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News and expectations about this recent Monkeypox outbreak. 

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News and expectations about this recent Monkeypox outbreak. 

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This news article gives us an insight and what to expect out of this Monkeypox outbreak.

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LONDON, May 21 (Reuters) - The World Health Organization is working on further guidance for countries on how to mitigate the spread of monkeypox, amid concerns cases could spike further in the summer months, a senior adviser for the U.N. agency told Reuters.

The WHO's working theory based on the cases identified so far is that the outbreak is being driven by sexual contact, said David Heymann, chair of the WHO's Strategic and Technical Advisory Group on Infectious Hazards with Pandemic and Epidemic Potential. He led a meeting on the outbreak on Friday.

Monkeypox is an infectious disease that is usually mild, and is endemic in parts of west and central Africa. It is spread by close contact, which means it can be relatively easily contained through such measures as self-isolation and hygiene once a new case is identified. See EXPLAINER: read more

The outbreak in 11 countries where it is not endemic is highly unusual, according to scientists. More than 100 confirmed or suspected cases have been reported, most of them in Europe.

Heymann, a professor at the London School of Hygiene and Tropical Medicine, said experts were likely to give more guidance to countries in the coming days. Health officials in several countries have warned that cases could rise further at major summer gatherings and festivals.

"What seems to be happening now is that it has got into the population as a sexual form, as a genital form, and is being spread as are sexually transmitted infections, which has amplified its transmission around the world," Heymann said.

He said the WHO's meeting was convened "because of the urgency of the situation". The committee is not the group that would suggest declaring a public health emergency of international concern, WHO's highest form of alert, which currently applies to the COVID-19 pandemic.

Instead Heymann said the international committee of experts, which met via video conference, looked at what needed to be studied about the outbreak and communicated to the public, including whether there is any asymptomatic spread, who are at most risk, and what the various routes of transmission are.

He said close contact was the key transmission route for the virus as the lesions that are typical of the disease are very infectious. For example, parents caring for sick children are at risk, as well as health workers, which is why some countries have started inoculating the teams treating monkeypox patients using vaccines for smallpox, a related virus.

Many of the current cases have been identified at sexual health clinics.

Early genomic sequencing of a handful of the cases in Europe has suggested a similarity with the strain that spread in a limited fashion in Britain, Israel and Singapore in 2018.

Heymann said it was "biologically plausible" that the virus had since been circulating outside of the countries where it is endemic, but had not led to major outbreaks as a result of COVID-19 lockdowns, social distancing and travel restrictions.

He stressed that the monkeypox outbreak did not resemble the early days of the COVID-19 pandemic because it does not transmit as easily. Those who suspect they may have been exposed or who are showing symptoms, including the typical bumpy rash and fever, should avoid close contact with others, he said.

"There are vaccines available, but the most important message is, you can protect yourself," he added.

Reporting by Jennifer Rigby; Editing by Pravin Char

Our Standards: The Thomson Reuters Trust Principles.

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WHO working on more monkeypox guidance as cases rise

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LONDON, May 21 (Reuters) - The World Health Organization is working on further guidance for countries on how to mitigate the spread of monkeypox, amid concerns cases could spike further in the summer months, a senior adviser for the U.N. agency told Reuters.

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This video talks about the Monkeypox outbreak Info, Impact, and Guidance.

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Monkeypox: All You Need To Know | Monkeypox Virus Explained | Times Now Plus

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The WHO's overview of this Monkeypox Outbreak.

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The WHO's overview of this Monkeypox Outbreak.

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The WHO is a global health organization working to address this Monkeypox Outbreak.

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Since early May 2022, cases of mpox (monkeypox) have been reported from countries where the disease is not endemic, and continue to be reported in several endemic countries. Most confirmed cases with travel history reported travel to countries in Europe and North America, rather than West or Central…

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PAHO'S response to the Monkeypox Outbreak.

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PAHO'S response to the Monkeypox Outbreak.

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The PAHO is a global health organization working to address this Monkeypox Outbreak.

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The goal of the global outbreak response for monkeypox is to control the outbreak, and to effectively use strong public health measures to prevent onward spread of the disease. Judicious use of vaccines can support this response. This interim guidance, developed with the advice and support of the Strategic Advisory Group of Experts (SAGE) Ad-hoc Working Group on smallpox and monkeypox vaccines, provides the first WHO recommendations on vaccines and immunization for monkeypox. Key points follow.

Mass vaccination is not required nor recommended for monkeypox at this time.

For contacts of cases, post-exposure prophylaxis (PEP) is recommended with an appropriate second- or third-generation vaccine, ideally within four days of first exposure to prevent onset of disease.

Pre-exposure prophylaxis (PrEP) is recommended for health workers at risk, laboratory personnel working with orthopoxviruses, clinical laboratory staff performing diagnostic testing for monkeypox, and others who may be at risk as per national policy.

