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1.
Aust Vet J ; 97(10): 390-393, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31328253

RESUMO

Recently, the Kunjin strain of West Nile virus (WNVKUN ) has been detected using qRT-PCR in belly skin lesions of farmed juvenile saltwater crocodiles. This follows an established association between similar lesions and West Nile virus in American alligators. The lesions present as cutaneous lymphohistiocytic aggregates in the dermal layers of both species. While these lesion do not create an obvious defect on the live crocodile, upon tanning the lesion area collapses and does not uptake the dye evenly, thus reducing its aesthetic appeal. As a result, skins are being rejected jeopardising the economic viability of the Australian crocodile industry. Over 50 skin lesions have since been confirmed as WNVKUN -positive and preliminary evidence of lesion restructuring is presented. Horizontal transmission of WNVKUN by mosquitoes is well-established but other transmission routes, such as ingestion and cloacal shedding, need further evaluation. An infection trial is currently underway to ensure WNVKUN is the causative agent of these skin lesions.


Assuntos
Jacarés e Crocodilos/virologia , Dermatopatias/veterinária , Vírus do Nilo Ocidental/isolamento & purificação , Criação de Animais Domésticos , Animais , Northern Territory , Pele/virologia , Dermatopatias/patologia , Dermatopatias/virologia
3.
Brain Nerve ; 71(4): 302-308, 2019 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-30988211

RESUMO

Among human herpes viruses, those known to cause neurological symptoms are the herpes simplex virus (HSV) types 1 and 2 and the varicella-zoster virus (VZV), which remain latent in the dorsal root ganglion. HSV causes herpes labialis, genital herpes, etc. VZV causes varicella during the primary infection, and shingles when reactivated. In this review, we present to the typical cases of each disease; in addition, we present several types of diseases that are closely related to neurological diseases.


Assuntos
Herpes Zoster/patologia , Infecções por Herpesviridae/patologia , Dermatopatias/virologia , Gânglios Espinais/virologia , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Herpesvirus Humano 3 , Humanos
5.
J Clin Immunol ; 39(1): 81-89, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30607663

RESUMO

The association of immunodeficiency-related vaccine-derived rubella virus (iVDRV) with cutaneous and visceral granulomatous disease has been reported in patients with primary immunodeficiency disorders (PIDs). The majority of these PID patients with rubella-positive granulomas had DNA repair disorders. To support this line of inquiry, we provide additional descriptive data on seven previously reported patients with Nijmegen breakage syndrome (NBS) (n = 3) and ataxia telangiectasia (AT) (n = 4) as well as eight previously unreported patients with iVDRV-induced cutaneous granulomas and DNA repair disorders including NBS (n = 1), AT (n = 5), DNA ligase 4 deficiency (n = 1), and Artemis deficiency (n = 1). We also provide descriptive data on several previously unreported PID patients with iVDRV-induced cutaneous granulomas including cartilage hair hypoplasia (n = 1), warts, hypogammaglobulinemia, immunodeficiency, myelokathexis (WHIM) syndrome (n = 1), MHC class II deficiency (n = 1), Coronin-1A deficiency (n = 1), X-linked severe combined immunodeficiency (X-SCID) (n = 1), and combined immunodeficiency without a molecular diagnosis (n = 1). At the time of this report, the median age of the patients with skin granulomas and DNA repair disorders was 9 years (range 3-18). Cutaneous granulomas have been documented in all, while visceral granulomas were observed in six cases (40%). All patients had received rubella virus vaccine. The median duration of time elapsed from vaccination to the development of cutaneous granulomas was 48 months (range 2-152). Hematopoietic cell transplantation was reported to result in scarring resolution of cutaneous granulomas in two patients with NBS, one patient with AT, one patient with Artemis deficiency, one patient with DNA Ligase 4 deficiency, one patient with MHC class II deficiency, and one patient with combined immunodeficiency without a known molecular etiology. Of the previously reported and unreported cases, the majority share the diagnosis of a DNA repair disorder. Analysis of additional patients with this complication may clarify determinants of rubella pathogenesis, identify specific immune defects resulting in chronic infection, and may lead to defect-specific therapies.


