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Tropical dermatology: viral tropical diseases.

Viruses are important pathogens in tropical areas; most of them, especially the tropical hemorrhagic fevers, produce mucocutaneous manifestations. More than any other kind of pathogen, viruses have the possibility for being widespread, since they have a greater probability of mutation than do bacteria, can cross species barriers easily, and infect both human beings and animals in habitats with a great biodiversity. Tropical habitats also have been subject to major ecologic changes in the last few decades, exposing humans to direct contact with these viruses and allowing hemorrhagic fevers due to new emergent viruses such as flaviviruses, filoviruses, arenaviruses, and hantaviruses to become major threats to public health. The collapse of eradication programs in many countries, as well as population increases and ecologic modifications, have led to the spread of dengue and yellow fever to large portions of the world owing to the dissemination of vectors, especially mosquitoes, with broad ecologic ranges. Viruses previously restricted to some geographic areas, such as Rift Valley fever, Crimean-Congo hemorrhagic fever, West Nile fever, and monkeypox are now affecting new countries and populations. Other viruses such as herpes B infection often affect travelers and animal handlers in most parts of the world. Dermatologic lesions occur in all these diseases and can facilitate a rapid diagnosis, leading to control of the virus and helping prevent possible outbreaks.

Animals↗

The confirmation and maintenance of smallpox eradication.

In December 1979, an independent scientific commission certified global eradication of smallpox. This conclusion was accepted at the 33d World Health Assembly of the World Health Organization (WHO) in May 1980. After WHO's intensified eradication program began in 1967, special certification procedures were used in 35 countries where the disease had been endemic and in 44 others at special risk. Six laboratories are known to retain variola virus; efforts have been made to ensure strict containment of these strains. There is no evidence that smallpox will recur as an endemic disease. Nevertheless, WHO will promote surveillance of smallpox-like disease and selected laboratory research on certain orthopoxviruses. These efforts will maintain confidence that smallpox has been eradicated and confirm that there are no animal reservoirs of variola virus. A more complete understanding of the orthopoxviruses, including monkeypox virus, should also be obtained.

Child↗

The evolving epidemiology of viral encephalitis.

PURPOSE OF REVIEW: The introduction of West Nile virus to North America illustrates the potential emergence of novel encephalitic agents in unexpected settings. There has been continued recognition of emerging neurotropic viruses in both the developed and developing world and novel modes of transmission of these agents. This review describes recent developments in the epidemiology of West Nile virus and several other emerging viral encephalitides in the developed and developing world and the emergence of novel mechanisms of transmitting viral encephalitis. RECENT FINDINGS: West Nile virus has continued to have a large public health impact in North America. Improvements in blood donor screening have decreased transfusion-associated transmission of the virus. Monkeypox, with associated encephalitis, occurred in the US. Chandipura virus, an infrequently recognized rhabdovirus, was attributed to large outbreaks of viral encephalitis; however, compelling evidence suggests that the relationship of illness and the virus are questionable. Recent cases of transfusion-associated and transplant-associated viral encephalitis, including West Nile virus, rabies virus, and lymphocytic choriomeningitis virus, were described. SUMMARY: Continued West Nile virus activity in North America reinforces the fact that viruses can emerge and thrive in new environments and unexpected settings and suggests the need for continued surveillance. Transfusion-associated and transplant-associated viral encephalitis may be an underrecognized risk of these procedures.

Animals↗

Potential of MRNA vaccines for mpox prevention: current evidence and future directions.

In 2022, the presumption of monkeypox (mpox) to be of limited epidemiology shifted when a global outbreak was announced. Being a member of the Orthopoxvirus genus in the Poxviridae family, it'd been reported in over 82 countries with over 17 000 confirmed cases by July 2022, thus showing its capability for spreading rapidly. As the smallpox vaccine offers 85% cross-immunity against mpox, the outbreak highlighted the attenuation of global immunity against orthopoxviruses after the cessation of vaccination campaigns against smallpox. The mortality of this virus is higher in vulnerable populations such as children, pregnant women, the elderly, and immunosuppressed individuals. With treatment methods being limited to off-label use of antivirals, the need for urgent and efficient preventative measures is emphasized. At present, JYNNEOS (Modified Vaccinia Ankara-Bavarian Nordic), showing favorable safety, and ACAM2000, a live attenuated virus with a high risk of side effects, are two vaccines that are indicated for mpox immunization. However, neither of them has proven full safety, efficacy, and widespread accessibility against mpox. Hence, the use of mRNA vaccines has emerged as a better alternative to traditional vaccinations, as they leverage synthetic messenger RNA to instruct host cells to produce antigens, eliciting both humoral and cellular immune responses. Though they provided rapid scalability, adaptability to emerging viral variants, and an established safety profile after the COVID-19 pandemic, their usage in preventing mpox remains an area of research. This paper elucidates the potential of mRNA technology to address the unmet needs in mpox prevention. It also highlights the need for genomic surveillance, immunological insights, and innovative delivery systems.

