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Monkeypox is a smallpox-like illness that can be accompanied by a range of significant medical complications. To date there are no standard or optimized guidelines for the clinical management of monkeypox (MPX) patients, particularly in low-resource settings. Consequently, patients can experience protracted illness and poor outcomes. Improving care necessitates developing a better understanding of the range of clinical manifestations—including complications and sequelae—as well as of features of illness that may be predictive of illness severity and poor outcomes. Experimental and natural infection of non-human primates with monkeypox virus can inform the approach to improving patient care, and may suggest options for pharmaceutical intervention. These studies have traditionally been performed to address the threat of smallpox bioterrorism and were designed with the intent of using MPX as a disease surrogate for smallpox. In many cases this necessitated employing high-dose, inhalational or intravenous challenge to recapitulate the severe manifestations of illness seen with smallpox. Overall, these data—and data from biomedical research involving burns, superficial wounds, herpes, eczema vaccinatum, and so forth—suggest that MPX patients could benefit from clinical support to mitigate the consequences of compromised skin and mucosa. This should include prevention and treatment of secondary bacterial infections (and other complications), ensuring adequate hydration and nutrition, and protecting vulnerable anatomical locations such as the eyes and genitals. A standard of care that considers these factors should be developed and assessed in different settings, using clinical metrics specific for MPX alongside consideration of antiviral therapies.

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