Essential role of the CCL2-CCR2 axis in Mayaro virus-induced disease.

Mayaro virus (MAYV) is an emerging arbovirus member of the Togaviridae family and Alphavirus genus. MAYV infection causes an acute febrile illness accompanied by persistent polyarthralgia and myalgia. Understanding the mechanisms involved in arthritis caused by alphaviruses is necessary to develop specific therapies. In this work, we investigated the role of the CCL2/CCR2 axis in the pathogenesis of MAYV-induced disease. For this, wild-type (WT) C57BL/6J and CCR2-/- mice were infected with MAYV subcutaneously and evaluated for disease development. MAYV infection induced an acute inflammatory disease in WT mice. The immune response profile was characterized by an increase in the production of inflammatory mediators, such as IL-6, TNF, and CCL2. Higher levels of CCL2 at the local and systemic levels were followed by the significant recruitment of CCR2+ macrophages and a cellular response orchestrated by these cells. CCR2-/- mice showed an increase in CXCL-1 levels, followed by a replacement of the macrophage inflammatory infiltrate by neutrophils. Additionally, the absence of the CCR2 receptor protected mice from bone loss induced by MAYV. Accordingly, the silencing of CCL2 chemokine expression in vivo and the pharmacological blockade of CCR2 promoted a partial improvement in disease. Cell culture data support the mechanism underlying the bone pathology of MAYV, in which MAYV infection promotes a pro-osteoclastogenic microenvironment mediated by CCL2, IL-6, and TNF, which induces the migration and differentiation of osteoclast precursor cells. Overall, these data contribute to the understanding of the pathophysiology of MAYV infection and the identification future of specific therapeutic targets in MAYV-induced disease.IMPORTANCEThis work demonstrates the role of the CCL2/CCR2 axis in MAYV-induced disease. The infection of wild-type (WT) C57BL/6J and CCR2-/- mice was associated with high levels of CCL2, an important chemoattractant involved in the recruitment of macrophages, the main precursor of osteoclasts. In the absence of the CCR2 receptor, there is a mitigation of macrophage migration to the target organs of infection and protection of these mice against bone loss induced by MAYV infection. Much evidence has shown that host immune response factors contribute significantly to the tissue damage associated with alphavirus infections. Thus, this work highlights molecular and cellular targets involved in the pathogenesis of arthritis triggered by MAYV and identifies novel therapeutic possibilities directed to the host inflammatory response unleashed by MAYV.

Zika Virus and Arthritis/Arthralgia: A Systematic Review and Meta-Analysis.

Dengue, chikungunya and Zika viruses share similar disease features, rendering them difficult to distinguish clinically. Incapacitating arthralgia/arthritis is a specific manifestation associated with chikungunya virus infection. However, the profile of arthralgia/arthritis in Zika virus (ZIKV) cases has not been well characterized. Articles were extracted from PubMed and Scopus databases reporting original data from patients with arthralgia/arthritis, according to the Cochrane Collaboration. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, 137 articles reporting ZIKV-associated joint symptoms were reviewed. Arthralgia was more frequently reported (n = 124 from case studies, n = 1779 from population-based studies) than arthritis (n = 7 and n = 121, respectively). Arthralgia was resolved in <1 week in 54%, and within 1-2 weeks in 40% of cases. The meta-analysis of cases in population-based studies identified a pooled prevalence of 53.55% for arthralgia. The pooled prevalence of arthralgia/arthritis during outbreaks depended on the geographic location, with a higher joint symptom burden observed in the Americas compared to South East Asia (Brazil: 60.79%; Puerto Rico: 68.89% and South East Asia: 26.46%). We conclude that non-specific constitutional arthralgia is the most common joint manifestation during ZIKV infection, being present in nearly half of cases but resolving by two weeks in >90% of these. We found no evidence of chronic rheumatic manifestations following ZIKV infection.

