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Sample records for chikungunya viruses imported

  1. Chikungunya Virus

    MedlinePlus

    ... traveling to countries with chikungunya virus, use insect repellent, wear long sleeves and pants, and stay in ... Chikungunya Prevention is key! Prevent Infection. Use mosquito repellent. Chikungunya Virus Distribution Chikungunya in the U.S. What's ...

  2. The First Imported Case Infected with Chikungunya Virus in Korea

    PubMed Central

    2015-01-01

    Chikungunya is caused by an arbovirus transmitted by Aedes mosquito vector. With the increase of habitat of mosquito by global warming and frequent international travel and interchange, chikungunya reemerged and showed global distribution recently. Until now there has not been reported any case infected with chikungunya virus in Korea. A 23-year-old man has been the Republic of the Philippines for 1 week, and visited our emergency center due to fever and back pain. Chikungunya viral infection was diagnosed by specific IgM for chickungunya virus by enzyme-linked immunosorbent assayin Korea Centers for Disease Control and Prevention. His clinical course was self limited. We introduce the first imported case infected with chikungunya virus in Korea. PMID:25844264

  3. Chikungunya virus

    MedlinePlus

    ... first time in the Americas in the Caribbean Islands. In the Americas, local transmission of the disease ... in Florida, Puerto Rico, and the U.S. Virgin Islands. How Chikungunya can spread Mosquitoes spread the virus ...

  4. Lymphadenopathy in Patients With Chikungunya Virus Infection Imported From Hispaniola: Case Reports.

    PubMed

    Norman, Francesca F; Monge-Maillo, Begoña; Perez-Molina, Jose-Antonio; de Ory, Fernando; Franco, Leticia; Sánchez-Seco, María-Paz; López-Vélez, Rogelio

    2015-01-01

    Chikungunya virus (CHIKV) is currently spreading in the Caribbean and America. Lymphadenopathy, described in infections with other alphaviruses, is not commonly reported in CHIKV infections. Painful lymphadenopathy was found in three of the first six CHIKV infections from the current outbreak diagnosed at a reference center in Madrid, Spain.

  5. An overview of Chikungunya virus.

    PubMed

    Busch, Mitchell; Erickson, Gerald

    2015-10-01

    Chikungunya fever is a viral infection caused by the Chikungunya virus that causes abrupt onset of fever, debilitating arthralgias and myalgias, and some rare but serious atypical presentations in infected patients. This mosquito-borne virus may not be familiar to North American healthcare providers. This article describes the causes, epidemiology, pathophysiology, clinical presentation, diagnostic and screening measures, management guidelines, and future research prospects for Chikungunya infection.

  6. Imported chikungunya fever in Madrid.

    PubMed

    Richi Alberti, Patricia; Steiner, Martina; Illera Martín, Óscar; Alcocer Amores, Patricia; Cobo Ibáñez, Tatiana; Muñoz Fernández, Santiago

    2016-01-01

    Chikungunya Fever is a mosquito-transmitted viral disease that causes fever, rash and musculoskeletal complaints. The latest may persist for several months, or even years or developed a relapsing course, that deserve an adequate treatment. Due to the large outbreak declared in the Caribbean in 2013, imported cases of Chikungunya as well as the risk of autochthonous transmission in case of available vectors have increased in non-endemic countries, like Spain. We described four cases of Chikungunya treated in our clinic.

  7. Trends in imported chikungunya virus infections in Germany, 2006-2009.

    PubMed

    Frank, Christina; Schöneberg, Irene; Stark, Klaus

    2011-06-01

    Chikungunya virus (CHIKV) has been previously reported in many African and Asian areas, but it recently reemerged strongly in countries bordering the Indian Ocean as well as caused an outbreak in northern Italy. In Germany, where potential CHIKV vectors are not yet established, CHIKV infection is mandatorily notifiable. Cases reported from 2006 through 2009 were analyzed for travel characteristics and demographic factors. 152 cases of symptomatic CHIKV infection were notified. Both sexes were affected, with a median age of 46 years. Over the years, countries of infection largely followed the outbreaks reported from various travel destinations. India and the Maldives were the countries of infection most frequently named. In Sri Lanka, India, and Thailand, which are also frequently named countries of infection for dengue virus, the median age of CHIKV-affected patients was higher than that of dengue fever patients. Taking traveler numbers into consideration, risk of CHIKV infection was higher in the Seychelles and Mauritius than in Thailand and India. Even though substantial underdiagnosis is suspected, this assessment of CHIKV importation to Germany offers valuable information about the details of travel-associated cases. Between 17 and 53 notified cases per year signify that CHIKV would be occasionally available for local transmission in Germany once a vector becomes present. Although CHIKV most often causes a comparatively mild disease, the high median age of notified cases and the higher age than dengue patients support more severe disease courses in older adults. Travelers to all CHIKV endemic areas should protect against mosquito bites. In Germany, CHIKV surveillance will be continued to monitor ongoing importation of the virus and to detect early potential autochthonous cases.

  8. Complete Genome Sequences of Chikungunya Virus Strains Isolated in Mexico: First Detection of Imported and Autochthonous Cases

    PubMed Central

    Ortiz-Alcántara, Joanna; Fragoso-Fonseca, David Esaú; Garcés-Ayala, Fabiola; Escobar-Escamilla, Noé; Vázquez-Pichardo, Mauricio; Núñez-León, Alma; Torres-Rodríguez, María de la Luz; Torres-Longoria, Belem; López-Martínez, Irma; Ruíz-Matus, Cuitláhuac; Kuri-Morales, Pablo; Ramírez-González, José Ernesto

    2015-01-01

    The mosquito-borne chikungunya virus, an alphavirus of the Togaviridae family, is responsible for acute polyarthralgia epidemics. Here, we report the complete genome sequences of two chikungunya virus strains, InDRE04 and InDRE51, identified in the Mexican states of Jalisco and Chiapas in 2014. Phylogenetic analysis showed that both strains belong to the Asian genotype. PMID:25953170

  9. First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean

    PubMed Central

    Therrien, Christian; Jourdan, Guillaume; Holloway, Kimberly; Tremblay, Cécile; Drebot, Michael A.

    2016-01-01

    This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas. PMID:27366163

  10. First Imported Case of Chikungunya Virus Infection in a Travelling Canadian Returning from the Caribbean.

    PubMed

    Therrien, Christian; Jourdan, Guillaume; Holloway, Kimberly; Tremblay, Cécile; Drebot, Michael A

    2016-01-01

    This is the first Canadian case of Chikungunya virus (CHIKV) infection reported in a traveller returning from the Caribbean. Following multiple mosquito bites in Martinique Island in January 2014, the patient presented with high fever, headaches, arthralgia on both hands and feet, and a rash on the trunk upon his return to Canada. Initial serological testing for dengue virus infection was negative. Support therapy with nonsteroidal anti-inflammatory drugs was administered. The symptoms gradually improved 4 weeks after onset with residual arthralgia and morning joint stiffness. This clinical feature prompted the clinician to request CHIKV virus serology which was found to be positive for the presence of IgM and neutralizing antibodies. In 2014, over four hundred confirmed CHIKV infection cases were diagnosed in Canadian travellers returning from the Caribbean and Central America. Clinical suspicion of CHIKV or dengue virus infections should be considered in febrile patients with arthralgia returning from the recently CHIKV endemic countries of the Americas.

  11. New approaches to chikungunya virus vaccine development.

    PubMed

    Garcia, Alexis; Diego, Lema; Judith, Barroso

    2015-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne human pathogen that affects millions of individuals each year by causing non-specific flu-like symptoms, with a characteristic rash accompanied by joint pain that may last for a long time after the resolution of the infection. Despite intense research efforts, no approved vaccine or antiviral therapy is yet available. This review is based on articles retrieved by PubMed and clinical trials since 1980 to present. Virus complexity, protective and non-protective immune responses against the virus, and the most important a new patented approaches for Chikungunya vaccine development are discussed.

  12. Chikungunya virus infection.

    PubMed

    Sam, I-C; AbuBakar, S

    2006-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus which causes epidemic fever, rash and polyarthralgia in Africa and Asia. Two outbreaks have been reported in Malaysia, in Klang, Selangor (1998) and Bagan Panchor, Perak (2006). It is not known if the outbreaks were caused by the recent introduction of CHIKV, or if the virus was already circulating in Malaysia. Seroprevalence studies from the 1960s suggested previous disease activity in certain parts of the country. In Asia, CHIKV is thought to be transmitted by the same mosquitoes as dengue, Aedes aegypti and Ae. albopictus. Due to similarities in clinical presentation with dengue, limited awareness, and a lack of laboratory diagnostic capability, CHIKV is probably often underdiagnosed or misdiagnosed as dengue. Treatment is supportive. The prognosis is generally good, although some patients experience chronic arthritis. With no vaccine or antiviral available, prevention and control depends on surveillance, early identification of outbreaks, and vector control. CHIKV should be borne in mind in sporadic cases, and in patients epidemiologically linked to ongoing local or international outbreaks or endemic areas.

  13. [Reemergence of Chikungunya virus].

    PubMed

    Weibel Galluzzo, C; Kaiser, L; Chappuis, F

    2015-05-01

    Arboviral diseases transmitted by mosquitoes such as Dengue, Chikungunya and West Nile are global health issues of growing magnitude. Their dissemination in new areas is triggered by increased mobility of persons, animal reservoirs and vectors. This article describes virological, epidemiological and clinical aspects of Chikungunya, which causes sporadic cases or epidemics, sometimes massive, such as the one spreading in the Americas since December 2013. Chikungunya should be suspected in all travellers presenting with fever, arthralgia and sometimes a rash returning from an endemic area. In the absence of vaccine, individual protection relies on the prevention of mosquito bites.

  14. Chikungunya

    MedlinePlus

    Chikungunya is a virus that spread by the same kinds of mosquitoes that spread dengue and Zika ... through infected blood. There have been outbreaks of chikungunya virus in Africa, Asia, Europe, the Indian and ...

  15. Towards antivirals against chikungunya virus.

    PubMed

    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2015-09-01

    Chikungunya virus (CHIKV) has re-emerged in recent decades, causing major outbreaks of chikungunya fever in many parts of Africa and Asia, and since the end of 2013 also in Central and South America. Infections are usually associated with a low mortality rate, but can proceed into a painful chronic stage, during which patients may suffer from polyarthralgia and joint stiffness for weeks and even several years. There are no vaccines or antiviral drugs available for the prevention or treatment of CHIKV infections. Current therapy therefore consists solely of the administration of analgesics, antipyretics and anti-inflammatory agents to relieve symptoms. We here review molecules that have been reported to inhibit CHIKV replication, either as direct-acting antivirals, host-targeting drugs or those that act via a yet unknown mechanism. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."

  16. Chikungunya virus was isolated in Thailand, 2010.

    PubMed

    Sasayama, Mikiko; Benjathummarak, Surachet; Kawashita, Norihito; Rukmanee, Prasert; Sangmukdanun, Suntaree; Masrinoul, Promsin; Pitaksajjakul, Pannamthip; Puiprom, Orapim; Wuthisen, Pitak; Kurosu, Takeshi; Chaichana, Panjaporn; Maneekan, Pannamas; Ikuta, Kazuyoshi; Ramasoota, Pongrama; Okabayashi, Tamaki; Singhasivanon, Pratap; Luplertlop, Natthanej

    2014-12-01

    Chikungunya fever (CHIKF) is an acute febrile illness caused by a mosquito-borne alphavirus, chikungunya virus (CHIKV). This disease re-emerged in Kenya in 2004, and spread to the countries in and around the Indian Ocean. The re-emerging epidemics rapidly spread to regions like India and Southeast Asia, and it was subsequently identified in Europe in 2007, probably as a result of importation of chikungunya cases. On the one hand, chikungunya is one of the neglected diseases and has only attracted strong attention during large outbreaks. In 2008-2009, there was a major outbreak of chikungunya fever in Thailand, resulting in the highest number of infections in any country in the region. However, no update of CHIKV circulating in Thailand has been published since 2009. In this study, we examined the viral growth kinetics and sequences of the structural genes derived from CHIKV clinical isolates obtained from the serum specimens of CHIKF-suspected patients in Central Thailand in 2010. We identified the CHIKV harboring two mutations E1-A226V and E2-I211T, indicating that the East, Central, and South African lineage of CHIKV was continuously circulating as an indigenous population in Thailand.

  17. Antiviral perspectives for chikungunya virus.

    PubMed

    Parashar, Deepti; Cherian, Sarah

    2014-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne pathogen that has a major health impact in humans and causes acute febrile illness in humans accompanied by joint pains and, in many cases, persistent arthralgia lasting for weeks to years. CHIKV reemerged in 2005-2006 in several parts of the Indian Ocean islands and India after a gap of 32 years, causing millions of cases. The re-emergence of CHIKV has also resulted in numerous outbreaks in several countries in the eastern hemisphere, with a threat to further expand in the near future. However, there is no vaccine against CHIKV infection licensed for human use, and therapy for CHIKV infection is still mainly limited to supportive care as antiviral agents are yet in different stages of testing or development. In this review we explore the different perspectives for chikungunya treatment and the effectiveness of these treatment regimens and discuss the scope for future directions.

  18. Chikungunya virus: emerging targets and new opportunities for medicinal chemistry.

    PubMed

    Rashad, Adel A; Mahalingam, Suresh; Keller, Paul A

    2014-02-27

    Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa and Asia and documented outbreaks in Europe and the Americas. It is having an increasingly major impact on humankind, with potentially life-threatening and debilitating arthritis. There is no treatment available, and only in the past 24 months have lead compounds for development as potential therapeutics been reported. This Perspective discusses the chikungunya virus as a significant, new emerging topic for medicinal chemistry, highlighting the key viral target proteins and their molecular functions that can be used in drug design, as well as the most important ongoing developments for anti-chikungunya virus research. It represents a complete picture of the current medicinal chemistry of chikungunya, supporting the development of chemotherapeutics through drug discovery and design targeting this virus.

  19. Chikungunya virus pathogenesis and immunity.

    PubMed

    Gasque, Philippe; Couderc, Therese; Lecuit, Marc; Roques, Pierre; Ng, Lisa F P

    2015-04-01

    Chikungunya virus (CHIKV) is an arbovirus associated with acute and chronic arthralgia that re-emerged in the Indian Ocean islands in 2005-2006 and is currently responsible for the ongoing outbreaks in the Caribbean islands and the Americas. We describe here the acute and chronic clinical manifestations of CHIKV in patients that define the disease. We also review the various animal models that have been developed to study CHIKV infection and pathology and further strengthened the understanding of the cellular and molecular mechanisms of CHIKV infection and immunity. A complete understanding of the immunopathogenesis of CHIKV infection will help develop the needed preventive and therapeutic approaches to combat this arbovirosis.

  20. Chikungunya Virus Infection of Aedes Mosquitoes.

    PubMed

    Wong, Hui Vern; Chan, Yoke Fun; Sam, I-Ching; Sulaiman, Wan Yusof Wan; Vythilingam, Indra

    2016-01-01

    In vivo infection of mosquitoes is an important method to study and characterize arthropod-borne viruses. Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is transmitted primarily by Aedes mosquitoes. In this chapter, we describe a protocol for infection of CHIKV in two species of Aedes mosquitoes, Aedes aegypti and Aedes albopictus, together with the isolation of CHIKV in different parts of the infected mosquito such as midgut, legs, wings, salivary gland, head, and saliva. This allows the study of viral infection, replication and dissemination within the mosquito vector. PMID:27233266

  1. Antiviral activity of silymarin against chikungunya virus.

    PubMed

    Lani, Rafidah; Hassandarvish, Pouya; Chiam, Chun Wei; Moghaddam, Ehsan; Chu, Justin Jang Hann; Rausalu, Kai; Merits, Andres; Higgs, Stephen; Vanlandingham, Dana; Abu Bakar, Sazaly; Zandi, Keivan

    2015-06-16

    The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection.

  2. The Global Virus Network: Challenging chikungunya

    PubMed Central

    McSweegan, Edward; Weaver, Scott C.; Lecuit, Marc; Frieman, Matthew; Morrison, Thomas E.; Hrynkow, Sharon

    2016-01-01

    The recent spread of chikungunya virus to the Western Hemisphere, together with the ongoing Ebola epidemic in West Africa, have highlighted the importance of international collaboration in the detection and management of disease outbreaks. In response to this need, the Global Virus Network (GVN) was formed in 2011. The GVN is a coalition of leading medical virologists in 34 affiliated laboratories in 24 countries, who collaborate to share their resources and expertise. The GVN supports research, promotes training for young scientists, serves as a technical resource for governments, businesses and international organizations, facilitates international scientific cooperation, and advocates for funding and evidence-based public policies. In response to the spread of chikungunya, the GVN formed a task force to identify research gaps and opportunities, including models of infection and disease, candidate vaccines and antivirals, epidemiology and vector control measures. Its members also serve as authoritative sources of information for the public, press, and policy-makers. This article forms part of a symposium in Antiviral Research on “Chikungunya discovers the New World”. PMID:26071007

  3. Antiviral Strategies Against Chikungunya Virus.

    PubMed

    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2016-01-01

    In the last few decades the Chikungunya virus (CHIKV) has evolved from a geographically isolated pathogen to a virus that is widespread in many parts of Africa, Asia and recently also in Central- and South-America. Although CHIKV infections are rarely fatal, the disease can evolve into a chronic stage, which is characterized by persisting polyarthralgia and joint stiffness. This chronic CHIKV infection can severely incapacitate patients for weeks up to several years after the initial infection. Despite the burden of CHIKV infections, no vaccine or antivirals are available yet. The current therapy is therefore only symptomatic and consists of the administration of analgesics, antipyretics, and anti-inflammatory agents. Recently several molecules with various viral or host targets have been identified as CHIKV inhibitors. In this chapter, we summarize the current status of the development of antiviral strategies against CHIKV infections.

  4. Antiviral Strategies Against Chikungunya Virus.

    PubMed

    Abdelnabi, Rana; Neyts, Johan; Delang, Leen

    2016-01-01

    In the last few decades the Chikungunya virus (CHIKV) has evolved from a geographically isolated pathogen to a virus that is widespread in many parts of Africa, Asia and recently also in Central- and South-America. Although CHIKV infections are rarely fatal, the disease can evolve into a chronic stage, which is characterized by persisting polyarthralgia and joint stiffness. This chronic CHIKV infection can severely incapacitate patients for weeks up to several years after the initial infection. Despite the burden of CHIKV infections, no vaccine or antivirals are available yet. The current therapy is therefore only symptomatic and consists of the administration of analgesics, antipyretics, and anti-inflammatory agents. Recently several molecules with various viral or host targets have been identified as CHIKV inhibitors. In this chapter, we summarize the current status of the development of antiviral strategies against CHIKV infections. PMID:27233277

  5. Detection of chikungunya virus antigen by a novel rapid immunochromatographic test.

    PubMed

    Okabayashi, Tamaki; Sasaki, Tadahiro; Masrinoul, Promsin; Chantawat, Nantarat; Yoksan, Sutee; Nitatpattana, Narong; Chusri, Sarunyou; Morales Vargas, Ronald E; Grandadam, Marc; Brey, Paul T; Soegijanto, Soegeng; Mulyantno, Kris Cahyo; Churrotin, Siti; Kotaki, Tomohiro; Faye, Oumar; Faye, Ousmane; Sow, Abdourahmane; Sall, Amadou Alpha; Puiprom, Orapim; Chaichana, Panjaporn; Kurosu, Takeshi; Kato, Seiji; Kosaka, Mieko; Ramasoota, Pongrama; Ikuta, Kazuyoshi

    2015-02-01

    Chikungunya fever is a mosquito-borne disease of key public health importance in tropical and subtropical countries. Although severe joint pain is the most distinguishing feature of chikungunya fever, diagnosis remains difficult because the symptoms of chikungunya fever are shared by many pathogens, including dengue fever. The present study aimed to develop a new immunochromatographic diagnosis test for the detection of chikungunya virus antigen in serum. Mice were immunized with isolates from patients with Thai chikungunya fever, East/Central/South African genotype, to produce mouse monoclonal antibodies against chikungunya virus. Using these monoclonal antibodies, a new diagnostic test was developed and evaluated for the detection of chikungunya virus. The newly developed diagnostic test reacted with not only the East/Central/South African genotype but also with the Asian and West African genotypes of chikungunya virus. Testing of sera from patients suspected to have chikungunya fever in Thailand (n = 50), Laos (n = 54), Indonesia (n = 2), and Senegal (n = 6) revealed sensitivity, specificity, and real-time PCR (RT-PCR) agreement values of 89.4%, 94.4%, and 91.1%, respectively. In our study using serial samples, a new diagnostic test showed high agreement with the RT-PCR within the first 5 days after onset. A rapid diagnostic test was developed using mouse monoclonal antibodies that react with chikungunya virus envelope proteins. The diagnostic accuracy of our test is clinically acceptable for chikungunya fever in the acute phase.

  6. Large number of imported chikungunya cases in mainland France, 2014: a challenge for surveillance and response.

    PubMed

    Paty, M C; Six, C; Charlet, F; Heuzé, G; Cochet, A; Wiegandt, A; Chappert, J L; Dejour-Salamanca, D; Guinard, A; Soler, P; Servas, V; Vivier-Darrigol, M; Ledrans, M; Debruyne, M; Schaal, O; Jeannin, C; Helynck, B; Leparc-Goffart, I; Coignard, B

    2014-01-01

    During the summer of 2014, all the pre-requisites for autochthonous transmission of chikungunya virus are present in southern France: a competent vector, Aedes albopictus, and a large number of travellers returning from the French Caribbean islands where an outbreak is occurring. We describe the system implemented for the surveillance of chikungunya and dengue in mainland France. From 2 May to 4 July 2014, there were 126 laboratory-confirmed imported chikungunya cases in mainland France.

  7. Infectious Viral Quantification of Chikungunya Virus-Virus Plaque Assay.

    PubMed

    Kaur, Parveen; Lee, Regina Ching Hua; Chu, Justin Jang Hann

    2016-01-01

    The plaque assay is an essential method for quantification of infectious virus titer. Cells infected with virus particles are overlaid with a viscous substrate. A suitable incubation period results in the formation of plaques, which can be fixed and stained for visualization. Here, we describe a method for measuring Chikungunya virus (CHIKV) titers via virus plaque assays.

  8. Myeloradiculopathy associated with chikungunya virus infection.

    PubMed

    Bank, Anna M; Batra, Ayush; Colorado, Rene A; Lyons, Jennifer L

    2016-02-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is endemic to parts of Africa, South and Southeast Asia, and more recently the Caribbean. Patients typically present with fever, rash, and arthralgias, though neurologic symptoms, primarily encephalitis, have been described. We report the case of a 47-year-old woman who was clinically diagnosed with CHIKV while traveling in the Dominican Republic and presented 10 days later with left lower extremity weakness, a corresponding enhancing thoracic spinal cord lesion, and positive CHIKV serologies. She initially responded to corticosteroids, followed by relapsing symptoms and gradual clinical improvement. The time lapse between acute CHIKV infection and the onset of myelopathic sequelae suggests an immune-mediated phenomenon rather than direct activity of the virus itself. Chikungunya virus should be considered in the differential diagnosis of myelopathy in endemic areas. The progression of symptoms despite corticosteroid administration suggests more aggressive immunomodulatory therapies may be warranted at disease onset.

  9. A fatal case of chikungunya virus infection with liver involvement.

    PubMed

    Chua, H H; Abdul Rashid, K; Law, W C; Hamizah, A; Chem, Y K; Khairul, A H; Chua, K B

    2010-03-01

    Recovery from chikungunya is previously considered universal and mortality due to the virus is rare and unusual. Findings from recent chikungunya outbreaks occurred in Reunion Island and India have since challenged the conventional view on the benign nature of the illness. Malaysia has experienced at least of 4 outbreaks of chikungunya since 1998. In the present on-going large outbreak due to chikungunya virus of Central/East African genotype, a previous healthy sixty six years gentleman without co-morbidity was noted to have severe systemic infection by the virus and involvement of his liver. He subsequently passed away due to cardiovascular collapse after 5 days of illness.

  10. Concentration of Rift Valley fever and Chikungunya viruses by precipitation.

    PubMed

    Klein, F; Mahlandt, B G; Cockey, R R; Lincoln, R E

    1970-09-01

    Simple and efficient methods for concentrating Rift Valley fever (RVF) virus and chikungunya (CHIK) virus are described. Ammonium sulfate, potassium sulfate, or alcohol was used as a precipitating agent and the precipitate was resuspended to volumes suitable for further processing and purification. The methods permitted concentration of live RVF virus and CHIK virus about 100-fold with negligible losses of virus. RVF virus retained a high level of infectivity with potassium aluminum sulfate and alcohol, but CHIK virus retained a higher infectivity level with ammonium sulfate than with potassium aluminum sulfate. The data indicate that serum plays an important role in the concentration of both viruses, at least when the sulfate methods are used.

  11. [Chikungunya virus infection: review through an epidemic].

    PubMed

    Pialoux, G; Gaüzère, B-A; Strobel, M

    2006-05-01

    The Chikungunya virus is an alpha arbovirus, first identified in 1953, transmitted by Aedes, mosquitoes, responsible for a little documented uncommon acute specifically tropical disease. Its main symptoms are fever, a rash, and debilitating arthralgia. An unprecedented Chikungunya epidemic is ongoing on the Reunion Island (775,000 inhabitants) with over 244,000 reported and 205 deaths (directly or indirectly linked) as of April 20 2006. Aedes albopictus, long present on the island, is the assumed vector. It had already been identified as the vector for type 2 Dengue fever in 1997-1978 (200,000 cases) for type 1 Dengue fever in 2004 (300 cases). After the Grande Comore Island epidemic, the first cases were reported in the Reunion Island in March 2005. The epidemic was a surprise because of its unexpected emergence, its magnitude, and clinical cases rarely or never described before: severe forms, central neurological involvement, hepatic cytolyse, severe lymphopenia, severe dermatological involvement, deaths, and neonatal infections. This is the first manifestation of the intrusion CHK virus on the island, which benefits from a sub-tropical climate, but also of an occidental healthcare environment, with a non-immune population. This is also the first time that a Chikungunya epidemic is described in this part of the world.

  12. Chikungunya Virus Growth and Fluorescent Labeling: Detection of Chikungunya Virus by Immunofluorescence Assay.

    PubMed

    Moi, Meng Ling; Takasaki, Tomohiko

    2016-01-01

    Immunofluorescence assay (IFA) is a highly versatile and sensitive assay for detection and titration of chikungunya virus (CHIKV). The IFA technique requires virus-infected cells (viral antigen) and antibodies specific to the viral antigens for detection. Suitable antibodies for detection include monoclonal antibodies specific to CHIKV structural and nonstructural proteins, polyclonal antibodies, and convalescent serum samples. Here, the details of virus antigen preparation, detection by IFA method, and applications are described. The described IFA method is potentially useful in a wide range of studies including virus growth kinetics and virus infection mechanism studies. Additionally, the described IFA method can be modified for applications in arbovirus diagnosis, including CHIKV.

  13. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses.

    PubMed

    Mardekian, Stacey K; Roberts, Amity L

    2015-01-01

    Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections.

  14. Diagnostic Options and Challenges for Dengue and Chikungunya Viruses

    PubMed Central

    Mardekian, Stacey K.; Roberts, Amity L.

    2015-01-01

    Dengue virus (DENV) and Chikungunya virus (CHIKV) are arboviruses that share the same Aedes mosquito vectors and thus overlap in their endemic areas. These two viruses also cause similar clinical presentations, especially in the initial stages of infection, with neither virus possessing any specific distinguishing clinical features. Because the outcomes and management strategies for these two viruses are vastly different, early and accurate diagnosis is imperative. Diagnosis is also important for surveillance, outbreak control, and research related to vaccine and drug development. Available diagnostic tests are aimed at detection of the virus, its antigenic components, or the host immune antibody response. In this review, we describe the recent progress and continued challenges related to the diagnosis of DENV and CHIKV infections. PMID:26509163

  15. How great is the threat of chikungunya virus?

    PubMed

    Waggoner, Jesse J; Pinsky, Benjamin A

    2015-03-01

    In the last decade, chikungunya virus has emerged from an obscure arbovirus that caused limited outbreaks of disease in Africa and Asia to the cause of a pandemic affecting millions of people and spanning five continents. Two separate chikungunya virus genotypes have been responsible for outbreaks during this period, including strains adapted to transmission in Aedes albopictus mosquitoes. Further spread of this virus into new regions of the Western Hemisphere is predicted during the present rainy season in the tropics, and recurrent viral introductions and disease outbreaks, as occurred in Réunion in 2010, should be expected. Chikungunya virus no longer simply threatens; it has arrived as a significant, global pathogen.

  16. Chikungunya virus pathogenesis: From bedside to bench.

    PubMed

    Couderc, Thérèse; Lecuit, Marc

    2015-09-01

    Chikungunya virus (CHIKV) is an arbovirus transmitted to humans by mosquito bite. A decade ago, the virus caused a major outbreak in the islands of the Indian Ocean, then reached India and Southeast Asia. More recently, CHIKV has emerged in the Americas, first reaching the Caribbean and now extending to Central, South and North America. It is therefore considered a major public health and economic threat. CHIKV causes febrile illness typically associated with debilitating joint pains. In rare cases, it may also cause central nervous system disease, notably in neonates. Joint symptoms may persist for months to years, and lead to arthritis. This review focuses on the spectrum of signs and symptoms associated with CHIKV infection in humans. It also illustrates how the analysis of clinical and biological data from human cohorts and the development of animal and cellular models of infection has helped to identify the tissue and cell tropisms of the virus and to decipher host responses in benign, severe or persistent disease. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World".

  17. First evidence of chikungunya virus infection in Assam, Northeast India.

    PubMed

    Dutta, P; Khan, S A; Khan, A M; Borah, J; Chowdhury, P; Mahanta, J

    2011-06-01

    During June-September 2008, an illness characterized by fever, headache and joint pain was reported in Assam state, northeast India. It presented characteristic features resembling chikungunya or dengue virus infection based on clinical symptoms. Dengue and chikungunya IgM antibody was detected in 10.0% (28/280) and 3.6% (10/280) patients respectively. The chikungunya positive patients did not travel to and from any endemic region confirming indigenous transmission. Persistent arthralgia and hearing loss has been observed in a recovered patient. Entomological surveys revealed the presence of vectors viz. Aedes aegypti and Aedes albopictus. This is the maiden report of chikungunya occurrence in Northeast India.

  18. A Case of Chikungunya Virus Induced Arthralgia Responsive to Colchicine.

    PubMed

    Redel, Henry

    2016-04-01

    Chikungunya virus is an emerging infectious disease that has started circulating throughout the Americas and Caribbean. It can lead to persistent arthralgia lasting months to years. Treatment has been symptomatic with nonsteroidal anti-inflammatory medications. This case report describes a trial of colchicine for chikungunya arthralgia in 1 patient. PMID:27419183

  19. Chikungunya Fever in Japan Imported from the Caribbean Islands.

    PubMed

    Imai, Kazuo; Nakayama, Eri; Maeda, Takuya; Mikita, Kei; Kobayashi, Yukiko; Mitarai, Aoi; Honma, Yasuko; Miyake, Satoru; Kaku, Koki; Miyahira, Yasushi; Kawana, Akihiko

    2016-01-01

    A 53-year-old Japanese woman who was working as a volunteer in the Commonwealth of Dominica in the Caribbean islands presented with a high-grade fever and severe incapacitating generalized arthralgia. The Asian genotype of the chikungunya virus was confirmed using reverse transcription-PCR and serology, based on the presence of a specific neutralization titer and immunoglobulin M antibodies. She was diagnosed with post-chikungunya chronic arthritis based on persistence of her polyarthritis for 3 months and the presence of rheumatoid factor, immunoglobulin G-rheumatoid factor, and matrix metalloproteinase-3. Chikungunya virus should be considered as a causative pathogen in travelers returning from Caribbean islands. Clinicians should consider chikungunya fever in the differential diagnosis of patients who complain of chronic arthritis and have a history of travel to an endemic area.

  20. Therapeutics and vaccines against chikungunya virus.

    PubMed

    Ahola, Tero; Couderc, Therese; Courderc, Therese; Ng, Lisa F P; Hallengärd, David; Powers, Ann; Lecuit, Marc; Esteban, Mariano; Merits, Andres; Roques, Pierre; Liljeström, Peter

    2015-04-01

    Currently, there are no licensed vaccines or therapies available against chikungunya virus (CHIKV), and these were subjects discussed during a CHIKV meeting recently organized in Langkawi, Malaysia. In this review, we chart the approaches taken in both areas. Because of a sharp increase in new data in these fields, the present paper is complementary to previous reviews by Weaver et al. in 2012 and Kaur and Chu in 2013 . The most promising antivirals so far discovered are reviewed, with a special focus on the virus-encoded replication proteins as potential targets. Within the vaccines in development, our review emphasizes the various strategies in parallel development that are unique in the vaccine field against a single disease.

  1. Proteomics Profiling of Chikungunya-Infected Aedes albopictus C6/36 Cells Reveal Important Mosquito Cell Factors in Virus Replication

    PubMed Central

    Lee, Regina Ching Hua; Chu, Justin Jang Hann

    2015-01-01

    Chikungunya virus (CHIKV) is the only causative agent of CHIKV fever with persistent arthralgia, and in some cases may lead to neurological complications which can be highly fatal, therefore it poses severe health issues in many parts of the world. CHIKV transmission can be mediated via the Aedes albopictus mosquito; however, very little is currently known about the involvement of mosquito cellular factors during CHIKV-infection within the mosquito cells. Unravelling the neglected aspects of mosquito proteome changes in CHIKV-infected mosquito cells may increase our understanding on the differences in the host factors between arthropod and mammalian cells for successful replication of CHIKV. In this study, the CHIKV-infected C6/36 cells with differential cellular proteins expression were profiled using two-dimensional gel electrophoresis (2DE) coupled with the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). 2DE analysis on CHIKV-infected C6/36 cells has shown 23 mosquito cellular proteins that are differentially regulated, and which are involved diverse biological pathways, such as protein folding and metabolic processes. Among those identified mosquito proteins, spermatogenesis-associated factor, enolase phosphatase e-1 and chaperonin-60kD have been found to regulate CHIKV infection. Furthermore, siRNA-mediated gene knockdown of these proteins has demonstrated the biological importance of these host proteins that mediate CHIKV infection. These findings have provided an insight to the importance of mosquito host factors in the replication of CHIKV, thus providing a potential channel for developing novel antiviral strategies against CHIKV transmission. PMID:25738640

  2. Temperature Tolerance and Inactivation of Chikungunya Virus.

    PubMed

    Huang, Yan-Jang S; Hsu, Wei-Wen; Higgs, Stephen; Vanlandingham, Dana L

    2015-11-01

    In late 2013, chikungunya virus (CHIKV) was introduced to the New World and large outbreaks occurred in the Caribbean islands causing over a million suspected and over 20,000 laboratory-confirmed cases. Serological analysis is an essential component for the diagnosis of CHIKV infection together with virus isolation and detection of viral nucleic acid. Demonstrating virus neutralizing by serum antibodies in a plaque reduction neutralization test (PRNT) is the gold standard of all serological diagnostic assays. Prior to the testing, heat inactivation of serum at 56°C for 30 min is required for the inactivation of complement activity and adventitious viruses. The presence of adventitious contaminating viruses may interfere with the results by leading to a higher number of plaques on the monolayers and subsequent false-negative results. This procedure is widely accepted for the inactivation of flaviviruses and alphaviruses. In this study, the thermostability of CHIKV was evaluated. Heat inactivation at 56°C for 30 min was demonstrated to be insufficient for the complete removal of infectious CHIKV virions present in the samples. This thermotolerance of CHIKV could compromise the accuracy of serum tests, and therefore longer treatment for greater than 120 min is recommended.

  3. Proteomic Analysis of Chikungunya Virus Infected Microgial Cells

    PubMed Central

    Abere, Bizunesh; Wikan, Nitwara; Ubol, Sukathida; Auewarakul, Prasert; Paemanee, Atchara; Kittisenachai, Suthathip; Roytrakul, Sittiruk; Smith, Duncan R.

    2012-01-01

    Chikungunya virus (CHIKV) is a recently re-emerged public health problem in many countries bordering the Indian Ocean and elsewhere. Chikungunya fever is a relatively self limiting febrile disease, but the consequences of chikungunya fever can include a long lasting, debilitating arthralgia, and occasional neurological involvement has been reported. Macrophages have been implicated as an important cell target of CHIKV with regards to both their role as an immune mediator, as well evidence pointing to long term viral persistence in these cells. Microglial cells are the resident brain macrophages, and so this study sought to define the proteomic changes in a human microglial cell line (CHME-5) in response to CHIKV infection. GeLC-MS/MS analysis of CHIKV infected and mock infected cells identified some 1455 individual proteins, of which 90 proteins, belonging to diverse cellular pathways, were significantly down regulated at a significance level of p<0.01. Analysis of the protein profile in response to infection did not support a global inhibition of either normal or IRES-mediated translation, but was consistent with the targeting of specific cellular pathways including those regulating innate antiviral mechanisms. PMID:22514668

  4. Chikungunya virus and its mosquito vectors.

    PubMed

    Higgs, Stephen; Vanlandingham, Dana

    2015-04-01

    Chikungunya virus (CHIKV), a mosquito-borne alphavirus of increasing public health significance, has caused large epidemics in Africa and the Indian Ocean basin; now it is spreading throughout the Americas. The primary vectors of CHIKV are Aedes (Ae.) aegypti and, after the introduction of a mutation in the E1 envelope protein gene, the highly anthropophilic and geographically widespread Ae. albopictus mosquito. We review here research efforts to characterize the viral genetic basis of mosquito-vector interactions, the use of RNA interference and other strategies for the control of CHIKV in mosquitoes, and the potentiation of CHIKV infection by mosquito saliva. Over the past decade, CHIKV has emerged on a truly global scale. Since 2013, CHIKV transmission has been reported throughout the Caribbean region, in North America, and in Central and South American countries, including Brazil, Columbia, Costa Rica, El Salvador, French Guiana, Guatemala, Guyana, Nicaragua, Panama, Suriname, and Venezuela. Closing the gaps in our knowledge of driving factors behind the rapid geographic expansion of CHIKV should be considered a research priority. The abundance of multiple primate species in many of these countries, together with species of mosquito that have never been exposed to CHIKV, may provide opportunities for this highly adaptable virus to establish sylvatic cycles that to date have not been seen outside of Africa. The short-term and long-term ecological consequences of such transmission cycles, including the impact on wildlife and people living in these areas, are completely unknown.

  5. Control of immunopathology during chikungunya virus infection.

    PubMed

    Petitdemange, Caroline; Wauquier, Nadia; Vieillard, Vincent

    2015-04-01

    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.

  6. Evidence for homologous recombination in Chikungunya Virus.

    PubMed

    Casal, Pablo E; Chouhy, Diego; Bolatti, Elisa M; Perez, Germán R; Stella, Emma J; Giri, Adriana A

    2015-04-01

    Chikungunya Virus (CHIKV), a mosquito-transmitted alphavirus, causes acute fever and joint pain in humans. Recently, endemic CHIKV infection outbreaks have jeopardized public health in wider geographical regions. Here, we analyze the phylogenetic associations of CHIKV and explore the potential recombination events on 152 genomic isolates deposited in GenBank database. The CHIKV genotypes [West African, Asian, East/Central/South African (ECSA)], and a clear division of ECSA clade into three sub-groups (I-II-III), were defined by Bayesian analysis; similar results were obtained using E1 gene sequences. A nucleotide identity-based approach is provided to facilitate CHIKV classification within ECSA clade. Using seven methods to detect recombination, we found a statistically significant event (p-values range: 1.14×10(-7)-4.45×10(-24)) located within the nsP3 coding region. This finding was further confirmed by phylogenetic networks (PHI Test, p=0.004) and phylogenetic tree incongruence analysis. The recombinant strain, KJ679578/India/2011 (ECSA III), derives from viruses of ECSA III and ECSA I. Our study demonstrates that recombination is an additional mechanism of genetic diversity in CHIKV that might assist in the cross-species transmission process.

  7. Detection of Chikungunya Virus in Nepal.

    PubMed

    Pandey, Basu Dev; Neupane, Biswas; Pandey, Kishor; Tun, Mya Myat Ngwe; Morita, Kouichi

    2015-10-01

    Chikungunya virus (CHIKV) is an emerging alphaviral disease and a public health problem in South Asia including Nepal in recent years. In this study, sera were collected from patients presenting with fever, headache, muscular pain, fatigue, and joint pain of both upper and lower extremities. A total of 169 serum samples were tested for CHIKV and dengue virus (DENV) by using Immunoglobulin M (IgM) and Immunoglobulin G (IgG) antibody using enzyme-linked immunosorbent assay (ELISA) method during August to November 2013. Results showed that 3.6% and 27.8% samples were positive for CHIKV and DENV IgM positive, respectively. Similarly, results of IgG showed 3.0% samples were positive for CHIKV IgG and 29.0% were for DENV IgG positive. Further, a 50% focal reduction neutralization test (FRNT50) was performed to confirm the presence of CHIKV, which demonstrated that 8.9% of CHIKV IgM and/or IgG ELISA positive possessed neutralizing anti-CHIK antibodies. To our knowledge, this is the first report in which the presence of CHIKV is confirmed in Nepalese patients by FRNT50. Basic scientists and clinicians need to consider CHIKV as a differential diagnosis in febrile Nepalese patients, and policy makers should consider appropriate surveillance and actions for control strategies.

