Emerging Technologies for the Detection of Rabies Virus: Challenges and Hopes in the 21st Century

Abstract

The diagnosis of rabies is routinely based on clinical and epidemiological information, especially when exposures are reported in rabies-endemic countries. Diagnostic tests using conventional assays that appear to be negative, even when undertaken late in the disease and despite the clinical diagnosis, have a tendency, at times, to be unreliable. These tests are rarely optimal and entirely dependent on the nature and quality of the sample supplied. In the course of the past three decades, the application of molecular biology has aided in the development of tests that result in a more rapid detection of rabies virus. These tests enable viral strain identification from clinical specimens. Currently, there are a number of molecular tests that can be used to complement conventional tests in rabies diagnosis. Indeed the challenges in the 21st century for the development of rabies diagnostics are not of a technical nature; these tests are available now. The challenges in the 21st century for diagnostic test developers are two-fold: firstly, to achieve internationally accepted validation of a test that will then lead to its acceptance by organisations globally. Secondly, the areas of the world where such tests are needed are mainly in developing regions where financial and logistical barriers prevent their implementation. Although developing countries with a poor healthcare infrastructure recognise that molecular-based diagnostic assays will be unaffordable for routine use, the cost/benefit ratio should still be measured. Adoption of rapid and affordable rabies diagnostic tests for use in developing countries highlights the importance of sharing and transferring technology through laboratory twinning between the developed and the developing countries. Importantly for developing countries, the benefit of molecular methods as tools is the capability for a differential diagnosis of human diseases that present with similar clinical symptoms. Antemortem testing for human rabies is now possible using molecular techniques. These barriers are not insurmountable and it is our expectation that if such tests are accepted and implemented where they are most needed, they will provide substantial improvements for rabies diagnosis and surveillance. The advent of molecular biology and new technological initiatives that combine advances in biology with other disciplines will support the development of techniques capable of high throughput testing with a low turnaround time for rabies diagnosis.

Re-emergence of rabies in dogs and other domestic animals in eastern Bhutan, 2005–2007

“…A thorough investigation is undertaken in the event of a suspected outbreak in animals. A fluorescent antibody test (FAT) -which is recommended by both the WHO and World Animal Health Organization (OIE) -is used to confirm rabies in animals (Dean et al, 1996;McElhinney et al, 2008;Fooks et al, 2009). The epidemiological data are collected and stored in the Veterinary Information System (VIS) database.…”

Bat Reservoirs for Rabies Virus and Epidemiology of Rabies in Colombia: a review

“…It is an alternative test that have been demonstrated to be more sensitive than Hn-RT-PCR and can be used to further extend the rabies RNA detection limits in decomposed samples 67 . This technique allows to assess gene expression analysis, determination of viral load and detection of genetically modified organisms 68 .…”

Evaluation of RT-PCR Assay for Routine Laboratory Diagnosis of Rabies in Post Mortem Brain Samples from Different Species of Animals

“…This genome sequence data will be useful in molecular epidemiological studies to trace the origin and movement of the viruses. Molecular tools based on the detection of the viral genome are becoming widely accepted and accessible for the diagnosis of rabies [8]. Although the FAT is a simple and rapid technique, the evaluation of results can be subjective.…”

“…An important factor influencing the interpretation of the FAT results is the strong background fluorescence of the visible field caused by the immunofluorescent conjugate [12]. Moreover for numerous diagnostic laboratories in rabies-endemic regions of the developing world, cost and simplicity are critical factors in disease diagnosis which cannot be neglected, even when the principal consideration is for rapid diagnosis [8]. RT-PCR is a suitable alternative for FAT in rabies diagnosis as the cost incurred per diagnostic sample is lesser than that of FAT.…”