Monkeypox Living Evidence Profile

August 19, 2022

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Introduction

This review details the best-available evidence related to the monkeypox outbreak addressing the literature up to August 15, 2022.

This rapid living evidence profile was authored by the McMaster Health Forum to help health- and social-system leaders as they respond to pressing challenges. In response to the 2022 monkeypox outbreak, this rapid evidence profile was commissioned to the McMaster Health Forum by the Office of the Chief Science Officer, Public Health Agency of Canada. The McMaster Health Forum will produce a biweekly living evidence profile to present the evolving scientific evidence on monkeypox. This work provides complementary evidence to inform guidance and decisions. The opinions, results, and conclusions are those of the McMaster Health Forum and are independent of the funder. No endorsement by the Public Health Agency of Canada is intended or should be inferred.

The following summarizes the findings, and excludes all tables and appendices. The full report available at the McMaster Health Forum website, and can be requested through ocsoevidence-bcscdonneesprobantes@phac-aspc.gc.ca. Previous versions of this report were published:

How to cite this work:

DeMaio P, Bhuiya A, Bain T, Al-Khateeb S, Mehta V, Sharma K, Wang A, Alam S, Soueidan S, Loeb M, Lavis JN, Wilson MG. Living evidence profile #6.7: What is the best-available evidence related to the monkeypox outbreak? Hamilton: McMaster Health Forum, 19 August 2022.

Research question

What is the best-available evidence related to the monkeypox outbreak?

What we found

To inform current knowledge related to monkeypox, we identified evidence, as well as experiences from 11 countries (Australia, Belgium, France, Germany, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom (U.K.), and the United States (U.S.), and from all Canadian provinces and territories. We organized our findings using the framework below.

Organizing framework

We identified 28 new evidence documents since the last update of this living evidence profile, of which 17 were deemed highly relevant. The newly added highly relevant evidence documents include:

The living evidence profile also includes evidence documents from the previous version that we deemed to still be highly relevant, for a total of 107 highly relevant documents.

We outline in narrative form below our key findings related to the question from highly relevant evidence documents, and based on experiences from other countries. The full report accessible at the McMaster Health Forum includes:

Key findings from highly relevant evidence sources

The number of new monkeypox cases continues to increase globally. The WHO global trends epidemiological report and health-emergency dashboard indicated that there are 37,736 confirmed cases and at least 12 deaths as of 14 August 2022, whereas the U.S. CDC global map reported a total of 38,019 confirmed cases as of 16 August 2022. The majority of reported cases continue to be primarily concentrated in the Region of the Americas and European region.

We identified research evidence on the biology, epidemiology, clinical presentation, prevention and control, and diagnosis of monkeypox. In terms of the biology of monkeypox, the authors of a pre-print single study concluded that the monkeypox genome is evolving and expanding quickly after analyzing the recombination of the monkeypox genome in natural transmission (last updated 13 August 2022). Similarly, a pre-print single study identified large number of mutations within the current outbreak clade. The authors urged for a fast response to genomic analysis of newly detected strains to develop better prevention and treatment methods (last updated 25 July 2022).

We found three single studies focusing on the epidemiology of monkeypox, which included:

We also identified a protocol for an upcoming systematic review related to spread of monkeypox by travelers.

Further research evidence on the clinical presentation of monkeypox was reported in two systematic reviews and three single studies. A high-quality systematic review found that the most prevalent clinical features of monkeypox included rashes, fever, pruritus, and lymphadenopathy (8/11 AMSTAR rating; literature last searched 7 June 2022). A low-quality systematic review identified neurological complications such as low mood, seizures, encephalitis, respiratory failure, and encephalopathy among 12 individuals with monkeypox. The authors emphasize the importance of appropriately identifying monkeypox in young children given their increased susceptibility to monkeypox-associated encephalitis (2/10 AMSTAR rating; literature last searched 19 June 2022). A single study conducted in Germany found that more than half of the individuals had a diagnosis of a sexually transmitted infection (STI) in the six months before their monkeypox infection (published 12 August 2022). Finally, two single studies conducted in Spain described variability in clinical presentation in terms of types of symptoms and who is impacted (i.e., some cases found among heterosexual men and women).