  8. Suramin Inhibits Chikungunya Virus Entry and Transmission.

    PubMed

    Ho, Yi-Jung; Wang, Yu-Ming; Lu, Jeng-wei; Wu, Tzong-Yuan; Lin, Liang-In; Kuo, Szu-Cheng; Lin, Chang-Chi

    2015-01-01

    The mosquito-borne Chikungunya virus (CHIKV) is a profound global threat due to its high rate of contagion and the lack of vaccine or effective treatment. Suramin is a symmetric polyanionic naphthylurea that is widely used in the clinical treatment of parasite infections. Numerous studies have reported the broad antiviral activities of suramin; however, inhibition effects against CHIKV have not yet been demonstrated. The aim of this study was thus to investigate the antiviral effect of suramin on CHIKV infection and to elucidate the molecular mechanism underlying inhibition using plaque reduction assay, RT-qPCR, western blot analysis, and plaque assay. Microneutralization assay was used to determine the EC50 of suramin in the CHIKV-S27 strain as well as in three other clinical strains (0611aTw, 0810bTw and 0706aTw). Time-of-addition was used to reveal the anti-CHIKV mechanism of suramin. We also evaluated anti-CHIKV activity with regard to viral entry, virus release, and cell-to-cell transmission. Cytopathic effect, viral RNA, viral protein, and the virus yield of CHIKV infection were shown to diminish in the presence of suramin in a dose-dependent manner. Suramin was also shown the inhibitory activities of the three clinical isolates. Suramin inhibited the early progression of CHIKV infection, due perhaps to interference with virus fusion and binding, which subsequently prevented viral entry. Results of a molecular docking simulation indicate that suramin may embed within the cavity of the E1/E2 heterodimer to interfere with their function. Suramin was also shown to reduce viral release and cell-to-cell transmission of CHIKV. In conclusion, Suramin shows considerable potential as a novel anti-CHIKV agent targeting viral entry, extracellular transmission, and cell-to-cell transmission. PMID:26208101

  9. Reemergence of chikungunya virus in Bo, Sierra Leone.

    PubMed

    Ansumana, Rashid; Jacobsen, Kathryn H; Leski, Tomasz A; Covington, Andrea L; Bangura, Umaru; Hodges, Mary H; Lin, Baochuan; Bockarie, Alfred S; Lamin, Joseph M; Bockarie, Moses J; Stenger, David A

    2013-07-01

    We diagnosed 400 possible IgM-positive cases of chikungunya virus in Bo, Sierra Leone, during July 2012-January 2013 by using lateral flow immunoassays. Cases detected likely represent only a small fraction of total cases. Further laboratory testing is required to confirm this outbreak and characterize the virus. PMID:23764023

  10. Reemergence of Chikungunya Virus in Bo, Sierra Leone

    PubMed Central

    Ansumana, Rashid; Leski, Tomasz A.; Covington, Andrea L.; Bangura, Umaru; Hodges, Mary H.; Lin, Baochuan; Bockarie, Alfred S.; Lamin, Joseph M.; Bockarie, Moses J.; Stenger, David A.

    2013-01-01

    We diagnosed 400 possible IgM-positive cases of chikungunya virus in Bo, Sierra Leone, during July 2012–January 2013 by using lateral flow immunoassays. Cases detected likely represent only a small fraction of total cases. Further laboratory testing is required to confirm this outbreak and characterize the virus. PMID:23764023

  11. Globalization of Chikungunya Virus: Threat to the U.S.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August, 2004, Kenyan health authorities and partners identified chikungunya virus as the cause of the febrile epidemic in a coastal island city. The virus is transmitted by Aedes mosquitoes in tropical Africa and Asia; the fever is rarely fatal but can incapacitate for weeks. Control was delayed,...

  12. Protective and Pathogenic Responses to Chikungunya Virus Infection

    PubMed Central

    Long, Kristin M.; Heise, Mark T.

    2015-01-01

    Chikungunya virus (CHIKV) is an arbovirus responsible for causing epidemic outbreaks of human disease characterized by painful and often debilitating arthralgia. Recently CHIKV has moved into the Caribbean and the Americas resulting in massive outbreaks in naïve human populations. Given the importance of CHIKV as an emerging disease, a significant amount of effort has gone into interpreting the virus-host interactions that contribute to protection or virus-induced pathology following CHIKV infection, with the long term goal of using this information to develop new therapies or safe and effective anti-CHIKV vaccines. This work has made it clear that numerous distinct host responses are involved in the response to CHIKV infection, where some aspects of the host innate and adaptive immune response protect from or limit virus-induced disease, while other pathways actually exacerbate the virus-induced disease process. This review will discuss mechanisms that have been identified as playing a role in the host response to CHIKV infection and illustrate the importance of carefully evaluating these responses to determine whether they play a protective or pathologic role during CHIKV infection. PMID:26366337

  13. Rapidly Evolving Outbreak of a Febrile Illness in Rural Haiti: The Importance of a Field Diagnosis of Chikungunya Virus in Remote Locations.

    PubMed

    McGraw, Ian T; Dhanani, Naila; Ray, Lee Ann; Bentley, Regina M; Bush, Ruth L; Vanderpool, David M

    2015-11-01

    Although rarely fatal, chikungunya virus (CHIKV) infection can lead to chronic debilitating sequelae. We describe the outbreak of suspected CHIKV in 93 subjects who presented voluntarily over 2 months to a remote rural Haitian general medical clinic staffed by international health care providers. Diagnosis was made on clinical signs and symptoms because no serum analysis was available in this remote rural site. The subjects were 18.0 ± 16.2 (median ± standard deviation) years of age and were of similar gender distribution. The presenting vital signs included a temperature of 102.3°F ± 0.6°F with fever lasting for 3.0 ± 0.7 days. Symptoms mainly consisted of symmetrical polyarthralgias in 82.8%, headache in 28.0%, abdominal pain in 17.2%, cough in 8.6%, maculopapular rash in 30.0%, and extremity bullae in 12.9%. In 84.9% of subjects, symptoms persisted for 7.1 ± 8.3 days with 16.1% having ongoing disability due to persistent pain (≥ 14 days duration). There were no deaths. In Haiti, especially in remote, rural regions, the risk for CHIKV spread is high given the shortage of detection methods and treatment in this tropical climate and the lack of preventative efforts underway. Implications for global public health are likely, with outbreak expansion and spread to neighboring countries, including the United States.

  14. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses.

    PubMed

    Waggoner, Jesse J; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K; Balmaseda, Angel; Harris, Eva; Pinsky, Benjamin A

    2016-07-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses.

  15. Cluster of chikungunya virus infection in travelers returning from Senegal, 2006.

    PubMed

    Pistone, Thierry; Ezzedine, Khaled; Boisvert, Marie; Receveur, Marie-Catherine; Schuffenecker, Isabelle; Zeller, Hervé; Lafon, Marie-Edith; Fleury, Hervé; Malvy, Denis

    2009-01-01

    Chikungunya virus (CHIKV) infection has been reported in West Africa since 1966, with the last outbreaks from Senegal in 1996 and 1997. We report a cluster of CHIKV infection among travelers returning from Senegal in 2006. Eight imported cases of dengue-like syndrome with fever, joint pain, and skin manifestations were investigated.

  16. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness

    PubMed Central

    Moulin, E.; Selby, K.; Cherpillod, P.; Kaiser, L.; Boillat-Blanco, N.

    2016-01-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm. PMID:27006779

  17. Simultaneous outbreaks of dengue, chikungunya and Zika virus infections: diagnosis challenge in a returning traveller with nonspecific febrile illness.

    PubMed

    Moulin, E; Selby, K; Cherpillod, P; Kaiser, L; Boillat-Blanco, N

    2016-05-01

    Zika virus is an emerging flavivirus that is following the path of dengue and chikungunya. The three Aedes-borne viruses cause simultaneous outbreaks with similar clinical manifestations which represents a diagnostic challenge in ill returning travellers. We report the first Zika virus infection case imported to Switzerland and present a diagnostic algorithm.

  18. Unusual presentation of chikungunya virus infection with concomintant erysipelas in a returning traveler from the Caribbean: a case report.

    PubMed

    Schechter, Marcos C; Workowski, Kimberly A; Fairley, Jessica K

    2014-12-01

    Chikungunya fever is a mosquito-borne febrile illness caused by Chikungunya virus (CHIKV), an alphavirus from the Togaviridae family. It is transmitted by primarily Aedes aegytpi and Aedes albopictus mosquitos [1]. Once of little importance in the Americas, local transmission was identified in the Caribbean in late 2013. More than 1000 travelers returning to the continental United States have been diagnosed with CHIKV. More importantly, there have been 9 documented cases of autochthonous disease in Florida as of September 16, 2014 [2].

  19. Neutralization Assay for Chikungunya Virus Infection: Plaque Reduction Neutralization Test.

    PubMed

    Azami, Nor Azila Muhammad; Moi, Meng Ling; Takasaki, Tomohiko

    2016-01-01

    Neutralization assay is a technique that detects and quantifies neutralizing antibody in serum samples by calculating the percentage of reduction of virus activity, as the concentration of virus used is usually constant. Neutralizing antibody titer is conventionally determined by calculating the percentage reduction in total virus infectivity by counting and comparing number of plaques (localized area of infection due to cytopathic effect) with a standard amount of virus. Conventional neutralizing test uses plaque-reduction neutralization test (PRNT) to determine neutralizing antibody titers against Chikungunya virus (CHIKV). Here we describe the plaque reduction neutralization assay (PRNT) using Vero cell lines to obtain neutralizing antibody titers.

  20. Independent Emergence of the Cosmopolitan Asian Chikungunya Virus, Philippines 2012.

    PubMed

    Tan, Kim-Kee; Sy, Ava Kristy D; Tandoc, Amado O; Khoo, Jing-Jing; Sulaiman, Syuhaida; Chang, Li-Yen; AbuBakar, Sazaly

    2015-01-01

    Outbreaks involving the Asian genotype Chikungunya virus (CHIKV) caused over one million infections in the Americas recently. The outbreak was preceded by a major nationwide outbreak in the Philippines. We examined the phylogenetic and phylogeographic relationships of representative CHIKV isolates obtained from the 2012 Philippines outbreak with other CHIKV isolates collected globally. Asian CHIKV isolated from the Philippines, China, Micronesia and Caribbean regions were found closely related, herein denoted as Cosmopolitan Asian CHIKV (CACV). Three adaptive amino acid substitutions in nsP3 (D483N), E1 (P397L) and E3 (Q19R) were identified among CACV. Acquisition of the nsP3-483N mutation in Compostela Valley followed by E1-397L/E3-19R in Laguna preceded the nationwide spread in the Philippines. The China isolates possessed two of the amino acid substitutions, nsP3-D483N and E1-P397L whereas the Micronesian and Caribbean CHIKV inherited all the three amino acid substitutions. The unique amino acid substitutions observed among the isolates suggest multiple independent virus dissemination events. The possible biological importance of the specific genetic signatures associated with the rapid global of the virus is not known and warrant future in-depth study and epidemiological follow-up. Molecular evidence, however, supports the Philippines outbreak as the possible origin of the CACV. PMID:26201250

  1. Independent Emergence of the Cosmopolitan Asian Chikungunya Virus, Philippines 2012.

    PubMed

    Tan, Kim-Kee; Sy, Ava Kristy D; Tandoc, Amado O; Khoo, Jing-Jing; Sulaiman, Syuhaida; Chang, Li-Yen; AbuBakar, Sazaly

    2015-01-01

    Outbreaks involving the Asian genotype Chikungunya virus (CHIKV) caused over one million infections in the Americas recently. The outbreak was preceded by a major nationwide outbreak in the Philippines. We examined the phylogenetic and phylogeographic relationships of representative CHIKV isolates obtained from the 2012 Philippines outbreak with other CHIKV isolates collected globally. Asian CHIKV isolated from the Philippines, China, Micronesia and Caribbean regions were found closely related, herein denoted as Cosmopolitan Asian CHIKV (CACV). Three adaptive amino acid substitutions in nsP3 (D483N), E1 (P397L) and E3 (Q19R) were identified among CACV. Acquisition of the nsP3-483N mutation in Compostela Valley followed by E1-397L/E3-19R in Laguna preceded the nationwide spread in the Philippines. The China isolates possessed two of the amino acid substitutions, nsP3-D483N and E1-P397L whereas the Micronesian and Caribbean CHIKV inherited all the three amino acid substitutions. The unique amino acid substitutions observed among the isolates suggest multiple independent virus dissemination events. The possible biological importance of the specific genetic signatures associated with the rapid global of the virus is not known and warrant future in-depth study and epidemiological follow-up. Molecular evidence, however, supports the Philippines outbreak as the possible origin of the CACV.

  2. Immunogenicity of Escherichia coli expressed envelope 2 protein of Chikungunya virus.

    PubMed

    Tripathi, Nagesh K; Priya, Raj; Shrivastava, Ambuj

    2014-01-01

    Chikungunya fever, a re-emerging infection, is an arthropod-borne viral disease prevalent in different parts of the world, particularly Africa and South East Asia. Chikungunya virus envelope 2 protein is involved in binding to host receptors and it contains specific epitopes that elicit virus neutralizing antibodies. A highly immunogenic, recombinant Chikungunya virus envelope 2 protein was produced by bioreactor in Escherichia coli for development of a suitable diagnostic and vaccine candidate. This protein was refolded and further purified to achieve biologically active protein. The biological function of refolded and purified recombinant envelope 2 protein of Chikungunya virus was confirmed by its ability to generate envelope 2 specific antibodies with high titers in animal models. These findings suggest that recombinant envelope 2 protein of Chikungunya virus in combination with compatible adjuvant is highly immunogenic. Thus, recombinant envelope 2 protein can be a potential diagnostic reagent and vaccine candidate against Chikungunya virus infection.

  3. Assessment of flavaglines as potential chikungunya virus entry inhibitors.

    PubMed

    Wintachai, Phitchayapak; Thuaud, Frédéric; Basmadjian, Christine; Roytrakul, Sittiruk; Ubol, Sukathida; Désaubry, Laurent; Smith, Duncan R

    2015-03-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that recently caused large epidemics in islands in, and countries around, the Indian Ocean. There is currently no specific drug for therapeutic treatment or for use as a prophylactic agent against infection and no commercially available vaccine. Prohibitin has been identified as a receptor protein used by chikungunya virus to enter mammalian cells. Recently, synthetic sulfonyl amidines and flavaglines (FLs), a class of naturally occurring plant compounds with potent anti-cancer and cytoprotective and neuroprotective activities, have been shown to interact directly with prohibitin. This study therefore sought to determine whether three prohibitin ligands (sulfonyl amidine 1 m and the flavaglines FL3 and FL23) were able to inhibit CHIKV infection of mammalian Hek293T/17 cells. All three compounds inhibited infection and reduced virus production when cells were treated before infection but not when added after infection. Pretreatment of cells for only 15 minutes prior to infection followed by washing out of the compound resulted in significant inhibition of entry and virus production. These results suggest that further investigation of prohibitin ligands as potential Chikungunya virus entry inhibitors is warranted.

  4. Molecular characterization of dengue and chikungunya virus strains circulating in New Delhi, India.

    PubMed

    Afreen, Nazia; Deeba, Farah; Khan, Wajihul H; Haider, Shakir H; Kazim, Syed Naqui; Ishrat, Romana; Naqvi, Irshad Hussain; Shareef, Mohammad Y; Broor, Shobha; Ahmed, Anwar; Parveen, Shama

    2014-12-01

    Dengue and chikungunya are acute viral infections with overlapping clinical symptoms. Both diseases are transmitted by common mosquito vectors resulting in their co-circulation in a region. Molecular and serological tests specific for both dengue and chikungunya infections were performed on 87 acute phase blood samples collected from patients with suspected dengue/chikungunya infections in Delhi from September to December, 2011. RT-PCR and IgM ELISA were performed to detect dengue virus (DENV) and chikungunya virus (CHIKV). NS1 and IgG ELISA were also performed to detect DENV specific antigen and secondary DENV infection. DENV infection was detected in 49%, CHIKV infection in 29% and co-infection with DENV and CHIKV in 10% of the samples by RT-PCR. DENV serotypes 1, 2 and 3 were detected in this study. Nine DENV-1 strains, six DENV-2 strains and 20 CHIKV strains were characterized by DNA sequencing and phylogenetic analysis of their respective envelope protein genes. DENV-1 strains grouped in the American African genotype, DENV-2 strains in the Cosmopolitan genotype and CHIKV strains in the East Central South African genotype by phylogenetic analysis. This is one of the few studies reporting the phylogeny of two dengue virus serotypes (DENV-1 and DENV-2) and CHIKV. Surveillance and monitoring of DENV and CHIKV strains are important for design of strategies to control impending epidemics.

  5. Chikungunya.

    PubMed

    Kamath, Sandhya; Das, A K; Parikh, Falguni S

    2006-09-01

    Chikungunya fever is a viral disease transmitted to humans by the bite of infected Aedes aegypti mosquito. Like malaria and dengue, this infection has almost become endemic in India, especially central and south India. Symptoms of sudden onset of fever, chills, headache, nausea, vomiting, joint pain with or without swelling, low back pain, and rash are very similar to those of dengue but, unlike dengue, there is no hemorrhagic or shock syndrome form. Chikungunya is a self-limiting illness with no specific treatment. Travellers visiting endemic areas should be careful and take precautions to see that they are not bitten by mosquitoes. PMID:17212022

  6. Chikungunya.

    PubMed

    Kamath, Sandhya; Das, A K; Parikh, Falguni S

    2006-09-01

    Chikungunya fever is a viral disease transmitted to humans by the bite of infected Aedes aegypti mosquito. Like malaria and dengue, this infection has almost become endemic in India, especially central and south India. Symptoms of sudden onset of fever, chills, headache, nausea, vomiting, joint pain with or without swelling, low back pain, and rash are very similar to those of dengue but, unlike dengue, there is no hemorrhagic or shock syndrome form. Chikungunya is a self-limiting illness with no specific treatment. Travellers visiting endemic areas should be careful and take precautions to see that they are not bitten by mosquitoes.

  7. Chikungunya Virus: Current Perspectives on a Reemerging Virus.

    PubMed

    Morrison, Clayton R; Plante, Kenneth S; Heise, Mark T

    2016-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus in the family Togaviridae that causes outbreaks of debilitating acute and chronic arthralgia in humans. Although historically associated with localized outbreaks in Africa and Asia, recent epidemics in the Indian Ocean region and the Americas have led to the recognition that CHIKV is capable of moving into previously unaffected areas and causing significant levels of human suffering. The severity of CHIKV rheumatic disease, which can severely impact life quality of infected individuals for weeks, months, or even years, combined with the explosive nature of CHIKV outbreaks and its demonstrated ability to quickly spread into new regions, has led to renewed interest in developing strategies for the prevention or treatment of CHIKV-induced disease. Therefore, this chapter briefly discusses the biology of CHIKV and the factors contributing to CHIKV dissemination, while also discussing the pathogenesis of CHIKV-induced disease and summarizing the status of efforts to develop safe and effective therapies and vaccines against CHIKV and related viruses. PMID:27337473

  8. Genetic characterization of Chikungunya virus in the Central African Republic.

    PubMed

    Desdouits, Marion; Kamgang, Basile; Berthet, Nicolas; Tricou, Vianney; Ngoagouni, Carine; Gessain, Antoine; Manuguerra, Jean-Claude; Nakouné, Emmanuel; Kazanji, Mirdad

    2015-07-01

    Chikungunya virus (CHIKV) is an alphavirus transmitted by the bite of mosquito vectors. Over the past 10 years, the virus has gained mutations that enhance its transmissibility by the Aedes albopictus vector, resulting in massive outbreaks in the Indian Ocean, Asia and Central Africa. Recent introduction of competent A. albopictus vectors into the Central African Republic (CAR) pose a threat of a Chikungunya fever (CHIKF) epidemic in this region. We undertook this study to assess the genetic diversity and background of CHIKV strains isolated in the CAR between 1975 and 1984 and also to estimate the ability of local strains to adapt to A. albopictus. Our results suggest that, local CHIKV strains have a genetic background compatible with quick adaptation to A. albopictus, as previously observed in other Central African countries. Intense surveillance of the human and vector populations is necessary to prevent or anticipate the emergence of a massive CHIKF epidemic in the CAR.

  9. The green tea catechin, epigallocatechin gallate inhibits chikungunya virus infection.

    PubMed

    Weber, Christopher; Sliva, Katja; von Rhein, Christine; Kümmerer, Beate M; Schnierle, Barbara S

    2015-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions, including Europe and the United States of America and might cause new, large outbreaks there. No treatment or licensed CHIKV vaccine exists. Epigallocatechin-3-gallate (EGCG), the major component of green tea, has, among other beneficial properties, antiviral activities. Therefore, we examined if EGCG has antiviral activity against CHIKV. EGCG inhibited CHIKV infection in vitro, blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV attachment to target cells. Thus EGCG might be used as a lead structure to develop more effective antiviral drugs.

  10. Clinical and molecular characterization of chikungunya virus in South Thailand.

    PubMed

    Theamboonlers, Apiradee; Rianthavorn, Pornpimol; Praianantathavorn, Kesmanee; Wuttirattanakowit, Norra; Poovorawan, Yong

    2009-07-01

    In 2008, an outbreak of chikungunya virus (CHIKV) occurred in Narathiwat province, south Thailand. To determine the clinical significance, molecular epidemiology and evolutionary origin of the CHIKV causing this outbreak, 47 patients who had been admitted to Narathiwatratchanakharin provincial hospital due to acute febrile illness were enrolled in this study. Sera were tested for IgM antibodies, and RT-PCR was performed for CHIKV and dengue virus. We diagnosed 10 patients with CHIKV infection and 5 with dengue virus infection. Joint pain is a significant symptom of chikungunya fever. Five strains of CHIKV were isolated. Their genome sequences were different from those isolated from the previous outbreaks in Thailand (1988, 1995-1996) but similar to the sequences isolated from the 2008 Singapore outbreak. We speculated that the outbreak was caused by a group of viruses different from the previous outbreaks. RT-PCR, serology to detect IgM antibodies or paired sera for IgG for CHIKV should be performed in all patients with presumed hemorrhagic fever to promptly detect outbreaks of CHIKV. This precaution would help control global epidemics of this virus.

  11. Chikungunya Fever: Obstetric Considerations on an Emerging Virus.

    PubMed

    Dotters-Katz, Sarah K; Grace, Matthew R; Strauss, Robert A; Chescheir, Nancy; Kuller, Jeffrey A

    2015-07-01

    Chikungunya fever is an increasingly common viral infection transmitted to humans by species of the Aedes mosquitoes. Characterized by fevers, myalgias, arthralgias, headache, and rash, the infection is endemic to tropical areas. However, identification of disease vectors to Europe and the Americas has raised concern for possible spread of chikungunya to these areas. More recently, these concerns have become a reality; with more than 500,000 new cases in the Western hemisphere in the last 2 years, questions have arisen about the implications of infection during pregnancy and delivery. A literature review was performed using MEDLINE in order to gather information regarding the obstetric implications of this infection. It appears that although this virus can cross the placenta in the first and second trimester leading to fetal infection and miscarriage, this is a very rare occurrence. In contrast, active maternal infection within 4 days of delivery conveys a high risk of vertical transmission. Maternal infection during pregnancy does not appear to be more severe than infection on the nonpregnant female. Given the increasing incidence of chikungunya, obstetric providers should be aware of the disease and its implication for the gravid female.

  12. [Situational panorama of Mexico against the chikungunya virus pandemic].

    PubMed

    Martínez-Sánchez, Abisai; Martínez-Ramos, Ericay Berenice; Chávez-Angeles, Manuel Gerardo

    2015-01-01

    Recent outbreaks of emerging diseases emphasize the vulnerability of health systems, as is the case of chikungunya fever. The wide geographical incidence of the virus in the last years requires alerting systems for the prevention, diagnosis, control and eradication of the disease. Given the ecological, epidemiological and socio-economic characteristic of Mexico, this disease affects directly or indirectly the health of the population and development of agricultural, livestock, industrial, fishing, oil and tourism activities in the country. Due to this situation it is essential to make a brief analysis on the main clinical data, epidemiological and preventive measures with which our country counts with to confront the situation.

  13. Chikungunya Virus: What You Need to Know

    MedlinePlus

    ... ye) is: A virus spread through Aedes species mosquito bites. Aedes mosquitoes also spread dengue and Zika ... 7 days after being bitten by an infected mosquito. Most patients will feel better within a week. ...

  14. Dynamics of Chikungunya Virus Cell Entry Unraveled by Single-Virus Tracking in Living Cells

    PubMed Central

    Hoornweg, Tabitha E.; van Duijl-Richter, Mareike K. S.; Ayala Nuñez, Nilda V.; Albulescu, Irina C.; van Hemert, Martijn J.

    2016-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne human pathogen causing major outbreaks in Africa, Asia, and the Americas. The cell entry pathway hijacked by CHIKV to infect a cell has been studied previously using inhibitory compounds. There has been some debate on the mechanism by which CHIKV enters the cell: several studies suggest that CHIKV enters via clathrin-mediated endocytosis, while others show that it enters independently of clathrin. Here we applied live-cell microscopy and monitored the cell entry behavior of single CHIKV particles in living cells transfected with fluorescent marker proteins. This approach allowed us to obtain detailed insight into the dynamic events that occur during CHIKV entry. We observed that almost all particles fused within 20 min after addition to the cells. Of the particles that fused, the vast majority first colocalized with clathrin. The average time from initial colocalization with clathrin to the moment of membrane fusion was 1.7 min, highlighting the rapidity of the cell entry process of CHIKV. Furthermore, these results show that the virus spends a relatively long time searching for a receptor. Membrane fusion was observed predominantly from within Rab5-positive endosomes and often occurred within 40 s after delivery to endosomes. Furthermore, we confirmed that a valine at position 226 of the E1 protein enhances the cholesterol-dependent membrane fusion properties of CHIKV. To conclude, our work confirms that CHIKV enters cells via clathrin-mediated endocytosis and shows that fusion occurs from within acidic early endosomes. IMPORTANCE Since its reemergence in 2004, chikungunya virus (CHIKV) has spread rapidly around the world, leading to millions of infections. CHIKV often causes chikungunya fever, a self-limiting febrile illness with severe arthralgia. Currently, no vaccine or specific antiviral treatment against CHIKV is available. A potential antiviral strategy is to interfere with the cell

  15. Diagnosis and management of imported Chikungunya fever in Taiwan: a case report.

    PubMed

    Chang, Ko; Hsieh, Hsiao-Chen; Tsai, Jih-Jin; Lin, Wei-Ru; Lu, Po-Liang; Chen, Yen-Hsu

    2010-05-01

    Chikungunya virus, a mosquito-borne alphavirus, is endemic in Africa and Southeast Asia but is rarely reported in Taiwan. We report the case of a Taiwanese woman who developed Chikungunya fever, which was first diagnosed by a clinician rather than by fever screening at an airport. The woman presented with fever, maculopapular rash, and arthralgia, the triad for the disease, on the day she returned home after a trip to Malaysia. These symptoms are very similar to those of dengue fever, which is endemic in Southern Taiwan. Chikungunya infection was confirmed by reverse transcriptase-polymerase chain reaction and seroconversion on paired serum specimens. For approximately 40 years until 2006, no cases of Chikungunya fever had been found in Taiwan. Clinicians in Taiwan should consider Chikungunya fever as a possible diagnosis for a febrile patient with arthralgia, rash, and a history of travel to an endemic area, such as Africa or Southeast Asia.

  16. Four cases of acute flaccid paralysis associated with chikungunya virus infection

    PubMed Central

    SINGH, S. S.; MANIMUNDA, S. P.; SUGUNAN, A. P.; SAHINA; VIJAYACHARI, P.

    2008-01-01

    SUMMARY The recent epidemic of chikungunya fever (2005–2006) in India has affected millions of people. The Andaman and Nicobar Islands, an archipelago situated in the Bay of Bengal 1200 km from peninsular India, also witnessed an outbreak of chikungunya fever starting in July 2006 which affected thousands of people. Chikungunya fever classically manifests as high fever, myalgia, arthralgia and arthritis and in a certain percentage of cases with maculopapular rashes. However, deviation from the classical clinical features of chikungunya fever was reported in the earlier and recent epidemics. During the recent epidemic in the Andaman and Nicobar Islands we came across ten cases of flaccid limb weakness following symptoms and signs suggestive of chikungunya fever. In four subjects we confirmed the diagnosis of chikungunya virus infection by serological method (IgM ELISA method). This is the case report of those four subjects. PMID:18634716

  17. Single-Reaction Multiplex Reverse Transcription PCR for Detection of Zika, Chikungunya, and Dengue Viruses

    PubMed Central

    Waggoner, Jesse J.; Gresh, Lionel; Mohamed-Hadley, Alisha; Ballesteros, Gabriela; Davila, Maria Jose Vargas; Tellez, Yolanda; Sahoo, Malaya K.; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Clinical manifestations of Zika virus, chikungunya virus, and dengue virus infections can be similar. To improve virus detection, streamline molecular workflow, and decrease test costs, we developed and evaluated a multiplex real-time reverse transcription PCR for these viruses. PMID:27184629

  18. Dengue virus serotype 4 and chikungunya virus coinfection in a traveller returning from Luanda, Angola, January 2014.

    PubMed

    Parreira, R; Centeno-Lima, S; Lopes, A; Portugal-Calisto, D; Constantino, A; Nina, J

    2014-03-13

    A concurrent dengue virus serotype 4 and chikungunya virus infection was detected in a woman in her early 50s returning to Portugal from Luanda, Angola, in January 2014. The clinical, laboratory and molecular findings, involving phylogenetic analyses of partial viral genomic sequences amplified by RT-PCR, are described. Although the circulation of both dengue and chikungunya viruses in Angola has been previously reported, to our knowledge this is the first time coinfection with both viruses has been detected there.

  19. Development of Neutralization Assay Using an eGFP Chikungunya Virus.

    PubMed

    Deng, Cheng-Lin; Liu, Si-Qing; Zhou, Dong-Gen; Xu, Lin-Lin; Li, Xiao-Dan; Zhang, Pan-Tao; Li, Peng-Hui; Ye, Han-Qing; Wei, Hong-Ping; Yuan, Zhi-Ming; Qin, Cheng-Feng; Zhang, Bo

    2016-06-28

    Chikungunya virus (CHIKV), a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV) with an isolated strain (assigned to Asian lineage) from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV.

  20. Development of Neutralization Assay Using an eGFP Chikungunya Virus

    PubMed Central

    Deng, Cheng-Lin; Liu, Si-Qing; Zhou, Dong-Gen; Xu, Lin-Lin; Li, Xiao-Dan; Zhang, Pan-Tao; Li, Peng-Hui; Ye, Han-Qing; Wei, Hong-Ping; Yuan, Zhi-Ming; Qin, Cheng-Feng; Zhang, Bo

    2016-01-01

    Chikungunya virus (CHIKV), a member of the Alphavirus genus, is an important human emerging/re-emerging pathogen. Currently, there are no effective antiviral drugs or vaccines against CHIKV infection. Herein, we construct an infectious clone of CHIKV and an eGFP reporter CHIKV (eGFP-CHIKV) with an isolated strain (assigned to Asian lineage) from CHIKV-infected patients. The eGFP-CHIKV reporter virus allows for direct visualization of viral replication through the levels of eGFP expression. Using a known CHIKV inhibitor, ribavirin, we confirmed that the eGFP-CHIKV reporter virus could be used to identify inhibitors against CHIKV. Importantly, we developed a novel and reliable eGFP-CHIKV reporter virus-based neutralization assay that could be used for rapid screening neutralizing antibodies against CHIKV. PMID:27367716

  1. Two Japanese siblings affected with Chikungunya fever with different clinical courses: Imported infections from the Cook Islands.

    PubMed

    Kondo, Makoto; Akachi, Shigehiro; Ando, Katsuhiko; Nomura, Tatsuma; Yamanaka, Keiichi; Mizutani, Hitoshi

    2016-06-01

    Two Japanese siblings visited the Cook Islands on business and stayed for 2 months. The sister developed a high fever, arthralgia, erythema and leg edema on the day after returning to Japan. The brother also developed neck and joint pain on the day following the sister's onset. Subsequently, his erythematous lesions spread over his whole body. Chikungunya virus was detected from the sister's blood and urine by specific reverse transcription polymerase chain reaction, but not in the brother's samples. Retrospectively, his history of Chikungunya fever was confirmed by the presence of the anti-Chikungunya virus immunoglobulin (Ig)M and IgG antibodies using the specific enzyme-linked immunoassay. In Japan, no autochthonous case of Chikungunya fever was reported previously. We should give attention to the imported infectious diseases for epidemic prevention. This report warns about the danger of the imported infectious diseases, and also suggests that covering the topic of infectious disease in the world is critical to doctors as well as travelers.

  2. Chikungunya in Mississippi: The Health Department Response to Imported Cases.

    PubMed

    Goddard, Jerome; Varnado, Wendy C; Hand, Sheryl; Meyer, Florencia

    2016-05-01

    Chikungunya (CHIK), a newly recognized mosquito-borne disease in the Western Hemisphere, has resulted in well over a million cases since December 2013. Only about a dozen locally-acquired cases thus far have been reported in the U. S. (Florida), but approximately 1500 imported cases have been seen in returning travelers from the Caribbean and Central and South America. Public health officials are concerned that imported cases may lead to infection of local mosquitoes and, thus disease transmission. This paper documents 9 confirmed CHIK cases in Mississippi: 5 resulting from travel to the Dominican Republic, 2 from Haiti, 1 from Honduras, and 1 from Puerto Rico. In addition, the Mississippi State Department of Health response to those cases is presented and discussed.

  3. Chikungunya in Mississippi: The Health Department Response to Imported Cases.

    PubMed

    Goddard, Jerome; Varnado, Wendy C; Hand, Sheryl; Meyer, Florencia

    2016-05-01

    Chikungunya (CHIK), a newly recognized mosquito-borne disease in the Western Hemisphere, has resulted in well over a million cases since December 2013. Only about a dozen locally-acquired cases thus far have been reported in the U. S. (Florida), but approximately 1500 imported cases have been seen in returning travelers from the Caribbean and Central and South America. Public health officials are concerned that imported cases may lead to infection of local mosquitoes and, thus disease transmission. This paper documents 9 confirmed CHIK cases in Mississippi: 5 resulting from travel to the Dominican Republic, 2 from Haiti, 1 from Honduras, and 1 from Puerto Rico. In addition, the Mississippi State Department of Health response to those cases is presented and discussed. PMID:27386666

  4. Emerging and re-emerging viruses: A global challenge illustrated by Chikungunya virus outbreaks

    PubMed Central

    Devaux, Christian A

    2012-01-01

    In recent decades, the issue of emerging and re-emerging infectious diseases, especially those related to viruses, has become an increasingly important area of concern in public health. It is of significance to anticipate future epidemics by accumulating knowledge through appropriate research and by monitoring their emergence using indicators from different sources. The objective is to alert and respond effectively in order to reduce the adverse impact on the general populations. Most of the emerging pathogens in humans originate from known zoonosis. These pathogens have been engaged in long-standing and highly successful interactions with their hosts since their origins are exquisitely adapted to host parasitism. They developed strategies aimed at: (1) maximizing invasion rate; (2) selecting host traits that can reduce their impact on host life span and fertility; (3) ensuring timely replication and survival both within host and between hosts; and (4) facilitating reliable transmission to progeny. In this context, Arboviruses (or ARthropod-BOrne viruses), will represent with certainty a threat for the coming century. The unprecedented epidemic of Chikungunya virus which occurred between 2005 and 2006 in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world, such as India and Southern Europe, has attracted the attention of medical and state authorities about the risks linked to this re-emerging mosquito-borne virus. This is an excellent model to illustrate the issues we are facing today and to improve how to respond tomorrow. PMID:24175207

  5. Association of ABO blood groups with Chikungunya virus.

    PubMed

    Kumar, Naresh C V M; Nadimpalli, Mahathi; Vardhan, Vishnu R; Gopal, Sai D V R

    2010-01-01

    Chikungunya virus (CHIKV) an emerging arboviral infection of public health concern belongs to the genus Alphavirus, family Togaviridae. Blood group antigens are generally known to act as receptors for various etiological agents. The studies defining the relationship between blood groups and CHIKV is limited and hence it is necessary to study these parameters in detail. In the present study 1500 subjects were enrolled and demographic data (Age, Gender, Blood group, CHIKV infection status, and CHIKV infection confirmation mode) was collected from them. The risk of acquiring CHIKV disease and its association with factors such as blood group, age and gender was analyzed statistically. The data of this study showed a possible association between blood group, age and gender of the study population with CHIKV infection. It is observed that CHIKV infections were higher in individuals with Rh positive blood group when compared to their Rh negative counterparts.CHIKV infections were found to be higher in Rh positive individuals of AB and A blood groups than that of Rh negative counterparts. Results also indicated that infections were higher in adults belonging to the age group > 30 years and also higher in males as compared to females enrolled in this study. These data present further evidence for the association of the blood groups, age and gender to susceptibility to CHIKV infection. Further studies are needed to confirm these findings. This is the second study showing the possible association of blood groups with chikungunya.

  6. Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica.

    PubMed

    Nsoesie, Elaine O; Ricketts, R Paul; Brown, Heidi E; Fish, Durland; Durham, David P; Ndeffo Mbah, Martial L; Christian, Trudy; Ahmed, Shalauddin; Marcellin, Clement; Shelly, Ellen; Owers, Katharine; Wenzel, Natasha; Galvani, Alison P; Brownstein, John S

    2015-01-01

    Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013-2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks.

  7. Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica

    PubMed Central

    Nsoesie, Elaine O.; Ricketts, R. Paul; Brown, Heidi E.; Fish, Durland; Durham, David P.; Ndeffo Mbah, Martial L.; Christian, Trudy; Ahmed, Shalauddin; Marcellin, Clement; Shelly, Ellen; Owers, Katharine; Wenzel, Natasha; Galvani, Alison P.; Brownstein, John S.

    2015-01-01

    Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013–2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks. PMID:26274813

  8. Spatial and Temporal Clustering of Chikungunya Virus Transmission in Dominica.

    PubMed

    Nsoesie, Elaine O; Ricketts, R Paul; Brown, Heidi E; Fish, Durland; Durham, David P; Ndeffo Mbah, Martial L; Christian, Trudy; Ahmed, Shalauddin; Marcellin, Clement; Shelly, Ellen; Owers, Katharine; Wenzel, Natasha; Galvani, Alison P; Brownstein, John S

    2015-01-01

    Using geo-referenced case data, we present spatial and spatio-temporal cluster analyses of the early spread of the 2013-2015 chikungunya virus (CHIKV) in Dominica, an island in the Caribbean. Spatial coordinates of the locations of the first 417 reported cases observed between December 15th, 2013 and March 11th, 2014, were captured using the Global Positioning System (GPS). We observed a preponderance of female cases, which has been reported for CHIKV outbreaks in other regions. We also noted statistically significant spatial and spatio-temporal clusters in highly populated areas and observed major clusters prior to implementation of intensive vector control programs suggesting early vector control measures, and education had an impact on the spread of the CHIKV epidemic in Dominica. A dynamical identification of clusters can lead to local assessment of risk and provide opportunities for targeted control efforts for nations experiencing CHIKV outbreaks. PMID:26274813

  9. Congenital Chikungunya Virus Infection in Sincelejo, Colombia: A Case Series.

    PubMed

    Villamil-Gómez, Wilmer; Alba-Silvera, Luz; Menco-Ramos, Antonio; Gonzalez-Vergara, Alfonso; Molinares-Palacios, Tatiana; Barrios-Corrales, María; Rodríguez-Morales, Alfonso J

    2015-10-01

    Congenital chikungunya virus (CHIK) infection has been infrequently reported, even more so during the current 2013-15 outbreak in Latin America. In this study, the consequences of CHIK on pregnancy outcomes and particularly consequences in infants born to infected women were assessed in a case series from a single private institution in the north of Colombia. During September 2014 to February 2015, seven pregnant women with serological and reverse transcription-polymerase chain reaction-positive test for CHIK delivered eight infants with CHIK. These newborns required admission to pediatric intensive care, and related support, owing to severe clinical manifestations, which included respiratory distress, sepsis, necrotizing enterocolitis, meningoencephalitis, myocarditis, edema, bullous dermatitis and pericarditis. There were three deaths (case fatality rate of 37.5%). Pregnant women and newborns with CHIK long term should be followed up, given the implications of chronic sequelae (e.g. chronic inflammatory rheumatism in women) as well as recently described neurocognitive impairment in infants.

