The infectious aetiology of disease: the search for new agents

There are many diseases for which a microbial aetiology is suspected. The hypothesis that a disease has an infectious cause is supported by: clinical features (similar to those of known infectious diseases, e.g. fever, leucocytosis), epidemiology (case clustering in time or location), histology (inflammation of affected tissues, e.g. granulomata) or characteristic microbial structures, treatment (clinical response to antimicrobial treatment), and prevention of disease by vaccines targeting microbial antigens. Proof that a microbe causes a disease requires more rigorous evidence. Future attempts to identify novel microbes associated with human disease may use sequence-based approaches. High-throughput sequencing may allow identification of unique microbial nucleic acid sequences in a background of host DNA. The complete sequencing of the human genome and multiple microbial genomes make this approach more feasible. DNA microarrays are also likely to be used in the search for novel pathogens.