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1.
PLoS Pathog ; 15(9): e1008050, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31557262

RESUMO

Crimean-Congo hemorrhagic fever (CCHF) is the most medically important tick-borne viral disease of humans and tuberculosis is the leading cause of death worldwide by a bacterial pathogen. These two diseases overlap geographically, however, concurrent infection of CCHF virus (CCHFV) with mycobacterial infection has not been assessed nor has the ability of virus to persist and cause long-term sequela in a primate model. In this study, we compared the disease progression of two diverse strains of CCHFV in the recently described cynomolgus macaque model. All animals demonstrated signs of clinical illness, viremia, significant changes in clinical chemistry and hematology values, and serum cytokine profiles consistent with CCHF in humans. The European and Asian CCHFV strains caused very similar disease profiles in monkeys, which demonstrates that medical countermeasures can be evaluated in this animal model against multiple CCHFV strains. We identified evidence of CCHFV persistence in the testes of three male monkeys that survived infection. Furthermore, the histopathology unexpectedly revealed that six additional animals had evidence of a latent mycobacterial infection with granulomatous lesions. Interestingly, CCHFV persisted within the granulomas of two animals. This study is the first to demonstrate the persistence of CCHFV in the testes and within the granulomas of non-human primates with concurrent latent tuberculosis. Our results have important public health implications in overlapping endemic regions for these emerging pathogens.


Assuntos
Febre Hemorrágica da Crimeia/complicações , Tuberculose Latente/complicações , Testículo/patologia , Animais , Anticorpos Antivirais/sangue , Doenças Transmissíveis Emergentes/complicações , Doenças Transmissíveis Emergentes/patologia , Doenças Transmissíveis Emergentes/virologia , Citocinas/sangue , Modelos Animais de Doenças , Progressão da Doença , Granuloma/microbiologia , Granuloma/patologia , Granuloma/virologia , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/imunologia , Vírus da Febre Hemorrágica da Crimeia-Congo/patogenicidade , Febre Hemorrágica da Crimeia/patologia , Febre Hemorrágica da Crimeia/virologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Tuberculose Latente/microbiologia , Tuberculose Latente/patologia , Macaca fascicularis , Masculino , Testículo/microbiologia , Testículo/virologia
3.
Intern Med ; 58(14): 2101-2105, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-30918176

RESUMO

A 43-year-old man with malignant lymphoma who had been treated with the cyclosphamide, vincrstine, procarbazine, and prednisolone (C-MOPP) regimen was admitted to our hospital with skin eruption. He was diagnosed to have varicella, and treatment with acyclovir and immune globulin was started. Chest computed tomography revealed multiple nodules in the both lung fields. Diagnostic thoracoscopic lung biopsy specimens revealed granuloma formation, and polymerase chain reaction testing revealed the presence of varicella-zoster virus DNA in the granulomatous tissue. It was unusual for the lung nodule in varicella pneumonia to increase in size over time in a patient who had undergone antiviral therapy, while also demonstrating multiple granulomas.


Assuntos
Granuloma/genética , Granuloma/virologia , Pneumonia/patologia , Pneumonia/virologia , Infecção pelo Vírus da Varicela-Zoster/complicações , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/genética , Aciclovir/uso terapêutico , Adulto , Antivirais/uso terapêutico , Ciclofosfamida/uso terapêutico , DNA Viral/isolamento & purificação , Humanos , Masculino , Pneumonia/etiologia , Reação em Cadeia da Polimerase , Prednisolona/uso terapêutico , Procarbazina/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Vincristina/uso terapêutico
4.
BMC Ophthalmol ; 19(1): 83, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30922271

RESUMO

BACKGROUND: To report 2 cases of bilateral granulomatous panuveitis accompanied by chronic active Epstein-Barr virus infection (CAEBV). CASE PRESENTATION: Case 1 was a 38-year-old man who had a history of bilateral mild panuveitis who was diagnosed with CAEBV. Fifteen months later, a severe bilateral granulomatous panuveitis developed. White infiltrates covered the optic disc and all the retinal vessels of the right eye, and white nodules were seen along the retinal veins and arteries of the left eye. Case 2 was a 34-year-old man with bilateral panuveitis showing mutton-fat keratic precipitates and diffuse vitreous opacity in both eyes. A snow ball-like vitreous opacity was present in the right eye. Systemic investigations revealed the presence of CAEBV. In both cases, a comprehensive polymerase chain reaction (PCR) analyses of the aqueous humor detected significant copy numbers of EBV-DNA. The intraocular inflammation did not respond to steroid, methotrexate, and other immunosuppressive therapies, but was ameliorated after hematopoietic stem cell transplantation with preceding chemotherapy and low-dose total body irradiation in both cases. CONCLUSION: Granulomatous panuveitis can develop in eyes with CAEBV as a primary symptom. Ophthalmologists should rule out CAEBV when EBV-DNA is positive in the intraocular fluids of steroid-resistant panuveitis.


