{ "abstract": "Substandard and falsified (SF) medicines are a neglected public health threat, with an estimated 7% of antimicrobials in low- and middle-income countries being SF. However, quantifying their clinical impact remains challenging. We developed a general framework for estimating population-level impacts of SF antimicrobials on patient outcomes and apply it to SF fluoroquinolones in typhoid treatment. The framework combines two data sources: published surveys of antimicrobial quality to characterize the distribution of active pharmaceutical ingredient (API) content and individual-level patient data to estimate dose-response relationships. These are synthesized to evaluate population-level impacts. We extracted data from surveys of fluoroquinolone quality and fitted generalized additive models to data from seven clinical trials to estimate the causal effect of ofloxacin dose on typhoid outcomes. Application to typhoid demonstrated that while dose had negligible overall effect within trial dose ranges, lower doses worsened outcomes for non-susceptible strains. When the minimum inhibitory concentration was 1 mg/L, ofloxacin matching observed ofloxacin quality (mean %API = 102.8%) improved fever clearance by 4.1 hours (90% CrI: 0.75–8.7) compared to 100% API. At the same minimum inhibitory concentration, ofloxacin whose %API instead matched the ciprofloxacin surveys (mean %API = 93.6%) worsened fever clearance by 11 hours (90% CrI: 1.9–25). This framework can quantify the impact of SF antimicrobials on different pathogen–antimicrobial pairs. For typhoid, it demonstrates that SF fluoroquinolones likely have a substantial impact on treatment outcomes in settings like South Asia where non-susceptible strains are prevalent. Increased vigilance around antimicrobial quality is important in such settings.", "abstract_shown": true, "affiliations": [ "Nuffield Department of Medicine, Drug Resistant Infections and Disease Dynamics (DRIaDD) Research Group, NDM Centre for Global Health Research, University of Oxford, Oxford, United Kingdom", "Nuffield Department of Medicine, Medicine Quality Research Group (MQRG), NDM Centre for Global Health Research, University of Oxford, Oxford, United Kingdom", "Nuffield Department of Medicine, Infectious Diseases Data Observatory, NDM Centre for Global Health Research, University of Oxford, Oxford, United Kingdom", "Mahidol Oxford Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand", "Nuffield Department of Medicine, Antimicrobial resistance, antimicrobial consumption and burden estimation (MICRoBE) research group, NDM Centre for Global Health Research, University of Oxford, Oxford, United Kingdom", "Nuffield Department of Medicine, Modernizing Medical Microbiology, University of Oxford, Oxford, United Kingdom", "NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance at University of Oxford in partnership with Public Health England, Nuffield Department of Medicine, Oxford, United Kingdom", "NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom", "Nuffield Department of Medicine, Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, United Kingdom" ], "article_type": "Research Article", "arxiv": null, "author_total": 12, "authors": [ { "affs": [ 0 ], "name": "Sean Cavany" }, { "affs": [ 1 ], "name": "Lawrence Adipo" }, { "affs": [ 2 ], "name": "Kerlijn van Assche" }, { "affs": [ 3 ], "name": "Celine Caillet" }, { "affs": [ 4 ], "name": "Christiane Dolecek" }, { "affs": [ 5 ], "name": "Cathrin Hauk" }, { "affs": [ 6 ], "name": "Jessica Mendes" }, { "affs": [ 7 ], "name": "Stella Nanyonga" }, { "affs": [ 8 ], "name": "Nicole Stoesser" }, { "name": "Paul N. Newton" }, { "name": "Christopher M. Parry" }, { "name": "Ben S. Cooper" } ], "bibtex": "https://research.draconitic.com/paper/d10vkpgc21zyb.bib", "cited_by": 0, "doi": "10.1371/journal.pgph.0007207", "fulltext_url": "https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0007207", "id": "d10vkpgc21zyb", "issns": [ "2767-3375" ], "landing_url": "https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0007207", "language": null, "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "openalex", "2739|Pharmaceutical Quality and Counterfeiting" ], [ "plos", "/Biology and life sciences/Microbiology/Medical microbiology/Microbial pathogens/Bacterial pathogens/Salmonella/Salmonella typhi" ], [ "plos", "/Biology and life sciences/Microbiology/Microbial control/Antimicrobials" ], [ "plos", "/Biology and life sciences/Microbiology/Microbial control/Antimicrobials/Antibiotics" ], [ "plos", "/Biology and life sciences/Organisms/Bacteria/Enterobacteriaceae/Salmonella/Salmonella typhi" ], [ "plos", "/Medicine and health sciences/Clinical medicine/Signs and symptoms/Fevers" ], [ "plos", "/Medicine and health sciences/Epidemiology/Medical risk factors" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Bacterial diseases/Salmonella/Salmonella typhi" ], [ "plos", "/Medicine and health sciences/Medical conditions/Infectious diseases/Bacterial diseases/Typhoid" ], [ "plos", "/Medicine and health sciences/Pathology and laboratory medicine/Pathogens/Microbial pathogens/Bacterial pathogens/Salmonella/Salmonella typhi" ], [ "plos", "/Medicine and health sciences/Pharmaceutics/Dose prediction methods" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drugs/Antimicrobials" ], [ "plos", "/Medicine and health sciences/Pharmacology/Drugs/Antimicrobials/Antibiotics" ], [ "plos", "/Medicine and health sciences/Public and occupational health" ] ], "openalex": "W4412354192", "pdf_url": "https://journals.plos.org/globalpublichealth/article/file?id=10.1371/journal.pgph.0007207&type=printable", "pmcid": null, "pmid": null, "published": "2026-08-31", "publisher": "Public Library of Science", "ris": "https://research.draconitic.com/paper/d10vkpgc21zyb.ris", "sources": [ { "first_seen": "2026-10-30T12:18:02Z", "native_id": "10.1371/journal.pgph.0007207", "source": "plos", "url": "https://journals.plos.org/globalpublichealth/article?id=10.1371/journal.pgph.0007207" } ], "subjects": [ { "field": "biology", "origin": "plos:microbiology", "subfield": "microbiology" }, { "field": "medicine", "origin": "plos:epidemiology", "subfield": "epidemiology-public-health" }, { "field": "medicine", "origin": "plos:infectious diseases", "subfield": "infectious-disease" } ], "title": "A novel framework for quantifying the clinical impact of substandard and falsified antimicrobials: Application to typhoid fever", "title_text": "A novel framework for quantifying the clinical impact of substandard and falsified antimicrobials: Application to typhoid fever", "type": "peer-reviewed", "updated_at": "2026-10-30T12:18:02Z", "url": "https://research.draconitic.com/paper/d10vkpgc21zyb", "venue": "PLOS Global Public Health", "versions": [] }