Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies.

Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines.

Adenovirus vectored IFN-α protects mice from lethal challenge of Chikungunya virus infection.

Chikungunya virus (CHIKV) is a mosquito-borne pathogen that is responsible for numerous large and geographical epidemics, causing millions of cases. However, there is no vaccine or therapeutics against CHIKV infection available. Interferon-alpha (IFN-α) has been shown to produce potent antiviral responses during viral infection. Herein we demonstrated the use of an adenovirus-vectored expressed mouse IFN-α (mDEF201) as a prophylactic and therapeutic treatment against CHIKV in vivo. 6-day-old BALB/c mice were pre- or post-treated intranasally with single dose of mDEF201 at 5 x 106 PFU per mouse and challenged with lethal dose of CHIKV. Complete survival protection was observed in mice upon a single dose of mDEF201 administration 1 days prior to virus challenge. Viral load in the serum and multiple organs were significantly reduced upon mDEF201 administration in a dose dependent manner as compare with adenovirus 5 vector placebo set. Histological analysis of the mice tissue revealed that mDEF201 could significantly reduce the tissue morphological abnormities, mainly infiltration of immune cells and muscle fibre necrosis caused by CHIKV infection. In addition, administration of mDEF201 at 6 hours post CHIKV challenge also showed promising inhibitory effect against viral replication and dissemination. In conclusion, single-dose of intranasal administration with mDEF201 as a prophylactic or therapeutic agent within 6 hours post CHIKV infection is highly protective against a lethal challenge of CHIKV in the murine model.

In vitro and in vivo efficacy of anti-chikungunya virus monoclonal antibodies produced in wild-type and glycoengineered Nicotiana benthamiana plants.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus, and its infection can cause long-term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti-CHIKV monoclonal antibody (mAb) produced in wild-type (WT) and glycoengineered (∆XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in ∆XFT carried a single N-glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N-glycans including the typical plant GnGnXF3 glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ∆XFT plant-produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the ∆XFT-produced mAbs. This is the first report of the efficacy of plant-produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation.

Update on the treatment of musculoskeletal manifestations in chikungunya fever: a guideline

Abstract Since the emergence of the chikungunya virus in Brazil in 2014, more than 700,000 cases have been reported throughout the country, corresponding to one-third of all cases reported in the Americas. In addition to its high attack rates, resulting in hundreds of thousands of cases, the disease has high chronicity rates with persistent joint manifestations for more than 3 months, which can spread to more than half of the patients affected in the acute phase. Pain associated with musculoskeletal manifestations, often disabling, has an effect on patients' quality of life at different stages of the disease. Currently, the challenge faced by specialists is identifying the best therapy to be instituted for symptom relief despite the limited number of published intervention studies. In 2016, a multidisciplinary group published pharmacological treatment protocols for pain in patients with chikungunya, which was incorporated into the guidelines for clinical management of the Brazilian Ministry of Health in 2017; in that same year, a consensus was published by the Brazilian Society of Rheumatology about diagnosis and treatment. After 5 years of experience with chikungunya epidemics, in 2019, specialists involved in the protocols of the Brazilian Society of Rheumatology and Brazilian Ministry of Health prepared an update with the main objective of developing flowcharts for the therapeutic approach of musculoskeletal manifestations in adult patients to enable specialists at different levels of healthcare to spread and apply this guideline in a systematic and simplified manner.

Manejo clínico da suspeita de febre de Chikungunya: conhecimento de profissionais de saúde da atenção básica / Manejo clínico de la fiebre de Chikungunya sospecha: conocimiento de profesionales de salud de atención básica / Clinical management of suspected Chikungunya fever: health professionals knowledge of basic attention