  10. Suramin inhibits chikungunya virus replication through multiple mechanisms.

    PubMed

    Albulescu, Irina C; van Hoolwerff, Marcella; Wolters, Laura A; Bottaro, Elisabetta; Nastruzzi, Claudio; Yang, Shih Chi; Tsay, Shwu-Chen; Hwu, Jih Ru; Snijder, Eric J; van Hemert, Martijn J

    2015-09-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe and often persistent arthritis. In recent years, millions of people have been infected with this virus for which registered antivirals are still lacking. Using our recently established in vitro assay, we discovered that the approved anti-parasitic drug suramin inhibits CHIKV RNA synthesis (IC50 of ∼5μM). The compound inhibited replication of various CHIKV isolates in cell culture with an EC50 of ∼80μM (CC50>5mM) and was also active against Sindbis virus and Semliki Forest virus. In vitro studies hinted that suramin interferes with (re)initiation of RNA synthesis, whereas time-of-addition studies suggested it to also interfere with a post-attachment early step in infection, possibly entry. CHIKV (nsP4) mutants resistant against favipiravir or ribavirin, which target the viral RNA polymerase, did not exhibit cross-resistance to suramin, suggesting a different mode of action. The assessment of the activity of a variety of suramin-related compounds in cell culture and the in vitro assay for RNA synthesis provided more insight into the moieties required for antiviral activity. The antiviral effect of suramin-containing liposomes was also analyzed. Its approved status makes it worthwhile to explore the use of suramin to prevent and/or treat CHIKV infections.

  11. Monoclonal antibody targeting chikungunya virus envelope 1 protein inhibits virus release.

    PubMed

    Masrinoul, Promsin; Puiprom, Orapim; Tanaka, Atsushi; Kuwahara, Miwa; Chaichana, Panjaporn; Ikuta, Kazuyoshi; Ramasoota, Pongrama; Okabayashi, Tamaki

    2014-09-01

    Chikungunya virus (CHIKV) causes an acute clinical illness characterized by sudden high fever, intense joint pain, and skin rash. Recent outbreaks of chikungunya disease in Africa and Asia are a major public health concern; however, there is currently no effective licensed vaccine or specific treatment. This study reported the development of a mouse monoclonal antibody (MAb), CK47, which recognizes domain III within the viral envelope 1 protein and inhibited the viral release process, thereby preventing the production of progeny virus. The MAb had no effect on virus entry and replication processes. Thus, CK47 may be a useful tool for studying the mechanisms underlying CHIKV release and may show potential as a therapeutic agent.

  12. Preparation of vesicular stomatitis virus pseudotype with Chikungunya virus envelope protein.

    PubMed

    Tong, W; Yin, X-X; Lee, B-J; Li, Y-G

    2015-06-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes Chikungunya fever (CHIKF) in millions of people mainly in developing countries. CHIKF is characterized by high fever, fatigue, headache, nausea, vomiting, rash, myalgia and severe arthralgia. To date, there is no specific treatment and no licensed vaccine against CHIKV infection. In this study, we developed a safe, efficient and easy neutralization assay of CHIKV based on vesicular stomatitis virus (VSV) pseudotype with CHIKV envelope protein and the green fluorescent protein (GFP) or luciferase as reporter gene, which could be used under a reduced safety level. The VSV pseudotype can be applied to the epidemic survey by measuring the expression of GFP or luciferase activity in infected cells. This system can also be used to study the mechanisms of virus entry.

  13. Development of a Hamster Model for Chikungunya Virus Infection and Pathogenesis.

    PubMed

    Bosco-Lauth, Angela M; Han, Sushan; Hartwig, Airn; Bowen, Richard A

    2015-01-01

    Chikungunya virus is transmitted by mosquitoes and causes severe, debilitating infectious arthritis in humans. The need for an animal model to study the disease process and evaluate potential treatments is imminent as the virus continues its spread into novel geographic locations. Golden hamsters (Mesocricetus auratus) are often used as outbred laboratory animal models for arboviral diseases. Here we demonstrate that hamsters inoculated with chikungunya virus developed viremia and histopathologic lesions in their limbs and joints similar to those seen in human patients. The virus disseminated rapidly and was found in every major organ, including brain, within a few days of infection. Hamsters did not manifest overt clinical signs, and the virus was generally cleared within 4 days, followed by a strong neutralizing antibody response. These results indicate that hamsters are highly susceptible to chikungunya virus infection and develop myositis and tenosynovitis similar to human patients followed by a complete recovery. This animal model may be useful for testing antiviral drugs and vaccines.

  14. Identification of Asian genotype of chikungunya virus isolated in Mexico.

    PubMed

    Díaz-Quiñonez, José Alberto; Escobar-Escamilla, Noé; Ortíz-Alcántara, Joanna; Vázquez-Pichardo, Mauricio; de la Luz Torres-Rodríguez, María; Nuñez-León, Alma; Torres-Longoria, Belem; López-Martínez, Irma; Ruiz-Matus, Cuitláhuac; Kuri-Morales, Pablo; Ramírez-González, José Ernesto

    2016-02-01

    We identified 25 autochthonous chikungunya virus cases in Mexico, initially detected by RT-PCR targeting the E1 gene and propagated in C6/36 Aedes albopictus cells, in 2014. To determine the type of virus found, in a previous report, the genomes of 2 CHIKV strains were fully sequenced. Genome sequence analysis revealed that these isolates from Mexico belonged to the Asian genotype, and a phylogenetic association with the circulating strain in the British Virgin Islands was also established in the same year. This was further supported by changes in specific amino acids, E2-V368A and 6K-L20M. For these reasons, it can be inferred that the route of virus entry to Mexico was held across the countries in the Caribbean and Central America. The presence of E1-A226V mutation associated with more efficient replication in the salivary gland of the A. albopictus mosquito was not observed. Interestingly, a newly acquired NSP4-S399C mutation was observed; however, the significance of changes in amino acid found in non-structural proteins in autochthonous strains remains to be elucidated.

  15. Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases.

    PubMed

    Pastula, Daniel M; Smith, Daniel E; Beckham, J David; Tyler, Kenneth L

    2016-06-01

    Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes, ticks, or sandflies. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, Jamestown Canyon, Powassan, chikungunya, and Zika viruses have emerged as increasingly important arboviruses that can cause human disease in North America. Unfortunately, there are currently no proven disease-modifying therapies for these arboviral diseases, so treatment is largely supportive. Given there are also no commercially available vaccines for these four arboviral infections, prevention is the key. To prevent mosquito or tick bites that might result in one of these arboviral diseases, people should wear long-sleeved shirts and pants while outside if feasible, apply insect repellant when going outdoors, using window screens or air conditioning to keep mosquitoes outside, and perform tick checks after being in wooded or brushy outdoor areas. PMID:26903031

  16. Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases.

    PubMed

    Pastula, Daniel M; Smith, Daniel E; Beckham, J David; Tyler, Kenneth L

    2016-06-01

    Arthropod-borne viruses, or arboviruses, are viruses that are transmitted through the bites of mosquitoes, ticks, or sandflies. There are numerous arboviruses throughout the world capable of causing human disease spanning different viral families and genera. Recently, Jamestown Canyon, Powassan, chikungunya, and Zika viruses have emerged as increasingly important arboviruses that can cause human disease in North America. Unfortunately, there are currently no proven disease-modifying therapies for these arboviral diseases, so treatment is largely supportive. Given there are also no commercially available vaccines for these four arboviral infections, prevention is the key. To prevent mosquito or tick bites that might result in one of these arboviral diseases, people should wear long-sleeved shirts and pants while outside if feasible, apply insect repellant when going outdoors, using window screens or air conditioning to keep mosquitoes outside, and perform tick checks after being in wooded or brushy outdoor areas.

  17. Seroprevalence of Anti-Chikungunya Virus Antibodies in Children and Adults in Managua, Nicaragua, After the First Chikungunya Epidemic, 2014-2015

    PubMed Central

    Ojeda, Sergio; Melendez, Marlon; Sanchez, Nery; Collado, Damaris; Garcia, Nadezna; Mercado, Juan Carlos; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Chikungunya is a viral disease transmitted by Aedes aegypti and Ae. albopictus mosquitoes. In late 2013, chikungunya virus (CHIKV) was introduced into the Caribbean island of St. Martin. Since then, approximately 2 million chikungunya cases have been reported by the Pan American Health Organization, and most countries in the Americas report autochthonous transmission of CHIKV. In Nicaragua, the first imported case was described in July 2014 and the first autochthonous case in September 2014. Here, we conducted two studies to analyze the seroprevalence of anti-CHIKV antibodies after the first chikungunya epidemic in a community-based cohort study (ages 2–14 years) and in a cross-sectional survey of persons aged ≥15 years in the same area of Managua, Nicaragua. Routine annual serum samples collected from 3,362 cohort participants in March/April 2014 and 2015, and 848 age-stratified samples collected from persons ≥15 years old at the end of May-beginning of June 2015 were used to estimate the seroprevalence of anti-CHIKV antibodies after the first epidemic (October 2014 to February 2015 in the study population). Using an Inhibition ELISA assay that measures total anti-CHIKV antibodies, the seroprevalence was significantly higher in those aged ≥15 (13.1% (95%CI: 10.9, 15.5)) than in the pediatric population (6.1% (95%CI: 5.3, 6.9)). The proportion of inapparent infections was 58.3% (95%CI: 51.5, 65.1) in children and 64.9% (95%CI: 55.2, 73.7) in the ≥15 study population. We identified age, water availability, household size, and socioeconomic status as factors associated with the presence of anti-CHIKV antibodies. Overall, this is the first report of CHIKV seropositivity in continental Latin America and provides useful information for public health authorities in the region. PMID:27322692

  18. Seroprevalence of Anti-Chikungunya Virus Antibodies in Children and Adults in Managua, Nicaragua, After the First Chikungunya Epidemic, 2014-2015.

    PubMed

    Kuan, Guillermina; Ramirez, Stephania; Gresh, Lionel; Ojeda, Sergio; Melendez, Marlon; Sanchez, Nery; Collado, Damaris; Garcia, Nadezna; Mercado, Juan Carlos; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2016-06-01

    Chikungunya is a viral disease transmitted by Aedes aegypti and Ae. albopictus mosquitoes. In late 2013, chikungunya virus (CHIKV) was introduced into the Caribbean island of St. Martin. Since then, approximately 2 million chikungunya cases have been reported by the Pan American Health Organization, and most countries in the Americas report autochthonous transmission of CHIKV. In Nicaragua, the first imported case was described in July 2014 and the first autochthonous case in September 2014. Here, we conducted two studies to analyze the seroprevalence of anti-CHIKV antibodies after the first chikungunya epidemic in a community-based cohort study (ages 2-14 years) and in a cross-sectional survey of persons aged ≥15 years in the same area of Managua, Nicaragua. Routine annual serum samples collected from 3,362 cohort participants in March/April 2014 and 2015, and 848 age-stratified samples collected from persons ≥15 years old at the end of May-beginning of June 2015 were used to estimate the seroprevalence of anti-CHIKV antibodies after the first epidemic (October 2014 to February 2015 in the study population). Using an Inhibition ELISA assay that measures total anti-CHIKV antibodies, the seroprevalence was significantly higher in those aged ≥15 (13.1% (95%CI: 10.9, 15.5)) than in the pediatric population (6.1% (95%CI: 5.3, 6.9)). The proportion of inapparent infections was 58.3% (95%CI: 51.5, 65.1) in children and 64.9% (95%CI: 55.2, 73.7) in the ≥15 study population. We identified age, water availability, household size, and socioeconomic status as factors associated with the presence of anti-CHIKV antibodies. Overall, this is the first report of CHIKV seropositivity in continental Latin America and provides useful information for public health authorities in the region.

  19. Seroprevalence of Anti-Chikungunya Virus Antibodies in Children and Adults in Managua, Nicaragua, After the First Chikungunya Epidemic, 2014-2015.

    PubMed

    Kuan, Guillermina; Ramirez, Stephania; Gresh, Lionel; Ojeda, Sergio; Melendez, Marlon; Sanchez, Nery; Collado, Damaris; Garcia, Nadezna; Mercado, Juan Carlos; Gordon, Aubree; Balmaseda, Angel; Harris, Eva

    2016-06-01

    Chikungunya is a viral disease transmitted by Aedes aegypti and Ae. albopictus mosquitoes. In late 2013, chikungunya virus (CHIKV) was introduced into the Caribbean island of St. Martin. Since then, approximately 2 million chikungunya cases have been reported by the Pan American Health Organization, and most countries in the Americas report autochthonous transmission of CHIKV. In Nicaragua, the first imported case was described in July 2014 and the first autochthonous case in September 2014. Here, we conducted two studies to analyze the seroprevalence of anti-CHIKV antibodies after the first chikungunya epidemic in a community-based cohort study (ages 2-14 years) and in a cross-sectional survey of persons aged ≥15 years in the same area of Managua, Nicaragua. Routine annual serum samples collected from 3,362 cohort participants in March/April 2014 and 2015, and 848 age-stratified samples collected from persons ≥15 years old at the end of May-beginning of June 2015 were used to estimate the seroprevalence of anti-CHIKV antibodies after the first epidemic (October 2014 to February 2015 in the study population). Using an Inhibition ELISA assay that measures total anti-CHIKV antibodies, the seroprevalence was significantly higher in those aged ≥15 (13.1% (95%CI: 10.9, 15.5)) than in the pediatric population (6.1% (95%CI: 5.3, 6.9)). The proportion of inapparent infections was 58.3% (95%CI: 51.5, 65.1) in children and 64.9% (95%CI: 55.2, 73.7) in the ≥15 study population. We identified age, water availability, household size, and socioeconomic status as factors associated with the presence of anti-CHIKV antibodies. Overall, this is the first report of CHIKV seropositivity in continental Latin America and provides useful information for public health authorities in the region. PMID:27322692

  20. Epidemiology of Chikungunya Virus in Bahia, Brazil, 2014-2015.

    PubMed

    Rodrigues Faria, Nuno; Lourenço, José; Marques de Cerqueira, Erenilde; Maia de Lima, Maricélia; Pybus, Oliver; Carlos Junior Alcantara, Luiz

    2016-01-01

    Chikungunya is an emerging arbovirus that is characterized into four lineages. One of these, the Asian genotype, has spread rapidly in the Americas after its introduction in the Saint Martin island in October 2013. Unexpectedly, a new lineage, the East-Central-South African genotype, was introduced from Angola in the end of May 2014 in Feira de Santana (FSA), the second largest city in Bahia state, Brazil, where over 5,500 cases have now been reported. Number weekly cases of clinically confirmed CHIKV in FSA were analysed alongside with urban district of residence of CHIKV cases reported between June 2014 and October collected from the municipality's surveillance network. The number of cases per week from June 2014 until September 2015 reveals two distinct transmission waves. The first wave ignited in June and transmission ceased by December 2014. However, a second transmission wave started in January and peaked in May 2015, 8 months after the first wave peak, and this time in phase with Dengue virus and Zika virus transmission, which ceased when minimum temperature dropped to approximately 15°C. We find that shorter travelling times from the district where the outbreak first emerged to other urban districts of FSA were strongly associated with incidence in each district in 2014 (R(2)). PMID:27330849

  1. Clinical and virological characterization of imported cases of Chikungunya fever.

    PubMed

    Pfeffer, Martin; Zöller, Gudrun; Essbauer, Sandra; Tomaso, Herbert; Behrens-Riha, Nicole; Löscher, Thomas; Dobler, Gerhard

    2008-01-01

    A Chikungunya virus (CHIKV) epidemic emerged in the Indian Ocean islands of the Comores, Reunion, Mayotte, Mauritius, the Seychelles and Madagascar in 2005 resulting in the infection of about 250.000 inhabitants and travellers in only one year. Beginning in March 2006 increasing numbers of CHIKV-like febrile illnesses were reported from various parts of India. We investigated 70 consecutive German travellers returning from the affected areas and presenting with arthralgia and/or fever suggestive of CHIKV infection. Eleven patients had serological evidence of CHIKV infection. Real-time RT-PCR for CHIKV was positive in two cases, one who returned from Mauritius and the other who came back from Rajasthan, Northern India. In both cases CHIKV was isolated and sequencing of the entire viral genome was performed. The nucleotide sequence data obtained for both CHIKV strains revealed a high level of identity to CHIKV isolates from the ongoing epidemic. In detail, we found only 18 nucleotide exchanges between the isolates from Mauritius and Rajasthan, resulting in only six amino acid changes (nsP1 T128K, T376M, nsP3 S472N, capsid P23S, V27I and E1-protein A226V). Although the excessive dimension of the 2005/2006 outbreak in the Indian Ocean islands was at least in part accounted to the naïve population affected, our results of the Rajasthan isolate support that the emergence of this CHIKV subtype may rather be a result of a better viral fitness. This has been previously accounted to a A226V change in the E1 protein of the new CHIKV variant when compared to other CHIKV data available. This mutation, supposedly resulting in high-titred viremia in humans and/or an enhanced adaptation to the vector population resulting in increased transmission rates, was also found in our CHIKV isolate from Mauritius. The spread of an African CHIKV to Asia further demonstrates how fast viruses can emerge and establish in places where competent vectors are prevalent.

  2. Early clearance of Chikungunya virus in children is associated with a strong innate immune response.

    PubMed

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H; Ng, Lisa F P

    2016-01-01

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children. PMID:27180811

  3. Early clearance of Chikungunya virus in children is associated with a strong innate immune response

    PubMed Central

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H.; Ng, Lisa F. P.

    2016-01-01

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawak, Malaysia. Unique immune mediators triggered upon CHIKV infection were identified through meta-analysis of the immune signatures between this pediatric group and cohorts from previous outbreaks. The data generated from this study revealed that a broad spectrum of cytokines/chemokines is up-regulated in a sub-group of virus-infected children stratified according to their viremic status during hospitalization. Furthermore, different immune mediator profiles (the levels of pro-inflammatory cytokines, chemokines and growth and other factors) were observed between children and adults. This study gives an important insight to understand the immune response of CHIKV infection in children and would aid in the development of better prognostics and clinical management for children. PMID:27180811

  4. Complete Genome Sequence of Chikungunya Virus Isolated from an Aedes aegypti Mosquito during an Outbreak in Yemen, 2011.

    PubMed

    Fahmy, Nermeen T; Klena, John D; Mohamed, Amr S; Zayed, Alia; Villinski, Jeffrey T

    2015-01-01

    Chikungunya virus is recognized as a serious public health problem. The complete genome was sequenced for a chikungunya virus isolated from the mosquito Aedes aegypti during a 2011 outbreak in Al Hodayda, Yemen, which resulted in significant human fatalities. Phylogenetic analysis demonstrated that this Yemeni isolate is most closely related to Indian Ocean strains of the east/central/south African genotype. PMID:26184944

  5. Complete Genome Sequence of Chikungunya Virus Isolated from an Aedes aegypti Mosquito during an Outbreak in Yemen, 2011

    PubMed Central

    Klena, John D.; Mohamed, Amr S.; Zayed, Alia; Villinski, Jeffrey T.

    2015-01-01

    Chikungunya virus is recognized as a serious public health problem. The complete genome was sequenced for a chikungunya virus isolated from the mosquito Aedes aegypti during a 2011 outbreak in Al Hodayda, Yemen, which resulted in significant human fatalities. Phylogenetic analysis demonstrated that this Yemeni isolate is most closely related to Indian Ocean strains of the east/central/south African genotype. PMID:26184944

  6. Utilization of an Eilat Virus-Based Chimera for Serological Detection of Chikungunya Infection.

    PubMed

    Erasmus, Jesse H; Needham, James; Raychaudhuri, Syamal; Diamond, Michael S; Beasley, David W C; Morkowski, Stan; Salje, Henrik; Fernandez Salas, Ildefonso; Kim, Dal Young; Frolov, Ilya; Nasar, Farooq; Weaver, Scott C

    2015-01-01

    In December of 2013, chikungunya virus (CHIKV), an alphavirus in the family Togaviridae, was introduced to the island of Saint Martin in the Caribbean, resulting in the first autochthonous cases reported in the Americas. As of January 2015, local and imported CHIKV has been reported in 50 American countries with over 1.1 million suspected cases. CHIKV causes a severe arthralgic disease for which there are no approved vaccines or therapeutics. Furthermore, the lack of a commercially available, sensitive, and affordable diagnostic assay limits surveillance and control efforts. To address this issue, we utilized an insect-specific alphavirus, Eilat virus (EILV), to develop a diagnostic antigen that does not require biosafety containment facilities to produce. We demonstrated that EILV/CHIKV replicates to high titers in insect cells and can be applied directly in enzyme-linked immunosorbent assays without inactivation, resulting in highly sensitive detection of recent and past CHIKV infection, and outperforming traditional antigen preparations. PMID:26492074

  7. Utilization of an Eilat Virus-Based Chimera for Serological Detection of Chikungunya Infection

    PubMed Central

    Erasmus, Jesse H.; Needham, James; Raychaudhuri, Syamal; Diamond, Michael S.; Beasley, David W. C.; Morkowski, Stan; Salje, Henrik; Fernandez Salas, Ildefonso; Kim, Dal Young; Frolov, Ilya; Nasar, Farooq; Weaver, Scott C.

    2015-01-01

    In December of 2013, chikungunya virus (CHIKV), an alphavirus in the family Togaviridae, was introduced to the island of Saint Martin in the Caribbean, resulting in the first autochthonous cases reported in the Americas. As of January 2015, local and imported CHIKV has been reported in 50 American countries with over 1.1 million suspected cases. CHIKV causes a severe arthralgic disease for which there are no approved vaccines or therapeutics. Furthermore, the lack of a commercially available, sensitive, and affordable diagnostic assay limits surveillance and control efforts. To address this issue, we utilized an insect-specific alphavirus, Eilat virus (EILV), to develop a diagnostic antigen that does not require biosafety containment facilities to produce. We demonstrated that EILV/CHIKV replicates to high titers in insect cells and can be applied directly in enzyme-linked immunosorbent assays without inactivation, resulting in highly sensitive detection of recent and past CHIKV infection, and outperforming traditional antigen preparations. PMID:26492074

  8. Chikungunya Virus in Febrile Humans and Aedes aegypti Mosquitoes, Yucatan, Mexico

    PubMed Central

    Cigarroa-Toledo, Nohemi; Blitvich, Bradley J.; Cetina-Trejo, Rosa C.; Talavera-Aguilar, Lourdes G.; Baak-Baak, Carlos M.; Torres-Chablé, Oswaldo M.; Hamid, Md-Nafiz; Friedberg, Iddo; González-Martinez, Pedro; Alonzo-Salomon, Gabriela; Rosado-Paredes, Elsy P.; Rivero-Cárdenas, Nubia; Reyes-Solis, Guadalupe C.; Farfan-Ale, Jose A.; Garcia-Rejon, Julian E.

    2016-01-01

    Chikungunya virus (CHIKV) was isolated from 12 febrile humans in Yucatan, Mexico, in 2015. One patient was co-infected with dengue virus type 1. Two additional CHIKV isolates were obtained from Aedes aegypti mosquitoes collected in the homes of patients. Phylogenetic analysis showed that the CHIKV isolates belong to the Asian lineage. PMID:27347760

  9. Co-circulation of Dengue and Chikungunya Viruses, Al Hudaydah, Yemen, 2012.

    PubMed

    Rezza, Giovanni; El-Sawaf, Gamal; Faggioni, Giovanni; Vescio, Fenicia; Al Ameri, Ranya; De Santis, Riccardo; Helaly, Ghada; Pomponi, Alice; Metwally, Dalia; Fantini, Massimo; Qadi, Hussein; Ciccozzi, Massimo; Lista, Florigio

    2014-08-01

    We investigated 400 cases of dengue-like illness in persons hospitalized during an outbreak in Al Hudaydah, Yemen, in 2012. Overall, 116 dengue and 49 chikungunya cases were diagnosed. Dengue virus type 2 was the predominant serotype. The co-circulation of these viruses indicates that mosquitoborne infections represent a public health threat in Yemen.

  10. Underdiagnosis of chikungunya virus infections in symptomatic dutch travelers returning from the Indian ocean area.

    PubMed

    Reusken, Chantal B E M; Bakker, Jacinta; Reimerink, Johan H J; Zelena, Hana; Koopmans, Marion G P

    2013-01-01

    A putative underdiagnosis of clinical chikungunya virus infection in Dutch travelers to the Indian Ocean area was addressed by retrospective screening of all sera for which requested dengue virus serology was negative in the period 2007 to 2010. Evidence for a recent infection was observed in 6.5% of 107 patients, indicating a substantial underdiagnosis and the need for increased awareness among physicians.

  11. Chikungunya Virus in Febrile Humans and Aedes aegypti Mosquitoes, Yucatan, Mexico.

    PubMed

    Cigarroa-Toledo, Nohemi; Blitvich, Bradley J; Cetina-Trejo, Rosa C; Talavera-Aguilar, Lourdes G; Baak-Baak, Carlos M; Torres-Chablé, Oswaldo M; Hamid, Md-Nafiz; Friedberg, Iddo; González-Martinez, Pedro; Alonzo-Salomon, Gabriela; Rosado-Paredes, Elsy P; Rivero-Cárdenas, Nubia; Reyes-Solis, Guadalupe C; Farfan-Ale, Jose A; Garcia-Rejon, Julian E; Machain-Williams, Carlos

    2016-10-01

    Chikungunya virus (CHIKV) was isolated from 12 febrile humans in Yucatan, Mexico, in 2015. One patient was co-infected with dengue virus type 1. Two additional CHIKV isolates were obtained from Aedes aegypti mosquitoes collected in the homes of patients. Phylogenetic analysis showed that the CHIKV isolates belong to the Asian lineage. PMID:27347760

  12. [An imported Chikungunya fever case from New Delhi, India to Ankara, Turkey: the first imported case of Turkey and review of the literature].

    PubMed

    Yağcı Çağlayık, Dilek; Uyar, Yavuz; Korukluoğlu, Gülay; Ertek, Mustafa; Unal, Serhat

    2012-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne alphavirus that causes an acute febrile illness, chikungunya fever. CHIKV virus is geographically distributed in Africa, India, and South-East Asia. Chikungunya fever outbreaks have been reported from India since 2006. The incubation period is 3-7 days, and the disease is characterized by sudden onset of high fever and severe arthralgia. Other symptoms can be rash, headache, fatigue, nausea-vomiting, and myalgias. Here, we report the first Chikungunya case imported from India, New-Delhi to Ankara, Turkey. In December 2010, a 55-year-old female Turkish government employee living in urban area of New Delhi for the last 3 years had sudden onset fever up to 38.4°C for 2 days. Itching rash and arthralgia also developed. Symptomatic treatment was given to patient in New Delhi. She returned to Turkey and was admitted to Hacettepe University Medical Faculty, Department of Internal Medicine, Infectious Diseases Unit, since arthralgia has continued on the 26th day of her complaints. Hepatomegaly and tenosynovitis were detected in her physical examination. Serum sample sent to Refik Saydam National Public Health Agency, Virology Reference and Research Laboratory, yielded negative results for specific IgM and IgG antibodies against Hantavirus and Dengue virus types 1-4; however, the results were positive for CHIKV specific IgM and IgG antibodies by commercial immunofluorescence method (Euroimmun, Germany). CHIKV RNA which was searched by in-house real-time RT-PCR was negative. The second serum sample obtained three weeks later also found positive for CHIKV specific IgM and IgG antibodies. This was the first laboratory confirmed imported Chikungunya case in Turkey. There are predictions regarding the presence of Aedes species mosquitos that can transmit this virus in Turkey. This case report will be an alarming signal for the clinicians in our country to consider Chikungunya fever in the differential diagnosis of patients

  13. No evidence of chikungunya virus and antibodies shortly before the outbreak on Sri Lanka.

    PubMed

    Panning, Marcus; Wichmann, Dominic; Grywna, Klaus; Annan, Augustina; Wijesinghe, Sriyal; Kularatne, S A M; Drosten, Christian

    2009-05-01

    A massive outbreak of chikungunya disease occurred on Sri Lanka in 2006. Reasons for the explosive nature of the epidemic are being intensively discussed. According to recognised and anecdotal concepts, absence of human population immunity against chikungunya virus (CHIKV) might have supported virus amplification. However, formal proof of concept is lacking. This study determined the prevalence of anti-CHIKV IgG antibodies as well as CHIKV RNA shortly before the outbreak. Two hundred and six human sera were collected from patients with acute febrile illness in 2004/2005. Validated indirect immunofluorescence and real-time RT-PCR assays for dengue as well as CHIKV were employed. Laboratory evidence of dengue virus infection was seen in 67% of patients, indicating virus activity and exposure to Aedes spp. vectors. These vectors are the same as for chikungunya. However, no evidence of acute or previous chikungunya infection could be demonstrated in the same cohort. This study gives formal evidence that the absence of human population immunity correlated with a large chikungunya epidemic.

  14. Chikungunya risk for Brazil

    PubMed Central

    Azevedo, Raimunda do Socorro da Silva; Oliveira, Consuelo Silva; Vasconcelos, Pedro Fernando da Costa

    2015-01-01

    This study aimed to show, based on the literature on the subject, the potential for dispersal and establishment of the chikungunya virus in Brazil. The chikungunya virus, a Togaviridae member of the genus Alphavirus, reached the Americas in 2013 and, the following year, more than a million cases were reported. In Brazil, indigenous transmission was registered in Amapa and Bahia States, even during the period of low rainfall, exposing the whole country to the risk of virus spreading. Brazil is historically infested by Ae. aegypti and Ae. albopictus, also dengue vectors. Chikungunya may spread, and it is important to take measures to prevent the virus from becoming endemic in the country. Adequate care for patients with chikungunya fever requires training general practitioners, rheumatologists, nurses, and experts in laboratory diagnosis. Up to November 2014, more than 1,000 cases of the virus were reported in Brazil. There is a need for experimental studies in animal models to understand the dynamics of infection and the pathogenesis as well as to identify pathophysiological mechanisms that may contribute to identifying effective drugs against the virus. Clinical trials are needed to identify the causal relationship between the virus and serious injuries observed in different organs and joints. In the absence of vaccines or effective drugs against the virus, currently the only way to prevent the disease is vector control, which will also reduce the number of cases of dengue fever. PMID:26398876

  15. Chikungunya risk for Brazil.

    PubMed

    Azevedo, Raimunda do Socorro da Silva; Oliveira, Consuelo Silva; Vasconcelos, Pedro Fernando da Costa

    2015-01-01

    This study aimed to show, based on the literature on the subject, the potential for dispersal and establishment of the chikungunya virus in Brazil. The chikungunya virus, a Togaviridae member of the genusAlphavirus, reached the Americas in 2013 and, the following year, more than a million cases were reported. In Brazil, indigenous transmission was registered in Amapa and Bahia States, even during the period of low rainfall, exposing the whole country to the risk of virus spreading. Brazil is historically infested by Ae. aegypti and Ae. albopictus, also dengue vectors. Chikungunya may spread, and it is important to take measures to prevent the virus from becoming endemic in the country. Adequate care for patients with chikungunya fever requires training general practitioners, rheumatologists, nurses, and experts in laboratory diagnosis. Up to November 2014, more than 1,000 cases of the virus were reported in Brazil. There is a need for experimental studies in animal models to understand the dynamics of infection and the pathogenesis as well as to identify pathophysiological mechanisms that may contribute to identifying effective drugs against the virus. Clinical trials are needed to identify the causal relationship between the virus and serious injuries observed in different organs and joints. In the absence of vaccines or effective drugs against the virus, currently the only way to prevent the disease is vector control, which will also reduce the number of cases of dengue fever.

  16. Chikungunya virus vaccines: Current strategies and prospects for developing plant-made vaccines.

    PubMed

    Salazar-González, Jorge A; Angulo, Carlos; Rosales-Mendoza, Sergio

    2015-07-17

    Chikungunya virus is an emerging pathogen initially found in East Africa and currently spread into the Indian Ocean Islands, many regions of South East Asia, and in the Americas. No licensed vaccines against this eminent pathogen are available and thus intensive research in this field is a priority. This review presents the current scenario on the developments of Chikungunya virus vaccines and identifies the use of genetic engineered plants to develop attractive vaccines. The possible avenues to develop plant-made vaccines with distinct antigenic designs and expression modalities are identified and discussed considering current trends in the field.

  17. Chikungunya virus vaccines: Current strategies and prospects for developing plant-made vaccines.

    PubMed

    Salazar-González, Jorge A; Angulo, Carlos; Rosales-Mendoza, Sergio

    2015-07-17

    Chikungunya virus is an emerging pathogen initially found in East Africa and currently spread into the Indian Ocean Islands, many regions of South East Asia, and in the Americas. No licensed vaccines against this eminent pathogen are available and thus intensive research in this field is a priority. This review presents the current scenario on the developments of Chikungunya virus vaccines and identifies the use of genetic engineered plants to develop attractive vaccines. The possible avenues to develop plant-made vaccines with distinct antigenic designs and expression modalities are identified and discussed considering current trends in the field. PMID:26073010

  18. Molecular Modeling and Docking Study to Elucidate Novel Chikungunya Virus nsP2 Protease Inhibitors

    PubMed Central

    Agarwal, T.; Asthana, Somya; Bissoyi, A.

    2015-01-01

    Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot+. The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease. PMID:26664062

  19. Inflammatory Cytokine Expression Is Associated with Chikungunya Virus Resolution and Symptom Severity

    PubMed Central

    Kelvin, Alyson A.; Banner, David; Silvi, Giuliano; Moro, Maria Luisa; Spataro, Nadir; Gaibani, Paolo; Cavrini, Francesca; Pierro, Anna; Rossini, Giada; Cameron, Mark J.; Bermejo-Martin, Jesus F.; Paquette, Stéphane G.; Xu, Luoling; Danesh, Ali; Farooqui, Amber; Borghetto, Ilaria; Kelvin, David J.; Sambri, Vittorio; Rubino, Salvatore

    2011-01-01

    The Chikungunya virus infection zones have now quickly spread from Africa to parts of Asia, North America and Europe. Originally thought to trigger a disease of only mild symptoms, recently Chikungunya virus caused large-scale fatalities and widespread economic loss that was linked to recent virus genetic mutation and evolution. Due to the paucity of information on Chikungunya immunological progression, we investigated the serum levels of 13 cytokines/chemokines during the acute phase of Chikungunya disease and 6- and 12-month post-infection follow-up from patients of the Italian outbreak. We found that CXCL9/MIG, CCL2/MCP-1, IL-6 and CXCL10/IP-10 were significantly raised in the acute phase compared to follow-up samples. Furthermore, IL-1β, TNF-α, Il-12, IL-10, IFN-γ and IL-5 had low initial acute phase levels that significantly increased at later time points. Analysis of symptom severity showed association with CXCL9/MIG, CXCL10/IP-10 and IgG levels. These data give insight into Chikungunya disease establishment and subsequent convalescence, which is imperative to the treatment and containment of this quickly evolving and frequently re-emerging disease. PMID:21858242

  20. Early Events in Chikungunya Virus Infection—From Virus Cell Binding to Membrane Fusion

    PubMed Central

    van Duijl-Richter, Mareike K. S.; Hoornweg, Tabitha E.; Rodenhuis-Zybert, Izabela A.; Smit, Jolanda M.

    2015-01-01

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complication of CHIKV infection is severe joint pain, which can last for months to years. There are no vaccines or specific therapeutics available to prevent or treat infection. This review describes the critical steps in CHIKV cell entry. We summarize the latest studies on the virus-cell tropism, virus-receptor binding, internalization, membrane fusion and review the molecules and compounds that have been described to interfere with virus cell entry. The aim of the review is to give the reader a state-of-the-art overview on CHIKV cell entry and to provide an outlook on potential new avenues in CHIKV research. PMID:26198242

  1. Early Events in Chikungunya Virus Infection-From Virus Cell Binding to Membrane Fusion.

    PubMed

    van Duijl-Richter, Mareike K S; Hoornweg, Tabitha E; Rodenhuis-Zybert, Izabela A; Smit, Jolanda M

    2015-07-07

    Chikungunya virus (CHIKV) is a rapidly emerging mosquito-borne alphavirus causing millions of infections in the tropical and subtropical regions of the world. CHIKV infection often leads to an acute self-limited febrile illness with debilitating myalgia and arthralgia. A potential long-term complication of CHIKV infection is severe joint pain, which can last for months to years. There are no vaccines or specific therapeutics available to prevent or treat infection. This review describes the critical steps in CHIKV cell entry. We summarize the latest studies on the virus-cell tropism, virus-receptor binding, internalization, membrane fusion and review the molecules and compounds that have been described to interfere with virus cell entry. The aim of the review is to give the reader a state-of-the-art overview on CHIKV cell entry and to provide an outlook on potential new avenues in CHIKV research.

  2. Aedes hensilli as a Potential Vector of Chikungunya and Zika Viruses

    PubMed Central

    Ledermann, Jeremy P.; Guillaumot, Laurent; Yug, Lawrence; Saweyog, Steven C.; Tided, Mary; Machieng, Paul; Pretrick, Moses; Marfel, Maria; Griggs, Anne; Bel, Martin; Duffy, Mark R.; Hancock, W. Thane; Ho-Chen, Tai; Powers, Ann M.

    2014-01-01

    An epidemic of Zika virus (ZIKV) illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s) involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to identify the major containers serving as oviposition habitat for the likely vector(s). Adult mosquitoes were also collected by backpack aspiration, light trap, and gravid traps at select sites around the capital city. The predominant species found on the island was Aedes (Stegomyia) hensilli. No virus isolates were obtained from the adult field material collected, nor did any of the immature mosquitoes that were allowed to emerge to adulthood contain viable virus or nucleic acid. Therefore, laboratory studies of the probable vector, Ae. hensilli, were undertaken to determine the likelihood of this species serving as a vector for Zika virus and other arboviruses. Infection rates of up to 86%, 62%, and 20% and dissemination rates of 23%, 80%, and 17% for Zika, chikungunya, and dengue-2 viruses respectively, were found supporting the possibility that this species served as a vector during the Zika outbreak and that it could play a role in transmitting other medically important arboviruses. PMID:25299181

  3. Aedes hensilli as a potential vector of Chikungunya and Zika viruses.

    PubMed

    Ledermann, Jeremy P; Guillaumot, Laurent; Yug, Lawrence; Saweyog, Steven C; Tided, Mary; Machieng, Paul; Pretrick, Moses; Marfel, Maria; Griggs, Anne; Bel, Martin; Duffy, Mark R; Hancock, W Thane; Ho-Chen, Tai; Powers, Ann M

    2014-10-01

    An epidemic of Zika virus (ZIKV) illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s) involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to identify the major containers serving as oviposition habitat for the likely vector(s). Adult mosquitoes were also collected by backpack aspiration, light trap, and gravid traps at select sites around the capital city. The predominant species found on the island was Aedes (Stegomyia) hensilli. No virus isolates were obtained from the adult field material collected, nor did any of the immature mosquitoes that were allowed to emerge to adulthood contain viable virus or nucleic acid. Therefore, laboratory studies of the probable vector, Ae. hensilli, were undertaken to determine the likelihood of this species serving as a vector for Zika virus and other arboviruses. Infection rates of up to 86%, 62%, and 20% and dissemination rates of 23%, 80%, and 17% for Zika, chikungunya, and dengue-2 viruses respectively, were found supporting the possibility that this species served as a vector during the Zika outbreak and that it could play a role in transmitting other medically important arboviruses. PMID:25299181

  4. Aedes hensilli as a potential vector of Chikungunya and Zika viruses.

    PubMed

    Ledermann, Jeremy P; Guillaumot, Laurent; Yug, Lawrence; Saweyog, Steven C; Tided, Mary; Machieng, Paul; Pretrick, Moses; Marfel, Maria; Griggs, Anne; Bel, Martin; Duffy, Mark R; Hancock, W Thane; Ho-Chen, Tai; Powers, Ann M

    2014-10-01

    An epidemic of Zika virus (ZIKV) illness that occurred in July 2007 on Yap Island in the Federated States of Micronesia prompted entomological studies to identify both the primary vector(s) involved in transmission and the ecological parameters contributing to the outbreak. Larval and pupal surveys were performed to identify the major containers serving as oviposition habitat for the likely vector(s). Adult mosquitoes were also collected by backpack aspiration, light trap, and gravid traps at select sites around the capital city. The predominant species found on the island was Aedes (Stegomyia) hensilli. No virus isolates were obtained from the adult field material collected, nor did any of the immature mosquitoes that were allowed to emerge to adulthood contain viable virus or nucleic acid. Therefore, laboratory studies of the probable vector, Ae. hensilli, were undertaken to determine the likelihood of this species serving as a vector for Zika virus and other arboviruses. Infection rates of up to 86%, 62%, and 20% and dissemination rates of 23%, 80%, and 17% for Zika, chikungunya, and dengue-2 viruses respectively, were found supporting the possibility that this species served as a vector during the Zika outbreak and that it could play a role in transmitting other medically important arboviruses.

