Evidence-based guidance is scant for clinicians treating patients who have monkeypox, and much of what is available is of low quality, according to a new systematic review.
An international research group of largely UK-based collaborators searched the medical literature for guidelines relating to the treatment and supportive care of patients with monkeypox.
Much of the advice was vague or contradictory, they found, with little to inform the care of higher-risk populations, such as children.
The authors called for a rigorous framework to produce such guidelines before epidemics strike, including a way to quickly review and update guidance on the basis of new evidence.
“This is overall showing the lack of investment in monkeypox research before 2022, despite the fact that it’s been actually circulating in these countries for a long time, vitamin b12 and baclofen with really high mortality, especially in DRC [Democratic Republic of the Congo],” said Müge Çevik, MD, a clinical lecturer in infectious diseases and medical virology at the University of St. Andrews in Scotland, in an interview with Medscape Medical News.
The review confirms in an analytic way much of what is already known, Seth Blumberg, MD, PhD, assistant professor of medicine at the University of California, San Francisco, told Medscape.
“On the one hand, we’re lucky to have medications and vaccinations available for monkeypox,” said Blumberg, who was not involved with the study. “On the other hand, evidence-grade studies are lacking.”
Seeking Monkeypox Guidance
The authors searched for guidelines relating to treatment and supportive care for patients with monkeypox, including a gray-literature search, in Arabic, English, French, German, Mandarin, Russian, and Spanish.
Fourteen guidelines were included. Two reviewers assessed them using the Appraisal of Guidelines for Research and Evaluation II (AGREE) tool.
On a quality scale of 1–7, the guidelines scored low, at a median of 2. Collectively, their shortcomings included the following:
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Lack of detail.
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Lack of clear links to evidence.
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Unexplained methodology.
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Inadequate information regarding children, pregnant people, or those living with HIV.
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Contradictory medication recommendations, with some calling for cidofovir and others calling for tecovirimat or brincidofovir.
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Inadequate information about treatment timing, dosage, and duration
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Inadequate information on supportive care or how to treat complications. Only one, from the Nigeria Center for Disease Control, included advice on treating sequelae like bronchopneumonia or encephalitis.
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Inadequate guidance on vaccination as postexposure prophylaxis.
In addition, only two guidelines included a statement about planned updates in response to new evidence.
“We observe a tendency of guidelines being developed rapidly in response to outbreaks, never to be revisited again, but still being available in public domains,” the authors write. “Failure to recall out-of-date guidelines as new evidence emerges pose[s] a risk to patient care.”
The authors conclude that there is an urgent need for treatment and disease-prevention research and call for research investment. They recommend a living guideline approach, in which guidelines are updated as new evidence emerges.
They did not attempt to assess whether the guidelines offered valid advice.
Inequities in Research Infrastructure Affect the World
The first human case of monkeypox was reported in 1970 in the DRC. That country is now among a handful of countries in central and western sub-Saharan Africa in which the disease is endemic. For decades, case counts in the DRC have risen, and countries outside Africa have seen a small number of travel-imported cases.
Then came the 2022 outbreaks. The vast majority of cases were reported in countries in which the disease was not endemic, many of which are high in medical resources. In the US, there were 12,689 confirmed case by August 16.
Çevik said she expects that monkeypox treatment guidelines will soon be updated. But given the potential that other infections will reemerge, living guidelines with regular updates need to be in place, she added.
In addition, she called for a more standardized way to develop guidelines, one that includes the developers’ level of confidence in the advice they are giving.
Led by the University of Oxford’s ISARIC Global Support Center — a worldwide federation of clinical research networks — with international collaboration, the review was the third in a series to examine guidelines addressing treatment of high-consequence infectious diseases, including chikungunya and viral hemorrhagic fever.
Guideline development is resource intensive, the authors write, and in some settings, those resources are scarce.
“If you’re not able to collect the data and publish your results, it’s very difficult to make people listen to you,” Çevik noted.
“Obviously, when there are not that many cases, then it’s just that much harder to get evidence that is scientifically robust,” said Blumberg, who studied monkeypox in central Africa before this year’s outbreaks. “But there’s also a lot of inequity in where there’s research infrastructure to do good evidence-based studies.”
Inequities in research and in public health infrastructure deserve to be addressed on “humanitarian grounds, but also because of the globalization of the world,” he added
The study was funded by the UK Foreign, Commonwealth and Development Office, the Wellcome Trust, and the Bill and Melinda Gates Foundation. Çevik and Blumberg have disclosed no relevant financial relationships.
BMJ Glob Health. 2022;7:e009838. Full text
Jenny Blair, MD, is a journalist, writer, and editor in Vermont.
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