Performance of plague rapid diagnostic test compared to bacteriology: a retrospective analysis of the data collected in Madagascar

Abstract

Background: Plague is a highly fatal disease caused by Yersinia pestis. Late diagnosis hampers disease outcome and effectiveness of control measures, induces death and disease spread. Advance on its diagnosis was the use of lateral flow rapid diagnostic test (RDT). Methods: We assessed the performance of the plague RDT based on Y. pestis F1 antigen detection more than 15 years after its deployment in Madagascar. We compared the RDT with bacteriological culture results, using data from plague notified cases collected during the periods for which both tests were performed independently and systematically. Results: Used with bubonic plague (BP) patient samples, RDTs had a sensitivity of 100% (95% CI: 99.7-100%), a specificity of 67% (95% CI: 64-70%) with a good agreement between bacteriology and RDT results (86%; κ = 0.70, 95% CI 0.67-0.73). For pneumonic plague (PP), RDT had a sensitivity of 100% (95% CI: 91-100%) and a specificity of 59% (95% CI: 49-68%) and concordance between the bacteriological and plague RDT results was moderate (70%; κ = 0.43, 95% CI 0.32-0.55). Analysis focusing on the 2017-2018 plague season including the unprecedented epidemic of PP showed that RDT used on BP samples still had a sensitivity of 100% (95% CI: 85-100%) and a specificity of 82% (95% CI: 48-98%) with a very good agreement with bacteriology 94% (κ = 0.86, 95% CI 0.67-1); for PP samples, concordance between the bacteriological and plague RDT results was poor (61%; κ = − 0.03, 95% CI-0.17-0.10). Conclusions: RDT performance appeared to be similar for the diagnosis of BP and PP except during the 2017 PP epidemic where RDT performance was low. This RDT, with its good sensitivity on both plague clinical forms during a normal plague season, remained a potential test for alert. Particularly for BP, it may be of great value in the decision process for the initiation of therapy. However, for PP, RDT may deliver false negative results due to inconsistent sample quality. Plague diagnosis could be improved through the development of next generation of RDTs.

Pulse-Controlled Amplification–A new powerful tool for on-site diagnostics under resource limited conditions

“…For plague outbreaks in China it has even been reported that it can take up to 15 days to obtain final laboratory results [6], further illustrating the urgent need for reliable decentralized diagnostics. This is also confirmed by Rajerison et al, stating that "improving all tools for plague diagnosis, including those suitable for point-of-care screening in remote areas remains a research priority to control human plague" [4]. Besides the risk of natural outbreaks, modern threats of bioterrorism have the potential to cause mass casualty incidents of serious infectious diseases, and therefore also require quick and reliable diagnostic tests that can be performed on-site rather than in a centralized laboratory [7].…”

“…During this outbreak immunochromatographic rapid tests were used for decentralized diagnostics. However a recently published study revealed that the tests used lack both sensitivity and specificity [4]. In addition, the only laboratory able to provide confirmatory diagnostics is located in the capital of Madagascar, Antananarivo.…”

“…Thus, they have become an indispensable technique in point of care (POC) testing and are used by first responders worldwide [8,9]. However, data on sensitivity and specificity of LFAs is limited but generally points to high detection limits and often lack of specificity [4,10,11]. Furthermore, sensitivity of detection methods based on antigen recognition is dependent on the permanent presence and sufficient concentration of the specific antigen.…”

The State of the Art in Biodefense Related Bacterial Pathogen Detection Using Bacteriophages: How It Started and How It’s Going

“…Alternatively, a positive diagnosis can be determined by observing a 4-fold difference in antibody titers to F1 capsular antigen [54]. Rapid test using ELISA, LFI, PCR, or real-time PCR have been developed to speed up the detection or diagnosis of plague [55][56][57][58][59][60][61][62].…”

Epitope Binning of Novel Monoclonal Anti F1 and Anti LcrV Antibodies and Their Application in a Simple, Short, HTRF Test for Clinical Plague Detection

“…Plague’s pathogen, Yersinia pestis , is categorized as a Tier 1 select agent [ 13 ], highlighting the need for specific assays that will enable rapid and accurate detection at the earliest possible stage of infection. Detection of F1, as a soluble protein in clinical specimens, has been reported as a reliable indication of plague infection [ 14 , 15 , 16 , 17 ]. Recently, we reported that Vag, which is a part of the type III secretion system of Y. pestis , could also be used as a soluble disease biomarker for the early detection of plague [ 18 ].…”