COVID-19↗

The surface antigens of orthopoxviruses detected by cross-neutralization tests on cross-absorbed antisera.

Cross-neutralization tests were done on accepted species and recently isolated members of the genus Orthopoxvirus using antisera which had been separately absorbed with the various viruses. The results provided evidence for the involvement of four neutralizing antigens, and their distribution among 13 virus strains was determined. Monkeypox (Congo-8-Lombe), camelpox (Gorgan), ectromelia (Mill Hill), 'Lenny' and elephant poxviruses had distinctive antigenic formulae. Lister and Wyeth vaccines were indistinguishable but different from Copenhagen and EM63 vaccines which were themselves distinct. Cowpox (Brighton), buffalopox (BP4), MK 10, and Moscow poxviruses were indistinguishable. Examples were found where viruses shared surface antigens but were not all neutralized by antibody to them. this reduced the practical value of the technique for virus identification. Evidence was also obtained for the existence in some viruses of a fifth antigen, antibody to which could block neutralization by antibody to one particular antigen.

Antigens, Surface↗

Rapid detection and differentiation of human pathogenic orthopox viruses by a fluorescence resonance energy transfer real-time PCR assay.

BACKGROUND: The orthopox viruses that are pathogenic for humans include variola major virus (VAR), monkeypox virus (MPV), cowpox virus (CPV), and to a lesser extent, camelpox virus (CML) and vaccinia virus (VAC). PCR is a powerful tool to detect and differentiate orthopox viruses, and real-time PCR has the further advantages of rapid turnaround time, low risk of contamination, capability of strain differentiation, and use of multiplexed probes. METHODS: We used real-time PCR with fluorescence resonance energy transfer technology to simultaneously detect and differentiate VAR, MPV, CPV/VAC, and CML. An internal control generated by cloning and mutating the PCR target gene facilitated monitoring of PCR inhibition in each individual test reaction. RESULTS: Strain differentiation results showed little interassay variability (CV, 0.4-0.6%), and the test was 100-fold more sensitive than virus culture on Vero cells. Low copy numbers of DNA could be detected with > or =95% probability (235-849 genome copies/mL of plasma). CONCLUSIONS: The real-time PCR assay can detect and differentiate human pathogenic orthopox viruses. The use of an internal control qualifies the assay for high sample throughput, as is likely to be needed in situations of suspected acts of biological terrorism, e.g., use of VAR.

Animals↗

Control of communicable diseases; restrictions on African rodents, prairie dogs, and certain other animals. Interim final rule; opportunity for public comment.

The Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA) are issuing this interim final rule to amend their regulations to establish new restrictions and modify existing restrictions on the import, capture, transport, sale, barter, exchange, distribution, and release of African rodents, prairie dogs, and certain other animals. We are taking this action to prevent the spread of monkeypox, a communicable disease, in the United States.

Africa↗

Emerging infectious diseases at the beginning of the 21st century.

The emergence and re-emergence of infectious diseases involves many interrelated factors. Global interconnectedness continues to increase with international travel and trade; economic, political, and cultural interactions; and human-to-human and animal-to-human interactions. These interactions include the accidental and deliberate sharing of microbial agents and antimicrobial resistance and allow the emergence of new and unrecognized microbial disease agents. As the 21st century begins, already new agents have been identified, and new outbreaks have occurred. Solutions to limiting the spread of emerging infectious diseases will require cooperative efforts among many disciplines and entities worldwide. This article defines emerging infectious diseases, summarizes historical background, and discusses factors that contribute to emergence. Seven agents that have made a significant appearance, particularly in the 21st century, are reviewed, including: Ebola and Marburg hemorrhagic fevers, human monkeypox, bovine spongiform encephalopathy, severe acute respiratory syndrome (SARS), West Nile virus, and avian influenza. The article provides for each agent a brief historical background, case descriptions, and health care implications.

Animals↗

[Emerging viral diseases].

Emerging and re-emerging infectious diseases have again entered the public arena in recent years. This is due to factors such as evolving lifestyles, ecological and socio-political upheavals, and recent diagnostic advances. Numerous pathogens, including viruses like West Nile, Chikungunya and Japanese encephalitis on the one hand, and hemorrhagic fever viruses like Ebola and Maburg, are particular concerns. Recently, the Corona virus responsible for SARS, which caused an epidemic sufficiently worrisome to challenge crisis management concepts, was successfully isolated. It is in this context that so-called "bird flu'", may be on the verge of causing a human pandemic. Pox and Monkeypox are "virtually emerging" viruses that have potential for use in bioterrorism. The management and treatment of these emerging infectious diseases calls for new approaches, organizations and infrastructures.