  5. First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia.

    PubMed

    Ooi, Man Kwan; Gan, Han Ming; Rohani, Ahmad; Syed Hassan, Sharifah

    2016-01-01

    Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID:27563048

  6. First Complete Genome Sequence of a Chikungunya Virus Strain Isolated from a Patient Diagnosed with Dengue Virus Infection in Malaysia

    PubMed Central

    Gan, Han Ming; Rohani, Ahmad

    2016-01-01

    Here, we report the complete genome sequence of a chikungunya virus coinfection strain isolated from a dengue virus serotype 2-infected patient in Malaysia. This coinfection strain was determined to be of the Asian genotype and contains a novel insertion in the nsP3 gene. PMID:27563048

  7. Nowcasting the Spread of Chikungunya Virus in the Americas

    PubMed Central

    Johansson, Michael A.; Powers, Ann M.; Pesik, Nicki; Cohen, Nicole J.; Staples, J. Erin

    2014-01-01

    Background In December 2013, the first locally-acquired chikungunya virus (CHIKV) infections in the Americas were reported in the Caribbean. As of May 16, 55,992 cases had been reported and the outbreak was still spreading. Identification of newly affected locations is paramount to intervention activities, but challenging due to limitations of current data on the outbreak and on CHIKV transmission. We developed models to make probabilistic predictions of spread based on current data considering these limitations. Methods and Findings Branching process models capturing travel patterns, local infection prevalence, climate dependent transmission factors, and associated uncertainty estimates were developed to predict probable locations for the arrival of CHIKV-infected travelers and for the initiation of local transmission. Many international cities and areas close to where transmission has already occurred were likely to have received infected travelers. Of the ten locations predicted to be the most likely locations for introduced CHIKV transmission in the first four months of the outbreak, eight had reported local cases by the end of April. Eight additional locations were likely to have had introduction leading to local transmission in April, but with substantial uncertainty. Conclusions Branching process models can characterize the risk of CHIKV introduction and spread during the ongoing outbreak. Local transmission of CHIKV is currently likely in several Caribbean locations and possible, though uncertain, for other locations in the continental United States, Central America, and South America. This modeling framework may also be useful for other outbreaks where the risk of pathogen spread over heterogeneous transportation networks must be rapidly assessed on the basis of limited information. PMID:25111394

  8. Evaluation of Commercially Available Chikungunya Virus Immunoglobulin M Detection Assays.

    PubMed

    Johnson, Barbara W; Goodman, Christin H; Holloway, Kimberly; de Salazar, P Martinez; Valadere, Anne M; Drebot, Michael A

    2016-07-01

    Commercial chikungunya virus (CHIKV)-specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits. PMID:26976887

  9. Evaluation of Commercially Available Chikungunya Virus Immunoglobulin M Detection Assays

    PubMed Central

    Johnson, Barbara W.; Goodman, Christin H.; Holloway, Kimberly; de Salazar, P. Martinez; Valadere, Anne M.; Drebot, Michael A.

    2016-01-01

    Commercial chikungunya virus (CHIKV)–specific IgM detection kits were evaluated at the Centers for Disease Control and Prevention (CDC), the Public Health Agency of Canada National Microbiology Laboratory, and the Caribbean Public Health Agency (CARPHA). The Euroimmun Anti-CHIKV IgM ELISA kit had ≥ 95% concordance with all three reference laboratory results. The limit of detection for low CHIK IgM+ samples, as measured by serial dilution of seven sera up to 1:12,800 ranged from 1:800 to 1:3,200. The Euroimmun IIFT kit evaluated at CDC and CARPHA performed well, but required more retesting of equivocal results. The InBios CHIKjj Detect MAC-ELISA had 100% and 98% concordance with CDC and CARPHA results, respectively, and had equal sensitivity to the CDC MAC-ELISA to 1:12,800 dilution in serially diluted samples. The Abcam Anti-CHIKV IgM ELISA had high performance at CARPHA, but at CDC, performance was inconsistent between lots. After replacement of the biotinylated IgM antibody controls with serum containing CHIKV-specific IgM and additional quality assurance/control measures, the Abcam kit was rereleased and reevaluated at CDC. The reformatted Abcam kit had 97% concordance with CDC results and limit of detection of 1:800 to 1:3,200. Two rapid tests and three other CHIKV MAC-ELISAs evaluated at CDC had low sensitivity, as the CDC CHIKV IgM in-house positive controls were below the level of detection. In conclusion, laboratories have options for CHIKV serological diagnosis using validated commercial kits. PMID:26976887

  10. Congenital Chikungunya Virus Infection after an Outbreak in Salvador, Bahia, Brazil.

    PubMed

    Lyra, Priscila Pinheiro Ribeiro; Campos, Gúbio Soares; Bandeira, Igor Dórea; Sardi, Silvia Ines; Costa, Lilian Ferreira de Moura; Santos, Flávia Rocha; Ribeiro, Carlos Alexandre Santos; Jardim, Alena Maria Barreto; Santiago, Ana Cecília Travassos; de Oliveira, Patrícia Maria Ribeiro; Moreira, Lícia Maria Oliveira

    2016-07-01

    There is little information about the congenital chikungunya virus (CHIKV) transmission. We describe two cases of well-documented congenital CHIKV infection in Salvador-Brazil, where CHIKV has been identified since 2014. The outbreak in the city led to the clinical CHIKV diagnoses of both pregnant women 2 days before delivery. Urine and blood samples from the mothers and newborns were collected and tested for reverse transcription-polymerase chain reaction (PCR) analysis for Zika, dengue, and CHIKV. Both neonates and mothers had positive urine and serum PCR results for CHIKV. The newborns had significant perinatal complications and were admitted to the neonatal intensive care unit. The purpose of our case report is to show how severe congenital CHIKV infection can be and the importance to include CHIKV infection in the differential diagnosis of neonatal sepsis when mothers have clinical signs of the disease and live in an affected area. PMID:27555980

  11. Congenital Chikungunya Virus Infection after an Outbreak in Salvador, Bahia, Brazil

    PubMed Central

    Lyra, Priscila Pinheiro Ribeiro; Campos, Gúbio Soares; Bandeira, Igor Dórea; Sardi, Silvia Ines; Costa, Lilian Ferreira de Moura; Santos, Flávia Rocha; Ribeiro, Carlos Alexandre Santos; Jardim, Alena Maria Barreto; Santiago, Ana Cecília Travassos; de Oliveira, Patrícia Maria Ribeiro; Moreira, Lícia Maria Oliveira

    2016-01-01

    There is little information about the congenital chikungunya virus (CHIKV) transmission. We describe two cases of well-documented congenital CHIKV infection in Salvador-Brazil, where CHIKV has been identified since 2014. The outbreak in the city led to the clinical CHIKV diagnoses of both pregnant women 2 days before delivery. Urine and blood samples from the mothers and newborns were collected and tested for reverse transcription-polymerase chain reaction (PCR) analysis for Zika, dengue, and CHIKV. Both neonates and mothers had positive urine and serum PCR results for CHIKV. The newborns had significant perinatal complications and were admitted to the neonatal intensive care unit. The purpose of our case report is to show how severe congenital CHIKV infection can be and the importance to include CHIKV infection in the differential diagnosis of neonatal sepsis when mothers have clinical signs of the disease and live in an affected area. PMID:27555980

  12. Congenital Chikungunya Virus Infection after an Outbreak in Salvador, Bahia, Brazil.

    PubMed

    Lyra, Priscila Pinheiro Ribeiro; Campos, Gúbio Soares; Bandeira, Igor Dórea; Sardi, Silvia Ines; Costa, Lilian Ferreira de Moura; Santos, Flávia Rocha; Ribeiro, Carlos Alexandre Santos; Jardim, Alena Maria Barreto; Santiago, Ana Cecília Travassos; de Oliveira, Patrícia Maria Ribeiro; Moreira, Lícia Maria Oliveira

    2016-07-01

    There is little information about the congenital chikungunya virus (CHIKV) transmission. We describe two cases of well-documented congenital CHIKV infection in Salvador-Brazil, where CHIKV has been identified since 2014. The outbreak in the city led to the clinical CHIKV diagnoses of both pregnant women 2 days before delivery. Urine and blood samples from the mothers and newborns were collected and tested for reverse transcription-polymerase chain reaction (PCR) analysis for Zika, dengue, and CHIKV. Both neonates and mothers had positive urine and serum PCR results for CHIKV. The newborns had significant perinatal complications and were admitted to the neonatal intensive care unit. The purpose of our case report is to show how severe congenital CHIKV infection can be and the importance to include CHIKV infection in the differential diagnosis of neonatal sepsis when mothers have clinical signs of the disease and live in an affected area.

  13. Detection of east/central/south African genotype of chikungunya virus in Myanmar, 2010.

    PubMed

    Tun, Mya Myat Ngwe; Thant, Kyaw Zin; Inoue, Shingo; Nabeshima, Takeshi; Aoki, Kotaro; Kyaw, Aung Kyaw; Myint, Tin; Tar, Thi; Maung, Kay Thwe Thwe; Hayasaka, Daisuke; Morita, Kouichi

    2014-08-01

    In 2010, chikungunya virus of the East Central South African genotype was isolated from 4 children in Myanmyar who had dengue-like symptoms. Phylogenetic analysis of the E1 gene revealed that the isolates were closely related to isolates from China, Thailand, and Malaysia that harbor the A226V mutation in this gene.

  14. Chikungunya Virus as Cause of Febrile Illness Outbreak, Chiapas, Mexico, 2014.

    PubMed

    Kautz, Tiffany F; Díaz-González, Esteban E; Erasmus, Jesse H; Malo-García, Iliana R; Langsjoen, Rose M; Patterson, Edward I; Auguste, Dawn I; Forrester, Naomi L; Sanchez-Casas, Rosa Maria; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M; Weaver, Scott C; Fernández-Salas, Ildefonso

    2015-11-01

    Since chikungunya virus (CHIKV) was introduced into the Americas in 2013, its geographic distribution has rapidly expanded. Of 119 serum samples collected in 2014 from febrile patients in southern Mexico, 79% were positive for CHIKV or IgM against CHIKV. Sequencing results confirmed CHIKV strains closely related to Caribbean isolates.

  15. Genomic Assays for Identification of Chikungunya Virus in Blood Donors, Puerto Rico, 2014.

    PubMed

    Chiu, Charles Y; Bres, Vanessa; Yu, Guixia; Krysztof, David; Naccache, Samia N; Lee, Deanna; Pfeil, Jacob; Linnen, Jeffrey M; Stramer, Susan L

    2015-08-01

    A newly developed transcription-mediated amplification assay was used to detect chikungunya virus infection in 3 of 557 asymptomatic donors (0.54%) from Puerto Rico during the 2014-2015 Caribbean epidemic. Viral detection was confirmed by using PCR, microarray, and next-generation sequencing. Molecular clock analysis dated the emergence of the Puerto Rico strains to early 2013.

  16. Detection of East/Central/South African Genotype of Chikungunya Virus in Myanmar, 2010

    PubMed Central

    Tun, Mya Myat Ngwe; Thant, Kyaw Zin; Inoue, Shingo; Nabeshima, Takeshi; Aoki, Kotaro; Kyaw, Aung Kyaw; Myint, Tin; Tar, Thi; Maung, Kay Thwe Thwe; Hayasaka, Daisuke

    2014-01-01

    In 2010, chikungunya virus of the East Central South African genotype was isolated from 4 children in Myanmyar who had dengue-like symptoms. Phylogenetic analysis of the E1 gene revealed that the isolates were closely related to isolates from China, Thailand, and Malaysia that harbor the A226V mutation in this gene. PMID:25062511

  17. Chikungunya Virus as Cause of Febrile Illness Outbreak, Chiapas, Mexico, 2014

    PubMed Central

    Kautz, Tiffany F.; Díaz-González, Esteban E.; Erasmus, Jesse H.; Malo-García, Iliana R.; Langsjoen, Rose M.; Patterson, Edward I.; Auguste, Dawn I.; Forrester, Naomi L.; Sanchez-Casas, Rosa Maria; Hernández-Ávila, Mauricio; Alpuche-Aranda, Celia M.; Fernández-Salas, Ildefonso

    2015-01-01

    Since chikungunya virus (CHIKV) was introduced into the Americas in 2013, its geographic distribution has rapidly expanded. Of 119 serum samples collected in 2014 from febrile patients in southern Mexico, 79% were positive for CHIKV or IgM against CHIKV. Sequencing results confirmed CHIKV strains closely related to Caribbean isolates. PMID:26488312

  18. Three-way interactions between mosquito population, viral strain and temperature underlying chikungunya virus transmission potential

    PubMed Central

    Zouache, Karima; Fontaine, Albin; Vega-Rua, Anubis; Mousson, Laurence; Thiberge, Jean-Michel; Lourenco-De-Oliveira, Ricardo; Caro, Valérie; Lambrechts, Louis; Failloux, Anna-Bella

    2014-01-01

    Interactions between pathogens and their insect vectors in nature are under the control of both genetic and non-genetic factors, yet most studies on mosquito vector competence for human pathogens are conducted in laboratory systems that do not consider genetic and/or environmental variability. Evaluating the risk of emergence of arthropod-borne viruses (arboviruses) of public health importance such as chikungunya virus (CHIKV) requires a more realistic appraisal of genetic and environmental contributions to vector competence. In particular, sources of variation do not necessarily act independently and may combine in the form of interactions. Here, we measured CHIKV transmission potential by the mosquito Aedes albopictus in all combinations of six worldwide vector populations, two virus strains and two ambient temperatures (20°C and 28°C). Overall, CHIKV transmission potential by Ae. albopictus strongly depended on the three-way combination of mosquito population, virus strain and temperature. Such genotype-by-genotype-by-environment (G × G × E) interactions question the relevance of vector competence studies conducted with a simpler set of conditions. Our results highlight the need to account for the complex interplay between vectors, pathogens and environmental factors to accurately assess the potential of vector-borne diseases to emerge. PMID:25122228

  19. Travelers With Chikungunya Virus Infection Returning to Northwest Italy From the Caribbean and Central America During June-November 2014.

    PubMed

    Burdino, Elisa; Ruggiero, Tina; Milia, Maria Grazia; Proietti, Alex; Sergi, Giuseppina; Torta, Ilaria; Calleri, Guido; Caramello, Pietro; Tiberti, Donatella; Ghisetti, Valeria

    2015-01-01

    Chikungunya virus (CHIKV) has recently emerged in the Caribbean. In Italy, CHIKV vector is documented in the Po river valley; therefore, a risk for autochthonous outbreaks is present. We report a case series of seven imported CHIKV infections in travelers returning from the Caribbean and Latin America occurring between June and November 2014, in the area of Turin, Northwest Italy, 3 years after the last imported cases were reported. These cases are a reminder of the need to always consider CHIKV infection in travelers from these epidemic areas as well as the importance of a prompt diagnosis. PMID:26080943

  20. Genetic divergence of Chikungunya virus plaque variants from the Comoros Island (2005).

    PubMed

    Wasonga, Caroline; Inoue, Shingo; Rumberia, Cecilia; Michuki, George; Kimotho, James; Ongus, Juliette R; Sang, Rosemary; Musila, Lillian

    2015-12-01

    Chikungunya virus (CHIKV) from a human sample collected during the 2005 Chikungunya outbreak in the Comoros Island, showed distinct and reproducible large (L2) and small (S7) plaques which were characterized in this study. The parent strain and plaque variants were analysed by in vitro growth kinetics in different cell lines and their genetic similarity assessed by whole genome sequencing, comparative sequence alignment and phylogenetic analysis. In vitro growth kinetic assays showed similar growth patterns of both plaque variants in Vero cells but higher viral titres of S7 compared to L2 in C6/36 cells. Amino acids (AA) alignments of the CHIKV plaque variants and S27 African prototype strain, showed 30 AA changes in the non-structural proteins (nsP) and 22 AA changes in the structural proteins. Between L2 and S7, only two AAs differences were observed. A missense substitution (C642Y) of L2 in the nsP2, involving a conservative AA substitution and a nonsense substitution (R524X) of S7 in the nsP3, which has been shown to enhance O'nyong-nyong virus infectivity and dissemination in Anopheles mosquitoes. The phenotypic difference observed in plaque size could be attributed to one of these AA substitutions. Phylogenetic analysis showed that the parent strain and its variants clustered closely together with each other and with Indian Ocean CHIKV strains indicating circulation of isolates with close evolutionary relatedness in the same outbreak. These observations pave way for important functional studies to understand the significance of the identified genetic changes in virulence and viral transmission in mosquito and mammalian hosts.

  1. Effective cutaneous vaccination using an inactivated chikungunya virus vaccine delivered by Foroderm.

    PubMed

    Rudd, Penny A; Raphael, Anthony P; Yamada, Miko; Nufer, Kaitlin L; Gardner, Joy; Le, Thuy T T; Prow, Natalie A; Dang, Nhung; Schroder, Wayne A; Prow, Tarl W; Suhrbier, Andreas

    2015-09-22

    Foroderm is a new cutaneous delivery technology that uses high-aspect ratio, cylindrical silica microparticles, that are massaged into the skin using a 3D-printed microtextured applicator, in order to deliver payloads across the epidermis. Herein we show that this technology is effective for delivery of a non-adjuvanted, inactivated, whole-virus chikungunya virus vaccine in mice, with minimal post-vaccination skin reactions. A single topical Foroderm-based vaccination induced T cell, Th1 cytokine and antibody responses, which provided complete protection against viraemia and disease after challenge with chikungunya virus. Foroderm vaccination was shown to deliver fluorescent, virus-sized beads across the epidermis, with beads subsequently detected in draining lymph nodes. Foroderm vaccination also stimulated the egress of MHC II(+) antigen presenting cells from the skin. Foroderm thus has potential as a simple, cheap, effective, generic, needle-free technology for topical delivery of vaccines.

  2. Isolation of infectious chikungunya virus and dengue virus using anionic polymer-coated magnetic beads.

    PubMed

    Patramool, Sirilaksana; Bernard, Eric; Hamel, Rodolphe; Natthanej, Luplertlop; Chazal, Nathalie; Surasombatpattana, Pornapat; Ekchariyawat, Peeraya; Daoust, Simon; Thongrungkiat, Supatra; Thomas, Frédéric; Briant, Laurence; Missé, Dorothée

    2013-10-01

    Mosquitoes-borne viruses are a major threat for human populations. Among them, chikungunya virus (CHIKV) and dengue virus (DENV) cause thousands of cases worldwide. The recent propagation of mosquito vectors competent to transmit these viruses to temperate areas increases their potential impact on susceptible human populations. The development of sensitive methods allowing the detection and isolation of infectious viruses is of crucial interest for determination of virus contamination in humans and in competent mosquito vectors. However, simple and rapid method allowing the capture of infectious CHIKV and DENV from samples with low viral titers useful for further genetic and functional characterization of circulating strains is lacking. The present study reports a fast and sensitive isolation technique based on viral particles adsorption on magnetic beads coated with anionic polymer, poly(methyl vinyl ether-maleic anhydrate) and suitable for isolation of infectious CHIKV and DENV from the four serotypes. Starting from quite reduced biological material, this method was accurate to combine with conventional detection techniques, including qRT-PCR and immunoblotting and allowed isolation of infectious particles without resorting to a step of cultivation. The use of polymer-coated magnetic beads is therefore of high interest for rapid detection and isolation of CHIKV and DENV from samples with reduced viral loads and represents an accurate approach for the surveillance of mosquito vector in area at risk for arbovirus outbreaks.

  3. Chikungunya virus RNA and antibody testing at a National Reference Laboratory since the emergence of Chikungunya virus in the Americas.

    PubMed

    Prince, Harry E; Seaton, Brent L; Matud, Jose L; Batterman, Hollis J

    2015-03-01

    Since first reported in the Americas in December 2013, chikungunya virus (CHIKV) infections have been documented in travelers returning from the Caribbean, with many cases identified by CHIKV antibody and/or RNA testing at our laboratory. We used our large data set to characterize the relationship between antibody titers and RNA detection and to estimate IgM persistence. CHIKV RNA was measured by nucleic acid amplification and CHIKV IgG/IgM by indirect immunofluorescence. Of the 1,306 samples submitted for RNA testing in January through September 2014, 393 (30%) were positive; for 166 RNA-positive samples, CHIKV antibody testing was also ordered, and 84% were antibody negative. Of the 6,971 sera submitted for antibody testing in January through September 2014, 1,811 (26%) were IgM positive; 1,461 IgM positives (81%) were also IgG positive. The relationship between the CHIKV antibody titers and RNA detection was evaluated using 376 IgM-positive samples (138 with RNA testing ordered and 238 deidentified and tested for RNA). RNA detection showed no significant association with the IgM titer but was inversely related to the IgG titer; 63% of the IgG negative sera were RNA positive, compared to 36% of sera with low IgG titers (1:10 to 1:80) and 16% with IgG titers of ≥1:160. Using second-sample results from 62 seroconverters, we estimated that CHIKV IgM persists for 110 days (95% confidence interval, 78 to 150 days) after the initial antibody-negative sample. These findings indicate that (i) RNA detection is more sensitive than antibody detection early in CHIKV infection, (ii) in the absence of RNA results, the IgG titer of the IgM-positive samples may be a useful surrogate for viremia, and (iii) CHIKV IgM persists for approximately 4 months after symptom onset.

  4. Molecular epidemiology, evolution and phylogeny of Chikungunya virus: An updating review.

    PubMed

    Lo Presti, Alessandra; Cella, Eleonora; Angeletti, Silvia; Ciccozzi, Massimo

    2016-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, causing a febrile illness associated with severe arthralgia and rash. In this review, we summarized a series of articles published from 2013 to 2016 concerning CHIKV epidemiology, phylogeny, vaccine and therapies, to give an update of our most recent article written in 2014 (Lo Presti et al.,2014). CHIKV infection was first reported in 1952 from Makonde plateaus and since this time caused many outbreaks worldwide, involving the Indian Ocean region, African countries, American continent and Italy. CHIKV infection is still underestimated and it is normally associated with clinical symptoms overlapping with dengue virus, recurring epidemics and mutations within the viral genome. These characteristics promote the geographical spread and the inability to control vector-mediated transmission of the virus. For these reasons, the majority of studies were aimed to describe outbreaks and to enhance knowledge on CHIKV biology, pathogenesis, infection treatment, and prevention. In this review, 16 studies on CHIKV phylogenetic and phylodinamics were considered, during the years 2013-2016. Phylogenetic and phylodinamic analysis are useful tools to investigate how the genealogy of a pathogen population is influenced by pathogen's demographic history, host immunological milieu and environmental/ecological factors. Phylogenetic tools were revealed important to reconstruct the geographic spread of CHIKV during the epidemics wave and to have information on the circulating strains of the virus, that are important for the prediction and control of the epidemics, as well as for vaccines and antiviral drugs development. In conclusion, this updating review can give a critical appraisal of the epidemiology, therapeutic and phylogenesis of CHIKV, reinforcing the need to monitor the geographic spread of virus and vectors. PMID:27085290

  5. Global distribution and environmental suitability for chikungunya virus, 1952 to 2015

    PubMed Central

    Golding, N; Pigott, DM; Brady, OJ; Moyes, CL; Johansson, MA; Gething, PW; Velayudhan, R; Khan, K

    2016-01-01

    Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV. PMID:27239817

  6. Global distribution and environmental suitability for chikungunya virus, 1952 to 2015.

    PubMed

    Nsoesie, Elaine O; Kraemer, Moritz Ug; Golding, Nick; Pigott, David M; Brady, Oliver J; Moyes, Catherine L; Johansson, Michael A; Gething, Peter W; Velayudhan, Raman; Khan, Kamran; Hay, Simon I; Brownstein, John S

    2016-05-19

    Chikungunya fever is an acute febrile illness caused by the chikungunya virus (CHIKV), which is transmitted to humans by Aedes mosquitoes. Although chikungunya fever is rarely fatal, patients can experience debilitating symptoms that last from months to years. Here we comprehensively assess the global distribution of chikungunya and produce high-resolution maps, using an established modelling framework that combines a comprehensive occurrence database with bespoke environmental correlates, including up-to-date Aedes distribution maps. This enables estimation of the current total population-at-risk of CHIKV transmission and identification of areas where the virus may spread to in the future. We identified 94 countries with good evidence for current CHIKV presence and a set of countries in the New and Old World with potential for future CHIKV establishment, demonstrated by high environmental suitability for transmission and in some cases previous sporadic reports. Aedes aegypti presence was identified as one of the major contributing factors to CHIKV transmission but significant geographical heterogeneity exists. We estimated 1.3 billion people are living in areas at-risk of CHIKV transmission. These maps provide a baseline for identifying areas where prevention and control efforts should be prioritised and can be used to guide estimation of the global burden of CHIKV. PMID:27239817

  7. A Single-Amino-Acid Polymorphism in Chikungunya Virus E2 Glycoprotein Influences Glycosaminoglycan Utilization

    PubMed Central

    Silva, Laurie A.; Khomandiak, Solomiia; Ashbrook, Alison W.; Weller, Romy; Heise, Mark T.; Morrison, Thomas E.

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a reemerging arbovirus responsible for outbreaks of infection throughout Asia and Africa, causing an acute illness characterized by fever, rash, and polyarthralgia. Although CHIKV infects a broad range of host cells, little is known about how CHIKV binds and gains access to the target cell interior. In this study, we tested whether glycosaminoglycan (GAG) binding is required for efficient CHIKV replication using CHIKV vaccine strain 181/25 and clinical isolate SL15649. Preincubation of strain 181/25, but not SL15649, with soluble GAGs resulted in dose-dependent inhibition of infection. While parental Chinese hamster ovary (CHO) cells are permissive for both strains, neither strain efficiently bound to or infected mutant CHO cells devoid of GAG expression. Although GAGs appear to be required for efficient binding of both strains, they exhibit differential requirements for GAGs, as SL15649 readily infected cells that express excess chondroitin sulfate but that are devoid of heparan sulfate, whereas 181/25 did not. We generated a panel of 181/25 and SL15649 variants containing reciprocal amino acid substitutions at positions 82 and 318 in the E2 glycoprotein. Reciprocal exchange at residue 82 resulted in a phenotype switch; Gly82 results in efficient infection of mutant CHO cells but a decrease in heparin binding, whereas Arg82 results in reduced infectivity of mutant cells and an increase in heparin binding. These results suggest that E2 residue 82 is a primary determinant of GAG utilization, which likely mediates attenuation of vaccine strain 181/25. IMPORTANCE Chikungunya virus (CHIKV) infection causes a debilitating rheumatic disease that can persist for months to years, and yet there are no licensed vaccines or antiviral therapies. Like other alphaviruses, CHIKV displays broad tissue tropism, which is thought to be influenced by virus-receptor interactions. In this study, we determined that cell-surface glycosaminoglycans are

  8. Cellular and molecular mechanisms of chikungunya pathogenesis.

    PubMed

    Lum, Fok-Moon; Ng, Lisa F P

    2015-08-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus that causes chikungunya fever, a disease characterized by the onset of fever and rashes, with arthralgia as its hallmark symptom. CHIKV has re-emerged over the past decade, causing numerous outbreaks around the world. Since late 2013, CHIKV has reached the shores of the Americas, causing more than a million cases of infection. Despite concentrated efforts to understand the pathogenesis of the disease, further outbreaks remain a threat. This review highlights important findings regarding CHIKV-associated immunopathogenesis and offers important insights into future directions. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."

  9. Outbreak of chikungunya fever in Thailand and virus detection in field population of vector mosquitoes, Aedes aegypti (L.) and Aedes albopictus Skuse (Diptera: Culicidae).

    PubMed

    Thavara, Usavadee; Tawatsin, Apiwat; Pengsakul, Theerakamol; Bhakdeenuan, Payu; Chanama, Sumalee; Anantapreecha, Surapee; Molito, Chusak; Chompoosri, Jakkrawarn; Thammapalo, Suwich; Sawanpanyalert, Pathom; Siriyasatien, Padet

    2009-09-01

    We investigated chikungunya fever outbreak in the southern part of Thailand. Human plasma specimens obtained from suspected patients and adult wild-caught mosquitoes were detected for chikungunya virus employing reverse transcriptase-polymerase chain reaction technique. Chikungunya virus was detected in about half of the blood specimens whereas a range of 5.5 to 100% relative infection rate was found in both sexes of the vector mosquitoes, Aedes aegypti (L.) and Ae. albopictus Skuse. The infection rate in Ae. albopictus was higher than in Ae. aegypti, with relative infection rate in male of both species being higher than in female. The appearance of chikungunya virus in adult male mosquitoes of both species reveals a role of transovarial transmission of the virus in field population of the mosquito vectors. These findings have provided further understanding of the relationship among mosquito vectors, chikungunya virus and epidemiology of chikungunya fever in Thailand.

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

    PubMed

    Raut, Chandrashekhar G; Hanumaiah, H; Raut, Wrunda C

    2016-01-01

    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. PMID:27233262

  11. Oral receptivity of Aedes aegypti from Cape Verde for yellow fever, dengue, and chikungunya viruses.

    PubMed

    Vazeille, Marie; Yébakima, André; Lourenço-de-Oliveira, Ricardo; Andriamahefazafy, Barrysson; Correira, Artur; Rodrigues, Julio Monteiro; Veiga, Antonio; Moreira, Antonio; Leparc-Goffart, Isabelle; Grandadam, Marc; Failloux, Anna-Bella

    2013-01-01

    At the end of 2009, 21,313 cases of dengue-3 virus (DENV-3) were reported in the islands of Cape Verde, an archipelago located in the Atlantic Ocean 570 km from the coast of western Africa. It was the first dengue outbreak ever reported in Cape Verde. Mosquitoes collected in July 2010 in the city of Praia, on the island of Santiago, were identified morphologically as Aedes aegypti formosus. Using experimental oral infections, we found that this vector showed a moderate ability to transmit the epidemic dengue-3 virus, but was highly susceptible to chikungunya and yellow fever viruses.

  12. Tigliane diterpenes from Croton mauritianus as inhibitors of chikungunya virus replication.

    PubMed

    Corlay, Nina; Delang, Leen; Girard-Valenciennes, Emmanuelle; Neyts, Johan; Clerc, Patricia; Smadja, Jacqueline; Guéritte, Françoise; Leyssen, Pieter; Litaudon, Marc

    2014-09-01

    A bioassay-guided purification of an EtOAc extract of the leaves of Croton mauritianus using a chikungunya virus-cell-based assay led to the isolation of 12-O-decanoylphorbol-13-acetate (1) and the new 12-O-decanoyl-7-hydroperoxy-phorbol-5-ene-13-acetate (2), along with loliolide, vomifoliol, dehydrovomifoliol, annuionone D and bluemol C. The planar structure and the relative configuration of compound 2 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Compounds 1 and 2 inhibited chikungunya virus-induced cell death in cell culture with EC50s of 2.4±0.3 and 4.0±0.8 μM, respectively.

  13. Development and evaluation of baculovirus-expressed Chikungunya virus E1 envelope proteins for serodiagnosis of Chikungunya infection.

    PubMed

    Kumar, Pankaj; Pok, Kwoon-Yong; Tan, Li-Kiang; Angela, Chow; Leo, Yee-Sin; Ng, Lee-Ching

    2014-09-01

    Population-based serosurveillance studies provide critical estimates on community-level immunity and the potential for future outbreaks. Currently, serological assays, such as IgG enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence tests (IIFT) based on the inactivated whole virus are used to determine past Chikungunya virus (CHIKV) infection. However, these commercially available tests have variable sensitivities. To develop and evaluate recombinant based CHIKV-specific IgG antibody capture ELISAs (GAC-ELISAs), baculoviruses carrying wild-type (E1-A226, named WT) or mutant (E1-A226V, named MUT) E1 envelope protein genes of CHIKV were generated. The seroreactivity of recombinant CHIKV WT and MUT envelope proteins were determined using residual blood, collected from CHIKV-confirmed patients. The sensitivities of both recombinant CHIKV envelope proteins were 83.0% as measured by GAC-ELISAs. The specificities of both recombinant proteins were 87.8%. These GAC-ELISAs were also able to detect the persistence of anti-CHIKV IgG antibodies up to 6 months after the disease onset, together with rise in sensitivities with increasing time. These results suggest that the baculovirus purified recombinant CHIKV envelope proteins react with anti-CHIKV IgG antibodies and may be useful in population-based seroprevalence surveys. In addition, these GAC-ELISAs offer good diagnostic value to determine the recent/past CHIKV infection status in non-endemic populations.

  14. Chikungunya Virus Replication in Salivary Glands of the Mosquito Aedes albopictus.

    PubMed

    Vega-Rúa, Anubis; Schmitt, Christine; Bonne, Isabelle; Krijnse Locker, Jacomine; Failloux, Anna-Bella

    2015-11-17

    Chikungunya virus (CHIKV) is an emerging arbovirus transmitted to humans by mosquitoes such as Aedes albopictus. To be transmitted, CHIKV must replicate in the mosquito midgut, then disseminate in the hemocele and infect the salivary glands before being released in saliva. We have developed a standardized protocol to visualize viral particles in the mosquito salivary glands using transmission electron microscopy. Here we provide direct evidence for CHIKV replication and storage in Ae. albopictus salivary glands.

  15. CCR2 Deficiency Promotes Exacerbated Chronic Erosive Neutrophil-Dominated Chikungunya Virus Arthritis

    PubMed Central

    Poo, Yee Suan; Nakaya, Helder; Gardner, Joy; Larcher, Thibaut; Schroder, Wayne A.; Le, Thuy T.; Major, Lee D.

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a member of a globally distributed group of arthritogenic alphaviruses that cause weeks to months of debilitating polyarthritis/arthralgia, which is often poorly managed with current treatments. Arthritic disease is usually characterized by high levels of the chemokine CCL2 and a prodigious monocyte/macrophage infiltrate. Several inhibitors of CCL2 and its receptor CCR2 are in development and may find application for treatment of certain inflammatory conditions, including autoimmune and viral arthritides. Here we used CCR2−/− mice to determine the effect of CCR2 deficiency on CHIKV infection and arthritis. Although there were no significant changes in viral load or RNA persistence and only marginal changes in antiviral immunity, arthritic disease was substantially increased and prolonged in CCR2−/− mice compared to wild-type mice. The monocyte/macrophage infiltrate was replaced in CCR2−/− mice by a severe neutrophil (followed by an eosinophil) infiltrate and was associated with changes in the expression levels of multiple inflammatory mediators (including CXCL1, CXCL2, granulocyte colony-stimulating factor [G-CSF], interleukin-1β [IL-1β], and IL-10). The loss of anti-inflammatory macrophages and their activities (e.g., efferocytosis) was also implicated in exacerbated inflammation. Clear evidence of cartilage damage was also seen in CHIKV-infected CCR2−/− mice, a feature not normally associated with alphaviral arthritides. Although recruitment of CCR2+ monocytes/macrophages can contribute to inflammation, it also appears to be critical for preventing excessive pathology and resolving inflammation following alphavirus infection. Caution might thus be warranted when considering therapeutic targeting of CCR2/CCL2 for the treatment of alphaviral arthritides. IMPORTANCE Here we describe the first analysis of viral arthritis in mice deficient for the chemokine receptor CCR2. CCR2 is thought to be central to the

  16. Cases of chikungunya virus infection in travellers returning to Spain from Haiti or Dominican Republic, April-June 2014.

    PubMed

    Requena-Méndez, A; Garcia, C; Aldasoro, E; Vicente, J A; Martínez, M J; Pérez-Molina, J A; Calvo-Cano, A; Franco, L; Parrón, I; Molina, A; Ruiz, M; Álvarez, J; Sánchez-Seco, M P; Gascón, J

    2014-01-01

    Ten cases of chikungunya were diagnosed in Spanish travellers returning from Haiti (n=2), the Dominican Republic (n=7) or from both countries (n=1) between April and June 2014. These cases remind clinicians to consider chikungunya in European travellers presenting with febrile illness and arthralgia, who are returning from the Caribbean region and Central America, particularly from Haiti and the Dominican Republic. The presence of Aedes albopictus together with viraemic patients could potentially lead to autochthonous transmission of chikungunya virus in southern Europe.

  17. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014

    PubMed Central

    Fernandez-Garcia, Maria Dolores; Bangert, Mathieu; de Ory, Fernando; Potente, Arantxa; Hernandez, Lourdes; Lasala, Fatima; Herrero, Laura; Molero, Francisca; Negredo, Anabel; Vázquez, Ana; Minguito, Teodora; Balfagón, Pilar; de la Fuente, Jesus; Puente, Sabino; Ramírez de Arellano, Eva; Lago, Mar; Martinez, Miguel; Gascón, Joaquim; Norman, Francesca; Lopez-Velez, Rogelio; Sulleiro, Elena; Pou, Diana; Serre, Nuria; Roblas, Ricardo Fernández; Tenorio, Antonio; Franco, Leticia; Sanchez-Seco, Maria Paz

    2016-01-01

    Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers. PMID:27631156

  18. Chikungunya virus infections among travellers returning to Spain, 2008 to 2014.

    PubMed

    Fernandez-Garcia, Maria Dolores; Bangert, Mathieu; de Ory, Fernando; Potente, Arantxa; Hernandez, Lourdes; Lasala, Fatima; Herrero, Laura; Molero, Francisca; Negredo, Anabel; Vázquez, Ana; Minguito, Teodora; Balfagón, Pilar; de la Fuente, Jesus; Puente, Sabino; Ramírez de Arellano, Eva; Lago, Mar; Martinez, Miguel; Gascón, Joaquim; Norman, Francesca; Lopez-Velez, Rogelio; Sulleiro, Elena; Pou, Diana; Serre, Nuria; Roblas, Ricardo Fernández; Tenorio, Antonio; Franco, Leticia; Sanchez-Seco, Maria Paz

    2016-09-01

    Since the first documented autochthonous transmission of chikungunya virus in the Caribbean island of Saint Martin in 2013, the infection has been reported within the Caribbean region as well as North, Central and South America. The risk of autochthonous transmission of chikungunya virus becoming established in Spain may be elevated due to the large numbers of travellers returning to Spain from countries affected by the 2013 epidemic in the Caribbean and South America, as well as the existence of the Aedes albopictus vector in certain parts of Spain. We retrospectively analysed the laboratory diagnostic database of the National Centre for Microbiology, Institute of Health Carlos III (CNM-ISCIII) from 2008 to 2014. During the study period, 264 confirmed cases, of 1,371 suspected cases, were diagnosed at the CNM-ISCIII. In 2014 alone, there were 234 confirmed cases. The highest number of confirmed cases were reported from the Dominican Republic (n = 136), Venezuela (n = 30) and Haiti (n = 11). Six cases were viraemic in areas of Spain where the vector is present. This report highlights the need for integrated active case and vector surveillance in Spain and other parts of Europe where chikungunya virus may be introduced by returning travellers. PMID:27631156

  19. Development of a multiplex real-time RT-PCR assay for simultaneous detection of dengue and chikungunya viruses.

    PubMed

    Cecilia, D; Kakade, M; Alagarasu, K; Patil, J; Salunke, A; Parashar, D; Shah, P S

    2015-01-01

    Dengue and chikungunya viruses co-circulate and cause infections that start with similar symptoms but progress to radically different outcomes. Therefore, an early diagnostic test that can differentiate between the two is needed. A single-step multiplex real-time RT-PCR assay was developed that can simultaneously detect and quantitate RNA of all dengue virus (DENV) serotypes and chikungunya virus (CHIKV). The sensitivity was 100 % for DENV and 95.8 % for CHIKV, whilst the specificity was 100 % for both viruses when compared with conventional RT-PCR. The detection limit ranged from 1 to 50 plaque-forming units. The assay was successfully used for differential diagnosis of dengue and chikungunya in Pune, where the viruses co-circulate.

  20. Fatal cases of Chikungunya virus infection in Colombia: Diagnostic and treatment challenges.

    PubMed

    Hoz, Juan M de la; Bayona, Brayan; Viloria, Samir; Accini, José L; Juan-Vergara, Homero San; Viasus, Diego

    2015-08-01

    Although Chikungunya infection is emerging as an important public health problem in many countries, it is not regarded as a life-threatening disease. Information dealing with fatal cases is scarce. We herein describe three patients with Chickungunya infection who presented with multiple organ failure and died within 24h of admission. Two cases had positive anti-dengue IgM, but dengue coinfection was rejected based on the clinical features and results of real-time reverse transcription polymerase chain reaction. These cases illustrate the challenges of the diagnosis and management of severe Chikungunya infection.

  1. A Rodent Model of Chikungunya Virus Infection in RAG1 -/- Mice, with Features of Persistence, for Vaccine Safety Evaluation.

