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

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.

Conflict of interest statement

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.

Figures

Fig 1. PRISMA flowchart.

Fig 2. Number of confirmed, probable, and/or possible monkeypox cases between 1970–1979.

[5,42,51] (base layer of the map: https://datawrapper.dwcdn.net/W7k0L/4/).

Fig 3. Number of confirmed, probable, and/or possible monkeypox cases between 1980–1989.

[20,21,31,34,50,52,54] (base layer of the map: https://datawrapper.dwcdn.net/lGHEu/1/).

Fig 4. Number of confirmed, probable, and/or possible monkeypox cases between 1990–1999.

[14,53] (base layer of the map: https://datawrapper.dwcdn.net/EAn8M/1/).

Fig 5. Number of confirmed, probable, and/or possible monkeypox cases between 2000–2009.

[6,18,46,58,69] * Number reflects suspected cases, since as of the year 2000, the number of suspected cases was primarily reported by the DRC. (base layer of the map: https://datawrapper.dwcdn.net/SXvj7/1/).

Fig 6. Number of confirmed, probable, and/or possible monkeypox cases between 2010–2019.

[,,,,,,,,,–,–,–,–74] * Number reflects suspected cases, since as of the year 2000, the number of suspected cases was primarily reported by the DRC. (base layer of the map: https://datawrapper.dwcdn.net/UUYbg/1/).

Fig 7. Evolution of number of cases per clade.

For 2000–2019, the numbers for the Central African clade are based largely on suspected cases, per the reporting system by the Democratic Republic of the Congo.

Fig 8. Incidence rate of suspected monkeypox cases per 100,000 (95% CI) individuals in the DRC, 2001–2013.

Data from Hoff et al [18].

Fig 9. Median age and range of confirmed, probable and/or possible monkeypox cases in Africa per decade.

Blue bars without range refer to the age of a single case. The grey horizontal line represents the weighted median. No data on median ages could be retrieved for the 1990s.