Pathogen sequencing from biopsy tissue for the diagnosis of infectious diseases not identified through conventional microbiological techniques. Direct sample pathogen sequencing for diagnosis

Infections with microbes intractable to culture in vitro remain diagnostically challenging. Some bacteria, such as Mycobacterium leprae, require cellular culture, while eukaryotic organisms cannot be cultured. Diagnosis of these infections historically depended on clinical and histological findings or targeted molecular detection. We describe a patient with uveitis, leg ulcers, splenomegaly and inguinal lymphadenopathy. Sequencing DNA from lymph node biopsy confirmed infection with Mycobacterium leprae. A second patient, presented with seizures and parietal lobe space occupying lesion. Sequencing from tissue revealed the tapeworm Taenia serialis confirming diagnosis of Coenurosis. Sequencing pathogen DNA renders the microbiological diagnosis of difficult pathogens tractable.