Le Infezioni in Medicina, n. 1, 13-19, 2023

doi: 10.53854/liim-3101-3


Overview of case definitions and contact tracing indications in the 2022 monkeypox outbreak

Giovanni Guarducci1, Barbara Rita Porchia2, Carlotta Lorenzini1, Nicola Nante1,3

1Post Graduate School of Public Health, University of Siena, Siena, Italy;

2Hygiene and Epidemiology Unit, Teaching Hospital of Siena, Siena, Italy;

3Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy

Article received 3 November 2022, accepted 28 January 2023

Corresponding author

Giovanni Guarducci

E-mail: giovanni.guarducc@student.unisi.it


Background: In 2022, a new outbreak of the Mpox virus occurred outside of Africa, its usual endemic area. The virus was detected in European, American, Asian, and Oceanian countries where Mpox is uncommon or had not been reported previously and where the spread was rapid. The study aims to compare the case definition and the indications for contact tracing in case of Mpox infection among the World Health Organization (WHO), the European Centre for Disease Prevention and Control (ECDC), and four European Countries.

Methods: From August 2022 to November 2022, we conducted research, first on the WHO and ECDC official websites and then on the official websites of the Ministry of Health or National Health Agencies of four European Countries (Italy, France, Spain, and Portugal). All reports found were compared to enlighten the differences in the definition of the case and indications for contact tracing.

Results: The WHO divides the case definition into four categories: suspected, probable, confirmed, and discarded, while the ECDC divides cases into confirmed and probable. The ECDC defines contact as close and others, while the WHO divides it into high, medium, and minimal risk. The four countries analyzed show heterogeneity in both the case definitions and the indications for contact tracing.

Conclusions: Our analysis revealed heterogeneity in the case definition between the WHO and ECDC. Different countries followed different indications or have given their indications for both the case definition and contact tracing indications. Harmonization strengthens public health preparedness and response and creates unified communication.

Keywords: Mpox outbreak, monkeypox, epidemiological and virological surveillance, public health authorities.


While the new variants of COVID-19 still challenge the world, the emergence of a new outbreak caused by the Mpox virus, an orthopoxvirus close relative of variola virus (smallpox), has raised concern among public health authorities as to whether it would constitute a new threat [1-3]. It is transmitted between animals and humans and from human to human. Mpox disease results in symptoms like those caused by the now-eradicated smallpox virus but is less clinically severe, usually only causing serious illness in young children and immunosuppressed persons [4].

The mortality rate ranged from 1% to 10% in occurrences, with the highest mortality rate in younger populations [5, 6]. Mpox’s incubation period is typically about 6-16 days but can vary from 5 to 21 days. The main signs and symptoms in the first 5 days are fever, lymphadenopathy, back pain, extreme headache, myalgia, and serious asthenia. After 1-3 days from the onset of fever, a maculopapular rash grows into pus-filled vesicles. Finally, they become scabs in about 10 days [5].

Mpox was first discovered in a monkey laboratory in Denmark in 1958, while the first human case was diagnosed in 1970 in a 9-month-old baby boy in Zaire (now Democratic Republic of the Congo, DRC). Since then, Mpox has become endemic in the DRC and has spread to other African countries, mainly in Central and West Africa [7, 8]. The first outbreak of Mpox outside of Africa was reported in 2003 in the United States. After that, Israel, the United Kingdom, Singapore, and other countries have reported Mpox cases among travelers returning from Nigeria since 2018 [9, 10].

In 2022, a new Mpox virus outbreak was occurring outside of its usual “endemic” base in Africa, and the virus has so far been detected in 47 countries, including Europe, America, Oceania, and Asia, where Mpox is uncommon or previously unreported. On 25 June 2022, the World Health Organization (WHO) Emergency Committee declared that the outbreak does not currently constitute a Public Health Emergency of International Concern (PHEIC) but unanimously acknowledged the emergency nature of the event and that controlling further spread will require a vigorous response [11, 12]. After a rapid increase in cases on 23 July, the same WHO Emergency Committee declared that the current Mpox outbreak constitutes a PHEIC [13].

