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Epidemiology and Health 2022Monkeypox, a rare zoonotic disease, is primarily prevalent in Central and Western Africa. However, monkeypox is emerging as a worldwide concern due to the 2022 monkeypox... (Review)
Review
Monkeypox, a rare zoonotic disease, is primarily prevalent in Central and Western Africa. However, monkeypox is emerging as a worldwide concern due to the 2022 monkeypox outbreak, which is the first instance of widespread community transmission outside Africa. Monkeypox is caused by the monkeypox virus, which belongs to the genus Orthopoxvirus and presents as a vesicular-pustular disease that may be preceded by fever, malaise, and other constitutional symptoms. If present, lymphadenopathy may distinguish it from chickenpox or smallpox. However, contrary to previous manifestations, most monkeypox patients presented with atypical features during the 2022 outbreak. Monkeypox is usually a self-limiting disease with symptoms lasting between 2 weeks and 4 weeks and is mainly transmitted when a person comes into contact with an infected animal, person, or fomites contaminated with the virus. Very few treatment options are available for this disease. Tecovirimat has been licensed in some countries for the treatment of smallpox and monkeypox infections. Two other medications, cidofovir and brincidofovir, have been found to be effective against poxviruses in in vitro and animal studies, but data on human cases of monkeypox are limited. Although Imvamune (JYNNEOS), a vaccine against monkeypox, is authorized in the United States, there are currently no established routine vaccination programs. Current preventive strategies focus on the detection of probable cases and containment of the outbreak through the implementation of selected ring vaccination programs. Fundamental principles to prevent the spread of monkeypox, including maintaining personal hygiene and avoiding close contact with symptomatic patients, are of paramount importance.
Topics: Animals; Humans; Mpox (monkeypox); Smallpox; Monkeypox virus; Cidofovir; Disease Outbreaks
PubMed: 36228673
DOI: 10.4178/epih.e2022082 -
Current Treatment Options in Infectious... 2014In treating cytomegalovirus (CMV) infection, it is crucial to decide whether one is treating pre-emptively or if one is treating established disease. Disease may be... (Review)
Review
In treating cytomegalovirus (CMV) infection, it is crucial to decide whether one is treating pre-emptively or if one is treating established disease. Disease may be further divided into viral syndrome and tissue-invasive disease. Generally, mild disease in immunosuppressed patients may be treated with oral valganciclovir. Treatment may also be started with valganciclovir for CMV retinitis in AIDS patients. In other tissue-invasive syndromes, starting with intravenous ganciclovir or foscarnet at full doses (adjusted for renal function) is preferred. Treatment at full doses should be continued until symptom resolution and until blood antigenemia (or DNAemia) is cleared. Patients receiving treatment must be closely monitored for side effects to the drugs, as well as for response. Drug-resistant CMV is a therapeutic challenge; combination therapy with both ganciclovir and foscarnet may be tried. In extreme cases, resorting to unconventional agents like leflunomide or maribavir may be necessary. Immune reconstitution, through reduction in immunosuppression, or the introduction of anti-retroviral therapy, should be attempted. CMX001 is a novel agent active against double-stranded viruses; thus far, resistance to CMX001 does not confer resistance to ganciclovir or foscarnet. Hence, prophylaxis or pre-emptive treatment with CMX001 may allow the use of ganciclovir or foscarnet for treatment.
PubMed: 25999800
DOI: 10.1007/s40506-014-0021-5 -
Clinics in Chest Medicine Mar 2017Polymerase chain reaction-based diagnosis has become the standard for viral pneumonia and other respiratory tract infections. Expansion of respiratory viral panels... (Review)
Review
Polymerase chain reaction-based diagnosis has become the standard for viral pneumonia and other respiratory tract infections. Expansion of respiratory viral panels (RVPs) outside of influenza and, possibly, respiratory syncytial virus has led to the ability to diagnose viral infections for which no approved specific antiviral treatment exists. Careful clinical evaluation of the patient with a positive RVP is, therefore, critical given the limited repertoire of treatments. Generic treatments with intravenous immunoglobulin, ribavirin, and interferons may benefit select severe viral pneumonia patients, whereas cidofovir has activity for severe adenoviral pneumonia.