Assuntos
Reparo do DNA/genética , Granuloma/complicações , Granuloma/virologia , Síndromes de Imunodeficiência/complicações , Vírus da Rubéola/patogenicidade , Dermatopatias/etiologia , Dermatopatias/virologia , Adolescente , Ataxia Telangiectasia/genética , Ataxia Telangiectasia/virologia , Criança , Pré-Escolar , Feminino , Granuloma/genética , Cabelo/anormalidades , Cabelo/virologia , Transplante de Células-Tronco Hematopoéticas/métodos , Doença de Hirschsprung/genética , Doença de Hirschsprung/virologia , Humanos , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/virologia , Masculino , Síndrome de Quebra de Nijmegen/genética , Síndrome de Quebra de Nijmegen/virologia , Osteocondrodisplasias/congênito , Osteocondrodisplasias/genética , Osteocondrodisplasias/virologia , Rubéola (Sarampo Alemão)/genética , Rubéola (Sarampo Alemão)/virologia , Pele/virologia , Dermatopatias/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/genética , Doenças por Imunodeficiência Combinada Ligada ao Cromossomo X/virologia
7.
Braz J Microbiol ; 50(1): 271-277, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30637633

RESUMO

Dermatitis might occur in mucosal disease (MD) caused by bovine viral diarrhea virus (BVDV). This study describes the pathological and virological features of skin lesions associated with BVDV infection in four persistently infected (PI) cattle. Skin samples were reprocessed for histopathology and IHC. BVDV isolates were obtained and were genetically characterized. In addition to upper alimentary system ulcerative lesions, all cattle (one outbreak and three individual cases) presented focal crusty and ulcerative lesions affecting the mucocutaneous and skin-horn junctions, interdigital clefts, pastern, and areas surrounding the dewclaws and diffuse thickened skin within 7-20 days of infection. Microscopic analysis revealed parakeratotic hyperkeratosis and single-cell keratinocyte death, accompanied by ballooning degeneration and spongiosis in the epidermis, as well as intraepithelial and subcorneal pustules. IHC showed BVDV antigen in the cytoplasm of keratinocytes undergoing individual cell death. Phylogenetic analysis revealed that the isolates from cattle #1, #2, and #4 belonged to BVDV-1a, whereas that from cattle #3 belonged to BVDV-1d. Cytopathic BVDV was isolated from cattle #2 and #3 (MD), and non-cytopathic BVDV was isolated from cattle #1 and #4. Thus, BVDV infection might cause acute disease, characterized by skin and upper alimentary system ulcerative lesions, in both MD and PI cattle.


Assuntos
Doença das Mucosas por Vírus da Diarreia Viral Bovina/virologia , Vírus da Diarreia Viral Bovina/isolamento & purificação , Dermatopatias/veterinária , Animais , Anticorpos Antivirais , Doença das Mucosas por Vírus da Diarreia Viral Bovina/patologia , Bovinos , Vírus da Diarreia Viral Bovina/classificação , Vírus da Diarreia Viral Bovina/genética , Vírus da Diarreia Viral Bovina/fisiologia , Filogenia , Pele/patologia , Pele/virologia , Dermatopatias/patologia , Dermatopatias/virologia
8.
J Infect Dis ; 219(10): 1564-1573, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30357388

RESUMO

BACKGROUND: Human skin microorganisms have been associated with various skin diseases. However, most studies have focused on bacterial communities, and little is known about normally resident skin viruses such as the Polyomaviridae and their association with cutaneous disorders. METHODS: We investigated the infection levels of Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7), using triplet skin swabs collected from lesional and nonlesional skins of 86 Japanese patients with inflammatory skin diseases and mycosis fungoides, and from 149 healthy control individuals. RESULTS: This age-matched case-control study provides the first analyses of the loads of polyomaviruses in association with various skin diseases. The viral loads were significantly higher for HPyV6/HPyV7 and lower for MCPyV in patients with psoriasis. The viral load variation was observed not only at lesion sites, but also at clinically unaffected skin sites in most of the patients. The viral strains tested were all of the Asian/Japanese genotype. CONCLUSIONS: Our findings suggest a covariation in the infection levels of cutaneous polyomaviruses in certain inflammatory skin conditions. Worldwide prospective longitudinal studies are warranted to understand the influence of such alterations on the pathogenesis of inflammatory skin disorders.


