Evaluating Diagnostic Strategies for Lower Respiratory Tract Infections in Sri Lanka: A Cost-Effectiveness Analysis

Abstract

Lower respiratory tract infections (LRTIs) remain a major cause of infectious disease morbidity and mortality worldwide, particularly in low- and middle-income countries (LMICs) where diagnostic capacity is often limited. In these settings, clinicians frequently rely on empiric treatment, contributing to inappropriate antibiotic use and accelerating antimicrobial resistance (AMR). This study evaluated the cost-effectiveness of diagnostic strategies for hospitalized LRTIs in Sri Lanka to identify approaches that improve clinical outcomes while supporting more appropriate antimicrobial use.A decision-analytic model was developed primarily using data from the Respiratory Infection Severity and Etiology in Sri Lanka (RISE-SL) cohort study. The model compared three categories of diagnostic strategies: underutilized diagnostics currently available in Sri Lanka, novel host-response and molecular diagnostics not yet implemented in the public health system, and hypothetical diagnostics aligned with a global Target Product Profile (TPP). Costs were evaluated from a societal perspective and health outcomes were measured in disability-adjusted life years (DALYs). Uncertainty was addressed through probabilistic sensitivity analysis using 10,000 Monte Carlo simulations. Procalcitonin testing was highly cost-effective among underutilized diagnostics, while FebriDx was the most economically favorable novel diagnostic strategy. Hypothetical diagnostics meeting ideal TPP specifications demonstrated particularly strong cost-effectiveness. Although several strategies improved detection of bacterial infections, many also increased false-positive results, leading to higher rates of unnecessary antibiotic prescribing. These findings suggest that host-response diagnostics may offer the greatest value for improving LRTI management in Sri Lanka, while highlighting the importance of balancing diagnostic sensitivity with antimicrobial stewardship considerations and clinical decision making.