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4.1 Medical Microbiology > Atypical Pneumonia > Flashcards

Atypical Pneumonia Flashcards

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1
Q

What is atypical pneumonia?
(3)

A

A Lower respiratory tract infection where traditional bacteria are not detected

Symptoms tend to be milder and can be both systemic and respiratory

It usually fails to respond to penicillin, ampicillin (or augmentin?)

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2
Q

What are the four TYPICAL pneumonia bacteria?

A

S. pneumoniae
Non typable H.influenzae
M, catarrhalis
GNBS/Enterobacterales

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3
Q

What are the four most common atypical bacteria?

A

Mycoplasma pneumoniae
Chlamydophila species
Legionella pneumophila
Coxiella burnetii

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4
Q

How do the symptoms of atypical pneumonia compare to that of typical pneumonia?
Give symptoms of both

A

milder symptoms

Typical: sudden onset, acute symptoms, fever >38.5, chils, productive purulent cough, very elevated wbc, lobular infection on xray

Atypical: gradual onset, malaise + fatigue, low grade fever, no chills, non-productive or purulent sputa, normal or mild lymphocytosis, patchy or diffuse infection on xray

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5
Q

What is the most common atypical pathogen?

A

Mycoplasma

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6
Q

Comment of the epidemiology of atypical bacterial pneumonia
(3)

A

Mycoplasma and legionella on the rise

In 2017, mycoplasma was the most common cause of atypical
CAP and legionella was the 12th (includes virlal causes of CAP!!)

Between 2015-2018, mycoplasma was the fourth most common cause of bacterial(!!) CAP

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7
Q

Comment on epidemiological trends in atypical penumonia in recent years (3)
- how frequent is atypical pneumonia
- who is affected by atypical pneumonia

A

Incidence of atypical pneumonia across the globe is high, detectable rate >20%

M. pneumonia and C. pneumonia are seen more frequently in younger patients as a milder infection

Legionella has a much higher mortality and is more frequently seen in ICU patients

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8
Q

What is thought to be one of the main reasons for increasing levels of atypical pneumonia being recorded in recent years?

A

This is mostly due to improvements in detection
The introduction of molecular methods of etection such as the BioFire Respiratory panel has meant we are now picking up a lot of these organisms which are generally difficult to culture e.g. Mycoplasma which you cant gram and chlamydia which is very fastidious

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9
Q

What are the three methods used to detect atypical pneumonia?

A

Culture

Serology to detect either Ab(sera) or Ag in patient

Molecular detection

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10
Q

What are some pros and cons of culturing for atypical pneumonia?

A

Cheap method

Usually organisms are fastidious and either do not grow, have limited growth or grow very slowly

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11
Q

What are some pros and cons of using serology for atypical pneumonia?

A

Cheap and rapid testing

Usually retrospective -> after infection has been cleared or treated

Poor sensitivity and specificity

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12
Q

What are some pros and cons of molecular detection for atypical pneumonia?
(5)

A

High senstiivty and specificity

High turn around time

Can use other sample types other than sputa -> sputa can be difficult to collect from atypical patients due to lack of productive cough in infection

Significant improvement in pathogen detection in patients on long term antimicrobial therapy -> this enables us to issue pathogen-directed therapy

Difficulties in interpreting what is infectious versus normal colonisation

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13
Q

In the lab why do we usually not culture atypical pneumonias?

A

These are usually really difficult to grow e.g. Chlamydia requires HELA cells

Atypical pneumonia is using a rate limiting infection -> will clear on its own -> no need to work up and do AST etc etc

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14
Q

What is the most common cause of atypical pneumonia?

A

Mycoplasma pneumoniae

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15
Q

What is Mycoplasma pneumonia, what kind of infections is it involved in, how frequent is it?
(4)

A

Cell wall deficient bactera of the mollicute family

Causes two respiratory syndromes:
- Febrile bronchitis
- Primary atypical pneumonia

Prevalence thought to be underestimated due to poor detection

Most common cause of atypical pneumonia with most people infected being asymptomatic

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16
Q

What two respiratory syndromes is M. pneumoniae involved in?