Assuntos
Infecções por Polyomavirus/epidemiologia , Polyomavirus/isolamento & purificação , Dermatopatias/epidemiologia , Pele/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA Viral/isolamento & purificação , Feminino , Humanos , Japão/epidemiologia , Masculino , Poliomavírus das Células de Merkel/isolamento & purificação , Pessoa de Meia-Idade , Micose Fungoide/epidemiologia , Micose Fungoide/virologia , Prevalência , Psoríase/virologia , Dermatopatias/virologia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/virologia , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/virologia , Carga Viral
9.
Int J Dermatol ; 58(4): 383-387, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30537078

RESUMO

A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 (HPyV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct "peacock plumage" histology. While expression of HPyV7 viral protein, namely small tumor (sT) antigen, is prominent within lesional tissue, the functional role of HPyV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HPyV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HPyV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK/ERK/c-Jun and 4E-BP1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HPyV7 actively infects keratinocytes and sT antigen is highly expressed in pruritic dyskeratotic/parakeratotic dermatoses, our data provide important mechanistic evidence supporting a pathogenic role for HPyV7 in cutaneous disease.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Antígenos Virais de Tumores/metabolismo , Sistema de Sinalização das MAP Quinases , Fosfoproteínas/metabolismo , Polyomaviridae/imunologia , Infecções por Polyomavirus/complicações , Proteína Fosfatase 2/metabolismo , Infecções Tumorais por Vírus/complicações , Antígenos Virais de Tumores/genética , Células HEK293 , Humanos , Infecções por Polyomavirus/virologia , Dermatopatias/metabolismo , Dermatopatias/virologia , Infecções Tumorais por Vírus/virologia
11.
Clin Exp Dermatol ; 44(1): 13-19, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30267436

RESUMO

Zika virus (ZIKV) is an emerging mosquito-borne flavivirus transmitted mainly by Aedes species of mosquitos. Although the infection is usually mild and self-limiting, it is emerging as a public health challenge in tropical and subtropical countries owing to its unprecedented pathogenicity and increased risk for fetal malformations and neurological symptoms. Cutaneous manifestations as for other mosquito-borne viruses remain a hallmark of the disease. This article provides a detailed overview on ZIKV infection, including its varied cutaneous clinical manifestations and diagnostic aspects, and also provides detailed insights into its pathogenesis in human skin.


Assuntos
Exantema/etiologia , Dermatopatias/virologia , Pele/patologia , Infecção por Zika virus/complicações , Zika virus , Diagnóstico Diferencial , Febre/etiologia , Humanos , Infecção por Zika virus/patologia
13.
Nat Med ; 24(12): 1815-1821, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30397357

RESUMO

Human microbiome studies have revealed the intricate interplay of host immunity and bacterial communities to achieve homeostatic balance. Healthy skin microbial communities are dominated by bacteria with low viral representation1-3, mainly bacteriophage. Specific eukaryotic viruses have been implicated in both common and rare skin diseases, but cataloging skin viral communities has been limited. Alterations in host immunity provide an opportunity to expand our understanding of microbial-host interactions. Primary immunodeficient patients manifest with various viral, bacterial, fungal, and parasitic infections, including skin infections4. Dedicator of cytokinesis 8 (DOCK8) deficiency is a rare primary human immunodeficiency characterized by recurrent cutaneous and systemic infections, as well as atopy and cancer susceptibility5. DOCK8, encoding a guanine nucleotide exchange factor highly expressed in lymphocytes, regulates actin cytoskeleton, which is critical for migration through collagen-dense tissues such as skin6. Analyzing deep metagenomic sequencing data from DOCK8-deficient skin samples demonstrated a notable increase in eukaryotic viral representation and diversity compared with healthy volunteers. De novo assembly approaches identified hundreds of novel human papillomavirus genomes, illuminating microbial dark matter. Expansion of the skin virome in DOCK8-deficient patients underscores the importance of immune surveillance in controlling eukaryotic viral colonization and infection.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Síndromes de Imunodeficiência/virologia , Dermatopatias/virologia , Pele/virologia , Adolescente , Bacteriófagos/genética , Criança , Feminino , Genoma Viral/genética , Fatores de Troca do Nucleotídeo Guanina/deficiência , Voluntários Saudáveis , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade/genética , Síndromes de Imunodeficiência/microbiologia , Síndromes de Imunodeficiência/patologia , Linfócitos/virologia , Masculino , Metagenoma/genética , Metagenoma/imunologia , Microbiota/genética , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Pele/microbiologia , Dermatopatias/genética , Dermatopatias/microbiologia , Dermatopatias/patologia
14.
Vet Microbiol ; 225: 89-100, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30322539

