Figure 2 - uploaded by Mir A Ali
Content may be subject to copyright.
Time course of treatment with CMX-001 and detection of molluscum contagiosum virus in plasma and peripheral blood mononuclear cells (PBMCs) in a patient with DOCK8 deficiency. Numbers next to plasma and PBMCs indicate molluscum contagiosum virus (MCV) DNA levels (copies per milliliter); dashes, undetectable MCV DNA. Abbreviation: ND, not done.
Source publication
Molluscum contagiosum virus (MCV) is a poxvirus that causes localized papules in healthy persons. We evaluated a woman with
severe immunodeficiency and disseminated MCV. During treatment with CMX-001, an antiviral with activity against other poxviruses,
MCV DNA was detected in 20% of plasma samples. When the patient was not receiving CMX-001, MCV D...
Contexts in source publication
Context 1
... CMX has activity against several poxviruses (reviewed in [4]), it is unknown whether CMX-001 also inhibits MCV, because MCV cannot be grown in cell culture. CMX-001 was given orally at 2 mg/kg for 1 dose and then 1 mg/kg each week thereafter (Figure 2). At week 3 the patient was found to have pneumonia due to Histoplasmosis capsulatum, and posaconazole treatment was begun. ...
Context 2
... persons performing the PCR analysis were blinded to the identity of the samples. MCV DNA was detected in 1 of 5 plasma samples (20%) obtained from the index patient with DOCK8 deficiency during CMX-001 therapy and in 3 of 6 (50%) ob- tained when she was not receiving CMX-001 ( Figure 2). The MCV DNA levels ranged from 15 to 58 copies/mL of plasma. ...
Citations
... The use of BCV to treat cytomegalovirus infection did not result in any severe side effects. In addition, BCV is effective against the human molluscum contagiosum poxvirus [99,100]. ...
The human monkeypox virus (MPV), a zoonotic illness that was hitherto solely prevalent in Central and West Africa, has lately been discovered to infect people all over the world and has become a major threat to global health. Humans unintentionally contract this zoonotic orthopoxvirus, which resembles smallpox, when they come into contact with infected animals. Studies show that the illness can also be transferred through frequent proximity, respiratory droplets, and household linens such as towels and bedding. However, MPV infection does not presently have a specified therapy. Smallpox vaccinations provide cross-protection against MPV because of antigenic similarities. Despite scant knowledge of the genesis, epidemiology, and ecology of the illness, the incidence and geographic distribution of monkeypox outbreaks have grown recently. Polymerase chain reaction technique on lesion specimens can be used to detect MPV. Vaccines like ACAM2000, vaccinia immune globulin intravenous (VIG-IV), and JYNNEOS (brand name: Imvamune or Imvanex) as well as FDA-approved antiviral medications such as brincidofovir (brand name: Tembexa), tecovirimat (brand name: TPOXX or ST-246), and cidofovir (brand name: Vistide) are used as therapeutic medications against MPV. In this overview, we provide an outline of the MPV's morphology, evolution, mechanism, transmission, diagnosis, preventative measures, and therapeutic approaches. This study offers the fundamental information required to prevent and manage any further spread of this emerging virus.
... Similarly, the efficacy of CMX001 against HSV in mice has also been reported [60]. Recently, Cohen et al. have demonstrated the efficacy of CMX001 in diminishing DNA levels of molluscum contagiosum virus (MCV) in plasma [61]. In vitro results demonstrated that CMX001 (EC 50 = 0.004 ± 0.001 μM) has 78-fold higher antiviral efficacy against GPCMV in guinea pig lung fibroblasts relative to cidofovir [62]. ...
Poor absorption, short half-life and resistance development are some of the major factors responsible for reduced drug efficacy. Lipophilic prodrugs can offer certain advantages to overcome these challenges. Chemical derivatization of hydrophilic agents with lipophilic pro-moieties can significantly elevate drug diffusion across absorptive membranes. Moreover, the desired linkage (ester vs amide) may be selected to improve stability in vivo. Importantly, an appropriate selection of pro-moiety (targeting ligand) may promote drug specificity and selectivity. In this review article, an attempt has been made to summarize lipophilic prodrugs employed to improve delivery and efficacy of a wide range of poorly permeable but highly potent therapeutic agents. In addition, a brief overview on recent application of lipophilic prodrugs to promote encapsulation of hydrophilic agents in nano-sized drug carriers has been provided.
... Immunocompromised patients can develop very large (.15 mm) and numerous lesions, and bacterial superinfections [2][3][4]. There has also been a report of molluscum contagiosum viral DNA in the blood of severely immunocompromised individuals, indicating possible viremia [5]. Children with atopic dermatitis may have higher numbers of MC lesions and an increased likelihood of molluscum dermatitis [6]. ...