Vaccination programmes must be backed by thorough surveillance and contact-tracing, and accompanied by a strong information campaign, robust pharmacovigilance, ideally in the context of collaborative vaccine effectiveness studies with standardized protocols and data collection tools.

Decisions on use of smallpox or monkeypox vaccines should be based on a full assessment of risks and benefits on a case-by-case basis.

Most interim recommendations provided here concern off-label use of vaccines. The guidance will be updated as more information becomes available.

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Vaccines and immunization for monkeypox: Interim guidance, 14 June 2022

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The goal of the global outbreak response for monkeypox is to control the outbreak, and to effectively use strong public health measures to prevent onward spread of the disease. Judicious use of vaccines can support this response.

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Peer reviewed Monkeypox Outbreak article.

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Peer reviewed Monkeypox Outbreak article.

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This peer reviewed article explains my topic more in depth.

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Eveline M. Bunge,

Bernard Hoet,

Liddy Chen,

Florian Lienert,

Heinz Weidenthaler,

Lorraine R. Baer,

Robert Steffen

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Abstract

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades-Central African 10.6% (95% CI: 8.4%- 13.3%) vs. West African 3.6% (95% CI: 1.7%- 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

Author summary

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. We conducted a systematic review to assess how monkeypox epidemiology has evolved since it was first diagnosed in 1970 in the Democratic Republic of the Congo. In total, human monkeypox has now appeared in 10 African countries and 4 countries elsewhere. Examples include Nigeria, where the disease re-emerged in the last decade after a 40-year hiatus, and the United States, where an outbreak occurred in 2003. The number of cases has increased at a minimum of 10-fold and median age at presentation has evolved from young children (4 years old) in the 1970s to young adults (21 years old) in 2010-2019. This may be related to the cessation of smallpox vaccinations, which provided some cross-protection against monkeypox. The case fatality rate for the Central African clade was 10.6% versus 3.6% for the West African clade. Overall, monkeypox is gradually evolving to become of global relevance. Surveillance and detection programs are essential tools for understanding the continuously changing epidemiology of this resurging disease.

Citation: Bunge EM, Hoet B, Chen L, Lienert F, Weidenthaler H, Baer LR, et al. (2022) The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Negl Trop Dis 16(2): e0010141. https://doi.org/10.1371/journal.pntd.0010141

Editor: Gregory Gromowski, WRAIR, UNITED STATES

Received: June 22, 2021; Accepted: January 4, 2022; Published: February 11, 2022

Copyright: © 2022 Bunge et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: This study was initiated and funded by Bavarian Nordic. The decision to publish the manuscript was made after the report of the paid systematic literature review by Pallas Health Research and Consultancy. The funder had a role in study design, data collection and analysis, decision to publish, and preparation of the manuscript. Baer PharMed Consulting, Ltd received funding for the development of the manuscript.

Competing interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Bernard Hoet, Liddy Chen, Florian Lienert, and Heinz Weidenthaler are employees of Bavarian Nordic. Eveline M. Bunge is an employee of Pallas Health Research Consultancy. Lorraine R. Baer is an employee of Baer PharMed Consulting, Ltd., which received funding for the preparation of the manuscript. Robert Steffen has been paid for lectures and participation in advisory boards by various vaccine manufacturers, including Bavarian Nordic. Please note that the study was fully funded by Bavarian Nordic with two contracts, first with Pallas Health Research and Consultancy to perform the systematic review, second with Baer PharMed Consulting, Ltd to support manuscript development. It is only after reviewing the data acknowledging the public health importance that the authors decided to submit a manuscript on the subject. The following authors received salary from the funder (BH, LC, FL, HW). The funder had a role in study design, data collection and analysis, decision to publish, and preparation of the manuscript.

Introduction

Monkeypox, currently a rare zoonotic disease, is caused by the monkeypox virus, which belongs to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus [ 1]. The variola virus (smallpox virus) is closely related [ 1], and monkeypox disease results in a smallpox-like disease. Historical data have indicated that smallpox vaccination with vaccinia virus (another orthopoxvirus) was approximately 85% protective against monkeypox [ 2]. However, following the eradication of smallpox in 1980, routine vaccination against smallpox was no longer indicated [ 3], and it has now been four decades since any orthopoxvirus vaccination program.

The name monkeypox originates from the initial discovery of the virus in monkeys in a Danish laboratory in 1958 [ 4]. The first case in humans was diagnosed in 1970 in a 9-month-old baby boy in Zaire (now the Democratic Republic of the Congo, DRC) [ 5]. Since that time, monkeypox has become endemic in the DRC, and has spread to other African countries, mainly in Central and West Africa. Outside of Africa, the first reported monkeypox cases were in 2003 [ 6] and, at the time of this systematic review, the most recent cases were in 2019 [ 7, 8].