RESUMO

The control of pathogens that target crocodilian skin is essential to the long-term success and sustainability of intensive farming operations worldwide. To understand the impact these pathogens may have on the skin, a brief overview of skin histology is given. A review of the known viral, bacterial, fungal and helminth taxa associated with skin conditions in commercially significant crocodilian species is presented. Best management practices are discussed, with an emphasis on addressing extrinsic factors that influence transmission and pathogenicity. It is argued that, in the past, reduced immune function arising from inadequate thermal regulation was the leading cause of skin disease in captive crocodilians. Consequently, innovations such as temperature control, coupled with the adoption of more stringent hygiene standards, have greatly reduced the prevalence of many infectious skin conditions in intensively farmed populations. However, despite improvements in animal husbandry and disease management, viral pathogens such as West Nile virus, herpesvirus and poxvirus continue to afflict crocodilians in modern captive production systems.


Assuntos
Jacarés e Crocodilos/microbiologia , Jacarés e Crocodilos/virologia , Dermatopatias/veterinária , Pele/ultraestrutura , Jacarés e Crocodilos/parasitologia , Criação de Animais Domésticos , Animais , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/veterinária , Comércio , Dermatologia , Fazendas , Fungos/isolamento & purificação , Fungos/patogenicidade , Micoses/prevenção & controle , Micoses/veterinária , Pele/microbiologia , Pele/parasitologia , Pele/virologia , Dermatopatias/microbiologia , Dermatopatias/prevenção & controle , Dermatopatias/virologia , Viroses/prevenção & controle , Viroses/veterinária , Vírus/isolamento & purificação , Vírus/patogenicidade
15.
BMJ Case Rep ; 20182018 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-29895579

RESUMO

Herpes zoster, caused by varicella zoster virus (VZV) reactivation, affects mainly the adult population, although it can occur in children. This happens when primary infection (varicella) has occurred at a very young age or in immunocompromised patients. Complications are rare in healthy individuals. They include VZV cutaneous dissemination, which affects 2%-10% of immunocompromised patients.We present a previously healthy child, with history of varicella during her first month of life, which presented at age 8 with a severe case of herpes zoster, complicated with cutaneous dissemination. Immunity study was unremarkable. Causes, management and follow-up are discussed.


Assuntos
Exantema/virologia , Herpes Zoster/complicações , Herpesvirus Humano 3/imunologia , Dermatopatias/virologia , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Administração Intravenosa , Assistência ao Convalescente , Antivirais/uso terapêutico , Criança , Exantema/patologia , Feminino , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpes Zoster/patologia , Herpesvirus Humano 3/genética , Humanos , Hospedeiro Imunocomprometido , Dermatopatias/patologia , Resultado do Tratamento
16.
mBio ; 9(3)2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29764943

RESUMO

Only eight families of double-stranded DNA (dsDNA) viruses are known to infect vertebrate animals. During an investigation of papillomatous skin disease in an elasmobranch species, the giant guitarfish (Rhynchobatus djiddensis), a novel virus, distinct from all known viral families in regard to particle size, morphology, genome organization, and helicase phylogeny was discovered. Large inclusion bodies containing 75-nm icosahedral viral particles were present within epithelial cell nuclei in the proliferative skin lesions. Deep metagenomic sequencing revealed a 22-kb circular dsDNA viral genome, tentatively named guitarfish "adomavirus" (GAdoV), with only distant homology to two other fish viruses, Japanese eel endothelial cell-infecting virus (JEECV) and a recently reported marbled eel virus. Phylogenetic analysis of the helicase domain places the guitarfish virus in a novel clade that is equidistant between members of the Papillomaviridae and Polyomaviridae families. Specific PCR, quantitative PCR, and in situ hybridization were used to detect, quantify, and confirm that GAdoV DNA was localized to affected epithelial cell nuclei. Changes in the viral titer, as well as the presence of a hybridization signal, coincided with the progression and then final resolution of gross and microscopic lesions. The results indicate that GAdoV is the causative agent of the proliferative skin lesions.IMPORTANCE Cartilaginous fish, including the sharks and rays, evolved from ancestral fish species at least 400 million years ago. Even though they are the descendants of one of the most ancient vertebrate lineages, reports of viral diseases in these species are rare and poorly documented. Deep sequencing revealed a highly divergent virus, tentatively named guitarfish adomavirus, that is distantly related to known papillomaviruses and polyomaviruses. Out of the eight predicted viral genes, only the helicase could be identified as viral by sequence homology searches (BLAST), exemplifying the difficulties of discovering novel viruses within seas of unidentifiable "dark matter" associated with deep sequencing data. The novel adomavirus represents the first viral genome shown to cause clinical disease in a cartilaginous fish species, the giant guitarfish. Our findings demonstrate that emerging fish viruses are fertile ground to expand our understanding of viral evolution in vertebrates.


