ObjectivesTo assess the effectiveness of respiratory interventions and case isolation measures in reducing or preventing the transmission of mpox in humans and to inform future focused reviews on mpox transmission.MethodsThe WHO Clinical Management and Infection Prevention and Control guideline 2022 development group developed three structured research questions concerning respiratory and isolation infection prevention control measures for mpox. We conducted a systematic review that included a broad search of five electronic databases. In a two-stage process, we initially sought only randomized controlled trials and observational comparative studies; when the search failed to yield eligible studies, the subsequent search included all study designs including clinical and environmental sampling studies.ResultsTo inform the questions the review team synthesized route of transmission data in mpox. There were 2420/3924 (61.7%) cases in which investigators identified transmission occurring through direct physical sexual contact. There proved to be no reported mpox cases in which investigators identified inhalation as a single route of transmission. There were 2/3924 (0.05%) cases in which investigators identified fomite as a single route of transmission. Clinical and environmental sampling studies generally failed to isolate mpox virus in saliva, oropharangeal swabs, mpox skin lesions, and hospital room air.ConclusionsCurrent findings provide compelling evidence that transmission of mpox occurs through direct physical contact. Because investigators have not reported any cases of transmission via inhalation alone the impact of respiratory infection prevention control measures in reducing transmission will be minimal. Avoiding physical contact with others, covering mpox lesions and wearing a medical mask is likely to reduce onward mpox transmission; there may be minimal reduction in transmission from additionally physically isolating patients.