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Cellular and Molecular Life Sciences :... Oct 2006Smallpox virus eradication was one of the greatest successes of the 20th century. Moreover, the quest to combat its use in biological warfare, has fueled efforts to... (Review)
Review
Smallpox virus eradication was one of the greatest successes of the 20th century. Moreover, the quest to combat its use in biological warfare, has fueled efforts to understand residual immune memory and to develop new animal models by the scientific community. Although the literature is full of animal studies of vaccinia virus infection, continuing efforts have helped to increase our knowledge regarding humoral and cellular memory to non-persistent pathogens and to study factors that might influence further vaccination strategies in humans. In addition, the potent immunostimulatory action of poxvirus vectors has led to development and evaluation of new-generation vaccine candidates, which will be discussed in this review.
Topics: Animals; B-Lymphocytes; History, 20th Century; Humans; Immunodominant Epitopes; Immunologic Memory; Smallpox; Smallpox Vaccine; T-Lymphocytes; Variola virus
PubMed: 16964577
DOI: 10.1007/s00018-006-6313-2 -
Malawi Medical Journal : the Journal of... Jun 2022
Topics: Humans; Variola virus
PubMed: 35991811
DOI: 10.4314/mmj.v34i2.1 -
MSphere Feb 2021Smallpox, caused by (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness...
Smallpox, caused by (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. (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 × 10 plaque-forming units (PFU; 90% lethal dose [LD]) 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 []) and the time of the last quantifiable concentration (AUC) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival. 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 against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.
Topics: Animals; Antiviral Agents; Benzamides; Cytosine; Disease Models, Animal; Dogs; Female; Isoindoles; Male; Monkeypox virus; Organophosphonates; Smallpox; Variola virus
PubMed: 33536322
DOI: 10.1128/mSphere.00927-20 -
Archives of Pathology & Laboratory... Jul 2023Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox)...
CONTEXT.—
Before its eradication, the smallpox virus was a significant cause of poor obstetric outcomes, including maternal and fetal morbidity and mortality. The mpox (monkeypox) virus is now the most pathogenic member of the Orthopoxvirus genus infecting humans. The 2022 global mpox outbreak has focused attention on its potential effects during pregnancy.
OBJECTIVE.—
To understand the comparative effects of different poxvirus infections on pregnancy, including mpox virus, variola virus, vaccinia virus, and cowpox virus. The impact on the pregnant individual, fetus, and placenta will be examined, with particular attention to the occurrence of intrauterine vertical transmission and congenital infection.
DATA SOURCES.—
The data are obtained from the authors' cases and from various published sources, including early historical information and contemporary publications.
CONCLUSIONS.—
Smallpox caused maternal and perinatal death, with numerous cases reported of intrauterine transmission. In endemic African countries, mpox has also affected pregnant individuals, with up to a 75% perinatal case fatality rate. Since the start of the 2022 mpox outbreak, increasing numbers of pregnant women have been infected with the virus. A detailed description is given of the congenital mpox syndrome in a stillborn fetus, resulting from maternal-fetal transmission and placental infection, and the potential mechanisms of intrauterine infection are discussed. Other poxviruses, notably vaccinia virus and, in 1 case, cowpox virus, can also cause perinatal infection. Based on the historical evidence of poxvirus infections, mpox remains a threat to the pregnant population, and it can be expected that additional cases will occur in the future.
Topics: Infant, Newborn; Female; Humans; Pregnancy; Monkeypox virus; Mpox (monkeypox); Placenta; Orthopoxvirus; Variola virus; Poxviridae Infections; Vaccinia virus
PubMed: 36857117
DOI: 10.5858/arpa.2022-0520-SA -
Viruses Aug 2022Among the family, is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus... (Review)
Review
Among the family, is the most notorious genus. Several DNA viruses belonging to this group are known to produce human disease from the life-threatening variola virus (VARV) (the causative agent of smallpox), monkeypox virus (MPXV), cowpox virus (CPXV), and vaccinia virus (VACV). These still remain a public health concern as VACV or CPXV still cause emerging endemic threads, especially in developing countries. MPXV is able to cause sporadic human outbreaks of a smallpox-like zoonotic disease and, in May 2022, hundreds of cases related to MPXV have been reported from more than 30 countries around the globe. At the end of July, monkeypox (MPX) outbreak was even declared a global health emergency by the World Health Organization (WHO). Many aspects remain unclear regarding this outbreak and a deep understanding of might have crucial and evident implications. During the era in which people under 45 years old are not protected against VACV, the potential use of as a biological weapon raises global concern considering the rapid spreading of the current MPX outbreak in vulnerable populations. Hence, we review the most recent evidence about phylogenesis, pathogenesis, prevention, and treatment for this concerning disease.
