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PubMed2000

[Risk and risk management connected with xenograft].

Transmission of an animal virus to man is probably a constant reality. Pathogenicity is is not inevitable. Some vaccines were contaminated by cell culture but remain safe. Haemorrhagic fevers, despite limited outbreaks, are often cited in the media. On the other hand, the influenza A virus has been responsible for a large mortality. The cases of human infection with simian viruses (herpes virus B, cytomegalovirus, spumavirus, immunodeficiency virus) were accidental and have always remained asymptomatic. Monkeypox virus emerges in only some outbreaks. No transmission of animal endogenous retrovirus has been described. The precautionary principle, in the face of an unquantifiable risk, supposes that preventive measures should be taken in advance to reduce the risk at each step: isolation of the animal source after hysterotomy, transport in a germ-free environment, procurement and transplantation in rigorous surgical conditions, long-term follow-up surveillance of the patient, his or her family and healthcare workers. All the phases of the xenotransplantation procedure should be taken to limit the number of places and persons coming into contact with the recipient. Surveillance means regular clinical information. Various samples should be taken from the animal source, recipient, his or her family contacts, medical staff and cryogenically preserved as 'biological memory'. A National Xenotransplantation Register should be set up to gather and share all information on incidents.

Animals↗
PubMed2000

[Circulation of virus and interspecies contamination in wild animals].

Paradoxically, just when we have succeeded in eradicating and/or bringing under control the major viral infections (smallpox, poliomyelitis, measles) numerous viral infections are emerging in man and in animals. Changes in our social environment, technological and ecological equilibrium have facilitated this phenomenon. Furthermore, certain of these viruses have demonstrated an almost unlimited capacity to adapt genetically to environmental change. HIV has already infected 40 million individuals, but monkeypox, Ebola, simian herpes can cause epidemics with serious if not fatal outcomes. Haemorrhagic fever epidemics have resulted from human contact with Flavivirus infected rodents and insects. Paramyxoviruses and morbiliviruses can cause fatal outcomes in man and animals. And the three influenza epidemics having occurred in the 20th century all came from the type A avian reservoir. The often complex combinations of predisposing factors having facilitated the emergence of several epidemics merit further consideration.

Animals↗
PubMed2000

A review of topical and intralesional cidofovir.

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.

Administration, Topical↗
PubMedDate not supplied

[Orthopoxvirus genes for Kelch-like proteins. I. Analysis of species specific differences by gene structure and organization].

Genes and proteins of the kelch superfamily were structurally analyzed in the smallpox (SPV), monkeypox (MPV), cowpox (CPV), and vaccinia (VV) viruses. Genes potentially coding for the kelch-like proteins were found only in the variable terminal regions of the orthopoxvirus genome. The set and sizes of their protein products varied with species. All genes of the superfamily proved to be disrupted by mutations in SPV, which is highly pathogenic for its only host, man. The largest set of kelch-like proteins was observed for CPV, which is low-pathogenic for humans and has the broadest animal host range. The kelch-like proteins of one virus showed low homology to each other, whereas isologs of different viruses were highly homologous. The results testified to the earlier assumption that CPV is the most ancient and an ancestor of the other orthopoxviruses pathogenic for humans.

Amino Acid Motifs↗
PubMedDate not supplied

[Immunomodulatory proteins of orthopoxviruses].

The review considers recent data on the structural-functional organization of the genome of orthopoxviruses pathogenic for humans, including the variola, monkeypox, cowpox, and vaccinia viruses. Emphasis was placed on the structure of molecular virulence factors that suppress the inflammatory reactions, immune response, and interferon effects induced by virus infection.

Amino Acid Sequence↗
PubMed2003

U.S. military officer participation in the Centers for Disease Control and Prevention's Epidemic Intelligence Service (1951-2001).

The Epidemic Intelligence Service (EIS) was created in 1951 to provide epidemiologists to investigate natural and intentional disease epidemics. From an initial class of 23 U.S. citizens, the program has evolved into a globally recognized, hands-on learning experience, accepting approximately 65 to 75 new officers each year. The first U.S. military epidemic intelligence service officer (EISO) was accepted into the program in 1994. Since that time, 12 such officers have completed, or have begun, EIS training. They have comprised 2.1% of all EISOs from 1994 to 2001 and 0.47% of all EISOs. This total has included nine Air Force veterinarians, one Army veterinarian, one Army physician, and one Navy physician. Each military EISO had the opportunity to lead investigations of significant public health events (e.g., Ebola, monkeypox, malaria, Nipah virus, West Nile fever, and anthrax outbreaks). All graduates from the military returned to active duty assignments in operational medical units, research institutes, or the intelligence community.

Adult↗
PubMed2004

[Bacterial and viral epidemics of zoonotic origin; the role of hunting and cutting up wild animals].