Efficacy of measures to control caprine arthritis-encephalitis in dairy herd with high clinical and serological prevalence / Eficácia das medidas de controle da artrite-encefalite caprina em rebanho leiteiro com alta prevalência clínica e sorológica

This study examined the effectiveness of control measures for caprine arthritis-encephalitis in a herd with 431 dairy goats in an intensive rearing system. All animals older than six months were initially tested by agar gel immunodiffusion (AGID) and separated into seropositive and seronegative. Control measures were implemented for two years and ten months. Five serological examinations were subsequently performed—two by AGID and three by the Western Blot (WB) technique. In these tests, animals that tested negative in the previous serological examination were evaluated along with those older than six months which had not yet been examined. The effectiveness of control was evaluated based on the incidence of the disease. Seroconverted animals were stratified according to age, physiological status and dam serology. For the effect of time, logistic regression was performed at the 5% significance level, with values converted into likelihood. General incidence and incidence as a function of age and physiological status were evaluated by analysis of variance, with means compared by Tukeys test at 5% significance. The ratio test was used for incidence and physiological status, and the agreement between the AGID and WB tests was determined by the Kappa coefficient. Animals that seroconverted and were born to positive dams were compared with those born to dams negative at birth by the Chi-square test, and the same was applied for the number of discarded animals. Initially, 54.24% (179/330) positive and 257 seroconverted animals were identified after the start of control. Higher incidence occurred in the animal saged between 13 and 36 months and in lactating does. Seroconversions among offspring of seropositive dams were higher than in the offspring of seronegative dams (p < 0.001). High infection rates were identified in the sires. The obtained [...].(AU)

Avaliou-se a eficácia das medidas de controle para a artrite-encefalite caprina em rebanho com 431 caprinos leiteiros em regime intensivo de criação. Todos os animais com idade superior a seis meses foram inicialmente testados por imunodifusão em gel de ágar (IDGA) e soropositivos e soronegativos separados. Durante dois anos e dez meses medidas de controle foram instituídas. Cinco testes sorológicos foram posteriormente realizados, dois por IDGA e três por Western Blot (WB). Nesses testes eram avaliados os animais negativos na sorologia anterior e acrescidos os com mais de seis meses, ainda não avaliados. A eficácia do controle foi avaliada pela incidência da enfermidade. Animais que soroconverteram foram estratificados quanto a idade, estado fisiológico e sorologia das progenitoras. Para o efeito do tempo foi realizado a regressão logística a 5% de significância, convertidos em razão de probabilidades. A incidência geral e incidência em função da idade e estado fisiológico foram avaliadas pela análise variância, comparando as médias pelo teste Tukey a 5 % de significância. O teste de proporções foi utilizado para incidência e estado fisiológico, e a concordância entre os testes IDGA e Wb realizada através do coeficiente Kappa. Os animais que soroconverteram e eram nascidos de progenitoras positivas foram comparados com aqueles de progenitoras negativas ao parto pelo teste de Qui-quadrado, assim como o número de animais descartados. Inicialmente identificou-se 54,24%(179/330) de animais positivos e 257 soroconverteram após início do controle. Incidências maiores ocorreram nos animais entre 13 e 36 meses e nas lactantes. Soroconversões em crias de progenitoras soropositivas foram maiores que nas de progenitoras soronegativas (p < 0,001). Altas taxas de infecção foram identificadas nos reprodutores. Os resultados obtidos não foram satisfatórios, pois as medidas não contribuíram para evitar novos casos, demonstrando que existem momentos de infecção que [...].(AU)

Efficacy of measures to control caprine arthritis-encephalitis in dairy herd with high clinical and serological prevalence / Eficácia das medidas de controle da artrite-encefalite caprina em rebanho leiteiro com alta prevalência clínica e sorológica

This study examined the effectiveness of control measures for caprine arthritis-encephalitis in a herd with 431 dairy goats in an intensive rearing system. All animals older than six months were initially tested by agar gel immunodiffusion (AGID) and separated into seropositive and seronegative. Control measures were implemented for two years and ten months. Five serological examinations were subsequently performed—two by AGID and three by the Western Blot (WB) technique. In these tests, animals that tested negative in the previous serological examination were evaluated along with those older than six months which had not yet been examined. The effectiveness of control was evaluated based on the incidence of the disease. Seroconverted animals were stratified according to age, physiological status and dam serology. For the effect of time, logistic regression was performed at the 5% significance level, with values converted into likelihood. General incidence and incidence as a function of age and physiological status were evaluated by analysis of variance, with means compared by Tukey’s test at 5% significance. The ratio test was used for incidence and physiological status, and the agreement between the AGID and WB tests was determined by the Kappa coefficient. Animals that seroconverted and were born to positive dams were compared with those born to dams negative at birth by the Chi-square test, and the same was applied for the number of discarded animals. Initially, 54.24% (179/330) positive and 257 seroconverted animals were identified after the start of control. Higher incidence occurred in the animal saged between 13 and 36 months and in lactating does. Seroconversions among offspring of seropositive dams were higher than in the offspring of seronegative dams (p < 0.001). High infection rates were identified in the sires. The obtained [...].