Given the rapid evolution of Mpox and the global alert, and the lesson learned from COVID-19, where the transition from epidemic to pandemic was rapid, causing significant harm to society, early identification of cases and contact management became necessary to contain the outbreak. For this reason, the need to identify uniform definitions to detect cases and contacts has arisen. Several national and international health agencies have published their classification and criteria to define cases and contacts. Therefore, we set out to overview on the official websites of the main health agencies to compare the definition of the case and the indications contact tracing indications in case of Mpox infection. Then, we checked which indications were implemented in four European countries: Italy, France, Spain, and Portugal.


From August 2022 to November 2022, we reviewed the available information about case definition and contact tracing indications of Mpox on the main health agencies’ official websites. We looked at the WHO reports and, at the European level, the European Centre for Disease Prevention and Control (ECDC) publications. At the European level, we chose two countries with a high incidence of cases (France and Spain) and two countries with a lower incidence of cases (Italy and Portugal) [14]. We searched the ministry of health and national health authority websites of the European countries chosen to find the criteria to identify the case and contact tracing indications of Mpox. Table 1 shows the eligible reports to achieve our goal of WHO, ECDC, the circular letter of the Italian Ministry of Health, the procedure to be followed by the France National Agency of Public Health, the protocol of the Spanish Ministry of Health, and the guideline of Portuguese Directorate-General of Health [15-21]. Reports of these agencies and the four European Countries under study were compared to identify differences in the definition of the case and indications for contact tracing.


Table 2 shows the case definitions used by the WHO and ECDC. The WHO divides the case definition into four categories: suspected, probable, confirmed, and discarded. While the ECDC divides cases into only two categories, confirmed and probable. No difference emerged in the definition of a confirmed case between the two agencies.

Meanwhile, in the probable case definition, there are some differences between WHO and ECDC.

In the probable case, ECDC includes travel to MPX endemic countries in the 21 days before symptom onset, a person (of any sexual orientation) who had multiple or anonymous sexual partners in the 21 days before symptom onset, and man who has sex with men.

Instead, the WHO, in its definition of probable case, considers not only positive laboratory test results on orthopoxvirus infection but also detectable levels of anti-orthopoxvirus antibody [IgM from 4 to 56 days after rash onset, or a four-fold rise in IgG antibody title based on acute (up to day 5-7) and convalescent (day 21 onwards) samples; in the absence of a recent smallpox/monkeypox vaccination or other known exposure to orthopoxvirus].

Table 3 shows the definition of contact by the WHO and ECDC. The ECDC defines contact as close and others, while the WHO divides it into high, medium, and minimal risk. The WHO estimates the permanence in the same room with a symptomatic MPX patient, without appropriate personal protective equipment (PPE) as a medium risk. It is impossible to determine whether the medium-risk contacts indicated by the WHO are close contacts or others for the ECDC.

Table 4 shows which indications for case definition and contact tracing indication were followed by four selected countries (France, Spain, Italy, and Portugal). There is heterogeneity in the case definitions and the indications for contact tracing. For case definitions, only Spain and Italy follow the precise indications of a major health agency (WHO), while France and Portugal give their definitions. Portugal seems to summarize the two case definitions (WHO and ECDC). As for contact tracing indications, Italy and Portugal follow the indications given by the ECDC, while Spain and France give their own indications without following either of the two main health agencies.


Our study aimed to compare the case definitions and the indications for contact tracing in the 2022 Mpox outbreak through an overview of reports issued by the main health agencies and by four European countries.

The emergence and re-emergence of new and old infectious diseases have been widely linked to poverty, vulnerability, malnutrition, and poor health behavior, which is more common in low-income countries, such as sub-Saharan Africa and some Asian countries [22-24].