Topics: Biological Warfare Agents; Cowpox virus; Humans; Middle Aged; Mpox (monkeypox); Monkeypox virus; Orthopoxvirus; Smallpox; Vaccinia virus; Variola virus
PubMed: 36146705
DOI: 10.3390/v14091894 -
Viruses Sep 2022An ongoing monkeypox outbreak in non-endemic countries has resulted in the declaration of a public health emergency of international concern by the World Health... (Review)
Review
An ongoing monkeypox outbreak in non-endemic countries has resulted in the declaration of a public health emergency of international concern by the World Health Organization (WHO). Though monkeypox has long been endemic in regions of sub-Saharan Africa, relatively little is known about its ecology, epidemiology, and transmission. Here, we consider the relevant research on both monkeypox and smallpox, a close relative, to make inferences about the current outbreak. Undetected circulation combined with atypical transmission and case presentation, including mild and asymptomatic disease, have facilitated the spread of monkeypox in non-endemic regions. A broader availability of diagnostics, enhanced surveillance, and targeted education, combined with a better understanding of the routes of transmission, are critical to identify at-risk populations and design science-based countermeasures to control the current outbreak.
Topics: Disease Outbreaks; Humans; Mpox (monkeypox); Monkeypox virus; Smallpox; Variola virus
PubMed: 36146818
DOI: 10.3390/v14092012 -
Bulletin of the World Health... 1987
Review
Topics: History, 20th Century; Humans; Research; Smallpox; Smallpox Vaccine; Vaccination; World Health Organization
PubMed: 3319266
DOI: No ID Found -
Antiviral Research Aug 2019The classification of smallpox by the U.S. Centers for Disease Control and Prevention (CDC) as a Category A Bioterrorism threat agent has resulted in the U.S. Government... (Review)
Review
The classification of smallpox by the U.S. Centers for Disease Control and Prevention (CDC) as a Category A Bioterrorism threat agent has resulted in the U.S. Government investing significant funds to develop and stockpile a suite of medical countermeasures to ameliorate the consequences of a smallpox epidemic. This stockpile includes both vaccines for prophylaxis and antivirals to treat symptomatic patients. In this manuscript, we describe the path to approval for the first therapeutic against smallpox, identified during its development as ST-246, now known as tecovirimat and TPOXX, a small-molecule antiviral compound sponsored by SIGA Technologies to treat symptomatic smallpox. Because the disease is no longer endemic, the development and approval of TPOXX was only possible under the U.S. Food and Drug and Administration Animal Rule (FDA 2002). In this article, we describe the combination of animal model studies and clinical trials that were used to satisfy the FDA requirements for the approval of TPOXX under the Animal Rule.
Topics: Animals; Antiviral Agents; Benzamides; Disease Models, Animal; Drug Development; Drug Evaluation, Preclinical; Humans; Isoindoles; Smallpox; United States; United States Food and Drug Administration; Variola virus
PubMed: 31181284
DOI: 10.1016/j.antiviral.2019.06.005 -
The New England Journal of Medicine Apr 2002
Topics: Bioterrorism; Humans; Smallpox; Smallpox Vaccine; United States; Vaccination; Variola virus
PubMed: 11923485
DOI: 10.1056/NEJM200204253461702 -
Public Health Reports (Washington, D.C.... Sep 1959
Topics: Biomedical Research; Humans; Smallpox; Variola virus
PubMed: 13824683
DOI: No ID Found