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A complicated case of monkeypox and viral shedding characteristics

Published:October 20, 2022DOI:https://doi.org/10.1016/j.jinf.2022.10.020

      Highligths

      • Management of a monkeypox case complicated with anal abscess relieved by colostomy.
      • The viral load and viable virus was highest in skin pustule and rectal smears.
      • Prolonged viable virus was detected in nasopharynx until 21th day of onset of symptoms.
      • No viable virus was detected in the patient room air, which provokes the re-consideration of using N95 respirators for daily caregivers.
      Dear editor,
      The report by Orviz et al. highlighted the relatively optimistic prognosis of monkeypox (MPX) with no serious complications in their case series from Madrid, Spain.
      • Orviz E.
      • Negredo A.
      • Ayerdi O.
      • Vázquez A.
      • Muñoz-Gomez A.
      • Monzón S.
      • Clavo P.
      • Zaballos A.
      • Vera M.
      • Sánchez P.
      • Cabello N.
      • Jiménez P.
      • Pérez-García J.A.
      • Varona S.
      • Del Romero J.
      • Cuesta I.
      • Delgado-Iribarren A.
      • Torres M.
      • Sagastagoitia I.
      • Palacios G.
      • Estrada V.
      • Sánchez-Seco M.P.
      Grupo Viruela del Simio Madrid CNM/ISCIII/HCSC/Sandoval. Monkeypox outbreak in Madrid (Spain): clinical and virological aspects.
      However, in another confirmed case series of 197 MPX patients, five (2.5%) had proctitis with one having a perforated rectum with HIV infection and one perianal abscess.
      • Patel A.
      • Bilinska J.
      • Tam J.C.H.
      • Da Silva Fontoura D.
      • Mason C.Y.
      • Daunt A.
      • Snell L.B.
      • Murphy J.
      • Potter J.
      • Tuudah C.
      • Sundramoorthi R.
      • Abeywickrema M.
      • Pley C.
      • Naidu V.
      • Nebbia G.
      • Aarons E.
      • Botgros A.
      • Douthwaite S.T.
      • van Nispen Tot Pannerden C.
      • Winslow H.
      • Brown A.
      • Chilton D.
      • Nori A
      Clinical features and novel presentations of human MPX in a central London centre during the 2022 outbreak: descriptive case series.
      The current MPX outbreak differs from its historical antecedents and has novel features, such as sexual transmission route and genital bacterial complications. Here we report a non-HIV case of MPX with proctitis and severe refractory anal abscess who had to be relieved by colostomy. We also examined his viral shedding characteristics including the patient room and the operating room (OR) air.
      A 31-year-old Canadian man visited Istanbul in July 2022. After 5 days of condomless receptive anal sexual practice with a male partner, he started to have anal pain and vesicular skin lesions. In an outpatient clinic, botulinum toxin was injected with a diagnosis of perianal fissure. With a stabbing pain, and difficulty of passing stool, a pelvic magnetic resonance imaging (MRI) was taken, which revealed proctitis and perianal abscess. He was hospitalized on August 02, 2022, in our clinic. He had history of bipolar type 2 disease and mini gastric bypass surgery. He used methamphetamine but had been clear for the last 5 months. The real-time PCR for MPX was positive from the skin and nasopharyngeal materials. He showed a lymphocytosis (max 8000 /uL) for the first 4 days, which then disappeared. An abscess drainage was applied. He was given intravenous (iv) piperacillin-tazobactam (TZP). The anal pain progressed, and an abdominopelvic computerized tomography (CT) scan revealed a deep abscess, and ESBL positive