Since the Prehistoric times hunting has been a vital activity for man. However, this may account for the contamination of the hunter, his family and relatives. Infections may occur by direct contact with blood or tissues of infected animal during handling and cutting up preys and when preparing or eating meat, or also when bitten by injured animal. Apes and antelopes hunting in sub-Saharan Africa proves to be particularly important since it has been well established that the recent or previous emergence of some viral zoonosis (Ebola, Aids, T lymphotropic viruses and Monkeypox) resulted from hunting and poaching. Moreover predation among different species of non human primates such as that practised by chimpanzees against monkeys, has led to the construction of recombinant simian Lentiviruses, such as SIV cpz able to infect man and then spread over the entire mankind as it was the case with HIV-1. SARS is another possible example of the zoonotic risks represented by the sale, handling and cutting up Chinese wild animals such as Himalayan civets for culinary purposes.

Acquired Immunodeficiency Syndrome↗
PubMed2004

Preparing for an era of weapons of mass destruction (WMD)--are we there yet? Why we should all be concerned. Part II.

September 11, 2001 demonstrated dramatic voids in national preparedness, and catalyzed massive efforts to identify and remedy vulnerabilities. Since Part I of this series appeared in August 2002, significant improvements have been achieved especially in bioterrorism and chemical terrorism for first responders and emergency medicine, law enforcement, and public health (surveillance). Such efforts manifested benefits during the SARS outbreaks and monkeypox cases of 2003. Nevertheless, emerging infectious diseases will continue to pose a threat if we do not remain vigilant and continue to invest in training, surveillance, and treatments. As expected, many poison centers and toxicologists have taken leadership roles nationwide. In regions where such leadership existed, preparedness levels are strong and collaborations resulted in the development of valuable response plans and training, including the Advanced Hazardous Life Support (AHLS) and Basic Disaster Life Support (BDLS) courses. Early success notwithstanding, experts suggest that current national preparedness has improved slightly from "1" (9/11) to "3" out of "10". Increasingly it has become evident that the nuclear threat, including radiation terrorism, is significant, against which the US remains inadequately prepared. Arguably the nuclear threat-whether accidental or planned-remains our highest consequence vulnerability, and we must rapidly improve our readiness across disciplines. Special populations including the elderly and children remain marginalized in preparedness protocols. Local vulnerabilities including chemical manufacturing and transportation--not just a risk for terrorism but industrial accidents--continue unabated. Our early success is not an endpoint; much work remains and time is fleeting. This report examines vulnerabilities that must be addressed to enhance preparedness.

Disaster Planning↗
PubMed2005

Rapid viral diagnosis: role of electron microscopy.

Starting in the 1960, electron microscopy (EM) became widely applied also in viral diagnosis. During the 1970th and 80th, many new agents were characterized from diagnostic cell cultures and clinical specimens. The wide introduction of ELISA- and PCR-techniques as well as cost-arguments recently reduced the role of EM in routine viral diagnosis. Compared to other diagnostic techniques, however, EM excells by speed and "open view", i.e. by the ability to detect also the "un-expected" without the need for specific reagents. As shown in 2003 by the elucidation of the SARS pandemia and the human monkeypox outbreak in US, EM is well suited as a safe, front-line diagnostic method in infectious diseases emergencies and/or in possible bioterrorist attacks.

Forecasting↗
PubMedDate not supplied

[Expression of genes for orthopoxviral TNF-binding proteins and study resulted recombinant proteins].

Genes for TNF-binding proteins (CrmBs) of variola virus (VARV), monkeypox virus (MPXV) or cowpox (CPXV) were isolated with PCR from viral genomes and expressed within baculovirus DNAs in Sf21 insect cell line. Properties of resulted recombinant proteins were studied with physical-chemical and immunological methods. It was shown with solid phase enzyme-linked immunoassay that viral proteins inhibited hTNF binding with polyclonal hTNF-antibodies. The strongest inhibitor was VARV-CrmB, the less one was MPXV-CrmB. Biological activity of recombinant protein preparations was studied in the test of neutralization of TNF cytotoxicity for L929 murine fibroblast cells. It was shown that recombinant CrmBs neutralized cytotoxicity of hTNF, mTNF or rTNF in species-specific manner. It was shown also that effectiveness of hTNF cytotoxicity inhibition in vitro with VARV-CrmB exceeded the same effect of polyclonal hTNF-antibody. A possibility of the elaboration of new therapeutics for anti-TNF therapy on the base of CrmB-like proteins is discussed.

Animals↗
PubMed2006

[An oligonucleotide microarray for detection and discrimination of orthopoxviruses based on oligonucleotide sequences of two viral genes].

An oligonucleotide microarray for detection and identification of orthopoxviruses was developed. Genus specific and orthopoxvirus species-specific regions of the genes encoding chemokine binding and alpha/beta-interferon binding proteins were used as a target. The developed microarray allows the variola, monkeypox, cowpox, vaccinia, camel-pox and ectromelia (mousepox) viruses to be distinguished with a high degree of reliability.