Topics: Humans; Respiratory Distress Syndrome; Respiratory Tract Infections; Virus Diseases
PubMed: 28159160
DOI: 10.1016/j.ccm.2016.11.003 -
Environmental Science and Pollution... Apr 2023The human monkeypox virus (MPXV) was first identified in 1959. Since then, the incidence of the disease has been sporadic. The endemic regions were identified in... (Review)
Review
The human monkeypox virus (MPXV) was first identified in 1959. Since then, the incidence of the disease has been sporadic. The endemic regions were identified in Africa's central and western areas. However, the infection started to spread in 2017 to non-endemic regions such as North and South America, Europe, and Asia. Since May 2022, the non-endemic areas reported 62,635 till 20th September 2022. Although the monkeypox virus has a mortality of ≥ 10%, it showed only 82 mortalities worldwide in 2022. The common symptoms include chills, fever, fatigue, and skin lesions, and the complications include secondary respiratory tract infections, encephalitis, blindness, and severe diarrhea. The factors responsible for spreading the virus include improper handling and consumption of infected bushmeat, unprotected sexual intercourse, contact with an infected person, no smallpox vaccination, improper hygiene, lower diagnostic capacity, and strong travel history from the endemic regions. The therapeutic strategy is symptom-based treatment and supportive care. Antivirals and vaccines such as Tecovirimat, Brincidofovir, Cidofovir, Imvamune, and ACAM2000 have shown promising results. The primary purpose of the review is to perform an epidemiological study and investigate the pathobiology, diagnosis, prevention, treatment, and some associated complications of the monkeypox virus in 2022.
Topics: Humans; Monkeypox virus; Pandemics; Disease Outbreaks; Antiviral Agents; Cidofovir
PubMed: 36854947
DOI: 10.1007/s11356-023-26098-y -
Journal of Clinical Medicine Jun 2023Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see... (Review)
Review
Anogenital warts (AWs) represent a therapeutic challenge, especially in infants, due to sensitive skin and frequent disease recurrence. Though the initial wait-and-see approach is often adopted in asymptomatic immunocompetent children, with spontaneous clearing in almost 90% of cases within two years, persistent or symptomatic lesions can be reasonably treated. However, few studies have been conducted on children. Consequently, most treatments on patients under age 12 are not approved by the Food and Drug Administration. Herein, we review possible therapies for pediatric use in AW and report an illustrative case of a two-year-old boy with atopic skin and symptomatic, persistent AWs who was successfully treated with topical podophyllotoxin, without adverse effects or recurrence. Among available therapies for AWs, topical therapies, such as immunomodulating-agents (topical imiquimod 5% and 3.75% cream, sinecatechins 15% ointment) and cytotoxic agents (podophyllotoxin and cidofovir) are considered manageable in children because of their low aggressiveness. In particular, podofillotoxin gel 5% and imiquimod 5% cream have been reported to be safe and efficacious in children. Currently, HPV vaccination is not recommended as a treatment for established HPV infection and AWs, yet a possible therapeutic role of HPV vaccination was recently suggested in the literature and deserves mention.
PubMed: 37445264
DOI: 10.3390/jcm12134230 -
Viruses Jul 2019Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled... (Review)
Review
Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled by the development of a specific immune response, but in many cases clinical situations can be more complex and require therapy. Presently available treatments are only supportive, symptomatic, or unspecific, such as administration of intravenous immunoglobulins, and often of limited efficacy. The development of antiviral strategies against B19V should be considered of highest relevance for increasing the available options for more specific and effective therapeutic treatments. This field of research has been explored in recent years, registering some achievements as well as interesting future perspectives. In addition to immunoglobulins, some compounds have been shown to possess inhibitory activity against B19V. Hydroxyurea is an antiproliferative drug used in the treatment of sickle-cell disease that also possesses inhibitory activity against B19V. The nucleotide analogues Cidofovir and its lipid conjugate Brincidofovir are broad-range antivirals mostly active against dsDNA viruses, which showed an antiviral activity also against B19V. Newly synthesized coumarin derivatives offer possibilities for the development of molecules with antiviral activity. Identification of some flavonoid molecules, with direct inhibitory activity against the viral non-structural (NS) protein, indicates a possible line of development for direct antiviral agents. Continuing research in the field, leading to better knowledge of the viral lifecycle and a precise understanding of virus-cell interactions, will offer novel opportunities for developing more efficient, targeted antiviral agents, which can be translated into available therapeutic options.
Topics: Animals; Antiviral Agents; Disease Susceptibility; Drug Development; Erythema Infectiosum; Genome, Viral; Genomics; Host-Pathogen Interactions; Humans; Immunization, Passive; Parvovirus B19, Human; Virus Replication
PubMed: 31323869
DOI: 10.3390/v11070659 -
Frontiers in Immunology 2023On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent... (Review)
Review
On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.