Assuntos
Infecções por Vírus Epstein-Barr/complicações , Granuloma/virologia , Pan-Uveíte/virologia , Adulto , Doença Crônica , Humanos , Masculino
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.
J Clin Immunol ; 39(1): 112-117, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30680653

RESUMO

PURPOSE: Nitazoxanide was recently reported as having in vitro effectiveness against the rubella virus. Immunodeficiency-related vaccine-derived rubella occurs in some patients who have an inherited immunodeficiency and who received the MMR vaccine. This study investigated the in vivo effectiveness of nitazoxanide therapy. METHODS: This is a retrospective analysis of seven patients treated with nitazoxanide as salvage therapy for immunodeficiency-related vaccine-derived rubella infection. The patients were recruited from an ongoing rubella detection surveillance project. RESULTS: Seven patients with persistent rubella were treated with nitazoxanide and one demonstrated significant clinical improvement. Two additional patients exhibited diminished viral capsid production with one patient having transient slowing of progression. The cohort overall generally had low T cell counts and had a high burden of comorbidities. There were three deaths. Two deaths were from PML and one was related to hematopoietic stem cell transplantation. CONCLUSIONS: Nitazoxanide has limited in vivo anti-viral effects for immunodeficiency-related vaccine-derived rubella. Most patients did not exhibit clinical improvement.


Assuntos
Granuloma/tratamento farmacológico , Síndromes de Imunodeficiência/virologia , Vírus da Rubéola/efeitos dos fármacos , Rubéola (Sarampo Alemão)/tratamento farmacológico , Tiazóis/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Granuloma/virologia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Rubéola (Sarampo Alemão)/virologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/virologia , Vacinação/métodos
9.
Transpl Infect Dis ; 20(5): e12939, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29863293

RESUMO

Evolving BK polyomavirus-associated nephropathy (BKPyVAN) is characterized by tubulointerstitial inflammation that closely resembles acute T-cell-mediated allograft rejection if tubulitis is significant. The cellular composition of the inflammation varies during the course of BKPyVAN, and clusters of plasma cells may herald resolution of the infection. Less commonly, BKPyVAN can present with a predominance of histiocytes and granuloma formation. Granulomatous interstitial nephritis is uncommon in biopsies of either native or transplant kidneys. In both settings, this distinctive type of inflammatory response requires a systematic approach with careful clinicopathological assessment to determine its etiology. We present three patients with granulomatous BKPyVAN in the first year post-transplantation. These allograft biopsies at 4, 6, and 12 months post-transplant exemplify spontaneously resolving BKPyVAN, resolving infection after immunosuppression reduction, and early BKPyVAN, respectively. In immunosuppressed patients, BKPyVAN should be added to the relatively broad differential diagnosis of granulomatous tubulointerstitial nephritis.


Assuntos
Granuloma/patologia , Transplante de Rim/efeitos adversos , Nefrite Intersticial/patologia , Infecções por Polyomavirus/patologia , Infecções Tumorais por Vírus/patologia , Idoso , Vírus BK/isolamento & purificação , Biópsia , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Granuloma/imunologia , Granuloma/virologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressão/efeitos adversos , Rim/patologia , Rim/virologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/imunologia , Nefrite Intersticial/virologia , Infecções por Polyomavirus/imunologia , Infecções por Polyomavirus/virologia , Infecções Tumorais por Vírus/imunologia , Infecções Tumorais por Vírus/virologia
10.
Ann Dermatol Venereol ; 145(5): 354-358, 2018 May.
Artigo em Francês | MEDLINE | ID: mdl-29673750

