we traded the

culture for blindness

Problem statement

Neisseria gonorrhoeae infects 82 million people per year and has sequentially developed resistance to every antibiotic class used against it over 80 years: sulfonamides, penicillins, tetracyclines, macrolides, and fluoroquinolones. Ceftriaxone resistance — the last-line treatment — rose from 0.8% to 5% globally between 2022 and 2024. Extensively drug-resistant "super-gonorrhea" strains resistant to both ceftriaxone and azithromycin have been reported across multiple continents. Yet the global shift from culture-based to molecular (NAAT) diagnostics, while improving detection sensitivity, has inadvertently destroyed our ability to perform antibiotic susceptibility testing — NAATs do not yield live organisms. Laboratories worldwide are losing the capacity and expertise to perform gonorrhea culture, creating a dangerous surveillance blind spot precisely as resistance accelerates.

Why this matters

Without point-of-care resistance information, clinicians must treat empirically with the most powerful remaining antibiotics, accelerating resistance selection. The WHO/FIND/GARDP collaboration developed two TPPs in 2020: one for a rapid diagnostic test (TPP1, <=30 minutes, <$3) and one for an AMR/susceptibility test (TPP2, <=60 minutes, <$25). Neither exists. The WHO's Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) has limited or no data from Eastern Europe, Central Asia, Latin America, the Eastern Mediterranean, and most of Africa — the regions with the majority of cases. We are losing the ability to track resistance in the pathogen most likely to become completely untreatable.

What’s been tried and why it hasn’t worked

Culture-based susceptibility testing is the gold standard but requires specialized media, controlled CO2 atmosphere, 24-48 hour incubation, and trained microbiologists — infrastructure that is disappearing even in high-income countries as NAATs take over routine diagnosis. Molecular prediction of resistance is complicated by N. gonorrhoeae's complex resistance mechanisms: cephalosporin resistance involves multiple interacting genes (penA, mtrR, porB, ponA), making genotype-to-phenotype prediction unreliable. ResistancePlus GC (SpeeDx) is FDA-approved for ciprofloxacin susceptibility detection (94.8% sensitivity, 100% specificity) but has limited clinical value since >95% of isolates are already ciprofloxacin-resistant in many regions. No molecular test reliably predicts ceftriaxone susceptibility — the drug that matters most.

What would unlock progress

Two TPP-aligned approaches are closest: (1) a novel non-molecular lateral flow assay (NG-LFA) for rapid diagnosis meeting TPP1 requirements, recently evaluated with promising results; and (2) a multiplex HRM PCR assay achieving 98.6% sensitivity and 99.2% specificity for AMR determinant detection across four drug classes at <$1/sample, though it still requires molecular infrastructure. The critical unmet need is a test that can predict ceftriaxone susceptibility from clinical specimens without culture — which likely requires either breakthrough genotype-phenotype mapping or a novel rapid phenotypic approach.

Entry points for student teams

A bioinformatics team could build a machine learning model that predicts ceftriaxone resistance from targeted gene panels and ask which minimal marker set reaches clinically useful accuracy, training on NCBI Pathogen Detection's Neisseria gonorrhoeae browser — a public, no-login FTP release whose metadata table carries paired `AST_phenotypes` and `AMR_genotypes` fields alongside the assemblies, refreshed weekly (https://ftp.ncbi.nlm.nih.gov/pathogen/Results/Neisseria_gonorrhoeae/). A microfluidics team could build the rapid phenotypic susceptibility device — capture organisms, expose them to ceftriaxone in microchannels, read growth/no-growth by fluorescence in 2–4 hours — and characterize it on spiked mock swab matrices: known-phenotype laboratory strains seeded into a cervical or urethral mucus simulant with commensal Neisseria as the interfering background, which is where the real engineering problem (viable capture from mixed flora without conventional culture) actually lives. That bench arm needs a BSL-2 microbiology lab and characterized strains — the 2024 WHO gonococcal reference panel of 15 strains spans every susceptible and resistant phenotype including new-penA ceftriaxone resistance (Unemo et al., J Antimicrob Chemother 2024) and is distributed through the WHO Collaborating Centre that curates it, so a faculty microbiologist has to request them. Running the device on actual clinical swabs takes an STI-clinic partnership and IRB approval that the clinic owns; the semester deliverable is the characterized device plus the clinical evaluation protocol. Relevant disciplines: microbiology, microfluidics, bioinformatics, antimicrobial resistance research.