Viruela símica: zoonosis emergente con impacto global / Monkeypox: emerging zoonosis with unprecedentedglobal impact

El virus de la viruela símica es un orthopoxvirus de características zoonóticas endémico en las regiones de África Central y África Occidental, donde causa brotes desde 1970. En las últimas décadas se registró un aumento exponencial de casos, probablemente asociado a la disminución en la inmunidad conferida por la vacuna antivariólica, discontinuada luego de la erradicación de la viruela. En los últimos años se registraron casos esporádicos fuera del continente africano, siempre relacionados epidemiológicamente a la permanencia en áreas endémicas o contacto con animales infectados. Desde el 13 de mayo de 2022 se encuentra en curso el mayor brote de viruela símica registrado fuera de las áreas endémicas de África, con casos en los cinco continentes. La extensión, el impacto y la duración del brote permanecen aún inciertos.

Monkeypox virus is an orthopoxvirus with zoonotic characteristics endemic in Central and West Africa regions, where it has caused outbreaks since 1970. An exponential increase in cases has been registered in the last decades, probably associated with a decrease in the immunity conferred by the smallpox vaccine, discontinued after smallpox eradication. In recent years, sporadic cases have been reported outside the African continent, always epidemiologically related to permanence in endemic areas or contact with infected animals. Since May 13, 2022, the largest monkeypox outbreak ever reported outside Africa endemic areas, with cases on the five continents, is unfolding. The extent, impact and duration of this outbreak still remain uncertain

Viral Infections in Burn Patients: A State-Of-The-Art Review.

Infections that are triggered by the accompanying immunosuppression in patients with burn wounds are very common regardless of age. Among burn patients, the most frequently diagnosed infections include the bacterial ones primarily caused by Pseudomonas aeruginosa or Klebsiella pneumonia, as well as fungal infections with the etiology of Candida spp. or Aspergillus spp. Besides, burn wounds are highly susceptible to viral infections mainly due to the impaired immune responses and defective functions of the immune cells within the wound microenvironment. The most prevalent viruses that invade burn wounds include herpes simplex virus (HSV), cytomegalovirus (CMV), human papilloma virus (HPV), and varicella zoster virus (VZV). Likewise, less prevalent infections such as those caused by the orf virus or Epstein-Barr Virus (EBV) might also occur in immunosuppressed burn patients. Viral infections result in increased morbidity and mortality rates in severely burned patients. Additionally, a positive correlation between the hospitalization duration and the severity of the viral infection has been demonstrated. Viral infections trigger the occurrence of various complications, ranging from mild symptoms to even fatal incidents. Accurate detection of viral infection is of great clinical importance because of the possibility for a quicker introduction of proper treatment therapy and shortening of hospitalization time. The aim of this paper is to provide a comprehensive review of the literature and summarize the findings regarding the most common viral infections in immunosuppressed burn patients.

SUCCESSFUL TREATMENT OF CLINICAL ORTHOPOXVIRUS INFECTION IN A GIANT ANTEATER (MYRMECOPHAGA TRIDACTYLA).

An anorexic 5-yr-old female giant anteater (Myrmecophaga tridactyla) developed multifocal ulcerative and vesicular lesions affecting the rostrum, oral cavity, and tongue. Disseminated skin lesions were also found on the body, affecting the feet, flanks, and genital area. Polymerase chain reaction confirmed a systemic viremic orthopoxvirus infection. Cowpox virus was considered to be the only likely etiological agent. Intensive supportive treatment, including daily fluid therapy, force-feeding, and anti-inflammatory administration achieved a successful outcome after 3 wk. To the authors' knowledge, this is the first time a giant anteater with severe orthopoxvirus lesions has survived the disease. This unique case discusses current and possible future therapeutic and prophylactic options for the treatment of orthopoxvirus infections in giant anteaters and other nondomestic animal species.

