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The changing epidemiology of human monkeypox—A potential threat? A systematic review
Eveline M. Bunge,Bernard Hoet ,Liddy Chen,Florian Lienert,Heinz Weidenthaler,Lorraine R. Baer,Robert Steffen
Published: February 11, 2022
This is an uncorrected proof.
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.
...
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]. 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 have 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 R0 >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].
...
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.
...
Eveline M. Bunge,Bernard Hoet ,Liddy Chen,Florian Lienert,Heinz Weidenthaler,Lorraine R. Baer,Robert Steffen
Published: February 11, 2022
This is an uncorrected proof.
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.
...
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]. 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 have 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 R0 >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].
...
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.
...
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