A

Febrile bronchitis

Primary atypical pneumonia
- a viral like pneumoniae
- known as ‘walking pneumoni’ -> mild symptoms

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17
Q

Comment on the transmission of Mycoplasma pneumoniae, when is incidence highest, what population is it highest in?
(3)

A

Spread via respiratory droplets often during close contact -> high frequency in college dorms

Incubation period of 1-4 weeks allowing for silent transmission in community

Disease occurs year round with increase in incidence in late summer - theorised possibly due to ghaeltachts in Ireland -> not much evidence to back this up

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18
Q

How frequent is Mycoplasma pneumonia in college students, why is this thought to be the case?

A

M. pneumoniae associated with 50% of all LRTI in college students (VERY HIGH INCIDENCE)

Thought to be due to close living quarters -> spread via respiratory droplets

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19
Q

What systems can M. pneumonia CAP affect/infect?
(4)

A

Respiratory symptoms

Skin rashes

Neurological symptoms

Haematological symptoms

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20
Q

What are the respiratory symptoms of M. pneumoniae CAP?
(3)

A

Persistent, non productive cough lasting weeks

Mild fever, sore throat, wheezing, fatigue

RARE: chest pain or difficulty breathing - comparable to typical pneumonia

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21
Q

How does M. pneumoniae affect the skin?

A

Causes skin rashes such as erythema multiforme

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22
Q

What neurological symptoms can M. pneumoniae cause?

A

Headache
Confusion
Encephalitis (very rare)

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23
Q

What haematologic symptoms can M. pneumoniae cause?

A

Very very rare complications

Haemolytic anaemia

Thrombocytopeniae

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24
Q

What are the M. pneumoniae virulence factors?
(3)

A

Adhesins such as P1 adhesin

CARDS toxin

Inflammation

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25
Q

What role does M. pneumoniae p1 adhesin have on virulence?

A

p1 adhesin allows bacteria to adhere to epithelial cells in LRT

This causes cilia dysfunction and cell damage

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26
Q

What is the CARDS toxin of M. pneumonia, what is its role in virulence?
(3)

A

Community-acquired respiratory distress syndrome toxin

Causes localised disruption and cytotoxicity

Inhibits cilary action

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27
Q

How does M. pneumonia utilse inflammation, how does inflammation affect virulence?

A

M. pneumonia causes prolonged inflammation

This causes tissue damage which can contribute to any chronic conditions such as asthma

This can also exacerbate symptoms in those already affected

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28
Q

What do we use to treat M. pneumoniae?

A

We use Macrolides

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29
Q

Why can’t we use B-lactam antibiotics for M. pnuemonia like we would for typical CAPS, why is this significant in diagnosis?
(3)

A

M. pneumonia lacks a cell wall

There is therefore nothing for a B lactam antibiotic to attack -> intrinsically B lactam resistant

This is why atypical pneumonia is queried after first round of antibiotic treatment (B-lactams) fails to clear infection

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30
Q

Comment on Macrolide resistance in M. pneumonia, how frequent is resistance?

A

We didnt have macrolide resistance until relatively recently

Rate of resistance highly dependent on region:
- 3% in Germany
- 10% in France
- 80% in China and Japan

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31
Q

What is challening about the lab detection of Mycoplasma pneumoniae?
(5)

A

Its a mollicute i.e. it has no cell wall which means it has no gram reaction -> cannot be Id’d on smear

Its fastidious and grows very slowly - takes 3 to 4 weeks on blood agar

Sputa sample hard to collect from these patients as they do not have a productive cough when infected

Hard to know what is asymptomatic carriage and what is infectious

Consdirable sero prevalence in up to 30%

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32
Q

Talk about M. pneumonia on culture
(3)

A

Takes 3 to 4 weeks to grow on blood agar

Colonies have a fried-egg appearance

Culture rarely used for routine diagnostics- takes too long

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33
Q

What serological detection methods are available for Mycoplasma pneumoniae?
(3)

A

Cold agglutinin screening test

IgM+IgG by ELISA

DFA-Antigen detection

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34
Q

What is the cold agglutinin screening test for M. pneumonia?
(3)

A

IgM Antibody production in 2nd week of illness

IgM agglutinates O human red cells at 4 degrees but not 37 degress

-> basically a cold agg test

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35
Q

What is the IgM + IgG ELISA for M. pneumoniae?
(5)

A

A retrospective form of IDing M. pneumonia

Antibodies are produced 7 days after onset of symptoms (IgM)

Sensitivity increases to >70% after 16 days of symptoms i.e. higher titre IgM

There is a four fold rise in titre between acute and convalescent phase sera -> ie can determine if carriage or infection

Serology available for both the detection of IgM (early infection) and IgG (after infection)

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36
Q

What is the DFA-Antigen detection kit for M. pneumonia?
(3)

A

A serological method of detecting M. pneumonia in nasopharyngeal samples

It targets L7/L12 ribosomal protein or P1 adhesion protein

Improves sensitivity and specificity (70-80%)

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37
Q

What molecular method do we use to detect Mycoplasma pneumonia?

