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• W4309409797 abstract "Recently Shafaati et al. described the current state of the monkeypox (MPX) outbreak, focusing on immune responses.1 To date, several MPX infections were observed among individuals with a known immune-impairment, predominantly people living with HIV.2, 3 An open question is how other immune deficiencies might influence prognosis: hemopoietic stem cells (HSCTs) and solid organ transplants are examples of conditions at increased risk of severe disease.4 We present the case of an autologous HSCT and heart transplant recipient with MPX infection. He was diagnosed in 2017 with AL amyloidosis with cardiac involvement, requiring heart transplant in 2018 and autologous hemopoietic stem cell transplant in 2019, achieving complete response to treatment in 2021 with daratumumab. Ongoing immunosuppressive medications at the time of MPX diagnosis were cyclosporine and mycophenolate mofetil. Other comorbidities were chronic kidney disease and osteoporosis. He received smallpox vaccination in his youth. He presented with fever and multiple vesicular lesions, following recent sexual contact with a known MPX case. Upon physical examination, presence of >30 tender, vesicular, umbilicated lesions at genital site, with a single tender, ulcerated tongue lesion, were observed; lymphadenopathy was present in both a lateral-cervical and inguinal site. Real-time PCR (RealStar® Orthopoxvirus PCR Kit1.0—altona DIAGNOSTICS) targeting variola virus and non-variola Orthopoxvirus species (cowpox, monkeypox, raccoonpox, camelpox, and vaccinia virus) was used to detect non-variola DNA; viral cultures were performed on positive samples, as previously described.5 Plaque reduction neutralization test (PRNT) was used to assess neutralizing antibodies. MPX virus was detected on oropharyngeal (cycle threshold [CT = 31], cutaneous [CT = 25], rectal [CT = 33] swabs, urines [CT = 25], and plasma [CT = 30], with positive viral cultures on the oropharyngeal and lesions swabs and urines (Table 1). Clinical worsening was documented in the following days. Thus, given the increased risk of progression, we cautiously decide to reduce the dosage of mycophenolate mofetil. In 12 days, substantial clinical stability was observed, with crusty evolution of the genital lesions. Although we obtained a negative rectal swab, the oropharyngeal (CT = 33) and cutaneous (CT = 23) swabs, urines (CT = 30), and plasma (CT = 37) tested positive, with positive viral cultures on the lesion swab and urines. On Day 23, scabs falling from the genital lesions were observed; the tongue ulcer appeared to have shrunk with resolution of the tenderness. Virologic analyses showed clearing of MPX virus from the oropharyngeal and lesions swab and plasma. Thus, we declared complete clinical healing and conclusion of home isolation, with reintroduction of prior immunosuppressive therapy. Though, we witnessed the persistence of MPX on urines (CT = 33) and seminal fluids (CT = 29), with positive viral cultures. On Day 60, further urines and seminal fluids samples were collected, showing complete virologic clearance. PRNT showed a 1:10 titer of neutralizing antibodies at time of diagnosis, with increase to 1:80 (Day 12) and 1:160 (Day 23). We witnessed a case of MPX infection in an autologous hemopoietic stem cell and heart transplant recipient. Clinical presentation was serious, with a great number of genital lesions.3 Moreover, disease duration reached almost 1 month, with infection clearance after 2 months; this could possibly be related to the concomitant immunosuppressive medications. The prolonged shedding of MPX in urines and seminal fluids, corroborated by the positive viral cultures, could pose a public health problem.6, 7 The need for adjustment of the immunosuppressive medications’ dosage is also a concern: luckily, complete response to treatment was already achieved before infection and no signs of rejection were previously documented. However, in other circumstances, modifying concurrent medications might prove to be challenging. We could not administer cidofovir, the only antiviral at the time available in Italy, being distinctly nephrotoxic, given the underlying chronic kidney disease.4, 8, 9 In a scenario of few treatment options, management of individuals with co-morbidities could prove to be challenging. Smallpox vaccination, indeed, explains the low titer of specific neutralizing antibodies observed at time of diagnosis. Though, cases of MPX have also been observed among vaccinated individuals.3, 10, 11 Likely, among HSCT or solid organ transplant recipients, the immune response to vaccination could be less effective in preventing infections. We believe that vaccination not only failed to protect against MPX, but also has not contributed in reducing symptoms. Immunosuppressed individuals can be to date vaccinated with licensed live, non-replicating MPX vaccines.12 We believe that, although their immune response might be less vigorous, the vaccination strategy, on a case-to-case level, should be prioritized in hematologic patients at risk of contracting MPX. All in all, HSCT and solid organ transplant are well-known conditions at higher risk of viral, bacterial, and fungal infection: emerging pathogens such as MPX should always be considered as new clinical challenges. Silvia Nozza and Angelo Roberto Raccagni visited the individual and contributed to writing the article. Caterina Candela and Elena Bruzzesi visited the individual and contributed to reviewing the article. Antonella Castagna, Magda Marcatti, and Fabio Ciceri contributed to the review of the article. Davide Mileto, Daniele Curreli, Fiorenza Bracchitta, and Maria Rita Gismondo coordinated virologic activities. All authors have read and agreed to the published version of the manuscript. The authors declare no conflicts of interest. The information of interest for this study (including risk factors, clinical history, laboratory, serologic and virologic data) were collected from the individuals followed at our center as part of routine clinical care and recorded in the database of the Infectious Diseases Unit of the San Raffaele Hospital (CSL Cohort). The CSL Cohort was approved by the ethics committee of the San Raffaele Hospital, Milan, Italy (date of approval 4th December 2017, protocol no. 34); on their first visit, individuals provided written informed consent on the use of their data in scientific analyses. Recorded data were anonymized and managed according to the Good Clinical Practice. Informed consent was obtained from the individual included in the study." @default.
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• W4309409797 date "2022-11-19" @default.
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• W4309409797 title "Monkeypox infection in a hemopoietic stem cell and heart transplant recipient" @default.
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