Animals↗

Poxvirus infection of the baboon (Papio cynocephalus).

Ten serial passages of monkeypox (MPV), vaccinia, variola, and chimpanzeepox (chimp-9) viruses were performed in baboons (Papio cynocephalus) via skin scarification. Comparisons of clinical and virological results indicate that MPV and vaccinia are very closely related and that variola and chimp-9 viruses are identical. These findings suggest that infections of simians with chimp-9 virus resulted from contact with variola virus, the source of which is still unknown. On the other hand, MPV in monkeys may have resulted from contact with recently vaccinated humans, serial passage through simian hosts resulting in the biological alterations that produced MPV.

Animals↗

[Use of the monkey pox virus for evaluating the intensity of the immunity against smallpox in experiments on M. rhesus].

Monkeypox virus causing in M, rhesus upon aerogenic infection a disease similar to human varioloid was used to evaluate the intensity of immunity against smallpox in immunized M. rhesus monkeys. Postvaccination immunity was solid in all the animals vaccinated intradermally or orally. In 2 out of 14 monkeys immunized orally, however, the immunity was partially overcome. Neutralizing antibody titers in these two monkeys were 1:5 and 1:25, respectively. This agreed with the observations made in Pakistan indicating the possibility that some humans having serum neutralizing antibody titers up to 1:32 could contract smallpox and develop the disease.

Animals↗

Exotic viral diseases.

Marburg virus disease, Lassa fever, monkeypox, and Ebola virus diseases of humans have all been recognized since 1967. These are examples of some of the exotic virus diseases which through importation may present a potential public health problem in the United States. Some of these viruses are also highly hazardous to laboratory and medical personnel. This paper is a review of the general characteristics, the epidemiology, and laboratory diagnosis of the exotic viruses which have been described during the last 25 years.

Animals↗

Surveillance of orthopoxvirus infections, and associated research, in the period after smallpox eradication.

In 1980, the World Health Assembly declared the global eradication of smallpox and recommended the universal discontinuation of smallpox vaccination; nevertheless, it recommended that surveillance and research on orthopoxvirus infections should continue. By early 1982, all except 8 countries in the world had stopped routine vaccination programmes and all except 1 no longer required an international certificate of smallpox vaccination for travellers. Since 1978, as a result of continuing active surveillance, 176 smallpox rumours have been investigated in 60 countries. Two of these concerned the two laboratory-associated cases that occurred in the United Kingdom in 1978; all the others were false alarms. Special surveillance programmes for human monkeypox have been developed in West and Central Africa. The number of laboratories retaining variola virus stocks has been reduced to four. Investigations to determine the identity and origin of the six known isolates of "whitepox" virus have continued. Research on mapping of variola DNA and on monoclonal antibodies against certain orthopoxvirus antigens is continuing. All these measures are aimed at ensuring that the achievement of smallpox eradication is permanent.

DNA, Viral↗

Cross-species transfer of viruses: implications for the use of viral vectors in biomedical research, gene therapy and as live-virus vaccines.

All living organisms are continuously exposed to a plethora of viruses. In general, viruses tend to be restricted to the natural host species which they infect. From time to time viruses cross the host-range barrier expanding their host range. However, in very rare cases cross-species transfer is followed by the establishment and persistence of a virus in the new host species, which may result in disease. Recent examples of viruses that have crossed the species barrier from animal reservoirs to humans are hantavirus, haemorrhagic fever viruses, arboviruses, Nipah and Hendra viruses, avian influenza virus (AI), monkeypox virus, and the SARS-associated coronavirus (SARS-CoV). The opportunities for cross-species transfer of mammalian viruses have increased in recent years due to increased contact between humans and animal reservoirs. However, it is difficult to predict when such events will take place since the viral adaptation that is needed to accomplish this is multifactorial and stochastic. Against this background the intensified use of viruses and their genetically modified variants as viral gene transfer vectors for biomedical research, experimental gene therapy and for live-vector vaccines is a cause for concern. This review addresses a number of potential risk factors and their implications for activities with viral vectors from the perspective of cross-species transfer of viruses in nature, with emphasis on the occurrence of host-range mutants resulting from either cell culture or tropism engineering. The issues are raised with the intention to assist in risk assessments for activities with vector viruses.

Animals↗

Effective poxvirus removal by sterile filtration during manufacture of plasma derivatives.

