Abstract
During the current multi-country outbreak of human monkeypox the hospitalisation rate observed in Milan, Italy was 8.8%. Bacterial superinfection and severe perianal pain were the main cause of hospitalisation requiring antibiotic treatment and analgesic therapy. One patient was treated with Cidofovir. All hospitalised patients were discharged and the outcome was favourable with full recovery.
Abbreviations: MPX, Monkeypox; MSM, Men who have sex with men; MPXV, Monkeypox virus; CAC, Central African Clade; WAC, West African Clade
The multi-country outbreak of human monkeypox (MPX), spreading all over the world since May 2022 with an epicentre in Europe and affecting mainly men who have sex with men (MSM), seems to be characterised by a milder course than in previously reported outbreaks in Africa [[1], [2], [3], [4], [5], [6]]. For MPX infection observed in Africa it has been estimated an overall case fatality of 8.7% with difference between the involved MPX virus (MPXV) clade: 10.6% for Central African Clade (CAC) and 3.6% for West African Clade (WAC) [7]. In the 2003 outbreak of MPX in USA among 34 confirmed cases of MPXV infection caused by the WAC no fatalities were registered but 26% of patients required hospitalisation for >48 h [8]. Two young patients required hospitalisation in the intensive care unit for encephalitis and tracheal airway narrowing due to a retropharyngeal abscess. Among the adult population, a bacterial superinfection and a keratitis with corneal ulceration was reported [8].
Up to July 18, 2022, 34 confirmed cases of MPXV infection were diagnosed at the Department of Infectious Diseases of Luigi Sacco Hospital in Milan, Italy. Overall, 4 patients (11.7%) required hospitalisation (Table 1 ) but only in three cases (8.8%) it was directly due to clinical worsening of MPX infection and bacterial superinfections. Patient # 1 presented initially with several vesicular lesions localised on the nose followed by the onset of high fever and a possible bacterial superinfection. Despite antibacterial treatment the lesions coalesced with ulceration and development of a large eschar (Fig. 1 ). He was hospitalised and treated with cidofovir (twice administration) - because of tecovirimat unavailability - associated with antibiotics. He had an encouraging healing in of the lesions within 3 weeks and a complete recovery with scarring in about 6 weeks (Fig. 1). Patient # 2 required hospitalisation for severe anal pain and peripheral leucocytosis. He received only analgesic therapy with recovery in a few days. Patient # 4 following the diagnosis of MPX presented a cellulitis with ulceration and important edema localised to the shaft of the penis and scrotum (Fig. 2 ). Staphylococcus aureus and Streptococcus pyogenes were cultured from the ulcerated lesion requiring prolonged antibiotic therapy and hospitalisation. The duration of hospital stay ranged from 5 to 13 days. As far as alterations of laboratory exams, all four patients had a mild increase of C-reactive protein (median value 26.5 mg/dL), and one patient each showed leucocytosis, thrombocytopenia and increase of D-dimer. During the current MPX outbreak the rate of hospitalisation has been reported between 2 and 3.7% in two Spanish series [2,3], 8.3% in Germany [9], 9.2% in UK [1] and 11.1% in Portugal [10]. Our experience considering only patients with a clinical cause of hospitalisation (8.8%) is in agreement with previous studies.
Table 1.
Characteristics of hospitalised subjects with monkeypox.
| Gender/Age | M/26y | M/35y | M/34y | M/37y |
|---|---|---|---|---|
| HIV status | Negative | Negative | Positive | Positive |
| Clinical manifestations | Lesion on the nose followed by high fever (39.3 °C), chills, sweats, lymphadenopathy | Vesicular rash on mouth, head, limbs, trunk followed by fever (38 °C), lymphadenopathy | Perianal lesion followed by fever (38.3 °C), lymphadenopathy | Skin lesion of inguinal areas, shaft of penis, scrotum followed by fever (38 °C), headache, lymphadenopathy |
| Location of skin lesions | Nose, limb | Head, limbs, trunk | Perianal, foot, face, arm | Inguinal, penis, scrotum, face |
| Samples positive for MPXV PCR | Vesicule (skin, nose), anal swab, pharynx, seminal fluid | Vesicule, pharynx | Vesicule, pharynx, anal swab | Vesicule, pharynx, anal and uretral swab |
| Cause of hospitalisation | Worsening nasal lesion with suspected bacterial infection | Severe anal pain | Inability to self isolate | Bacterial infection (S. aureus, Streptococcus pyogenes) |
| Time of hospitalisation (days) | 8 | 5 | 8 | 13 |
| Abnormalities of laboratory findings | Increased C-reactive protein (45.1 mg/L) | Increased white blood cells (11,440/μL, N 40% L50%), increased C-reactive protein (12 mg/L) | Mild thrombocytopenia (146,000/μL), increased C-reactive protein (30 mg/L) | Increased C-reactive protein (23,1 mg/L), increased D-dimer (1930 ng/mL) |
| Treatment | Amox/clav 3 g/d for 8 days; Cidofovir 5 mg/kg day 1 and 7 | Analgesic therapy | None | Ceftriaxone 2 g/d for 7 days + daptomycin 500 mg/d for 5 days |
| Outcome | Recovery | Recovery | Recovery | Recovery |
N, neutrophils; L, lymphocytes; Amox/clav, amoxicillin/clavunalic acid; C-reactive protein normal value 10 mg/L.
Fig. 1.
Evolution of nasal lesion of patient #1: A-I (in order): day 7, 9, 13, 19, 20, 22, 29, 33, 41.
Cidofovir infusion at day 13 and 20.
Fig. 2.
Patient # 4: penile pustule in its stages of complication.
1A: day 1; 1B: day 3; 1C: day 5; 1D: day 11; 1E: day 22.