RESUMO

BACKGROUND: Granuloma faciale (GF), or facial granuloma of Lever, is an uncommon dermatosis occurring classically on the face. We report a case of a GF on zoster scars located on the trunk, which is a highly particular isotopic response. PATIENTS AND METHODS: A 60-year-old man with a sole history of left lumbar zoster presented with a skin lesion present for two months. Clinical examination revealed a 2.5-cm papular erythematous lesion that was both infiltrated and pruritic. This lesion was situated precisely on zoster scars. Lab tests revealed no abnormalities. Histopathologic examination showed an inflammatory process without neovessels but rich in eosinophils with chronic vasculitis and polymorphic infiltrate, on which basis GF was diagnosed. DISCUSSION: GF is a localized form of cutaneous small-vessel vasculitis. Although it usually affects the face, extra-facial locations also exist. The original character of this presentation, aside from the location, is the occurrence of this GF on a zoster scar, which corresponds to Wolf's isotopic response. This phenomenon, described by R. Wolf, comprises the occurrence of a new skin disorder at the site of another unrelated and already healed skin disease, usually herpes. The physiopathology is still unclear. This differs from isomorphic reactions such as Koebner's reaction, which consists of the appearance at an injury site of skin lesions typical of an existing dermatosis but not a new disorder. CONCLUSION: This is a rare case of Wolf's isotopic response with GF, of which, to our knowledge, there are no reports in the literature.


Assuntos
Cicatriz/patologia , Granuloma/virologia , Herpes Zoster/complicações , Herpes Zoster/patologia , Humanos , Masculino , Pessoa de Meia-Idade
11.
Vet Pathol ; 55(2): 268-272, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29050543

RESUMO

Porcine circovirus type 2 (PCV2) is associated with multiple clinical syndromes in pigs, known as porcine circovirus diseases. This work describes an outbreak of porcine circovirus diseases with severe lesions affecting the skeletal muscle. Ninety-two pigs had apathy, weight loss, and diarrhea over a clinical course of 7 to 10 days. Approximately 30 of the pigs had stiff gait, muscle weakness, hind limb paresis, and recumbency. Twelve of the 92 pigs were necropsied, and 4 had pale discoloration of skeletal muscles with microscopic lesions of granulomatous necrotizing myositis. Immunohistochemistry of skeletal muscle showed that PCV2 antigen was located primarily in the cytoplasm and nuclei of macrophages, lymphocytes, and multinucleated giant cells, with a lower amount in the cytoplasm of endothelial cells, necrotic fibers, and satellite cells. Affected muscle samples were polymerase chain reaction-positive for PCV2 and the amplicon exhibited 99% identity with sequences belonging to the PCV2b genotype. Locomotor clinical signs and granulomatous necrotizing myositis should be considered as another expression of PCV2 infection in pigs.


Assuntos
Infecções por Circoviridae/veterinária , Circovirus , Miosite/veterinária , Doenças dos Suínos/virologia , Animais , Infecções por Circoviridae/complicações , Infecções por Circoviridae/patologia , Feminino , Granuloma/patologia , Granuloma/veterinária , Granuloma/virologia , Músculo Esquelético/patologia , Miosite/etiologia , Miosite/patologia , Miosite/virologia , Necrose , Suínos , Doenças dos Suínos/patologia
12.
Antiviral Res ; 147: 58-66, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28974385

RESUMO

Persistent rubella virus (RV) infection has been associated with various pathologies such as congenital rubella syndrome, Fuchs's uveitis, and cutaneous granulomas in patients with primary immune deficiencies (PID). Currently there are no drugs to treat RV infections. Nitazoxanide (NTZ) is an FDA-approved drug for parasitic infections, and has been recently shown to have broad-spectrum antiviral activities. Here we found that empiric 2-month therapy with oral NTZ was associated in the decline/elimination of RV antigen from lesions in a PID patient with RV positive granulomas, while peginterferon treatment had no effect. In addition, we characterized the effects of NTZ on cell culture models of persistent RV infection. NTZ significantly inhibited RV replication in a primary culture of human umbilical vein endothelial cells (HUVEC) and Vero and A549 epithelial cell lines in a dose dependent manner with an average 50% inhibitory concentration of 0.35 µg/ml (1.1 µM). RV strains representing currently circulating genotypes were inhibited to a similar extent. NTZ affected early and late stages of infection by inhibiting synthesis of cellular and RV RNA and interfering with intracellular trafficking of the RV surface glycoproteins, E1 and E2. These results suggest a potential application of NTZ for the treatment of persistent rubella infections, but more studies are required.


