Monkeypox Outbreak in Spain

Clinical and Epidemiological Findings in a Prospective Cross-sectional Study of 185 Cases

Alba Català; Petunia Clavo-Escribano; Josep Riera-Monroig; Gemma Martín-Ezquerra; Pablo Fernandez-Gonzalez; Leonor Revelles-Peñas; Ana Simon-Gozalbo; Francisco José Rodríguez-Cuadrado; Vanessa Guilera Castells; Francisco Javier de la Torre Gomar; Alicia Comunión-Artieda; Laura de Fuertes de Vega; José Luis Blanco; Susana Puig; Ángela María García-Miñarro; Esther Fiz Benito; Carlos Muñoz-Santos; Juan Bosco Repiso-Jiménez; Cristina López Llunell; Carmen Ceballos-Rodríguez; Víctor García Rodríguez; Juan Luis Castaño Fernández; Irene Sánchez-Gutiérrez; Ricardo Calvo-López; Emilio Berna-Rico; Belén de Nicolás-Ruanes; Francesca Corella Vicente; Eloy José Tarín Vicente; Laura de la Fernández de la Fuente; Nuria Riera-Martí; Miguel Angel Descalzo-Gallego; Mercè Grau-Perez; Ignacio García-Doval; Irene Fuertes


The British Journal of Dermatology. 2022;187(5):765-772. 

In This Article

Abstract and Introduction


Background: Since May 2022, a new outbreak of monkeypox has been reported in several countries, including Spain. The clinical and epidemiological characteristics of the cases in this outbreak may differ from those in earlier reports.

Objectives: To document the clinical and epidemiological characteristics of cases of monkeypox in the current outbreak.

Methods: We conducted a prospective cross-sectional study in multiple medical facilities in Spain to describe the cases of monkeypox in the 2022 outbreak.

Results: In total, 185 patients were included. Most cases started with primarily localized homogeneous papules, not pustules, in the probable area of inoculation, which could be cutaneous or mucous, including single lesions. Generalized small pustules appeared later in some of them. Heterogeneous lesions occurred during this generalized phase. All patients had systemic symptoms. Less common lesions included mucosal ulcers (including pharyngeal ulcers and proctitis) and monkeypox whitlows. Four patients were hospitalized, none died. Smallpox vaccination and well-controlled HIV disease were not associated with markers of severity. Contact during sex is the most likely mechanism of transmission. In this outbreak, cases have been described in men who have sex with men and are strongly associated with high-risk sexual behaviours. Seventy-six per cent of the patients had other sexually transmitted diseases upon screening.

Conclusions: The clinical findings in this outbreak differ from previous findings and highly suggest contact transmission and initiation at the entry site. The characterization of the epidemiology of this outbreak has implications for control.


Monkeypox is a zoonotic disease caused by the monkeypox virus, which belongs to the genus Orthopoxvirus. This genus also comprises variola virus (the causative agent of smallpox), vaccinia virus and cowpox virus.

Monkeypox disease was endemic in Africa, causing periodic outbreaks,[1,2] but a change seems to have taken place from a predominantly animal-to-human transmission to a more common human-to-human transmission.[3] Outside Africa, the first cases were reported in 2003 in the USA, also likely to be due to animal-to-human transmission.[3,4] Since May 2022, an outbreak of monkeypox has been reported in countries across five World Health Organization (WHO) regions: the Americas and the African, European, Eastern Mediterranean and Western Pacific regions. As of 15 June 2022, a total of 2103 laboratory confirmed cases have been reported to the WHO, 497 in Spain.[5,6]

The incubation period is 5–21 days[7] and patients with cutaneous lesions are considered infectious, but transmission might start with prodromic symptoms before the onset of cutaneous lesions.[8,9] The classically described clinical picture of monkeypox has consisted of fever and lymphadenopathy, followed by a generalized rash. The skin eruption has been described as beginning on the face and then spreading to other parts of the body (legs, trunk, arms, palms, soles, genitalia, etc.). The evolution of the rash progresses through the following stages: maculopapular (lesions with a flat base), vesicular (small fluid-filled blisters), pustular (pus-containing rash) and crust (dried blisters).[10]

Cases in this new outbreak have been described as atypical, with few lesions, sometimes localized to a single area, and with lesions appearing at various stages of development (asynchronous).[5,7] Other orthopoxviruses (e.g. cowpox virus, camelpox virus, buffalopox virus) and parapoxviruses (e.g. orf virus, pseudocowpox virus, bovine papular stomatitis virus) usually cause localized skin lesions in humans at the site of inoculation, and this might be the situation in the current outbreak.[7]

Human-to-human or secondary transmission was considered to occur mostly through respiratory droplets during direct and prolonged face-to-face contact; by direct contact with body fluids of an infected person, by contact of mucosa or nonintact skin with open rash lesions; or by contact with contaminated objects.[7] Sexual transmission was first suggested in the 2017 outbreak in Nigeria,[11] occurring in male and female patients, and is considered possible in the current outbreak,[7] as it primarily affects men who self-identify as having sex with men and have reported recent sex with new or multiple partners. More invasive routes of inoculation (i.e. mucocutaneous vs. transdermal) have been linked to more severe disease and a shorter incubation period,[12] and this might explain the clinical differences in this new outbreak.

Regarding factors for severity, in a small retrospective series of 34 patients in the USA, smallpox vaccination was not associated with disease severity or hospitalization.[13] The effect of HIV on the severity of monkeypox is unknown.

Our aims were to describe the clinical findings in the current outbreak in Spain, to explore the possibility of a localized form of the disease and whether it is linked to differences in incubation period or severity, to describe associated factors for severity, including the effect of previous smallpox vaccination and HIV, and to investigate the epidemiological characteristics of the current outbreak.