A

PCR
- done as part of respiratory panel on BioFIRE

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38
Q

What are some pros and cons of molecular methods of Iding M. pneumonia?
(2 pros, 3 cons)

A

Pros:
- Fast, great reduction in detection time
- For respiratory tract samples, PCR is far superior than serology during early phase infection

Cons
- Varying senstivity between 60-90%
- Sample quality influences performance
- PCR sensitivty decreases after day 7 of infection/contrast to serology

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39
Q

What has been our newest PCR product for M. pneumonia detection?

A

Can now detect the CARDS toxin - can affect virulence etc

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40
Q

How sensitive is the biofire film array for detection of M. pneumonia in respiratory sample?

A

Sputum:
- 96% sensitive
- 97.2% specific

BAL:
- 96% sensitive
- 98% specific

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41
Q

Why are we not super concerned with ability to detect M. pneumonia in BAL samples?

A

Patients with atypical pneumonia will never really need a BAL
-> they should never be this sick
-> only acception maybe legionares ??

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42
Q

What three atypical pneumonia bacteria can the biofire detect?

A

M. pneumonia
C. pneumoniae
Legionella pneumophila

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43
Q

What kind of PCR is the BIOFIRE film array?

A

Multiplex PCR array-based detection

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44
Q

What are the benefits of the BIOFIRE film array for detection of atypical pneumonia?
(6)

A

Its a fully automated platform carried out on a single cartridge, easy to use

4 hour turn around times

On board, DNA isolation, amplification, hybridisation and detection

Validated for both sputa and BALS

Qualitative detection

Targets 3/4 of our most common atypical pneumonias

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45
Q

What are the two cons of the BIOFIRE for atypical pneumonia?

A

Carriage vs prolonged shedding vs infection
Detection of more than 1 LRTI agent -> how do we know which is causative etc

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46
Q

What is legionella pneumophila, where is it found, what disease does it cause?
(4)

A

A gram-negative aerobic bacterium

Its found naturally in freshwater environments such as rivers lakes and streams

Thrives in man-made water systems such as sinks, shower taps, air conditioning cooling towers, whirlpools etc etc

Causes pontiac fever or rapidly progressive fatal pneumonia

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47
Q

What is L. pneumophila pontiac fever?

A

An acute respiratory illness ranging in severity from mild self-limited illness

Mild condition

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48
Q

What is L. pneumophila pontiac fever?

A

An acute respiratory illness ranging in severity from mild self-limited illness

Mild condition

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49
Q

What is L. pneumophila rapidly progressive fatal pneumonia, how fatal is the condition?
(2)

A

Atypical pneumonia with a mortality rate of 15-20% in previously healthy subjects

Its of a major concern in health care acquired cases especially in ICU as mortality can increase to 30-50% in these settings

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50
Q

What was the first outbreak of L. pneumophila, what happened?
(5)

A

First outbreak in July 1976 at an American legion convention in Philadelphia (hence the name)

140 people at the convention and 72 people in/near the hotel got pneumonia

34 patients died from the disease and its complications

A year later in 1977, the CDC announced the isolation of a bacterium from the lung of one of the patients, later named L. pneumophila

Since 1977 there has been a number of L. pneumophila outbreaks

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51
Q

Where are outbreaks of L. pneumophilia associated with?

A

Large building water systems such as hospitals, hotels and cruise ships

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52
Q

What is Legionnaires’ Disease?

A

A severe, potentially life-threatening pneumonia caused by L. pneumophila

53
Q

How is Legionnaries’ Disease transmissed?
(3)

A

Not spread person-to-person

Acquired by inhaling aerosolized water droplets containing the bacteria (NB-different to other organisms)

Water droplets are often from contaminated sources such as showers, air condiitoning systems or fountains

54
Q

What is the incubation period for Legionnaires’ Disease?

