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As in other medical fields, the availability of next generation sequencing (NGS) techniques is about to revolutionize diagnostics of infectious diseases. The demonstration of the microbial origin of diseases and their diagnosis were initially based on the demonstration of the presence of a given pathogen in a given clinical sample, and was first dominated by culture assay for bacteria and later for viruses. These techniques do not advance prior hypotheses regarding the causative agents except their cultivability. In order to seek specific pathogens, specialized media—rich or selective—and culture conditions—defined oxygen tension or temperature—can be used. These techniques suffer a number of limitations, including the need for a dedicated specialized staff and their intrinsic inefficiency in the propagation of fastidious bacteria and several major viruses (Treponema palidum, Mycobacterium leprae, Hepatitis A, B, C and E viruses). They have been progressively complemented and sometimes replaced by nucleic acid-based tests like PCR or NASBA. The advantages of PCR are numerous: speed, low cost, automation, sensitivity, and specificity. The main drawback of targeted, pathogen-specific PCR is that it is only able to identify predefined targets, which supposes that the physician has elaborated an etiological hypothesis. Moreover, for a series of pathogens, and in particular highly variable RNA viruses like enteroviruses or DNA viruses such as papillomaviruses and adenoviruses that comprise multiple types, PCR-based tests target conserved loci that do not discriminate between genotypes.

The diagnosis of infectious diseases by whole genome next generation sequencing: a new era is opening