The current Mpox outbreak also involved middle- and high-income countries, and its rapid spread in Europe has generated intense scientific, political, and media activity [25]. In this context, surveillance systems are essential to create a fair epidemiological and virological view, to stop an epidemic before it can explode and become uncontrollable. The consequences of large-scale viral infection can be severe for persons healthcare systems still facing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic [26-28]. The WHO and ECDC agree on the definition of a confirmed case; in fact, the infectious agent must be identified by culture or PCR, but in the classification of the non-confirmed case (probable, suspected, discarded), there are some differences [29]. The problem of case definition, as identified in our study, of an infectious disease is already known in Europe, which could lead to incomplete epidemiological data [30]. As already suggested, the case definition should be homogenized between the main health agencies [13]. This would make epidemiological surveillance more effective and give the countries clear guidance for managing the Mpox outbreaks with the same criteria. The current case definitions of Mpox given by the WHO and ECDC would miss the case of a heterosexual patients with a characteristic vesicular-pustular rash but no travel history or contact with confirmed infection [31]. Mpox, unlike SARS-CoV-2, is rarely thought to spread asymptomatically. Therefore, more information on the Mpox infection in asymptomatic high-risk persons would be needed to determine whether any screening in persons without skin lesions is justified [32]. The outbreaks in several countries raise concerns that potential genotypic mutations could change the phenotype of the virus. This could be a sign of increased transmissibility of the virus or of a progressive and slow transmission which is more difficult to trace, making contact tracing, in this case already challenged by the high number of anonymous sexual partners, even more challenging [33, 34]. In addition, contacts, once traced, may have generated other cases: contact tracing strategies should also consider a pre-symptomatic infectious period when trying to find the contacts of confirmed cases [35].

Given this Mpox outbreak in non-endemic countries, which now seems to manifest itself as a sexually transmitted infection, it is highly concerning, not least because of possible new transmission routes [36]. This makes it crucial for contact tracing services to identify people at risk quickly and subsequently curb super-diffuse transmission events [37].


Our analysis has revealed heterogeneity in the case definition and in the definition of contacts between the main health agencies. Certainly, harmonizing case definition is important to strengthen public health preparedness and response and create unified communication. Moreover, uniform contact tracing is a key public health measure to control the spread of infectious diseases, such as Mpox. Each of the four countries followed different directions or provided its own directions for case definitions and contact tracing. Italy was the only country to stringently follow the case definitions and contact tracing directions of the main health agencies. Given this, the lessons learnt from SARS-CoV-2 should teach us that its early spread could have been mitigated if the initial case definitions had been less strict and if extensive community-based testing had been carried out earlier.


There was no funding for this study.

Conflict of interest

The authors declare no conflict of interest.


[1] Rizk JG, Lippi G, Henry BM, Forthal DN, Rizk Y. Prevention and Treatment of Monkeypox. Drugs 2022; 82 (9), 957-963. Doi: 10.1007/s40265-022-01742-y.

[2] Aler H, Gould S, Hine P, et al. Clinical features and management of human monkeypox: a retrospective observational study in the UK. Lancet Infect Dis. 2022; 22 (8), 1153-1162. Doi: 10.1016/S1473-3099(22)00228-6.

[3] Yang Z. Monkeypox: A potential global threat? J Med Virol. 2022; 94 (9), 4034-4036. Doi: 10.1002/jmv.27884.

[4] Venkatesan P. Global monkeypox outbreak. Lancet Infect Dis. 2022; 22 (7), 950. Doi: 10.1016/S1473-3099(22)00379-6.

[5] Peter OJ, Kumar S, Kumari N, Oguntolu FA, Oshinubi K, Musa R. Transmission dynamics of Monkeypox virus: a mathematical modelling approach. Model Earth Syst Environ. 2022; 8 (3), 3423-3434. Doi: 10.1007/s40808-021-01313-2.

[6] Hutson CL, Gallardo-Romero N, Carroll DS, et al. Transmissibility of the monkeypox virus clades via respiratory transmission: investigation using the prairie dog-monkeypox virus challenge system. PLoS One. 2013; 8(2), e55488. Doi: 10.1371/journal.pone.0055488.

[7] Burki T. Investigating monkeypox. Lancet. 2022; 399 (10343): 2254-2255. Doi: 10.1016/S0140-6736(22)01096-0.