A

Typically 2 to 10 days after exposure

55
Q

What are some risk factors associated with Legionnaries?
(5)

A

more common in those >50, highest rate in men >65
Smokers
High alcohol intake
Immunocompromised -> hence ICU risk

Those with underlying lung conditions such as COPD (or other underlying health conditinos) are at higher risk

56
Q

Why is Legionnaires associated with travel?

A

Travel associated with seasonal accommodation i.e. hotels or BNBs used only in the summer months

Water facilities at these locations may only be used intermittently which allows for long periods of stagnation -> allowing bacteria to grow

57
Q

What are the symptoms of Legionnares?
(5)

A

Flu-like symptoms (fever, chills, muscle aches, headache, fatigue, malaise)

Cough (dry or productive), shortness of breath, chest pain

GIT symptoms (diarrhea, nausea, vomiting, abdominal pain)

Neurological symptoms (confusion, dizziness, lack of coordination)

High fever, loss of apetite, muscle aches

58
Q

What are the complications of Legionnares?
(8)

A

Need for mechanical ventilation

Septic shock -> severe drop in blood pressure

Kidney failure

Liver dysnfunction

Multi-organ failure

Encephalopathy (brain dysfunction)

In survivors of sever cases -> long term cognitive impairment

Death (5-30% mortality, higher in elderly and immunocompromised)

59
Q

Comment on the incidence of L. pneumophila
(6)

A

Uncommon, causes sporadic respiratory infection, low notification rates in EU

No human to human transmission

2.4 cases per 100,000 but 8.9 cases per 100,000 males >65

75% of all cases are from Italy, France, Spain and Germany

Only 11% of cases are culture confirmed

Most cases are community acquired

60
Q

What could be a possible reason for 75% of legionnaires cases being from Italy, France, Spain and Germany?

A

Could be due to poorer water quality

Or better detection methods

61
Q

What could be a possible reason for 75% of legionnaires cases being from Italy, France, Spain and Germany?

A

Could be due to poorer water quality

Or better detection methods

62
Q

What percentage of Legionnaires are culture positive? Why is this significant?
(3)

A

Only 11% of cases are culture positive

This is likely leading to an underestimation of cases

If not doing serology or PCR for legionnaires there is a very small chance you will catch it

63
Q

How does the rate of Legionnaires in Ireland compare to the rest of Europe, why is this significant?
(2)

A

Ireland has a low rate of Legionnaires compared to many European countries

This could suggest Ireland has a really good water quality supply but its more realistic to say we are under-diagnosing and under-reporting cases

64
Q

Explain in your own words how legionnella is spread?

A

Spread through aerosylised droplets:
- bacteria present in water
- some kind of system which aerosylises water e.g. a shower, fountain, jaccuzi or cooling system is ideal for transmission
- all of these systems incorporate air into water which leads to droplet formation in the air
- these droplets are then inhalled when person is in close proximity to the water e.g. showering

65
Q

How does L. pneumophila survive in water?
(4)

A

A dual host system

Legionella lives as an intracellular parasite inside a variety of species of protozoa

Legionella multiply within amoebae, using them as protective host

Can be found in both natural and man made water systems

66
Q

Give two examples of protozoa in which L. pneumophila can live inside

A

Acanthamoeba castellanii

Slime moulds

67
Q

Talk about the relationship between biofilms and L. pneumophila
(4)

A

Biofilms are found in both natural and man-made water systems

Legionella infected amoebae thrive in these microbial biofilms

The biofilms shield them from environmental threats

Sediment, sludge and biofilms provide ideal conditions for Legionella persistance and growt

68
Q

Why can it be difficult to prevevnt Legionella in water sources?
(3)

A

Legionella can survive in water of different temperatures from 0 degrees to 68 degrees

-> think of hot water tap in hospital, its roasting to avoid legionella

Infected ameobae can also undergo encystment if required

69
Q

What is amoebae encystment?

A

When conditions become unfavourable e.g. water temperature change, amoebae under go encystment

Amoeba form cysts in order to survive

70
Q

What happens if a L. pneumophilia biofilm is disrupted, why is this signficant?

A

If biofilm disrupted there is a sudden massive release of Legionella bacteria into the water system

This increases likelihood of infection

e.g. if you use a tap which hasnt been used in months, reservoir for bacteria, the first person to come close to the water will have the highest likelihood of infection

71
Q

When a legionella bacteria gets inside a human host how does it survive, no amoeba present here?
(2)

A

Legionella bacteria invade alveolar macrophages

From inside the macrophages the legionella multiply

72
Q

How does Legionella survive phagocytosis?
(3)

A

Production of a pseudopod + membrane-bound vacuole

Pseudopod coils around the bacterium which allows the bacterium to be internalised by macrophages without damage

Once inside, Legionella remains inside a membrane-bound vacuole which does not fuse with macrophage lysosomes -> this allows bacteria to evade destruction and multiply

73
Q

What are the three methods of L. pneumophilia detection?