E.coli and C. glabrata were isolated. We added micafungin 1 × 100 mg iv and switched TZP to meropenem 3 × 1 gr iv. We couldn't access to the tecovirimat. He then had severe rectal bleeding with abdominal pain and high fever. In rectosigmoidocopy, rectal ulcers were observed. A new CT scan showed no perforation, but a pelvic abscess with inflammation of rectum and adjacent tissue. General surgery department applied a transverse end-loop colostomy to by-pass stool from rectum. At the last abscess drainage MPX PCR positivity with a cycle of threshold (Ct) value of 26 was detected. We accounted this low Ct value to start cidofovir iv in combination with probenecid that could be supplied 18 days after the onset of lesions. No adverse effect was observed. Psychiatric support was provided because of his mood fluctuations. His follow up continues in Montreal, Canada.
      Our patient had an unfortunate course complicated by colostomy. In a case series of 181 patients, two (1%) had reported having anal abscess, who were treated conservatively,
      • Tarín-Vicente E.J.
      • Alemany A.
      • Agud-Dios M.
      • Ubals M.
      • Suñer C.
      • Antón A.
      • Arando M.
      • Arroyo-Andrés J.
      • Calderón-Lozano L.
      • Casañ C.
      • Cabrera J.M.
      • Coll P.
      • Descalzo V.
      • Folgueira M.D.
      • García-Pérez J.N.
      • Gil-Cruz E.
      • González-Rodríguez B.
      • Gutiérrez-Collar C.
      • Hernández-Rodríguez Á.
      • López-Roa P.
      • de Los Ángeles Meléndez M.
      • Montero-Menárguez J.
      • Muñoz-Gallego I.
      • Palencia-Pérez S.I.
      • Paredes R.
      • Pérez-Rivilla A.
      • Piñana M.
      • Prat N.
      • Ramirez A.
      • Rivero Á.
      • Rubio-Muñiz C.A.
      • Vall M.
      • Acosta-Velásquez K.S.
      • Wang A.
      • Galván-Casas C.
      • Marks M.
      • Ortiz-Romero P.L.
      • Mitjà O.
      Clinical presentation and virological assessment of confirmed human MPX virus cases in Spain: a prospective observational cohort study.
      and another one treated by incision and drainage.
      • Pfafflin F.
      • Wendisch D.
      • Scherer R.
      • Jürgens L.
      • Godzick-Njomgang G.
      • Tranter E.
      • Tober-Lau P.
      • Stegemann M.S.
      • Corman V.M.
      • Kurth F.
      • Schürmann D.
      MPX in-patients with severe anal pain.
      In our case, both tranverse end-loop colostomy and iv cidofovir were applied in the same time. So, we could not estimate properly the true effect of each on the recovery of the abscess. He had also lymphocytosis. Atypical lymphocytes associated with MPX infection is reported in a small case series (6 out of 14 patients).
      • Debuysschere C.
      • Beukinga I.
      • Hernando C.
      • Blairon L.
      • Tré-Hardy M.
      • Cupaiolo R.
      Atypical lymphocytes associated with monkeypox virus infection.
      A nurse was exposed to the urine of the patient while handling urinary bag (spilled over her clothes) on day 3 of admission. The nurse had no history of smallpox vaccine, and no vaccine for post-exposure was available in Turkey. She did not show any symptoms for the next 21 days.
      The samples from skin lesions, anal, nasopharynx swabs, anal abscess, serum, urine, tear, and air were consecutively collected (Fig. 1). Air samples from the patient room and OR were collected by Coriolis Micro® portable biological air sampler. All samples were examined by RT-PCR for MPXV DNA and PCR positive samples were cultured on Vero-E6 cells (Fig. 1). We defined a threshold (Ct≤38; viral load, PFU/ml ≥103) for the PCR positivity. This value can vary, ie. Paran et al. defined a threshold (Cq≥35; viral DNA≤4,300copies/mL) that predicts poorly- or non-infectious specimens.