Avaliou-se a eficácia das medidas de controle para a artrite-encefalite caprina em rebanho com 431 caprinos leiteiros em regime intensivo de criação. Todos os animais com idade superior a seis meses foram inicialmente testados por imunodifusão em gel de ágar (IDGA) e soropositivos e soronegativos separados. Durante dois anos e dez meses medidas de controle foram instituídas. Cinco testes sorológicos foram posteriormente realizados, dois por IDGA e três por Western Blot (WB). Nesses testes eram avaliados os animais negativos na sorologia anterior e acrescidos os com mais de seis meses, ainda não avaliados. A eficácia do controle foi avaliada pela incidência da enfermidade. Animais que soroconverteram foram estratificados quanto a idade, estado fisiológico e sorologia das progenitoras. Para o efeito do tempo foi realizado a regressão logística a 5% de significância, convertidos em razão de probabilidades. A incidência geral e incidência em função da idade e estado fisiológico foram avaliadas pela análise variância, comparando as médias pelo teste Tukey a 5 % de significância. O teste de proporções foi utilizado para incidência e estado fisiológico, e a concordância entre os testes IDGA e Wb realizada através do coeficiente Kappa. Os animais que soroconverteram e eram nascidos de progenitoras positivas foram comparados com aqueles de progenitoras negativas ao parto pelo teste de Qui-quadrado, assim como o número de animais descartados. Inicialmente identificou-se 54,24%(179/330) de animais positivos e 257 soroconverteram após início do controle. Incidências maiores ocorreram nos animais entre 13 e 36 meses e nas lactantes. Soroconversões em crias de progenitoras soropositivas foram maiores que nas de progenitoras soronegativas (p < 0,001). Altas taxas de infecção foram identificadas nos reprodutores. Os resultados obtidos não foram satisfatórios, pois as medidas não contribuíram para evitar novos casos, demonstrando que existem momentos de infecção que [...].

Systems analysis of subjects acutely infected with the Chikungunya virus.

The largest ever recorded epidemic of the Chikungunya virus (CHIKV) broke out in 2004 and affected four continents. Acute symptomatic infections are typically associated with the onset of fever and often debilitating polyarthralgia/polyarthritis. In this study, a systems biology approach was adopted to analyze the blood transcriptomes of adults acutely infected with the CHIKV. Gene signatures that were associated with viral RNA levels and the onset of symptoms were identified. Among these genes, the putative role of the Eukaryotic Initiation Factor (eIF) family genes and apolipoprotein B mRNA editing catalytic polypeptide-like (APOBEC3A) in the CHIKV replication process were displayed. We further compared these signatures with signatures induced by the Dengue virus infection and rheumatoid arthritis. Finally, we demonstrated that the CHIKV in vitro infection of murine bone marrow-derived macrophages induced IL-1 beta production in a mechanism that is significantly dependent on the inflammasome NLRP3 activation. The observations provided valuable insights into virus-host interactions during the acute phase and can be instrumental in the investigation of new and effective therapeutic interventions.

Animal model of arthritis and myositis induced by the Mayaro virus.