In terms of prevention and control, we identified findings from one medium-quality systematic review that described the use of saliva-based polymerase chain reaction (PCR) for orthopoxviruses as potential tools for outbreak control (5/10 AMSTAR rating; published 9 August 2022). In addition, four pre-print studies focused on prevention and control. First, a survey was conducted with 394 men who have sex with men (MSM) in the Netherlands about intentions and determinants to adopt behavioural measures to reduce monkeypox transmission. The authors concluded that there was an overall intention from individuals to reduce the number of sexual partners, especially among individuals who were not on PrEP (published 3 August 2022). Second, a modelling study assessed the critical threshold to vaccinate individuals, which indicated that the threshold is dependent on the basic reproduction number of the monkeypox virus and on other public-health measures (published 2 August 2022). Third, an observational analysis on the vaccination of high-risk contacts receiving the IMVANEX smallpox vaccine as an early post-exposure ring vaccination, indicated that the vaccine was effective and well-tolerated against monkeypox (last updated 4 August 2022). Lastly, the risk factors and definition of highest-risk populations for monkeypox virus infection were assessed in a cohort study, which found a 20-fold increased risk for monkeypox virus among those have that used HIV-PrEP or erectile-dysfunction therapy or that were diagnosed with STIs by rectal PCR, as compared to others in the cohort where were deemed to be at moderate risk (published 25 July 2022).

Finally, a non-systematic review by the European Centre for Disease Prevention and Control and a pre-print single study described the use and conduct of PCR tests in the diagnosis of monkeypox. Specifically, the non-systematic review outlined optimal approaches and recommendations for laboratories assessing PCR tests (published 11 August 2022). The pre-print single study found wide variations in the primer and probe sequences of PCR assays currently recommended by the U.S. CDC compared to the genome of the current circulating monkeypox strains. The authors concluded that it is critical to develop updated assays for the detection of monkeypox so that accurate and specific data is used to inform public-health risk mitigation strategies (last updated 11 August 2022).

Key findings from the jurisdictional scan

Epidemiology (including transmission)

Monkeypox case numbers are climbing steadily, with a total of 1,059 cases of monkeypox in Canadian provinces and territories as of 12 August 2022, including 511 cases in Ontario, 426 cases confirmed in Québec, 19 cases in Alberta, 98 cases in British Columbia, three cases in Saskatchewan, and two cases in Yukon. In other jurisdictions, as of 16 August 2022, 12,688 cases have been reported in the U.S., 3,186 in Germany, 662 in Italy, 546 in Belgium and 130 in Sweden. On 15 August 2022, the UK confirmed 3,081 cases with another 114 identified as highly probable. As of 17 August 2022, Spain has 5,792 cases, which is the highest in the European region, and second highest around the globe. As of 11 August 2022, 2,673 cases were reported in France, 1,025 in the Netherlands, and 70 cases in Australia, and, on 10 August 2022 770 confirmed cases were reported in Portugal.

As cases rise and local transmission increases, jurisdictions are providing additional communication about the nature of monkeypox transmission. On 13 August 2022, the Saskatchewan Health Authority warned the public about an "elevated risk" of contracting monkeypox through anonymous sexual contact as a result of the recently identified cases associated with this source of transmission. In the UK, the Health Security Agency released a fifth technical briefing about the monkeypox outbreak in England on 12 August 2022. In the U.S., a report by the CDC suggests that among the cases with reported classification by health departments, 74% of cases were locally acquired and this percentage is growing, with locally acquired cases accounting for 51% from 17 May to 2 July 2022 and 82% from 3 July to 22 July 2022.

Prevention and control

Many jurisdictions have advanced their efforts to procure, disseminate, and administer vaccines for monkeypox. As of 11 August 2022, the Government of Canada has distributed over 99,000 doses of IMVAMUNE vaccine to provinces and territories and more than 50,000 people having been vaccinated in Canada. In Australia, the New South Wales government began vaccinating people at highest risk from monkeypox from 8 August 2022 using the Jynneos vaccine. Belgium has approved the Imvanex and Jynneos vaccines for monkeypox and are beginning vaccination among the most vulnerable populations on an invitational basis or through referrals from specialists. The campaign is expected to expand considerably in November 2022 when vaccine delivery to Belgium is increased. France has now distributed more than 52,000+ doses to the territories, while the Netherlands have made 70,000 doses available for those at high-risk of contracting monkeypox. The UK has now procured a total of 150,000 doses of the smallpox vaccine from Bavarian Nordic to offer to those eligible for vaccination and, as of 10 August 2022, roughly 50,000 have arrived in the UK and 27,000 doses have been administered.

