To assess gaps and barriers to effective health communication during epidemics, pandemics, and mass health emergencies. A systematic literature review was conducted in PubMed (National Library of Medicine, Maryland, USA), SCOPUS (Elsevier, Amsterdam, Netherlands), Cochrane (Cochrane, London, UK), and grey literature between 2000 to 2020. 16043 of 16535 identified citations were eliminated through title/ abstracts screening, 437 through full-text review and 55 articles were assessed qualitatively. Key barriers to effective health communication included misinformation, distrust, limited collaboration, and messaging inconsistency. Lack of information/ research was not the primary challenge. Major gaps were in mass and social media strategies, characteristics of messages, sociocultural contexts, digital communication, rapid response, providers' attitude and perception, and information source characteristics. Health messaging should be adaptable to information outlets and tailored for the most vulnerable. Denigration of individuals with inaccurate beliefs increases misinformation and baseline knowledge differences and fears should be addressed without polarization. Involving frontline providers in health communication strategies is crucial. Primary reason for misinformation is the failure of health sector to convincingly convey accurate information. With input from all stakeholders, especially trusted members of communities and providers, health communication should include reinvestment in methods, multidimensional and multidisciplinary approaches, consistent frameworks, improved social media usage, clear, simple, and targeted messaging, and addressing systematic disinformation and misinformation with intention.
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