Laboratory evaluation of immunochromatographic rapid diagnostic tests for cholera in Haiti

Abstract

BackgroundRapid diagnostic tests (RDT) for cholera are promising tools for detecting cholera in areas with limited laboratory infrastructure. However, evidence on the characteristics of the many available RDTs is scarce, and their use has been limited by suboptimal performance. We evaluated the performance characteristics of three cholera RDTs from Span Diagnostics, Artron Laboratories, and Standard Diagnostics in a regional laboratory in Haiti.Methodology/Principal findingsWe retrospectively reviewed records from May 2014 to October 2015 of a laboratory-based surveillance program for Vibrio cholerae at Hôpital Saint-Nicolas in Saint-Marc, Haiti. We compared the results of 511 Crystal VC, 129 Artron and 451 SD Bioline RDTs to bacterial culture as the gold standard. Of 905 cultures, 477 (52.7%) were positive for V. cholerae O1, of which 27.7% were serotype Inaba. No cultures grew V. cholerae O139. Sensitivity and specificity of Crystal VC were 98.6% (95%CI: 96.5%-99.6%) and 71.1% (95%CI: 64.7%-76.9%), respectively. Artron demonstrated a sensitivity of 98.6% (95%CI: 92.7%-100%) and specificity of 69.1% (95%CI: 55.2%-80.9%). SD Bioline demonstrated a sensitivity of 81.1% (95%CI: 75.6%-85.8%) and specificity of 92.8% (95%CI: 88.4%-95.9%). Crystal VC and Artron frequently showed false positive O139 bands, whereas none were seen with SD Bioline.Conclusions/SignificanceThere is significant variation in the performance of different cholera diagnostic RDTs. Artron and Crystal VC RDTs have high sensitivity and low specificity, while SD Bioline RDT has low to moderate sensitivity and high specificity when performed by laboratory technicians in Haiti. Study limitations included its retrospective design. The suboptimal characteristics of these tests limit their use as clinical point-of-care tests; however, they may be useful in outbreak response, surveillance, and research in resource-limited settings.

Evaluation of the SD bioline cholera rapid diagnostic test during the 2016 cholera outbreak in Lusaka, Zambia

“…The performance of the SD Bioline test reported here and in Haiti suggest that the specificity of SD Bioline might be better than that of Crystal VC (49–88%), but that its sensitivity might be lower than Crystal VC (consistently around 92–97%) . High sensitivity is generally considered the most important criterion for screening tests, while moderate specificity can be overcome by re‐testing initially reactive samples using more specific confirmation assays.…”

“…This test also matches the recommendations from a target product profile for cholera RDTs recently developed by the GTFCC , in terms of cost (~2€ per test), ease of use and clinical performance, although the confidence intervals are too wide due to the relatively small sample size in our study. This, together with the recent retrospective analysis of routine results in Haiti showing a more modest sensitivity (81.1%) of the SD Bioline RDT compared to culture , highlight the need for additional prospective results on larger sample sizes and in different contexts.…”

“…First, the sample size was limited, in particular for cholera‐confirmed cases, leading to wide confidence intervals in the estimates. Whereas studies set up in outbreak situations with comprehensive outbreak response measures often have limited sample sizes , larger sample sizes can be obtained in endemic settings . Alternately, performing meta‐analyses using data from different studies and settings with similar study methods might be another way forward to get better insights into the performance of these tests.…”

“…Although several immunochromatographic RDTs are commercially available, most of the recent diagnostic evaluations have focused on one product, Crystal VC (Arkray Health Care Private Limited, India; previously Span Diagnostics, India), which has shown high sensitivity of more than 90%, but moderate specificity (49–88%) when used directly on stools . In addition, relatively high proportions of false‐positive results with the O139 line have been reported by several teams . The specificity of this test can be improved by a 4‐ to 6‐h enrichment step in alkaline peptone water (APW), with the disadvantage of increasing the necessary logistics required and delaying the turn‐around time for results to be available .…”

“…The specificity of this test can be improved by a 4‐ to 6‐h enrichment step in alkaline peptone water (APW), with the disadvantage of increasing the necessary logistics required and delaying the turn‐around time for results to be available . First data on two other tests, Artron Vibrio cholerae O139 and O1 Combo Test (Artron Laboratories Inc, Canada) and SD Bioline Cholera Ag O1/O139 RDT (Standard Diagnostics Inc., Korea), recently came from a retrospective analysis of routine data in Haiti comparing results of cholera RDTs to culture results . Whereas the Artron test, like Crystal VC, showed very high sensitivity of 98.6% and modest specificity around 70%, the SD Bioline RDT had a lower sensitivity of 81.1% but specificity of 92.8%.…”