An Mpox-Related Death in the United States

Alarcón, Jemma; Kim, Moon J.; Terashita, Dawn; Davar, Kusha; Garrigues, Jacob M.; Guccione, Jack P; Evans, Mark G.; Hemarajata, Peera; Wald-Dickler, Noah; Holtom, Paul; Tome, Rodrigo García; Anyanwu, Lovelyn; Shah, Naman K.; Miller, Matthew W.; Smith, T.; Matheny, Audrey; Davidson, Whitni; Hutson, Christina L.; Lucas, Jonathan; Ukpo, Odey C.; Green, Nicole M.; Balter, Sharon

doi:10.1056/nejmc2214921

Cited by 43 publications

(40 citation statements)

References 2 publications

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“…Rapid emergence of tecovirimat resistance in mpox patients has been documented 14 . The resistance has been attributed to several mutations located in the F13L gene, a target of tecovirimat (Figure 2A).…”

Section: Resultsmentioning

confidence: 98%

“…Two drugs that received emergency use authorization by the FDA against smallpox virus, tecovirimat and brincidofovir, have been used for the treatment of mpox infection 1 . Worryingly, an increasing number of studies have reported on the development of tecovirimat resistance in mpox‐infected patients during the recent outbreak 14,15 . In addition, TFT eye drops have been applied in a clinical setting for therapy of ophthalmic mpox infection 4 .…”

Section: Discussionmentioning

confidence: 99%

“…Rapid emergence of tecovirimat resistance in mpox patients has been documented. 14 The resistance has been attributed to several mutations located in the F13L gene, a target of tecovirimat (Figure 2A). We have recently selected a tecovirimat-resistant mpox strain, MPXV1 R Teco, by one-round selection in cell culture in the presence of 4 µM of tecovirimat.…”

Section: Tft Efficacy Against Tecovirimat-resistant Strainsmentioning

confidence: 99%

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Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models

Cinatl,

Bechtel,

Reus

et al. 2024

Journal of Medical Virology

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The Mpox virus can cause severe disease in the susceptible population with dermatologic and systemic manifestations. Furthermore, ophthalmic manifestations of mpox infection are well documented. Topical trifluridine (TFT) eye drops have been used for therapy of ophthalmic mpox infection in patients, however, its efficacy against mpox virus infection in this scenario has not been previously shown. In the present study, we have established ophthalmic cell models suitable for the infection with mpox virus. We show, that TFT is effective against a broad range of mpox isolates in conjunctival epithelial cells and keratocytes. Further, TFT remained effective against a tecovirimat‐resistant virus strain. In the context of drug combinations, a nearly additive effect was observed for TFT combinations with brincidofovir and tecovirimat in conjunctival epithelial cells, while a slight antagonism was observed for both combinations in keratocytes. Altogether, our findings demonstrate TFT as a promising drug for treatment of ophthalmic mpox infection able to overcome tecovirimat resistance. However, conflicting results regarding the effect of drug combinations with approved compounds warrant close monitoring of such use in patients.

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Section: Resultsmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Tft Efficacy Against Tecovirimat-resistant Strainsmentioning

confidence: 99%

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Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models

Cinatl,

Bechtel,

Reus

et al. 2024

Journal of Medical Virology

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“…Clinicians should carefully consider the risks and benefits of extending treatment, and extensions of short, defined intervals should be used (e.g., an additional 3-7 days) with close monitoring for safety signals and clinical response. Tecovirimat resistance has been detected in a small † † † † https://www.cdc.gov/poxvirus/monkeypox/clinicians/obtainingtecovirimat.html number of patients with advanced HIV who received tecovirimat for periods of weeks to months (19). Resistance can also develop as the result of subtherapeutic levels of tecovirimat (e.g., because of medication noncompliance or because fatty meals are not taken with the oral formulation).…”

Section: Approach To Using Mcms To Treat Mpoxmentioning

confidence: 99%

Interim Clinical Treatment Considerations for Severe Manifestations of Mpox — United States, February 2023

Rao¹,

Schrodt²,

Minhaj³

et al. 2023

MMWR Morb. Mortal. Wkly. Rep.

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pain-management.html § CDC offered an mpox clinical consultation service for the ongoing mpox outbreak. The existence of this service was widely publicized during CDC Clinician Outreach and Communication Activity calls, CDC's Health Alert Network messages, national conference presentations, and other communications. Health care providers seeking clinical consultations can continue to contact CDC mpox experts through the CDC Emergency Operations (770-488-7100

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“…People living with HIV accounted for 38-50% of the cases 10 . The case fatality rate was low (0.1%) but most of severe and fatal cases occurred in individuals with undiagnosed advanced HIV infection [10][11][12] . About 97% of cases reported during this recent outbreak were young men (median age 34), thus not previously vaccinated against smallpox.…”

Section: Introductionmentioning

confidence: 99%

Complement-dependent mpox virus-neutralizing antibodies in infected and vaccinated individuals

Hubert

Guivel‐Benhassine

Bruel

et al. 2023

Preprint

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Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. The Modified Vaccinia Ankara (MVA)-based vaccine was used as prophylaxis, but its effectiveness remains poorly characterized. Here, we developed two assays for quantification of neutralizing antibodies (NAbs), using MVA-GFP or a recently isolated MPXV. We measured NAb levels in 470 sera from control, MPXV-infected or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox or MVA vaccination. MPXV was barely sensitive to neutralization. Addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement-dependent and help uncover the mechanisms underlying vaccine effectiveness.

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An Mpox-Related Death in the United States

Cited by 43 publications

References 2 publications

Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models

Trifluridine for treatment of mpox infection in drug combinations in ophthalmic cell models

Interim Clinical Treatment Considerations for Severe Manifestations of Mpox — United States, February 2023

Complement-dependent mpox virus-neutralizing antibodies in infected and vaccinated individuals

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