Clinical Microbiology

Question 1

personalised treatment is enabled by?

Answer 1

rapid testing and Point of Care Diagnostic

Question 2

what is point of care diagnostics?

Answer 2

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

Question 3

what are the requirements of a diagnostics for point of care

Answer 3

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

Question 4

what are lateral flow devices?

Answer 4

simple devices intended to detect the presence (or absence) of a target analyte in sample (matrix) without the need for specialized and costly equipment

Question 5

what is nucleic acid lateral flow (NALF)?

Answer 5

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

Question 6

what are the advances in rapid poc dx?

Answer 6

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

Question 7

Cepheid GeneXpert: what is it?

Answer 7

Range of off the shelf real-time PCR assays

Question 8

what does cepheid genexpert do?

Answer 8

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

Question 9

example of clinical need?

Answer 9

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

Question 10

control of STI transmission

Answer 10

case reprouctive rate= biological efficiency of transmission x rate of partner change/sexual behaviour x duration of infectiousness

Question 11

why is treatment for STI target not met?

Answer 11

Main reason given for failure is patient loss to follow up

Question 12

what does inappropriate/incorrect treatment result in?

Answer 12

Unnecessary costs of treatment
Continuing symptoms or progression
Selection pressure for drug resistance
Delay in correct treatment

Question 13

why is rapid POC dx important in STIs?

Answer 13

Early intervention by Diagnosis at POC where correct

Treatment is determined by test result for the individual

Question 14

how can medicine be personalised for infectious disease bases on an individuals molecular diagnosis ?

Answer 14

The genetic profile of the infectious agent
The composition of the population of organisms inhabiting a wound or biological niche
The genetics of susceptibility

Question 15

what does genetic profiling for clinical microbiology offer?

Answer 15

Allows unambiguous identification
Genetic determinants of 
Antibiotic resistance (antibiogram)
Virulence factors
Toxin production

Question 16

key advantages od NGS

Answer 16

Encapsulates all genetic determinants
Definitive identification 
Detects mix infections (metagenomics) 
Captures information for surveillance, infection control
Does not require a priori knowledge

Question 17

obstactles/disadv of NGS?

Answer 17

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

Question 18

what is ‘population genetics in a patient’?

Answer 18

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

Question 19

mutation rates of HIV make drug resistance highly likely upon prolong exposure to?

Answer 19

A narrow spectrum of drugs
Recurrent missed dosage
High viral load

Question 20

why is ability to detect emerging resistanc critical to good clinical practice?

Answer 20

The detection of emerging mutations within a population of microorganisms is critical for the management of drug-resistant infections.