Objetivo: identificar o conhecimento de profissionais de saúde de unidades básicas de saúde da família sobre o manejo clínico da suspeita de febre de Chikungunya. Método: realizou-se um estudo transversal com 31 profissionais de saúde de unidades básicas e saúde da família, localizadas no Município de Quixadá-Ceará, nos meses de janeiro e fevereiro de 2018. Resultados: quase todos relatam que ao avaliar sinais de gravidade, critérios de internação e grupos de risco, se o paciente não apresentar sinais de gravidade, não tiver critérios de internação e/ou condições de risco, o mesmo deve permanecer em acompanhamento ambulatorial; se o paciente for apenas do grupo de risco, o mesmo deve receber acompanhamento ambulatorial em observação; e se o paciente apresentar sinais de gravidade e/ou tiver critérios de internação, ele deve receber acompanhamento em internação. Conclusão: os profissionais de saúde possuem conhecimento satisfatório sobre o manejo clínico da doença baseado nas orientações do Ministério da Saúde

Objective: to identify the knowledge of health professionals of family health basic units on the clinical management of suspected chikungunya fever. Method: a cross-sectional study with 31 healthcare professionals of basic units and family health, located in the city of Quixadá - Ceará, in the months of January and February 2018. Results: almost all report to evaluate signs of severity, admission criteria and risk groups, if the patient does not show signs of seriousness does not meet criteria for hospitalization and risk conditions/or should stay in outpatient follow-up; If the patient is only a risk group, he/she must be referred to outpatient follow-up for observation; and if the patient shows signs of severity and/or admission criteria, he should receive follow-up in hospital. Conclusion: health professionals have satisfactory knowledge on the clinical management of the disease based on the guidelines of the Ministry of Health

Objetivo: identificar el conocimiento de la salud profesionales de unidades básicas de salud de la familiaenel manejo clínico de só pecha Chikungunya fiebre. Método: estudio transversal con 31 profesionales de la salud de unidades básicas y de salud familiar, ubicado em la ciudad de Quixadá - Ceará, em los meses de enero y febrero de 2018. Resultados: informe casi todos para evaluar signos de gravedad, grupos de criterios de admisión y el riesgo, si el paciente no no mostrar signos de seriedad no tienen criterios para las condiciones de la hospitalización y el riesgo/unidad organizativa, debe mantenerse en seguimiento ambulatorio; Si el paciente es sóloel grupo de riesgo, el mismo debe recibir seguimento ambulatorio de observación; y si el paciente muestra signos de criterios de severidad y/o admisión, deben recibir seguimento em hospitalización. Conclusión: profesionales de la salud tienen conocimiento satisfactorio em el manejo clínico de la enfermedad basada en las directrices del Ministerio de Salud

Chikungunya in a kidney transplant recipient: a case report / Chikungunya em um receptor de transplante renal: relato de caso

ABSTRACT In 2004, a global spread of Chikungunya fever affected most tropical and subtropical regions of the world. In 2016, an outbreak occurred in Northeast Brazil with hundreds of cases documented. Solid organ transplant recipients have a modified immune response to infection and the clinical course is usually different from immunocompetent patients. The diagnosis can be challenging in this population. Most reports describe patients residing in endemic areas, although we must emphasize the importance of differential diagnosis in kidney transplanted travelers who visit endemic regions, such as Northeast Brazil. Here, we reported a case of a kidney transplant recipient that acquired Chikungunya fever after a trip to an endemic region at Northeast Brazil during the outbreak in 2016, with a good clinical evolution. We also present warning recommendations for travelers to endemic areas as additional measures to prevent disease outbreaks.

RESUMO Em 2004, um surto global de Chikungunya afetou a maioria das regiões tropicais e subtropicais do mundo. Em 2016, um surto ocorreu no Nordeste do Brasil com centenas de casos documentados. Receptores de transplantes de órgãos sólidos têm uma resposta imune modificada à infecção, e o curso clínico é geralmente diferente daquele em pacientes imunocompetentes. O diagnóstico pode ser desafiador nessa população. A maioria dos relatos descreve pacientes residentes em áreas endêmicas, embora devamos enfatizar a importância do diagnóstico diferencial em viajantes transplantados renais que visitam regiões endêmicas, como o Nordeste do Brasil. Aqui, nós relatamos o caso de um receptor de transplante renal que adquiriu febre Chikungunya após uma viagem a uma região endêmica no Nordeste do Brasil durante o surto de 2016, com uma boa evolução clínica. Também apresentamos recomendações de alerta para viajantes em áreas endêmicas, como medidas adicionais para prevenir surtos de doenças.