[8] Bunge EM, Hoet B, Chen L, et al. The changing epidemiology of human monkeypox - A potential threat? A systematic review. PLoS Negl Trop Dis. 2022; 16 (2), e0010141. Doi: 10.1371/journal.pntd.0010141.

[9] Reed KD, Melski JW, Graham MB, et al. The detection of monkeypox in humans in the Western Hemisphere. N Engl J Med. 2004; 350 (4), 342-350. Doi: 10.1056/NEJMoa032299.

[10] Zhang Y, Zhang JY, Wang, FS. Monkeypox outbreak: A novel threat after COVID-19? Mil Med Res. 2022; 9 (1), 29. Doi: 10.1186/s40779-022-00395-y.

[11] Song TZ, Zheng YT. Monkeypox, wild animals, and potential big problem. Zool Res. 2022; 43 (4), 612-614. Doi: 10.24272/j.issn.2095-8137.2022.217.

[12] Philpott D, Hughes CM, Alroy KA, et al. Epidemiologic and Clinical Characteristics of Monkeypox Cases - United States, May 17 - July 22, 2022. MMWR Morb Mortal Wkly Rep. 2022; 71 (32), 1018-1022. Doi: 10.15585/mmwr.mm7132e3.

[13] The Lancet. Monkeypox: a global wake-up call. Lancet. 2022; 400 (10349), 337. Doi: 10.1016/S0140-6736(22)01422-2.

[14] European Centre for Disease Prevention and Control/WHO Regional Office for Europe. Mpox, Joint Epidemiological overview, 4 January 2023. Available on: https://monkeypoxreport.ecdc.europa.eu Accessed on: 18/01/23.

[15] World Health Organization (WHO). Surveillance, case investigation and contact tracing for monkeypox. Geneva: WHO; 2022. Available at: https://www.who.int/publications/i/item/WHO-MPX-Surveillance-2022.2 Accessed on: 02/08/22.

[16] European Centre for Disease Prevention and Control (ECDC). Risk assessment: Monkeypox multi-country outbreak. Stockholm: ECDC, 2022. Available at: https://www.ecdc.europa.eu/en/publications-data/risk-assessment-monkeypox-multi-country-outbreak Accessed on: 02/08/22.

[17] European Centre for Disease Prevention and Control (ECDC). Considerations for contact tracing during the monkeypox outbreak in Europe, 2022. Stockholm: ECDC, 2022. Available at: https://www.ecdc.europa.eu/en/publications-data/considerations-contact-tracing-during-monkeypox-outbreak-europe-2022 Accessed on: 02/08/22.

[18] Ministero della Salute. Circolare del Ministero della Salute 0034905-02/08/2022-DGPRE-DGPRE-P. Roma, 2022. Available at: https://www.trovanorme.salute.gov.it/norme/renderNormsanPdf?anno=2022&codLeg=88439&parte=1%20&serie=null Accessed on: 07/08/22.

[19] Santé Publique France. Conduite à tenir autour des cas de Monkeypox. Saint-Maurice, 2022. Available at: https://www.santepubliquefrance.fr/les-actualites/2022/cas-de-variole-du-singe-point-de-situation-au-8-septembre-2022#block-468837 Accessed on: 01/11/22.

[20] Ministerio de Sanidad. Protocolo para la detección precoz y manejo de casos de viruela de los monos (Monkeypox) en España. Madrid, 2022. Available at: https://www.sanidad.gob.es/profesionales/saludPublica/ccayes/alertasActual/alertaMonkeypox/docs/ProtocoloMPX_20221102.pdf Accessed on: 10/11/22.

[21] Direção-Geral da Saúde. Abordagem de casos de infeção humana por vírus Monkeypox (VMPX). Lisboa 2022. Available at: https://www.dgs.pt/normas-orientacoes-e-informacoes/orientacoes-e-circulares-informativas/orientacao-n-0042022-de-31052022-pdf.aspx Accessed on 11/11/22.

[22] Tambo E, Al-Nazawi AM. Combating the global spread of poverty-related Monkeypox outbreaks and beyond. Infect Dis Poverty. 2022; 11 (1), 80. Doi: 10.1186/s40249-022-01004-9.