Gene Amplification↗
PubMedDate not supplied

[Possible mechanism of orthopoxvirus preservation in nature].

Until recently, virus carrier state in the absence of overt clinical infection has been known for only one species of orthopoxviruses, namely, ectromelia virus. The paper describes the results of the modelling of asypmtomatic infection caused by monkeypox, cowpox, and ratpox viruses. Persistence of these viruses up to 6 weeks in animals (hamsters, cotton and white rats) with experimental asymptomatic infection as well as in apparently normal naturally infected white rats was established by isolation of virus from the organs of these animals. These results suggest that asymptomatic virus carrier state may occur both with ectromelia and a number of other orthopoxviruses. The mechanism may be of ecological importance, providing for circulation of these viruses and their preservation as biological species in nature.

Animals↗
PubMed1985

[Danger to the human caused by animal poxvirus following discontinuation of mandatory vaccination against smallpox].

The discontinuation of smallpox vaccination will lead to a gradual decrease or disappearance of immunity to poxviruses of the genus Orthopoxvirus. It is discussed whether orthopoxviruses of animals may then constitute a potential danger to man, with respect to their mutagenic and adaptation capabilities as well as their possible genetic interactions. Infection of man with these viruses is generally possible, but at present, not of acute importance. Monkeypox and cowpox viruses, as well as their variants occurring in carnivores and rodents, are of primary interest for individuals who have not been vaccinated against smallpox. Suggestions are put forward on how the human population, as well as domestic and laboratory animals, may be protected against infection with orthopoxviruses originating from animals. In particular, it is recommended that endangered groups of people should receive voluntary vaccination with genetically stable, attenuated vaccinia virus strains.

Animals↗
PubMed1979

Experimental smallpox in chimpanzees.

In an attempt to prepare highly specific antiserum to variola virus, a chimpanzee was inoculated with a virulent human strain of this virus. Three uninoculated chimpanzees were housed in the same room; two of these developed clinical disease with seroconversion, while the third developed no evidence of infection and no antibody. The three animals that became ill also developed antibody to vaccinia and monkeypox viruses. Human contacts during the study and following a break in containment showed no evidence of infection as determined by serological tests and lack of clinical disease.

Animals↗
PubMed1969

Trsmission of smallpox by contact and by aerosol routes in Macaca irus.

Smallpox is believed not to occur naturally in species other than man. However, reports of several epizootics of an exanthematous disease, similar to smallpox, in wild monkeys have raised the question of a simian reservoir. If such a reservoir for smallpox exists, the eradication of this disease from the world would be a difficult or impossible task. Transmission of smallpox in Macaca irus has been studied to determine whether transmission occurs and if infection chains can be maintained by this species.Transmission was consistently accomplished by both contact and aerosol routes. In the contact transmission studies, the smallpox infection was maintained through 6 passages but was lost with the seventh passage. The virulence of the virus did not appear to increase as the virus was serially passed in monkeys. Continuing studies of the possible occurrence of smallpox and of monkeypox in simian populations are warranted.

Aerosols↗
PubMed1977

Identification of Orthopox virus by isoelectrofocusing in a granulated gel.

Twenty strains of Orthopox viruses (vaccina (3), cowpox (2), monkeypox (2), variola major and minor (7) and whitepox (6)) have been tested by electrofocusing in a granulated gel. From our preliminary results, it appears that there is a clearcut distinction between smallpox and whitepox. If our results are confirmed, it will be the first real genetic marker identified because other in vitro or in vivo test have heretofore failed to differentiate between smallpox and whitepox. Further work is now in progress, to evaluate of the test and it is hoped to find and explanation for the observations now reported.

Isoelectric Focusing↗
PubMed1981

ELISA--a simple test for detecting and differentiating antibodies to closely related orthopoxviruses.

In this paper, the results are reported of experiments to investigate the optimum conditions for determining, and differentiating between, the antibodies against closely related poxviruses using the ELISA technique. This assay was found to be considerably more sensitive than the virus neutralization, haemagglutination inhibition, passive haemagglutination, and indirect fluorescent antibody tests for detecting antibodies, but has not yet been compared with radioimmunoassay. The use of ELISA made it possible to differentiate between antibodies to vaccinia, whitepox, and monkeypox viruses.

Antibodies, Viral↗
PubMed1982

Enzyme studies for the characterization of some orthopoxvirus isolates.

The thymidine kinase produced in cell cultures by several orthopoxviruses has been tested for sensitivity to inhibition by thymidine triphosphate (TTP). Thymidine kinase preparations from eleven variola isolates and from five "whitepox" isolates were all found to be sensitive to inhibition by TTP. Preparations from other orthopoxviruses, including vaccinia, cowpox, and monkeypox, were all resistant to inhibition by TTP. There was no overlap between the two groups of results and no viruses were found which gave intermediate results. Tests with hybrid viruses showed that this character segregated independently of other biological marker characters and is thus a valuable additional marker for variola and variola-related viruses.

Poxviridae↗