      • Paran N.
      • Yahalom-Ronen Y.
      • Shifman O.
      • Lazar S.
      • Ben-Ami R.
      • Yakubovsky M.
      • Levy I.
      • Wieder-Feinsod A.
      • Amit S.
      • Katzir M.
      • Carmi-Oren N.
      • Levcovich A.
      • Hershman-Sarafov M.
      • Paz A.
      • Thomas R.
      • Tamir H.
      • Cherry-Mimran L.
      • Erez N.
      • Melamed S.
      • Barlev-Gross M.
      • Karmi S.
      • Politi B.
      • Achdout H.
      • Weiss S.
      • Levy H.
      • Schuster O.
      Beth-Din A, Israely T. Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022.
      In the RT-PCR, the viral load in skin lesions (the lowest Ct value: 14; 109 PFU/ml) was the highest, and followed by rectal smear (the lowest Ct value: 17; 108 PFU/ml), and nasopharyngeal swabs (the lowest Ct value: 27; 105 PFU/ml). No viable virus was isolated from any of the air samples. Viral culture was positive in nasopharygeal, vesiculopustular, rectal smear and rectal ulcer, and tear samples. Viral particles were visualised in rectal ulcer biopsy sample stained with anti-vaccina antibody (Fig. 2). He had also a prolonged viable virus positivity in nasopharynx until 20th day of skin rash. The latest time point at which a lesion remained positive was reported as 21 days after onset of symptom.
      • Tarín-Vicente E.J.
      • Alemany A.
      • Agud-Dios M.
      • Ubals M.
      • Suñer C.
      • Antón A.
      • Arando M.
      • Arroyo-Andrés J.
      • Calderón-Lozano L.
      • Casañ C.
      • Cabrera J.M.
      • Coll P.
      • Descalzo V.
      • Folgueira M.D.
      • García-Pérez J.N.
      • Gil-Cruz E.
      • González-Rodríguez B.
      • Gutiérrez-Collar C.
      • Hernández-Rodríguez Á.
      • López-Roa P.
      • de Los Ángeles Meléndez M.
      • Montero-Menárguez J.
      • Muñoz-Gallego I.
      • Palencia-Pérez S.I.
      • Paredes R.
      • Pérez-Rivilla A.
      • Piñana M.
      • Prat N.
      • Ramirez A.
      • Rivero Á.
      • Rubio-Muñiz C.A.
      • Vall M.
      • Acosta-Velásquez K.S.
      • Wang A.
      • Galván-Casas C.
      • Marks M.
      • Ortiz-Romero P.L.
      • Mitjà O.
      Clinical presentation and virological assessment of confirmed human MPX virus cases in Spain: a prospective observational cohort study.
      ,
      • Veintimilla C.
      • Catalán P.
      • Alonso R.
      • de Viedma D.G.
      • Pérez-Lago L.
      • Palomo M.
      • Cobos A.
      • Aldamiz-Echevarria T.
      • Muñoz P.
      The relevance of multiple clinical specimens in the diagnosis of MPX virus, Spain, June 2022.
      In our case, we detected prolonged rectal PCR positivity until day 30. We also detected viral DNA in pelvic abscess until the day 20 with no viral growth.
      Fig 1
      Fig. 1Viable monkeypox (MPX) virus and viral DNA shedding in 30 days after onset of skin rash. Green box: Nor MPX DNA neither viable virus detected. Red box: MPX viral DNA detected. Star within red box: Viable MPX was isolated.
      Fig. 2
      Fig. 2Rectum epithelium in crypt infected with monkeypox (MPX) virus by using immunofluorescent staining for anti-vaccina (FITC, DAPI counterstaining). Nuclei was stained with DAPI in blue, MPX virus in green. A. 40x magnification. B. 63x magnification.
      We found no viable MPX virus in the room air, but detected viral DNA by PCR. Marimuthu et al. found no viable virus from the air, but yet viable MPX virus from surfaces and dust samples.

