Why, when, and how should rabies be diagnosed?

A recent open access review paper by Veasna Duong and colleagues summarises the different techniques available for the laboratory diagnosis of rabies in animals and humans and goes on to recommend how these techniques should be applied in a variety of settings to best inform rabies control efforts. Because laboratory diagnostic capacity is often a crucial bottleneck to implementing and monitoring community-based elimination intervention programs, the review’s information should be very useful to rabies control program managers.

Evidence of infection with the rabies virus can be detected directly by culturing the virus, detecting its RNA, detecting its antigens, or indirectly by detecting antibodies raised against it by the host’s immune system. Several diagnostic techniques within each category exist, and the paper briefly reviews the advantages and challenges of each, along with the type and quality of samples that can be analysed.

Genetic analysis of viral RNA can help identify the virus’ origin, but this method requires skilled laboratory staff with reliable supplies of reagents and stable infrastructure such as constant cold storage. Whilst the direct fluorescent antibody test (FAT) remains the only recommended technique for routine use in national reference laboratories, in more remote settings the direct rapid immunohistochemical test (DRIT) might be a good fit, so long as a reliable source of antibodies is available. Although highly promising and simple, lateral flow tests are currently not recommended for routine diagnosis by OIE or WHO because of their variable properties and the need for further validation. The lateral flow tests do, however, have a role to play in research or where sample transportation to more central facilities is difficult.

Techniques for taking samples from suspected cases, analysing samples of poor quality, and taking both ante- and post-mortem human samples without the need for removal of the brain are also reviewed.

In non-endemic settings, any suspected case of rabies in human or animals should be investigated thoroughly to determine the origin of the infection and quickly identify rabies re-emergence, to guide outbreak responses, and inform patient management.

Ideally in canine rabies endemic settings, laboratory confirmation would be carried out routinely on the brains from suspected rabid animals to ensure that post-exposure prophylaxis (PEP) is supplied as necessary. Human case laboratory diagnosis is extremely valuable where the biting animal is not available for testing, for non-typical (e.g., paralytic) rabies encephalitis cases, and for apparent PEP failures. However, in most settings with high case loads, a diagnosis of “probable rabies” in humans can routinely rely on the occurrence of a bite from a potentially rabid animal and clinical signs in the patient.

Without laboratory confirmation, it is impossible to be sure of the true burden of rabies in a country and to advocate for more resources to control it. As control efforts start to have their impact, more widespread use of rabies diagnostics can inform the refinement of control approaches, and the diagnostic strategy should evolve towards that of a non-endemic area as elimination of the virus is approached.

Summarised by Louise Taylor from the paper “Laboratory diagnostics in dog-mediated rabies–an overview of performance and a proposed strategy for various settings”, by Duong, et al. (2016) published in International Journal of Infectious Diseases.