of IgM and IgG.
21
Q
What are the advantages of PCR over culture based techniques?
A
Faster turnaround time, the ability to detect low levels of a pathogen, a lack of dependence on the viability of the target microorganism, little influence of antimicrobial therapy on diagnostic sensitivity, and the ability to be automated.
22
Q
What is whooping cough?
A
A bacterial disease of the lungs and airways.
23
Q
Describe the symptoms and progression of whooping cough.
A
o Paroxysms of many rapid coughs followed by a high-pitched “whoop” sound.
o Vomiting during or after coughing fits is likely.
o Exhaustion after coughing fits.
24
Q
Describe the organism Bordetella pertussis
A
- Gram -ve
- Aerobic
- Coccobacillus
- Multiple virulence factors
25
Name some of the virulence factors of Bordetella pertussis.
o Pertussis toxin (these are thought to mediate whooping cough) , adenylate cyclase toxin, filamentous hemagglutinin and haemolysin.
26
Where do Bordetella pertussis colonise?
Ciliates cells of the mucosa.
27
How is bordetta pertussis transmit?
- Transmission via droplets from the respiratory mucous membranes of infected individuals.
28
What is the causative agent of whooping cough?
Bordetella pertussis
29
Outline the steps in the diagnosis of whooping cough.
- Regan-Lowe Agar
| - Bordet-Gengou Agar
30
Describe how Regan-Lowe agar is used to diagnose whooping cough.
Regan-Lowe Agar consists of charcoal agar with defibrinated horse blood. Charcoal, along with starch, neutralises fatty acids and peroxides, which are toxic to B. pertussis. Horse blood is an added enrichment which supports the growth. Cephalexin inhibits the growth of normal flora of the nasopharynx. Yeasts and fungi are inhibited by the inclusion of amphotericin B. Beef extract and enzymatic digest are incorporated to supply amino acids and other nitrogenous substances that are necessary for growth. Osmotic equilibrium is maintained by the addition of sodium chloride. Niacin (nicotinic acid) is a vitamin which is added for growth promotion.
31
Describe the use of Bordet-Gengou agar to diagnose whooping cough.
Bordet-Gengou agar contains blood, potato extract, and glycerol, with an antibiotic such as cephalexin or penicillin and sometimes nicotinamide. The potato extract provides nitrogen and vitamins, and potato starch absorbs fatty acids; glycerol is used as a carbon source. Regan-Lowe medium has however has replaced Bordet-Gengou medium as the medium of choice for routine diagnosis.
32
How is whooping cough treated?
- Treat persons older than 1 year within 3 weeks of cough onset
- Infants younger than 1 and pregnant women within 6 weeks of cough onset.
Generally treated with antibiotics such as azithromycin, clarithromycin and erythromycin (antibiotic). These are macrolide antibiotics. - Penicillin antibiotic can also be used.
o Beta lactam antibiotic.
33
What are macrolide antibiotics and how do they work to treat whooping cough ?
These are macrolide antibiotics that work by inhibiting bacterial protein synthesis by preventing peptidyltransferase from adding the peptide chain attached to tRNA to the next amino acid.
34
How does penicillin and other beta lactam antibiotics work to treat whooping cough?
Inhibits bacterial cell wall synthesis by binding and inactivating penicillin binding proteins in the cell wall.
Also inhibit the transpeptidation reaction and block cross-linking of the cell wall.
35
What is Diptheria and what is it caused by?
- Bacterial disease caused by Corynebacterium diphtheriae
36
Describe the symptoms and effects caused by Diptheria.
- Sort throat and low grade fever within the first few days
- Development of a dense membrane in more severe cases
o This could be local (e.g. just on the tonsils or pharynx)
o This could be widespread (could cover a wide area of the patient’s respiratory tract).
- ‘Bull’s neck’ in severe cases.
37
Describe the organism Corynebacterium diptheriae.
- Aerobic
- Gram +ve
- Bacillus
38
Where is Corynebacterium diptheriae found?
Inner lining of the throat, mouth and nose.
39
How is Corynebacterium diptheriae transmitted.
Airborne or via close contact with discharge from an infected person's eyes, nose, throat or skin.
40
How do bacteria infect a person and cause diptheria.
When infected by a specific bacteriophage, the bacteria produce a toxin that kills cells in the throat. These cells then join to form the grey-white membrane that is typically seen in cases of diphtheria.
41
Outline the steps used for diagnosis of Diptheria.