      Kalisvar Marimuthu, Judith Chui Ching Wong, Poh Lian Lim, Sophie Octavia, Xiaowei Huan, Yi Kai Ng, Jun Jing Yang, Stephanie Sutjipto, Kyaw Zaw Linn, Yin Xiang Setoh, Chong Hui Clara Ong, Jane Griffiths, Sharifah Farhanah, Thai Shawn Cheok, Nur Ashikin Binti Sulaiman, Sipaco Barbara Congcong, Erica Sena Neves, Liang Hui Loo, Luqman Hakim, Shuzhen Sim, Merrill Lim, Mohammad Nazeem, Shawn Vasoo, Kwok Wai Tham, Oon Tek Ng, Lee Ching Ng Viable Monkeypox virus in the environment of a patient room medRxiv 2022.09.15.22280012; doi:10.1101/2022.09.15.22280012.

      Gould et al. identified a replication-competent virus in air samples collected during the bed linen change.

      Susan Gould, Barry Atkinson, Okechukwu Onianwa, Antony Spencer, Jenna Furneaux, James Grieves, Caroline Taylor, Iain Milligan, Allan Bennett, Tom Fletcher, Jake Dunning, N.H.S. England Airborne HCID Network. Air and surface sampling for monkeypox virus in UK hospitals. medRxiv 2022.07.21.22277864; doi:10.1101/2022.07.21.22277864.

      We think that more studies are needed to confirm that N95 instead of surgical mask is really necessary during daily routine care of the patient. Such an information is critical because of the cost and availability of the N95 respirators.
      In conclusion, anal abscess as a less, but proctitis as a more frequent manifestation in the current outbreak of MPX among men practicing anal-receptive sex should be kept in mind by the clinician. MPX could be disturbingly morbid because of its complications. MPX virus shedding dynamics with viral culture studies should be investigated much more detailed in future studies. By this case, we highlight the importance of multidisciplinary management of MPX and its expanding clinical variety.

      Funding information

      None declared.

      Ethical approval

      Koç University Institutional Review Board approved the study. The patient consented the publication.

      Declaration of Competing Interest

      The authors declare that they have no competing interest.

      Acknowledgements

      We thank our patient who had consented for clinical information to be shared in this manuscript. We also thank our great administrator Erdal Aksoy MD and his team for their unique support, and medical and nursing staff at Koc University Hospital. We are grateful to Vugar Samadlı MD from Interventional Radiology Dept. of Koç University School of Medicine (KUSOM), İrem Özdemir MD and Akın Akbulut MD from Anesthesiology Dept. of KUSOM, Aslı Ercan Doğan MD from Psychiatry Dept. of KUSOM, Pelin İrkören MD, Yağmur Nur Abik MD, Lal Sude Gucer MD, İbrahim Beyhan MD from Infectious Diseases and Clinical Microbiology Dept. of KUSOM, Sevket Ruacan, MD, Prof, and Orhun Çığ Taşkın, MD from Pathology Dept. of KUSOM for their assistance in the patient's clinical follow-up. Also thankful to Mr. Ali Pekşen from www.dotdoc.com.tr for his unique contribution to brilliant figure designs of this study.

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      1. Kalisvar Marimuthu, Judith Chui Ching Wong, Poh Lian Lim, Sophie Octavia, Xiaowei Huan, Yi Kai Ng, Jun Jing Yang, Stephanie Sutjipto, Kyaw Zaw Linn, Yin Xiang Setoh, Chong Hui Clara Ong, Jane Griffiths, Sharifah Farhanah, Thai Shawn Cheok, Nur Ashikin Binti Sulaiman, Sipaco Barbara Congcong, Erica Sena Neves, Liang Hui Loo, Luqman Hakim, Shuzhen Sim, Merrill Lim, Mohammad Nazeem, Shawn Vasoo, Kwok Wai Tham, Oon Tek Ng, Lee Ching Ng Viable Monkeypox virus in the environment of a patient room medRxiv 2022.09.15.22280012; doi:10.1101/2022.09.15.22280012.

      2. Susan Gould, Barry Atkinson, Okechukwu Onianwa, Antony Spencer, Jenna Furneaux, James Grieves, Caroline Taylor, Iain Milligan, Allan Bennett, Tom Fletcher, Jake Dunning, N.H.S. England Airborne HCID Network. Air and surface sampling for monkeypox virus in UK hospitals. medRxiv 2022.07.21.22277864; doi:10.1101/2022.07.21.22277864.