Further Evidence of Inadequate Quality in Lateral Flow Devices Commercially Offered for the Diagnosis of Rabies

Abstract

As a neglected zoonotic disease, rabies causes approximately 5.9 × 104 human deaths annually, primarily affecting low- and middle-income countries in Asia and Africa. In those regions, insufficient surveillance is hampering adequate medical intervention and is driving the vicious cycle of neglect. Where resources to provide laboratory disease confirmation are limited, there is a need for user-friendly and low-cost reliable diagnostic tools that do not rely on specialized laboratory facilities. Lateral flow devices (LFD) offer an alternative to conventional diagnostic methods and may strengthen control efforts in low-resource settings. Five different commercially available LFDs were compared in a multi-centered study with respect to their diagnostic sensitivity and their agreement with standard rabies diagnostic techniques. Our evaluation was conducted by several international reference laboratories using a broad panel of samples. The overall sensitivities ranged from 0% up to 62%, depending on the LFD manufacturer, with substantial variation between the different laboratories. Samples with high antigen content and high relative viral load tended to test positive more often in the Anigen/Bionote test, the latter being the one with the best performance. Still, the overall unsatisfactory findings corroborate a previous study and indicate a persistent lack of appropriate test validation and quality control. At present, the tested kits are not suitable for in-field use for rabies diagnosis, especially not for suspect animals where human contact has been identified, as an incorrect negative diagnosis may result in human casualties. This study points out the discrepancy between the enormous need for such a diagnostic tool on the one hand, and on the other hand, a number of already existing tests that are not yet ready for use.

Evaluation of a Rapid Immunochromatographic test kit to the Gold Standard Fluorescent Antibody test for diagnosis of rabies in animals in Bhutan

“…Thus, no fatal outcome in human was reported due to false negative results of the rapid test in Bhutan. Like in our study, many studies [18,26] have reported high specificity (98.9 to 100%) of the rapid test (BioNote), so the false positive outcomes were low which would otherwise may lead to unnecessary use of limited resources including PEP and response activities [26]. However, to our knowledge, only one study has reported false positive results (two false positive among 30 FAT negative specimens), with a specificity of 93.3% [16].…”

“…Other studies have also evaluated the rapid kit BioNote, Inc. (Hwaseong-si, Korea) relative to the FAT for detecting rabies virus in the brain samples and have reported diagnostic sensitivities either higher (95 to 100%) [15][16][17][18][19][20][21] or lower (88.3 to 91.7%) [22][23][24] while most of the diagnostic specificities were also between 98.9 to 100% [18]. However, two studies [25,26] detected poor sensitivity of the existing commercially available rapid kits when compared with FAT and the molecular test, but the sensitivity of rapid kit (BioNote) was higher (62-100%) than the other commercially available rapid test kits. The Rapid kit produced by the BioNote target the N-gene (nucleoprotein) while other kits do not have information on which antigen it is targeted and thus may be related to poor sensitivities [22,26].…”

“…However, two studies [25,26] detected poor sensitivity of the existing commercially available rapid kits when compared with FAT and the molecular test, but the sensitivity of rapid kit (BioNote) was higher (62-100%) than the other commercially available rapid test kits. The Rapid kit produced by the BioNote target the N-gene (nucleoprotein) while other kits do not have information on which antigen it is targeted and thus may be related to poor sensitivities [22,26].…”

Evaluation of a Rapid Immunochromatographic test kit to the Gold Standard Fluorescent Antibody Test for Diagnosis of Rabies in Animals in Bhutan

“…So, no fatal outcome in human was reported due to false negative results of the rapid test in Bhutan. Like in our study, many studies [18,26] have reported high specificity (98.9 to 100%) of the rapid test (BioNote), so the false positive outcomes were low which would otherwise may lead to unnecessary use of limited resources including PEP and response activities [26]. However, one study has reported false positive results (two false positive among 30 FAT negative specimens), with a specificity of 93.3% [16].…”

“…to 100% [18]. However, two studies [25,26] In Bhutan, FAT is the only reference standard test available for diagnosis of rabies and is a routine diagnostic test for rabies recommended both by WHO and OIE [13]. Although FAT is highly sensitive and specific (between 98% and 100%) it depends heavily on the quality of the immunofluorescent conjugate, the maintenance of the fluorescent microscope and on an experienced technician performing test and reading the microscope slides [13].…”