Actualización sobre el tratamiento de moluscos contagiosos en los niños / Update on the Treatment of molluscum Contagiosum in children

El molusco contagioso es una de las infecciones virales más frecuente en los niños. Aunque se trata de una infección de curso benigno y generalmente autolimitada, el tratamiento puede resultar complicado en la edad pediátrica cuando las lesiones son muy numerosas, están en áreas visibles, o producen molestias. Existen diversos tratamientos disponibles, cuya selección depende del número y localización de las lesiones, de la experiencia del médico que las trata, y de las preferencias de los padres o cuidadores. Este artículo proporciona una actualización sobre las diferentes terapias contra los moluscos contagiosos particularmente enfocadas a los pacientes pediátricos

Molluscum contagiosum is one of the most common viral infections in childhood. It is a benign and usually self-limiting infection, but its treatment in children can be challenging, particularly when the patient presents multiple lesions or when lesions are symptomatic or highly visible. Several treatment options exist. Choice of treatment depends on the number and location of lesions, the prior experience of the treating physician, and the preferences of the child's parents or carers. This article provides an update on treatment options for molluscum contagiosum, with a particular focus on immunocompetent pediatric patients

Review of poxvirus: emergence of monkeypox.

This article reviews the different types of poxvirus infections. Smallpox, although eradicated, must continue to be monitored because of the potential risk of accidental or voluntary (by bioterrorism) reintroduction. Monkeypox and cowpox viruses are considered to be emergent today ; their high risk of dissemination is due to the increase in international transport as well as trends for new animals as pets and the loss of vaccinal protection against smallpox. Molluscum contagiosum (molluscipoxvirus) causes mild infections, is particularly frequent in children ; in adults it is a marker of the risk of sexually transmitted infections and can, in cases with profuse lesions, reveal AIDS.

Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection.

Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

Specific inhibition of orthopoxvirus replication by a small interfering RNA targeting the D5R gene.

BACKGROUND: Concerns about the potential use of smallpox in bioterrorism have stimulated interest in the development of novel antiviral treatments. Currently, there are no effective therapies against smallpox and new treatment strategies are greatly needed. METHODS: In this study, specifically designed small interfering RNAs (siRNAs), targeting five proteins essential for orthopoxvirus replication, were investigated for their ability to inhibit vaccinia virus strain Western Reserve (VACVWR) replication. RESULTS: Among these siRNAs, 100 nM siD5R-2, an siRNA targeting the D5 protein, decreased VACVWR replication up to 90% when used either prophylactically or therapeutically in human lung carcinoma A549 cells. This siRNA induced a striking concentration-dependent inhibition of VACVWR replication and a prolonged prophylactic antiviral effect that lasted for 72 h, at a concentration of 100 nM. Confocal microscopy of Alexa-siD5R-2-treated VACVWR-infected cells confirmed a decrease in viral replication. Furthermore, siD5R-2 was shown to specifically reduce the D5R mRNA and protein expression using real-time reverse transcriptase-PCR and western blotting analysis, without inducing interferon-13 in A549 cells. We also demonstrated the antiviral potency of siD5R-2 against different pathogenic orthopoxviruses, such as cowpox and monkeypox viruses, which were inhibited up to 70% at the lowest concentration (1 nM) tested. Finally, siD5R-2 showed antiviral effects in VACVWR-infected human keratinocyte and fibroblast cell cultures. CONCLUSIONS: These results suggest that siD5R-2 could be a potential candidate to treat poxvirus infections.

Nódulo de los ordeñadores / Milker's nodule

El nódulo de los ordeñadores es una afección viral benigna que por lo general se presenta como un nódulo en la mano de personas que manipulan ganado bovino infectado. Reportamos el caso de una mujer de 36 años con infrecuente localización facial consecutivo a cornada de vaca. Los rasgos clínicos característicos, la autorresolución del cuadro, así como los cambios citopáticos virales en la biopsia fueron significativos para establecer el diagnóstico. Es una enfermedad que podemos encontrarla en zonas periurbanas de nuestro país y factible de condicionar error diagnóstico.

Diseases caused by poxvirus - orf and milker's nodules - a review

Sheep and cattle parapoxviruses cause in human beings diseases of very similar aspect, named orf and milker's nodules, respectively. These infections are generically called farmyard pox. In the present article, we show the epidemiological, clinical, and histopathological aspects, as well as the treatment of these two viral diseases that are very similar, being differentiated only by their epidemiological aspects

Manipulating the local tumor microenvironment with poxviruses expressing costimulatory molecules.