As a consequence of the September 2001 terrorist events, programs to protect against further such acts including potentially the use of biological warfare agents have been launched in the USA and elsewhere. As part of these initiatives, Vaccinia virus was procured for the pre-emptive vaccination of key personnel against smallpox as well as population-wide protection after an eventual exposure. The introduction of this live virus into a population at a relatively large scale represents a theoretical challenge for the safety of the blood supply, and potentially for plasma for fractionation. To strengthen further the demonstration of safety margins for plasma derived products against Vaccinia virus, the capacity of sterile filtration procedures to remove the virus was investigated. An infectivity assay for the Vaccinia virus strain which represents the majority of smallpox vaccine stocks available currently was used to investigate the potential removal of this virus by sterile filtration processes during the manufacture of plasma derivatives. Vaccinia virus behaves as predicted based on its size, i.e., an artificially added virus load is removed about 10,000-fold by the sterile filtration procedures tested. As the current investigation covered a range of different protein concentrations, filter materials and filters from different manufacturers, the results obtained are considered to be widely applicable. The current investigation supports further the high safety margins of plasma derivatives against any potential Vaccinia virus content of plasma for fractionation. As the large size is a general feature of Orthopox viruses, the results would also provide assurance against poxviruses identified more recently, for example, Monkeypox virus.

Animals↗

Microarray assay for detection and discrimination of Orthopoxvirus species.

A microarray method was developed for simultaneous detection and identification of six species of Orthopoxvirus (OPV) including Variola, Monkeypox, Cowpox, Camelpox, Vaccinia, and Ectromelia viruses. The method allowed us to discriminate OPV species from varicella-zoster virus (VZV), Herpes Simplex 1 virus (HSV-1), and Herpes Simplex 2 virus (HSV-2) that cause infections with clinical manifestations similar to OPV infections. The nucleotide sequences of the C23L/B29R and the B19R genes identified for 86 and 72 different OPV strains, respectively, were used to design species-specific microarray oligonucleotide probes (oligoprobes). The microarray also contained several oligoprobes selected from the ORF31, US4, and US5 genes of VZV, HSV-1, and HSV-2, respectively. The samples (from HSVs or OPVs) of ssDNAs for analyses were prepared by using asymmetric PCR followed by chemical labeling of ssDNA with Cy3 dye. DNA from 52 samples of various OPV species, two isolates of VZV, two of HSV-1, and three of HSV-2 were tested using the developed microarray assay; all tested viruses were accurately identified. To ensure the robustness of the microarray assay, three additional unrelated variola virus strains with unknown sequences of the C23L/B29R and the B19R genes were tested. In each instance the microarray unambiguously identified them as Variola virus species. The results obtained in this study demonstrated that this new microarray method is a valuable tool for the rapid and accurate detection and differentiation of these important viral pathogens.

Carbocyanines↗

Therapeutic potential of nucleoside/nucleotide analogues against poxvirus infections.

Several nucleoside and nucleotide analogues have been identified as potent antiviral agents with convincing activity against poxviruses (including variola, vaccinia, monkeypox, cowpox, molluscum contagiosum, orf). Among the nucleoside analogues, 8-methyladenosine and 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S2242), have been identified as promising anti-poxvirus agents. Among the nucleotide analogues, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC, cidofovir], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP] and (S)-6-(3-hydroxy-2-phosphonylmethoxypropyl)oxy-2,4-diaminopyrimidine [(S)-HPMPO-DAPy] have been identified as promising anti-poxvirus agents. These nucleoside and nucleotide analogues have proved to be efficacious in various animal models for poxvirus infections. Only one compound, cidofovir, has also proved efficacious against poxvirus infections in humans, i.e. molluscum contagiosum and orf (sheep pox). Cidofovir is formally licensed for clinical use (intravenous administration for the treatment of cytomegalovirus retinitis in AIDS patients); however, it could also be formulated for topical administration, or for oral administration in prodrug form, i.e. as 1-O-hexadecyloxypropyl-cidofovir.

Animals↗

The potential of 5' nuclease PCR for detecting a single-base polymorphism in Orthopoxvirus.

A fluorogenic 5' nuclease PCR assay was evaluated for its ability to specifically detect and differentiate DNA of two Orthopoxvirus species. A pair of consensus primers that target a DNA segment of the Orthopoxvirus haemagglutinin gene, and two oligonucleotide probes; each labelled with a different fluorescent reporter dye and the same quencher dye, were used in a single-tube assay. The assay is based on the 5'-->3' nuclease activity of AmpliTaq DNA polymerase that cleaves a fluorescein-labelled hybridized probe. Probe cleavage generates specific fluorescent signals whose intensity can be quantified by fluorometry. After evaluating the effects of various annealing temperatures and probe concentrations and normalizing the emission intensities of the reporter dyes, it was possible to detect and differentiate monkeypox and vaccinia virus DNAs on the basis of a single-base polymorphism. The sensitivity of the 5' nuclease PCR assay is comparable to the sensitivity of ethidium bromide-stained gels, but the assay provides higher specificity and virtually eliminates the need for laborious post-PCR processing.

DNA Primers↗