News Archives |
Volume 3 No 12; 27 March 2009
World TB day update – 24 March 2009
To mark World TB Day 2009, the Health Protection Agency (HPA) has published a newsletter providing an update on the activities of numerous organisations to control tuberculosis (TB) in the UK and globally [1]. Activities highlighted include initiatives such as the Department of Health funded TB Find and Treat project, the MDRTB Service and the London TB Workforce group, as well as action at the local and regional level and in the devolved administrations aimed at delivering a first class tuberculosis service.
Improvements in surveillance are being made with the implementation of a national web-based enhanced surveillance system and the UK Mycobacterium tuberculosis Strain-Typing Database. Such developments will improve the timeliness and availability of surveillance data including laboratory information, which will assist the public health management of cases and clusters.
The newsletter also releases provisional national figures for TB in the UK in 2008. A total of 8679 new cases were provisionally reported in 2008 (14.2 cases per 100,000 population), an increase of 2.2% compared to the number of cases provisionally reported in 2007. Finalised 2008 data will be published later this year.
The HPA acknowledges the assistance of colleagues within its Local and Regional Services network, and of Health Protection Scotland, the National Public Health Service for Wales and the Communicable Disease Surveillance Centre Northern Ireland, in providing provisional TB figures referred to above.
The World Health Organization (WHO) has also published its most recent data on TB incidence in 2007 [2]. It estimates that there were 9.27 million new TB cases worldwide in 2007 (139 per 100,000) and 1.3 million people dying of TB. Although the number of new cases increased compared to previous years due to population growth (9.24 million in 2006), the rate is slowly declining at about 1% per year. Further information can be obtained from the WHO report "Global tuberculosis control - epidemiology, strategy, financing" [2].
References
1. Tuberculosis Update, Health Protection Agency, London, March 2009, http://www.hpa.org.uk/web/HPAwebFile/HPAweb_C/1237797271436.
2. Global tuberculosis control - epidemiology, strategy, financing, World Health Organization, Geneva , 2009, http://www.who.int/tb/publications/global_report/2009/en/.
Accuracy of Clostridium difficile toxin detection kits
The NHS Purchasing and Supplies Agency's Centre for Evidence-based Purchasing (CEP) has published an evaluation report on the accuracy of Clostridium difficile toxin detection kits [1]. The CEP evaluation is the largest single study of such kits to date, examining six immunoassays and three membrane-bound assays, and using 600 faecal samples. The report details the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the kits using two gold standard methods (a cytotoxin assay and cytotoxigenic culture).
Significant differences between the accuracy of kits were seen. None of the nine assays tested had a particularly high sensitivity (67-92%), meaning that a significant proportion of true positives will be missed by these kits. The PPVs also varied markedly; at a 10% prevalence of toxin positive faecal samples, which approximates to the positivity rate in a diagnostic laboratory, the best PPV was less than 88%. This raises concerns about potential false positive results, which will be more likely in settings where C. difficile infection (CDI) is uncommon. In the community setting only circa. 2% of diarrhoeal samples tested may be positive for C. difficile toxin [2]. In such settings the best PPV in the CEP study was less than 60%. A key problem with low sensitivity tests, which also have suboptimal specificity, is that repeat testing, while increasing the likelihood of obtaining a true positive result, also increases the chance of a false positive.
Accurate diagnosis of CDI is important to determine whether prompt treatment, or further diagnostic testing (eg for other causes of diarrhoea), is required, to optimise the use of isolation facilities and other healthcare resources, and for surveillance. Toxin detection kits allow more rapid diagnosis of CDI, and were introduced as alternatives to the slower cytotoxin assay, which also needs a cell culture line to be maintained. However, it is not difficult to maintain a continuous cell line, and thus this approach is still an option for some laboratories. There is also the possibility of sending faecal samples to another laboratory, as these may be stored at 4°C for several days before re-testing [3]. As cytotoxicity assays are slower, this may require the use of another rapid assay as an initial screen, particularly in outbreak or endemic settings.
In summary, the currently available kits for detection of C. difficile toxins have variable performance. Recent studies show that these kits may miss about one-in-five to one-in-10 cases of CDI and falsely identify some cases as positive when they are not [1,4]. The poor positive predictive values of toxin detection kits, especially in the context of widespread testing, and the possibility of missing true positives mean there are limitations to using these as single tests for the laboratory diagnosis of CDI. If a kit is used then it should be one of the better performing assays [1]. Caution is required in the interpretation of toxin-positive results from diagnostic kits to ensure that these are consistent with the clinical presentation. The issuing of interpretive comments with reports may aid clinicians in interpreting results. The use of a confirmatory test, as part of a diagnostic algorithm, will increase the accuracy of toxin-positive results. However, the optimum combination of diagnostic tests for CDI needs to be defined. Well-performed cell-culture cytotoxicity assays remain a gold standard for diagnostic testing. The HPA has issued a series of questions and answers in response to the CEP evaluation [5].
References
1. NHS Purchasing and Supplies Agency, Centre for Evidence based Purchasing. Clostridium difficile toxin detection assays. Evaluation report CEP08054, 2009. Wilcox MH, Eastwood KA. Available at: www.pasa.nhs.uk/pasa/Doc.aspx?Path=%5bMN%5d%5bSP%5d/NHSprocurement/CEP/CEP08054.pdf. Accessed 17 March 2009.
2. Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN. A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 2008; 62:388-96.
3. Freeman J, Wilcox MH. The effects of storage conditions on viability of Clostridium difficile vegetative cells and spores and toxin activity in human faeces. J Clin Pathol 2003;56:126-8.
4. Planche T, Aghaizu A, Holliman R, Riley P, Poloniecki J, Breathnach A, Krishna S. Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review. Lancet Infect Dis 2008; 8:777-84.
5. Health Protection Agency C. difficile Diagnosis Working Group:Questions and answers about the laboratory diagnosis of Clostridium difficile infection, www.hpa.org.uk/infections/cdifficileq&a.