The identification of tumor-associated antigens and new insights into the molecular and cellular basis of tumor immunology have generated a variety of vaccine strategies. Although promising in animal models, data from early-phase clinical trials have not been encouraging. These studies have documented the ability of vaccines to prime T cells, but these responses have not correlated with therapeutic effectiveness. Because the location of T-cell activation and effector activity may impact T-cell function significantly, attention has been placed on the tumor microenvironment. There is now evidence that T-cell responses may be altered in the setting of established tumor growth. To alter the balance between local immune responses and tumor growth, a vaccine regimen using direct intratumoral delivery of poxvirus vaccines expressing costimulatory molecules was developed. An initial series of clinical trials has documented the safety profile of this approach and has suggested that local and systemic immunity can be induced. Herein, we review the general rationale for this approach, discuss the results of ongoing clinical trials, and highlight critical questions that can be addressed in well-designed preclinical and clinical studies.

Evidence that vaccinia virulence factor E3L binds to Z-DNA in vivo: Implications for development of a therapy for poxvirus infection.

The E3L gene product found in all poxviruses is required for the lethality of mice in vaccinia virus infection. Both the C-terminal region, consisting of a double-stranded RNA-binding motif, and the N-terminal region (vZ(E3L)), which is similar to the Zalpha family of Z-DNA-binding proteins, are required for infection. It has recently been demonstrated that the function of the N-terminal domain depends on its ability to bind Z-DNA; Z-DNA-binding domains from unrelated mammalian proteins fully complement an N-terminal deletion of E3L. Mutations that decrease affinity for Z-DNA have similar effects in decreasing pathogenicity. Compounds that block the Z-DNA-binding activity of E3L may also limit infection by the poxvirus. Here we show both an in vitro and an in vivo assay with the potential to be used in screening for such compounds. Using a conformation-specific yeast one-hybrid assay, we compared the results for Z-DNA binding of vZ(E3L) with those for human Zbeta(ADAR1), a peptide that has similarity to the Zalpha motif but does not bind Z-DNA, and with a mutant of hZbeta(ADAR1), which binds Z-DNA. The results suggest that this system can be used for high-throughput screening.

Viral infections in atopic dermatitis: pathogenic aspects and clinical management.

A number of different widespread and disseminated viral infections can occur in patients with atopic dermatitis. Eczema molluscatum is troublesome but not dangerous. Although eczema vaccinatum is rare, it is life-threatening and of increased concern as smallpox vaccinations are reintroduced as a response to possible bioterrorism. There is little information on the course of smallpox itself in atopic dermatitis. Eczema herpeticum is the most common member of this group; recent advances in understanding its pathogenesis might contribute to a more successful management of this serious complication.

Feline orthopoxvirus infection transmitted from cat to human.

We report the case of a 56-year-old female patient who presented with an inflamed, ulcerated lesion on the left side of her neck after contact (scratch) with a cat living in the patient's house. Satellite lesions developed despite local treatment and parenteral clindamycin. Histopatholgic examination and the Tzanck test showed evidence of a viral infection. Subsequent transmission electron microscopy of scrap tissue and material from a fresh pustule exhibited multiple typical poxvirus particles, predominantly in remnants of scaled-off layers of degenerated keratinocytes, and virus particles in intermingled phagocytes, leading to the diagnosis of feline Orthopoxvirus (cowpox virus) infection. These results were verified by polymerase chain reaction and sequencing. Concern has been raised as to whether discontinuation of smallpox vaccine would cause an increase in Orthopoxvirus infection, but this has not yet shown to be the case.

Medical dilemmas associated with rehabilitating confiscated houbara bustards (Chlamydotis undulata macqueenii) after avian pox and paramyxovirus type 1 infection.