A previous systematic review, which evaluated the literature through summer 2018, described the epidemiology of monkeypox outbreaks [ 9]. In view of the recent increase in reports from Nigeria and elsewhere, we initiated a new systematic literature review with a focus on the changes in the evolution of the epidemiology of human monkeypox since the first cases in the 1970s through the present day.

Methods

This systematic review was performed in accordance with international standards for conducting and reporting systematic reviews, including guidelines from the Cochrane Collaboration [ 10] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) [ 11]. The review is registered with PROSPERO (CRD42020208269).

Searches were performed in MEDLINE (accessed using PubMed), Embase, African Journals Online (AJOL) and the Internet Library sub-Saharan Africa (ilissAfrica), with no language restrictions. All published literature reported through September 7, 2020, the date of last search, was considered for eligibility. In PubMed, searches included Medical Subject Headings (MeSH) and limits to title and abstract (tiab). The search string used in PubMed was Monkeypox[MeSH] OR "Monkeypox virus"[MeSH] OR monkeypox[tiab] OR "monkey pox"[tiab] OR "variole du singe"[tiab] OR "variole simienne"[tiab] and in Embase was 'monkeypox'/exp OR 'monkeypox virus'/exp OR monkeypox:ti,ab OR "monkey pox":ti,ab. In AJOL and illissAfrica, separate searches were conducted for each of the following terms: monkeypox, variole du singe, and variole simienne. We aimed to explore how monkeypox epidemiology has evolved regarding incidence, case characteristics, clades, transmission, and case fatality rate. We also sought to explore the risk factors for acquiring human monkeypox.

After all articles were identified from the four databases and duplicates removed, screening of the title and abstract was performed in duplicate by two researchers (EMB [author] and BVD). Articles that seemed to contain relevant data for the review objectives, which included all age populations, were selected for full-text screening. Excluded were non-human studies, modelling studies that did not provide original data, articles that focused primarily on smallpox, and articles with data not related to the topics of interest. In cases of doubt, the article was selected for full-text screening. Full text articles were then reviewed to determine whether at least one of the review objectives was met. At this stage, other articles such as conference abstracts or narrative reviews were also excluded. The first 10% of full text articles was critically evaluated in duplicate by two researchers (EMB and BVD), and the remaining 90% were reviewed by EMB. Each article was then further reviewed during data-extraction. Some additional exclusions occurred in this step. For example, for articles with similar results from largely identical data sets, only one article was included, generally the most recent. In some instances, there was a partial overlap of data, such that different articles included the same cases plus some unique cases. In these situations, only the unique cases in each article were included in the data extraction sheet. One researcher (EMB) created the data extraction sheet for the eligible articles, and these were reviewed by a second researcher (RVH). A random check of 10% of the data extraction was performed by RVH.

Articles suitable for extraction from the literature searches were case reports, outbreak investigations, epidemiological studies, and surveillance studies. For these types of articles, no formal checklists for critical appraisal are available, so no formal quality assessments were performed. Information on study quality as reported by the authors of the selected articles were added as comments in the data extraction sheet.

In addition to the four primary search sources, seven sources of grey literature and Google were searched during weeks 41-44 of 2020. These sources were the websites of the World Health Organization (WHO), specifically a review of the Weekly Bulletins on Outbreaks and other Emergencies, United States Centers for Disease Control and Prevention (CDC), Africa CDC, Nigeria CDC, African Field Epidemiology Network, Epicentre, and ProMed. The Google search was performed on the African countries known to have monkeypox cases, including a check on the websites of their ministries of health. No formal search strategy was employed, and therefore no denominator on number of reports is described. One researcher performed the search of the grey literature (LM) and a second researcher (EMB) reviewed the findings and added the relevant information to the data extraction sheet.

Pooled analysis

For age at monkeypox infection, a weighted average of the median ages per decade was calculated, based on investigations where median age was reported and on single cases where age was presented. In each respective decade, these single cases were treated as a unit, and median age determined.

Data on case fatality rate (CFR) were pooled, and 95% confidence intervals (CIs) were calculated using the binomial (Clopper-Pearson) exact method. Both overall CFR and CFR per clade were calculated. Since specific clade data were not always reported in the literature, we used the geographical spread of the clades as described by WHO [ 12] to assign the clade variant. Monkeypox cases from the DRC, Gabon, Central African Republic (CAR), South Sudan, and Republic of the Congo were assumed to be of the Central African clade, while cases in all other countries were assumed to be of the West African clade. Cameroon was not included in the number of cases per clade or the calculation of CFR by clade, as WHO has reported that both clades have been detected there [ 12].

Case definitions

Case definitions were not standardized across sources, but in general the definitions displayed in Table 1 were used.

Results

The search strategy yielded a total of 1,995 publications, 129 of which were selected for full-text screening. Of these, 48 articles were suitable for data extraction. An additional 18 records from the grey literature (primarily the WHO website) were also included for data extraction. The PRISMA flowchart of the selection process for the systematic review is in shown in Fig 1.

