Exam 1 - Introduction to Infectious Disease Diagnostics Flashcards
with diagnostic tests, when should you screen your patients?
prior to breeding, exposure, or acquisition
prior to domestic or international travel
for regionally common diseases
for highly dangerous diseases
prior to making a preventative care decision
when using diagnostic tests for diagnosing a patient, when should you use them?
after a known/suspected exposure
after a period of compatible clinical signs
prior to making a therapeutic care decision
screening tests are highly _________ while confirmatory tests are highly _________ (sensitive/specific)
sensitive
specific
why do you want your screening tests to be highly sensitive?
you’re using it to rule out a disease - you will pursue more diagnostics to confirm whether or not your results were correct
T/F: screening tests may tolerate more false positives
true
what are the benefits of using screening tests for large numbers/populations?
they are simple & fast
affordable
& generate simple results
confirmatory tests are used to ______ disease
diagnose
T/F: confirmatory tests may tolerate more false negatives
true
what patients should you use confirmatory tests for?
smaller numbers of patients with the highest index of suspicion
what are the cons of using confirmatory tests?
more expensive, inconvenient, & nuanced interpretation
T/F: a diagnostic test result is a diagnosis
FALSE - you must interpret the test result in regards to your patient
T/F: tests yield results, not answers
TRUE
_______/_______ are features of the tests
sensitivity/specificity
_______/_______ _______ _______ are features of how you use a test
positive & negative predictive value
T/F: you have some control over your positive & negative predictive values
true - you are determining how you will use the test
in regards to interpreting a test result with positive & negative predictive values, what are you considering?
knowledge of the patient
knowledge of the disease in question
knowledge of how the test works
what is sensitivity?
probability that an animal that has the disease will test positive
(probability that an animal has a positive test result given it has the disease)
evaluating your test!!!
what is specificity?
probability that an animal that does not have the disease will test negative
(probability that an animal has a negative test result given it does not have the disease)
likelihood that a healthy, disease free animal will get a negative test result
what is positive predictive value?
probability that an animal that tests positive has the disease
(probability of an animal having the disease given the test is positive)
probability that a sick animal has a positive test result
what is negative predictive value?
probability that an animal that tests negative does not have the disease
(probability of an animal not having the disease given a negative result)
likelihood that a healthy, disease free animal will get an accurate negative test result
predictive values depend on the probability of what?
the animal having the disease before you test it - if your probability of disease is high (pre-test probability), then your PPV is inherently high & NPV is low
how is sensitivity calculated?
TP/(TP + FN) = sensitivity
A/(A+C)
how is specificity calculated?
TN/(FP+TN) = specificity
D/(B+D)
T/F: false positives do not affect sensitivity
true
how is PPV calculated?
TP/(TP + FP) = PPV
A/(A + B)
how is NPV calculated?
TN/(FN + TN)
D/(C + D)
what is prevalence?
frequency of an occurrence (diagnosis) in the population at the moment
(# of animals just like your patient that have the disease right now)
__________ is a reflection of the population your patient is a member of
prevalence
what is incidence?
frequency of an occurrence (diagnosis) that will happen in the population over some set time
(projection of future values in a year)
what is population?
the group in which your patient is a member of
why is prevalence important to consider diagnostically?
you need to consider it when choosing a diagnostic test! want to use the test to the best of its ability - high prevalence groups, use in certain settings
what may happen if you apply a diagnostic test in a low prevalence group?
may end up with false positives
_______ patients on whom to run ____ test
preselect
any
when considering prevalence & choosing a diagnostic test, what 3 things should you consider?
decide in advance what that patient’s pre-test probability is
decide in advance what you will do with a positive result
decide in advance what you will do with a negative result
why are false positives important to consider when it comes to PPV?
a small number of false positives can greatly affect your PPV
if you get a positive result on a test with a lower PPV, how would you give your positive result more value?
retest using a different test
retest using the same test - different lot number
retest patient in a few weeks
what would your estimate prevalence be on a sick puppy with bloody diarrhea having parvo? (low/medium/high)
high
what 3 components of diagnostic test characteristics should you consider?
how the test works
limits of the method
cross-reactions or other pitfalls
rational use of any diagnostic test requires an understanding of what?
patient risk (pre-test probability/prevalence)
patient history, physical/clinical presentation, & lifestyle
what does NAATs stand for? what common test does this group include?
nucleic acid amplification tests
PCR tests
what are examples of immunoassay diagnostic tests?
antigen/antibody tests, serology, IFA/IHC, ELISA, agglutination, & immunodiffusion
what are examples of microscopic identification tests?
fecal floats, skin scrape, urine sediment, blood smear
what are the benefits to using microscopic identification as a diagnostic approach?
provides direct evidence, often rapid/patient side, & sample represents a small amount of a specific site
what are the downfalls of using microscopic identification as a diagnostic approach?
requires expertise, can’t see viruses, may not be enough bacteria present to make an identification, & can’t determine species of bacteria
what is this?
blastomycosis
what is this?
babesia in a blood smear
what may you use a culture for?
extracellular bacteria (aerobic/anaerobic), fungi, urine, discharge/swabbed materials, aspirated materials, & indwelling devices
what are the benefits to using culture as your diagnostic approach?