Nose/throat swab
Loeffler agar
Mueller-miller tellurite agar
Tinsdale tellurite agar
Toxigenic tests
42
How is Loeffler agar used to diagnose Corynebacterium diptheria?
Contains horse serum, beef extract, dextrose and proteose peptones which supply the complex nitrogenous substances and nutrients necessary to support growth of C. diptheriae.
Sodium chloride is added to supply essential oils.
The medium enhances the development of metachromatic granules as seen in the methylene blue stains.
Formation of granules demonstrates the characteristic celllar morphology of C. diphtheriae.
43
How is Mueller-miller tellurite agar used to diagnose Corynebacterium diptheria?
Contains casein acid hydrolysate and L-tryptophan to provide nitrogenous compounds and magnesium sulphate to supply essential oils.
44
How is Tinsdale tellurite agar used to treat Corynebcterium diptheria?
Supports the growth of all species of Corynebacterium while inhibiting the growth of normal inhabitants of the upper respiratory tract.
Potassium tellurite inhibits all Gram -ve bacteria and most of the upper respiratory tract normal flora.
L-cysteine and sodium thiosulphate form the H2S indicator system.
Black coloration of the colonies results from tellurite reductase activity, resulting in the reduction of tellurium.
Brown halos indicate cystinase activity.
45
Outline the in vitro toxigenic tests used to diagnose Corynebacterium diptheria.
Immunodiffusion, tissue culture
• Elek immunodiffusion test
o Based on double diffusion of diphtheria toxin and antitoxin in an agar medium.
o A sterile, antitoxin-saturated filter paper strip is embedded in the culture medium, and C diphtheriae isolates are streak-inoculated at a 90° angle to the filter paper. The production of diphtheria toxin can be detected within 18 to 48 hours by the formation of a toxin-antitoxin precipitin band in the agar.
46
What in vivo tests are used to diagnose Corynebacterium diptheria.
Rabbit skin test, guinea pig challenge
47
What type of organism causes Legionnaire's disease?
Bacterium
48
What are the symptoms of Legionnaires disease ?
- Cough, shortness of breath, fever, aches and headaches
| - Diarrhoea, nausea and confusion
49
How is Legionnaires disease caught and transmitted?
- Caught from contaminated water systems - linked to air conditioning and water cooling systems
- Aerosol transmission (most common by inhalation of aerosols produced in conjunction with water sprays, jets or mists).
50
What is Legionnaires disease often confused with?
Often confused for Pontiac fever which is a similar but milder infection.
51
What organism causes Legionnaires disease?
Legionella pneumophila
52
Describe the organism Legionella pneumophila
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Gram -ve- Aerobic
- Pleiomorphic (can be many shapes).
o Most commonly seen as bacilli or coccobacilli
- Flagellated
o One monopolar flagella
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53
Why does Legionella pneumophila have a poor gram stain?
may stain poorly due to its unique lipopolysaccharide content in the outer membrane.
54
Outline the steps used to diagnose Legionnaires disease.
Urinary antigen test
Growth of Legionella on media that supports it. Such as Buffered Charcoal YEast Extract Agar.
55
Describe how the urinary antigen test is used to diagnose Legionnaires disease.
o Detects soluble Legionella antigen urine.
| o Detects the most common cause of Legionaire’s disease – L. pneumophila serogroup 1
56
Describe the treatment of Legionnaires disease and explain how these work.
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Antibiotics:
- Macrolides
- Fluroquinolones
o Moxifloxacin
o Gemifloxacin
o Levofloxacin
These antibiotics act by inhibiting the replication and transcription of bacterial DNA by preventing DNA from unwinding and replication.
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57
Describe treatment for Pontiac fever.
For Pontiac fever, antibiotic treatment isn’t prescribed as it is a self-limited illness that patients usually recover from within 1 week.
58
What type of organism causes Tuberculosis?
Bacteria
59
What are the symptoms of Tuberculosis?
- Cough that lasts 3+ weeks
- Chest pain
- Coughing up blood pr sputum
60
How is Tuberculosis transmitted?
- Transmitted by airborne droplets produced when an infected individual coughs, sneezes, shouts or sighs
61
What organism causes Tuberculosis?
Mycobacterium tuberculosis
62
Describe the appearance of Mycobacterium Tuberculosis on a gram stain and why this occurs.
- Appears gram -ve or +ve. This is because of the presence of mycolic acid on the cells surface that makes it impervious to the Gram stain.
