Clinical Microbiology Flashcards
personalised treatment is enabled by?
rapid testing and Point of Care Diagnostic
what is point of care diagnostics?
A diagnostic test delivered in near real-time at the point of care the interaction between clinician and
A diagnostic conducted & delivered during the patient’s appointment
Enabling clinical decision making at the point of delivery
In the clinic
In the home
In the community
what are the requirements of a diagnostics for point of care
low cost (capital vs consumable) or have a high value return - cost effectiveness
Rapid
Must provide a clear diagnostic threshold
Provides an answer that can be acted upon - actionable
Any technique must have appropriate “simple” operation
At least match the current Gold Standard and/or offer greater utility
what are lateral flow devices?
simple devices intended to detect the presence (or absence) of a target analyte in sample (matrix) without the need for specialized and costly equipment
what is nucleic acid lateral flow (NALF)?
is
designed for testing the presence of
an amplified
double-stranded nucleic acid sequence specific
to the analysed organism using primers with two
different tags
what are the advances in rapid poc dx?
This is only possible because of a revolution in technology
Smart materials – nanomaterials, nanowires, paramagnetic beads
Miniaturisation enabled by microfluidics and microelectronic machines (MEMs)
Disposible Cartridges
Low power requirement means mobile diagnostic
Smart Communications - smart phone connectivity eHealth / mHealth allows reporting and electronic prescribing anywhere
Cepheid GeneXpert: what is it?
Range of off the shelf real-time PCR assays
what does cepheid genexpert do?
looks for: M. tuberculosis, Chlamydia trachomatis, Neisseria gonorrhoea
performs:
Detection – is it there?
Quantification – bacterial/viral load, how much?
Variant detection –resistance profile?
Simple microflidic cartridge allows non-expert handling and containment
While-U-Wait processing 90min
Easy to read & interpret results
example of clinical need?
curable STI’s:
Untreated early syphilis, 25% of pregnancies result in stillbirth and 14% in neonatal death.
Sexually transmitted infections are the main preventable cause of infertility, particularly in women.
Undermines national development in many countries
control of STI transmission
case reprouctive rate= biological efficiency of transmission x rate of partner change/sexual behaviour x duration of infectiousness
why is treatment for STI target not met?
Main reason given for failure is patient loss to follow up
what does inappropriate/incorrect treatment result in?
Unnecessary costs of treatment
Continuing symptoms or progression
Selection pressure for drug resistance
Delay in correct treatment
why is rapid POC dx important in STIs?
Early intervention by Diagnosis at POC where correct
Treatment is determined by test result for the individual
how can medicine be personalised for infectious disease bases on an individuals molecular diagnosis ?
The genetic profile of the infectious agent
The composition of the population of organisms inhabiting a wound or biological niche
The genetics of susceptibility
what does genetic profiling for clinical microbiology offer?
Allows unambiguous identification Genetic determinants of Antibiotic resistance (antibiogram) Virulence factors Toxin production
key advantages od NGS
Encapsulates all genetic determinants Definitive identification Detects mix infections (metagenomics) Captures information for surveillance, infection control Does not require a priori knowledge
obstactles/disadv of NGS?
Currently requires prior culture, unculturable organisms a problem
cost
Sample to diagnosis duration is long
Scope & completeness of high quality sequence data for comparison
Poor level and quality of annotation of sequence information
Limited by the lack of phenotypic resistance testing in relationship to genetic markers
Validation procedures, reporting & regulatory mechanisms for testing are ill defined
what is ‘population genetics in a patient’?
Some organism utilise a strategy of error-prone replication
human immunodeficiency virus, hepatitis B virus, and hepatitis C virus,
10-5 to 10-3 substitutions per/position/cycle
Combined with the high replication rate, this results, the individual hosting a population of genetically related variants (quasi-species)
Advantageous or Neutral mutations accumulate
Prolonged infection see emerging quasi-species
Selective pressures such as the immune system and drug treatment combined with population variation -> emergent resistance & treatment failure
mutation rates of HIV make drug resistance highly likely upon prolong exposure to?
A narrow spectrum of drugs
Recurrent missed dosage
High viral load
why is ability to detect emerging resistanc critical to good clinical practice?
The detection of emerging mutations within a population of microorganisms is critical for the management of drug-resistant infections.