A

Culture

Serology

Molecular

74
Q

How does L. pneumophilia look on gram?

A

Short rod/coccobacilli

Will stain poorly with gram but should be gram negative

75
Q

What remains the gold standard for L. pneumophilia, why is this significant?

A

Culture remains the gold standard

However sensitivity is poor so it cannot be used on its own, other methods must be used in combination to diagnose

76
Q

How do we culture Legionella?

A

Blood agar or Buffered Charcoal Yeast Extract (BCYE) agar

Incubated for up to 10 days at 35 degrees at 5% CO2

77
Q

What is the Legionella selective agar, what is it differential for?
(3)

A

BCYE agar - Buffered Charcoal yeast Extract agar

Used for presumptive ID and differentiation of Legionella species

L. pneumophila produces blue colonies

78
Q

What are the five main problems encountered when culturing Legionella pneumophilia

A

Slow growth - up to 10 day on blood or BYCE

Loss of viability after collection - bacterial cells die quickly

Bio-contaminated samples

Bacterial loss during processing

Underestimation of the real number of bacteria present in sample as very little usually grow

79
Q

What points in processing a sample can accidently kill L. pneumophilia?

A

Centrifugation
Filtration of sample
Decontamination of sample with heat or acid -> often done on water samples

80
Q

What serological methods of detection are available for L. pneumophila?
(3)

A

Direct Fluorescent Antibody (DFA) test

ELISA

Urinary Antigen Test

81
Q

When is Direct Fluorescent Antibody (DFA) testing done for L. pneumophila? How sensitive is this test?

A

Can be done on respiratory secretions and lung tissue both autopsy and biopsies

70% sensitive (too low to realistically be used- 90% and up is required really)

82
Q

Talk about the use of ELISA for L. pneumophilia, what are some cons?

A

Paired serum specimens collected 3-6 weeks apart (acute and convalescent) are ideal

Paired samples show a fourfold rise in antibody titre

However antibodies take at least 8 days to develop after onset of infection

Retrospective ID of Legionella so not really used

83
Q

Talk about the urinary antigen test for L. pneumophilia? What does it target, when do we use this?
(2)

A

In 1979 is was found that a legionella lipopolysaccharide was present in the urine of Legionnaires’ patients -> this became the target for urinary antigen tests

Urinary antigen ELISA is now our primary diagnostic tool for Legionnaires

84
Q

What are some cons of the urinary antigen ELISA?
(4)

A

Only 80% of Legionnaires patients will be positive

Antigen excretion in urine can vary among individuals

Test may remain positive for several months following pneumoniae

It specifically detects only L. pneumophila serogroup 1

85
Q

What are some cons of the urinary antigen ELISA?
(4)

A

Only 80% of Legionnaires patients will be positive

Antigen excretion in urine can vary among individuals

Test may remain positive for several months following pneumoniae

It specifically detects only L. pneumophila serogroup 1

86
Q

According to EU what are the only three ways to confirm a case of Legionnaires disease
(3)

A

Isolation of bacteria from respiratory secretions or any normal sterile site

Detection of urinary antigen

Significant rise (usually 4 fold) in specific antibody level to L. pneunophilia serogroup 1 in paired serum samples

87
Q

According to EU what are the only three ways to confirm a case of Legionnaires disease
(3)

A

Isolation of bacteria from respiratory secretions or any normal sterile site

Detection of urinary antigen

Significant rise (usually 4 fold) in specific antibody level to L. pneunophilia serogroup 1 in paired serum samples

88
Q

What are the targets for molecular detection of L. pneumophila?

A

Target 16S rRNA gene

And macrophage infectivity potentiator gene mip42 gene

89
Q

What is the mip42 gene?

A

Macrophage infectivity potentiator gene

90
Q

What are the pros and cons on molecular detection of L. pnumophila?
(2 pros and 3 cons)

A

Pros
- Can be used on BALS, pharyngeal swabs, peripheral blood mononuclear cells, urine and serum
- Can be included as part of a LRTI NAAT panel e.g. biofire

Cons
- problems with PCR inhibition in environmental sample types causing false negatives
- effective DNA purification and PCR inhibition controls are required
- cannot determine if current infection or past infection

91
Q

What contaminants of environmental water sources for L. pneumophilia detection cause issues with PCR?