63
What staining is used to identify Mycobacterium tuberculosis and what should the result be.
Acid fast stain turns red
64
Describe the organism mycobacterium tuberculosis.
Bacilli
| Aerobic
65
Outline the steps used to diagnose Tuberculosis
TB skin test
TB blood test
Chest X-ray
66
Describe how the TB skin test is used to diagnose Tuberculosis.
o Tuberculin, a purified protein derivative from M. tuberculosis, is injected into the skin on the arm. After 48-72 hours, the test is read and the result will be dependent on the size of the raised area and the category an individual is in. Categories are based on the presence of other diseases such as HIV or recent contact with TB patients (category 1), recent immigration from places with high levels of TB, intravenous drug users, children or those that work in TB labs (category 2) or people with no known risk factors for TB (category 3). There are other characteristics for categories 1 and 2.
67
Describe how the TB blood test is used to diagnose Tuberculosis.
o The TB blood test, also known as an interferon-gamma release assay, tests for the immune reactivity to M. tuberculosis. If someone has been infected with M. tuberculosis, their white blood cells will release interferon gamma. If a blood sample contains interferon gamma, it will react when mixed with M. tuberculosis antigens. ELISAs are generally used to determine the result. The advantage of this test over the skin test is that there is less time to a result.
68
Describe how a Chest X-ray can be used to diagnose Tuberculosis ?
Used to identify lesions that may be related to TB.
69
Outline culturing used to identify Tuberculosis.
Lowenstein-Jensen Agar
Middlebrook Agar
Blood Agar
70
How is Lowenstein-Jensen Agar used to diagnose Tuberculosis.
o Contains egg albumin which when heated, coagulates, providing a solid surface for inoculation. Nitrogen, fatty acids, and proteins are supplied by egg and asparagine. Glycerol serves as a carbon source and is favourable human type rather than bovine type. The green colour comes from malachite green which acts as an inhibitory agent toward microorganisms other than mycobacteria.
71
How is Middlebrook agar used to diagnose Tuberculosis.
o Middlebrook 7H11 Agar contains inorganic salts which are essential for the growth of mycobacteria. Casein hydrolysate serves as a growth stimulant for drug-resistant strains. Glycerol is a source of carbon and energy. It also contains a range of inorganic salts that are essential for growth.
72
How is Tuberculosis treated?
6 months of antibiotics (isoniazid and rifampicin).
Pyrazinamide and ehtambutol used for the first 2 months.
73
How do Isoniazid and rifampicin treat Tuberculosis.
Isoniazid is specific to mycobacteria and inhibits growth by blocking mycolic acid synthesis.
Rifampicin inhibits bacterial cell wall synthesis.
74
How do pyrazinamide and ethanbutol used to treat Tuberculosis?
Pyrazinamide inhibits fatty acid synthesis.
| Ethambutol is thought to inhibit cell wall synthesis by blocking arabinosyl transferase activity.
75
What is pneumonia?
Inflammation of one or both of the lungs.
76
What are the symptoms of Pneumonia?
```
- Multiple symptoms
o Cough
May produce greenish, yellow or bloody mucous
o Fever, sweating and shaking chills
o Shortness of breath
o Rapid, shallow breathing
o Chest pain
o Loss of appetite, low energy and fatigue
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77
What are the causes and transmission methods of pneumonia?
- Multiple causative agents and transmission routes
| o Inhalation of organisms from the nose or throat, via airborne droplets from coughs and sneezes and also via blood.
78
Name some of the possible organisms that cause Pneumonia.
* Chlamydia pneumoniae (bacteria)
* Mycoplasma pneumoniae (bacteria)
* Haemophilus influenzae (bacteria)
* Streptococcus pneumoniae (bacteria)
* Pneumocystis jiroveci (fungi)
* Parainfluenza (viral)
79
Describe how Chlamydia pneummonia are transmitted, the type of Pneumonia caused and describe the organism itself.
* Obligate intracellular
* Gram negative
* Droplet transmission
* Mild pneumonia or bronchitis in adolescents and young adults
* Older adults may experience more severe disease and repeated infections
* Can be asymptomatic to full blown pneumonia
* Outside of the host it exists as an inactive extracellular body which may be taken into a host cell by phagocytosis where it becomes active.
80
Describe how Mycoplasma pneummonia are transmitted, the type of Pneumonia caused and describe the organism itself.