BACKGROUND: The Mayaro virus (MAYV) is an endemic arbovirus in South American countries, where it is responsible for sporadic outbreaks of Mayaro fever. Clinical manifestations include fever, headache, ocular pain, rash, myalgia, and debilitating and persistent polyarthralgia. Understanding the mechanisms associated with MAYV-induced arthritis is of great importance due to the potential for its emergence, urbanization and dispersion to other regions. METHODS: 15-day old Balb/c mice were infected by two distinct pathways, below the forelimb and in the rear footpad. Animals were observed for a period of 21 days. During this time, they were monitored every 24 hours for disease signs, such as weight loss and muscle weakness. Histological damage in the muscles and joints was evaluated 3, 7, 10, 15 and 20 days post-infection. The cytokine profile in serum and muscles during MAYV infection was evaluated by flow cytometry at different post-infection times. For pain analysis, the animals were submitted to the von Frey test and titre in different organs was evaluated throughout the study to obtain viral kinetics. FINDINGS: Infection by two distinct pathways, below the forelimb and in the rear footpad, resulted in a homogeneous viral spread and the development of acute disease in animals. Clinical signs were observed such as ruffled fur, hunched posture, eye irritation and slight gait alteration. In the physical test, both groups presented loss of resistance, which was associated with histopathological damage, including myositis, arthritis, tenosynovitis and periostitis. The immune response was characterized by a strong inflammatory response mediated by the cytokines TNF-α, IL-6 and INF-γ and chemokine MCP-1, followed by the action of IL-10 and IL-4 cytokines. INTERPRETATION: The results showed that Balb/c mice represent a promising model to study mechanisms involved in MAYV pathogenesis and for future antiviral testing.

The Clinical Features, Pathogenesis and Methotrexate Therapy of Chronic Chikungunya Arthritis.

Chikungunya fever (CHIKF) is an emerging viral infection that has spread widely, along with its Aedes vectors, throughout the tropics and beyond, causing explosive epidemics of acute illness and persistent disabling arthritis. The rheumatic symptoms associated with chikungunya virus (CHIKV) infection include polyarthralgia, polyarthritis, morning stiffness, joint edema, and erythema. Chronic CHIK arthritis (CCA) often causes severe pain and associated disability. The pathogenesis of CCA is not well understood. Proposed hypotheses include the persistence of a low level of replicating virus in the joints, the persistence of viral RNA in the synovium, and the induction of autoimmunity. In this review, we describe the main hypotheses of CCA pathogenesis, some of which support methotrexate (MTX) treatment which has been shown to be effective in preliminary studies in CCA.

Treatment of chikungunya chronic arthritis: A systematic review.

INTRODUCTION: Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated. METHOD: A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity. RESULTS: Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report. CONCLUSION: When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.

Treatment of chikungunya chronic arthritis: A systematic review / Tratamento de artralgia crônica da chikungunya: uma revisão sistemática

Summary Introduction: Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated. Method: A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity. Results: Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report. Conclusion: When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.

Resumo Introdução: A chikungunya é uma arbovirose tropical, transmitida pela fêmea dos mosquitos Aedes aegypti e Aedes albopictus. No Brasil, existem casos relatados desde 2014. As manifestações iniciais dessa virose são: febre alta de início súbito, cefaleia, calafrios, erupções cutâneas, mialgia e dor articular intensa. Normalmente, a chikungunya apresenta as fases aguda e crônica, sendo a última caracterizada pela poliartralgia bilateral, que pode durar meses e até anos. Durante esse período, doenças autoimunes podem ser desencadeadas, tornando o quadro ainda mais complicado. Método: Foi realizada uma revisão sistemática nos bancos de dados PubMed e Scielo em janeiro de 2017. Ensaios clínicos, coortes, casos-controle e relatos de caso foram incluídos na pesquisa. Opiniões de especialista, consensos de sociedades e revisões literárias foram critérios de exclusão. Foram avaliados estudos nas línguas inglesa, espanhola e portuguesa. Os estudos foram analisados descritivamente, e os dados agrupados, conforme semelhança metodológica. Resultados: Foram selecionados 24 artigos; em obediência aos critérios de inclusão e exclusão, 18 foram eliminados, restando seis estudos na presente revisão: cinco ensaios clínicos e um relato de caso. Conclusão: Quando as manifestações da chikungunya se tornam crônicas, quanto mais tempo duram, mais complicações surgem. A poliartralgia pode ser incapacitante, afastando os indivíduos das suas atividades de vida diária. Anti-inflamatórios (esteroides ou não), somados a imunossupressores, homeopatia e fisioterapia são medidas de tratamento que, conforme a literatura, têm alcançado êxito no alívio ou na extinção dos sintomas. Todavia, é fundamental que os estudos do tratamento da chikungunya sejam mais aprofundados.