Assuntos
Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Elasmobrânquios/virologia , Doenças dos Peixes/virologia , Dermatopatias/veterinária , Animais , Vírus de DNA/classificação , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Dermatopatias/virologia , Proteínas Virais/genética
17.
Ann Lab Med ; 38(5): 440-445, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29797814

RESUMO

BACKGROUND: Human herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are responsible for a plethora of human diseases, of which cutaneous and mucocutaneous infections are the most prevalent. In its most severe form, HSV infection can cause meningitis/encephalitis. We compared the Luminex ARIES HSV 1&2 assay (Luminex Corp., Austin, TX, USA), an automated sample-to-result molecular solution, to two non-automated HSV DNA assays. METHODS: A total of 116 artificial controls were used to determine the analytical performance of the ARIES assay. Controls were prepared by spiking universal transport medium (UTM) and cerebrospinal fluid (CSF) samples from patients who tested negative for HSV by an in-house HSV-1 and -2 DNA assay with reference materials (SeraCare Life Sciences, MA, USA; ZeptoMetrix Corp., MA, USA). Another 117 clinical samples were then used to compare the clinical performance of the ARIES assay with those of an in-house assay and the FTD Neuro 9 assay (Fast Track Diagnostics, Junglinster, Luxembourg). RESULTS: The analytical sensitivity (95% limit of detection) of the ARIES assay was 318 copies/mL (UTM samples) and 935 copies/mL (CSF samples) for HSV-1 strain 96 and 253 copies/mL (UTM samples) and 821 copies/mL (CSF samples) for HSV-2 strain 09. No cross-reactivity was observed in samples spiked with 14 non-HSV microorganisms. Compared with the reference result (agreement between the in-house and FTD Neuro 9 results), the ARIES assay had overall concordance rates of 98.2% (111/113) and 100% (113/113) for HSV-1 and HSV-2, respectively. CONCLUSIONS: The ARIES assay appears to be an excellent alternative for rapid detection and differentiation of HSV in skin and genital infections, meningitis, and encephalitis.


Assuntos
Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , DNA Viral/líquido cefalorraquidiano , DNA Viral/metabolismo , Herpes Simples/diagnóstico , Herpes Simples/virologia , Humanos , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Dermatopatias/diagnóstico , Dermatopatias/virologia
18.
Biomed Pharmacother ; 104: 275-279, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29775895

RESUMO

Infection with high-risk human papillomavirus (HPV), most often HPV16, is associated with the development of anogenital and oropharyngeal cancers. Recently, ozone therapy was reported to have considerable efficacy against rabbit VX2 tumors, induced by the cottontail rabbit papillomavirus. The present study aims to determine whether similar results can be obtained in HPV16-transgenic mice, possibly paving the way for new therapeutic options against HPV-induced cancers. HPV16-transgenic and wild-type, female, 20 weeks-old mice were injected intraperitoneally with medical O3/O2 (80░mL/kg, at O3 50░µg/mL), once a day, for 5 consecutive days. The animals were sacrificed at 25 weeks-old, and skin samples were analyzed histologically to study tumour progression. Blood and internal organ samples were used to study toxicological parameters. 85.7% of untreated transgenic mice showed dysplastic skin lesions, compared with 28.6% of O3-treated mice. This was associated with a marked reduction of dermal inflammation associated with those lesions. No significant changes were observed in any toxicological parameters. These preliminary results support the hypothesis that O3 therapy is effective against papillomavirus-induced lesions, particularly against those induced by the most common high-risk virus, HPV16. Further studies are needed to confirm the mechanisms underlying these effects.


