TB NETWORK

At several of the loci the number of repeats varies between strains. This property is used as the basis for the MIRU-VNTR typing system to distinguish different M. tuberculosis strains. In MIRU-VNTR typing the number of repeats is counted at 24 different loci in order to produce a 24-digit code, which is used as the strain type designation for an isolate.At least 95% of first M. tuberculosis isolates will have 24 loci MIRU-VNTR typing performed as part of the routine reference service, with results available within 21 days of confirmation of species identification. It is not always feasible to obtain a MIRU-VNTR profile for 100% of isolates, despite repeated testing, due to sample contamination or mixed cultures.

Nationally, MIRU-VNTR typing is performed at one of three reference laboratories. Isolates from Greater Manchester patients will usually be typed in the Newcastle laboratory.

Why use TB strain typing?
TB strain typing results, when combined with epidemiological data, can help to identify TB patients who are involved in the same chain of TB transmission. This can expedite the initiation of appropriate control measures. TB strain typing also helps to distinguish TB patients whose disease is a result of reactivation of an infection acquired in the past and cases of re-infection with a new TB strain.
 
The introduction of universal TB strain typing i.e. submitting one isolate from every culture-positive patient with TB for strain typing will provide the best understanding of the epidemiology of TB transmission and help to uncover the greatest number of unexpected outbreaks, clusters, and false positives. It will also allow us for the first time to monitor our progress towards eliminating TB transmission by monitoring the changes in the percentage of strain type clustered cases.

What are the main objectives of TB strain typing? To identify epidemiological links between TB patients to detect and control outbreaks early and rapidly.To identify incorrect TB diagnosis based on false-positive cultures and thus avoid unnecessary investigation and treatment.To distinguish exogenous re-infection from endogenous reactivation in patients with a past history of TB.To monitor effectiveness of TB control activities by using recent TB transmission rates as a surrogate measure.

Additional benefitsStrain typing can also be a very useful tool to identify nosocomial transmission that cannot be identified by conventional methods, and to identify transmission that occurs between patients in different jurisdictions more readily. It can also be useful to show that TB cases occurring in the same time and place can have unrelated strain typing and not belong to the same chain of recent transmission, thus requiring no further action. It is a useful tool to distinguish the overall diverse Mycobacterium tuberculosis strain pattern and identify endemic strains circulating in a given population. It may support the identification of different genetic lineages and the study of their geographical distribution and pathophysiology which has implications for the development of new tools for TB control.

What is a TB strain typing cluster?
A TB strain typing cluster is defined as one with two or more persons with TB caused by indistinguishable 24 locus strains occurring within 24 months (2 years). A cluster may contain isolates with the following characteristics: All 24 loci of the MIRU VNTR profiles of the isolates are complete and identical, or Some members of the cluster may have up to but no more than one (1) missing / unmapped locus, so long as the missing locus is the same for all incomplete isolates within the cluster

The HPU threshold for cluster investigation will usually be a cluster with 5 or more persons within 24 months, of which 2 have occurred in the last 6 months. All clusters of 2 or more cases will, however, be subject to a preliminary review and if this reveals the presence of certain characteristics (e.g. the cluster includes a child, a prisoner, drug resistant cases etc), consideration will be given to starting active cluster investigation for fewer than 5 cases.

A strain type cluster may, of course, not be a ‘true’ cluster. Epidemiological information is required to determine if this is a genuine cluster i.e. if some or all of the patients are likely to be in a chain of transmission.

Investigation of TB strain typing clusters in Greater Manchester
These investigations will be undertaken in line with the Health Protection Agency (HPA) National TB strain typing project (see link below). They will be led by the Greater Manchester Health Protection Unit (HPU), working in partnership with the Greater Manchester TB services and the HPA TB strain-typing co-ordinator.

Further information on the HPA National TB Strain Typing Project is available at:

HPA - TB Strain Typing Project

If you would like any further information on this subject then please email: info@tbnetwork.co.uk.