Poliartritis agudas virales / Viral acute polyarthritis

Las poliartritis agudas son cuadros de menos seis semanas de duración, cuyas causas pueden o no ser infecciosas. Entre las primeras, destacan las virales, con gran varie-dad de agentes causales. Entre ellos se distinguen por su frecuencia: virus hepatitis B,virus hepatitis C, parvovirus B19, virus rubéola y la fiebre Chicungunya. Tienen elementos comunes, como su expresión poliarticular, generalmente simétrica, con predilección por las pequeñas articulaciones de las manos, siendo habitualmente autolimitadas. A su vez, poseen elementos propios, clínicos y de laboratorio, que permiten diferenciarlos, teniendo algunos una evolución más agresiva con morbilidad más significativa. A su vez, por sus características clínicas y de laboratorio, plantean el diagnóstico diferencial con enfermedades inmunoreumatológicas, como la artritis reumatoidea y el lupus eritematoso sistémico, entre otras.Se realiza una revisión del cuadro clínico y de laboratorio de las poliartritis causadas por los virus señalados, su diagnóstico diferencial y posibilidades terapéuticas.

The acute polyarthritis are pictures of less six weeks duration, whose causes can be or not to be infectious. Among the first, the viral ones stand out with a variety of causal agents. Among there distinguished by their frequency: virus hepatitis B, hepatitis C virus, parvovirus B19, rubella virus and the fever Chicungunya. They have common elements, such as his expression polyarticular, usually symmetrical, with a predilection for the small joints of the hands, being usually self-limiting. At the same time, they have own laboratory and clinical elements that allow differentiation, some having a more aggressive evolution with more significant morbidity. At the same time, for its clinical and laboratory characteristics, raise the differential diagnosis of immunohematological diseases, such as arthritis rheumatoid and systemic lupus erythematosus among others.Is done a review of clinical and laboratory of the polyarthritis caused by the mentioned viruses, differential diagnosis and therapeutic possibilities.

A case of chikungunya virus disease presenting with remarkable acute arthritis of a previously damaged finger joint.

Chikungunya virus (CHIKV) is a mosquito-borne arthritogenic alphavirus that has recently been introduced to Brazil. We report the case of a 36-year-old male patient from the City of Rio de Janeiro who developed molecularly-confirmed CHIKV disease and whose clinical picture was remarkable because of acute arthritis of an interphalangeal joint that had been damaged by trauma 8 years previously. This case illustrates that acute CHIKV disease may preferentially target previously damaged joints. Careful study of individual cases may provide valuable information on the presentation and management of this emerging zoonosis in Brazil.

A case of chikungunya virus disease presenting with remarkable acute arthritis of a previously damaged finger joint

Abstract: Chikungunya virus (CHIKV) is a mosquito-borne arthritogenic alphavirus that has recently been introduced to Brazil. We report the case of a 36-year-old male patient from the City of Rio de Janeiro who developed molecularly-confirmed CHIKV disease and whose clinical picture was remarkable because of acute arthritis of an interphalangeal joint that had been damaged by trauma 8 years previously. This case illustrates that acute CHIKV disease may preferentially target previously damaged joints. Careful study of individual cases may provide valuable information on the presentation and management of this emerging zoonosis in Brazil.

Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication.

Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.

Fiebre de Chikungunya: reporte de tres casos del Hospital Naval Almirante Nef / Chikungunya fever: report of three cases from Almirante Nef Naval Hospital

Chikungunya fever is an emerging infection in our country due to travelers to endemic areas. It presents acutely with high fever, fatigue, headache, myalgia, skin rash and arthritis, usually as a symmetric polyarthritis compromising the interphalangeal and metacarpophalangeal joints, wrist, elbow, ankle and knee. While most of the symptoms last about a week, arthralgias may become chronic and generate significant functional impairment. Chikungunya has been postulated as a triggering factor for rheumatoid arthritis because of the presence of positive rheumatoid factor. We present the three confirmed cases in Almirante Nef Naval Hospital with the review of the published literature...

La fiebre de Chikungunya es una infección novedosa en nuestro país pues su contagio se produce por viajeros en zonas endémicas. Se presenta generalmente en forma aguda con fiebre alta, astenia, cefalea, mialgia, rash cutaneo y artritis, mayoritariamente como poliartritis simétrica comprometiendo las articulaciones interfalángicas, metacarpofalángicas, muñecas, codos, tobillo y rodillas. Si bien la mayoría de los síntomas duran aproximadamente una semana, las artralgias pueden hacerse crónicas y generar un importante deterioro funcional. Se ha postulado que podría ser un factor gatillante de artritis reumatoide ante la presencia de factor reumatoideo positivo. A continuación se presentan los tres casos confirmados del Hospital Naval Almirante Nef junto a la revisión de la literatura publicada hasta el momento...