direct evidence of viable agent, agent species can be identified, & agent species can be tested for susceptibility
what are the downfalls to using culture as your diagnostic approach?
some organisms are hard to grow/won’t grow without special mediums (obligate intracellular), early antibiotic treatment can wipe out the pathogen you’re looking for, need sufficient numbers of pathogens, & competition within the sample (some species will grow readily & take over)
what are you looking for if using isolation in cell culture diagnostically?
intracellular bacteria, viruses, protozoa, & pathogens to use in vaccines
what are the benefits to using isolation in cell culture?
vaccine development! & confirms organisms are viable
what are the downfalls to using isolation in cell culture?
it’s slow, technically challenging, requires prior knowledge of probably pathogen (what are you trying to isolate), & high risk of false negatives
who is quarantined? for how long?
quarantine the exposed - as long as the incubation period
who is isolated? for how long?
infected people - until the shedding period ends
T/F: there is more signal from the immune system than the pathogen requiring careful interpretation of immunoassays
true
T/F: if using an antigen test to detect antibodies to a pathogen in a patient, the immunoassay is able to differentiate between infection from exposure
false - there is also a lag time after infection for antibodies
when using an immunoassay diagnostic test, what are you looking for?
evidence of a pathogen by presence of either antigen or antibody
what is NAATs?
nucleic acid amplification tests
when would you use NAATs/PCR?
detecting nucleic acid - use for bacteria, fungi, DNA/RNA, organisms that are slow to culture, viruses, & organisms that are dangerous to culture
what are the benefits of NAATs?
nucleic acid sequences are specific to their pathogen
tests can detect dead pathogens
tests can be optimized to many tissues/fluids
& DNA is stable to use in these tests
what are the downfalls of NAATs?
RNA is easily degradable
presence of a pathogen doesn’t equal causation
high tech/labor intensive
extremely sensitive - may be overly sensitive
what kind of virus is canine distemper virus?
enveloped, ssRNA, morbilivirus - RNA is less stable
what animals serve as the primary reservoir for distemper? what about other outside sources?
dogs
coyotes, dingos, raccoon, fox, badger, etc
when does shedding begin in an animal infected with distemper?
day 7 post infection
how is distemper virus shed?
primarily in respiratory secretions, but also urine & other tissues
when are clinical signs seen in animals infected with distemper?
clinical signs seldom seen until day 9 or later
what is the pathogenesis of distemper virus?
virus enters respiratory system - replicates in epithelium & enters tissue macrophages which are then carried to lymphoid tissue
multiplies extensively in lymphoid tissues (lymph nodes, tonsil, thymus, GALT)
hematogenous spread back to the epithelium (includes CNS)
resulting in viremia & cell-associated viremia
footpad tropism - hard pad disease
what is the presentation of acute encephalitis in an animal infected with distemper?
typically young/immunocompromised dogs
viral replication in CNS without inflammation
CSF tap may be normal
will not see antibodies at this time because immune system isn’t working
what is the presentation of sub-acute to chronic encephalitis in an animal infected with distemper?
dogs with a moderate immune response
CNS invasion occurs as lymphoid tissue is recovering
CSF tap should detect inflammation
what is the presentation of old dog encephalitis in an animal infected with distemper?
rare, chronic, progressive form
replication-incompetent CDV in neurons
what are the classical respiratory clinical signs seen in an animal infected with distemper virus?
serous to muco-purulent oculonasal discharge
viral pneumonia usually complicated by secondary bacterial infection
what are the classical gastrointestinal clinical signs seen in an animal infected with distemper virus?
anorexia & vomiting
diarrhea may become severe - intussusceptions
what are the classical neurological clinical signs seen in an animal infected with distemper virus?
seizures, tremors, myoclonus - often manifest after systemic signs have resolved
in what order do clinical signs show up in an animal infected with distemper virus?
respiratory, GI, then neurological
what is the typical history of a dog with suspect distemper?
undervaccinated animal
respiratory then gi & then maybe neuro signs
what are the typical physical exam findings of a dog with suspect distemper?
sick, febrile dog with oculonasal discharge
what lab work abnormalities would you expect to get with an animal infected with distemper virus?
lymphopenia but otherwise unremarkable
what may you see with microscopic identification of distemper virus?
inclusion bodies
what would be your next tier diagnostics pursued for distemper virus?
maybe immunoassays - paired titers
IFA of skin biopsy also used
what is a paired titer?
samples taken 3 weeks apart from CSF & blood - looking for rise/fall of antibodies
If an animal presented clinically healthy & later went on to exhibit more severe clinical signs of distemper, what would you expect their titer results to be if you took the first sample upon initial presentation?
4 fold increase
if you use an immunoassay looking for the presence of antibodies on an animal that has suspect distemper, & has never been vaccinated, what would be supportive of distemper?
presence of antibodies - positive result
why is a PCR test utilized as a next tier diagnostic for canine distemper virus?
easy to use - use urine, blood, or CSF
can also do nasal, pharyngeal, or conjunctival swab
T/F: a distemper vaccine can potentially cause a transient positive RT-PCR
true - would be somewhat of a false positive result
what should you consider before using an immunoassay test on a possible distemper patient?
timing
vaccine status
locations to test
(often used test)
why are RT-PCR tests often used for diagnosing possible distemper patients?
widespread pathogen - many fluid & tissue sources can be used for testing