* Bacterium – smallest known genome
* Community Acquired Respiratory Distress Syndrome (CARDS) toxin
* This is a unique virulence factor which helps with colonisation and pathogenesis.
* Lack of cell wall makes it difficult to Gram stain. So cholesterol in membrane is used to keep membrane integrity.
* Lack of cell wall also means it is susceptible to desiccation so airborne droplet transmission only occurs through close contact.
* Also means can’t be treated with some antibiotics
* Lives in mucosa - also strains which reside in genital tract
* Illness ranging in severity from mild respiratory illness to severe pneumonia
* Airborne droplets
* Causes atypical pneumonia
81
Describe how Haemophilus influenzae are transmitted, the type of Pneumonia caused and describe the organism itself.
* Gram negative coccobacilli
* Encapsulated, immotile, non-spore forming
* Encapsulated strains (a-f) express 6 antigentically distinct capsular polysaccharides.
* Serotype b has a polyribosyl ribitol phosphate (PRP) polysaccharide capsule that is a major virulence factor as it protects from phagocytosis in the absence of anticapsular antibodies and facilitates penetration to the blood stream and the cerebrospinal fluid.
* Causes many types of infections, especially in young children
* Pneumonia, meningitis, arthritis
* Transmission occurs through direct contact with respiratory droplets
82
Describe how Streptococcus pneumoniae are transmitted, the type of Pneumonia caused and describe the organism itself.
* Gram positive diplococcus
* Transmitted by direct person to person contact via respiratory droplets
* Causes pneumonia in elderly patients
* Invasive pneumococcal infection
83
Describe how Pneumocystis jiroveci are transmitted, the type of Pneumonia caused and describe the organism itself.
* Several species of Pneumocystis can cause infections in immunocompromised patients (such as those with HIV/ AIDS and PCP).
* Pneumocystis jiroveci: PCP
* Long thought to be a protist
* Mounting evidence, including the identification of genetic sequence homologies with fungi, led to the recategorisation as a fungus
* Symptoms often develop over a few days, often with a high fever.
84
Describe how parainfluenza is transmitted, the type of Pneumonia caused and describe the organism itself.
* Paramyxoviridae
* Four ssRNA viruses
* 1 & 2 associated with croup
* 3 associated with bronchitis & pneumonia
* 4 less common, mild to severe respiratory tract illnesses
* Direct contact with infectious droplets
* Airborne spread from breathing, coughs, or sneezes
85
Describe the diagnosis of pneumonia caused by Chlamydia pneumoniae.
- Can’t grow Chlamydia as they are obligate intracellular.
o Can grow in tissue culture but takes a long time and needs specialised cell set ups such as McCoy cells (mouse fibroblast cells).
o Immunofluorescence, serology and PCR used
o Also rise in antibody titres
o Treatment = tetracyclines
These inhibit protein synthesis by binding to the 30s ribosomal subunit.
86
Describe the diagnosis of pneumoniae caused by mycoplasma pneumoniae
- Difficult to grow as it has no cell wall
- Specialised media used
o SP4 media
o It is highly nutritious due to the addition of beef heart infusion, peptone supplement and yeast extract, and foetal bovine serum.
Yeast extract – provides diphosphopyridine nucleotides
Serum provides cholesterol for cell membrane production and an additional source of protein.
Specific substrates, such as glucose, arginine, or urea, may be added and used in conjunction with pH to differentiate and select for certain mycoplasma.
Amphotericin B, polymyxin B, and penicillin are added to inhibit faster growing contaminants. Phenol Red is added to broth media as a pH indicator.
o Uninoculated broth remains red. But with active metabolism of cultured M.pneumoniae broth acidifies and turns and orange-yellow.
- Complement fixation test (CFT)
- ELISA
- Treatment
o Antimicrobials against M.pneumoniae are bacteriostatic, not bactericidal.
o Second generation tetracyclines
o Macrolides
- Resistant to penicillin
87
Describe the diagnosis of pneumonia caused by Streptococcus pneumoniae.
* Sputum, blood for culture, CSF and urine are used for c-polusaccharide antigen detection
* Microscopy
* Culture
* Blood agar
* Shows alpha-haemolysis under aerobic conditions and beta haemolysis under anaerobic conditions.
* Antigenic detection
* SSS (pneumococcal polysaccharide) in CSF by precipitation with antisera or the latex agglutination test
* Molecular methods
* Susceptible to optochin
88
DEscribe the diagnosis of pneumoniae caused by H.influenzae.