Comparative study by computed radiography, histology, and scanning electron microscopy of the articular cartilage of normal goats and in chronic infection with caprine arthritis-encephalitis virus.

In the northeast of Brazil, caprine arthritis-encephalitis (CAE) is one of the key reasons for herd productivity decreasing that result in considerable economic losses. A comparative study was carried out using computed radiography (CR), histological analysis (HA), and scanning electronic microscopy (SEM) of the joints of CAE infected and normal goats. Humerus head surface of positive animals presented reduced joint space, increased bone density, and signs of degenerative joint disease (DJD). The carpal joint presented no morphological alterations in CR in any of the animals studied. Tarsus joint was the most affected, characterized by severe DJD, absence of joint space, increased periarticular soft tissue density, edema, and bone sclerosis. Histological analysis showed chronic tissue lesions, complete loss of the surface zone, absence of proteoglycans in the transition and radial zones and destruction of the cartilage surface in the CAE positive animals. Analysis by SEM showed ulcerated lesions with irregular and folded patterns on the joint surface that distinguished the limits between areas of normal and affected cartilage. The morphological study of the joints of normal and CAE positive goats deepened understanding of the alteration in the tissue bioarchitecture of the most affected joints. The SEM finding sustained previous histological reports, similar to those found for rheumatoid arthritis, suggesting that the goat infected with CAE can be considered as a potential model for research in this area.

Influência do vírus da artrite encefalite caprina no imunograma sanguíneo e lácteo de cabras naturalmente infectadas / Influence of caprine arthritis encephalitis virus on blood and milk immunogram of naturally infected goats

A Artrite Encefalite Caprina (AEC) é uma lentivirose multisistêmica que tem a glândula mamária caprina como um dos alvos lesionais da doença. Pode causar uma manifestação mamária específica, chamada de mastite endurativa, além da mama representar uma importante via de eliminação do vírus, mesmo em animais que não apresentam a forma clínica. Considerando-se a possibilidade desta virose, cuja célula alvo predominante é o monócito, levar a alterações imunológicas que influenciem a susceptibilidade do animal a outras doenças, objetivou-se avaliar essa interação do vírus e da imunidade do hospedeiro por meio de fenotipagem, fagocitose e produção de Espécies reativas de oxigênio (ERO) e dos mecanismos de morte das células sanguíneas e lácteas de cabras naturalmente infectadas. Para isso 200 cabras foram triadas e, destas selecionadas oito fêmeas não sororreagentes e dez sororreagentes na pesquisa de anticorpos séricos para AEC, dentro dos padrões hematológicos da espécie e com dois exames bacteriológicos do leite negativos. O leite e o sangue colhido destes animais foram submetidos às seguintes provas: fenotipagem dos leucócitos CD4+, CD8+, CD14+, PG68A+ e CD45+, fagocitose de Staphylococcus aureus e de Escherichia coli por células CD14+ e PG68A+, produção de ERO e marcação com Anexina-V e Iodeto de Propídeo (PI) por granulócitos e células mononucleares. A infecção pelo VAEC pode ser associada a um aumento de células CD14+ no leite, mas não no sangue. Os outros perfis celulares não sofreram alterações. Quanto a função fagocítica, o vírus reduziu a porcentagem de fagocitose de Staphylococcus aureus por granulócitos PG68A+ do leite. Esta alteração não ocorreu na fagocitose de Escherichia coli e na produção de ERO dessas células, nem na fagocitose e produção de ERO pelas células CD14+ ressaltando que nesses processos a espécie bacteriana pode sofrer interações com o vírus ou mesmo com a resposta imune do organismo infectado. O VAEC não influenciou significativamente os mecanismos de morte ora investigados, mas a tendência dos resultados sugere que possa haver indução de morte por apoptose e/ou por necrose nos granulócitos do sangue e influenciar no processo de necrose destas células no leite, sem alterar esses processos nas células mononucleares. Ressalta-se a importância da interação monócito-neutrófilo na glândula mamária, principalmente nos animais sororreagentes para AEC, mesmo na ausência de mastite bacteriana