Mode of transmission and risk factors

In 29 peer-reviewed articles, attempts were made to establish the mode of transmission for confirmed, probable, and/or possible monkeypox cases. The transmission details, by country, including number of cases and mode of transmission, are summarized in S6 Table.

A study from the 1980s involving 338 monkeypox cases from the DRC concluded that an animal source was suspected in 72.5% (245/338) of cases and a human source in 27.5% (93/338) of cases [ 21]. In contrast, in an investigation of 419 cases from the DRC in the 1990s, only 22% were primary cases (i.e., a person who reported no contact with another person with monkeypox), while 78% were secondary cases (i.e., monkeypox in a person who had contact with an infected person 7-21 days before onset of disease) [ 14]. Data from the Nigerian outbreak (Sept 2017-Sept 2018) found that transmission was unknown for 62.3% (76/122) of cases [ 44]. Of the remaining 46 cases, 36 or 78.3% had an epidemiological link to people with similar lesions before the onset of monkeypox and 10 or 8.2% reported contact with animals [ 44].

All but one of the cases outside of Africa were the result of confirmed or suspected animal-to-human transmission [ 6, 8, 41, 55, 57]. This exception was a human-to-human transmission in the UK in a healthcare worker who provided care to one of the UK confirmed monkeypox cases [ 56].

The risk factors or risk behaviors for contracting monkeypox were reported in only five studies from three countries (DRC [ 17, 22, 26], US [ 41], Republic of the Congo [ 45]), and in general reinforced what has been suspected factors. For example, sleeping in the same room or bed, living in the same household, or drinking or eating from the same dish were risk behaviors associated with human-to-human transmission [ 22, 26]. On the other hand, sleeping outside or on the ground or living near or visiting the forest were identified as factors that increase the risk for exposure to animals and subsequent risk for animal-to-human transmission of monkeypox [ 17, 45]. Unexpectedly, assisting with toileting and hygiene and laundering clothes did not have a significant association with acquiring monkeypox, and preparing wild animal for consumption or eating duiker were identified as protective factors [ 26]. After adjusting for smallpox vaccination status, daily exposure to sick animals (adjusted odds ratio [aOR]: 4.0 (95% CI: 1.2-13.4) or cleaning their cages/bedding (aOR: 5.3 (95% CI: 1.4-20.7) were identified as risk factors for acquiring monkeypox in the 2003 outbreak in the US [ 41]. Touching or been scratched by an infected animal sufficient to sustain a break in skin were each found to be both significant and nonsignificant risk factors [ 41].

Discussion

This systematic review provides a comprehensive overview of the evolution of the epidemiology of monkeypox since it was first detected in humans in 1970. Using a structured format, we describe the greater than 10-fold increase in confirmed, probable, and/or possible monkeypox cases over the past 5 decades, from 48 cases in the 1970s to 520 cases in the 1990s. Increases in the recent two decades may be confounded by the numbers coming out of the DRC, the country with the most reported cases. Beginning in the year 2000, the DRC started reporting primarily the number of suspected cases, and these have increased from >10,000 cases in 2000-2009 [ 18] to >18,000 in 2010-2019 [ 18, 63- 65]. In the first nine months of 2020 alone, another 4,594 suspected cases were reported in the DRC [ 66], and the WHO bulletin of the 12-month data for 2020, which was available following completion of this systematic review, reported a total of 6,257 suspected cases [ 75].

As a result of the recent outbreak, the number of confirmed and probable cases in Nigeria has dramatically escalated as well, from 3 cases in the 1970s [ 5, 42] to 181 cases in 2017-2019 [ 74]. The surge in cases in the DRC from the 1990s (n = 511) through 2000-2019 (>28,000) is of a similar magnitude. The data from these two countries therefore suggest that the trend is not due to improved reporting alone. This is consistent with the analysis by Hoff and colleagues [ 18] who found that the rise in monkeypox cases in the DRC from 2001-2013 were likely actual disease increases and not merely a result of improved surveillance, since the reporting system was considered stable by 2008.

