Viperin controls chikungunya virus-specific pathogenic T cell IFNγ Th1 stimulation in mice.

Chikungunya virus (CHIKV) has been a worldwide threat since its reemergence in La Reunion Island in 2004. Expression of the interferon-stimulated protein Viperin correlates with viral load burden in patients, and studies in mice have demonstrated its role to limit disease severity against CHIKV infection. Using Viperin -/- mice, we aimed to understand the contribution of Viperin to the T-cell immune response against CHIKV. CD4 T-cell depletion in Viperin -/- mice showed that increased late acute joint inflammation (5-8 d postinfection) was exclusively mediated by T cells. Specifically, CHIKV-infected Viperin -/- mice showed an increased INFγ Th1 profile of CD4 T cells, enhanced INFγ stimulation by APCs, an increased INFγ secretion profile in the joint microenvironment, and increased numbers of inflammatory monocytes in virus-infected joints compared with WT mice. Bone marrow grafting experiments showed that Viperin expression in both hematopoietic and non-hematopoietic cells is instrumental in reducing disease severity associated with a CD4 T-cell response.

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.

Hypericum japonicum: a Double-Headed Sword to Combat Vector Control and Cancer.

Mosquito control with naturally derived herbal insecticides has gained much momentum, with the increased insecticide resistance of vectors and the multiple infectious diseases spread by them. Yet, recent studies also suggest that mosquitoes could probably transmit some cancerous cells or cancer-causing viruses from one individual to another between their blood meals. The current research thus focused on the screening and characterization of novel plants with both mosquitocidal and anticancerous properties. Accordingly, different solvent extracts of Hypericum japonicum, a key plant in Chinese medicine, were screened for its larvicidal efficacy using the fourth instar larvae of Aedes aegypti (major vector of Dengue and chikungunya). Methanolic extracts of the plant showed effective larvicidal property with LC50 7.37 ppm and LC9011.59 ppm values. The anticancerous property of the plant extract was also evaluated by in vitro cytotoxicity assay against Daltons Lymphoma Ascites (DLA) cells. The results indicated that H. japonicum plant extracts at very low concentrations of LC500.95 ppm and LC901.85 ppm were potent cytotoxic agents. To the best of our knowledge, this is the first and the foremost report of Hypericum japonicum as a potent mosquitocidal and anticancerous agent. Identification and characterization of such plant-derived bioactive plants thus could serve as a double-headed sword against the spread of infectious diseases and cancer.

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.

Utilization and Assessment of Throat Swab and Urine Specimens for Diagnosis of Chikungunya Virus Infection.

Chikungunya is a mosquito-borne infection with clinical presentation of fever, arthralgia, and rash. The etiological agent Chikungunya virus (CHIKV) is generally transmitted from primates to humans through the bites of infected Aedes aegypti and Aedes albopictus mosquitoes. Outbreaks of Chikungunya occur commonly with varied morbidity, mortality, and sequele according to the epidemiological, ecological, seasonal, and geographical impact. Investigations are required to be conducted as a part of the public health service to understand and report the suspected cases as confirmed by laboratory diagnosis. Holistic sampling at a time of different types would be useful for laboratory testing, result conclusion, and reporting in a valid way. The use of serum samples for virus detection, virus isolation, and serology is routinely practiced, but sometimes serum samples from pediatric and other cases may not be easily available. In such a situation, easily available throat swabs and urine samples could be useful. It is already well reported for measles, rubella, and mumps diseases to have the virus diagnosis from throat swabs and urine. Here, we present the protocols for diagnosis of CHIKV using throat swab and urine specimens.

Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/ß receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from <10% to >30%) and mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

Retrospective survey of Chikungunya disease in Réunion Island hospital staff.

Réunion Island (Indian Ocean) has been suffering from its first known Chikungunya virus (CHIKV) epidemic since February 2005. To achieve a better understanding of the disease, a questionnaire was drawn up for hospital staff members and their household. CHIKV infected about one-third of the studied population, the proportion increasing with age and being higher in women. Presence of a garden was associated with CHIKV infection. The geographical distribution of cases was concordant with insect vector Aedes albopictus distribution. The main clinical signs were arthralgia and fever. The disease evolved towards full recovery in 34.4% of cases, a relapse in 55.6%, or a chronic form in 10%. Paracetamol was used as a painkiller in 95% of cases, sometimes associated with non-steroidal anti-inflammatory drugs, corticoids, or traditional herbal medicine. The survey provided valuable information on the factors that favour transmission, the clinical signs, the importance of relapses and the therapies used.