Molluscum contagiosum is a common superficial skin infection caused by the poxvirus, Molluscum Contagiosum virus. The study objective is to obtain a better understanding of physician practices and experiences with molluscum contagiosum in order to focus informational and guidance material.
A cross-sectional survey to assess medical practitioners' knowledge and practices with molluscum contagiosum was conducted using the 2009 DocStyles survey. Questions regarding category and number of molluscum contagiosum patients seen, treatments used and advice given to patients were included in the survey.
Dermatologists saw the most cases, with the majority seeing 51-100 molluscum contagiosum cases/year. The most common cases seen were children with multiple lesions and adults with genital lesions. Respondents were most likely to recommend treatment to immunocompromised individuals, HIV patients, adults with genital lesions and children with multiple lesions. Cryotherapy was the top choice for all specialties with the exception of OB/GYNs, whose top choice was curettage. "Avoid intimate contact until lesions resolve", "Avoid touching lesions to reduce further spread", and "Don't be concerned, this will go away" were the top advice choices.
Most survey respondents have dealt with molluscum contagiosum in their practice during the previous year. Overall, respondents picked appropriate choices for treatment and advice given; however some ineffective or unnecessary treatments were chosen and recommendations to prevent spread were chosen infrequently. Knowledge gaps for appropriate transmission precaution advice might cause unnecessary spread or autoinoculation. This survey has demonstrated that molluscum contagiosum is a common infection seen by many types of practitioners and therefore guidance on treatment considerations and infection control is valuable.
... Since their discovery and development, these compounds, along with vaccinia immune globulin, have been used to treat humans with serious complications from smallpox vaccinations, or who became seriously infected after exposure to smallpox vaccinees [5,[21][22][23]. Additionally, human infections caused by the molluscum contagiosum poxvirus have been treated with cidofovir [24] and CMX001 [25]. Treatment of infections with immunosuppressive agents is not a viable approach, since orthopoxvirus infections are more severe in immunodeficient humans [6] and immunocompromised animals [26,27]. ...
Antiviral agents are being sought as countermeasures for the potential deliberate release of smallpox (variola) and monkeypox viruses, for the treatment of naturally acquired monkeypox virus infections, and as therapy for complications due to smallpox (live-attenuated vaccinia virus) vaccination or accidental infection after exposure to vaccinated persons. Reviews of the scientific literature spanning 1950-2008 have documented the progress made in developing small-animal models of poxvirus infection and identifying novel antiviral agents. Compounds of considerable interest include cidofovir, CMX001 and ST-246® (tecovirimat; SIGA Technologies, NY, USA). New inhibitors have been identified since 2008, most of which do not exhibit the kind of potency and selectivity required for drug development. Two promising agents include 4'-thioidoxuridine (a nucleoside analog) and mDEF201 (an adenovirus-vectored interferon). Compounds that have been effectively used in combination studies include vaccinia immune globulin, cidofovir, ST-246 and CMX001. In the future there may be an increase in experimental work using active compounds in combination.
Viruses can cause disease in the skin or mucosa by direct infection or, via a systemic infection, produce secondary skin abnormalities. The chapter reviews the viruses associated with skin lesions, outlining the pathophysiology, the clinical features, diagnostic methods and the approaches to treatment. Primary skin infection following direct contact occurs with poxviruses, some herpesviruses and papillomaviruses leading to visible features which may be readily diagnostic. Less specific skin changes are seen with systemic infections, when infection is often via mucosae or inoculation, for example with parvovirus, measles or coronavirus and for these infections, diagnosis will usually involve body fluid analysis.
Zusammenfassung
Die Familie Poxviridae umfasst derzeit 22 Gattungen, die Wirbeltiere infizieren können. Humanpathogene Pockenviren gehören den Gattungen Ortho‐ , Para‐ , Mollusci‐ und Yatapoxvirus an. Bis zur Eradikation der Variola vera im Jahr 1979 waren die Pocken, im Volksmund auch Blattern genannt, eine schwerwiegende Gesundheitsbedrohung für die Bevölkerung. Noch heute sind Dermatologen mit zahlreichen Pockenvirusinfektionen konfrontiert, wie den Bauernhofpocken, die als Zoonosen nach Tierkontakten in ländlichen Gebieten oder nach Massenversammlungen auftreten können. In den Tropen können Erkrankungen durch Tanapox‐ oder Vaccinia‐Viren zu den Differenzialdiagnosen gehören. Dellwarzen sind weltweit verbreitet und werden in bestimmten Fällen als sexuell übertragbare Pockenvirusinfektion angesehen. In jüngster Zeit hatten sich Mpox (Affenpocken) zu einer gesundheitlichen Notlage von internationaler Tragweite entwickelt, die eine rasche Identifizierung und angemessene Behandlung durch Dermatologen und Infektiologen erfordert. Fortschritte und neue Erkenntnisse über Epidemiologie, Diagnose, klinische Manifestationen und Komplikationen sowie Behandlung und Prävention von Pockenvirusinfektionen erfordern ein hohes Maß an Fachwissen und interdisziplinärer Zusammenarbeit in den Bereichen Virologie, Infektiologie und Dermatologie. Dieser CME‐Artikel bietet einen aktualisierten systematischen Überblick, um praktizierende Dermatologen bei der Identifizierung, Differenzialdiagnose und Behandlung klinisch relevanter Pockenvirusinfektionen zu unterstützen.