There are mounting concerns about the geographical spread and further resurgence of monkeypox. Over the past 5 decades, monkeypox outbreaks have been reported in 10 African countries and 4 countries outside of Africa. In addition to the re-emergence of monkeypox in Nigeria after nearly 40 years, in the years between 2010 and 2019, cases also re-emerged in Liberia and Sierra Leone (after 4 decades) and in the CAR (after 3 decades). First outbreaks emerged in the Republic of the Congo in 2000-2009 and in South Sudan (first appearance in East Africa) in 2005. From 2003, cases of monkeypox have occurred outside of Africa. Infected rodents from Ghana, a country that has not reported any human cases as of this review, were imported into the US. Animal-to-animal transmission then led to animal-to-human transmission, ultimately resulting in an outbreak of 47 confirmed or probable cases [ 6]. Beginning in 2018 through 2021, adults travelling from Nigeria were diagnosed with monkeypox in Israel [ 57], the UK [ 7, 55, 76], Singapore [ 8], and the US [ 77]. These cases were suspected to be the result of animal-to-human transmission. Three additional cases, one resulting from a nosocomial infection and two via transmission to a family member, occurred in the UK [ 56, 76, 78]. Of the four monkeypox cases imported into the UK, two have been associated with local transmission and each has resulted in either one or two subsequent cases, illustrating that infected travelers can act as index cases of local outbreaks. Interestingly, the infection imported to the UK in May 2021 [ 76] and to the US in July 2021[ 77] occurred at a time where the reported cases of monkeypox in Nigeria were at a very low level. Only 32 suspected cases of disease had been reported to the authorities since the beginning of 2021 [ 79]. Significant human-to-human transmission has been reported as well in the CAR [ 30, 33, 35], DRC [ 14, 21, 25], Republic of the Congo [ 46], South Sudan [ 58], and Nigeria [ 5, 44], demonstrating the susceptibility of both clades to this type of transmission. Mathematical modelling of human-to-human transmission found that monkeypox has epidemic potential, with R ₀ >1 [ 80].

There has been much discussion about the reasons for the resurgence in monkeypox cases, the most prevailing being waning immunity, although deforestation may be a factor or can even act in potentiation [ 81- 83]. Monkeypox virus, variola virus (smallpox), and vaccinia virus (smallpox vaccination) are closely related orthopoxviruses [ 1]. At the time when smallpox was rampant, no cases of monkeypox were reported. This could have been either because the focus was on smallpox and the presentation of the two diseases are similar or the lack of laboratory confirmation of the etiologic agent led to an assumption of smallpox [ 84]. Historical data have shown that smallpox vaccination was approximately 85% protective against monkeypox [ 2]. Following the successful vaccination campaign against smallpox, the disease was declared eradicated in 1980 by the World Health Assembly, and routine vaccination was halted [ 3].

Using statistical modeling, Nguyen and colleagues [ 81] estimated that in 2016, the year before the outbreak in Nigeria began, only 10.1% of the population was vaccinated, and the population immunity, which takes into account waning individual-level immunity, was 2.6%, down from 65.6% in 1970. By 2018, the vaccinated population had decreased to 9.3% and the estimated population immunity had declined to 2.2%. In our review of the literature, we found that unvaccinated individuals accounted for approximately 80-96% of monkeypox cases.

One other possible factor influencing the resurgence of monkeypox might be the genetic evolution of the monkeypox virus. An analysis of the virus genome diversity of 60 samples obtained from humans with primary and secondary cases of infection from Sankuru District, DRC, led to the detection of four distinct lineages within the Central African clade and revealed a gene loss in 17% of the samples that seemed to correlate with human-to-human transmission [ 85].

Our analysis shows that in the early years (1970-1989), monkeypox was primarily a disease of young children, with a median age at presentation of 4 to 5 years old; this increased to 10 years of age in 2000-2009 and 21 years in 2010-2019. Regarding age at death in monkeypox cases, 100% of deaths were in children <10 years of age in the early years, while for the years 2000-2019, age <10 years accounted for only 37.5% of deaths. These data appear to be consistent with the global intensified smallpox eradication program that began in 1967 [ 86] and the cease of routine smallpox vaccination by the 1980s following its eradication [ 3]. In the 2000s, only adults older than 20-25 years would have had a history of smallpox vaccination, leaving the age groups below 20 years vulnerable. Interestingly, the median age of monkeypox cases increased from 10 to 21 years in the next decade. Indeed, most cases were either likely too young to have been vaccinated or were born after the cessation of routine smallpox vaccination, as in the more recent outbreaks.

Strengths and limitations

The strengths of this review are that basing on Cochrane [ 10] and PRISMA [ 11], it included a broad search strategy on monkeypox worldwide, without time or language limits, which reduced selection bias. In addition, there was a thorough review of the grey literature. Overall, more than 60 relevant sources were identified for comprehensive data extraction. There are also limitations.

