Institutional Readiness and Diagnostic Challenges for the Management of Pyrexia of Unknown Origin (PUO) in Nepal: A Mixed-Methods Study at Tertiary Level Hospitals.

Background: Pyrexia of Unknown Origin (PUO) remains a significant diagnostic challenge in low-resource settings, where limited laboratory capacity and fragmented health systems impede timely etiologic identification. In Nepal, evidence on institutional readiness, diagnostic capacity, and system-level barriers for PUO care is limited, hindering standardized clinical decision-making and timely diagnosis. This study assessed the diagnostic capacity, workforce expertise, and governance structures for PUO management across Nepal. Methods: A concurrent mixed-methods study was conducted across 11 tertiary care hospitals in six provinces of Nepal. Quantitative data on governance, service delivery, diagnostics, human resources, infrastructure, and financing were collected using standardized facility assessment tools and descriptively analyzed using SPSS version 23. Qualitative data were obtained from 33 key informant semi-structured interviews (hospital administrators, clinicians, and laboratory personnel), transcribed verbatim, and subjected to thematic analysis in NVivo with intercoder reliability assessment. Findings were integrated through triangulation. Results: Quantitative assessments revealed limited institutional preparedness for PUO management, characterized by the absence of dedicated clinical guidelines, formal referral pathways, and designated focal points in most hospitals. Basic diagnostic services were widely available; however, access to advanced molecular diagnostics was inconsistent and often dependent on external laboratories, contributing to diagnostic delays. Qualitative findings contextualized these gaps, highlighting fragmented governance, weak interdisciplinary coordination, and heavy reliance on empirical treatment of pyrexia, frequently influenced by prior antibiotic exposure. Human resource constraints were prominent, particularly shortages of infectious disease specialists, pediatric expertise, microbiologists, and trained laboratory personnel. Infrastructure limitations, inefficient referral mechanisms, and substantial out-of-pocket expenditures further constrained optimal care. Digital health tools, including electronic medical records and telemedicine, were inconsistently implemented despite being viewed as potential facilitators of improved coordination and follow-up. Conclusions: Management of PUO in Nepal is limited by system-level weaknesses in governance, diagnostic capacity, workforce skills, financing, and digital health integration. Closing these gaps through standardized clinical guidelines, strengthened laboratory systems, focused workforce training, improved referral pathways, and strategic digital health investments could shorten diagnostic timelines, improve patient outcomes, and advance national priorities such as antimicrobial stewardship and epidemic preparedness.