The family Poxviridae currently comprises 22 genera that infect vertebrates. Of these, members of the Ortho‐ , Para‐ , Mollusci‐ and Yatapoxvirus genera have been associated with human diseases of high clinical relevance in dermatology. Historically, smallpox was a notorious health threat until it was declared eradicated by the World Health Organization in 1979. Today, dermatologists are confronted with a variety of poxviral infections, such as farmyard pox, which occurs as a zoonotic infection after contact with animals. In the tropics, tanapox or vaccinia may be in the differential diagnosis as neglected tropical dermatoses. Molluscum contagiosum virus infection accounts for significant disease burden worldwide and is classified as a sexually transmitted infection in certain scenarios. Recently, mpox (monkeypox) has emerged as a public health emergency of international concern, requiring rapid recognition and appropriate management by dermatologists and infectious disease specialists. Advances and new insights into the epidemiology, diagnosis, clinical manifestations and complications, treatment, and prevention of poxviral infections require a high level of expertise and interdisciplinary skills from healthcare professionals linking virology, infectious diseases, and dermatology. This CME article provides a systematic overview and update to assist the practicing dermatologist in the identification, differential diagnosis, and management of poxviral infections.
Skin disease due to viruses may be a primary infection of the epidermis or may arise secondary to systemic infection. Depending on the virus, the effects may be necrotic damage of the infected cells, proliferation and tumour formation or inflammation without major skin cell damage. The features of DNA and RNA virus infections and their skin manifestations are covered in this chapter.
Background and aims
There is a sought for vaccines and antiviral agents as countermeasures for the recent monkeypox outbreak. Here, we aimed to review and discuss the repurposing potentials of smallpox vaccines and drugs in monkeypox outbreaks based on their comparative benefits and risks. Therefore, we conducted this rapid review and discussed the repurposing potentials of smallpox vaccines and drugs in monkeypox infection.
Methods
Here, we searched Google Scholar and PubMed for relevant information and data. We found many articles that have suggested the use of smallpox vaccines and antiviral drugs in monkeypox outbreaks according to the study findings. We read the relevant articles to extract information.
Results
According to the available documents, we found two replication‐competent and one replication‐deficient vaccinia vaccines were effective against Orthopoxvirus. However, the healthcare authorities have authorized second‐generation live vaccina virus vaccines against Orthopoxvirus in many countries. Smallpox vaccine is almost 85% effective in preventing monkeypox infection as monkeypox virus, variola virus, and vaccinia virus are similar. The United States and Canada have approved a replication‐deficient third‐generation smallpox vaccine for the prevention of monkeypox infection. However, the widely used second‐generation smallpox vaccines contain a live virus and replicate it into the human cell. Therefore, there is a chance to cause virus‐induced complications among the vaccinated subjects. In those circumstances, the available Orthopoxvirus inhibitors might be a good choice for treating monkeypox infections as they showed similar efficacy in monkeypox infection in different animal model clinical trials. Also, the combined use of antiviral drugs and vaccinia immune globulin can enhance significant effectiveness in immunocompromised subjects.
Conclusion
Repurposing of these smallpox vaccines and antiviral agents might be weapons to fight monkeypox infection. Also, we recommend further investigations of smallpox vaccines and Orthopoxvirus inhibitors in a human model study to explore their exact role in human monkeypox infections.
Molluscum contagiosum (MC) is the most common poxvirus infection circulating in humans. Prevalence/incidence studies indicate the infection is frequently seen in general practice with a case incidence rate of 1295/100 000 person‐years in the UK. Molluscum contagiosum virus (MCV) seroprevalences vary between 6% and 77% in different geographical locations and subpopulations, suggesting many infections are either subclinical or not reported. MC is normally self‐limiting with few lesions disappearing spontaneously without need for treatment. Extensive cases are seen in immunosuppressed individuals and those with atopic dermatitis. MC can persist for years, and treatment should be considered in those cases.