Assuntos
Antígenos Virais/metabolismo , Transporte Proteico/efeitos dos fármacos , Vírus da Rubéola/efeitos dos fármacos , Tiazóis/farmacologia , Tiazóis/uso terapêutico , Replicação Viral/efeitos dos fármacos , Células A549 , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Feminino , Granuloma/complicações , Granuloma/tratamento farmacológico , Granuloma/virologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Síndromes de Imunodeficiência/complicações , Síndromes de Imunodeficiência/virologia , Concentração Inibidora 50 , Rubéola (Sarampo Alemão)/complicações , Rubéola (Sarampo Alemão)/tratamento farmacológico , Rubéola (Sarampo Alemão)/virologia , Pele/patologia , Pele/virologia , Tiazóis/toxicidade , Resultado do Tratamento , Células Vero
13.
Pathol Res Pract ; 213(10): 1306-1309, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28756985

RESUMO

Epstein-Barr Virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor typically seen in immunocompromised patients. Here, we report a case of EBV-SMT and associated granulomatous inflammation in the liver of a 32-year-old man with history of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). To our knowledge, an association of these two lesions has not been previously reported. We review the literature and discuss pathogenesis, differential diagnosis and immunohistochemical (IHC) stains helpful for the diagnosis of this rare entity. Finally, we consider possible explanations for the concomitant presence of these lesions.


Assuntos
Infecções por Vírus Epstein-Barr/virologia , Granuloma/virologia , Hepatite/virologia , Tumor de Músculo Liso/virologia , Síndrome de Imunodeficiência Adquirida/diagnóstico , Síndrome de Imunodeficiência Adquirida/imunologia , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Biópsia com Agulha de Grande Calibre , Diagnóstico Diferencial , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Infecções por Vírus Epstein-Barr/diagnóstico , Infecções por Vírus Epstein-Barr/imunologia , Granuloma/diagnóstico , Granuloma/imunologia , Hepatite/diagnóstico , Hepatite/imunologia , Humanos , Hospedeiro Imunocomprometido , Imuno-Histoquímica , Masculino , Valor Preditivo dos Testes , Tumor de Músculo Liso/diagnóstico , Tumor de Músculo Liso/imunologia
15.
J Infect Dis ; 214(9): 1309-1318, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27462092

RESUMO

BACKGROUND: Human immunodeficiency virus type 1 (HIV)-infected persons are more susceptible to tuberculosis than HIV-uninfected persons. Low peripheral CD4+ T-cell count is not the sole cause of higher susceptibility, because HIV-infected persons with a high peripheral CD4+ T-cell count and those prescribed successful antiretroviral therapy (ART) remain more prone to active tuberculosis than HIV-uninfected persons. We hypothesized that the increase in susceptibility is caused by the ability of HIV to manipulate Mycobacterium tuberculosis-associated granulomas. METHODS: We examined 71 excised cervical lymph nodes (LNs) from persons with HIV and M. tuberculosis coinfection, those with HIV monoinfection, and those with M. tuberculosis monoinfection with a spectrum of peripheral CD4+ T-cell counts and ART statuses. We quantified differences in M. tuberculosis levels, HIV p24 levels, cellular response, and cytokine presence within granulomas. RESULTS: HIV increased M. tuberculosis numbers and reduced CD4+ T-cell counts within granulomas. Peripheral CD4+ T-cell depletion correlated with granulomas that contained fewer CD4+ and CD8+ T cells, less interferon γ, more neutrophils, more interleukin 10 (IL-10), and increased M. tuberculosis numbers. M. tuberculosis numbers correlated positively with IL-10 and interferon α levels and fewer CD4+ and CD8+ T cells. ART reduced IL-10 production. CONCLUSIONS: Peripheral CD4+ T-cell depletion correlated with increased M. tuberculosis presence, increased IL-10 production, and other phenotypic changes within granulomas, demonstrating the HIV infection progressively changes these granulomas.