The caprine arthritis encephalitis (CAE) is a multisystem lentivirose that have the goat mammary gland as one target of the lesional disease. May cause a mammary specific expression, called indurative mastitis, beyond these organ represent a major route of virus elimination, even in animals that do not exhibit this clinical manifestation. Considering the possibility of this virus, whose target cell are predominantly monocyte, lead to immunological changes that influence the animal's susceptibility to other diseases, this study aimed to evaluate the interaction of virus and host immunity by phenotyping, phagocytosis and production of reactive oxygen species (ROS) and the mechanisms of cell death, in blood and milk of goats naturally infected. For that, 200 goats were screened and was selected eight females non sero-reagents and ten seroreagents for serum antibodies against CAE, with the haematological analises within the species standards and two negative bacteriological tests of milk. Milk and blood from these animals underwent the following tests: phenotyping of leukocytes CD4+, CD8+, CD14+, PG68A+ and CD45+, phagocytosis of Staphylococcus aureus and Escherichia coli ROS production by CD14+ and PG68A+ cells, and labeling with Annexin-V and propidium iodide (PI) for granulocytes and mononuclear cells. CAEV infection may be associated with an increase in CD14+ cells in milk, but not in blood. The other cellular profile did not change. In the phagocytic function, the virus reduced the percentage of phagocytosis of Staphylococcus aureus by granulocytes PG68A+ milk. This change did not occur in the phagocytosis of Escherichia coli and production of ROS in these cells, nor in phagocytosis and ROS production by CD14+ cells, noting that in those cases the bacterial species may undergo interactions with the virus or even with the immune response of the infected organism. The VAEC not significantly affect the mechanism of death now investigated, but the tendency of the results suggests that can induce apoptosis and/or necrosis in the blood granulocytes and influence the process of necrosis of these cells in milk, without changing these processes mononuclear cells. We emphasize the importance of monocyte-neutrophil interaction in the mammary gland, especially in animals seropositive for CAE, even in the absence of bacterial mastitis

Viral infections: alpha-viral arthropathy.

Six different mosquito-borne viruses (Chikungunya, O'nyong-nyong, Mayaro, Ross River, Sindbis and Barmah Forest) have been associated with arthritis in humans. These viruses are prevalent in the tropics and subtropics and they produce similar symptoms, consisting of fever, joint pains and rash. The symptoms are usually of short duration, around 1 week; complete recovery is the rule apart from exceptional cases of Chik infection. Precise diagnosis requires a serological service which is not available in many parts of the tropics these days. Treatment is symptomatic and there is no vaccine currently available. With an increasing number of visitors to the tropics being exposed to potential infection and with rapid air transport it is possible that visitors may return home during the viraemic incubation stage, infect the local mosquito populations and then develop clinical disease.

Polyarthritis in HTLV-1-infected patients. A review of 17 cases.

A retrospective study was conducted in Martinique to identify patients with polyarthritis and positive serologic tests for the human T-cell lymphotropic virus Type I (HTLV-1). Patients with metabolic or bacterial causes of polyarthritis were excluded. We found 17 cases of HTLV-1-positive polyarthritis (6.7% of the total of polyarthritis patients followed in our department); there were 14 females and three males, and all the patients were West-Indian blacks. Mean age at diagnosis was 50 years. Five patients also had tropical spastic paraparesis. The polyarthritis was the inaugural manifestation of T-cell leukemia in one patient. Four patients had received blood transfusions. Fever, myalgia, and/or skin lesions were present at onset of the polyarthritis in seven cases. All 17 patients had peripheral, bilateral, symmetric polyarthritis; the most commonly involved sites were the hands (17/17) and knees (14/17). Three patients had rheumatoid factor and five had antinuclear antibody. Ten patients met at least four American Rheumatism Association criteria for rheumatoid arthritis; they accounted for 6.7% (10/150) of all polyarthritis patients managed in the same hospital department during the same period. We compared these ten patients with 20 HTLV-1-negative rheumatoid arthritis patients matched on gender, ethnic origin, and disease duration. There were no significant differences between the two groups for any of the parameters studied.