Topics: Humans; Antigens, Viral; Antiviral Agents; Cidofovir; Mpox (monkeypox); Prevalence
PubMed: 37026012
DOI: 10.3389/fimmu.2023.1132250 -
Dermatology Online Journal Sep 2000Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency... (Review)
Review
Cidofovir is a potent nucleoside analog antiviral drug approved for the treatment of cytomegalovirus (CMV) retinitis in patients with the Acquired Immune Deficiency Syndrome (AIDS). It is currently available only for intravenous infusion. Several small studies and case reports describe the successful use of cidofovir applied either topically or by intralesional injection in several virally induced cutaneous diseases. Available information demonstrates that cidofovir is a potent antiviral agent with activity against several DNA viruses that cause cutaneous disease when applied topically or administered by intralesional injection. No significant systemic side effects have been noted, although application site reactions are common and can occasionally be severe. The effective use of topical and intralesional cidofovir for the treatment of diseases of the skin caused by DNA viruses has been demonstrated in animals and a limited number of patients including those infected with human immunodeficiency virus (HIV). This article reviews the pharmacology of cidofovir and the utility of topical and intralesional cidofovir for the treatment of viral infections caused by human papillomavirus, herpesviruses (including acyclovir resistant strains), Kaposi's sarcoma-associated herpesvirus, molluscum contagiosum and monkeypox.
Topics: Administration, Topical; Animals; Antiviral Agents; Cidofovir; Cytosine; DNA Virus Infections; DNA Viruses; Humans; Injections, Intralesional; Organophosphonates; Organophosphorus Compounds; Skin Diseases, Viral
PubMed: 11328613
DOI: No ID Found -
Expert Opinion on Pharmacotherapy 2015Human adenoviruses can cause serious disseminated infections including death in immunosuppressed patients, especially pediatric allogeneic hematopoietic stem cell...
Human adenoviruses can cause serious disseminated infections including death in immunosuppressed patients, especially pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. There are no drugs approved to treat such infections. Cidofovir is used intravenously in many transplant clinics, probably with some effect, but controlled trials have not been completed. Cidofovir is an acyclic nucleoside phosphonate analog of cytidine monophosphate. Following conversion to its diphosphate form within cells, cidofovir is a preferred substrate for the adenovirus DNA polymerase, leading to viral DNA chain termination. Problems with cidofovir include poor cellular uptake and nephrotoxicity. Brincidofovir, a lipid-linked derivative of cidofovir which is active against five families of double-stranded DNA viruses, represents a major advance in anti-adenovirus therapy. It is administered orally, taken up readily by cells followed by release of cidofovir within cells, and is not nephrotoxic. Brincidofovir, under development by Chimerix, Inc., is being evaluated against adenovirus infections in transplant patients including allo-HSCT patients in a phase III clinical trial (AdVise Study). Preliminary results indicate that brincidofovir is safe and very effective at decreasing adenovirus viremia and adenovirus-induced pathogenicity and mortality. Anti-adenovirus adoptive T cell therapy is another very promising approach to treating allo-HSCT patients as demonstrated in clinical studies.
Topics: Adenoviridae Infections; Adenoviruses, Human; Adoptive Transfer; Animals; Antiviral Agents; Cidofovir; Cytosine; DNA, Viral; Humans; Immunocompromised Host; Organophosphonates; T-Lymphocytes
PubMed: 26330121
DOI: 10.1517/14656566.2015.1083975 -
Vaccines Jan 2018Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated... (Review)
Review
Declaration of smallpox eradication by the WHO in 1980 led to discontinuation of the worldwide vaccination campaign. The increasing percentage of unvaccinated individuals, the existence of its causative infectious agent variola virus (VARV), and the recent synthetic achievements increase the threat of intentional or accidental release and reemergence of smallpox. Control of smallpox would require an emergency vaccination campaign, as no other protective measure has been approved to achieve eradication and ensure worldwide protection. Experimental data in surrogate animal models support the assumption, based on anecdotal, uncontrolled historical data, that vaccination up to 4 days postexposure confers effective protection. The long incubation period, and the uncertainty of the exposure status in the surrounding population, call for the development and evaluation of safe and effective methods enabling extension of the therapeutic window, and to reduce the disease manifestations and vaccine adverse reactions. To achieve these goals, we need to evaluate the efficacy of novel and already licensed vaccines as a sole treatment, or in conjunction with immune modulators and antiviral drugs. In this review, we address the available data, recent achievements, and open questions.
PubMed: 29382130
DOI: 10.3390/vaccines6010008