Chikungunya: educación y prevención como pilares fundamentales para enfermedad sin cura / Chikungunya: education and prevention as fundamental support for disease without cure

Chikungunya virus is an alphavirus, member of the Togaviridae family, first discovered in Africa in 1952. Since then it caused sporadic outbreaks in Africa and Asia, but since 2000, outbreaks had been more frequent, being identified in Europe, America and the Caribbean. Chikungunya virus can cause chronic and incapacitating arthralgia, with an important morbidity, being considered as a relevant re-emerging public health problem. This review intends to update our knowledge in epidemiology, transmission, pathogenesis, treatment and vaccination strategies of Chikungunya virus. (AU)

Cellular and Molecular Immune Response to Chikungunya Virus Infection.

Chikungunya virus (CHIKV) is a re-emergent arthropod-borne virus (arbovirus) that causes a disease characterized primarily by fever, rash and severe persistent polyarthralgia. In the last decade, CHIKV has become a serious public health problem causing several outbreaks around the world. Despite the fact that CHIKV has been around since 1952, our knowledge about immunopathology, innate and adaptive immune response involved in this infectious disease is incomplete. In this review, we provide an updated summary of the current knowledge about immune response to CHIKV and about soluble immunological markers associated with the morbidity, prognosis and chronicity of this arbovirus disease. In addition, we discuss the progress in the research of new vaccines for preventing CHIKV infection and the use of monoclonal antibodies as a promising therapeutic strategy.

A recombinant virus vaccine that protects against both Chikungunya and Zika virus infections.

Chikungunya virus (CHIKV) and Zika virus (ZIKV) have recently expanded their range in the world and caused serious and widespread outbreaks of near pandemic proportions. There are no licensed vaccines that protect against these co-circulating viruses that are transmitted by invasive mosquito vectors. We report here on the development of a single-dose, bivalent experimental vaccine for CHIKV and ZIKV. This vaccine is based on a chimeric vesicular stomatitis virus (VSV) that expresses the CHIKV envelope polyprotein (E3-E2-6K-E1) in place of the VSV glycoprotein (G) and also expresses the membrane-envelope (ME) glycoproteins of ZIKV. This vaccine induced neutralizing antibody responses to both CHIKV and ZIKV in wild-type mice and in interferon receptor-deficient A129 mice, animal models for CHIKV and ZIKV infection. A single vaccination of A129 mice with the vector protected these mice against infection with both CHIKV and ZIKV. Our single-dose vaccine could provide durable, low-cost protection against both CHIKV and ZIKV for people traveling to or living in areas where both viruses are circulating, which include most tropical regions in the world.

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.

Perfil e sintomas apresentados por pacientes com febre Chikungunya notificados em uma unidade de pronto atendimento: contribuição para a equipe de enfermagem / Profile and symptoms presented by patients with Chikungunya fever reported in a ready service unit: contribution to the nursing team

Objetivo: identificar o perfil dos pacientes por idade, sexo e sintomatologia como também analisar a área de abrangênciadas notificações realizadas pela Unidade de Pronto Atendimento. Método: trata-se de uma pesquisa descritiva, com abordagemquantitativa, com corte transversal e dados secundários. A coleta foi realizada por meio das fichas de notificação incluídas noSistema de Informação de Agravos de Notificação. Registros notificados no período de novembro/2015 a fevereiro/2016. Apopulação e amostra foram as mesmas 230 notificações. Resultados: quando avaliada a variável faixa etária mais acometida,percebe-se que esta corresponde às idades entre 30 e 40 anos incompletos, com 22,61% (n=52). Ao ser analisado o sexo,observou-se a predominância do feminino, com 58,85% (n=133) das notificações. Quando analisada a variável sintoma artralgia,observa-se 94,78% (n=218). Considerações: é necessário o treinamento das equipes de saúde para atendimento da população.

