Underhill, R A · Medical hypotheses · 2015 · DOI
This paper argues that ME/CFS may be caused by an infectious agent that persists in the body, based on evidence like flu-like onset, clustering of cases in outbreaks, and immune responses similar to other infections. The author reviews existing clinical and epidemiological patterns to support an infectious disease hypothesis. However, the paper is a theoretical argument rather than a study presenting new experimental evidence, and no specific pathogen has been identified.
This paper articulates a major theoretical framework—that ME/CFS is an infectious disease with a persistent pathogen—which has implications for patient management, research direction, infection control measures, and disease legitimacy. Establishing ME/CFS as organic rather than psychological has been crucial for patient advocacy and clinical recognition. Identifying a causal pathogen could enable diagnosis, treatment, and prevention strategies.
This paper does not identify or confirm any specific causative pathogen, which is essential for establishing ME/CFS as definitively infectious. The hypothesis-based approach cannot prove causation or definitively rule out alternative explanations (autoimmune, metabolic, or multifactorial mechanisms). The paper's conclusions require experimental confirmation through pathogen identification and mechanistic studies before clinical practice changes are warranted.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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