A recent article posted to the medRxiv* preprint server demonstrated the scarcity of appropriate clinical management guidelines for monkeypox (MPX) infections across the globe.
MPX is a zoonotic illness caused by a smallpox-related orthopoxvirus. In the Democratic Republic of Congo (DRC), the first human MPX infection was discovered in 1970. Subsequently, human MPX has been documented primarily in Western and Central African nations.
In non-endemic and endemic locations, there has been an upsurge in MPX cases and outbreaks in recent decades. With 257 confirmed MPX cases in 23 nations as of May 26, 2022, the continuing 2022 MPX outbreak is the first known multi-nation outbreak among non-endemic countries. Contacts with infected people and animals are linked to an increased risk of infection. Antibody and antigen detection methods do not offer MPX-specific confirmation due to serological cross-reactivity of orthopoxviruses.
The smallpox vaccination is anticipated to be 85% effective against MPX. The first-generation live smallpox vaccination is not advised for pregnant women or immunosuppressed individuals. In some areas, novel third-generation non-replicating, live vaccinations for monkeypox and smallpox in adults have been approved. Yet, none are included in standard vaccination programs, and they are not widely available for general usage around the world.
Moreover, there are few therapeutic choices available for MPX. In certain nations, Tecovirimat is approved for treating smallpox in children and adults and MPX in outbreaks. Furthermore, in animal and in vitro trials, brincidofovir and cidofovir showed activity against MPX. However, there is a scarcity of evidence of brincidofovir and cidofovir on MPX treatment in humans, and they are only approved for usage in some countries.
Additionally, the rise in MPX cases in recent decades underscores the necessity for physicians globally to have access to clinical management policies that can help them guide treatment and improve patient care and outcomes.
About the study
In the present study, the scientists evaluated the scope, availability, inclusivity, and quality of clinical management guidelines for MPX worldwide. The team explored six databases (Ovid Embase, Ovid Medline, Ovid Global Health, Web of Science Core Collection, Scopus, and World Health Organization (WHO) Global Index Medicus) from inception till October 14, 2021, and a grey literature search till May 17, 2022.
MPX guidelines offering supportive care and treatment recommendations were incorporated, with no language exclusions. Two reviewers evaluated the guidelines. Quality was examined employing the Appraisal of Guidelines for Research and Evaluation (AGREE) 2 tool.
Furthermore, this research was part of a comprehensive systematic review of clinical management and supportive care guidelines for high-risk infectious illnesses. The study was registered with PROSPERO, the prospective international register of systematic reviews, and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards for carrying out the systematic reviews.
The study results demonstrated that among 2026 records reviewed, 14 MPX guidelines were found. Generally, most guidelines were of poor quality (scoring two out of seven, ranging from one to seven), lacked details, and addressed a limited range of matters. The majority of the guidelines concentrated on adults; however, five, i.e., 36%, gave some advice to children, three, i.e., 21%, to pregnant women, and three, i.e., 21%, to people living with human immunodeficiency virus (HIV).
Treatment recommendations were primarily limited to antivirals. Seven guidelines recommended cidofovir, four of which were solely for severe MPX. Besides, 29%, i.e., four of 14, advised tecovirimat, and 7%, i.e., one of 14, recommended brincidofovir. Just one guideline included treatment and supportive care recommendations for complications.
Vaccination was suggested as post-exposure prophylaxis (PEP) in all guidelines. Three guidelines recommended vaccinia immune globulin as a PEP for severe cases in immunocompromised individuals.
The present review found a significant absence of treatment and PEP guidance, as well as often contradictory advice, for many demographic groups, including pregnant women, children, and persons living with immunosuppression, which could worsen their susceptibility to outbreaks. The researchers noticed a pattern of guidelines being established quickly in response to outbreaks, then seldom revisited, yet remained accessible across the public domains. The failure to revise out-of-date recommendations as new evidence becomes available puts patient care at risk. Additionally, a few guidelines include systems for monitoring or updates.
Taken together, the current findings show that there was a global shortage of high-quality, up-to-date evidence-based MPX clinical management guidelines. The scientists depicted that as the number of MPX cases and outbreaks rises, there is an immediate and obvious requirement for research on prophylaxis and treatment of MPX infections, including for varied risk groups.
The team discovered that most guidelines failed to report the methodology employed, which was mirrored in the quality evaluation, with the majority of the guidelines rated as poor quality. The low scores observed for the rigor of development were due to a shortage of documentation, systematic methodologies, and clear connections to the information that backs up suggestions.
Furthermore, the authors mentioned that the current MPX outbreak offers a chance to speed forward this study by coordinating high-quality investigations. Newer evidence should be integrated into globally available guidelines to benefit patients and epidemic outcomes. In addition, the investigators suggested a living guideline system for infectious illnesses management, including MPX.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
- Eika Webb, Ishmeala Rigby, Melina Michelen, Andrew Dagens, Vincent Cheng, Amanda Rojek, Dania Dahmash, Susan Khader, Keerti Gedela, Alice Norton, Muge Cevik, Erhui Cai, Eli Harriss, Samuel Lipworth, Robert Nartowski, Helen Groves, Peter Hart, Lucille Blumberg, Tom Fletcher, Shevin T Jacob, Louise Sigfrid, Peter Horby. (2022). Availability, scope, and quality of monkeypox clinical management guidelines globally: a systematic review. medRxiv. doi: https://doi.org/10.1101/2022.06.09.22276219 https://www.medrxiv.org/content/10.1101/2022.06.09.22276219v1