    PubMed

    Seymour, Robert L; Adams, A Paige; Leal, Grace; Alcorn, Maria D H; Weaver, Scott C

    2015-01-01

    Chikungunya virus (CHIKV) is a positive sense, single stranded RNA virus in the genus Alphavirus, and the etiologic agent of epidemics of severe arthralgia in Africa, Asia, Europe and, most recently, the Americas. CHIKV causes chikungunya fever (CHIK), a syndrome characterized by rash, fever, and debilitating, often chronic arthritis. In recent outbreaks, CHIKV has been recognized to manifest more neurologic signs of illness in the elderly and those with co-morbidities. The syndrome caused by CHIKV is often self-limited; however, many patients develop persistent arthralgia that can last for months or years. These characteristics make CHIKV not only important from a human health standpoint, but also from an economic standpoint. Despite its importance as a reemerging disease, there is no licensed vaccine or specific treatment to prevent CHIK. Many studies have begun to elucidate the pathogenesis of CHIKF and the mechanism of persistent arthralgia, including the role of the adaptive immune response, which is still poorly understood. In addition, the lack of an animal model for chronic infection has limited studies of CHIKV pathogenesis as well as the ability to assess the safety of vaccine candidates currently under development. To address this deficiency, we used recombination activating gene 1 (RAG1-/-) knockout mice, which are deficient in both T and B lymphocytes, to develop a chronic CHIKV infection model. Here, we describe this model as well as its use in evaluating the safety of a live-attenuated vaccine candidate.

  2. Chikungunya from the Caribbean: the importance of appropriate laboratory tests to confirm the diagnosis.

    PubMed

    Magurano, Fabio; Zammarchi, Lorenzo; Baggieri, Melissa; Fortuna, Claudia; Farese, Alberto; Benedetti, Eleonora; Fiorentini, Cristiano; Rezza, Giovanni; Nicoletti, Loredana; Bartoloni, Alessandro

    2015-04-01

    Chikungunya virus (CHIKV) appeared for the first time in the Western Hemisphere--the French West Indies--in December of 2013. From there, the virus has spread to other Caribbean islands. Following the diagnosis of first autochthonous CHIKV cases in the Caribbean island of Saint Martin, a large outbreak is ongoing in the Americas. As of September 12, 2014, a total of 706,093 suspected and 9803 confirmed CHIKV cases have been reported in the Americas. This case study highlights the possibility of false-negative immunochromatographic CHIKV immunoglobulin M (IgM) tests and the need of confirmatory tests for suspected cases. Moreover, a greater spread of virus together with the presence of a mosquito vector (Aedes albopictus) enhances the risk of autochthonous transmission in Europe.

  3. The Usual Suspects: Comparison of the Relative Roles of Potential Urban Chikungunya Virus Vectors in Australia

    PubMed Central

    Jansen, Cassie C.; Williams, Craig R.; van den Hurk, Andrew F.

    2015-01-01

    The global re-emergence of chikungunya virus (CHIKV) over the last decade presents a serious public health risk to Australia. An increasing number of imported cases further underline the potential for local transmission to occur if local mosquitoes bite an infected traveller. Laboratory experiments have identified a number of competent Australian mosquito species, including the primary vectors of CHIKV abroad, Aedes aegypti and Aedes albopictus, and local endemic species Aedes vigilax and Aedes notoscriptus. The implication of these additional endemic species as potential vectors has generated much uncertainty amongst public health professionals regarding their actual role in CHIKV transmission in the field. Using data estimated from or documented in the literature, we parameterise a simple vectorial capacity model to evaluate the relative roles of Australian mosquito species in potential CHIKV transmission. The model takes into account a number of key biological and ecological variables which influence the role of a species in field transmission, including population density, human feeding rates, mosquito survival rates and vector competence. We confirm the relative importance of Ae. aegypti and Ae. albopictus in sustaining potential CHIKV transmission in Australia. Even at maximum estimated densities and human feeding rates, Ae. vigilax and Ae. notoscriptus are likely to play a relatively minor role in CHIKV transmission, when compared with either Ae. aegypti or Ae. albopictus. This relatively straightforward analysis has application for any region where mosquito species have been incriminated in vector competence experiments, but where their actual role in CHIKV transmission has not been established. PMID:26247366

  4. Surveillance for West Nile, dengue, and chikungunya virus infections, Veneto Region, Italy, 2010.

    PubMed

    Gobbi, Federico; Barzon, Luisa; Capelli, Gioia; Angheben, Andrea; Pacenti, Monia; Napoletano, Giuseppina; Piovesan, Cinzia; Montarsi, Fabrizio; Martini, Simone; Rigoli, Roberto; Cattelan, Anna M; Rinaldi, Roberto; Conforto, Mario; Russo, Francesca; Palù, Giorgio; Bisoffi, Zeno

    2012-04-01

    In 2010, in Veneto Region, Italy, surveillance of summer fevers was conducted to promptly identify autochthonous cases of West Nile fever and increase detection of imported dengue and chikungunya in travelers. Surveillance highlighted the need to modify case definitions, train physicians, and when a case is identified, implement vector control measures.

  5. γδ T Cells Play a Protective Role in Chikungunya Virus-Induced Disease

    PubMed Central

    Ferris, Martin T.; Whitmore, Alan C.; Montgomery, Stephanie A.; Thurlow, Lance R.; McGee, Charles E.; Rodriguez, Carlos A.; Lim, Jean K.; Heise, Mark T.

    2015-01-01

    ABSTRACT Chikungunya virus (CHIKV) is an alphavirus responsible for causing epidemic outbreaks of polyarthralgia in humans. Because CHIKV is initially introduced via the skin, where γδ T cells are prevalent, we evaluated the response of these cells to CHIKV infection. CHIKV infection led to a significant increase in γδ T cells in the infected foot and draining lymph node that was associated with the production of proinflammatory cytokines and chemokines in C57BL/6J mice. γδ T cell−/− mice demonstrated exacerbated CHIKV disease characterized by less weight gain and greater foot swelling than occurred in wild-type mice, as well as a transient increase in monocytes and altered cytokine/chemokine expression in the foot. Histologically, γδ T cell−/− mice had increased inflammation-mediated oxidative damage in the ipsilateral foot and ankle joint compared to wild-type mice which was independent of differences in CHIKV replication. These results suggest that γδ T cells play a protective role in limiting the CHIKV-induced inflammatory response and subsequent tissue and joint damage. IMPORTANCE Recent epidemics, including the 2004 to 2007 outbreak and the spread of CHIKV to naive populations in the Caribbean and Central and South America with resultant cases imported into the United States, have highlighted the capacity of CHIKV to cause explosive epidemics where the virus can spread to millions of people and rapidly move into new areas. These studies identified γδ T cells as important to both recruitment of key inflammatory cell populations and dampening the tissue injury due to oxidative stress. Given the importance of these cells in the early response to CHIKV, this information may inform the development of CHIKV vaccines and therapeutics. PMID:26491151

  6. A Single Mutation in Chikungunya Virus Affects Vector Specificity and Epidemic Potential

    PubMed Central

    Tsetsarkin, Konstantin A; Vanlandingham, Dana L; McGee, Charles E; Higgs, Stephen

    2007-01-01

    Chikungunya virus (CHIKV) is an emerging arbovirus associated with several recent large-scale epidemics. The 2005–2006 epidemic on Reunion island that resulted in approximately 266,000 human cases was associated with a strain of CHIKV with a mutation in the envelope protein gene (E1-A226V). To test the hypothesis that this mutation in the epidemic CHIKV (strain LR2006 OPY1) might influence fitness for different vector species, viral infectivity, dissemination, and transmission of CHIKV were compared in Aedes albopictus, the species implicated in the epidemic, and the recognized vector Ae. aegypti. Using viral infectious clones of the Reunion strain and a West African strain of CHIKV, into which either the E1–226 A or V mutation was engineered, we demonstrated that the E1-A226V mutation was directly responsible for a significant increase in CHIKV infectivity for Ae. albopictus, and led to more efficient viral dissemination into mosquito secondary organs and transmission to suckling mice. This mutation caused a marginal decrease in CHIKV Ae. aegypti midgut infectivity, had no effect on viral dissemination, and was associated with a slight increase in transmission by Ae. aegypti to suckling mice in competition experiments. The effect of the E1-A226V mutation on cholesterol dependence of CHIKV was also analyzed, revealing an association between cholesterol dependence and increased fitness of CHIKV in Ae. albopictus. Our observation that a single amino acid substitution can influence vector specificity provides a plausible explanation of how this mutant virus caused an epidemic in a region lacking the typical vector. This has important implications with respect to how viruses may establish a transmission cycle when introduced into a new area. Due to the widespread distribution of Ae. albopictus, this mutation increases the potential for CHIKV to permanently extend its range into Europe and the Americas. PMID:18069894

  7. Chikungunya virus infection amongst the acute encephalitis syndrome cases in West Bengal, India.

    PubMed

    Taraphdar, D; Roy, B K; Chatterjee, S

    2015-02-01

    Chikungunya virus (CHIKV) infection from the acute encephalitis syndrome cases is an uncommon form and has been observed in the year 2010-11 from West Bengal, India. The case-1 and case-2 had the acute encephalitis syndrome; case-3 was of acute disseminated encephalomyelitis whereas the case-4 had the symptoms of meningo-encephalopathy with bulbar involvement. We are reporting four cases with neurological complications involving central nervous system (CNS) due to CHIKV infection from this state for the first time. The virus has spread almost every districts of this state rapidly. At this stage, these cases are public health threat.

  8. Structure based design towards the identification of novel binding sites and inhibitors for the chikungunya virus envelope proteins.

    PubMed

    Rashad, Adel A; Keller, Paul A

    2013-07-01

    Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa, Asia, Europe and the Americas. It is having an increasingly major impact on humans with potentially life-threatening and debilitating arthritis. Thus far, neither vaccines nor medications are available to treat or control the virus and therefore, the development of medicinal chemistry is a vital and immediate issue that needs to be addressed. The viral envelope proteins play a major role during infection through mediation of binding and fusion with the infected cell surfaces. The possible binding target sites of the chikungunya virus envelope proteins have not previously been investigated; we describe here for the first time the identification of novel sites for potential binding on the chikungunya glycoprotein complexes and the identification of possible antagonists for these sites through virtual screening using two successive docking scores; FRED docking for fast precise screening, with the top hits then subjected to a ranking scoring using the AUTODOCK algorithm. Both the immature and the mature forms of the chikungunya envelope proteins were included in the study to increase the probability of finding positive and reliable hits. Some small molecules have been identified as good in silico chikungunya virus envelope proteins inhibitors and these could be good templates for drug design targeting this virus.

  9. [Chikungunya virus infection in the Indian Ocean: lessons learned and perspectives].

    PubMed

    Gaüzère, B A; Gérardin, P; Vandroux, D; Aubry, P

    2012-03-01

    After a brief overview of the history of arbovirus epidemics in the Indian Ocean in XIXth and XXth centuries, a full evaluation of the chikungunya epidemic that occurred in 2005-2006 is provided including both lessons learned and future perspectives. On the positive side, the epidemic has allowed improvement of clinical and pathophysiological knowledge, epidemiological surveillance, vector control, awareness of entomology, avenues for research, and understanding of economic and societal repercussions. On the negative side, the epidemic revealed the limitations of a health care system in an island setting, need for an effective sanitary policy, low public-spiritedness, poor diffusion and understanding of public health announcements, endemization of chikungunya virus in the Indian Ocean, absence of vaccine, and global spread of tropical disease. Discussion of perspectives for future arbovirus disease outbreaks in the Indian Ocean is set against the background of climatic change, unequal socioeconomic progress, and high population growth in the Indian Ocean region.

  10. First Report of Aedes aegypti Transmission of Chikungunya Virus in the Americas.

    PubMed

    Díaz-González, Esteban E; Kautz, Tiffany F; Dorantes-Delgado, Alicia; Malo-García, Iliana R; Laguna-Aguilar, Maricela; Langsjoen, Rose M; Chen, Rubing; Auguste, Dawn I; Sánchez-Casas, Rosa M; Danis-Lozano, Rogelio; Weaver, Scott C; Fernández-Salas, Ildefonso

    2015-12-01

    During a chikungunya fever outbreak in late 2014 in Chiapas, Mexico, entomovirological surveillance was performed to incriminate the vector(s). In neighborhoods, 75 households with suspected cases were sampled for mosquitoes, of which 80% (60) harbored Aedes aegypti and 2.7% (2) Aedes albopictus. A total of 1,170 Ae. aegypti and three Ae. albopictus was collected and 81 pools were generated. Although none of the Ae. albopictus pools were chikungunya virus (CHIKV)-positive, 18 Ae. aegypti pools (22.8%) contained CHIKV, yielding an infection rate of 32.3/1,000 mosquitoes. A lack of herd immunity in conjunction with high mosquito populations, poor vector control services in this region, and targeted collections in locations of human cases may explain the high infection rate in this vector. Consistent with predictions from experimental studies, Ae. aegypti appears to be the principal vector of CHIKV in southern Mexico, while the role of Ae. albopictus remains unknown.

  11. Interferon-Induced Spermidine-Spermine Acetyltransferase and Polyamine Depletion Restrict Zika and Chikungunya Viruses.

    PubMed

    Mounce, Bryan C; Poirier, Enzo Z; Passoni, Gabriella; Simon-Loriere, Etienne; Cesaro, Teresa; Prot, Matthieu; Stapleford, Kenneth A; Moratorio, Gonzalo; Sakuntabhai, Anavaj; Levraud, Jean-Pierre; Vignuzzi, Marco

    2016-08-10

    Polyamines are small, positively charged molecules derived from ornithine and synthesized through an intricately regulated enzymatic pathway. Within cells, they are abundant and play several roles in diverse processes. We find that polyamines are required for the life cycle of the RNA viruses chikungunya virus (CHIKV) and Zika virus (ZIKV). Depletion of spermidine and spermine via type I interferon signaling-mediated induction of spermidine/spermine N1-acetyltransferase (SAT1), a key catabolic enzyme in the polyamine pathway, restricts CHIKV and ZIKV replication. Polyamine depletion restricts these viruses in vitro and in vivo, due to impairment of viral translation and RNA replication. The restriction is released by exogenous replenishment of polyamines, further supporting a role for these molecules in virus replication. Thus, SAT1 and, more broadly, polyamine depletion restrict viral replication and suggest promising avenues for antiviral therapies.

  12. Zika Virus Emergence and Expansion: Lessons Learned from Dengue and Chikungunya May Not Provide All the Answers.

    PubMed

    Christofferson, Rebecca C

    2016-07-01

    Following the emergence of Zika in the past decade, there are lessons to be learned from similar emergence events of dengue (DENV) and chikungunya (CHIKV). Specifically, as Zika emerges in the Americas there is a natural tendency to apply the knowledge base of DENV and CHIKV to mitigation and control of a virus with such a similar transmission system. However, there are marked differences that may preclude such broad stroke application of this knowledge base without making potentially faulty assumptions. Herein, Zika virus (ZIKV) transmission is reviewed, and the commonalities among these three arboviruses are discussed. Importantly, the divergence of this particular arbovirus is discussed, as is the need to develop ZIKV-specific knowledge base for mitigation of this disease. Specifically reviewed are 1) emergence and persistence patterns, 2) genetic and phenotypic diversity, 3) vector host range, and finally, 4) alternate transmission routes and added complexity of ZIKV transmission and presentation.

  13. Antiviral Activity of Diterpene Esters on Chikungunya Virus and HIV Replication.

    PubMed

    Nothias-Scaglia, Louis-Félix; Pannecouque, Christophe; Renucci, Franck; Delang, Leen; Neyts, Johan; Roussi, Fanny; Costa, Jean; Leyssen, Pieter; Litaudon, Marc; Paolini, Julien

    2015-06-26

    Recently, new daphnane, tigliane, and jatrophane diterpenoids have been isolated from various Euphorbiaceae species, of which some have been shown to be potent inhibitors of chikungunya virus (CHIKV) replication. To further explore this type of compound, the antiviral activity of a series of 29 commercially available natural diterpenoids was evaluated. Phorbol-12,13-didecanoate (11) proved to be the most potent inhibitor, with an EC50 value of 6.0 ± 0.9 nM and a selectivity index (SI) of 686, which is in line with the previously reported anti-CHIKV potency for the structurally related 12-O-tetradecanoylphorbol-13-acetate (13). Most of the other compounds exhibited low to moderate activity, including an ingenane-type diterpene ester, compound 28, with an EC50 value of 1.2 ± 0.1 μM and SI = 6.4. Diterpene compounds are known also to inhibit HIV replication, so the antiviral activities of compounds 1-29 were evaluated also against HIV-1 and HIV-2. Tigliane- (4β-hydroxyphorbol analogues 10, 11, 13, 15, 16, and 18) and ingenane-type (27 and 28) diterpene esters were shown to inhibit HIV replication in vitro at the nanomolar level. A Pearson analysis performed with the anti-CHIKV and anti-HIV data sets demonstrated a linear relationship, which supported the hypothesis made that PKC may be an important target in CHIKV replication.

  14. Structure-activity relationship study of arbidol derivatives as inhibitors of chikungunya virus replication.

    PubMed

    Di Mola, Antonia; Peduto, Antonella; La Gatta, Annalisa; Delang, Leen; Pastorino, Boris; Neyts, Johan; Leyssen, Pieter; de Rosa, Mario; Filosa, Rosanna

    2014-11-01

    Chikungunya virus (CHIKV), a mosquito-borne arthrogenic Alphavirus, causes an acute febrile illness in humans, that is, accompanied by severe joint pains. In many cases, the infection leads to persistent arthralgia, which may last for weeks to several years. The re-emergence of this infection in the early 2000s was exemplified by numerous outbreaks in the eastern hemisphere. Since then, the virus is rapidly spreading. Currently, no drugs have been approved or are in development for the treatment of CHIKV, which makes this viral infection particularly interesting for academic medicinal chemistry efforts. Several molecules have already been identified that inhibit CHIKV replication in phenotypic virus-cell-based assays. One of these is arbidol, a molecule that already has been licensed for the treatment of influenza A and B virus infections. For structural optimization, a dedicated libraries of 43 indole-based derivatives were evaluated leading to more potent analogues (IIIe and IIIf) with anti-chikungunya virus (CHIKV) activities higher than those of the other derivatives, including the lead compound, and with a selective index of inhibition 13.2 and 14.6, respectively, higher than that of ARB (4.6).

  15. Virus replicon particle based Chikungunya virus neutralization assay using Gaussia luciferase as readout

    PubMed Central

    2013-01-01

    Background Chikungunya virus (CHIKV) has been responsible for large epidemic outbreaks causing fever, headache, rash and severe arthralgia. So far, no specific treatment or vaccine is available. As nucleic acid amplification can only be used during the viremic phase of the disease, serological tests like neutralization assays are necessary for CHIKV diagnosis and for determination of the immune status of a patient. Furthermore, neutralization assays represent a useful tool to validate the efficacy of potential vaccines. As CHIKV is a BSL3 agent, neutralization assays with infectious virus need to be performed under BSL3 conditions. Our aim was to develop a neutralization assay based on non-infectious virus replicon particles (VRPs). Methods VRPs were produced by cotransfecting baby hamster kidney-21 cells with a CHIKV replicon expressing Gaussia luciferase (Gluc) and two helper RNAs expressing the CHIKV capsid protein or the remaining structural proteins, respectively. The resulting single round infectious particles were used in CHIKV neutralization assays using secreted Gluc as readout. Results Upon cotransfection of a CHIKV replicon expressing Gluc and the helper RNAs VRPs could be produced efficiently under optimized conditions at 32°C. Infection with VRPs could be measured via Gluc secreted into the supernatant. The successful use of VRPs in CHIKV neutralization assays was demonstrated using a CHIKV neutralizing monoclonal antibody or sera from CHIKV infected patients. Comparison of VRP based neutralization assays in 24- versus 96-well format using different amounts of VRPs revealed that in the 96-well format a high multiplicity of infection is favored, while in the 24-well format reliable results are also obtained using lower infection rates. Comparison of different readout times revealed that evaluation of the neutralization assay is already possible at the same day of infection. Conclusions A VRP based CHIKV neutralization assay using Gluc as readout

  16. Zika virus infections imported from Brazil to Portugal, 2015.

    PubMed

    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present. PMID:27134823

  17. Zika virus infections imported from Brazil to Portugal, 2015.

    PubMed

    Zé-Zé, L; Prata, M B; Teixeira, T; Marques, N; Mondragão, A; Fernandes, R; Saraiva da Cunha, J; Alves, M J

    2016-01-01

    Zika virus is an emerging arbovirus transmitted by Aedes sp. mosquitoes like the Dengue and Chikungunya viruses. Zika virus was until recently considered a mild pathogenic mosquito-borne flavivirus with very few reported benign human infections. In 2007, an epidemic in Micronesia initiated the turnover in the epidemiological history of Zika virus and more recently, the potential association with congenital microcephaly cases in Brazil 2015, still under investigation, led the World Health Organization (WHO) to declare a Public Health Emergency of International Concern on February 1, 2016. Here, we present the clinical and laboratory aspects related to the first four imported human cases of Zika virus in Portugal from Brazil, and alert, regarding the high level of traveling between Portugal and Brazil, and the ongoing expansion of this virus in the Americas, for the threat for Zika virus introduction in Europe and the possible introduction to Madeira Island where Aedes aegypti is present.

  18. Differential Protein Modulation in Midguts of Aedes aegypti Infected with Chikungunya and Dengue 2 Viruses

    PubMed Central

    Tchankouo-Nguetcheu, Stéphane; Khun, Huot; Pincet, Laurence; Roux, Pascal; Bahut, Muriel; Huerre, Michel; Guette, Catherine; Choumet, Valérie

    2010-01-01

    Background Arthropod borne virus infections cause several emerging and resurgent infectious diseases. Among the diseases caused by arboviruses, dengue and chikungunya are responsible for a high rate of severe human diseases worldwide. The midgut of mosquitoes is the first barrier for pathogen transmission and is a target organ where arboviruses must replicate prior to infecting other organs. A proteomic approach was undertaken to characterize the key virus/vector interactions and host protein modifications that happen in the midgut for viral transmission to eventually take place. Methodology and Principal Findings Using a proteomics differential approach with two-Dimensional Differential in-Gel Electrophoresis (2D-DIGE), we defined the protein modulations in the midgut of Aedes aegypti that were triggered seven days after an oral infection (7 DPI) with dengue 2 (DENV-2) and chikungunya (CHIKV) viruses. Gel profile comparisons showed that the level of 18 proteins was modulated by DENV-2 only and 12 proteins were modulated by CHIKV only. Twenty proteins were regulated by both viruses in either similar or different ways. Both viruses caused an increase of proteins involved in the generation of reactive oxygen species, energy production, and carbohydrate and lipid metabolism. Midgut infection by DENV-2 and CHIKV triggered an antioxidant response. CHIKV infection produced an increase of proteins involved in detoxification. Conclusion/Significance Our study constitutes the first analysis of the protein response of Aedes aegypti's midgut infected with viruses belonging to different families. It shows that the differentially regulated proteins in response to viral infection include structural, redox, regulatory proteins, and enzymes for several metabolic pathways. Some of these proteins like antioxidant are probably involved in cell protection. On the other hand, we propose that the modulation of other proteins like transferrin, hsp60 and alpha glucosidase, may favour

  19. Species-specific impact of the autophagy machinery on Chikungunya virus infection

    PubMed Central

    Judith, Delphine; Mostowy, Serge; Bourai, Mehdi; Gangneux, Nicolas; Lelek, Mickaël; Lucas-Hourani, Marianne; Cayet, Nadège; Jacob, Yves; Prévost, Marie-Christine; Pierre, Philippe; Tangy, Frédéric; Zimmer, Christophe; Vidalain, Pierre-Olivier; Couderc, Thérèse; Lecuit, Marc

    2013-01-01

    Chikungunya virus (CHIKV) is a recently re-emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes. By contrast, the human autophagy receptor NDP52—but not its mouse orthologue—interacts with the non-structural protein nsP2, thereby promoting viral replication. These results highlight the distinct roles of p62 and NDP52 in viral infection, and identify NDP52 as a cellular factor that accounts for CHIKV species specificity. PMID:23619093

  20. An outbreak of yellow fever with concurrent chikungunya virus transmission in South Kordofan, Sudan, 2005.

    PubMed

    Gould, L Hannah; Osman, Magdi S; Farnon, Eileen C; Griffith, Kevin S; Godsey, Marvin S; Karch, Said; Mulenda, Basimike; El Kholy, Amgad; Grandesso, Francesco; de Radiguès, Xavier; Brair, Maria-Emanuela; Briand, Sylvie; El Tayeb, El Sadig Mahgoub; Hayes, Edward B; Zeller, Herve; Perea, William

    2008-12-01

    From September through December 2005, an outbreak of hemorrhagic fever occurred in South Kordofan, Sudan. Initial laboratory test results identified IgM antibodies against yellow fever (YF) virus in patient samples, and a YF outbreak was declared on 14 November. To control the outbreak, a YF mass vaccination campaign was conducted and vector control implemented in parts of South Kordofan. Surveillance data were obtained from the Sudan Federal Ministry of Health. Clinical information and serum samples were obtained from a subset of patients with illness during the outbreak. Nomads, health personnel and village chiefs were interviewed about the outbreak. Mosquitoes were collected in 11 villages and towns in North and South Kordofan. From 10 September to 9 December 2005 a total of 605 cases of outbreak-related illness were reported, of which 45% were in nomads. Twenty-nine percent of 177 patients seen at clinics in Julud and Abu Jubaiyah had illness consistent with YF. Five of 18 unvaccinated persons with recent illness and 4 of 16 unvaccinated asymptomatic persons had IgM antibodies to YF virus. IgM antibodies to chikungunya virus were detected in five (27%) ill persons and three (19%) asymptomatic persons. These results indicate that both chikungunya and YF occurred during the outbreak.

  1. Human keratinocytes restrict chikungunya virus replication at a post-fusion step.

    PubMed

    Bernard, Eric; Hamel, Rodolphe; Neyret, Aymeric; Ekchariyawat, Peeraya; Molès, Jean-Pierre; Simmons, Graham; Chazal, Nathalie; Desprès, Philippe; Missé, Dorothée; Briant, Laurence

    2015-02-01

    Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses.

  2. Coinfections of Zika and Chikungunya Viruses in Bahia, Brazil, Identified by Metagenomic Next-Generation Sequencing.

    PubMed

    Sardi, Silvia I; Somasekar, Sneha; Naccache, Samia N; Bandeira, Antonio C; Tauro, Laura B; Campos, Gubio S; Chiu, Charles Y

    2016-09-01

    Metagenomic next-generation sequencing (mNGS) of samples from 15 patients with documented Zika virus (ZIKV) infection in Bahia, Brazil, from April 2015 to January 2016 identified coinfections with chikungunya virus (CHIKV) in 2 of 15 ZIKV-positive cases by PCR (13.3%). While generally nonspecific, the clinical presentation corresponding to these two CHIKV/ZIKV coinfections reflected infection by the virus present at a higher titer. Aside from CHIKV and ZIKV, coinfections of other viral pathogens were not detected. The mNGS approach is promising for differential diagnosis of acute febrile illness and identification of coinfections, although targeted arbovirus screening may be sufficient in the current ZIKV outbreak setting. PMID:27413190

  3. Coinfections of Zika and Chikungunya Viruses in Bahia, Brazil, Identified by Metagenomic Next-Generation Sequencing.

    PubMed

    Sardi, Silvia I; Somasekar, Sneha; Naccache, Samia N; Bandeira, Antonio C; Tauro, Laura B; Campos, Gubio S; Chiu, Charles Y

    2016-09-01

    Metagenomic next-generation sequencing (mNGS) of samples from 15 patients with documented Zika virus (ZIKV) infection in Bahia, Brazil, from April 2015 to January 2016 identified coinfections with chikungunya virus (CHIKV) in 2 of 15 ZIKV-positive cases by PCR (13.3%). While generally nonspecific, the clinical presentation corresponding to these two CHIKV/ZIKV coinfections reflected infection by the virus present at a higher titer. Aside from CHIKV and ZIKV, coinfections of other viral pathogens were not detected. The mNGS approach is promising for differential diagnosis of acute febrile illness and identification of coinfections, although targeted arbovirus screening may be sufficient in the current ZIKV outbreak setting.

  4. Production of Chikungunya Virus-Like Particles and Subunit Vaccines in Insect Cells.

    PubMed

    Metz, Stefan W; Pijlman, Gorben P

    2016-01-01

    Chikungunya virus is a reemerging human pathogen that causes debilitating arthritic disease in humans. Like dengue and Zika virus, CHIKV is transmitted by Aedes mosquitoes in an epidemic urban cycle, and is now rapidly spreading through the Americas since its introduction in the Caribbean in late 2013. There are no licensed vaccines or antiviral drugs available, and only a few vaccine candidates have passed Phase I human clinical trials. Using recombinant baculovirus expression technology, we have generated CHIKV glycoprotein subunit and virus-like particle (VLP) vaccines that are amenable to large scale production in insect cells. These vaccines, in particular the VLPs, have shown high immunogenicity and protection against CHIKV infection in different animal models of CHIKV-induced disease. Here, we describe the production, purification, and characterization of these potent CHIKV vaccine candidates. PMID:27233282

  5. Evidence for natural vertical transmission of chikungunya viruses in field populations of Aedes aegypti in Delhi and Haryana states in India-a preliminary report.

    PubMed

    Jain, Jaspreet; Kushwah, Raja Babu S; Singh, Shashi S; Sharma, Anil; Adak, Tridibes; Singh, Om P; Bhatnagar, Raj Kamal; Subbarao, Sarala K; Sunil, Sujatha

    2016-10-01

    Aedes aegypti and Aedes albopictus are principal vectors for the transmission of chikungunya virus (CHIKV). India is a hub for both dengue and chikungunya infections and there are several reports of co-infection of dengue and chikungunya virus in the clinical scenario. The present pilot entomological survey was conducted to evaluate vertical transmission of CHIKV in Aedes field populations. Aedes immature (larvae and pupae) collection was done in 2012, over a period of six months from selected sites in Delhi and Haryana, India. The immatures collected were reared for adult emergence and species identification was done. A. aegypti male and female mosquitoes were separated and pooled collection spot-wise, RNA extracted and RT PCR performed to test for the presence of CHIKV in the pools. Container index (CI) and minimum infection rate (MIR) were estimated. From study areas that tested positive for CHIKV, adult collections were made and females upon feeding on uninfected blood in laboratory were allowed to lay eggs. The progeny that emerged from these field-collected mothers were tested for CHIKV presence. Our pilot survey showed the existence of A. aegypti population even during peak summer season in a few foci which eventually helped the mosquitoes to tide over adverse environmental conditions and with the start of rainfall, the population exploded within a short period of time. Immatures collected from field and progeny of adults collected from the field were CHIKV positive demonstrating the presence of vertical transmission of chikungunya virus in field population of A. aegypti. The present study further demonstrates the importance of identifying permanent breeding sites for proper Aedes species control. PMID:27282096

  6. Vector Competence of Aedes aegypti and Aedes polynesiensis Populations from French Polynesia for Chikungunya Virus

    PubMed Central

    Richard, Vaea; Paoaafaite, Tuterarii; Cao-Lormeau, Van-Mai

    2016-01-01

    Background From October 2014 to March 2015, French Polynesia experienced for the first time a chikungunya outbreak. Two Aedes mosquitoes may have contributed to chikungunya virus (CHIKV) transmission in French Polynesia: the worldwide distributed Ae. aegypti and the Polynesian islands-endemic Ae. polynesiensis mosquito. Methods To investigate the vector competence of French Polynesian populations of Ae. aegypti and Ae. polynesiensis for CHIKV, mosquitoes were exposed per os at viral titers of 7 logs tissue culture infectious dose 50%. At 2, 6, 9, 14 and 21 days post-infection (dpi), saliva was collected from each mosquito and inoculated onto C6/36 mosquito cells to check for the presence of CHIKV infectious particles. Legs and body (thorax and abdomen) of each mosquito were also collected at the different dpi and submitted separately to viral RNA extraction and CHIKV real-time RT-PCR. Results CHIKV infection rate, dissemination and transmission efficiencies ranged from 7–90%, 18–78% and 5–53% respectively for Ae. aegypti and from 39–41%, 3–17% and 0–14% respectively for Ae. polynesiensis, depending on the dpi. Infectious saliva was found as early as 2 dpi for Ae. aegypti and from 6 dpi for Ae. polynesiensis. Our laboratory results confirm that the French Polynesian population of Ae. aegypti is highly competent for CHIKV and they provide clear evidence for Ae. polynesiensis to act as an efficient CHIKV vector. Conclusion As supported by our findings, the presence of two CHIKV competent vectors in French Polynesia certainly contributed to enabling this virus to quickly disseminate from the urban/peri-urban areas colonized by Ae. aegypti to the most remote atolls where Ae. polynesiensis is predominating. Ae. polynesiensis was probably involved in the recent chikungunya outbreaks in Samoa and the Cook Islands. Moreover, this vector may contribute to the risk for CHIKV to emerge in other Polynesian islands like Fiji, and more particularly Wallis where there

  7. A comprehensive immunoinformatics and target site study revealed the corner-stone toward Chikungunya virus treatment.

    PubMed

    Hasan, Md Anayet; Khan, Md Arif; Datta, Amit; Mazumder, Md Habibul Hasan; Hossain, Mohammad Uzzal

    2015-05-01

    Recent concerning facts of Chikungunya virus (CHIKV); a Togaviridae family alphavirus has proved this as a worldwide emerging threat which causes Chikungunya fever and devitalizing arthritis. Despite severe outbreaks and lack of antiviral drug, a mere progress has been made regarding to an epitope-based vaccine designed for CHIKV. In this study, we aimed to design an epitope-based vaccine that can trigger a significant immune response as well as to prognosticate inhibitor that can bind with potential drug target sites by using various immunoinformatics and docking simulation tools. Initially, whole proteome of CHIKV was retrieved from database and perused to identify the most immunogenic protein. Structural properties of the selected protein were analyzed. The capacity to induce both humoral and cell-mediated immunity by T cell and B cell were checked for the selected protein. The peptide region spanning 9 amino acids from 397 to 405 and the sequence YYYELYPTM were found as the most potential B cell and T cell epitopes respectively. This peptide could interact with as many as 19 HLAs and showed high population coverage ranging from 69.50% to 84.94%. By using in silico docking techniques the epitope was further assessed for binding against HLA molecules to verify the binding cleft interaction. In addition with this, the allergenicity of the epitopes was also evaluated. In the post therapeutic strategy, three dimensional structure was predicted along with validation and verification that resulted in molecular docking study to identify the potential drug binding sites and suitable therapeutic inhibitor against targeted protein. Finally, pharmacophore study was also performed in quest of seeing potent drug activity. However, this computational epitope-based peptide vaccine designing and target site prediction against CHIKV opens up a new horizon which may be the prospective way in Chikungunya virus research; the results require validation by in vitro and in vivo

  8. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

    PubMed

    von Rhein, Christine; Weidner, Tatjana; Henß, Lisa; Martin, Judith; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites.

  9. LC-MS²-Based dereplication of Euphorbia extracts with anti-Chikungunya virus activity.

    PubMed

    Nothias-Scaglia, Louis-Félix; Dumontet, Vincent; Neyts, Johan; Roussi, Fanny; Costa, Jean; Leyssen, Pieter; Litaudon, Marc; Paolini, Julien

    2015-09-01

    Recently, phorbol esters from Euphorbiaceae have been shown to elicit potent and selective antiviral activity on the replication of Chikungunya virus (CHIKV) in cell culture. With the objective to found new compounds with anti-CHIKV activities, 45 extracts from various plant parts of 11 Mediterranean Euphorbia and one Mercurialis species were evaluated for selective inhibition of CHIKV replication. All EtOAc extracts, especially those prepared from latex, exhibited significant and selective antiviral activity in a Chikungunya virus-cell-based assay. An LC-MS(2) dereplication method was then developed to investigate whether known diterpenoids with anti-CHIKV activity, such as the potent anti-CHIKV 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol-12,13-didecanoate, and prostratin as well as 24 other commercially available diterpenoids of tigliane-, ingenane-, and daphnane-type for which the anti-CHIKV activity have been established in advance (Nothias-Scaglia et al. 2015), were present in the Euphorbia extracts. Only ingenol-3-mebutate, 13-O-isobutyryl-12-deoxyphorbol-20-acetate, and ingenol-3,20-dibenzoate, all exhibiting weak anti-CHIKV activities, were detected in the EtOAc extracts of Euphorbia peplus, Euphorbia segetalis ssp. pinea, and Euphorbia pithyusa ssp. pithyusa. Given the potent anti-CHIKV activities of these Euphorbia extracts, the present study suggested that their antiviral activities are probably due to untargeted diterpenoids.

  10. Curcumin and Boswellia serrata gum resin extract inhibit chikungunya and vesicular stomatitis virus infections in vitro.

    PubMed

    von Rhein, Christine; Weidner, Tatjana; Henß, Lisa; Martin, Judith; Weber, Christopher; Sliva, Katja; Schnierle, Barbara S

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes chikungunya fever and has infected millions of people mainly in developing countries. The associated disease is characterized by rash, high fever, and severe arthritis that can persist for years. CHIKV has adapted to Aedes albopictus, which also inhabits temperate regions including Europe and the United States of America. CHIKV has recently caused large outbreaks in Latin America. No treatment or licensed CHIKV vaccine exists. Traditional medicines are known to have anti-viral effects; therefore, we examined whether curcumin or Boswellia serrata gum resin extract have antiviral activity against CHIKV. Both compounds blocked entry of CHIKV Env-pseudotyped lentiviral vectors and inhibited CHIKV infection in vitro. In addition, vesicular stomatitis virus vector particles and viral infections were also inhibited to the same extent, indicating a broad antiviral activity. Although the bioavailability of these compounds is rather poor, they might be used as a lead structure to develop more effective antiviral drugs or might be used topically to prevent CHIKV spread in the skin after mosquito bites. PMID:26611396

  11. Estimating risks of importation and local transmission of Zika virus infection

    PubMed Central

    Nah, Kyeongah; Mizumoto, Kenji; Miyamatsu, Yuichiro; Yasuda, Yohei; Kinoshita, Ryo

    2016-01-01

    Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience. PMID:27069825

  12. Estimating risks of importation and local transmission of Zika virus infection.

    PubMed

    Nah, Kyeongah; Mizumoto, Kenji; Miyamatsu, Yuichiro; Yasuda, Yohei; Kinoshita, Ryo; Nishiura, Hiroshi

    2016-01-01

    Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience.

  13. Estimating risks of importation and local transmission of Zika virus infection.

    PubMed

    Nah, Kyeongah; Mizumoto, Kenji; Miyamatsu, Yuichiro; Yasuda, Yohei; Kinoshita, Ryo; Nishiura, Hiroshi

    2016-01-01

    Background. An international spread of Zika virus (ZIKV) infection has attracted global attention. ZIKV is conveyed by a mosquito vector, Aedes species, which also acts as the vector species of dengue and chikungunya viruses. Methods. Arrival time of ZIKV importation (i.e., the time at which the first imported case was diagnosed) in each imported country was collected from publicly available data sources. Employing a survival analysis model in which the hazard is an inverse function of the effective distance as informed by the airline transportation network data, and using dengue and chikungunya virus transmission data, risks of importation and local transmission were estimated. Results. A total of 78 countries with imported case(s) have been identified, with the arrival time ranging from 1 to 44 weeks since the first ZIKV was identified in Brazil, 2015. Whereas the risk of importation was well explained by the airline transportation network data, the risk of local transmission appeared to be best captured by additionally accounting for the presence of dengue and chikungunya viruses. Discussion. The risk of importation may be high given continued global travel of mildly infected travelers but, considering that the public health concerns over ZIKV infection stems from microcephaly, it is more important to focus on the risk of local and widespread transmission that could involve pregnant women. The predicted risk of local transmission was frequently seen in tropical and subtropical countries with dengue or chikungunya epidemic experience. PMID:27069825

  14. Phylogenetic analyses of chikungunya virus among travelers in Rio de Janeiro, Brazil, 2014-2015

    PubMed Central

    Conteville, Liliane Costa; Zanella, Louise; Marín, Michel Abanto; de Filippis, Ana Maria Bispo; Nogueira, Rita Maria Ribeiro; Vicente, Ana Carolina Paulo; de Mendonça, Marcos César Lima

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne pathogen that emerged in Brazil by late 2014. In the country, two CHIKV foci characterized by the East/Central/South Africa and Asian genotypes, were established in North and Northeast regions. We characterized, by phylogenetic analyses of full and partial genomes, CHIKV from Rio de Janeiro state (2014-2015). These CHIKV strains belong to the Asian genotype, which is the determinant of the current Northern Brazilian focus, even though the genome sequence presents particular single nucleotide variations. This study provides the first genetic characterisation of CHIKV in Rio de Janeiro and highlights the potential impact of human mobility in the spread of an arthropod-borne virus. PMID:27120007

  15. Phylogenetic analyses of chikungunya virus among travelers in Rio de Janeiro, Brazil, 2014-2015.

    PubMed

    Conteville, Liliane Costa; Zanella, Louise; Marín, Michel Abanto; Filippis, Ana Maria Bispo de; Nogueira, Rita Maria Ribeiro; Vicente, Ana Carolina Paulo; Mendonça, Marcos César Lima de

    2016-05-01

    Chikungunya virus (CHIKV) is a mosquito-borne pathogen that emerged in Brazil by late 2014. In the country, two CHIKV foci characterized by the East/Central/South Africa and Asian genotypes, were established in North and Northeast regions. We characterized, by phylogenetic analyses of full and partial genomes, CHIKV from Rio de Janeiro state (2014-2015). These CHIKV strains belong to the Asian genotype, which is the determinant of the current Northern Brazilian focus, even though the genome sequence presents particular single nucleotide variations. This study provides the first genetic characterisation of CHIKV in Rio de Janeiro and highlights the potential impact of human mobility in the spread of an arthropod-borne virus.