Assuntos
Papillomavirus Humano 16/patogenicidade , Neoplasias/tratamento farmacológico , Ozônio/farmacologia , Dermatopatias/tratamento farmacológico , Animais , Progressão da Doença , Feminino , Camundongos , Camundongos Transgênicos , Neoplasias/virologia , Infecções por Papillomavirus/complicações , Coelhos , Pele/efeitos dos fármacos , Pele/virologia , Dermatopatias/virologia , Resultado do Tratamento
19.
Cochrane Database Syst Rev ; 5: CD011403, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29734473

RESUMO

BACKGROUND: Hepatitis C virus (HCV)-associated mixed cryoglobulinaemia is the manifestation of an inflammation of small and medium-sized vessels produced by a pathogenic IgM with rheumatoid factor activity generated by an expansion of B-cells. The immune complexes formed precipitate mainly in the skin, joints, kidneys or peripheral nerve fibres. Current therapeutic approaches are aimed at elimination of HCV infection, removal of cryoglobulins and also of the B-cell clonal expansions. The optimal treatment for it has not been established. OBJECTIVES: This review aims to look at the benefits and harms of the currently available treatment options to treat the HCV-associated mixed cryoglobulinaemia with active manifestations of vasculitis (cutaneous or glomerulonephritis). SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 30 November 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs looking at interventions directed at treatment of HCV-associated cryoglobulinaemic vasculitis (immunosuppressive medications and plasma exchange therapy) have been included. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the retrieved titles and abstracts. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). The planned primary outcomes were kidney disease, skin vasculitis, musculoskeletal symptoms, peripheral joint arthralgia, peripheral neuropathies, liver involvement, interstitial lung involvement, widespread vasculitis and death. Other planned outcomes were: therapy duration, laboratory findings, adverse effects, antiviral therapy failure, B-cell lymphoma, endocrine disorders and costs of treatment. MAIN RESULTS: Ten studies were included in the review (394 participants). None of them evaluated direct-acting antivirals. Seven studies were single-centre studies and three were multicentre. The duration of the studies varied from six to 36 months. The risk of bias was generally unclear or low. Three different interventions were examined: use of rituximab (3 studies, 118 participants); interferon (IFN) (IFN compared to other strategies (5 studies, 223 participants); six IFN months versus one year (1 study, 36 participants), and immunoadsorption apheresis versus only immunosuppressive therapy (1 study, 17 participants).The use of rituximab may slightly improve skin vasculitis (2 studies, 78 participants: RR 0.57, 95% CI 0.28 to 1.16; moderate certainty evidence) and made little of no difference to kidney disease (moderate certainty evidence). In terms of laboratory data, the effect of rituximab was uncertain for cryocrit (MD -2.01%, 95% CI -10.29% to 6.27%, low certainty evidence) and HCV replication. Rituximab may slightly increase infusion reactions compared to immunosuppressive medication (3 studies, 118 participants: RR 4.33, 95%CI 0.76 to 24.75, moderate certainty evidence) however discontinuations of the treatment due to adverse reactions were similar (3 studies, 118 participants: RR 0.97, 95% CI 0.22 to 4.36, moderate certainty evidence).Effects of lFN on clinical symptoms were evaluated only in narrative results. When laboratory parameters were assessed, IFN made little or no difference in levels of alanine transaminase (ALT) at six months (2 studies, 39 participants: MD -5.89 UI/L, 95%CI -55.77 to 43.99); rheumatoid factor activity at six months (1 study, 13 participants: MD 97.00 UI/mL, 95%CI -187.37 to 381.37), or C4 levels at 18 months (2 studies, 49 participants: MD -0.04 mg/dL, 95%CI -2.74 to 2.67). On the other hand, at 18 months IFN may probably decrease ALT (2 studies, 39 participants: MD -28.28 UI/L, 95%CI -48.03 to -8.54) and Ig M (-595.75 mg/dL, 95%CI -877.2 to -314.3), but all with low certainty evidence. One study reported infusion reactions may be higher in IFN group compared to immunosuppressive therapy (RR 27.82, 95%CI 1.72 to 449.18), and IFN may lead to higher discontinuations of the treatment due to adverse reactions (4 studies, 148 participants: RR 2.32, 95%CI 0.91 to 5.90) with low certainty evidence. Interferon therapy probably improved skin vasculitis (3 studies, 95 participants: RR 0.60, 95% CI 0.36 to 1.00) and proteinuria (2 studies, 49 participants: MD -1.98 g/24 h, 95% CI -2.89 to -1.07), without changing serum creatinine at 18 months (2 studies, 49 participants: MD -30.32 µmol/L, 95%CI -80.59 to 19.95).Six months versus one year treatment with IFN resulted in differences terms of the maintenance of the response, 89% of patients in the six months group presented a relapse and only 11% maintained a long-term response at one year, while in the one year group only 78% relapsed and long-term response was observed in 22%. The one-year therapy was linked to a higher number of side-effects (severe enough to cause the discontinuation of treatment in two cases) than the six-month schedule.One study reported immunoadsorption apheresis had uncertain effects on skin vasculitis (RR 0.44, 95% CI 0.05 to 4.02), peripheral neuropathies (RR 2.70, 95%CI 0.13 to 58.24), and peripheral joint arthralgia (RR 2.70, 95%CI 0.13 to 58.24), cryocrit (MD 0.01%, 95%CI -1.86 to 1.88) at six months, and no infusion reactions were reported. However when clinical scores were evaluated, they reported changes were more favourable in immunoadsorption apheresis with higher remission of severe clinical complications (80% versus 33%, P = 0.05) compared to immunosuppressive treatment alone.In terms of death, it was not possible to present a pooled intervention effect estimate because most of the studies reported no deaths, or did not report death as an outcome. AUTHORS' CONCLUSIONS: To treat HCV-associated mixed cryoglobulinaemia, it may be beneficial to eliminate HCV infection by using antiviral treatment and to stop the immune response by using rituximab. For skin vasculitis and for some laboratory findings, it may be appropriate to combine antiviral treatment with deletion of B-cell clonal expansions by using of rituximab. The applicability of evidence reviewed here is limited by the absence of any studies with direct-acting antivirals, which are urgently needed to guide therapy.


