New STI diagnostics Nicola Low, Institute of Social and Preventive Medicine, University of Bern, Switzerland Sunday 22nd July, 2018, Session 7 Diagnostics STI 2018 Understanding and addressing HIV and STI syndemics Amsterdam, 21-22 July 2018 @nicolamlow

̴1 million new infections every day Where the STIs are ̴1 million new infections every day Chlamydia; gonorrhoea; syphilis; trichomonas; Mycoplasma genitalium; genital herpes; HPV; hepatitis @nicolamlow

Outline Prioritising development of a new STI test Multiplex tests The lens of antimicrobial resistance The future? Conclusions @nicolamlow

Prioritising the development of a new STI test What we need What is commercially viable High burden of disease Near patient Simple, robust technologies Tricky targets Antimicrobial resistance detection High value market Laboratory-based Large multipurpose machines Easy targets @nicolamlow mChip: Junco Labs, Columbia University, with OPKO Health, Inc. Roche cobas® 6800 system

WHO essential diagnostics list, 2018 “Other tests are designed to detect, diagnose and monitor “priority” diseases, such as HIV, tuberculosis, malaria, hepatitis B and C, human papillomavirus and syphilis.” @nicolamlow http://www.who.int/medical_devices/diagnostics/WHO_EDL_2018.pdf

Technology revolution 1. Specimen 2. Extract nucleic acids 3. Amplify nucleic acids 4. Detect product New STI diagnostics Technology revolution Source: Seegene Anyplex II STI 7

Point-of-care or near point-of-care STI tests Unemo M, et al. Lancet Infect Dis 2017; Murtagh M. The Point-of-Care Diagnostic Landscape for STIs @nicolamlow

Multiplex pathogen detection New STI diagnostics Multiplex pathogen detection

Mycoplasma genitalium @nicolamlow

Just because we can… @nicolamlow http://www.randox.com/wp-content/uploads/delightful-downloads/2015/09/LT250.pdf

New STI diagnostics Diagnostics: the “Achilles Heel” of antimicrobial resistance containment Okeke IN et al. Drug Resistance Updates 2011

Detection of antimicrobial resistance Pathogen Antimicrobial resistance Test for pathogen? Test for resistance? Chlamydia trachomatis No Yes N/A Neisseria gonorrhoeae Mycoplasma genitalium Trichomonas vaginalis (Yes) Treponema pallidum “[A] reasonable question is whether diagnostic test manufacturers, regulators, and researchers should have considered the implications that [nucleic acid amplification tests for gonorrhoea diagnosis might have on AMR before promoting and expanding their use so widely.” Low N, et al. PLOS Medicine 2014 @nicolamlow

Mycoplasma genitalium resistance Resistance-guided therapy algorithm Cadosch DR et al. biorXiv 2018 Read TR et al. Clin Infect Dis 2018 @nicolamlow

Tests for N. gonorrhoeae resistance markers @nicolamlow Whiley DM et al. Emerg Infect Dis 2017

Ciprofloxacin-resistant N. gonorrhoeae 2014 3.4 billion people live in countries with >70% ciprofloxacin resistance @nicolamlow

New STI diagnostics The future?

Nanopore MinION “In this first MinION study for gonococci, we show that MinION-derived sequences analysed with existing open-access, web-based sequence analysis tools are not sufficiently accurate to identify key gonococcal AMR determinants.” @nicolamlow Golparian D et al. bioRxiv 2018

Conclusions Available new diagnostic tests Cannot replace syndromic management in resource poor settings Could cause more problems than they solve in resource rich settings through overdiagnosis Targets for multiplex tests need to be chosen rationally Molecular diagnostic tests for antimicrobial resistance are essential, but complicated Incentives need to influence development The right test for the right infection in the right place @nicolamlow

Acknowledgements Igor Toskin, WHO Magnus Unemo, Rosanna Peeling RaDAR-Go (Rapid Diagnosis of Antimicrobial Resistance in Gonorrhoea) project funded by SwissTransMed