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

    PubMed

    Smith, Scott A; Silva, Laurie A; Fox, Julie M; Flyak, Andrew I; Kose, Nurgun; Sapparapu, Gopal; Khomandiak, Solomiia; Khomadiak, Solomiia; Ashbrook, Alison W; Kahle, Kristen M; Fong, Rachel H; Swayne, Sherri; Doranz, Benjamin J; McGee, Charles E; Heise, Mark T; Pal, Pankaj; Brien, James D; Austin, S Kyle; Diamond, Michael S; Dermody, Terence S; Crowe, James E

    2015-07-01

    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.

  17. Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus

    PubMed Central

    Smith, Scott A.; Silva, Laurie A.; Fox, Julie M.; Flyak, Andrew; Kose, Nurgun; Sapparapu, Gopal; Khomadiak, Solomiia; Ashbrook, Alison W.; Kahle, Kristen M.; Fong, Rachel H.; Swayne, Sherri; Doranz, Benjamin J.; McGee, Charles E.; Heise, Mark T.; Pal, Pankaj; Brien, James D.; Austin, S. Kyle; Diamond, Michael S.; Dermody, Terence S.; Crowe, James E.

    2015-01-01

    SUMMARY 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. PMID:26159721

  18. Chikungunya Virus Transmission Potential by Local Aedes Mosquitoes in the Americas and Europe

    PubMed Central

    Vega-Rúa, Anubis; Lourenço-de-Oliveira, Ricardo; Mousson, Laurence; Vazeille, Marie; Fuchs, Sappho; Yébakima, André; Gustave, Joel; Girod, Romain; Dusfour, Isabelle; Leparc-Goffart, Isabelle; Vanlandingham, Dana L.; Huang, Yan-Jang S.; Lounibos, L. Philip; Mohamed Ali, Souand; Nougairede, Antoine; de Lamballerie, Xavier; Failloux, Anna-Bella

    2015-01-01

    Background Chikungunya virus (CHIKV), mainly transmitted in urban areas by the mosquitoes Aedes aegypti and Aedes albopictus, constitutes a major public health problem. In late 2013, CHIKV emerged on Saint-Martin Island in the Caribbean and spread throughout the region reaching more than 40 countries. Thus far, Ae. aegypti mosquitoes have been implicated as the sole vector in the outbreaks, leading to the hypothesis that CHIKV spread could be limited only to regions where this mosquito species is dominant. Methodology/Principal Findings We determined the ability of local populations of Ae. aegypti and Ae. albopictus from the Americas and Europe to transmit the CHIKV strain of the Asian genotype isolated from Saint-Martin Island (CHIKV_SM) during the recent epidemic, and an East-Central-South African (ECSA) genotype CHIKV strain isolated from La Réunion Island (CHIKV_LR) as a well-characterized control virus. We also evaluated the effect of temperature on transmission of CHIKV_SM by European Ae. albopictus. We found that (i) Aedes aegypti from Saint-Martin Island transmit CHIKV_SM and CHIKV_LR with similar efficiency, (ii) Ae. aegypti from the Americas display similar transmission efficiency for CHIKV_SM, (iii) American and European populations of the alternative vector species Ae. albopictus were as competent as Ae. aegypti populations with respect to transmission of CHIKV_SM and (iv) exposure of European Ae. albopictus to low temperatures (20°C) significantly reduced the transmission potential for CHIKV_SM. Conclusions/Significance CHIKV strains belonging to the ECSA genotype could also have initiated local transmission in the new world. Additionally, the ongoing CHIKV outbreak in the Americas could potentially spread throughout Ae. aegypti- and Ae. albopictus-infested regions of the Americas with possible imported cases of CHIKV to Ae. albopictus-infested regions in Europe. Colder temperatures may decrease the local transmission of CHIKV_SM by European Ae

  19. Deliberate attenuation of chikungunya virus by adaptation to heparan sulfate-dependent infectivity: a model for rational arboviral vaccine design.

    PubMed

    Gardner, Christina L; Hritz, Jozef; Sun, Chengqun; Vanlandingham, Dana L; Song, Timothy Y; Ghedin, Elodie; Higgs, Stephen; Klimstra, William B; Ryman, Kate D

    2014-02-01

    Mosquito-borne chikungunya virus (CHIKV) is a positive-sense, single-stranded RNA virus from the genus Alphavirus, family Togaviridae, which causes fever, rash and severe persistent polyarthralgia in humans. Since there are currently no FDA licensed vaccines or antiviral therapies for CHIKV, the development of vaccine candidates is of critical importance. Historically, live-attenuated vaccines (LAVs) for protection against arthropod-borne viruses have been created by blind cell culture passage leading to attenuation of disease, while maintaining immunogenicity. Attenuation may occur via multiple mechanisms. However, all examined arbovirus LAVs have in common the acquisition of positively charged amino acid substitutions in cell-surface attachment proteins that render virus infection partially dependent upon heparan sulfate (HS), a ubiquitously expressed sulfated polysaccharide, and appear to attenuate by retarding dissemination of virus particles in vivo. We previously reported that, like other wild-type Old World alphaviruses, CHIKV strain, La Réunion, (CHIKV-LR), does not depend upon HS for infectivity. To deliberately identify CHIKV attachment protein mutations that could be combined with other attenuating processes in a LAV candidate, we passaged CHIKV-LR on evolutionarily divergent cell-types. A panel of single amino acid substitutions was identified in the E2 glycoprotein of passaged virus populations that were predicted to increase electrostatic potential. Each of these substitutions was made in the CHIKV-LR cDNA clone and comparisons of the mutant viruses revealed surface exposure of the mutated residue on the spike and sensitivity to competition with the HS analog, heparin, to be primary correlates of attenuation in vivo. Furthermore, we have identified a mutation at E2 position 79 as a promising candidate for inclusion in a CHIKV LAV.

  20. Chikungunya infection in a human immunodeficiency virus-infected kidney transplant recipient returning to Italy from the Dominican Republic.

    PubMed

    Dalla Gasperina, D; Balsamo, M L; Garavaglia, S D; Rovida, F; Baldanti, F; Grossi, P A

    2015-12-01

    Since December 2013, chikungunya virus (CHIKV) spread in many countries of the Western Hemisphere, and during the last year some cases of infected European travelers, coming back from the Caribbean, have been reported. The risk of acquiring severe travel-related illness is higher in immunocompromised subjects, such as patients with human immunodeficiency virus (HIV) infection or solid organ transplant recipients. We reported the first case, to our knowledge, of CHIKV infection in an HIV-infected kidney transplant recipient.

  1. Chikungunya and Dengue Virus Infections Among United States Community Service Volunteers Returning from the Dominican Republic, 2014.

    PubMed

    Millman, Alexander J; Esposito, Douglas H; Biggs, Holly M; Decenteceo, Michelle; Klevos, Andrew; Hunsperger, Elizabeth; Munoz-Jordan, Jorge; Kosoy, Olga I; McPherson, Heidi; Sullivan, Carmen; Voorhees, Dayton; Baron, David; Watkins, Jim; Gaul, Linda; Sotir, Mark J; Brunette, Gary; Fischer, Marc; Sharp, Tyler M; Jentes, Emily S

    2016-06-01

    Chikungunya spread throughout the Dominican Republic (DR) after the first identified laboratory-confirmed cases were reported in April 2014. In June 2014, a U.S.-based service organization operating in the DR reported chikungunya-like illnesses among several staff. We assessed the incidence of chikungunya virus (CHIKV) and dengue virus (DENV) infection and illnesses and evaluated adherence to mosquito avoidance measures among volunteers/staff deployed in the DR who returned to the United States during July-August 2014. Investigation participants completed a questionnaire that collected information on demographics, medical history, self-reported illnesses, and mosquito exposures and avoidance behaviors and provided serum for CHIKV and DENV diagnostic testing by reverse transcription polymerase chain reaction and IgM enzyme-linked immunosorbent assay. Of 102 participants, 42 (41%) had evidence of recent CHIKV infection and two (2%) had evidence of recent DENV infection. Of the 41 participants with evidence of recent CHIKV infection only, 39 (95%) reported fever, 37 (90%) reported rash, and 37 (90%) reported joint pain during their assignment. All attended the organization's health trainings, and 89 (87%) sought a pretravel health consultation. Most (∼95%) used insect repellent; however, only 30% applied it multiple times daily and < 5% stayed in housing with window/door screens. In sum, CHIKV infections were common among these volunteers during the 2014 chikungunya epidemic in the DR. Despite high levels of preparation, reported adherence to mosquito avoidance measures were inconsistent. Clinicians should discuss chikungunya with travelers visiting areas with ongoing CHIKV outbreaks and should consider chikungunya when diagnosing febrile illnesses in travelers returning from affected areas.

  2. Chikungunya and Dengue Virus Infections Among United States Community Service Volunteers Returning from the Dominican Republic, 2014.

    PubMed

    Millman, Alexander J; Esposito, Douglas H; Biggs, Holly M; Decenteceo, Michelle; Klevos, Andrew; Hunsperger, Elizabeth; Munoz-Jordan, Jorge; Kosoy, Olga I; McPherson, Heidi; Sullivan, Carmen; Voorhees, Dayton; Baron, David; Watkins, Jim; Gaul, Linda; Sotir, Mark J; Brunette, Gary; Fischer, Marc; Sharp, Tyler M; Jentes, Emily S

    2016-06-01

    Chikungunya spread throughout the Dominican Republic (DR) after the first identified laboratory-confirmed cases were reported in April 2014. In June 2014, a U.S.-based service organization operating in the DR reported chikungunya-like illnesses among several staff. We assessed the incidence of chikungunya virus (CHIKV) and dengue virus (DENV) infection and illnesses and evaluated adherence to mosquito avoidance measures among volunteers/staff deployed in the DR who returned to the United States during July-August 2014. Investigation participants completed a questionnaire that collected information on demographics, medical history, self-reported illnesses, and mosquito exposures and avoidance behaviors and provided serum for CHIKV and DENV diagnostic testing by reverse transcription polymerase chain reaction and IgM enzyme-linked immunosorbent assay. Of 102 participants, 42 (41%) had evidence of recent CHIKV infection and two (2%) had evidence of recent DENV infection. Of the 41 participants with evidence of recent CHIKV infection only, 39 (95%) reported fever, 37 (90%) reported rash, and 37 (90%) reported joint pain during their assignment. All attended the organization's health trainings, and 89 (87%) sought a pretravel health consultation. Most (∼95%) used insect repellent; however, only 30% applied it multiple times daily and < 5% stayed in housing with window/door screens. In sum, CHIKV infections were common among these volunteers during the 2014 chikungunya epidemic in the DR. Despite high levels of preparation, reported adherence to mosquito avoidance measures were inconsistent. Clinicians should discuss chikungunya with travelers visiting areas with ongoing CHIKV outbreaks and should consider chikungunya when diagnosing febrile illnesses in travelers returning from affected areas. PMID:26976891

  3. Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India.

    PubMed

    Ramachandran, V G; Das, Shukla; Roy, Priyamvada; Hada, Vivek; Mogha, Narendra Singh

    2016-06-01

    Chikungunya fever is an important reemerging arbovirus illness, which is transmitted by the same vector as of dengue virus. Many cases of concurrent infections with multiple dengue virus serotypes have been reported in many countries. Also, concurrent infection with Chikungunya virus and dengue virus has been reported in the past in Delhi. Therefore, this study was done to detect Chikungunya IgM antibodies in suspected dengue fever patients. In this study, 1666 serum samples suspected of dengue fever and collected during the outbreak period (August 2010-December 2010) were tested for dengue IgM antibodies, of which 736 tested negative. Of the 736 dengue IgM negative sera, 666 were tested for Chikungunya IgM antibodies. The demographic profile and essential laboratory investigations were recorded. Chikungunya IgM was detected in 9.91 % of the patients. During the post-monsoon period though dengue dominated in numbers, the number of Chikungunya fever cases increased gradually followed by an abrupt decrease with the onset of winter. The Chikungunya IgM positive patients were suffering from fever of more than 5 days duration and had thrombocytopenia. Due to similarity in clinical features and vector transmitting dengue and Chikungunya virus, continuous surveillance of both dengue fever and Chikungunya fever is desirable for better management and epidemiological assessment.

  4. Chikungunya: a reemerging infection spreading during 2010 dengue fever outbreak in National Capital Region of India.

    PubMed

    Ramachandran, V G; Das, Shukla; Roy, Priyamvada; Hada, Vivek; Mogha, Narendra Singh

    2016-06-01

    Chikungunya fever is an important reemerging arbovirus illness, which is transmitted by the same vector as of dengue virus. Many cases of concurrent infections with multiple dengue virus serotypes have been reported in many countries. Also, concurrent infection with Chikungunya virus and dengue virus has been reported in the past in Delhi. Therefore, this study was done to detect Chikungunya IgM antibodies in suspected dengue fever patients. In this study, 1666 serum samples suspected of dengue fever and collected during the outbreak period (August 2010-December 2010) were tested for dengue IgM antibodies, of which 736 tested negative. Of the 736 dengue IgM negative sera, 666 were tested for Chikungunya IgM antibodies. The demographic profile and essential laboratory investigations were recorded. Chikungunya IgM was detected in 9.91 % of the patients. During the post-monsoon period though dengue dominated in numbers, the number of Chikungunya fever cases increased gradually followed by an abrupt decrease with the onset of winter. The Chikungunya IgM positive patients were suffering from fever of more than 5 days duration and had thrombocytopenia. Due to similarity in clinical features and vector transmitting dengue and Chikungunya virus, continuous surveillance of both dengue fever and Chikungunya fever is desirable for better management and epidemiological assessment. PMID:27366770

  5. Mathematical Model of Three Age-Structured Transmission Dynamics of Chikungunya Virus

    PubMed Central

    Agusto, Folashade B.; Easley, Shamise; Freeman, Kenneth; Thomas, Madison

    2016-01-01

    We developed a new age-structured deterministic model for the transmission dynamics of chikungunya virus. The model is analyzed to gain insights into the qualitative features of its associated equilibria. Some of the theoretical and epidemiological findings indicate that the stable disease-free equilibrium is globally asymptotically stable when the associated reproduction number is less than unity. Furthermore, the model undergoes, in the presence of disease induced mortality, the phenomenon of backward bifurcation, where the stable disease-free equilibrium of the model coexists with a stable endemic equilibrium when the associated reproduction number is less than unity. Further analysis of the model indicates that the qualitative dynamics of the model are not altered by the inclusion of age structure. This is further emphasized by the sensitivity analysis results, which shows that the dominant parameters of the model are not altered by the inclusion of age structure. However, the numerical simulations show the flaw of the exclusion of age in the transmission dynamics of chikungunya with regard to control implementations. The exclusion of age structure fails to show the age distribution needed for an effective age based control strategy, leading to a one size fits all blanket control for the entire population. PMID:27190548

  6. Structural analyses at pseudo atomic resolution of Chikungunya virus and antibodies show mechanisms of neutralization.

    PubMed

    Sun, Siyang; Xiang, Ye; Akahata, Wataru; Holdaway, Heather; Pal, Pankaj; Zhang, Xinzheng; Diamond, Michael S; Nabel, Gary J; Rossmann, Michael G

    2013-04-02

    A 5.3 Å resolution, cryo-electron microscopy (cryoEM) map of Chikungunya virus-like particles (VLPs) has been interpreted using the previously published crystal structure of the Chikungunya E1-E2 glycoprotein heterodimer. The heterodimer structure was divided into domains to obtain a good fit to the cryoEM density. Differences in the T = 4 quasi-equivalent heterodimer components show their adaptation to different environments. The spikes on the icosahedral 3-fold axes and those in general positions are significantly different, possibly representing different phases during initial generation of fusogenic E1 trimers. CryoEM maps of neutralizing Fab fragments complexed with VLPs have been interpreted using the crystal structures of the Fab fragments and the VLP structure. Based on these analyses the CHK-152 antibody was shown to stabilize the viral surface, hindering the exposure of the fusion-loop, likely neutralizing infection by blocking fusion. The CHK-9, m10 and m242 antibodies surround the receptor-attachment site, probably inhibiting infection by blocking cell attachment. DOI:http://dx.doi.org/10.7554/eLife.00435.001.

  7. Global protein profiling studies of chikungunya virus infection identify different proteins but common biological processes.

    PubMed

    Smith, Duncan R

    2015-01-01

    Chikungunya fever (CHIKF) caused by the mosquito-transmitted chikungunya virus (CHIKV) swept into international prominence from late 2005 as an epidemic of CHIKF spread around countries surrounding the Indian Ocean. Although significant advances have been made in understanding the pathobiology of CHIKF, numerous questions still remain. In the absence of commercially available specific drugs to treat the disease, or a vaccine to prevent the diseases, the questions have particular significance. A number of studies have used global proteome analysis to increase our understanding of the process of CHIKV infection using a number of different experimental techniques and experimental systems. In all, over 700 proteins have been identified in nine different analyses by five different groups as being differentially regulated. Remarkably, only a single protein, eukaryotic elongation factor 2, has been identified by more than two different groups as being differentially regulated during CHIKV infection. This review provides a critical overview of the studies that have used global protein profiling to understand CHIKV infection and shows that while a broad consensus is emerging on which biological processes are altered during CHIKV infection, this consensus is poorly supported in terms of consistent identification of any key proteins mediating those biological processes.

  8. Genetic Characterization of Northwestern Colombian Chikungunya Virus Strains from the 2014-2015 Epidemic.

    PubMed

    Rodas, Juan D; Kautz, Tiffany; Camacho, Erwin; Paternina, Luis; Guzmán, Hilda; Díaz, Francisco J; Blanco, Pedro; Tesh, Robert; Weaver, Scott C

    2016-09-01

    Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne alphavirus, chikungunya virus (CHIKV), spread into the Americas in late 2013. Since then it has caused epidemics in nearly all New World countries, the second largest being Colombia with over 450,000 suspected cases beginning in September, 2014, and focused in Bolivar Department in the north. We examined 32 human sera from suspected cases, including diverse age groups and both genders, and sequenced the CHIKV envelope glycoprotein genes, known determinants of vector host range. As expected for Asian lineage CHIKV strains, these isolates lacked known Aedes albopictus-adaptive mutations. All the Colombian strains were closely related to those from the Virgin Islands, Saint Lucia, Mexico, Puerto Rico, and Brazil, consistent with a single, point-source introduction from the southeast Asia/Pacific region. Two substitutions in the E2 and E1 envelope glycoprotein genes were found in the Colombian strains, especially E1-K211E involving a residue shown previously to affect epistatically the penetrance of the E1-A226V A. albopictus-adaptive substitution. We also identified two amino acid substitutions unique to all American CHIKV sequences: E2-V368A and 6K-L20M. Only one codon, 6K-47, had a high nonsynonymous substitution rate suggesting positive selection. PMID:27430542

  9. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

    PubMed

    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate.

  10. Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans

    PubMed Central

    Gardner, Joy; Rudd, Penny A.; Prow, Natalie A.; Belarbi, Essia; Roques, Pierre; Larcher, Thibaut; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Schroder, Wayne A.; Suhrbier, Andreas

    2015-01-01

    Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities. PMID:26447467

  11. Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans.

    PubMed

    Gardner, Joy; Rudd, Penny A; Prow, Natalie A; Belarbi, Essia; Roques, Pierre; Larcher, Thibaut; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Schroder, Wayne A; Suhrbier, Andreas

    2015-01-01

    Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.

  12. Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.

    PubMed

    Calvo, Eliana P; Sánchez-Quete, Fernando; Durán, Sandra; Sandoval, Isabel; Castellanos, Jaime E

    2016-11-01

    Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate. PMID:27477452

  13. Development of field-based real-time reverse transcription-polymerase chain reaction assays for detection of Chikungunya and O'nyong-nyong viruses in mosquitoes.

    PubMed

    Smith, Darci R; Lee, John S; Jahrling, Jordan; Kulesh, David A; Turell, Michael J; Groebner, Jennifer L; O'Guinn, Monica L

    2009-10-01

    Chikungunya (CHIK) and O'nyong-nyong (ONN) are important emerging arthropod-borne diseases. Molecular diagnosis of these two viruses in mosquitoes has not been evaluated, and the effects of extraneous mosquito tissue on assay performance have not been tested. Additionally, no real-time reverse transcription-polymerase chain reaction (RT-PCR) assay exists for detecting ONN virus (ONNV) RNA. We describe the development of sensitive and specific real-time RT-PCR assays for detecting CHIK and ONN viral RNA in mosquitoes, which have application for field use. In addition, we compared three methods for primer/probe design for assay development by evaluating their sensitivity and specificity. This comparison resulted in development of virus-specific assays that could detect less than one plaque-forming unit equivalent of each of the viruses in mosquitoes. The use of these assays will aid in arthropod-borne disease surveillance and in the control of the associated diseases.

  14. Chikungunya, climate change, and human rights.

    PubMed

    Meason, Braden; Paterson, Ryan

    2014-06-14

    Chikungunya is a re-emerging arbovirus that causes significant morbidity and some mortality. Global climate change leading to warmer temperatures and changes in rainfall patterns allow mosquito vectors to thrive at altitudes and at locations where they previously have not, ultimately leading to a spread of mosquito-borne diseases. While mutations to the chikungunya virus are responsible for some portion of the re-emergence, chikungunya epidemiology is closely tied with weather patterns in Southeast Asia. Extrapolation of this regional pattern, combined with known climate factors impacting the spread of malaria and dengue, summate to a dark picture of climate change and the spread of this disease from south Asia and Africa into Europe and North America. This review describes chikungunya and collates current data regarding its spread in which climate change plays an important part. We also examine human rights obligations of States and others to protect against this disease.

  15. Development and Evaluation of a SYBR Green-Based Real-Time Multiplex RT-PCR Assay for Simultaneous Detection and Serotyping of Dengue and Chikungunya Viruses.

    PubMed

    Chen, Huixin; Parimelalagan, Mariya; Lai, Yee Ling; Lee, Kim Sung; Koay, Evelyn Siew-Chuan; Hapuarachchi, Hapuarachchige C; Ng, Lee Ching; Ho, Phui San; Chu, Justin Jang Hann

    2015-11-01

    Chikungunya virus (CHIKV) and dengue virus (DENV) have emerged as the two most important arbovirus diseases of global health significance. Similar clinical manifestations, transmission vectors, geographical distribution, and seasonal correlation often result in misdiagnosis of chikungunya infections as dengue cases and vice versa. In this study, we developed a rapid and accurate laboratory confirmative method to simultaneously detect, quantify, and differentiate DENV serotypes 1, 2, 3, and 4 and CHIKV. This SYBR Green I-based one-step multiplex real-time RT-PCR assay is highly sensitive and specific for CHIKV and DENV. Melting temperature analysis of PCR amplicons was used to serotype DENV and to differentiate from CHIKV. The detection limit of the assay was 20, 10, 50, 5, and 10 RNA copies/reaction for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV, respectively. Our assay did not cross-react with a panel of viruses that included other flaviviruses, alphaviruses, influenza viruses, human enteroviruses, and human coronaviruses. The feasibility of using this assay for clinical diagnosis was evaluated in DENV- and CHIKV-positive patient sera. Accordingly, the assay sensitivity for DENV-1, DENV-2, DENV-3, DENV-4, and CHIKV was 89.66%, 96.67%, 96.67%, 94.12%, and 95.74%, respectively, with 100% specificity. These findings confirmed the potential of our assay to be used as a rapid test for simultaneous detection and serotyping of DENV and CHIKV in clinical samples.

  16. [Epidemiological study of arboviruses in the Central African Republic: demonstration of Chikungunya virus during 1978 and 1979].

    PubMed

    Saluzzo, J F; Gonzalez, J P; Hervé, J P; Georges, A J

    1980-01-01

    From January 1978 to May 1979, the Chikungunya virus came out in several places in south of Central African Republic. We isolated one strain of virus from a human serum and 33 from pools of Aedes africanus group collected in two forest galleries situated near the village of Bozo, in the semi-humid savanna. Several serological conversions were observed in patients with fever joint pain and sometimes macular eruption. The intensive activity of Chikungunya virus was confirmed by serological survey in south-east of the country, i. e.: 17% sera were positive by IHA test with high level (greater than or equal to 1 280) according to recent infection. Mosquitoes strains isolated in 1978 seem to proceed from epizootic manifestation, as we observed in 1975 in the same area. Epidemiologic findings of periodic recurrence is discussed. PMID:7460128

  17. Clinical and radiological features of imported chikungunya fever in Japan: a study of six cases at the National Center for Global Health and Medicine.

    PubMed

    Mizuno, Yasutaka; Kato, Yasuyuki; Takeshita, Nozomi; Ujiie, Mugen; Kobayashi, Taiichiro; Kanagawa, Shuzo; Kudo, Koichiro; Lim, Chang-Kweng; Takasaki, Tomohiko

    2011-06-01

    Chikungunya fever (CHIKF) is currently distributed in Africa and in South and Southeast Asia; outbreaks have occurred periodically in the region over the past 50 years. After a large outbreak had occurred in countries in the western Indian Ocean region in 2005, several countries reported cases of CHIKF from travelers who had visited affected areas. In Japan, there have been only 15 cases of CHIKF patients so far, according to the National Institute of Infectious Diseases. Therefore, to evaluate the clinical and radiological features associated with the disease, we describe 6 imported cases of CHIKF. All of the patients had had prolonged arthralgia on admission to our hospital, and diagnosis was confirmed with specific antibodies by using an IgM-capture enzyme-linked immunoassay and a plaque reduction neutralizing antibody assay. Magnetic resonance imaging (MRI) of one patient revealed erosive arthritis and tenosynovitis during the convalescence stage. Clinicians should be aware of the late consequences of infection by the chikungunya virus (CHIKV) and recognize the possible association of subacute and chronic arthritis features. In addition, competent vectors of CHIKV, Aedes aegypti, can now be found in many temperate areas of the eastern and western hemispheres, including Japan. This fact raises concern that the virus could be introduced and become established in these areas. This necessitates an increased awareness of the disease, because imported cases are likely to contribute to the spread of CHIKV infection wherever the competent mosquito vectors are distributed.

  18. Western Blot Detection of Human Anti-Chikungunya Virus Antibody with Recombinant Envelope 2 Protein.

    PubMed

    Yang, Zhaoshou; Lee, Jihoo; Ahn, Hye-Jin; Chong, Chom-Kyu; Dias, Ronaldo F; Nam, Ho-Woo

    2016-04-01

    Chikungunya virus (CHIKV), a tropical pathogen, has re-emerged and has massive outbreaks abruptly all over the world. Containing many dominant epitopes, the envelope E2 protein of CHIKV has been explored for the vaccination or diagnosis. In the present study, the antigenicity of a recombinant expressed intrinsically disorder domain (IUD) of E2 was tested for the detection of the antibody against CHIKV through western blot method. The gene of the IUD of E2 was inserted into 2 different vectors and expressed as recombinant GST-E2 and recombinant MBP-E2 fusion protein, respectively. Two kinds of fusion proteins were tested with 30 CHIKV patient sera and 30 normal sera, respectively. Both proteins were detected by 25 patients sera (83.3%) and 1 normal serum (3.3%). This test showed a relatively high sensitivity and very high specificity of the recombinant E2 proteins to be used as diagnostic antigens against CHIKV infection. PMID:27180586

  19. Seroprevalence and entomological study on Chikungunya virus at the Croatian littoral.

    PubMed

    Vilibic-Cavlek, Tatjana; Pem-Novosel, Iva; Kaic, Bernard; Babić-Erceg, Andrea; Kucinar, Jasmina; Klobucar, Ana; Medic, Alan; Pahor, Djana; Barac-Juretic, Katija; Gjenero-Margan, Ira

    2015-06-01

    During 2011-2012, a total of 1008 serum samples from randomly selected inhabitants of seven Croatian counties located on the Adriatic Coast were tested for the presence of chikungunya virus (CHIKV) IgG antibodies using indirect immunofluorescence assay. Nine participants (0.9%) from four counties were found to be seropositive to CHIKV. Seroprevalence varied from 0.5% to 1.8% between counties. Additionally, a total of 3,699 mosquitoes were captured in 126 localities from August 16 to September 24, 2011. Three mosquito species were found: Ae. albopictus (3010/81.4%), Cx. pipiens (688/18.6%) and only one specimen of the Cs. longiareolata. Female mosquitoes (N = 1,748) were pooled. All pools tested negative for CHIKV RNA using a real-time RT-PCR.

  20. Western Blot Detection of Human Anti-Chikungunya Virus Antibody with Recombinant Envelope 2 Protein

    PubMed Central

    Yang, Zhaoshou; Lee, Jihoo; Ahn, Hye-Jin; Chong, Chom-Kyu; Dias, Ronaldo F.; Nam, Ho-Woo

    2016-01-01

    Chikungunya virus (CHIKV), a tropical pathogen, has re-emerged and has massive outbreaks abruptly all over the world. Containing many dominant epitopes, the envelope E2 protein of CHIKV has been explored for the vaccination or diagnosis. In the present study, the antigenicity of a recombinant expressed intrinsically disorder domain (IUD) of E2 was tested for the detection of the antibody against CHIKV through western blot method. The gene of the IUD of E2 was inserted into 2 different vectors and expressed as recombinant GST-E2 and recombinant MBP-E2 fusion protein, respectively. Two kinds of fusion proteins were tested with 30 CHIKV patient sera and 30 normal sera, respectively. Both proteins were detected by 25 patients sera (83.3%) and 1 normal serum (3.3%). This test showed a relatively high sensitivity and very high specificity of the recombinant E2 proteins to be used as diagnostic antigens against CHIKV infection. PMID:27180586

  1. Dysregulated TGF-β Production Underlies the Age-Related Vulnerability to Chikungunya Virus

    PubMed Central

    Uhrlaub, Jennifer L.; Pulko, Vesna; DeFilippis, Victor R.; Streblow, Daniel N.; Coleman, Gary D.; Lindo, John F.; Vickers, Ivan; Anzinger, Joshua J.; Nikolich-Žugich, Janko

    2016-01-01

    Chikungunya virus (CHIKV) is a re-emerging global pathogen with pandemic potential, which causes fever, rash and debilitating arthralgia. Older adults over 65 years are particularly susceptible to severe and chronic CHIKV disease (CHIKVD), accounting for >90% of all CHIKV-related deaths. There are currently no approved vaccines or antiviral treatments available to limit chronic CHIKVD. Here we show that in old mice excessive, dysregulated TGFβ production during acute infection leads to a reduced immune response and subsequent chronic disease. Humans suffering from CHIKV infection also exhibited high TGFβ levels and a pronounced age-related defect in neutralizing anti-CHIKV antibody production. In vivo reduction of TGFβ levels minimized acute joint swelling, restored neutralizing antibody production and diminished chronic joint pathology in old mice. This study identifies increased and dysregulated TGFβ secretion as one key mechanism contributing to the age-related loss of protective anti-CHIKV-immunity leading to chronic CHIKVD. PMID:27736984

  2. Landscape Ecology of Sylvatic Chikungunya Virus and Mosquito Vectors in Southeastern Senegal

    PubMed Central

    Diallo, Diawo; Sall, Amadou A.; Buenemann, Michaela; Chen, Rubing; Faye, Oumar; Diagne, Cheikh T.; Faye, Ousmane; Ba, Yamar; Dia, Ibrahima; Watts, Douglas; Weaver, Scott C.; Hanley, Kathryn A.; Diallo, Mawlouth

    2012-01-01

    The risk of human infection with sylvatic chikungunya (CHIKV) virus was assessed in a focus of sylvatic arbovirus circulation in Senegal by investigating distribution and abundance of anthropophilic Aedes mosquitoes, as well as the abundance and distribution of CHIKV in these mosquitoes. A 1650 km2 area was classified into five land cover classes: forest, barren, savanna, agriculture and village. A total of 39,799 mosquitoes was sampled from all classes using human landing collections between June 2009 and January 2010. Mosquito diversity was extremely high, and overall vector abundance peaked at the start of the rainy season. CHIKV was detected in 42 mosquito pools. Our data suggest that Aedes furcifer, which occurred abundantly in all land cover classes and landed frequently on humans in villages outside of houses, is probably the major bridge vector responsible for the spillover of sylvatic CHIKV to humans. PMID:22720097

  3. Antagonism of the Sodium-Potassium ATPase Impairs Chikungunya Virus Infection

    PubMed Central

    Ashbrook, Alison W.; Lentscher, Anthony J.; Zamora, Paula F.; Silva, Laurie A.; May, Nicholas A.; Bauer, Joshua A.; Morrison, Thomas E.

    2016-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus that has caused epidemics of fever, arthralgia, and rash worldwide. There are currently no licensed vaccines or antiviral therapies available for the prevention or treatment of CHIKV disease. We conducted a high-throughput, chemical compound screen that identified digoxin, a cardiac glycoside that blocks the sodium-potassium ATPase, as a potent inhibitor of CHIKV infection. Treatment of human cells with digoxin or a related cardiac glycoside, ouabain, resulted in a dose-dependent decrease in infection by CHIKV. Inhibition by digoxin was cell type-specific, as digoxin treatment of either murine or mosquito cells did not diminish CHIKV infection. Digoxin displayed antiviral activity against other alphaviruses, including Ross River virus and Sindbis virus, as well as mammalian reovirus and vesicular stomatitis virus. The digoxin-mediated block to CHIKV and reovirus infection occurred at one or more postentry steps, as digoxin inhibition was not bypassed by fusion of CHIKV at the plasma membrane or infection with cell surface-penetrating reovirus entry intermediates. Selection of digoxin-resistant CHIKV variants identified multiple mutations in the nonstructural proteins required for replication complex formation and synthesis of viral RNA. These data suggest a role for the sodium-potassium ATPase in promoting postentry steps of CHIKV replication and provide rationale for modulation of this pathway as a broad-spectrum antiviral strategy. PMID:27222471

  4. Nonhuman Primate Models of Chikungunya Virus Infection and Disease (CHIKV NHP Model)

    PubMed Central

    Broeckel, Rebecca; Haese, Nicole; Messaoudi, Ilhem; Streblow, Daniel N.

    2015-01-01

    Chikungunya virus (CHIKV) is a positive-sense RNA virus transmitted by Aedes mosquitoes. CHIKV is a reemerging Alphavirus that causes acute febrile illness and severe and debilitating polyarthralgia of the peripheral joints. Huge epidemics and the rapid spread of CHIKV seen in India and the Indian Ocean region established CHIKV as a global health concern. This concern was further solidified by the recent incursion of the virus into the Western hemisphere, a region without pre-existing immunity. Nonhuman primates (NHPs) serve as excellent animal models for understanding CHIKV pathogenesis and pre-clinical assessment of vaccines and therapeutics. NHPs present advantages over rodent models because they are a natural amplification host for CHIKV and they share significant genetic and physiological homology with humans. CHIKV infection in NHPs results in acute fever, rash, viremia and production of type I interferon. NHPs develop CHIKV-specific B and T-cells, generating neutralizing antibodies and CHIKV-specific CD4+ and CD8+ T-cells. CHIKV establishes a persistent infection in NHPs, particularly in cynomolgus macaques, because infectious virus could be recovered from spleen, liver, and muscle as late as 44 days post infection. NHPs are valuable models that are useful in preclinical testing of vaccines and therapeutics and uncovering the details of CHIKV pathogenesis. PMID:26389957

  5. Chikungunya fever in Los Angeles, California.

    PubMed

    Harter, Katherine R; Bhatt, Sanjay; Kim, Hyung T; Mallon, William K

    2014-11-01

    We report the case of a 33-year-old woman returning from Haiti, presenting to our emergency department (ED) with fever, rash and arthralgia. Following a broad workup that included laboratory testing for dengue and malaria, our patient was diagnosed with Chikungunya virus, which was then reported to the Centers for Disease Control and Prevention for initiation of infection control. This case demonstrates the importance of the ED for infectious disease case identification and initiation of public health measures. This case also addresses public health implications of Chikungunya virus within the United States, and issues related to the potential for local spread and autochthonous cases.

  6. Chikungunya, an epidemic arbovirosis.

    PubMed

    Pialoux, Gilles; Gaüzère, Bernard-Alex; Jauréguiberry, Stéphane; Strobel, Michel

    2007-05-01

    Chikungunya is an arboviral disease transmitted by aedes mosquitoes. The virus was first isolated in 1953 in Tanzania. Chikungunya virus is a member of the genus Alphavirus and the family Togaviridae. The disease typically consists of an acute illness characterised by fever, rash, and incapacitating arthralgia. The word chikungunya, used for both the virus and the disease, means "to walk bent over" in some east African languages, and refers to the effect of the joint pains that characterise this dengue-like infection. Chikungunya is a specifically tropical disease, but it is geographically restricted and outbreaks are relatively uncommon. It is only occasionally observed in travellers and military personnel. More than 266 000 people have been infected during the ongoing outbreak in Réunion, in which Aedes albopictus is the presumed vector. In the ongoing Indian outbreak, in which Aedes aegypti is the presumed vector, 1 400 000 cases of chikungunya were reported during 2006. The reasons for the re-emergence of chikungunya on the Indian subcontinent, and for its unprecedented incidence rate in the Indian Ocean region, are unclear. Plausible explanations include increased tourism, chikungunya virus introduction into a naive population, and viral mutation.

  7. The wMel Strain of Wolbachia Reduces Transmission of Chikungunya Virus in Aedes aegypti

    PubMed Central

    Aliota, Matthew T.; Walker, Emma C.; Uribe Yepes, Alexander; Dario Velez, Ivan; Christensen, Bruce M.; Osorio, Jorge E.

    2016-01-01

    Background New approaches to preventing chikungunya virus (CHIKV) are needed because current methods are limited to controlling mosquito populations, and they have not prevented the invasion of this virus into new locales, nor have they been sufficient to control the virus upon arrival. A promising candidate for arbovirus control and prevention relies on the introduction of the intracellular bacterium Wolbachia into Aedes aegypti mosquitoes. This primarily has been proposed as a tool to control dengue virus (DENV) transmission; however, evidence suggests Wolbachia infections confer protection for Ae. aegypti against CHIKV. Although this approach holds much promise for limiting virus transmission, at present our understanding of the ability of CHIKV to infect, disseminate, and be transmitted by wMel-infected Ae. aegypti currently being used at Wolbachia release sites is limited. Methodology/Principal Findings Using Ae. aegypti infected with the wMel strain of Wolbachia that are being released in Medellin, Colombia, we report that these mosquitoes have reduced vector competence for CHIKV, even with extremely high viral titers in the bloodmeal. In addition, we examined the dynamics of CHIKV infection over the course of four to seven days post feeding. Wolbachia-infected mosquitoes remained non-infective over the duration of seven days, i.e., no infectious virus was detected in the saliva when exposed to bloodmeals of moderate viremia, but CHIKV-exposed, wild type mosquitoes did have viral loads in the saliva consistent with what has been reported elsewhere. Finally, the presence of wMel infection had no impact on the lifespan of mosquitoes as compared to wild type mosquitoes following CHIKV infection. Conclusions/Significance These results could have an impact on vector control strategies in areas where Ae. aegypti are transmitting both DENV and CHIKV; i.e., they argue for further exploration, both in the laboratory and the field, on the feasibility of expanding this

  8. Genetic diversity of Chikungunya virus, India 2006-2010: evolutionary dynamics and serotype analyses.

    PubMed

    Sumathy, K; Ella, Krishna M

    2012-03-01

    The genetic diversity of Chikungunya virus (CHIKV) causing recurring outbreaks in India since 2006 was studied. The 2006 epidemic was caused by a virus strain of the East, Central and South African (ECSA) genotype with 226A in the E1 glycoprotein. The variant strain with E1-A226V mutation caused outbreaks since 2007 in the state of Kerala where Aedes albopictus is the abundant mosquito vector. Molecular epidemiology data since 2007 is scarce from other regions of the country. RT-PCR, sequencing and phylogenetic analyses of CHIKV isolates from the 2009 to 2010 epidemics in the States of Tamil Nadu and Andhra Pradesh placed them in a separate clade within the ECSA lineage. The isolates of the study had 226A in the E1 glycoprotein. The isolates had a novel E1-K211E mutation that was under significant positive selection. E1-211E is highly conserved in the Asian genotype of the virus circulated by Aedes aegypti. Unique mutations in E2 glycoprotein were identified. The two sub-lineages of ECSA genotype circulating in India parallel the abundance of Ae. albopictus and Ae. aegypti. Novel mutations in the envelope glycoproteins suggest adaptive evolution of the virus to local vector abundance. Cross neutralization of the virus isolates from recurring Indian epidemics indicated that no distinct serotypes had evolved. The study has provided insights into the origin, distribution and evolutionary adaptation of the virus to local vector abundance in the region that has reportedly, the highest incidence of CHIKV infection in the world.

