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3/15

How will you get extra information?

  • How will you obtain the information you need to make a decision on which groups should be offered prophylaxis?

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Answers to Exercise 1

Information on other notified cases that have occurred within the same area should be available local case management and surveillance databases such as HPZone currently used in PHE. Cases that occur in neighbouring areas can also be traced by liaising with the relevant PHEC team. Meningococcal serogroup can often be determined locally (in around 24 -48 hours from receipt of sample) and is also available from the Meningococcus Reference Unit (Manchester). All isolates should be sent for confirmation of serogroup. Further serological information may be requested when isolates are available.

Serology

(a) Serogroup - identification of capsular polysaccharide antigens by serological reactions using antibodies.

(b) Serotype - identification of PorB outer membrane protein type using antibodies.

(c) Serosubtype - identification of PorA outer membrane protein type using antibodies.

Genetic sequence based molecular typing

Molecular typing can be requested from the Meningococus Reference Unit to establish genotype of meningococci as part of an outbreak investigation.

(a) Serogroup - use of PCR based serogroup confirmation enables identification of non-viable organisms.

(b) Serosubtype – genetic characterisation of serosubtype by DNA sequencing provides an alternative to serological methods to find serotype and serosubtype. (Routinely tested and reported on all clinical isolates since October 2007).

(c) Multi Locus Sequence Typing (MLST) - performed and reported on strains collected for epidemiological monitoring and in some outbreak investigations.

MLST is DNA sequencing of seven genes spread around different parts of the genome, the genes are selected to represent areas of the genome that are not subject to vaccine or immune pressure and so relationships between Sequence Types can be considered to represent relatedness between strains. Molecular typing techniques such as these, which are based on PCR or sequencing of genes, and others, which are based on the presence or different sized repeat regions within the genome, exist for a range of different microorganisms. Different techniques have been developed before whole genome sequencing was available for discriminating isolates within different species, for monitoring the main subtypes causing disease such as in monitoring the response to vaccines, and for some other purposes.

Genomics

A genomics approach is to extract DNA from available meningococcal isolates and sequence this using one of the available validated high throughput platforms such as Hi Seq (Illumina), 454 (Roche) or Ion Torrentor (PacBio). The resultant overlapping DNA sequences would then be assembled to produce a Whole Genome Sequence for the organisms, or large sections of the whole genome. Given the tight temporal, spatial and institutional links between the three cases, genomics may not be appropriate at this stage of an investigation even if available in a timely way.

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