Strengthening diagnosis through pathogen discovery and host genomic approaches

Newer diagnostic approaches, including those we have been developing in Liverpool, offer the best prospect for improving the diagnostic yield. These include multiplex PCR of CSF for common pathogens, VIRCAP enriched high throughput sequencing to improve pathogen detection, rapid diagnostic antibody detection kits, and characterising host response genes through mRNA microarray [8, 10, 14, 15]. This latter approach, for example our TRIM test (patent filed, in partnership with Fast Track Diagnostics) is proving especially useful distinguishing viral from bacterial infections, thus supporting appropriate use of antibiotics and helping to combat antimicrobial resistance. Automated molecular diagnostic approaches are reducing in price, and becoming especially suitable for settings where traditional microbiological skill sets are limited. 

We will apply these approaches to increase the diagnostic yield for brain infection patients in our partner countries, through longitudinal cohort studies. As far as possible, we will work in country, but where facilities are not available, and regulations allow sample transfer, work will be done in Liverpool. Our aim is to train, and roll-out technologies so that ultimately appropriate testing is available in all partner countries.

References

8. Mallewa M, Vallely P, Faragher B, et al. Viral central nervous system infections in children from a malaria-endemic area of Malawi: a prospective cohort study Lancet Global Health 2013; 1:e153–e60.

10. Benjamin LA, Lewthwaite P, Vasanthapuram R, et al. Human parvovirus 4 as potential cause of encephalitis in children, India. Emerg Infect Dis 2011; 17: 1484-7.

14. Lewthwaite P, Shankar MV, Tio P-H, et al. Evaluation of two commercially available ELISAs for the diagnosis of Japanese encephalitis applied to field samples. Tropical Medicine & International Health 2010; 15: 811-8.

15. Sweeney TE, Wong HR, Khatri P. Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. Sci Transl Med 2016; 8: 346ra91.