[23] Troiano G, Nante N. Emerging fungal infections: focus on Saksenaea Erythrospora. J Prev Med Hyg. 2021; 62 (2), E382-E385. Doi: 10.15167/2421-4248/jpmh2021.62.2.1953.

[24] Napolitani M, Troiano G, Bedogni C, Messina G, Nante N. Kocuria kristinae: an emerging pathogen in medical practice. J Med Microbiol. 2019; 68 (11), 1596-1603. Doi: 10.1099/jmm.0.001023.

[25] Zumla A, Valdoleiros SR, Haider N, et al. Monkeypox outbreaks outside endemic regions: scientific and social priorities. Lancet Infect Dis. 2022; 22 (7), 929-931. Doi: 10.1016/S1473-3099(22)00354-1.

[26] Capitani E. Montomoli E, Camarri A, et al. Epidemiological and virological surveillance of Severe Acute Respiratory Infections in the 2019/2020 season in Siena, Tuscany, Italy. J Prev Med Hyg. 2021; 62 (3), E782-E788. Doi: 10.15167/2421-4248/jpmh2021.62.3.2297.

[27] Farahat RA, Sah R, El-Sakka AA, et al. Human monkeypox disease (MPX). Infez Med. 2022; 3 (30), 372-391. Doi: 10.53854/liim-3003-6.

[28] Stang A, Standl F, Jöckel KH. Characteristics of COVID-19 pandemic and public health consequences. Herz. 2020; 45 (4), 313-315. Doi: 10.1007/s00059-020-04932-0.

[29] Sipahi OR. What Should Be the Ideal Definite Coronavirus Disease 2019 (COVID-19) Case Definition? Clin Infect Dis. 2021; 73 (2), e434-e436. Doi: 10.1093/cid/ciaa1179.

[30] Steinbrink A, Brugger K, Margos G, Kraiczy P, Klimpel S. The evolving story of Borrelia burgdorferi sensu lato transmission in Europe. Parasitol Res. 2022; 121 (3), 781-803. Doi: 10.1007/s00436-022-07445-3.

[31] Pan D, Sze S, Nazareth J, et al. Monkeypox in the UK: arguments for a broader case definition. Lancet. 2022; 399 (10344), 2345-2346. Doi: 10.1016/S0140-6736(22)01101-1.

[32] Wong L, Gonzales-Zamora JA, Beauchamps L, Henry Z, Lichtenberger P. Clinical presentation of Monkeypox among people living with HIV in South Florida: a case series. Infez Med. 2022; 30 (4), 610-618. Doi: 10.53854/liim-3004-17.

[33] Farahat RA, Abdelaal A, Shah J, et al. Monkeypox outbreaks during COVID-19 pandemic: are we looking at an independent phenomenon or an overlapping pandemic? Ann Clin Microbiol Antimicrob. 2022; 21 (1), 26. Doi: 10.1186/s12941-022-00518-2.

[34] Saied AA, Dhawan M, Metwally AA, Fahrni ML, Choudhary P, Choudhary OP. Disease History, Pathogenesis, Diagnostics, and Therapeutics for Human Monkeypox Disease: A Comprehensive Review. Vaccines (Basel). 2022; 10 (12), 2091. Doi: 10.3390/vaccines10122091.

[35] Ward T, Christie R, Paton RS, Cumming F, Overton CE. Transmission dynamics of monkeypox in the United Kingdom: contact tracing study. BMJ. 2022; 2, 379: e073153. Doi: 10.1136/bmj-2022-073153.

[36] Amer FA, Hammad NM, Wegdan AA, ElBadawy NE, Pagliano P, Rodríguez-Morales AJ. Growing shreds of evidence for monkeypox to be a sexually transmitted infection. Infez Med. 2022; 30 (3), 323-327. Doi: 10.53854/liim-3003-1.

[37] Cuypers L, Bode J, Beuselinck K, et al. Nationwide Harmonization Effort for Semi-Quantitative Reporting of SARS-CoV-2 PCR Test Results in Belgium. Viruses. 2022; 14 (6), 1294. Doi: 10.3390/v14061294.