  9. In silico study on anti-Chikungunya virus activity of hesperetin

    PubMed Central

    Oo, Adrian; Hassandarvish, Pouya; Chin, Sek Peng; Abu Bakar, Sazaly

    2016-01-01

    Background The re-emerging, Aedes spp. transmitted Chikungunya virus (CHIKV) has recently caused large outbreaks in a wide geographical distribution of the world including countries in Europe and America. Though fatalities associated with this self-remitting disease were rarely reported, quality of patients’ lives have been severely diminished by polyarthralgia recurrence. Neither effective antiviral treatment nor vaccines are available for CHIKV. Our previous in vitro screening showed that hesperetin, a bioflavonoid exhibits inhibitory effect on the virus intracellular replication. Here, we present a study using the computational approach to identify possible target proteins for future mechanistic studies of hesperetin. Methods 3D structures of CHIKV nsP2 (3TRK) and nsP3 (3GPG) were retrieved from Protein Data Bank (PDB), whereas nsP1, nsP4 and cellular factor SPK2 were modeled using Iterative Threading Assembly Refinement (I-TASSER) server based on respective amino acids sequence. We performed molecular docking on hesperetin against all four CHIKV non-structural proteins and SPK2. Proteins preparation and subsequent molecular docking were performed using Discovery Studio 2.5 and AutoDock Vina 1.5.6. The Lipinski’s values of the ligand were computed and compared with the available data from PubChem. Two non-structural proteins with crystal structures 3GPG and 3TRK in complexed with hesperetin, demonstrated favorable free energy of binding from the docking study, were further explored using molecular dynamics (MD) simulations. Results We observed that hesperetin interacts with different types of proteins involving hydrogen bonds, pi-pi effects, pi-cation bonding and pi-sigma interactions with varying binding energies. Among all five tested proteins, our compound has the highest binding affinity with 3GPG at −8.5 kcal/mol. The ligand used in this study also matches the Lipinski’s rule of five in addition to exhibiting closely similar properties with that of

  10. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells

    PubMed Central

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H. Lie; Smit, Jolanda M.; Rodenhuis-Zybert, Izabela A.

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  11. Mechanism and role of MCP-1 upregulation upon chikungunya virus infection in human peripheral blood mononuclear cells.

    PubMed

    Ruiz Silva, Mariana; van der Ende-Metselaar, Heidi; Mulder, H Lie; Smit, Jolanda M; Rodenhuis-Zybert, Izabela A

    2016-01-01

    Monocyte chemoattractant protein-1 (MCP-1/CCL2)-mediated migration of monocytes is essential for immunological surveillance of tissues. During chikungunya virus (CHIKV) infection however, excessive production of MCP-1 has been linked to disease pathogenesis. High MCP-1 serum levels are detected during the viremic phase of CHIKV infection and correlate with the virus titre. In vitro CHIKV infection was also shown to stimulate MCP-1 production in whole blood; yet the role and the mechanism of MCP-1 production upon infection of human peripheral blood mononuclear cells remain unknown. Here we found that active CHIKV infection stimulated production of MCP-1 in monocytes. Importantly however, we found that communication with other leukocytes is crucial to yield MCP-1 by monocytes upon CHIKV infection. Indeed, blocking interferon-α/β receptor or the JAK1/JAK2 signalling downstream of the receptor abolished CHIKV-mediated MCP-1 production. Additionally, we show that despite the apparent correlation between IFN type I, CHIKV replication and MCP-1, modulating the levels of the chemokine did not influence CHIKV infection. In summary, our data disclose the complexity of MCP-1 regulation upon CHIKV infection and point to a crucial role of IFNβ in the chemokine secretion. We propose that balance between these soluble factors is imperative for an appropriate host response to CHIKV infection. PMID:27558873

  12. Human keratinocytes restrict chikungunya virus replication at a post-fusion step

    SciTech Connect

    Bernard, Eric; Simmons, Graham; Chazal, Nathalie; and others

    2015-02-15

    Transmission of chikungunya virus (CHIKV) to humans is initiated by puncture of the skin by a blood-feeding Aedes mosquito. Despite the growing knowledge accumulated on CHIKV, the interplay between skin cells and CHIKV following inoculation still remains unclear. In this study we questioned the behavior of human keratinocytes, the predominant cell population in the skin, following viral challenge. We report that CHIKV rapidly elicits an innate immune response in these cells leading to the enhanced transcription of type I/II and type III interferon genes. Concomitantly, we show that despite viral particles internalization into Rab5-positive endosomes and efficient fusion of virus and cell membranes, keratinocytes poorly replicate CHIKV as attested by absence of nonstructural proteins and genomic RNA synthesis. Accordingly, human keratinocytes behave as an antiviral defense against CHIKV infection rather than as a primary targets for initial replication. This picture significantly differs from that reported for Dengue and West Nile mosquito-borne viruses. - Highlights: • Human keratinocytes support endocytosis of CHIKV and fusion of viral membranes. • CHIKV replication is blocked at a post entry step in these cells. • Infection upregulates type-I, –II and –III IFN genes expression. • Keratinocytes behave as immune sentinels against CHIKV.

  13. That Which Bends Up: A Case Report and Literature Review of Chikungunya Virus.

    PubMed

    Peper, Shana M; Monson, Benjamin J; Van Schooneveld, Trevor; Smith, Christopher J

    2016-05-01

    We present a case of chikungunya virus (CHIKV) in a 39-year-old female who developed an acute febrile illness marked by polyarthralgia and rash after returning from Saint Lucia. This epidemic-prone pathogen is increasingly likely to be encountered by primary care and hospital physicians in the coming months. The virus was first locally transmitted in the Caribbean in December 2013 and has since spread to 44 countries and 47 US states, affecting a suspected 1.2 million people. A mosquito-borne virus, CHIKV causes a severe and symmetric polyarthralgia that can relapse for months to years, creating debilitating illness and profound socioeconomic consequences. Current treatment is limited to supportive measures, which are dependent on nonsteroidal anti-inflammatory drugs. Research into immunomodulatory agents, antiviral therapies, and vaccines is ongoing. Prevention remains key in slowing the spread of disease. Patient education should focus on personal protective measures, such as insect repellant and remaining indoors, while public health departments should implement strategies to control vector breeding grounds. Given the possibility of relapsing and debilitating disease, general internists should consider CHIKV in the differential diagnosis of a returning traveler with acute onset of fever, polyarthralgia, and rash.

  14. Interferon Response Factors 3 and 7 Protect against Chikungunya Virus Hemorrhagic Fever and Shock

    PubMed Central

    Rudd, Penny A.; Wilson, Jane; Gardner, Joy; Larcher, Thibaut; Babarit, Candice; Le, Thuy T.; Anraku, Itaru; Kumagai, Yutaro; Loo, Yueh-Ming; Gale, Michael; Akira, Shizuo; Khromykh, Alexander A.

    2012-01-01

    Chikungunya virus (CHIKV) infections can produce severe disease and mortality. Here we show that CHIKV infection of adult mice deficient in interferon response factors 3 and 7 (IRF3/7−/−) is lethal. Mortality was associated with undetectable levels of alpha/beta interferon (IFN-α/β) in serum, ∼50- and ∼10-fold increases in levels of IFN-γ and tumor necrosis factor (TNF), respectively, increased virus replication, edema, vasculitis, hemorrhage, fever followed by hypothermia, oliguria, thrombocytopenia, and raised hematocrits. These features are consistent with hemorrhagic shock and were also evident in infected IFN-α/β receptor-deficient mice. In situ hybridization suggested CHIKV infection of endothelium, fibroblasts, skeletal muscle, mononuclear cells, chondrocytes, and keratinocytes in IRF3/7−/− mice; all but the latter two stained positive in wild-type mice. Vaccination protected IRF3/7−/− mice, suggesting that defective antibody responses were not responsible for mortality. IPS-1- and TRIF-dependent pathways were primarily responsible for IFN-α/β induction, with IRF7 being upregulated >100-fold in infected wild-type mice. These studies suggest that inadequate IFN-α/β responses following virus infection can be sufficient to induce hemorrhagic fever and shock, a finding with implications for understanding severe CHIKV disease and dengue hemorrhagic fever/dengue shock syndrome. PMID:22761364

  15. Seroprevalence of antibodies against Chikungunya, Dengue, and Rift Valley fever viruses after febrile illness outbreak, Madagascar.

    PubMed

    Schwarz, Norbert G; Girmann, Mirko; Randriamampionona, Njary; Bialonski, Alexandra; Maus, Deborah; Krefis, Anne Caroline; Njarasoa, Christine; Rajanalison, Jeanne Fleury; Ramandrisoa, Herly Daniel; Randriarison, Maurice Lucien; May, Jürgen; Schmidt-Chanasit, Jonas; Rakotozandrindrainy, Raphael

    2012-11-01

    In October 2009, two-3 months after an outbreak of a febrile disease with joint pain on the eastern coast of Madagascar, we assessed serologic markers for chikungunya virus (CHIKV), dengue virus (DENV), and Rift Valley fever virus (RVFV) in 1,244 pregnant women at 6 locations. In 2 eastern coast towns, IgG seroprevalence against CHIKV was 45% and 23%; IgM seroprevalence was 28% and 5%. IgG seroprevalence against DENV was 17% and 11%. No anti-DENV IgM was detected. At 4 locations, 450-1,300 m high, IgG seroprevalence against CHIKV was 0%-3%, suggesting CHIKV had not spread to higher inland-altitudes. Four women had IgG against RVFV, probably antibodies from a 2008 epidemic. Most (78%) women from coastal locations with CHIKV-specific IgG reported joint pain and stiffness; 21% reported no symptoms. CHIKV infection was significantly associated with high bodyweight. The outbreak was an isolated CHIKV epidemic without relevant DENV co-transmission.

  16. Incrimination of Aedes (Stegomyia) hensilli Farner as an Epidemic Vector of Chikungunya Virus on Yap Island, Federated States of Micronesia, 2013

    PubMed Central

    Savage, Harry M.; Ledermann, Jeremy P.; Yug, Laurence; Burkhalter, Kristen L.; Marfel, Maria; Hancock, W. Thane

    2015-01-01

    Two species of Aedes (Stegomyia) were collected in response to the first chikungunya virus (CHIKV) outbreak on Yap Island: the native species Ae. hensilli Farner and the introduced species Ae. aegypti (L.). Fourteen CHIKV-positive mosquito pools were detected. Six pools were composed of female Ae. hensilli, six pools were composed of female Ae. aegypti, one pool was composed of male Ae. hensilli, and one pool contained female specimens identified as Ae. (Stg.) spp. Infection rates were not significantly different between female Ae. hensilli and Ae. aegypti. The occurrence of human cases in all areas of Yap Island and the greater number of sites that yielded virus from Ae. hensilli combined with the ubiquitous distribution of this species incriminate Ae. hensilli as the most important vector of CHIKV during the outbreak. Phylogenic analysis shows that virus strains on Yap are members of the Asia lineage and closely related to strains currently circulating in the Caribbean. PMID:25404070

  17. Kinetic characterization of trans-proteolytic activity of Chikungunya virus capsid protease and development of a FRET-based HTS assay

    PubMed Central

    Aggarwal, Megha; Sharma, Rajesh; Kumar, Pravindra; Parida, Manmohan; Tomar, Shailly

    2015-01-01

    Chikungunya virus (CHIKV) capsid protein (CVCP) is a serine protease that possesses cis-proteolytic activity essential for the structural polyprotein processing and plays a key role in the virus life cycle. CHIKV being an emerging arthropod-borne pathogenic virus, is a public health concern worldwide. No vaccines or specific antiviral treatment is currently available for chikungunya disease. Thus, it is important to develop inhibitors against CHIKV enzymes to block key steps in viral reproduction. In view of this, CVCP was produced recombinantly and purified to homogeneity. A fluorescence resonance energy transfer (FRET)-based proteolytic assay was developed for high throughput screening (HTS). A FRET peptide substrate (DABCYL-GAEEWSLAIE-EDANS) derived from the cleavage site present in the structural polyprotein of CVCP was used. The assay with a Z’ factor of 0.64 and coefficient of variation (CV) is 8.68% can be adapted to high throughput format for automated screening of chemical libraries to identify CVCP specific protease inhibitors. Kinetic parameters Km and kcat/Km estimated using FRET assay were 1.26 ± 0.34 μM and 1.11 × 103 M−1 sec−1 respectively. The availability of active recombinant CVCP and cost effective fluorogenic peptide based in vitro FRET assay may serve as the basis for therapeutics development against CHIKV. PMID:26439734

  18. Copy number variation of Chikungunya ECSA virus with disease symptoms among Indian patients.

    PubMed

    Dutta, Sudip Kumar; Pal, Tithi; Saha, Bibhuti; Mandal, Syamsundar; Tripathi, Anusri

    2014-08-01

    After a gap of three decades, from 2005 onwards, a series of Chikungunya virus (CHIKV) outbreaks occurred worldwide. This study was performed to detect CHIKV infection, its genotype among symptomatic Eastern Indian patients and to analyze any association between the presence of CHIKV genome in patient body with appearance of disease symptoms (n = 199). Plasma-extracted viral RNA was reverse transcribed to cDNA and PCR-amplified followed by agarose gel electrophoresis. Viral load among CHIKV-positive patients was determined by real time RT-PCR. CHIKV-IgM in sera was detected by ELISA. Sequencing and phylogenetic analysis of plasma-extracted PCR products was done. CHIKV genome and IgM were detected among 65.3% (n = 130) and 41.2% (n = 82) patients respectively. Joint swelling was significantly associated with CHIKV infection (P-value: 0.0003). CHIKV PCR positive patients were grouped in two categories: Group-I: viral load <10(4)  copies/ml and Group-II: viral load ≥10(4)  copies/ml. Higher number of acute stage patients clustered in Group-II. Fever and joint swelling were significantly more prevalent among Group-II patients, whereas rash and diarrhoea among Group-I patients (P-value <0.05). Patient-isolated CHIKV sequences clustered with CHIKV ECSA genotypes in the phylogenetic tree, with two types of CHIKV strains found to circulate among them-as indicated by their different nucleotide sequences. This is the first study detecting the presence of CHIKV ECSA genotype among Eastern Indian patients. Fever and joint swelling might have appeared first followed by rash, diarrhea during disease progression-as indicated by CHIK viral load in patients. Thus, viral load can be used as unique diagnostic and prognostic marker of Chikungunya disease pathogenesis.

  19. Copy number variation of Chikungunya ECSA virus with disease symptoms among Indian patients.

    PubMed

    Dutta, Sudip Kumar; Pal, Tithi; Saha, Bibhuti; Mandal, Syamsundar; Tripathi, Anusri

    2014-08-01

    After a gap of three decades, from 2005 onwards, a series of Chikungunya virus (CHIKV) outbreaks occurred worldwide. This study was performed to detect CHIKV infection, its genotype among symptomatic Eastern Indian patients and to analyze any association between the presence of CHIKV genome in patient body with appearance of disease symptoms (n = 199). Plasma-extracted viral RNA was reverse transcribed to cDNA and PCR-amplified followed by agarose gel electrophoresis. Viral load among CHIKV-positive patients was determined by real time RT-PCR. CHIKV-IgM in sera was detected by ELISA. Sequencing and phylogenetic analysis of plasma-extracted PCR products was done. CHIKV genome and IgM were detected among 65.3% (n = 130) and 41.2% (n = 82) patients respectively. Joint swelling was significantly associated with CHIKV infection (P-value: 0.0003). CHIKV PCR positive patients were grouped in two categories: Group-I: viral load <10(4)  copies/ml and Group-II: viral load ≥10(4)  copies/ml. Higher number of acute stage patients clustered in Group-II. Fever and joint swelling were significantly more prevalent among Group-II patients, whereas rash and diarrhoea among Group-I patients (P-value <0.05). Patient-isolated CHIKV sequences clustered with CHIKV ECSA genotypes in the phylogenetic tree, with two types of CHIKV strains found to circulate among them-as indicated by their different nucleotide sequences. This is the first study detecting the presence of CHIKV ECSA genotype among Eastern Indian patients. Fever and joint swelling might have appeared first followed by rash, diarrhea during disease progression-as indicated by CHIK viral load in patients. Thus, viral load can be used as unique diagnostic and prognostic marker of Chikungunya disease pathogenesis. PMID:24132555

  20. Mutations Conferring a Noncytotoxic Phenotype on Chikungunya Virus Replicons Compromise Enzymatic Properties of Nonstructural Protein 2

    PubMed Central

    Utt, Age; Das, Pratyush Kumar; Varjak, Margus; Lulla, Valeria; Lulla, Aleksei

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) (genus Alphavirus) has a positive-sense RNA genome. CHIKV nonstructural protein 2 (nsP2) proteolytically processes the viral nonstructural polyprotein, possesses nucleoside triphosphatase (NTPase), RNA triphosphatase, and RNA helicase activities, and induces cytopathic effects in vertebrate cells. Although alphaviral nsP2 mutations can result in a noncytotoxic phenotype, the effects of such mutations on nsP2 enzymatic activities are not well understood. In this study, we introduced a P718G (PG) mutation and selected for additional mutations in CHIKV nsP2 that resulted in a CHIKV replicon with a noncytotoxic phenotype in BHK-21 cells. Combinations of PG and either an E116K (EK) substitution or a GEEGS sequence insertion after residue T648 (5A) markedly reduced RNA synthesis; however, neither PG nor 5A prevented nsP2 nuclear translocation. Introducing PG into recombinant nsP2 inhibited proteolytic cleavage of nsP1/nsP2 and nsP3/nsP4 sites, reduced GTPase and RNA helicase activities, and abolished RNA stimulation of GTPase activity. 5A and EK modulated the effects of PG. However, only the RNA helicase activity of nsP2 was reduced by both of these mutations, suggesting that defects in this activity may be linked to a noncytotoxic phenotype. These results increase our understanding of the molecular basis for the cytotoxicity that accompanies alphaviral replication. Furthermore, adaptation of the CHIKV replicon containing both 5A and PG allowed the selection of a CHIKV replicon with adaptive mutations in nsP1 and nsP3 that enable persistence in human cell line. Such cell lines represent valuable experimental systems for discovering host factors and for screening inhibitors of CHIKV replication at lower biosafety levels. IMPORTANCE CHIKV is a medically important pathogen that causes febrile illness and can cause chronic arthritis. No approved vaccines or antivirals are available for CHIKV. The attenuation of CHIKV is critical to the

  1. Native Wolbachia from Aedes albopictus Blocks Chikungunya Virus Infection In Cellulo.

    PubMed

    Raquin, Vincent; Valiente Moro, Claire; Saucereau, Yoann; Tran, Florence-Hélène; Potier, Patrick; Mavingui, Patrick

    2015-01-01

    Wolbachia, a widespread endosymbiont of terrestrial arthropods, can protect its host against viral and parasitic infections, a phenotype called "pathogen blocking". However, in some cases Wolbachia may have no effect or even enhance pathogen infection, depending on the host-Wolbachia-pathogen combination. The tiger mosquito Aedes albopictus is naturally infected by two strains of Wolbachia, wAlbA and wAlbB, and is a competent vector for different arboviruses such as dengue virus (DENV) and chikungunya virus (CHIKV). Interestingly, it was shown in some cases that Ae. albopictus native Wolbachia strains are able to inhibit DENV transmission by limiting viral replication in salivary glands, but no such impact was measured on CHIKV replication in vivo. To better understand the Wolbachia/CHIKV/Ae. albopictus interaction, we generated a cellular model using Ae. albopictus derived C6/36 cells that we infected with the wAlbB strain. Our results indicate that CHIKV infection is negatively impacted at both RNA replication and virus assembly/secretion steps in presence of wAlbB. Using FISH, we observed CHIKV and wAlbB in the same mosquito cells, indicating that the virus is still able to enter the cell in the presence of the bacterium. Further work is needed to decipher molecular pathways involved in Wolbachia-CHIKV interaction at the cellular level, but this cellular model can be a useful tool to study the mechanism behind virus blocking phenotype induced by Wolbachia. More broadly, this put into question the ecological role of Wolbachia symbiont in Ae. albopictus, but also the ability of the CHIKV to counteract Wolbachia's antiviral potential in vivo.

  2. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007

    PubMed Central

    Ochieng, Caroline; Ahenda, Petronella; Vittor, Amy Y.; Nyoka, Raymond; Gikunju, Stella; Wachira, Cyrus; Waiboci, Lilian; Umuro, Mamo; Kim, Andrea A.; Nderitu, Leonard; Juma, Bonventure; Montgomery, Joel M.; Breiman, Robert F.; Fields, Barry

    2015-01-01

    Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007) to test for the presence of IgG antibodies to dengue virus (DENV), chikungunya virus (CHIKV) and Rift Valley fever virus (RVFV).The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2%) were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive), followed by RVFV and CHIKV (4.5% and 0.97%, respectively). For DENV and RVFV, the participant’s province of residence was significantly associated (P≤.01) with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01). These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV. PMID:26177451

  3. Seroprevalence of Infections with Dengue, Rift Valley Fever and Chikungunya Viruses in Kenya, 2007.

    PubMed

    Ochieng, Caroline; Ahenda, Petronella; Vittor, Amy Y; Nyoka, Raymond; Gikunju, Stella; Wachira, Cyrus; Waiboci, Lilian; Umuro, Mamo; Kim, Andrea A; Nderitu, Leonard; Juma, Bonventure; Montgomery, Joel M; Breiman, Robert F; Fields, Barry

    2015-01-01

    Arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in Kenya and East Africa. In this study, we used 1,091 HIV-negative blood specimens from the 2007 Kenya AIDS Indicator Survey (KAIS 2007) to test for the presence of IgG antibodies to dengue virus (DENV), chikungunya virus (CHIKV) and Rift Valley fever virus (RVFV).The KAIS 2007 was a national population-based survey conducted by the Government of Kenya to provide comprehensive information needed to address the HIV/AIDS epidemic. Antibody testing for arboviruses was performed on stored blood specimens from KAIS 2007 through a two-step sandwich IgG ELISA using either commercially available kits or CDC-developed assays. Out of the 1,091 samples tested, 210 (19.2%) were positive for IgG antibodies against at least one of the three arboviruses. DENV was the most common of the three viruses tested (12.5% positive), followed by RVFV and CHIKV (4.5% and 0.97%, respectively). For DENV and RVFV, the participant's province of residence was significantly associated (P≤.01) with seropositivity. Seroprevalence of DENV and RVFV increased with age, while there was no correlation between province of residence/age and seropositivity for CHIKV. Females had twelve times higher odds of exposure to CHIK as opposed to DENV and RVFV where both males and females had the same odds of exposure. Lack of education was significantly associated with a higher odds of previous infection with either DENV or RVFV (p <0.01). These data show that a number of people are at risk of arbovirus infections depending on their geographic location in Kenya and transmission of these pathogens is greater than previously appreciated. This poses a public health risk, especially for DENV.

  4. Temporal SILAC-based quantitative proteomics identifies host factors involved in chikungunya virus replication.

    PubMed

    Treffers, Emmely E; Tas, Ali; Scholte, Florine E M; Van, Myrthe N; Heemskerk, Matthias T; de Ru, Arnoud H; Snijder, Eric J; van Hemert, Martijn J; van Veelen, Peter A

    2015-07-01

    Chikungunya virus (CHIKV) is an arthropod-borne reemerging human pathogen that generally causes a severe persisting arthritis. Since 2005, the virus has infected millions of people during outbreaks in Africa, Indian Ocean Islands, Asia, and South/Central America. Many steps of the replication and expression of CHIKV's 12-kb RNA genome are highly dependent on cellular factors, which thus constitute potential therapeutic targets. SILAC and LC-MS/MS were used to define the temporal dynamics of the cellular response to infection. Using samples harvested at 8, 10, and 12 h postinfection, over 4700 proteins were identified and per time point 2800-3500 proteins could be quantified in both biological replicates. At 8, 10, and 12 h postinfection, 13, 38, and 106 proteins, respectively, were differentially expressed. The majority of these proteins showed decreased abundance. Most subunits of the RNA polymerase II complex were progressively degraded, which likely contributes to the transcriptional host shut-off observed during CHIKV infection. Overexpression of four proteins that were significantly downregulated (Rho family GTPase 3 (Rnd3), DEAD box helicase 56 (DDX56), polo-like kinase 1 (Plk1), and ubiquitin-conjugating enzyme E2C (UbcH10) reduced susceptibility of cells to CHIKV infection, suggesting that infection-induced downregulation of these proteins is beneficial for CHIKV replication. All MS data have been deposited in the ProteomeXchange with identifier PXD001330 (http://proteomecentral.proteomexchange.org/dataset/PXD001330).

  5. Rapid spread of chikungunya virus following its resurgence during 2006 in West Bengal, India.

    PubMed

    Taraphdar, Debjani; Sarkar, Arindam; Mukhopadhyay, Bansi B; Chakrabarti, Shekhar; Chatterjee, Shyamalendu

    2012-03-01

    Re-emergence of chikungunya virus (CHIKV) in West Bengal was detected after almost 40 years when an outbreak of fever occurred in Baduria village (West Bengal, India) in October 2006. The symptoms of CHIKV infection are similar to those of dengue virus (DENV) infection. Serum samples were tested for detection of IgM antibody to CHIKV and DENV and the aetiological agent was detected as CHIKV. RT-PCR was carried out for confirmation of CHIKV infection. By 2009, CHIKV had spread rapidly within ten districts of West Bengal. Middle-aged women (age group 31-40 years) were predominantly affected. Here we report the analysis of 2134 serum samples collected during 2006-2009 from the different districts of West Bengal, among which IgM antibody to CHIKV and DENV was detected in 403 and 199 samples, respectively. This report highlights the gradual dominating activity of CHIKV with dengue-like clinical features in dengue-endemic regions such as West Bengal.

  6. Viremia in North American Mammals and Birds After Experimental Infection with Chikungunya Viruses.

    PubMed

    Bosco-Lauth, Angela M; Nemeth, Nicole M; Kohler, Dennis J; Bowen, Richard A

    2016-03-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus, which is known to cause severe disease only in humans. To investigate its potential zoonotic host range and evaluate reservoir competence among these hosts, experimental infections were performed on individuals from nine avian and 12 mammalian species representing both domestic and wild animals common to North America. Hamsters and inbred mice have previously been shown to develop viremia after inoculation with CHIKV and were used as positive controls for infection. Aside from big brown bats (Eptesicus fuscus), none of the mammals or birds developed detectable viremia or overt clinical disease. However, most mammals and a smaller proportion of birds developed neutralizing antibody responses to CHIKV. On the basis of these results, it seems unlikely that CHIKV poses a significant health threat to most domestic animals or wildlife and that the species examined do not likely contribute to natural transmission cycles. Additional studies should further evaluate bats and wild rodents as potential reservoir hosts for CHIKV transmission during human epidemics.

  7. Infection of Aedes albopictus with chikungunya virus rectally administered by enema.

    PubMed

    Nuckols, John T; Ziegler, Sarah A; Huang, Yan-Jang Scott; McAuley, Alex J; Vanlandingham, Dana L; Klowden, Marc J; Spratt, Heidi; Davey, Robert A; Higgs, Stephen

    2013-02-01

    Chikungunya virus (CHIKV) is an alphavirus transmitted by Aedes albopictus and Aedes aegypti mosquitoes in tropical areas of Africa, Asia, and the islands of the Indian Ocean. In 2007 and 2009, CHIKV was transmitted outside these tropical areas and caused geographically localized infections in people in Italy and France. To temporally and spatially characterize CHIKV infection of Ae. albopictus midguts, a comparison of viral distribution in mosquitoes infected per os or by enema was conducted. Ae. albopictus infected with CHIKV LR 5' green fluorescent protein (GFP) at a titer 10(6.95) tissue culture infective dose(50) (TCID(50))/mL, were collected and analyzed for virus dissemination by visualizing GFP expression and titration up to 14 days post inoculation (dpi). Additionally, midguts were dissected from the mosquitoes and imaged by fluorescence microscopy for comparison of midgut infection patterns between orally- and enema-infected mosquitoes. When virus was delivered via enema, the anterior midgut appeared more readily infected by 3 dpi, with increased GFP presentation observed in this same location of the midgut at 7 and 14 dpi when compared to orally-infected mosquitoes. This work demonstrates that enema delivery of virus is a viable technique for use of mosquito infection. Enema injection of mosquitoes may be an alternative to intrathoracic inoculation because the enema delivery more closely models natural infection and neither compromises midgut integrity nor involves a wound that can induce immune responses. Furthermore, unlike intrathoracic delivery, the enema does not bypass midgut barriers to infect tissues artificially in the hemocoel of the mosquito.

  8. Phylogeny of Dengue and Chikungunya viruses in Al Hudayda governorate, Yemen.

    PubMed

    Ciccozzi, Massimo; Lo Presti, Alessandra; Cella, Eleonora; Giovanetti, Marta; Lai, Alessia; El-Sawaf, Gamal; Faggioni, Giovanni; Vescio, Fenicia; Al Ameri, Ranya; De Santis, Riccardo; Helaly, Ghada; Pomponi, Alice; Metwally, Dalia; Fantini, Massimo; Qadi, Hussein; Zehender, Gianguglielmo; Lista, Florigio; Rezza, Giovanni

    2014-10-01

    Yemen, which is located in the southwestern end of the Arabian Peninsula, is one of countries most affected by recurrent epidemics caused by emerging vector-borne viruses. Dengue virus (DENV) outbreaks have been reported with increasing frequency in several governorates since the year 2000, and the Chikungunya virus (CHIKV) has been also responsible of large outbreaks and it is now a major public health problem in Yemen. We report the results of the phylogenetic analysis of DENV-2 and CHIKV isolates (NS1 and E1 genes, respectively) detected in an outbreak occurred in Al-Hudayda in 2012. Estimates of the introduction date of CHIKV and DENV-2, and the phylogeographic analysis of DENV-2 are also presented. Phylogenetic analysis showed that the Yemen isolates of DENV belonged to the lineage 2 Cosmopolitan subtype, whereas CHIKV isolates from Yemen belonged to the ECSA genotype. All the CHIKV isolates from Yemen were statistically supported and dated back to the year 2010 (95% HPD: 2009-2011); these sequences showed an alanine in the aminoacid position 226 of the E1 protein. Phylogeographic analysis of DENV-2 virus showed that cluster 1, which included Yemen isolates, dated back to 2003 Burkina Faso strains (95% HPD 1999-2007). The Yemen, cluster dated back to 2011 (95% HPD 2009-2012). Our study sheds light on the global spatiotemporal dynamics of DENV-2 and CHIKV in Yemen. This study reinforces both the need to monitor the spread of CHIKV and DENV, and to apply significant measures for vector control.

  9. Characterization of Synthetic Chikungunya Viruses Based on the Consensus Sequence of Recent E1-226V Isolates

    PubMed Central

    Scholte, Florine E. M.; Tas, Ali; Martina, Byron E. E.; Cordioli, Paolo; Narayanan, Krishna; Makino, Shinji; Snijder, Eric J.; van Hemert, Martijn J.

    2013-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that re-emerged in 2004 and has caused massive outbreaks in recent years. The lack of a licensed vaccine or treatment options emphasize the need to obtain more insight into the viral life cycle and CHIKV-host interactions. Infectious cDNA clones are important tools for such studies, and for mechanism of action studies on antiviral compounds. Existing CHIKV cDNA clones are based on a single genome from an individual clinical isolate, which is expected to have evolved specific characteristics in response to the host environment, and possibly also during subsequent cell culture passaging. To obtain a virus expected to have the general characteristics of the recent E1-226V CHIKV isolates, we have constructed a new CHIKV full-length cDNA clone, CHIKV LS3, based on the consensus sequence of their aligned genomes. Here we report the characterization of this synthetic virus and a green fluorescent protein-expressing variant (CHIKV LS3-GFP). Their characteristics were compared to those of natural strain ITA07-RA1, which was isolated during the 2007 outbreak in Italy. In cell culture the synthetic viruses displayed phenotypes comparable to the natural isolate, and in a mouse model they caused lethal infections that were indistinguishable from infections with a natural strain. Compared to ITA07-RA1 and clinical isolate NL10/152, the synthetic viruses displayed similar sensitivities to several antiviral compounds. 3-deaza-adenosine was identified as a new inhibitor of CHIKV replication. Cyclosporin A had no effect on CHIKV replication, suggesting that cyclophilins -opposite to what was found for other +RNA viruses- do not play an essential role in CHIKV replication. The characterization of the consensus sequence-based synthetic viruses and their comparison to natural isolates demonstrated that CHIKV LS3 and LS3-GFP are suitable and representative tools to study CHIKV-host interactions, screen for antiviral compounds and

  10. Probing the Attenuation and Protective Efficacy of a Candidate Chikungunya Virus Vaccine in Mice with Compromised Interferon (IFN) Signaling

    PubMed Central

    Partidos, Charalambos D.; Weger, James; Brewoo, Joseph; Seymour, Robert; Borland, Erin M.; Ledermann, Jeremy P.; Powers, Ann M.; Weaver, Scott C.; Stinchcomb, Dan T.; Osorio, Jorge E.

    2011-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes explosive outbreaks of febrile illness associated with rash, and painful arthralgia. The CHIK vaccine strain 181/clone25 (181/25) developed by the United States Army Medical Research Institute of Infectious Diseases (USAMRIID) was shown to be well-tolerated and highly immunogenic in phase I and II clinical trials although it induced transient arthralgia in some healthy adult volunteers. In an attempt to better understand the host factors that are involved in the attenuating phenotype of CHIK 181/25 vaccine virus we conducted studies in interferon (IFN)-compromised mice and also evaluated its immunogenic potential and protective capacity. Infection of AG129 mice (defective in IFN-α/β and IFN-γ receptor signaling) with CHIK 181/25 resulted in rapid mortality within 3-4 days. In contrast, all infected A129 mice (defective in IFN-α/β receptor signaling) survived with temporary morbidity characterized by ruffled appearance and body weight loss. A129 heterozygote mice that retain partial IFN-α/β receptor signaling activity remained healthy. Infection of A129 mice with CHIK 181/25 induced significant levels of IFN-γ and IL-12 while the inflammatory cytokines, TNFα and IL-6 remained low. A single administration of the CHIK 181/25 vaccine provided both short-term and long-term protection (38 days and 247 days post-prime, respectively) against challenge with wt CHIKV-La Reunion (CHIKV-LR). This protection was at least partially mediated by antibodies since passively transferred immune serum protected both A129 and AG129 mice from wt CHIKV-LR and 181/25 virus challenge. Overall, these data highlight the importance of IFNs in controlling CHIK 181/25 vaccine and demonstrate the ability of this vaccine to elicit neutralizing antibody responses that confer short-and long-term protection against wt CHIKV-LR challenge. PMID:21300099

  11. The first dominant co-circulation of both dengue and chikungunya viruses during the post-monsoon period of 2010 in Delhi, India.

    PubMed

    Singh, P; Mittal, V; Rizvi, M M A; Chhabra, M; Sharma, P; Rawat, D S; Bhattacharya, D; Chauhan, L S; Rai, A

    2012-07-01

    Independent outbreaks of dengue virus (DENV) infection and sporadic cases of chikungunya virus (CHIKV) have been recorded in the metropolitan city of Delhi on several occasions in the past. However, during a recent 2010 arboviral outbreak in Delhi many cases turned negative for DENV. This prompted us to use duplex reverse transcriptase-polymerase chain reaction (D-RT-PCR) to establish the aetiology of dengue/chikungunya through sequencing of CprM and E1 genes of dengue and chikungunya viruses. Interestingly, for the first time, both DENV and CHIKV co-circulated simultaneously and in equally dominant proportion during the post-monsoon period of 2010. DENV-1 genotype III and the East Central South African genotype of CHIKV were associated with post-monsoon spread of these viruses.

  12. Application of GelC-MS/MS to Proteomic Profiling of Chikungunya Virus Infection: Preparation of Peptides for Analysis.

    PubMed

    Paemanee, Atchara; Wikan, Nitwara; Roytrakul, Sittiruk; Smith, Duncan R

    2016-01-01

    Gel-enhanced liquid chromatography coupled with tandem mass spectrometry (GeLC-MS/MS) is a labor intensive, but relatively straightforward methodology that generates high proteome coverage which can be applied to the proteome analysis of a range of starting materials such as cells or patient specimens. Sample proteins are resolved electrophoretically in one dimension through a sodium dodecyl sulfate (SDS) polyacrylamide gel after which the lanes are sliced into sections. The sections are further diced and the gel cubes generated are subjected to in-gel tryptic digestion. The resultant peptides can then be analyzed by tandem mass spectroscopy to identify the proteins by database searching. The methodology can routinely detect several thousand proteins in one analysis. The protocol we describe here has been used with both cells in culture that have been infected with chikungunya virus and specimens from Chikungunya fever patients. This protocol details the process for generating peptides for subsequent mass spectroscopic and bioinformatic analysis. PMID:27233271

  13. Development and Validation of a Quantitative, One-Step, Multiplex, Real-Time Reverse Transcriptase PCR Assay for Detection of Dengue and Chikungunya Viruses.

    PubMed

    Simmons, Monika; Myers, Todd; Guevara, Carolina; Jungkind, Donald; Williams, Maya; Houng, Huo-Shu

    2016-07-01

    Dengue virus (DENV) and chikungunya virus (CHIKV) are important human pathogens with common transmission vectors and similar clinical presentations. Patient care may be impacted by the misdiagnosis of DENV and CHIKV in areas where both viruses cocirculate. In this study, we have developed and validated a one-step multiplex reverse transcriptase PCR (RT-PCR) to simultaneously detect, quantify, and differentiate between four DENV serotypes (pan-DENV) and chikungunya virus. The assay uses TaqMan technology, employing two forward primers, three reverse primers, and four fluorophore-labeled probes in a single-reaction format. Coextracted and coamplified RNA was used as an internal control (IC), and in vitro-transcribed DENV and CHIKV RNAs were used to generate standard curves for absolute quantification. The diagnostic 95% limits of detection (LOD) within the linear range were 50 and 60 RNA copies/reaction for DENV (serotypes 1 to 4) and CHIKV, respectively. Our assay was able to detect 53 different strains of DENV, representing four serotypes, and six strains of CHIKV. No cross-reactivity was observed with related flaviviruses and alphaviruses, To evaluate diagnostic sensitivity and specificity, 89 clinical samples positive or negative for DENV (serotypes 1 to 4) and CHIKV by the standard virus isolation method were tested in our assay. The multiplex RT-PCR assay showed 95% sensitivity and 100% specificity for DENV and 100% sensitivity and specificity for CHIKV. With an assay turnaround time of less than 2 h, including extraction of RNA, the multiplex quantitative RT-PCR assay provides rapid diagnosis for the differential detection of two clinically indistinguishable diseases, whose geographical occurrence is increasingly overlapping. PMID:27098955

  14. Endocytosis of Chikungunya Virus into Mammalian Cells: Role of Clathrin and Early Endosomal Compartments

    PubMed Central

    Gay, Bernard; Chazal, Nathalie; Higgs, Stephen; Devaux, Christian; Briant, Laurence

    2010-01-01

    Background The replicative cycle of chikungunya virus (CHIKV), an alphavirus that recently re-emerged in India and in Indian Ocean area, remains mostly unknown. The aim of the present study was to investigate the intracellular trafficking pathway(s) hijacked by CHIKV to enter mammalian cells. Methodology/Principal Findings Entry pathways were investigated using a variety of pharmacological inhibitors or overexpression of dominant negative forms of proteins perturbating cellular endocytosis. We found that CHIKV infection of HEK293T mammalian cells is independent of clathrin heavy chain and- dependent of functional Eps15, and requires integrity of Rab5-, but not Rab7-positive endosomal compartment. Cytoskeleton integrity is crucial as cytochalasin D and nocodazole significantly reduced infection of the cells. Finally, both methyl β-cyclodextrin and lysomotropic agents impaired CHIKV infection, supporting that a cholesterol-, pH-dependent step is required to achieve productive infection. Interestingly, differential sensitivity to lysomotropic agents was observed between the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in Reunion Island. Conclusions Together our data indicate that CHIKV entry in its target cells is essentially mediated by clathrin-independent, Eps15-dependent endocytosis. Despite that this property is shared by the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in La Réunion Island, differential sensitivity to lysomotropic agents may support that the LR-OPY1 strain has acquired specific entry mechanisms. PMID:20628602

  15. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes.

    PubMed

    Mishra, Priya; Furey, Colleen; Balaraman, Velmurugan; Fraser, Malcolm J

    2016-06-10

    The chikungunya virus (CHIKV) is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs) targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNA(val) Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE) Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR), comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA) and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies.