First, our ability to present a complete picture of the number of confirmed, probable, and/or possible cases was sometimes limited, as data quantity and quality varied across regions. This is especially true for Central African countries, and in particular the DRC, where a systematic accounting and reporting of the number of cases per year is lacking. The number of cases presented in the maps in this review, especially after 1986 when WHO stopped their surveillance program in the DRC, are likely lower than the actual number of cases [ 28] and underreporting is quite probable, despite implementation of the Integrated Disease Surveillance and Response in the DRC in 2000 [ 18]. Furthermore, no national estimates of the number of confirmed cases in the DRC can be made, as polymerase chain reaction testing is infrequently performed in the field [ 18, 25]. Second, there is a paucity of data on the age of cases, which could call into question the results of our analysis of median age at monkeypox diagnosis. For example, a report from the DRC, published after completion of this systematic review, found a median age of 14 years for confirmed cases in the Tshuapa Province during 2011-2015 [ 87]. These investigators did note, however, that median age at onset has increased over time [ 87], which corresponds to our findings. Furthermore, our review of the literature found that age at death from monkeypox has also increased, which is then consistent with our age-at-diagnosis findings. Third, since specific data on clades was infrequently reported, we assigned clades based upon the geographical spread described by WHO [ 12] and drew conclusions about both number of cases per clade and mortality per clade. These results did not allow for the possibility that one clade may invade other geographies or consider that factors other than clade (e.g., access to healthcare) might account for the mortality differences. Fourth, although more than half of the included articles presented data on transmission of monkeypox, in many studies not all cases could be definitively attributed to either animal-to-human transmission or human-to-human transmission. Therefore, an in-depth analysis about the proportion of cases being infected by human-to-human transmission could not be performed. Fifth, while a changing epidemiology of monkeypox could be linked to the genetic evolution of the monkeypox virus, a review of the literature on the latter was not within scope of our work. Lastly, data on risk factors for acquiring monkeypox are rather scarce, and some incongruous results were found. In one study, for example, eating duiker and preparing wild animal for food were identified as protective factors [ 26], which appears in contrast to factors identified in animal-to-human transmission cases [ 15, 29]. Thus, more formal studies of risk factors are warranted.

Conclusions

The waning population immunity associated with discontinuation of smallpox vaccination has established the landscape for the resurgence of monkeypox. This is demonstrated by the increases in number of cases and median age of individuals acquiring monkeypox as well as the re-emergence of outbreaks in some countries after an absence of 30-40 years. Further, the appearance of cases outside of Africa highlights the risk for geographical spread and the global relevance of the disease. The possibility for human-to-human transmission is a concern not just among household members, but also among providers of care to diseased individuals. In light of the current environment for pandemic threats, the public health importance of monkeypox disease should not be underestimated. International support for increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

Acknowledgments

The authors would like to thank Babette van Deursen (BVD), Rosa van Hoorn (RVH), Lauren Mason (LM), and Femke van Kessel (FVK), current (LM and FVK) and former (BVD and RVH) employees of Pallas Health Research and Consultancy, for assistance with performing the literature searches (BVD, LM), quality review of the findings (RVH), and creating figures and maps (FVK).

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The changing epidemiology of human monkeypox-A potential threat? A systematic review

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Author summary Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. We conducted a systematic review to assess how monkeypox epidemiology has evolved since it was first diagnosed in 1970 in the Democratic Republic of the Congo.

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Monkeypox Outbreak case study that is peer reviewed. 

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Monkeypox Outbreak case study that is peer reviewed. 

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This peer reviewed case study explains my topic more in depth.

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Peer-reviewed/ Case study/ People

An analysis of seven cases of monkeypox that occurred in the UK between 2018-2021 reports on the first instances of in-hospital transmission and household transmission outside of Africa. All patients in the study recovered following treatment in isolation in UK hospital units.

Researchers observed patient responses to two different antiviral medications (brincidofovir and tecovirimat), suggesting that tecovirimat might shorten the duration of monkeypox symptoms and reduce the length of time a patient is contagious.

However, the authors caution that due to the study's small cohort further research into antivirals as a treatment for monkeypox is urgently needed, especially as countries in Europe and North America report new monkeypox outbreaks in May 2022.

Authors also highlight the importance of maintaining response centres to manage future monkeypox outbreaks.

A new retrospective study of seven patients diagnosed with monkeypox in the UK between 2018 and 2021, suggests that some antiviral medications might have the potential to shorten symptoms and reduce the amount of time a patient is contagious. The cases analysed in the study, published in The Lancet Infectious Diseases journal, represent the first instances of in-hospital transmission and household transmission outside of Africa, as well as reporting the patient response to the first off-label use of two different antiviral medications - brincidofovir and tecovirimat - to treat the disease.

The study found little evidence that brincidofovir was of clinical benefit but concluded that further research into the potential of tecovirimat would be warranted. The authors also report detection of monkeypox virus in blood and throat swabs. As optimum infection control and treatment strategies for this disease are not yet established, data from the study could help inform global efforts to further understand the clinical features of the disease as well as transmission dynamics.

"As public health officials are trying to understand what is causing the May 2022 monkeypox outbreaks in Europe and North America - which have affected several patients who reported neither travel nor an identified link to a previously known case - our study offers some of the first insights into the use of antivirals for the treatment of monkeypox in humans," says Dr Hugh Adler of the Liverpool University Hospitals NHS Foundation Trust, lead author on the paper. "Although this latest outbreak has affected more patients than we had previously encountered in the UK, historically monkeypox has not transmitted very efficiently between people, and overall the risk to public health is low."

"The cases reported in our study, in addition to the recent outbreaks, highlight the importance of maintaining a collaborative network of centres on standby to manage sporadic, outbreaks of high consequence pathogens, such as monkeypox. The cases we observed were challenging and resource-intensive to manage, even in the high-income setting of the UK. With international travel returning to pre-pandemic levels, public health officials and healthcare workers around the world must remain vigilant to the possibility of new cases of monkeypox," says Dr Nick Price of Guy's & St Thomas' NHS Foundation Trust, senior author on the paper. [1]

They add: "Until now, monkeypox has been a rare, imported condition in the UK and the NHS High Consequence Infectious Diseases Network has treated all seven of the UK's confirmed cases until 2021. Outbreaks outside of Africa are unusual but in recent days, significant outbreaks have been reported in several European countries, including the UK, and further afield globally. Clinical trial data is lacking and we are pleased to share some of our collective experience in managing this previously rare and sporadic condition."

Monkeypox, a close relative of the smallpox virus, is a rare disease classified as a High Consequence Infectious Disease (HCID) by the UK Health Security Agency [2]. There are currently no licensed treatments for monkeypox and there is limited data on the duration of its contagiousness, with the incubation period ranging from five to 21 days. Patients typically stay in isolation in a specialty hospital to prevent spreading the virus to others.

Monkeypox is spread via animal-to-human transmission, typically from an animal bite or eating improperly cooked meat. In rare cases, the virus can spread via human-to-human transmission. The first human case of monkeypox was reported in 1970 in the Democratic Republic of the Congo [3] and rarely occurs outside central and western African countries. To date, there has been little research into cases of monkeypox in high income countries.

The reported symptoms of monkeypox include fever, rash, and swollen lymph nodes. Complications have also been reported, including inflammation of the lungs, inflammation of the brain, sight-threatening inflammation of the cornea, and secondary bacterial infections. Published mortality rates vary greatly, from between 1-10% in the Congo Basin, and less than 3% in Nigeria. Most deaths from monkeypox occur in children and people living with HIV.

Of the seven UK monkeypox cases analysed in this study, four were imported from West Africa with three further cases occurring due to human-to-human transmission within the case clusters. The study authors observed clinical data alongside laboratory results from blood tests and nose-and-throat swabs to describe the duration and clinical features of monkeypox in a high-income setting. Researchers also reported patient response to antiviral medications developed to treat smallpox - brincidofovir and tecovirimat - which have previously demonstrated some efficacy against monkeypox in animals.

Between 2018 and 2019, four patients observed in this study were treated for monkeypox in HCID units in England. Three of these cases were imported from West Africa. The fourth case occurred in a healthcare worker 18 days after initial exposure to the virus and was the first example of monkeypox transmission in a hospital setting outside of Africa.

The initial three patients were treated with brincidofovir seven days after the initial onset of the rash. Brincidofovir was not observed to have any convincing clinical benefit in treating monkeypox and alterations in liver blood tests were observed. The researchers note that it is not known whether brincidofovir administration earlier in the course the of disease or at a different dosing schedule would have yielded different clinical outcomes. Despite this, all three patients, plus the fourth hospital transmission patient, made a full recovery.

Three further cases of monkeypox were reported in the UK in 2021 in a family travelling from Nigeria, with two of these cases being the first examples of household transmission outside of Africa. One of these cases occurred in a child, who was observed carefully due to the association of a higher likelihood of mortality from monkeypox in children. Fortunately, this individual experienced mild illness and fully recovered.

One of the 2021 UK patients was treated with tecovirimat and experienced a shorter duration of symptoms and upper respiratory tract viral shedding than the other cases in this cluster. However, the authors note that conclusions are unable to be drawn on antiviral effectiveness against monkeypox in such a small cohort, calling for further research into antivirals to treat this neglected tropical disease.

All patients experienced mild disease and were treated in a hospital setting for infection control purposes and not due to the severity of the infection. No patients experienced the commonly recognised severe complications of monkeypox such as pneumonia or sepsis, however, one patient experienced a mild relapse six weeks following hospital discharge, and another patient developed a deep tissue abscess that required drainage. Patients were also found to experience low mood, likely stemming from isolation in HCID facilities.

"During previous outbreaks of monkeypox, patients were considered infectious until all lesions crusted over. In these seven UK cases, viral shedding was observed for at least three weeks following infection. However, data on infectivity remains limited, and is an important area for future study," says Dr Catherine Houlihan, of the UK Health Security Agency and University College London, one of the co-authors of the paper. [1]

The authors acknowledge some limitations with this study, primarily its observational nature and the small number of cases analysed. The researchers were also unable to confirm positive monkeypox PCR test results with laboratory samples of the virus, meaning that ongoing shedding of contagious virus was unable to be verified.

NOTES TO EDITORS

A full list of authors and institutions is available in the paper.