Assuntos
Coinfecção/metabolismo , Granuloma/metabolismo , Infecções por HIV/metabolismo , Interleucina-10/metabolismo , Linfonodos/metabolismo , Tuberculose/metabolismo , Adulto , Idoso , Contagem de Linfócito CD4/métodos , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/microbiologia , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/microbiologia , Linfócitos T CD8-Positivos/virologia , Coinfecção/microbiologia , Coinfecção/virologia , Feminino , Granuloma/microbiologia , Granuloma/virologia , Infecções por HIV/microbiologia , Infecções por HIV/virologia , HIV-1/patogenicidade , Humanos , Interferon gama/metabolismo , Linfonodos/microbiologia , Linfonodos/virologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/patogenicidade , Tuberculose/microbiologia , Tuberculose/virologia , Adulto Jovem
16.
Vet Pathol ; 53(6): 1180-1186, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27106741

RESUMO

Multisystemic granulomatous lesions are the most common finding in ferrets infected by ferret systemic coronavirus (FRSCV). To characterize the inflammatory response developed against this virus, lesions from 4 naturally infected ferrets were examined. Lesions were classified into the 4 known types of granulomas (granulomas without necrosis [G], granulomas with necrosis [G-N], granulomas with neutrophils [G-NL], and diffuse granulomatous inflammation [DG]). The cellular composition of the lesions was characterized on the basis of cellular morphology and immunohistochemistry using markers for T and B-lymphocytes, plasma cells, macrophages, and neutrophils. The extent and distribution of viral antigen expression was also assessed. In G lesions, macrophages were mainly located in the center of the granuloma, with a moderate number of T-lymphocytes scattered among the macrophages, plasma cells, and B-lymphocytes. G-N lesions exhibited a necrotic center surrounded by abundant macrophages, some T-lymphocytes, plasma cells, and a few B-lymphocytes. In G-NL lesions, there was a central area dominated by neutrophils with low numbers of macrophages, plasma cells, and lymphocytes. DG presented similar cell proportions, but distributed evenly throughout the lesions. FRSCV was expressed in G, G-NL, G-N, and DG, with decreasing numbers of immunoreactive cells. This study reveals the important role of macrophages in the inflammatory response of ferrets against the virus and the variable proportions of leukocytes among different types of lesions, indicating their variable age. The results also confirm the similarities of the disease in ferrets to feline infectious peritonitis.


Assuntos
Antígenos Virais/imunologia , Infecções por Coronavirus/veterinária , Furões/virologia , Inflamação/veterinária , Animais , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Feminino , Furões/imunologia , Granuloma/veterinária , Granuloma/virologia , Imunidade Celular/imunologia , Inflamação/imunologia , Inflamação/patologia , Inflamação/virologia , Rim/patologia , Rim/virologia , Macrófagos/imunologia , Masculino
17.
Am J Dermatopathol ; 38(12): 892-899, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26909591

RESUMO

Treatment with interferon (IFN) could be associated with variable cutaneous adverse reactions. The aim of this study was to describe the clinicopathological spectrum of cutaneous granulomas associated with IFN therapy and identify the causal relation between IFN therapy and granulomatous reactions. The study included 18 patients (16 males and 2 females) with an average age of 48 years. Clinically, most of the lesions were solitary (83.3%) and located on the face (44.4%) and/or trunk (38.9%). The lesions were commonly presented as nodules (33.3%) or plaques (27.8%) with a common size of 5-10 cm. Granulomatous reactions were localized to the injection site in 4 cases, distributed on other body areas (remote granuloma) in 11 cases, and associated with lung involvement (systemic granuloma) in 3 cases. Histologically, injection site granuloma showed suppurative reaction in 75% and sarcoidal reaction in 25%. Remote granuloma showed tuberculoid reaction in 27.3%, interstitial in 27.3%, and sarcoidal in 45.4%. Systemic granuloma showed sarcoidal reaction in all cases. After withdrawal of IFN, only 3 lesions showed spontaneous complete clearance, whereas most of the lesions (83.3%) showed only partial improvement. Our results suggested that IFN is not a causal agent of all associated cutaneous granulomas but it mostly provokes the appearance of granulomatous reactions in susceptible individuals. Findings that prove this concept include the formation of granuloma in body sites away from the injection site, the heterogeneous pattern of granuloma both clinically and histologically, and incomplete clearance of most of the lesions after withdrawal of IFN.