Projects to rehabilitate confiscated animals must carefully consider the risks of disease when determining whether to release these animals back into the wild or to incorporate them into captive breeding programs. Avipox and paramyxovirus type 1 (PMV-1) infections are important causes of morbidity and mortality during rehabilitation of confiscated houbara bustards (Chlamydotis undulata macqueenii). This paper presents key findings of an intensive health monitoring program (physical condition, hematology, serology, endoscopy, microbiology, and virology) of two flocks of houbara bustards that survived outbreaks of septicemic avipox and PMV-1 respectively. Mortality in each flock from avipox and PMV-1 infections were 47% and 25% respectively, and the clinicopathologic features and management of each outbreak are presented. Avipox and PMV-1 viruses were not isolated from surviving birds monitored monthly for 11 mo after initial infection nor were septicemic or diptheritic avipox and PMV-1 infections detected in the captive breeding collection into which surviving birds were ultimately integrated up to 24 mo later. Adenovirus was isolated from four birds during the study demonstrating that novel disease agents of uncertain pathogenicity may be carried latently and intermittently shed by confiscated birds. This paper demonstrates the risk of importing pathogens with illegally traded houbara bustards and reinforces the need for surveillance programs at rehabilitation centers for these birds. We recommend that confiscated houbara bustards integrated into captive breeding programs be managed separately from captive-bred stock. Other measures should include separate facilities for adult birds and rearing facilities for offspring derived from different stock lines and strict sanitary measures. Additionally, health monitoring of confiscated birds should continue after birds are integrated into captive flocks.

A review of the dermatologic manifestations of poxvirus infections.

Physicians need to be familiar with the presentation of poxvirus infections. The poxvirus infections that are common, such as MCV, are rarely serious; however, physicians need to understand them because they can be bothersome to patients and require reassurance and, if available, treatment. The more rare poxvirus infections, such as variola, need to be recognized because they are generally serious. It is important to consider that these infections can suggest underlying systemic disease, as in the case of severe, recalcitrant MCV infection, which may be indicative of HIV infection or another immunocompromised state.

Exotic virus infections of military significance. Hemorrhagic fever viruses and pox virus infections.

Military personnel are frequently deployed to distant locations around the world under conditions of great stress, which involve potential exposure to hazardous viruses that are not commonly seen in the developed world. This article will provide an overview of two clinical presentations of viral infections of potential military significance: hemorrhagic fever and poxvirus infections. The three viral hemorrhagic fever viruses described--dengue, hemorrhagic fever with renal syndrome, and Congo-Crimean hemorrhagic fever--represent the diversity of potential hemorrhagic fever viruses that military forces may be exposed. Human poxvirus infections are currently uncommon but knowledge of these agents, will again become important should a terrorist threat of the use of smallpox become real and widespread use of vaccinia be considered to protect the military force.

[Milker's nodules]. / Malkerknuder.

Milker's nodule is a parapox virus infection seen mostly on the hands of dairy farmers. We saw 15 cases over a period of two years in the County of North Jutland. Clinically, milker's nodule goes through a papular, a nodular and a crusted stage. Most patients were seen when the infection was in the nodular stage, an often painful condition requiring treatment. Three patients developed an erythema multiformelike secondary eruption. Lesions from nine patients were removed for histological examination. The histology of all lesions was consistent with milker's nodule. In three of seven patients parapox virus was demonstrated by electron microscopy. Treatment was commonly curettage followed by cauterization.

[Localized cowpox/cat pox virus infection. Aspects of epidemiology, diagnosis and therapy]. / Lokalisierte Infektion mit dem Kuhpocken-/Katzenpockenvirus. Aktuelles zur Epidemiologie, Diagnostik und Therapie.

Only few human cowpox/catpox infections have been reported until now. The diagnosis of bland localized infections may be missed, if this disease is not well known. However, early diagnosis of localized cowpox/catpox infections is important, since at least immunocompromised patients are at risk of potential lethal generalization similar to generalized variola vera. Using a typical case report, the characteristics of the disease, as well as the current aspects of epidemiology, diagnosis and therapy are summarized. The characteristic finding of intracytoplasmatic inclusion bodies by light microscopy can be demonstrated in a human biopsy-specimen for the first time and greatly facilitated the diagnosis.