A

Rust
Organic polymers found in soil and streams

92
Q

How sensitive is the urinary antigen test for L. pnuemophilia?

A

80%

93
Q

How sensitive is PCR for L. pneumophila?

A

70-90% sensitive
-> usually used in combination with urinary antigen test

94
Q

What are chlamydiae, what three species are significant to humans?

A

Obligate intracellular bacteria

Three affect humans:
- Chlamydia trachomatis
- Chlamydophila pneumoniae
- Chlamydophila psittaci

95
Q

What infections does Chlamydia trachomatis cause?

A

Chlamydia trachomatis -> infection of genital tract infections (STI)

96
Q

What infections does Chlamydophila pneumoniae cause?

A

Chlamydophila pneumoniae -> bronchitis and pneumonia

97
Q

What infections does Chlamydophila psittaci cause?

A

Chlamydophila psittaci -> can cause pneumonia and systemmic infection but usually only a secondary infection after something else

98
Q

How frequent is Chlamydophila pneumonia infection, who is it most frequently isolated in?

A

It has been a significant cause of community acquired pneumonia since 1980

5% of bronchitis
15% of COPD exacerbations
10% of CAP

Nearly everyone will be infected at least once in their life

Incidence peaks between ages of 5 and 14

99
Q

How does Chlamydophila pneumonia manifest, who does it most affect?
(3)

A

Most commonly manifests as pneumonia and bronchitis

Usually a mild, self limiting illness

In Elderly or those with existing pulmonary disease it can cause systemic disease

100
Q

If Chlamydophila pneumonia becomes systemic (in very rare cases), what systems does it affect?
(4)

A

Cardiovascular system

Central nervous system

Systemic - reactive arthritis

Hepatosplenomegaly

101
Q

How does C. pneumonia affect the cardiovascular system, in the very rare case that it causes systemic infection?
(2)

A

It contributes to plaque formation in arteries leading to atheroscelrosis

It can cause inflammation of the heart muscle (myocarditis) and of the heart’s inner lining (endocarditis)

102
Q

How does C. pneumonia affect the cardiovascular system, in the very rare case that it causes systemic infection?
(2)

A

It contributes to plaque formation in arteries leading to atheroscelrosis

It can cause inflammation of the heart muscle (myocarditis) and of the heart’s inner lining (endocarditis)

103
Q

In the rare case that C. pneumophila becomes systemic, how does it affect the central nervous system?
(3)

A

It has been detected in the cerebrospinal fluid in a limited number of patients

Studies are limited but it is though to have neurological implications and maybe even play a role in neurodegenrative conditions such as MS

There is thought to be a possible association with development or exacerbation of MS with C. pneumonia infection

104
Q

What are the three methods of detecting C. pneumonia?

A

Culture

Serology

Molecular

105
Q

How do we culture C. pneumoniae?
(3)

A

Since C. pneumoniae is an obligate intracellular pathogen it is dificult to culture

Bacteria requires cell culture using HeLa cells

A BAL sample must also be used, again making culture very difficult

106
Q

What serological method is used for the detection of C. pneumonia?

A

MIF test - Microimmunofluorescence

*this is the gold standard

107
Q

What is the MIF test for C. pneumoniae, how does it work, how do we carry it out?
(4)

A

An indirect fluorescent antibody test

It uses purified antigen (TWAR) plus fluorescein isothiocyanate (fluorescent marker) spored onto a microscope slide

A dilution series of patient sera is added, washed, fluorescein is added and conjugate anti-human antibodies

Any fluorescence, if antibodies present will be detect by fluorescent microscopy

108
Q

What are some pros and cons of the C. pneumonia MIF?
(2 pros, 3 cons)

A

Pros:
- sensitive
- allows us to quantify antibody titre, can be used to indicate acute infection (4 fold rise in IgG tire)

Cons:
- False IgM antibody reaction due to rheamuatoid factor cause false positives
- test interpretation variable results in inter-laboratory variability in reporting MIF tires
- retrospective - samples taken 3/4 weeks after symptoms

109
Q

What sample is used for the MIF for C. pneumoniae?

