Comparison of established and emerging biodosimetry assays

Rapid biodosimetry tools are required to assist with triage in the case of a large-scale radiation incident. Here, we aimed to determine the dose-assessment accuracy of the well-established dicentric chromosome assay (DCA) and cytokinesis-block micronucleus assay (CBMN) in comparison to the emerging γ-H2AX foci and gene expression assays for triage mode biodosimetry and radiation injury assessment. Coded blood samples exposed to 10 X-ray doses (240 kVp, 1 Gy/min) of up to 6.4 Gy were sent to participants for dose estimation. Report times were documented for each laboratory and assay. The mean absolute difference (MAD) of estimated doses relative to the true doses was calculated. We also merged doses into binary dose categories of clinical relevance and examined accuracy, sensitivity and specificity of the assays. Dose estimates were reported by the first laboratories within 0.3-0.4 days of receipt of samples for the γ-H2AX and gene expression assays compared to 2.4 and 4 days for the DCA and CBMN assays, respectively. Irrespective of the assay we found a 2.5-4-fold variation of interlaboratory accuracy per assay and lowest MAD values for the DCA assay (0.16 Gy) followed by CBMN (0.34 Gy), gene expression (0.34 Gy) and γ-H2AX (0.45 Gy) foci assay. Binary categories of dose estimates could be discriminated with equal efficiency for all assays, but at doses ≥1.5 Gy a 10% decrease in efficiency was observed for the foci assay, which was still comparable to the CBMN assay. In conclusion, the DCA has been confirmed as the gold standard biodosimetry method, but in situations where speed and throughput are more important than ultimate accuracy, the emerging rapid molecular assays have the potential to become useful triage tools

Klebsiella pneumoniae resistant to third-generation cephalosporins in five African and two Vietnamese major towns: multiclonal population structure with two major international clonal groups, CG15 and CG258.

International audienceThe molecular epidemiology of third-generation cephalosporin-resistant (3GC-R) Klebsiella pneumoniae in developing countries is poorly documented. From February 2007 to March 2008, we collected 135 3GC-R K. pneumoniae isolates from seven major towns in Maghreb (Morocco), West Africa (Senegal, Côte d'Ivoire), Central Africa (Cameroon), East Africa (Madagascar) and Southeast Asia (Vietnam). Their genetic diversity, assessed by multilocus sequence typing, was high (60 sequence types), reflecting multiclonality. However, two major clonal groups, CG15 (n = 23, 17% of isolates) and CG258 (n = 18, 13%), were detected in almost all participating centres. The two major clonal groups have previously been described in other parts of the world, indicating their global spread. The high diversity of enterobacterial repetitive intergenic consensus sequence-PCR banding patterns at the local level indicates that most isolates were epidemiologically unrelated. The isolates were characterized by the presence of multiple resistance determinants, most notably the concomitant presence of the aac(6')-Ib-cr, qnr and bla(CTX-M-15) genes in 61 isolates (45%) belonging to 31 sequence types. These isolates were detected across a large geographical area including Cameroon (n = 1), Vietnam (n = 4), Madagascar (n = 10), Côte d'Ivoire (n = 12), Morocco (n = 13) and Senegal (n = 21). These results have major implications for patient management and highlight a potential reservoir for resistance determinants