Bacterial cellulitis localized to the penis as observed in one of our patients has been described initially by Hammershlag [11] and was reported in 11.1% of UK patients [1]. Proctitis and severe perianal pain directly caused by MPXV seems to be another frequent complication reported in up to 30% of subjects [12,13]. In conclusion, the proportion of hospitalised cases affected by human MPX during the current outbreak is about one out of ten with pain or bacterial superinfection representing the main responsible clinical condition. Despite the small number of patients observed in our experience clinical outcomes were reassuring with complete recovery.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Institutional review board statement
The study was conducted according to the guidelines of the Declaration of Helsinki. The study was approved by the Comitato Etico Interaziendale Area 1 (Protocol number 2022/ST/124).
Ethics
All patients provided written consent for the use of their case details and medical images in this publication.
CRediT authorship contribution statement
Davide Moschese: Conceptualization, Data curation, Formal analysis. Andrea Giacomelli: Conceptualization, Data curation, Formal analysis. Martina Beltrami: Data curation, Formal analysis. Giacomo Pozza: Conceptualization, Data curation. Davide Mileto: Validation, Formal analysis. Serena Reato: Data curation, Formal analysis. Martina Zacheo: Data curation, Formal analysis. Mario Corbellino: Data curation, Formal analysis. Giuliano Rizzardini: Conceptualization, Data curation, Formal analysis. Spinello Antinori: Conceptualization, Formal analysis, Writing – review & editing.
Declaration of competing interest
The authors declare no conflict of interest.
References
- 1.Girometti N., Byrne R., Bracchi M., Heskin J., McOwan A., Tittle V., et al. Demographic and clinical characteristics of confirmed human monkeypox virus cases in individuals attending a sexual health centre in London, UK: an observational analysis. Lancet Infect Dis. 2022 doi: 10.1016/S1473-3099(22)00411-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Orviz E., Negredo A., Ayerdi O., Vazquez A., Munoz-Gomez A., Monzon S., et al. Monkeypox outbreak in Madrid (Spain): clinical and virological aspects. J Infect. 2022 doi: 10.1016/j.jinf.2022.07.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Inigo Martinez J., Montalbans E.G., Bueno S.J., Martinez F.M., Julia A.N., Diaz J.S., et al. Monkeypox outbreak predominantly affecting men who have sex with men, Madrid, Spain, 26 April to 16 June 2022. Euro Surveill. 2022;27(27) doi: 10.2807/1560-7917.ES.2022.27.27.2200471. pii=2200471. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Jezek Z., Szczeniowski M., Paluku K.M., Mutombo M. Human monkeypox: clinical features of 282 patients. J Infect Dis. 1987;156:293–298. doi: 10.1093/infdis/156.2.293. [DOI] [PubMed] [Google Scholar]
- 5.Ogoina D., Iroezindu M., James H.I., Oladokun R., Yinka-Ogunleye A., Wakama P., et al. Clinical course and outcome of human monkeypox in Nigeria. Clin Infect Dis. 2020;71(8):e210–e214. doi: 10.1093/cid/ciaa143. [DOI] [PubMed] [Google Scholar]
- 6.Ynka-Ogunleye A., Aruna O., Dalhat M., Ogoina D., McCallum A., Disu Y., et al. Outbreak of human monkeypox in Nigeria in 2017-18: a clinical and epidemiological report. Lancet Infect Dis. 2019;19:872–879. doi: 10.1016/S1473-3099(19)30294-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Bunge E.M., Hoet B., Chen L., Lienert F., Weidenthaler H., Baer L.R., et al. The changing epidemiology of human monkeypox-A potential threat? A systematic review. PLoS Neglected Trop Dis. 2022;16(2) doi: 10.1371/journal.pntd.0010141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Huhn G.D., Bauer A.M., Yorita K., Graham M.B., Sejvar J., Likos A., et al. Clinical characteristics of human monkeypox, and risk factors for severe disease. Clin Infect Dis. 2005;41:1742–1751. doi: 10.1086/498115. [DOI] [PubMed] [Google Scholar]
- 9.Selb R., Werber D., Falkenhorst G., Steffen G., Lachmann R., Ruscher C., et al. A shift from travel-associated cases to autochthonous transmission with Berlin as epicentre of the monkeypox outbreak in Germany, May to June 2022. Euro Surveill. 2022;27(27) doi: 10.2807/1560-7917.ES.2022.27.27.2200499. pii=2200499. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Perez Duque M., Ribeiro S., Martins J.V., Casaca P., Leite P.P., Tavares M., et al. Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022. Euro Surveill. 2022;27(22) doi: 10.2807/1560-7917.ES.2022.27.22.2200424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Hammerschlag Y., MacLeod G., Papadakis G., Sanchez A.A., Druce J., Taiaroa G., et al. Monkeypox infection presenting as genital rash, Australia, May 2022. Euro Surveill. 2022;27(22) doi: 10.2807/1560-7917.ES.2022.27.22.2200411. pii=2200411. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.de Nicolas-Ruanes B., Vivancos M.J., Azcarraga-Llobet C., Moreno A.M., Rodriguez-Dominguez M., Berna-Rico E., et al. Monkeypox virus case with maculopapular exanthem and proctitis during the Spanish outbreak in 2022. J Eur Acad Dermatol Venereol. 2022;36(8):e658–e660. doi: 10.1111/jdv.18300. [DOI] [PubMed] [Google Scholar]
- 13.Peirò-Mestres A., Fuertes I., Camprubi-Ferrer D., Marcos M.A., Vilella A., Navarro M., et al. Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022. Euro Surveill. 2022;27(28) doi: 10.2807/1560-7917.ES.2022.27.28.2200503. pii=2200503. [DOI] [PMC free article] [PubMed] [Google Scholar]