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Monkeypox Living Evidence Profile

On November 28, 2022, the World Health Organization began using ‘mpox’ as the preferred term for monkeypox disease. We’ll be updating our content to reflect this change.

Sept 15, 2022

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Introduction

This review details the best-available evidence related to the monkeypox outbreak addressing the literature up to September 12 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:

Bhuiya A, DeMaio P, Bain T, Al-Khateeb S, Wang A, Sharma K, Alam S, El-Kadi A, Vélez CM, Soueidan S, Loeb M, Lavis JN, Wilson MG. Living evidence profile #6.9: What is the best-available evidence related to the monkeypox outbreak? Hamilton: McMaster Health Forum, 15 September 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 29 new evidence documents since the last update of this living evidence profile, of which 15 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 126 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 have decreased globally since the last update. The WHO global trends epidemiological report and health-emergency dashboard indicated that there are 59,147 confirmed cases and at least 22 deaths, whereas the U.S. CDC global map reported a total of 59,606 confirmed cases as of 14 September 2022. The Americas and the European region continue to report the majority of cases.

We identified highly relevant evidence on the epidemiology, clinical presentation, prevention and control, and treatment of monkeypox.

Epidemiology (including transmission)

We identified four primary studies that described changes to the epidemiology and the rate of transmission of monkeypox. A single study reported that high risk of infection with monkeypox usually comes from close contacts with skin lesions, and that skin lesions swabs are effective at detecting monkeypox DNA using PCR testing. A U.S. CDC Morbidity and Mortality Weekly Report (MMWR) reported that persons with HIV infection or sexually transmitted infections (STIs) living in eight jurisdictions in the U.S. were disproportionately represented among persons with monkeypox, and that consideration should be given to prioritizing persons with HIV infection and STIs for monkeypox vaccination plans.

Two U.S. CDC MMWR studies reported on prevention measures that the men who have sex with men (MSM) community have taken to reduce the transmission of monkeypox. One of the studies indicated that MSM have taken measures such as reducing one-time sexual partners, which the authors concluded will have important implications for the trajectory of the monkeypox outbreak. The other MMWR study surveyed 824 men about their willingness to reduce their chances of monkeypox infection in response to public-health messaging, of which 48% of survey respondents reported reducing their number of partners and 50% reported reducing sex with partners who they met on dating apps or at sex venues since learning about the monkeypox outbreak.

In addition to these findings, we identified three upcoming systematic reviews, that are focusing on zoonotic characteristics, transmission dynamics, and transmission among pregnant people.

Clinical presentation

Clinical presentation of monkeypox continues to emerge in the literature. A recent single study that was conducted in 42 health centres and clinics from 17 German cities reported that all 546 monkeypox infections were in MSM, and almost half were living with HIV infection. However, the study noted that there were no apparent differences in clinical presentation between MSM with or without HIV infection.

In addition, we identified one upcoming systematic review and meta-analysis that will describe clinical characteristics of monkeypox.

Prevention and control

We identified one high-quality guideline and three single studies that reported on prevention and control measures, communication with the public, and vaccine efficacy. The high-quality guideline from France describes prevention and control measures for patients, healthcare workers, children, schools, transportation (high-quality AGREE II rating). A pre-print single study from Bangladesh indicated that while individuals were aware of monkeypox, there was limited understanding of its transmission pathways. Another single study used Natural Language Processing (NLP) techniques to understand the attitudes of the public towards monkeypox on Twitter, and the authors suggested that the public has not yet panicked about monkeypox. However, the same study reported that negative public sentiments about monkeypox included deaths, the severity of the virus, lesions, whether the virus is airborne, vaccines, and how the virus would affect daily and travel activities. Finally, a pre-print single study measured antibodies among historically smallpox-vaccinated, monkeypox PCR-positive and recently vaccinated individuals with Jynneos, and reported that the immunization series yielded low levels of neutralizing antibodies but a third vaccination further boosted the response.

Treatment

A high-quality guideline published in France indicated that all symptomatic cases should not be treated with a drug, but only people at higher risk should be considered for treatment with tecovirimat, brincidofovir, cidofovir, and anti-monkeypox immunoglobulins (high-quality AGREE II rating).

In addition, we identified an upcoming systematic review on the use of antivirals during the monkeypox outbreak.

Key findings from the jurisdictional scan

Key findings from the jurisdictional scan are summarized below according to each of the categories in the organizing framework.

The growth of monkeypox cases in Canada appears to have slowed down, with the Public Health Agency of Canada (PHAC) reporting a total of 1,321 cases of monkeypox in nine Canadian provinces and territories as of 9 September 2022. The Director-General of the WHO, Tedros Adhanom Ghebreyesus, said at a press conference on 31 August 2022 that the “sustained downward trend” of monkeypox cases in Canada is an encouraging sign, and highlighted that despite several countries in the Americas seeing increased case counts, Canada appears to be an outlier. Ontario remains the epicentre of monkeypox in Canada, with 631 monkeypox cases being reported as of 9 September 2022.

Other countries continue to see case totals rise, but at varying rates. As of 7 September 2022, there have been 1,195 cases of monkeypox reported in the Netherlands. As of 8 September 2022, the government of Australia has reported 129 confirmed and probable cases of monkeypox. As of 12 September 2022, the U.K. has reported 3,407 confirmed and 145 highly probable cases. As of 13 September 2022, Belgium has reported a total of 744 monkeypox cases and one death, and there have been 3,833 confirmed cases in France, 3,747 confirmed cases in Germany, 898 confirmed cases in Portugal, 813 cases in Italy, 165 cases in Sweden, and 22,629 confirmed cases in the U.S. As of 9 September, Spain has reported 6,884 cases, which is the highest case count among European countries.

In addition to Canada, the rate of infection also appears to be slowing in a few other countries. The Ministry of Health in Spain highlighted a reduction in the number of new cases. According to the health authorities, this decline cannot be attributed to vaccination efforts, given that a large vaccination campaign has not taken place in Spain, and most of the people immunized have only received a fraction of a dose. Similarly, the UK Health Security agency’s seventh technical briefing about the monkeypox outbreak released on 2 September 2022 notes that the observed reduction in incident cases occurred too soon after the introduction of the vaccination program for vaccines to be a major driver of the reduction. Rather, the briefing states that cases are more likely declining due to a combination of infection saturation, changes in case ascertainment, and behavioural changes.

Clinical presentation

Few recent insights about clinical presentation were identified during our jurisdictional scans. In Belgium, researchers at the Institute of Tropical Medicine identified three positive samples of monkeypox within asymptomatic patients who were initially testing for STIs (e.g., gonorrhea and chlamydia). They noted that the virus itself does not differ between patients who present with symptoms versus patients who do not have symptoms.

Prevention and control

The vaccine campaign continues to progress across Canada. As of 13 September 2022, 902 doses of vaccine have been administered across Manitoba. On 9 September 2022, Nova Scotia announced that it aims to soon offer the monkeypox vaccine to people at highest risk of exposure, such as members of the LGBTQ2 community. The Halifax Sexual Health Centre will host a free pre-exposure clinic as soon as the week of 19 September 2022. In Nunavut, the Nunavik Regional Board of Health and Social Services noted that for now, the supply of vaccines are reserved for those who have had close contact with someone who has tested positive and for men who have had or will have sexual contacts with at least one new male partner.

Other countries continue to work towards disseminating and administering vaccines to slow the spread of monkeypox. In France, as of 8 September 2022, 152,000+ doses have been delivered by the agency to the territories and 84,740 doses have been administered to those at risk across the country. In Germany, 5,300 monkeypox doses were delivered to the federal states in July 2022 and another 19,500 were delivered during the week of 29 August 2022. In the United States, as of 6 September 2022, 461,049 vaccine doses were administered across 35 jurisdictions. Additionally, on 6 September 2022 The U.S. Department of Health and Human Services (HHS) awarded a $20 million dollar contract to AmerisourceBergen to expand and quicken the distribution of vaccines and treatments for monkeypox.

In response to vaccine shortages, several countries are working to produce additional reserves of vaccines or change vaccination approaches to maximize coverage. On 29 August 2022, HHS in the U.S. announced that it will provide approximately $11 million to support the first U.S.-based fill and finish manufacturing of the Jynneos vaccine. On 1 September 2022, the Institute of Tropical Medicine in Belgium announced that moving forward, they will be administering monkeypox vaccines intradermally through a micro-dosing technique; this economical process will enable 2.5x more vaccines to be given to those at risk.

Diagnosis

In the U.S., recent efforts are being made to expand the availability to speed up monkeypox testing. The HHS secretary signed a declaration under section 564 of the Federal Food, Drug, and Cosmetic Act to allow the U.S. Food and Drug Administration (FDA) Commissioner to issue emergency-use authorizations for in vitro diagnostics to expand the availability of tests for monkeypox.

Prognosis

The prognosis of monkeypox cases appears to remain consistent in Canada. In Ontario, as of September 6, 2022, of the 631 confirmed cases of monkeypox in Ontario, 2.9% have been hospitalized, 0.3% have been admitted to the ICU, and no deaths have been reported. Belgium has reported their first death in a monkeypox case. In Germany, updates to the expected incubation periods of monkeypox are being made a result of on-going data collection. On 9 September 2022, the Robert Koch Institut (RKI) pre-published an article that investigated the current incubation period of monkeypox during the ongoing outbreak in Germany, finding that nearly 20% of the cases had an incubation period of one to three days.

Treatment

Provinces in Canada are providing guidance on monkeypox treatments. The British Columbia Centre for Disease Control maintains a webpage for health professionals about monkeypox treatment options that briefly outlines the potential for using tecovirimat, cidofovir, brincodofovir, and vaccinia immunoglobulin. The use of cidofovir, brincodofovir, and vaccinia immunoglobulin is not recommended. Prince Edward Island’s chief public health officer announced that the province has a supply of tecovirimat antiviral treatment for anyone who becomes ill with the monkeypox virus and a limited supply of Imvamune vaccine for post-exposure prophylaxis (PEP) available for anyone identified as a close contact of a positive case.

In the U.S., tecovirimat is being evaluated for its use in treating monkeypox. The Morbidity and Mortality Weekly Report (MMWR) for treatment of monkeypox dated 9 September 2022 concluded that Tecovirimat is tolerated and current data supports continued treatment for monkeypox.

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 2 September 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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