Dataset Information

Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf.

ABSTRACT: Therapeutic and vaccine development for human poxvirus infections (e.g., monkeypox (mpox) virus, variola virus, molluscum contagiosum virus, orf virus) has been largely deserted, especially after the eradication of smallpox by 1980. Human mpox is a self-limited disease confined to Central and West Africa for decades. However, since April 2022, mpox has quickly emerged as a multi-country outbreak, urgently calling for effective antiviral agents and vaccines to control mpox. Here, this review highlights possible therapeutic options (e.g., tecovirimat, brincidofovir, cidofovir) and other strategies (e.g., vaccines, intravenous vaccinia immune globulin) for the management of human poxvirus infections worldwide.

SUBMITTER: De Clercq E

PROVIDER: S-EPMC9758798 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf.

De Clercq Erik E Jiang Yike Y Li Guangdi G

Travel medicine and infectious disease 20221217

Therapeutic and vaccine development for human poxvirus infections (e.g., monkeypox (mpox) virus, variola virus, molluscum contagiosum virus, orf virus) has been largely deserted, especially after the eradication of smallpox by 1980. Human mpox is a self-limited disease confined to Central and West Africa for decades. However, since April 2022, mpox has quickly emerged as a multi-country outbreak, urgently calling for effective antiviral agents and vaccines to control mpox. Here, this review high ...[more]

PMID: 36539022

Similar Datasets

Project description:The widespread outbreak of the monkeypox virus (MPXV) recognized in 2022 poses new challenges for public healthcare systems worldwide. With more than 86,000 people infected, there is concern that MPXV may become endemic outside of its original geographical area leading to repeated human spillover infections or continue to be spread person-to-person. Fortunately, classical public health measures (e.g., isolation, contact tracing and quarantine) and vaccination have blunted the spread of the virus, but cases are continuing to be reported in 28 countries in March 2023. We describe here the vaccines and drugs available for the prevention and treatment of MPXV infections. However, although their efficacy against monkeypox (mpox) has been established in animal models, little is known about their efficacy in the current outbreak setting. The continuing opportunity for transmission raises concerns about the potential for evolution of the virus and for expansion beyond the current risk groups. The priorities for action are clear: 1) more data on the efficacy of vaccines and drugs in infected humans must be gathered; 2) global collaborations are necessary to ensure that government authorities work with the private sector in developed and low and middle income countries (LMICs) to provide the availability of treatments and vaccines, especially in historically endemic/enzootic areas; 3) diagnostic and surveillance capacity must be increased to identify areas and populations where the virus is present and may seed resurgence; 4) those at high risk of severe outcomes (e.g., immunocompromised, untreated HIV, pregnant women, and inflammatory skin conditions) must be informed of the risk of infection and be protected from community transmission of MPXV; 5) engagement with the hardest hit communities in a non-stigmatizing way is needed to increase the understanding and acceptance of public health measures; and 6) repositories of monkeypox clinical samples, including blood, fluids, tissues and lesion material must be established for researchers. This MPXV outbreak is a warning that pandemic preparedness plans need additional coordination and resources. We must prepare for continuing transmission, resurgence, and repeated spillovers of MPXV.

Project description:The World Health Organization (WHO) proclaimed a public health emergency in July 2022 due to the emergence of Mpox (formerly monkeypox) while the globe was still dealing with the COVID-19 epidemic. The characteristics of mpox in immunocompetent individuals are well-characterized, despite difficulties in diagnostics, immunization, and access to treatment that persist in low-income countries. Patients with weakened immune systems are more likely to spread an illness and die from it than healthy people because they cannot mount a protective immune response against it, such as a neutralizing IgG and poxvirus-specific Th1 response. A health warning on severe mpox in people who are immunocompromised due to Human Immunodeficiency virus (HIV) and other illnesses was released by the U.S. Centers for Disease Control and Prevention (CDC) on September 29, 2022. The advice does not specifically include primary immunodeficiency, but it does define other immunocompromising disorders as "having autoimmune disease with immunodeficiency as a clinical component". Both those with healthy immune systems and those with weakened immune systems, such as those who are immunosuppressed, older people, children, etc., have encountered serious health issues, but the latter group is more likely to do so. According to the advisory, "of the people with severe mpox manifestations for whom CDC has been consulted, the majority have had HIV with CD4 counts 200 cells/ml, indicating substantial immunosuppression". However, new cases are still expected to be discovered, especially in low-income countries with limited access to diagnosis, treatment, and prevention, and where a large percentage of the mpox-infected population also has advanced HIV infection. Thus, further research is always needed to determine the best way to treat mpox in immunocompromised people. In this context, we discussed /reviewed the mpox clinical presentation, available treatment options and current preventive guidelines in immunocompromised patients.

Project description:Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 105 plaque-forming units (PFU; 90% lethal dose [LD90]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID-1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID-1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [C max]) and the time of the last quantifiable concentration (AUClast) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival.IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.

Dataset Information

Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf.

Publications

Therapeutic strategies for human poxvirus infections: Monkeypox (mpox), smallpox, molluscipox, and orf.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets