2.3 Detecting old and new pathogens

In a clinical setting, when a patient shows the symptoms of an infection, the identification of the responsible pathogen relies on targeted assays that only detect organisms we already suspect. However, it is possible that the pathogen may be entirely new to science or is appearing in an unusual host or location.

This is a scenario where metagenomics can play a crucial role. As you have learned across the previous sections, metagenomics is an agnostic approach. In medicine and microbiology, an agnostic approach refers to testing or investigation methods that do not target a specific suspected pathogen in advance but instead look broadly for any possible cause. By sequencing all genetic material in a sample, clinicians can move beyond ‘negative test’ results and uncover hidden or unexpected causes of illness.

Acute febrile illness (AFI) is one of the most common reasons for healthcare attendance in sub‑Saharan Africa, yet a large proportion of cases remain without an identified cause after routine testing.

In a recent study in Uganda (Ashraf et al, 2025) researchers looked at 210 patients where standard diagnostics could not determine the cause of their fever, along with 20 samples from known outbreak situations. Following metagenomic sequencing, viral pathogens were identified in 19% (44 out of 230) of the sequenced samples. The detected viruses included respiratory, gastrointestinal, blood-borne, hepatitis, and mosquito‑ or tick‑borne viruses.

Importantly, the study uncovered pathogens that had not been clinically suspected, including Crimean–Congo haemorrhagic fever virus, Rift Valley fever virus, dengue virus, and yellow fever virus, together accounting for 3% of cases. All these are high-consequence pathogens, meaning that they can cause severe disease and have major public health, economic, or societal impacts. The researchers also detected Le Dantec virus, which was not seen in Uganda since 1969.