Assuntos
Antivirais/uso terapêutico , Crioglobulinemia/terapia , Hepatite C/tratamento farmacológico , Dermatopatias/terapia , Vasculite/terapia , Remoção de Componentes Sanguíneos/métodos , Crioglobulinemia/virologia , Hepacivirus , Hepatite C/complicações , Humanos , Fatores Imunológicos/uso terapêutico , Técnicas de Imunoadsorção , Imunossupressores/uso terapêutico , Interferons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rituximab/uso terapêutico , Dermatopatias/virologia , Vasculite/etiologia
20.
Sci Rep ; 8(1): 5623, 2018 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-29618766

RESUMO

Crocodilepox virus is a large dsDNA virus belonging to the genus Crocodylidpoxvirus, which infects a wide range of host species in the order Crocodylia worldwide. Here, we present genome sequences for a novel saltwater crocodilepox virus, with two subtypes (SwCRV-1 and -2), isolated from the Australian saltwater crocodile. Affected belly skins of juvenile saltwater crocodiles were used to sequence complete viral genomes, and perform electron microscopic analysis that visualized immature and mature virions. Analysis of the SwCRV genomes showed a high degree of sequence similarity to CRV (84.53% and 83.70%, respectively), with the novel SwCRV-1 and -2 complete genome sequences missing 5 and 6 genes respectively when compared to CRV, but containing 45 and 44 predicted unique genes. Similar to CRV, SwCRV also lacks the genes involved in virulence and host range, however, considering the presence of numerous hypothetical and or unique genes in the SwCRV genomes, it is completely reasonable that the genes encoding these functions are present but not recognized. Phylogenetic analysis suggested a monophyletic relationship between SwCRV and CRV, however, SwCRV is quite distinct from other chordopoxvirus genomes. These are the first SwCRV complete genome sequences isolated from saltwater crocodile skin lesions.


Assuntos
Jacarés e Crocodilos/virologia , Chordopoxvirinae/genética , Genoma Viral , Genômica/métodos , Infecções por Poxviridae/genética , Dermatopatias/genética , Animais , Austrália , Chordopoxvirinae/classificação , Filogenia , Infecções por Poxviridae/virologia , Análise de Sequência de DNA , Dermatopatias/virologia , Virulência
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