Assuntos
Erupção por Droga/etiologia , Granuloma/induzido quimicamente , Fatores Imunológicos/efeitos adversos , Interferons/efeitos adversos , Pele/efeitos dos fármacos , Tuberculose Cutânea/induzido quimicamente , Adulto , Idoso , Biópsia , DNA Bacteriano/genética , DNA Viral/genética , Erupção por Droga/microbiologia , Erupção por Droga/patologia , Erupção por Droga/virologia , Feminino , Granuloma/microbiologia , Granuloma/patologia , Granuloma/virologia , Vírus de Hepatite/genética , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Reação em Cadeia da Polimerase , Ribotipagem , Pele/microbiologia , Pele/patologia , Pele/virologia , Teste Tuberculínico , Tuberculose Cutânea/microbiologia , Tuberculose Cutânea/patologia
19.
AIDS Res Hum Retroviruses ; 32(3): 262-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26564424

RESUMO

Extrapulmonary tuberculosis (TB) is a significant public health challenge in South Africa and worldwide, largely fuelled by the HIV epidemic. In spinal TB, Mycobacteria infect the spinal column without dissemination to the spinal cord. The immune microenvironment, target cell characteristics, and other evolutionary forces within granulomas during HIV/TB coinfection are poorly characterized. We investigated whether spinal TB granulomas represent a sequestered anatomical site where independent HIV evolution occurs, and assessed the role of macrophages as a target cell for both HIV and mycobacteria. RNA was extracted from plasma and granulomatous tissue from six antiretroviral-naive HIV-1/spinal TB-coinfected patients, RT-PCR amplified, and the C2-V5 env segment was cloned and sequenced. Analysis of genetic diversity, phylogeny and coalescence patterns was performed on clonal sequences. To investigate their role in HIV sequestration, macrophages and the HIV-1 p24 protein were immune localized and ultrastructural features were studied. Intercompartment diversity measurements and phylogenetic reconstruction revealed anatomically distinct monophyletic HIV-1 clusters in four of six patients. Genotypic CCR5-tropic variants were predominant (98.9%) with conservation of putative N-linked glycosylation sites in both compartments. CD68(+) reactivity was associated with higher tissue viral load (r = 1.0; p < 0.01) but not greater intrapatient diversity (r = 0.60; p > 0.05). Ultrastructural imaging revealed the presence of bacterial and virus-like particles within membrane-bound intracellular compartments of macrophages. Spinal tuberculosis granulomas may form anatomically discreet sites of divergent viral evolution. Macrophages in these granulomas harbored both pathogens, suggesting that they may facilitate the process of viral sequestration within this compartment.


Assuntos
Variação Genética , Granuloma/virologia , Infecções por HIV/complicações , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Tuberculose da Coluna Vertebral/complicações , Adulto , Pré-Escolar , Clonagem Molecular , Coinfecção/virologia , Feminino , Genótipo , HIV-1/isolamento & purificação , Humanos , Masculino , Filogenia , RNA Viral/genética , RNA Viral/isolamento & purificação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , África do Sul , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética
20.
Am J Trop Med Hyg ; 93(3): 612-4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26123955

RESUMO

Ocular Baylisascaris procyonis infection results from ingestion of infective eggs of B. procyonis, the raccoon ascarid. Herpes simplex virus type 2 (HSV-2) infection of the retina is the result of either primary infection or reactivated disease. Herein, we report a case of a 12-year-old female resident of the Bronx in New York City, who presented with pan-uveitis and vision loss. Initial evaluation for etiologic causes was nondiagnostic. Serology for anti-Baylisascaris procyonis antibodies in serum and vitreous fluid were both positive. Polymerase chain reaction (PCR) of vitreous fluid was positive for HSV-2. Treatment with vitrectomy, albendazole, and acyclovir resulted in mild improvement of visual acuity. The atypical presentation of B. procyonis in this case, as ocular larva migrans with a peripheral granuloma and retinal detachment, underscores the importance of maintaining a high degree of suspicion for this pathogen even in non-diffuse unilateral subacute neuroretinitis (DUSN) patients in urban areas. This case further illustrates that it is possible to have coexisting infections in cases of posterior uveitis.


Assuntos
Infecções por Ascaridida/complicações , Ascaridoidea , Infecções Oculares Parasitárias/complicações , Ceratite Herpética/complicações , Larva Migrans/diagnóstico , Animais , Infecções por Ascaridida/diagnóstico , Criança , Coinfecção , Diagnóstico Diferencial , Infecções Oculares Parasitárias/diagnóstico , Feminino , Fundo de Olho , Granuloma/diagnóstico , Granuloma/etiologia , Granuloma/parasitologia , Granuloma/virologia , Herpesvirus Humano 2 , Humanos , Ceratite Herpética/diagnóstico , Ceratite Herpética/virologia
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