A

Paired sera, one acute one convalescent

Samples must be obtained 3-4 weeks after onset of symptoms

110
Q

What molecular detection methods are available for C. pneumonia, what is the benefit of molecular methods?

A

C. pneumonia is included in the BIOFire film array respiratory panel

The NVRL also has its own C. pneumoniae PCR set up

Overall PCR improves speed and sensitivity

111
Q

What molecular detection methods are available for C. pneumonia, what is the benefit of molecular methods?

A

C. pneumonia is included in the BIOFire film array respiratory panel

The NVRL also has its own C. pneumoniae PCR set up

Overall PCR improves speed and sensitivity

112
Q

What is Coxiella burnetti, what kind of organism is it?

A

A ‘small bacteria’ below the resolution of a normal light microscope -> it’s tiny, only 0.45um

Its classified amongst the Rickettsia

Its an obligate intracellular pathogen

Its gram negative

It only grows in eukaryotic cells

Its spore forming

113
Q

What is the preferred cell for Coxiella burnetti to invade?

A

Preffers the phagolysosome of macrophages

114
Q

What are the two phases to Coxiella burnetti infections?

A

2 antigenic phases:
- 1 - persistent infection
- II - primary infection

115
Q

What disease is C. burnetti asociated with?

A

Q fever

116
Q

When was the first Q fever outbreak, how did it get its name?

A

First outbreak in 1937 in workers of a meat-packing plant in Australia

The Q was originally QQ fever? as in query query fever?

117
Q

How is Q fever transmissed?
(4)

A

It is a zoonotic disease - most common in cattle, sheep and goats

It grows well in the placenta of animals, when a birth ocurs large numbers are liberated onto the ground

Outbreaks occur wherever these animals are raised, housed or transported

Transmission primarily through inhalation of airborne dust

118
Q

How frequent is Q fever, how does Ireland compare to other european countries?
(3)

A

True incidence is unknown as geographic variation in symptoms meaning patients not ID’d as atypical pneumonia and therefore testing is not done

In 2007-2010 there was a large epidemic in the Netherlands with >4000 cases and 25 deaths

In Ireand the most we have had is 6 cases in 2016 (no deaths)

119
Q

How infectious is C. burnetti?
(2)

A

It is the lowest bacterial infectious dose known to man with <10 bacteria known to cause infection

*Shigella very close with >10 bacteria required ot cause infection

120
Q

What are the two ways C, burnetti infection can present itself, compare the symptoms of both, what is this dependent on?
(3)

A

Primary: typical presentation, often involves pneumonia

Persistant: rare but much more serious illness, can lead to endocarditis and vascular/osteo-articular infections

The clinical presentation of infection is highely dependent on virulence of the infecting strain and patient associated risk factors

121
Q

What are the two ways C, burnetti infection can present itself, compare the symptoms of both, what is this dependent on?
(3)

A

Primary: typical presentation, often involves pneumonia

Persistant: rare but much more serious illness, can lead to endocarditis and vascular/osteo-articular infections

The clinical presentation of infection is highely dependent on virulence of the infecting strain and patient associated risk factors

122
Q

How does C. burnetti infect a patient?
(2)

A

The organism first proliferates into the lung

From here it can (in rare cases) invade the bloodstream and causes systemic infection

123
Q

What are three methods of detecting C. burnetti in the lab?

A

Culture

Serology

Molecular

124
Q

Talk about culture methods for C. burnetti?

A

Culture cant really be done

Isolation is extremely difficult

Intracellular organism

125
Q

What serology method is used for C. burnetti detection?

A

MIF-reference method (same as C. pneumonia)

126
Q

How is the MIF-reference method used to diagnose C. burnetti infection?

A

For primary infections:
- anti-phase II Ag IgG is measured, titre >=1:200

For persistant infections:
- anti-phase I IgG is measured, titre f >= 1:800

127
Q

What molecular methods are available for the detection of C. burnetti, what sens and spec, what target, main benefit?
(4)

A

PCR on a blood sample

High sensitivity (93% and high specificity 98%)

IS1111 most senstive target

Serology often not available for primarly cases so PCR allows timely diagnosis and treatment

128
Q

For our four atypical pneumonia bacteria, which ones is there a vaccine available for, for who are these available for?

A

Coxiella burnetti

These vaccines are available for at risk groups only

Only really given to farmers in outbreak zones or to those in the military

4.1 Medical Microbiology (30 decks)

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