Pharmacogenomics testing to optimize medical countermeasures against chemical warfare agents and bacterial biothreats in military settings

Introduction: Pharmacogenomics testing is a promising tool for strengthening medical countermeasures against military threats such as chemical warfare agents and bacterial biothreats. This review assesses the role of pharmacogenomics in military healthcare, highlighting distinct requirements in defence compared to civilian settings. Methods: We conducted a systematic review (PubMed, 2010-2025) to identify publications focusing on pharmacogenomics, nerve agent susceptibility, and tularemia treatment. Key search terms included combinations relevant to genetic factors affecting chemical and bacterial threat responses. Studies were evaluated for genetic variations influencing nerve agent toxicity, related treatment responses, and antibiotic pharmacogenomics. Results: Genetic variants substantially impact susceptibility to nerve agents and the effectiveness of countermeasures. Polymorphisms in acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) modify toxicity risk and treatment response to oximes, atropine, and benzodiazepines. For bacterial biothreats, genetic factors affect antibiotic efficacy and risk for adverse reactions, especially with aminoglycosides, fluoroquinolones, and tetracyclines. Sex and gender differences in pharmacogenomic responses are important yet under-recognized. Discussion: Integrating pharmacogenomic testing in military health care has the potential to improve force protection and operational readiness for chemical and biological threats. Nonetheless, challenges remain, including cost, logistical feasibility in mass casualty events, and the development of rapid deployable testing platforms. Future research should emphasize validation studies and implementation strategies tailored for military needs.