Future State of Smallpox Medical Countermeasures (2024) / Chapter Skim
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2 State of Smallpox Medical Countermeasures Readiness
2 State of Smallpox Medical Countermeasures Readiness
Pages 41-72
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A variety of medical countermeasures (MCMs) have been developed to detect (diagnostics)
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in 2017. The FDA-approved Variola Virus Nucleic Acid-Based Detection Assay is indicated for "individuals presenting with pustular or vesicular rash illness or other signs and symptoms of Variola virus infection" (FDA, 2024b)
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. During the 2022 mpox outbreak, once CDC and FDA began supporting orthopoxvirus testing in five commercial laboratory companies, clinicians preferred to use these laboratories over the public health laboratories of the LRN due to more streamlined patient data requirements and perhaps the perception of a more rapid availability of actionable results initially made possible by higher throughput testing capabilities at commercial laboratories (APHL, 2023)
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. Any work which uses live variola virus to validate smallpox diagnostics must also be approved by the World Health Organization (WHO)
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. Given the high public health concern regarding smallpox cases, rapid diagnostics aimed at the consumer are unlikely to have a role in most smallpox outbreaks.
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. Although the pathogenic mechanism for this observation may differ between clade IIb monkeypoxvirus infection and variola virus infection, this compares to reports of finding variola virus in saliva, conjunctiva, and urine in patients with hemorrhagic smallpox (Sarkar et al., 1973)
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. Ring vaccination is also still recommended by both WHO and CDC as the first-line response strategy for a smallpox outbreak (CDC, 2019b; WHO, 2023)
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stockpile maintains three different smallpox vaccines, all of which are based on vaccinia virus: two types of live, replicating virus vaccines; and an attenuated live, non-replicating vaccine as well as ancillary supplies for their administration (Table 2-1)
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1st generation • Emergency Use Formulation contains Live, replicating Authorization (EUA) / live vaccinia virus in vaccinia virus, Investigational New Drug 50% glycerol, 0.4% NYCBOH-derived (IND)
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. Non-replicating vaccines were acquired more recently to provide an alternative for individuals contraindicated to receiving replicating smallpox vaccine.
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• Live vaccinia virus vaccines developed using clonal derivatives of 1st genera tion vaccines (Dryvax)
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. CDC's clinical use guidelines for smallpox vaccine indicate that there are no absolute contraindications for a smallpox vaccination in a post-event setting but that there are certain "relative" contraindications due to the possibility of adverse events associated with certain conditions (Table 2-2)
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, 1–2 deaths per million progressive vaccinia (fatality rate primary vaccinations. nearly 100% and eczema vaccinatum Often in young children or (10% before vaccinia immune globulin those with unrecognized [VIG]
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Non-infectious Generalized rash occurring 1–2 weeks 51.5–164.6 per million rashes (erythema after vaccination. Most resolve primary vaccinations multiforme)
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Reliance on the U.S. Strategic National Stockpile and Concerns with Manufacturing Capacity Dependence on the SNS smallpox vaccine stockpile as the primary form of smallpox readiness has required that sufficient inventory be maintained to respond to a smallpox event where the entire U.S.
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. Research on fourth generation smallpox vaccines could explore potential subunit or nucleic acid vaccines (protein, peptide, mRNA)
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The development of novel smallpox vaccines using multi-vaccine platforms (i.e., use common vaccine vectors, manufacturing ingredients, and processes) would improve the capacity for rapid vaccine production in response to a smallpox event and reduce the need for stockpiling in the SNS at current levels.
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. Brincidofovir Pro-drug of cidofovirf; • Treatment of human smallpox • The lipid modification Oral suspension -- expiry (CMX001/ following phosphorylation infections only (FDA approved)
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CDC = U.S. Centers for Disease Control and Prevention; EA = expanded access; EIND = emergency investigational new drug application; IND = investigational new drug application; OPXV = orthopoxvirus; VARV = variola virus.
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is uncertain. Experience with the mpox outbreak revealed that those with severe immunosuppression required extended courses of treatment, often using multiple therapeutics (Pinnetti et al., 2023)
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. Adverse events, such as serious renal toxicity, have been observed during treatment of CMV retinitis infections with cidofovir (Skiest et al., 1999)
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; (3) Vaccinia immune globulin intravenous (VIGIV)
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2023. Strategic National Stockpilesmallpox medical countermeasuresoverview.
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population at risk of severe adverse events from replicating smallpox vaccine. Public Health Nursing 34(3)
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2024b. Product classification: Variola virus nucleic acid-based detection assay.
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2023. mRNA vaccines encoding fusion proteins of monkeypox virus antigens protect mice from vaccinia virus challenge.
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2023. Variola virus research: Overview of main activities and use of live virus.
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2015. Safety and immunogenicity of modified vaccinia Ankara-Bavarian Nordic smallpox vaccine in vaccinia-naive and experienced human immu nodeficiency virus-infected individuals: An open-label, controlled clinical phase II trial.
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2008. Pregnancy, birth, and infant health outcomes from the national smallpox vaccine in pregnancy registry, 2003–2006.
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2013. Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000® compared with Dryvax®.
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2015. Cardiac safety of modified vaccinia Ankara for vaccination against smallpox in a young, healthy study population.
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