[1] Quote direct from author and cannot be found in the text of the Article.
[2] https://www.gov.uk/guidance/high-consequence-infectious-diseases-hcid
[3] Marennikova SS, Seluhina EM, Mal'ceva NN, Cimiskjan KL, Macevic GR. Isolation and
properties of the causal agent of a new variola-like disease (monkeypox) in man. Bulletin of the
World Health Organization 1972; 46(5): 599-611.

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THE LANCET INFECTIOUS DISEASES: Study reports first use of antivirals in monkeypox patients, highlighting challenges in understanding and treating this rare disease

# data[].attributes.attachment_link.description
A new retrospective study of seven patients diagnosed with monkeypox in the UK between 2018 and 2021, suggests that some antiviral medications might have the potential to shorten symptoms and reduce the amount of time a patient is contagious.

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This news article talks about my topic, while also explaining the severity of this outbreak.

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The World Health Organization said it is planning to assess whether the monkeypox outbreak spreading around the world is a public health emergency.

According to Global Health, more than 1,700 monkeypox cases have been identified in non-endemic countries, mostly in Europe and North America.

In the U.S., there are 65 confirmed or suspected cases in 17 states and the District of Columbia, data from the Centers for Disease Control and Prevention shows.

Because of the highly unusual nature of the outbreak, WHO Director-General Dr. Tedros Adhanom Ghebreyesus said he has decided to convene an emergency committee under the International Health Regulations next week.

"The global outbreak of monkeypox is clearly unusual and concerning," he told reporters during a briefing on Tuesday held in Geneva. "I think it's now clear that there is an unusual situation meaning even the virus is behaving unusually from how it used to behave in the past."

A healthcare worker prepares a syringe at a monkeypox vaccination clinic run by CIUSSS public health authorities in Montreal, Canada, June 6, 2022.

Christinne Muschi/Reuters

He continued, "But not only that, but it's also affecting more and more countries and we believe that it needs also some coordinated response because of the geographic spread."

The first case of monkeypox among humans was recorded in the Democratic Republic of the Congo in 1970, and the illness has since spread to several other nations, mostly in central and western Africa.

Typically, the disease does not naturally occur on other continents, and infections are usually identified among people who recently traveled to countries where monkeypox is more commonly found.

However, lately the virus has been identified in people with no history of travel or known contact with anyone who tested positive for monkeypox, which many indicate evidence of community transmission.

According to the National Library of Medicine, between 2007 and 2020, there have been six events declared public health emergencies of international concern.

These include the H1N1 influenza pandemic of 2009; the Ebola outbreak in West Africa from 2013 to 2015; the Ebola outbreak in the Democratic Republic of the Congo from 2018 to 2020; the Zika outbreak in 2016; the ongoing spread of poliovirus that started in 2014; and the ongoing COVID-19 pandemic.

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WHO to assess whether monkeypox outbreak is a public health emergency

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The WHO Director-General said a meeting will be held next week to determine if the monkeypox outbreak is a public health emergency of international concern.

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Monkeypox outbreak research that is peer reviewed.

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Monkeypox outbreak research that is peer reviewed.

# data[].attributes.body
This research explains that this disease has been emerging before this outbreak.

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doi: 10.3389/fpubh.2018.00241.

Affiliation

¹ Laboratory of Clinical Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Free PMC article

Nikola Sklenovská et al. Front Public Health.

Free PMC article

doi: 10.3389/fpubh.2018.00241.

Affiliation

¹ Laboratory of Clinical Virology, Department of Microbiology & Immunology, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

Abstract

Monkeypox is an emerging zoonotic disease recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era. The clinical presentation of monkeypox is similar to the one of smallpox. The case fatality rate of monkeypox (10%) lies between the case fatality rate of variola major (30%) and variola minor (1%). The disease is endemic in the Democratic Republic of the Congo, but other countries of Central and West Africa either reported cases of monkeypox in humans or circulation in wildlife. The disease was also imported once into the USA. The disease has always been considered rare and self-limiting, however recent sporadic reports suggest otherwise. Unfortunately, the collected data is limited, dispersed and often incomplete. Therefore, the objective of this review is to trace all reported human monkeypox outbreaks and relevant epidemiological information. The frequency and geographical spread of human monkeypox cases have increased in recent years, and there are huge gaps in our understanding of the disease's emergence, epidemiology, and ecology. The monkeypox virus is considered a high threat pathogen causing a disease of public health importance. Therefore, there is an urgent need to focus on building surveillance capacities which will provide valuable information for designing appropriate prevention, preparedness and response activities.

Keywords: disease outbreaks; emerging infectious diseases; monkeypox; one health; orthopoxvirus; zoonosis.

Figures

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national center for biotechnology information

# data[].attributes.attachment_link.title
Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans - PubMed

# data[].attributes.attachment_link.description
Monkeypox is an emerging zoonotic disease recognized as the most important orthopoxvirus infection in humans in the smallpox post-eradication era. The clinical presentation of monkeypox is similar to the one of smallpox. The case fatality rate of monkeypox (10%) lies between the case fatality rate o ...