* Grows on chocolate agar, but not blood
* Identification using X (nicotinamide adenine dinucleotide) and V (hemin) factors
* Growth factors
* Latex agglutination and PCR also used
* Treatment varies
* Cephalosporins common as resistance to penicillin exists
* These are beta lactam antibiotics that disrupt the synthesis of the peptidoglycan layer in the bacterial cell wall.
89
Describe the diagnosis of pneumoniae caused by Pneumocystis jiroveci (fungal)
* Does not grow on media so microscopy staining usually used for diagnosis
* Immunofluorescence or Giemsa (purple)
* Blood test for beta-D-glycan cell wall component used
* Treatment
* Trimethoprim/sulfamethoxazole (co-trimoxazole)
* Trimethoprim inhibits the reduction of dihydrofolic acid to tetrhydrofolic acid by binding the enzyme dihydrofolate reductase. Tetrahydrofolic acid is an essential precursor in the thymidine synthesis pathway and interference here will block DNA synthesis. Sulfamethoxazole inhibits dihydropteroate synthase, the enzyme responsible for conversion of PABA to dihydrofolic acid. Inhibition of this pathway prevents the synthesis of tetrahydrofolate and the synthesis of purines and DNA
* PCP is diagnosed using sputum or biopsy
90
Describe the diagnosis of Pneumonia caused by parainfluenza virus.
* PCR
* Uses a respiratory wash which is then used for PCR or antigen tests.
* ELISA
* Viral antigens
* Specific IgG/IgM antibodies
* Cell culture
* Treatment
* None
* Most parainfluenza viruses are mild and only the symptoms are treated.
91
What is Aspergillosis?
A fungal infction of the lungs.
92
Describe the symptoms of Aspergillosis in immunosupressed hosts.
* Invasive pulmonary infection, usually with fever, cough, and chest pain
* May disseminate to other organs, including brain, skin and bone
* Invasive
93
Describe the symptoms of Aspergillosis in immunocompetent hosts.
* Localised pulmonary infection in people with underlying lung disease, allergic bronchopulmonary disease, allergic sinusitis
* Non-invasive
94
How is Aspergillosis transmitted?
• Transmission is by inhalation of airborne conidia (asexual fungal spores).
95
Describe the organisms that cause Aspergillosis and the conditions / areas they live in.
* Aerobic
* Can live in high concentrations of sugar or salt
* Found in a variety of locations such as damp walls, bathrooms and pillows
96
Outline the diagnosis of Aspergillosis.
Clinical X-rays
Culture from sputum of Sabouraud's agar
Cell wall component tests such as ELISA
PCR of ribosomal DNA
97
Why are X-rays used to diagnose Aspergillosis?
To visualise fungi in the lungs
98
How is Sabouraud's agar used in the diagnosis of Aspergillosis?
* The lower pH (5) inhibits bacterial growth
* It contains an enzymatic digest of casein and animal tissues which provides a source of amino acids and nitrogenous compounds.
* It contains dextrose as a carbohydrate and energy source and may contain antibiotics such as chloramphenicol or gentamicin to further inhibit bacterial growth
99
What is Aspergillosis treated with and how do each of these treatments work?
* Antifungals
* Voriconazole
* Works by inhibiting cytochrome P450-dependent 14a-ansterol demethylation, which is a vital step in cell membrane ergosterol synthesis.
* Amphotericin B
* An antifungal which can bind to ergosterol in the membrane and form pores, or may induce ergosterol sequestration away from the membrane, resulting in membrane instability.
* Surgery
* Removal of fungal mass
100
What is flu?
A viral respiratory disease.
101
What are the symptoms of flu?
* Fever
* Headache
* Tiredness (can be extreme)
* Dry cough
* Sore throat
* Nasal congestion
* Body aches
102
How is flu transmitted?
• Transmission by respiratory droplets in coughs and sneezes
103
What virus causes influenza?
Orthomyxovirus
104
What type of genome does the influenza virus have?
ssRNA
105
How any species of influenza virus are there?
4
106
How is influenza virus treated?
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• Mild/moderate
• Management of symptoms
• Severe
• Antivirals
• Oseltamivir (Tamiflu)
• Zanamivir
(For inpatients, oral or enterically administered Oseltamivir may be recommended. For outpatients oral oseltamivir or inhaled zanamivir may be recommended)
They both inhibit neuraminidase which in turn inhibits budding from the hos cell, replication and infectivity.
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