Chikungunya virus: clinical aspects and treatment: a review

Chikungunya is a severe and debilitating disease. Currently, Brazil is experiencing an epidemic caused by three arboviruses, which has changed the way health professionals have diagnosed and treated infected patients. The difficulty of diagnosis and the lack of a protocol for patient treatment, which fits Brazilian health system models, have made it difficult to manage this disease. It is necessary to implement a multidisciplinary network of patient care, in which primary care units play the main role. This review aims to present current information regarding the clinical aspects and treatment of Chikungunya virus infection.

Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations / Recomendações da Sociedade Brasileira de Reumatologia para diagnóstico e tratamento da febre chikungunya. Parte 1 - Diagnóstico e situações especiais

Abstract Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.

Resumo A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias. Até 2013, as Américas haviam registrado apenas casos importados quando, em outubro desse mesmo ano, foram notificados os primeiros casos na Ilha de Saint Martin, no Caribe. No Brasil, os primeiros relatos autóctones foram confirmados em setembro de 2014 e até a semana epidemiológica 37 de 2016 já haviam sido registrados 236.287 casos prováveis de infecção pelo chikungunya vírus (CHIKV), 116.523 confirmados sorologicamente. As mudanças ambientais causadas pelo homem, o crescimento urbano desordenado e o número cada vez maior de viagens internacionais têm sido apontados como os fatores responsáveis pela reemergência de epidemias em grande escala. Caracterizada clinicamente por febre e dor articular na fase aguda, em cerca de metade dos casos existe evolução para a fase crônica (além de três meses), com dor persistente e incapacitante. O objetivo deste trabalho foi elaborar recomendações para diagnóstico e tratamento da febre chikungunya no Brasil. Para isso, foi feita revisão da literatura nas bases de dados Medline, SciELO e PubMed, para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Foram geradas 25 recomendações, divididas em três grupos temáticos: (1) diagnóstico clínico, laboratorial e por imagem; (2) situações especiais e (3) tratamento. Na primeira parte estão os dois primeiros temas e o tratamento na segunda.

Physiotherapeutic approach on the late phase of chikungunya: a case report / Abordagem fisioterapêutica na fase tardia da chikungunya: um relato de caso

Abstract Introduction: in April of 2016, the epidemiological bulletin reported 39,017 suspected cases of chikungunya fever in Brazil. The main symptoms of the disease in the acute phase are: high fever, polyarthralgia, back pain, headache and fatigue; while in the late phase present polyarthralgia or musculoskeletal pain which often has prolonged duration. Description: in the late phase, the patient presented complaints mainly of: severe pain on the ankle joints wrists, elbows and shoulders. The medical handling consisted of continuous ultrasound sessions with the frequency of 1 MHz. The infrared laser with a dosage of 4J and 3s per point; TENS-burst with a pulse width of 250 us and the frequency of 2Hz, carried out for 10 days. The physiotherapeutic treatment proposal was an innovation, however there are no medical literatures for completementary medication for the treatment which could reduce the use of analgesics and could cause prolonged comfort to the patient ratified by EVA and the SF-36. Discussion: the use of ultrasound and low intensity laser are performed on the signs of chronic articular treatment in order to reduce inflammation, pain and joint stiffness. Therefore, a remarkable reduction of the algic state and the improvement of the patient's life along the r ten consecutive sessions of a proposed protocol in this study, thus there is a need for further researches on this issue so it is possible to perform a medical handling based on evidences on the theme.