As vaccination campaigns begin to scale up in some jurisdictions, efforts are being made to evaluate the uptake of vaccines among those eligible. In Portugal, the Directorate-General for Health stated that as of 8 August 2022, 133 contacts (71.1%) of all those eligible have been vaccinated. A U.S. report by the CDC analyzing 2,891 monkeypox cases reported between May 17 and July 22 indicated that among 339 persons with vaccination status available, 48 (14%) reported previous receipt of smallpox vaccine, including 11 (23%) who received 1 of 2 Jynneos doses during the current outbreak, 11 (23%) who received pre-exposure prophylaxis at an unknown time before the current outbreak, and 26 (54%) who did not provide information about when vaccine was administered.

Some additional prevention and control strategies have been initiated in Canada and in other jurisdictions. On 12 August 2022, the Government of Canada announced funding from the HIV and Hepatitis C Community Action Fund to support community-based organizations in Vancouver and Edmonton in addressing the monkeypox outbreak. Additionally, an environmental scan by Public Health Ontario published in August 2022 on guidance for monkeypox waste disposal indicates that items contaminated in the care of a monkeypox patient should be considered infectious waste and discarded according to jurisdictional protocols. France's successful digital campaign has been further supplemented with broadcasting efforts on community radio and the distribution of over 2,800+ posters and 94,000+ flyers. In the U.S., the Department of Health and Human Services declared the U.S. monkeypox outbreak to be a public-health emergency on 4 August 2022.

Clinical presentation

Jurisdictions are continuing to monitor clinical presentations of monkeypox, given the differences in symptoms shown compared to previous outbreaks. In the Netherlands, the National Institute for Public Health and the Environment updated their report on 16 August 2022 noting that a number of patients had proctitis, an inflammation of the lining of the rectum, which is sometimes the only symptom and that individuals may already be contagious before developing visible symptoms. To help standardize case reporting, the U.K. Health Security Agency has produced guidance regarding case definitions of possible, probable, highly probable, and confirmed cases of monkeypox with guidance for clinicians about actions to take when presented with possible, probably, highly probable, or confirmed cases.

Prognosis

With more cases, including hospitalized cases, and the first recorded deaths occurring in recent weeks, jurisdictions continue to monitor case severity. A report by Public Health Ontario dated 15 August 2022 indicates that 16/529 (3%) of confirmed cases have been hospitalized, and 0.4% have been in the ICU, and no deaths have been reported.

Methods

We identified evidence published from 2017 onwards (to capture any evidence related to recent outbreaks outside Africa) addressing the question by searching Health Systems Evidence (HSE), Health Evidence, ACCESSSS, PROSPERO (review protocols and registered titles), Pubmed and MedRxiv on 15 August 2022. We identified jurisdictional experiences by hand searching government and stakeholder websites. We selected 11 countries (Australia, Belgium, France, Germany, Italy, Netherlands, Portugal, Spain, Sweden, United Kingdom, and the United States) that are non-endemic for monkeypox and that have had recent documented cases.

We searched for guidelines, full systematic reviews (or review-derived products such as overviews of systematic reviews), rapid reviews, protocols for systematic reviews, and titles/questions for systematic reviews or rapid reviews that have been identified as either being conducted or prioritized to be conducted.

We appraised the methodological quality of full systematic reviews and rapid reviews that were deemed to be highly relevant using AMSTAR. Note that quality appraisal scores for rapid reviews are often lower because of the methodological shortcuts that need to be taken to accommodate compressed timeframes. AMSTAR rates overall quality on a scale of 0 to 11, where 11/11 represents a review of the highest quality. It is important to note that the AMSTAR tool was developed to assess reviews focused on clinical interventions, so not all criteria apply to systematic reviews pertaining to delivery, financial or governance arrangements within health systems or to broader social systems. We appraised the quality of the highly relevant guidelines using three domains in AGREE II (stakeholder involvement, rigour of development, and editorial independence) and classified guidelines as high quality if they were scored as 60% or higher on each domain.

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