Resumo Introdução: o boletim epidemiológico de abril de 2016 informou 39.017 casos prováveis de febre de chikungunya no país. Na fase aguda da doença os principais sintomas são: febre alta, poliartralgia, dores nas costas, dor de cabeça e fadiga; enquanto que na fase tardia estão presentes a poliartralgia ou dores músculo-esqueléticas, que frequentemente apresentam-se com duração prolongada. Descrição: o paciente apresentava na fase tardia como principais queixas: dores severas nas articulações dos tornozelos, punhos, cotovelos e ombros. O manejo clínico foi constituído de sessões com ultrassom contínuo com frequência de 1 MHz, Laser infravermelho com dosagem de 4J e 3s por ponto; TENS-burst com largura de pulso de 250 us e Frequência de 2Hz, realizado por 10 dias. O tratamento fisioterapêutico proposto foi inovador, pois não há na literatura tratamentos complementares que possam diminuir o uso de analgésicos e causar conforto prolongado ao paciente ratificado pelo EVA e o SF-36. Discussão: o uso do ultrassom e do laser de baixa intensidade são utilizados no tratamento de manifestações reumáticas crônicas com o objetivo de reduzir a inflamação, dor e rigidez articular. Por conseguinte, foi notável a redução do quadro álgico e melhora da qualidade de vida da paciente ao longo de dez sessões consecutivas com o protocolo proposto no presente estudo, sendo assim surge à necessidade de novas pesquisas acerca do assunto para que seja possível fazer um manejo clínico baseado em evidências sobre o tema.

Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus.

Chikungunya virus (CHIKV) is a mosquito-transmitted RNA virus that causes acute febrile infection associated with polyarthralgia in humans. Mechanisms of protective immunity against CHIKV are poorly understood, and no effective therapeutics or vaccines are available. We isolated and characterized human monoclonal antibodies (mAbs) that neutralize CHIKV infectivity. Among the 30 mAbs isolated, 13 had broad and ultrapotent neutralizing activity (IC50 < 10 ng/ml), and all of these mapped to domain A of the E2 envelope protein. Potent inhibitory mAbs blocked post-attachment steps required for CHIKV membrane fusion, and several were protective in a lethal challenge model in immunocompromised mice, even when administered at late time points after infection. These highly protective mAbs could be considered for prevention or treatment of CHIKV infection, and their epitope location in domain A of E2 could be targeted for rational structure-based vaccine development.

Control of immunopathology during chikungunya virus infection.

After several decades of epidemiologic silence, chikungunya virus (CHIKV) has recently re-emerged, causing explosive outbreaks and reaching the 5 continents. Transmitted through the bite of Aedes species mosquitoes, CHIKV is responsible for an acute febrile illness accompanied by several characteristic symptoms, including cutaneous rash, myalgia, and arthralgia, with the latter sometimes persisting for months or years. Although CHIKV has previously been known as a relatively benign disease, more recent epidemic events have brought waves of increased morbidity and fatality, leading it to become a serious public health problem. The host's immune response plays a crucial role in controlling the infection, but it might also contribute to the promotion of viral spread and immunopathology. This review focuses on the immune responses to CHIKV in human subjects with an emphasis on early antiviral immune responses. We assess recent developments in the understanding of their possible Janus-faced effects in the control of viral infection and pathogenesis. Although preventive vaccination and specific therapies are yet to be developed, exploring this interesting model of virus-host interactions might have a strong effect on the design of novel therapeutic options to minimize immunopathology without impairing beneficial host defenses.

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...

Chikungunya virus glycoproteins pseudotype with lentiviral vectors and reveal a broad spectrum of cellular tropism.

BACKGROUND: Outbreaks of the Chikungunya virus (CHIKV) infection has been documented in over 40 countries, resulting in clinical symptoms characterized by fever and joint pain. Diagnosing CHIKV in a clinical lab setting is often omitted because of the high lab safety requirement. An infection system that mimics CHIKV infection will permit clinical evaluation of the production of neutralizing antibody for both disease diagnostics and treatment. METHODOLOGY/PRINCIPAL FINDINGS: We generated a CHIKV construct expressing CHIKV structural proteins. This construct permits the production of CHIKV pseudo-viral particles with a luciferase reporter. The pseudo-virus was able to infect a wide range of cell lines. The pseudovirus could be neutralized by the addition of neutralizing antibodies from patients. CONCLUSIONS: Taken together, we have developed a powerful system that can be handled at biosafety level 2 laboratories for evaluation of existence of CHIKV neutralizing antibodies.