  16. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

    PubMed

    Poo, Yee Suan; Rudd, Penny A; Gardner, Joy; Wilson, Jane A C; Larcher, Thibaut; Colle, Marie-Anne; Le, Thuy T; Nakaya, Helder I; Warrilow, David; Allcock, Richard; Bielefeldt-Ohmann, Helle; Schroder, Wayne A; Khromykh, Alexander A; Lopez, José A; Suhrbier, Andreas

    2014-12-01

    The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV) has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA) in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells) in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection) was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  17. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes

    PubMed Central

    Mishra, Priya; Furey, Colleen; Balaraman, Velmurugan; Fraser, Malcolm J.

    2016-01-01

    The chikungunya virus (CHIKV) is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs) targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNAval Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE) Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR), comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA) and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies PMID:27294950

  18. Chikungunya virus fusion properties elucidated by single-particle and bulk approaches.

    PubMed

    van Duijl-Richter, Mareike K S; Blijleven, Jelle S; van Oijen, Antoine M; Smit, Jolanda M

    2015-08-01

    Chikungunya virus (CHIKV) is a rapidly spreading, enveloped alphavirus causing fever, rash and debilitating polyarthritis. No specific treatment or vaccines are available to treat or prevent infection. For the rational design of vaccines and antiviral drugs, it is imperative to understand the molecular mechanisms involved in CHIKV infection. A critical step in the life cycle of CHIKV is fusion of the viral membrane with a host cell membrane. Here, we elucidate this process using ensemble-averaging liposome-virus fusion studies, in which the fusion behaviour of a large virus population is measured, and a newly developed microscopy-based single-particle assay, in which the fusion kinetics of an individual particle can be visualised. The combination of these approaches allowed us to obtain detailed insight into the kinetics, lipid dependency and pH dependency of hemifusion. We found that CHIKV fusion is strictly dependent on low pH, with a threshold of pH 6.2 and optimal fusion efficiency below pH 5.6. At this pH, CHIKV fuses rapidly with target membranes, with typically half of the fusion occurring within 2 s after acidification. Cholesterol and sphingomyelin in the target membrane were found to strongly enhance the fusion process. By analysing our single-particle data using kinetic models, we were able to deduce that the number of rate-limiting steps occurring before hemifusion equals about three. To explain these data, we propose a mechanistic model in which multiple E1 fusion trimers are involved in initiating the fusion process.

  19. Antiviral Hammerhead Ribozymes Are Effective for Developing Transgenic Suppression of Chikungunya Virus in Aedes aegypti Mosquitoes.

    PubMed

    Mishra, Priya; Furey, Colleen; Balaraman, Velmurugan; Fraser, Malcolm J

    2016-01-01

    The chikungunya virus (CHIKV) is an emerging pathogen with widespread distribution in regions of Africa, India, and Asia that threatens to spread into temperate climates with the introduction of its major vector, Aedes albopictus. CHIKV causes a disease frequently misdiagnosed as dengue fever, with potentially life-threatening symptoms that can result in a longer-term debilitating arthritis. The increasing risk of spread from endemic regions via human travel and commerce and the current absence of a vaccine put a significant proportion of the world population at risk for this disease. In this study we designed and tested hammerhead ribozymes (hRzs) targeting CHIKV structural protein genes of the RNA genome as potential antivirals both at the cellular and in vivo level. We employed the CHIKV strain 181/25, which exhibits similar infectivity rates in both Vero cell cultures and mosquitoes. Virus suppression assay performed on transformed Vero cell clones of all seven hRzs demonstrated that all are effective at inhibiting CHIKV in Vero cells, with hRz #9 and #14 being the most effective. piggyBac transformation vectors were constructed using the Ae. aegypti t-RNA(val) Pol III promoted hRz #9 and #14 effector genes to establish a total of nine unique transgenic Higgs White Eye (HWE) Ae. aegypti lines. Following confirmation of transgene expression by real-time polymerase chain reaction (RT-PCR), comparative TCID50-IFA analysis, in situ Immuno-fluorescent Assays (IFA) and analysis of salivary CHIKV titers demonstrated effective suppression of virus replication at 7 dpi in heterozygous females of each of these transgenic lines compared with control HWE mosquitoes. This report provides a proof that appropriately engineered hRzs are powerful antiviral effector genes suitable for population replacement strategies. PMID:27294950

  20. Genome-Scale Phylogenetic Analyses of Chikungunya Virus Reveal Independent Emergences of Recent Epidemics and Various Evolutionary Rates▿ ‡

    PubMed Central

    Volk, Sara M.; Chen, Rubing; Tsetsarkin, Konstantin A.; Adams, A. Paige; Garcia, Tzintzuni I.; Sall, Amadou A.; Nasar, Farooq; Schuh, Amy J.; Holmes, Edward C.; Higgs, Stephen; Maharaj, Payal D.; Brault, Aaron C.; Weaver, Scott C.

    2010-01-01

    Chikungunya virus (CHIKV), a mosquito-borne alphavirus, has traditionally circulated in Africa and Asia, causing human febrile illness accompanied by severe, chronic joint pain. In Africa, epidemic emergence of CHIKV involves the transition from an enzootic, sylvatic cycle involving arboreal mosquito vectors and nonhuman primates, into an urban cycle where peridomestic mosquitoes transmit among humans. In Asia, however, CHIKV appears to circulate only in the endemic, urban cycle. Recently, CHIKV emerged into the Indian Ocean and the Indian subcontinent to cause major epidemics. To examine patterns of CHIKV evolution and the origins of these outbreaks, as well as to examine whether evolutionary rates that vary between enzootic and epidemic transmission, we sequenced the genomes of 40 CHIKV strains and performed a phylogenetic analysis representing the most comprehensive study of its kind to date. We inferred that extant CHIKV strains evolved from an ancestor that existed within the last 500 years and that some geographic overlap exists between two main enzootic lineages previously thought to be geographically separated within Africa. We estimated that CHIKV was introduced from Africa into Asia 70 to 90 years ago. The recent Indian Ocean and Indian subcontinent epidemics appear to have emerged independently from the mainland of East Africa. This finding underscores the importance of surveillance to rapidly detect and control African outbreaks before exportation can occur. Significantly higher rates of nucleotide substitution appear to occur during urban than during enzootic transmission. These results suggest fundamental differences in transmission modes and/or dynamics in these two transmission cycles. PMID:20410280

  1. Knowledge and use of prevention measures for chikungunya virus among visitors — Virgin Islands National Park, 2015

    PubMed Central

    Cherry, Cara C.; Beer, Karlyn D.; Fulton, Corey; Wong, David; Buttke, Danielle; Staples, J. Erin; Ellis, Esther M.

    2016-01-01

    Summary Background In June 2014, the mosquito-borne chikungunya virus (CHIKV) emerged in the U.S. Virgin Islands (USVI), a location where tourists comprise the majority of the population during peak season (January–April). Limited information is available concerning visitors’ CHIKV awareness and prevention measures. Methods We surveyed a convenience sample of Virgin Islands National Park visitors aged ≥18 years. Respondents completed a questionnaire assessing CHIKV knowledge, attitudes, and practices; health information-seeking practices; and demographics. Results Of 783 persons contacted, 443 (57%) completed the survey. Fewer than half (208/441 [47%]) were aware of CHIKV. During trip preparation, 28% of respondents (126/443) investigated USVI-specific health concerns. Compared with persons unaware of CHIKV, CHIKV-aware persons were more likely to apply insect repellent (134/207 [65%] versus 111/231 [48%]; p < 0.001), wear long-sleeves and long pants (84/203 [41%] versus 57/227 [25%]; p < 0.001), and wear insect repellent-treated clothing (36/204 [18%] versus 22/227 [10%]; p = 0.02). Conclusions The majority of visitors surveyed did not research destination-related health concerns and were unaware of CHIKV. However, CHIKV awareness was associated with using multiple prevention measures to reduce disease risk. These findings underscore the importance of providing tourists with disease education upon destination arrival. PMID:27597388

  2. Chikungunya on the move.

    PubMed

    Johansson, Michael A

    2015-02-01

    In December 2013, chikungunya virus (CHIKV) transmission was reported for the first time in the Americas. Since then it has spread quickly, with more than 1 million suspected and confirmed cases being reported in one year, where previously there were only sporadic travel-related cases. Transmission patterns suggest that the epidemic in the southern hemisphere is only beginning and that chikungunya will not go away anytime soon.

  3. Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus infection.

    PubMed

    Mahauad-Fernandez, Wadie D; Jones, Philip H; Okeoma, Chioma M

    2014-11-01

    Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN-inducible gene that functions to block the release of a range of nascent enveloped virions from infected host cells. However, the role of BST-2 in viral pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate immunity, as it hinders retroviral infection and possibly promotes infection with some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered exploration of BST-2 antiviral function in vivo. We reported previously that BST-2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane. To explore the role of BST-2 in CHIKV replication and host protection, we utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a BST-2(-/-) mouse model. We observed an interesting dichotomy between WT and BST-2(-/-) mice. BST-2 deficiency increased inoculation site viral load, culminating in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed inflammatory innate response demonstrated by impaired expression of IFN-α, IFN-γ and CD40 ligand was observed in BST-2(-/-) mice compared with the WT controls. These findings suggested that, in part, BST-2 protects lymphoid tissues from CHIKV infection and regulates CHIKV-induced inflammatory response by the host.

  4. Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus infection.

    PubMed

    Mahauad-Fernandez, Wadie D; Jones, Philip H; Okeoma, Chioma M

    2014-11-01

    Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN-inducible gene that functions to block the release of a range of nascent enveloped virions from infected host cells. However, the role of BST-2 in viral pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate immunity, as it hinders retroviral infection and possibly promotes infection with some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered exploration of BST-2 antiviral function in vivo. We reported previously that BST-2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane. To explore the role of BST-2 in CHIKV replication and host protection, we utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a BST-2(-/-) mouse model. We observed an interesting dichotomy between WT and BST-2(-/-) mice. BST-2 deficiency increased inoculation site viral load, culminating in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed inflammatory innate response demonstrated by impaired expression of IFN-α, IFN-γ and CD40 ligand was observed in BST-2(-/-) mice compared with the WT controls. These findings suggested that, in part, BST-2 protects lymphoid tissues from CHIKV infection and regulates CHIKV-induced inflammatory response by the host. PMID:25053563

  5. Critical role for bone marrow stromal antigen 2 in acute Chikungunya virus infection

    PubMed Central

    Mahauad-Fernandez, Wadie D.; Jones, Philip H.

    2014-01-01

    Bone marrow stromal antigen 2 (BST-2; also known as tetherin or CD317) is an IFN-inducible gene that functions to block the release of a range of nascent enveloped virions from infected host cells. However, the role of BST-2 in viral pathogenesis remains poorly understood. BST-2 plays a multifaceted role in innate immunity, as it hinders retroviral infection and possibly promotes infection with some rhabdo- and orthomyxoviruses. This paradoxical role has probably hindered exploration of BST-2 antiviral function in vivo. We reported previously that BST-2 tethers Chikungunya virus (CHIKV)-like particles on the cell plasma membrane. To explore the role of BST-2 in CHIKV replication and host protection, we utilized CHIKV strain 181/25 to examine early events during CHIKV infection in a BST-2−/− mouse model. We observed an interesting dichotomy between WT and BST-2−/− mice. BST-2 deficiency increased inoculation site viral load, culminating in higher systemic viraemia and increased lymphoid tissues tropism. A suppressed inflammatory innate response demonstrated by impaired expression of IFN-α, IFN-γ and CD40 ligand was observed in BST-2−/− mice compared with the WT controls. These findings suggested that, in part, BST-2 protects lymphoid tissues from CHIKV infection and regulates CHIKV-induced inflammatory response by the host. PMID:25053563

  6. Chikungunya fever.

    PubMed

    Kucharz, Eugene J; Cebula-Byrska, Ilona

    2012-06-01

    Chikungunya fever (CF) is an acute illness caused by Chikungunya virus (CHIKV) belonging to the alphavirus genus of the Alphaviruses (Togaviridae) family. The virus is transmitted by Aedes mosquitoes. CF is primarily tropical disease occurring in Africa, Asia and Indian Ocean islands but in the last decade an outbreak of CHIKV autochthonous infections were reported in Italy and France. It is associated with viral genome mutations facilitating transmission of the disease by Aedes albopictus, a mosquito occurring in several European countries. The CF is highly symptomatic, characterized by fever, cutaneuos rash and severe athralgia and arthritis. In some patients severe neurological or hemorrhagic manifestations occur. The disease is self-limiting but a part of the patients suffers from a long-lasting arthritis akin to rheumatoid arthritis. Treatment is only symptomatic. Prevention includes reduction of mosquito bite (mosquito net, repellent) or application of measures against mosquito larvae. Vaccination is not currently available but investigations are in progress. CF presents a significant worldwide health problem affecting in the last decade millions of person, and currently dangerous also for European countries.

  7. [Chikungunya fever - A new global threat].

    PubMed

    Montero, Antonio

    2015-08-01

    The recent onset of epidemics caused by viruses such as Ebola, Marburg, Nipah, Lassa, coronavirus, West-Nile encephalitis, Saint Louis encephalitis, human immunodeficiency virus, dengue, yellow fever and Venezuelan hemorrhagic fever alerts about the risk these agents represent for the global health. Chikungunya virus represents a new threat. Surged from remote African regions, this virus has become endemic in the Indic ocean basin, the Indian subcontinent and the southeast of Asia, causing serious epidemics in Africa, Indic Ocean Islands, Asia and Europe. Due to their epidemiological and biological features and the global presence of their vectors, chikungunya represents a serious menace and could become endemic in the Americas. Although chikungunya infection has a low mortality rate, its high attack ratio may collapse the health system during epidemics affecting a sensitive population. In this paper, we review the clinical and epidemiological features of chikungunya fever as well as the risk of its introduction into the Americas. We remark the importance of the epidemiological control and mosquitoes fighting in order to prevent this disease from being introduced into the Americas.

  8. Residue 82 of the Chikungunya Virus E2 Attachment Protein Modulates Viral Dissemination and Arthritis in Mice

    PubMed Central

    Ashbrook, Alison W.; Burrack, Kristina S.; Silva, Laurie A.; Montgomery, Stephanie A.; Heise, Mark T.; Morrison, Thomas E.

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that has reemerged to cause profound epidemics of fever, rash, and arthralgia throughout sub-Saharan Africa, Southeast Asia, and the Caribbean. Like other arthritogenic alphaviruses, mechanisms of CHIKV pathogenesis are not well defined. Using the attenuated CHIKV strain 181/25 and virulent strain AF15561, we identified a residue in the E2 viral attachment protein that is a critical determinant of viral replication in cultured cells and pathogenesis in vivo. Viruses containing an arginine at E2 residue 82 displayed enhanced infectivity in mammalian cells but reduced infectivity in mosquito cells and diminished virulence in a mouse model of CHIKV disease. Mice inoculated with virus containing an arginine at this position exhibited reduced swelling at the site of inoculation with a concomitant decrease in the severity of necrosis in joint-associated tissues. Viruses containing a glycine at E2 residue 82 produced higher titers in the spleen and serum at early times postinfection. Using wild-type and glycosaminoglycan (GAG)-deficient Chinese hamster ovary (CHO) cell lines and soluble GAGs, we found that an arginine at residue 82 conferred greater dependence on GAGs for infection of mammalian cells. These data suggest that CHIKV E2 interactions with GAGs diminish dissemination to lymphoid tissue, establishment of viremia, and activation of inflammatory responses early in infection. Collectively, these results suggest a function for GAG utilization in regulating CHIKV tropism and host responses that contribute to arthritis. IMPORTANCE CHIKV is a reemerging alphavirus of global significance with high potential to spread into new, immunologically naive populations. The severity of CHIKV disease, particularly its propensity for chronic musculoskeletal manifestations, emphasizes the need for identification of genetic determinants that dictate CHIKV virulence in the host. To better understand mechanisms of

  9. Loss of Glycosaminoglycan Receptor Binding after Mosquito Cell Passage Reduces Chikungunya Virus Infectivity

    PubMed Central

    Acharya, Dhiraj; Paul, Amber M.; Anderson, John F.; Huang, Faqing; Bai, Fengwei

    2015-01-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that can cause fever and chronic arthritis in humans. CHIKV that is generated in mosquito or mammalian cells differs in glycosylation patterns of viral proteins, which may affect its replication and virulence. Herein, we compare replication, pathogenicity, and receptor binding of CHIKV generated in Vero cells (mammal) or C6/36 cells (mosquito) through a single passage. We demonstrate that mosquito cell-derived CHIKV (CHIKVmos) has slower replication than mammalian cell-derived CHIKV (CHIKVvero), when tested in both human and murine cell lines. Consistent with this, CHIKVmos infection in both cell lines produce less cytopathic effects and reduced antiviral responses. In addition, infection in mice show that CHIKVmos produces a lower level of viremia and less severe footpad swelling when compared with CHIKVvero. Interestingly, CHIKVmos has impaired ability to bind to glycosaminoglycan (GAG) receptors on mammalian cells. However, sequencing analysis shows that this impairment is not due to a mutation in the CHIKV E2 gene, which encodes for the viral receptor binding protein. Moreover, CHIKVmos progenies can regain GAG receptor binding capability and can replicate similarly to CHIKVvero after a single passage in mammalian cells. Furthermore, CHIKVvero and CHIKVmos no longer differ in replication when N-glycosylation of viral proteins was inhibited by growing these viruses in the presence of tunicamycin. Collectively, these results suggest that N-glycosylation of viral proteins within mosquito cells can result in loss of GAG receptor binding capability of CHIKV and reduction of its infectivity in mammalian cells. PMID:26484530

  10. A sensitive epitope-blocking ELISA for the detection of Chikungunya virus-specific antibodies in patients.

    PubMed

    Goh, Lucas Y H; Kam, Yiu-Wing; Metz, Stefan W; Hobson-Peters, Jody; Prow, Natalie A; McCarthy, Suzi; Smith, David W; Pijlman, Gorben P; Ng, Lisa F P; Hall, Roy A

    2015-09-15

    Chikungunya fever (CHIKF) has re-emerged as an arboviral disease that mimics clinical symptoms of other diseases such as dengue, malaria, as well as other alphavirus-related illnesses leading to problems with definitive diagnosis of the infection. Herein we describe the development and evaluation of a sensitive epitope-blocking ELISA (EB-ELISA) capable of specifically detecting anti-chikungunya virus (CHIKV) antibodies in clinical samples. The assay uses a monoclonal antibody (mAb) that binds an epitope on the E2 protein of CHIKV and does not exhibit cross-reactivity to other related alphaviruses. We also demonstrated the use of recombinant CHIK virus-like particles (VLPs) as a safe alternative antigen to infectious virions in the assay. Based on testing of 60 serum samples from patients in the acute or convalescent phase of CHIKV infection, the EB-ELISA provided us with 100% sensitivity, and exhibited 98.5% specificity when Ross River virus (RRV)- or Barmah Forest virus (BFV)-immune serum samples were included. This assay meets the public health demands of a rapid, robust, sensitive and specific, yet simple assay for specifically diagnosing CHIK-infections in humans.

  11. Dengue, Japanese encephalitis and Chikungunya virus antibody prevalence among captive monkey (Macaca nemestrina) colonies of Northern Thailand.

    PubMed

    Nakgoi, Khajornpong; Nitatpattana, Narong; Wajjwalku, Worawidh; Pongsopawijit, Pornsawan; Kaewchot, Supakarn; Yoksan, Sutee; Siripolwat, Voravit; Souris, Marc; Gonzalez, Jean-Paul

    2014-01-01

    The potential of macaque Macaca nemestrina leonina in Thailand to be infected by endemic arboviruses was assessed. The prevalence of antibodies of three arboviruses actively circulating in Thailand was determined by Plaque Reduction Neutralization assay procedures using samples from captive colonies in Northern Thailand. Out of 38 macaques, 9 (24%) presented reacting antibodies against dengue virus, 5 (13%) against Japanese encephalitis virus, and 4 (10%) against Chikungunya virus. Our results indicate that the northern pig-tailed macaque in Thailand can be infected by these arboviruses, inferring therefore that their virus specific vectors have bitten them. Given that, northern pig-tailed macaque represents an abundant population, living in close range to human or in peridomestic setting, they could play a role as potential reservoir host for arboviruses circulating in Thailand.

  12. Chikungunya vaccines in development

    PubMed Central

    Schwameis, Michael; Buchtele, Nina; Wadowski, Patricia Pia; Schoergenhofer, Christian; Jilma, Bernd

    2016-01-01

    ABSTRACT Chikungunya virus has become a global health threat, spreading to the industrial world of Europe and the Americas; no treatment or prophylactic vaccine is available. Since the late 1960s much effort has been put into the development of a vaccine, and several heterogeneous strategies have already been explored. Only two candidates have recently qualified to enter clinical phase II trials, a chikungunya virus-like particle-based vaccine and a recombinant live attenuated measles virus-vectored vaccine. This review focuses on the current status of vaccine development against chikungunya virus in humans and discusses the diversity of immunization strategies, results of recent human trials and promising vaccine candidates. PMID:26554522

  13. [Dengue, Zika and Chikungunya].

    PubMed

    Kantor, Isabel N

    2016-01-01

    Arboviruses are transmitted by arthropods, including those responsible for the current pandemic: alphavirus (Chikungunya) and flaviviruses (dengue and Zika). Its importance increased in the Americas over the past 20 years. The main vectors are Aedes aegypti and A. albopictus. Dengue infection provides long lasting immunity against the specific serotype and temporary to the other three. Subsequent infection by another serotype determines more serious disease. There is a registered vaccine for dengue, Dengvaxia (Sanofi Pasteur). Other two (Butantan and Takeda) are in Phase III in 2016. Zika infection is usually asymptomatic or occurs with rash, conjunctivitis and not very high fever. There is no vaccine or specific treatment. It can be transmitted by parental, sexual and via blood transfusion. It has been associated with microcephaly. Chikungunya causes prolonged joint pain and persistent immune response. Two candidate vaccines are in Phase II. Dengue direct diagnosis is performed by virus isolation, RT-PCR and ELISA for NS1 antigen detection; indirect methods are ELISA-IgM (cross-reacting with other flavivirus), MAC-ELISA, and plaque neutralization. Zika is diagnosed by RT-PCR and virus isolation. Serological diagnosis cross-reacts with other flavivirus. For CHIKV culture, RT-PCR, MAC-ELISA and plaque neutralization are used. Against Aedes organophosphate larvicides (temephos), organophosphorus insecticides (malathion and fenitrothion) and pyrethroids (permethrin and deltamethrin) are usually employed. Resistance has been described to all these products. Vegetable derivatives are less expensive and biodegradable, including citronella oil, which microencapsulated can be preserved from evaporation.

  14. Chikungunya: epidemiology

    PubMed Central

    Petersen, Lyle R.; Powers, Ann M.

    2016-01-01

    Chikungunya virus is a mosquito-borne alphavirus that causes fever and debilitating joint pains in humans. Joint pains may last months or years. It is vectored primarily by the tropical and sub-tropical mosquito, Aedes aegypti, but is also found to be transmitted by Aedes albopictus, a mosquito species that can also be found in more temperate climates. In recent years, the virus has risen from relative obscurity to become a global public health menace affecting millions of persons throughout the tropical and sub-tropical world and, as such, has also become a frequent cause of travel-associated febrile illness. In this review, we discuss our current understanding of the biological and sociological underpinnings of its emergence and its future global outlook. PMID:26918158

  15. Arbovirus Surveillance and First Report of Chikungunya Virus in Wild Populations of Aedes aegypti from Guerrero, Mexico.

    PubMed

    Dzul-Manzanilla, Felipe; Martínez, Norma E; Cruz-Nolasco, Maximina; Gutiérrez-Castro, Cipriano; López-Damián, Leonardo; Ibarra-López, Jesús; Martini, Andres; Torres-Leyva, Joel; Bibiano-Marín, Wilbert; Tornez-Benitez, Citlalli; Ayora-Talavera, Guadalupe; Manrique-Saide, Pablo

    2015-09-01

    We carried out dengue (DENV) and chikungunya virus (CHIKV) surveillance in wild populations of Aedes aegypti from Guerrero, Mexico, from 2012 to 2014 following a standard national protocol of the Mexican Dengue Control Program. A total of 284 pools (15-30 specimens/pool) of female mosquitoes were tested with real-time reverse transcriptase-polymerase chain reaction to detect DENV and CHIKV. We report for the 1st time the detection of CHIKV from field-collected mosquitoes at Acapulco and Juchitán in 2014. Results from DENV are also reported.

  16. Surge of Dengue Virus Infection and Chikungunya Fever in Bali in 2010: The Burden of Mosquito-Borne Infectious Diseases in a Tourist Destination

    PubMed Central

    Yoshikawa, Minako Jen; Kusriastuti, Rita

    2013-01-01

    Labor flow and travelers are important factors contributing to the spread of Dengue virus infection and chikungunya fever. Bali Province of Indonesia, a popular resort and tourist destination, has these factors and suffers from mosquito-borne infectious diseases. Using area study approach, a series of fieldwork was conducted in Bali to obtain up-to-date primary disease data, to learn more about public health measures, and to interview health officers, hotel personnel, and other resource persons. The national data including information on two other provinces were obtained for comparison. The health ministry reported 5,810 and 11,697 cases of dengue hemorrhagic fever in Bali in 2009 and 2010, respectively. Moreover, two densely populated tourist areas and one district have shown a particularly high incidence and sharp increases in 2010. Cases of chikungunya fever reported in Bali more than doubled in 2010 from the previous year. Our findings suggest that Bali can benefit from a significant reduction in vector populations and dissemination of disease preventive knowledge among both local residents and foreign visitors. This will require a concerted and trans-border approach, which may prove difficult in the province. PMID:23874141

  17. Surge of dengue virus infection and chikungunya Fever in bali in 2010: the burden of mosquito-borne infectious diseases in a tourist destination.

    PubMed

    Yoshikawa, Minako Jen; Kusriastuti, Rita

    2013-06-01

    Labor flow and travelers are important factors contributing to the spread of Dengue virus infection and chikungunya fever. Bali Province of Indonesia, a popular resort and tourist destination, has these factors and suffers from mosquito-borne infectious diseases. Using area study approach, a series of fieldwork was conducted in Bali to obtain up-to-date primary disease data, to learn more about public health measures, and to interview health officers, hotel personnel, and other resource persons. The national data including information on two other provinces were obtained for comparison. The health ministry reported 5,810 and 11,697 cases of dengue hemorrhagic fever in Bali in 2009 and 2010, respectively. Moreover, two densely populated tourist areas and one district have shown a particularly high incidence and sharp increases in 2010. Cases of chikungunya fever reported in Bali more than doubled in 2010 from the previous year. Our findings suggest that Bali can benefit from a significant reduction in vector populations and dissemination of disease preventive knowledge among both local residents and foreign visitors. This will require a concerted and trans-border approach, which may prove difficult in the province.

  18. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis.

    PubMed

    Jin, Jing; Liss, Nathan M; Chen, Dong-Hua; Liao, Maofu; Fox, Julie M; Shimak, Raeann M; Fong, Rachel H; Chafets, Daniel; Bakkour, Sonia; Keating, Sheila; Fomin, Marina E; Muench, Marcus O; Sherman, Michael B; Doranz, Benjamin J; Diamond, Michael S; Simmons, Graham

    2015-12-22

    We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value. PMID:26686638

  19. Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis.

    PubMed

    Jin, Jing; Liss, Nathan M; Chen, Dong-Hua; Liao, Maofu; Fox, Julie M; Shimak, Raeann M; Fong, Rachel H; Chafets, Daniel; Bakkour, Sonia; Keating, Sheila; Fomin, Marina E; Muench, Marcus O; Sherman, Michael B; Doranz, Benjamin J; Diamond, Michael S; Simmons, Graham

    2015-12-22

    We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value.

  20. Detection of Chikungunya virus in Aedes aegypti during 2011 outbreak in Al Hodayda, Yemen.

    PubMed

    Zayed, Alia; Awash, Abdullah A; Esmail, Mohammed A; Al-Mohamadi, Hani A; Al-Salwai, Mostafa; Al-Jasari, Adel; Medhat, Iman; Morales-Betoulle, Maria E; Mnzava, Abraham

    2012-07-01

    In October 2010, the Ministry of Public Health and Population reported an outbreak of dengue-like acute febrile illness in Al Hodayda governorate. By January 2011, a total of 1542 cases had been recorded from 19 of the 26 districts in the governorate with 104 purportedly associated deaths. In response this event, in January 2011 entomological investigations aimed at identifying the primary vector and the epidemic associated etiological agent were carried out. Based on the reported cases and the progress of the outbreak in the governorate, mosquito collection was undertaken in two of the most recent outbreak areas; Al Khokha district (130km south of Al Hodayda) and Al Muneera district (100km north). Mosquito adults were collected from houses using BG-sentinel™ traps, aspiration of resting mosquitoes and knock-down spraying. Indoor and outdoor containers adjacent to the houses were inspected for larvae. Subsequently mosquito pools were analyzed by RT-PCR for detection of the four dengue virus serotypes (DENV-1, DENV-2, DENV-3, DENV-4), and for Chikungunya virus (CHIKV). Aedes aegypti was the dominant mosquito species collected. Four pools represent 40% of the tested pools, all containing adult female Ae. aegypti, were positive for CHIKV. Three CHIKV isolates were obtained from the RNA positive mosquito pools and identified by rRT-PCR. This finding marks the first record of CHIKV isolated from Ae. aegypti in Yemen. The larval container and Breteau indices in the visited localities surveyed were estimated at 53.8 and 100, respectively. The emergence of this unprecedented CHIKV epidemic in Al Hodayda is adding up another arboviral burden to the already existing vector-borne diseases. Considering the governorate as one focal port in the Red Sea region, the spread of the disease to other areas in Yemen and in neighboring countries is anticipated. Public health education and simple measures to detect and prevent mosquito breeding in water storage containers could prevent

  1. Sphingosine kinase 2 is a chikungunya virus host factor co-localized with the viral replication complex.

    PubMed

    Reid, St Patrick; Tritsch, Sarah R; Kota, Krishna; Chiang, Chih-Yuan; Dong, Lian; Kenny, Tara; Brueggemann, Ernest E; Ward, Michael D; Cazares, Lisa H; Bavari, Sina

    2015-10-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus which causes severe and prolonged arthralgic febrile illness. The recent global spread of the virus and lack of approved therapeutic options makes it imperative to gain greater insight into the molecular mechanisms underlying CHIKV pathogenesis, in particular host factors recruited by the virus. In the current study, we identify sphingosine kinase 2 (SK2) as a CHIKV host factor co-localized with the viral replication complex (VRC) during infection. SK2 was demonstrated to co-localize with viral RNA and nonstructural proteins. Targeted impairment of SK2 expression or function significantly inhibited CHIKV infection. Furthermore, affinity purification-mass spectrometry studies revealed that SK2 associates with a number of proteins involved in cellular gene expression specifically during viral infection, suggesting a role in replication. Collectively these results identify SK2 as a novel CHIKV host factor.

  2. Inhibitory effects of a peptide-fusion protein (Latarcin-PAP1-Thanatin) against chikungunya virus.

    PubMed

    Rothan, Hussin A; Bahrani, Hirbod; Shankar, Esaki M; Rahman, Noorsaadah Abd; Yusof, Rohana

    2014-08-01

    Chikungunya virus (CHIKV) outbreaks have led to a serious economic burden, as the available treatment strategies can only alleviate disease symptoms, and no effective therapeutics or vaccines are currently available for human use. Here, we report the use of a new cost-effective approach involving production of a recombinant antiviral peptide-fusion protein that is scalable for the treatment of CHIKV infection. A peptide-fusion recombinant protein LATA-PAP1-THAN that was generated by joining Latarcin (LATA) peptide with the N-terminus of the PAP1 antiviral protein, and the Thanatin (THAN) peptide to the C-terminus, was produced in Escherichia coli as inclusion bodies. The antiviral LATA-PAP1-THAN protein showed 89.0% reduction of viral plaque formation compared with PAP1 (46.0%), LATA (67.0%) or THAN (79.3%) peptides alone. The LATA-PAP1-THAN protein reduced the viral RNA load that was 0.89-fold compared with the untreated control cells. We also showed that PAP1 resulted in 0.44-fold reduction, and THAN and LATA resulting in 0.78-fold and 0.73-fold reductions, respectively. The LATA-PAP1-THAN protein inhibited CHIKV replication in the Vero cells at an EC50 of 11.2μg/ml, which is approximately half of the EC50 of PAP1 (23.7μg/ml) and protected the CHIKV-infected mice at the dose of 0.75mg/ml. We concluded that production of antiviral peptide-fusion protein in E. coli as inclusion bodies could accentuate antiviral activities, enhance cellular internalisation, and could reduce product toxicity to host cells and is scalable to epidemic response quantities.

  3. Whole-Genome Sequencing Analysis from the Chikungunya Virus Caribbean Outbreak Reveals Novel Evolutionary Genomic Elements

    PubMed Central

    Stapleford, Kenneth A.; Moratorio, Gonzalo; Henningsson, Rasmus; Chen, Rubing; Matheus, Séverine; Enfissi, Antoine; Weissglas-Volkov, Daphna; Isakov, Ofer; Blanc, Hervé; Mounce, Bryan C.; Dupont-Rouzeyrol, Myrielle; Shomron, Noam; Weaver, Scott; Fontes, Magnus; Rousset, Dominique; Vignuzzi, Marco

    2016-01-01

    Background Chikungunya virus (CHIKV), an alphavirus and member of the Togaviridae family, is capable of causing severe febrile disease in humans. In December of 2013 the Asian Lineage of CHIKV spread from the Old World to the Americas, spreading rapidly throughout the New World. Given this new emergence in naïve populations we studied the viral genetic diversity present in infected individuals to understand how CHIKV may have evolved during this continuing outbreak. Methodology/Principle Findings We used deep-sequencing technologies coupled with well-established bioinformatics pipelines to characterize the minority variants and diversity present in CHIKV infected individuals from Guadeloupe and Martinique, two islands in the center of the epidemic. We observed changes in the consensus sequence as well as a diverse range of minority variants present at various levels in the population. Furthermore, we found that overall diversity was dramatically reduced after single passages in cell lines. Finally, we constructed an infectious clone from this outbreak and identified a novel 3’ untranslated region (UTR) structure, not previously found in nature, that led to increased replication in insect cells. Conclusions/Significance Here we preformed an intrahost quasispecies analysis of the new CHIKV outbreak in the Caribbean. We identified novel variants present in infected individuals, as well as a new 3’UTR structure, suggesting that CHIKV has rapidly evolved in a short period of time once it entered this naïve population. These studies highlight the need to continue viral diversity surveillance over time as this epidemic evolves in order to understand the evolutionary potential of CHIKV. PMID:26807575

  4. Reduced Incidence of Chikungunya Virus Infection in Communities with Ongoing Aedes Aegypti Mosquito Trap Intervention Studies - Salinas and Guayama, Puerto Rico, November 2015-February 2016.

    PubMed

    Lorenzi, Olga D; Major, Chelsea; Acevedo, Veronica; Perez-Padilla, Janice; Rivera, Aidsa; Biggerstaff, Brad J; Munoz-Jordan, Jorge; Waterman, Stephen; Barrera, Roberto; Sharp, Tyler M

    2016-05-13

    Aedes species mosquitoes transmit chikungunya virus, as well as dengue and Zika viruses, and bite most often during the day.* Infectious mosquito bites frequently occur in and around homes (1,2). Caribbean countries first reported local transmission of chikungunya virus in December 2013, and soon after, chikungunya virus spread throughout the Americas (3). Puerto Rico reported its first laboratory-positive chikungunya case in May 2014 (4), and subsequently identified approximately 29,000 suspected cases throughout the island by the end of 2015.(†) Because conventional vector control approaches often fail to result in effective and sustainable prevention of infection with viruses transmitted by Aedes mosquitoes (5), and to improve surveillance of mosquito population densities, CDC developed an Autocidal Gravid Ovitrap (AGO) (6) to attract and capture the female Aedes aegypti mosquitoes responsible for transmission of infectious agents to humans (Figure). The AGO trap is a simple, low-cost device that requires no use of pesticides and no servicing for an extended period of time (6).

  5. Reduced Incidence of Chikungunya Virus Infection in Communities with Ongoing Aedes Aegypti Mosquito Trap Intervention Studies - Salinas and Guayama, Puerto Rico, November 2015-February 2016.

    PubMed

    Lorenzi, Olga D; Major, Chelsea; Acevedo, Veronica; Perez-Padilla, Janice; Rivera, Aidsa; Biggerstaff, Brad J; Munoz-Jordan, Jorge; Waterman, Stephen; Barrera, Roberto; Sharp, Tyler M

    2016-01-01

    Aedes species mosquitoes transmit chikungunya virus, as well as dengue and Zika viruses, and bite most often during the day.* Infectious mosquito bites frequently occur in and around homes (1,2). Caribbean countries first reported local transmission of chikungunya virus in December 2013, and soon after, chikungunya virus spread throughout the Americas (3). Puerto Rico reported its first laboratory-positive chikungunya case in May 2014 (4), and subsequently identified approximately 29,000 suspected cases throughout the island by the end of 2015.(†) Because conventional vector control approaches often fail to result in effective and sustainable prevention of infection with viruses transmitted by Aedes mosquitoes (5), and to improve surveillance of mosquito population densities, CDC developed an Autocidal Gravid Ovitrap (AGO) (6) to attract and capture the female Aedes aegypti mosquitoes responsible for transmission of infectious agents to humans (Figure). The AGO trap is a simple, low-cost device that requires no use of pesticides and no servicing for an extended period of time (6). PMID:27171600

  6. [The expansion of vector-borne diseases and the implications for blood transfusion safety: The case of West Nile Virus, dengue and chikungunya].

    PubMed

    Paty, M-C

    2013-05-01

    Arbovirus infections are increasing in prevalence worldwide. This presents new risks for blood transfusion. This article describes the epidemiology and surveillance of West Nile Virus, dengue and chikungunya and their role in the risk management of transfusions. Arboviruses are RNA viruses and very adaptable by nature. The majority of arbovirus infections are zoonoses. The risk of transmission is multifactorial and concerns the virus, vectors, animal reservoirs, the environment and human behaviour. In recent years, West Nile Virus has become established and widespread in North America, the number of cases of dengue worldwide has increased dramatically, and major epidemics of chikungunya have occurred in the Indian Ocean and Asia. The transmission of dengue and chikungunya is demonstrated in temperate zones. All arboviruses are potentially transmissible by transfusion due to their capacity to induce an asymptomatic viremic phase. The risk of West Nile Virus transmission via transfusion is recognised and prevention measures are well established. The risk of transmission via transfusion of dengue and chikungunya is real but difficult to quantify and the optimum prevention strategy is currently the subject of research. Access to up-to-date epidemiological data is an essential aid to decision-making, especially for donors returning from endemic areas to Europe. The challenge is to define and implement appropriate measures in unpredictable situations.

  7. Enhanced Production of Chikungunya Virus-Like Particles Using a High-pH Adapted Spodoptera frugiperda Insect Cell Line

    PubMed Central

    Wagner, James M.; Pajerowski, J. David; Daniels, Christopher L.; McHugh, Patrick M.; Flynn, Jessica A.; Balliet, John W.; Casimiro, Danilo R.; Subramanian, Shyamsundar

    2014-01-01

    Chikungunya virus-like particles (VLPs) have potential to be used as a prophylactic vaccine based on testing in multiple animal models and are currently being evaluated for human use in a Phase I clinical trial. The current method for producing these enveloped alphavirus VLPs by transient gene expression in mammalian cells presents challenges for scalable and robust industrial manufacturing, so the insect cell baculovirus expression vector system was evaluated as an alternative expression technology. Subsequent to recombinant baculovirus infection of Sf21 cells in standard culture media (pH 6.2–6.4), properly processed Chikungunya structural proteins were detected and assembled capsids were observed. However, an increase in culture pH to 6.6–6.8 was necessary to produce detectable concentrations of assembled VLPs. Since this elevated production pH exceeds the optimum for growth medium stability and Sf21 culture, medium modifications were made and a novel insect cell variant (SfBasic) was derived by exposure of Sf21 to elevated culture pH for a prolonged period of time. The high-pH adapted SfBasic insect cell line described herein is capable of maintaining normal cell growth into the typical mammalian cell culture pH range of 7.0–7.2 and produces 11-fold higher Chikungunya VLP yields relative to the parental Sf21 cell line. After scale-up into stirred tank bioreactors, SfBasic derived VLPs were chromatographically purified and shown to be similar in size and structure to a VLP standard derived from transient gene expression in HEK293 cells. Total serum anti-Chikungunya IgG and neutralizing titers from guinea pigs vaccinated with SfBasic derived VLPs or HEK293 derived VLPs were not significantly different with respect to production method, suggesting that this adapted insect cell line and production process could be useful for manufacturing Chikungunya VLPs for use as a vaccine. The adaptation of Sf21 to produce high levels of recombinant protein and VLPs in an

  8. Imported vector- and rodent-borne virus infections--an introduction.

    PubMed

    Schwarz, T F

    1996-01-01

    Travel is a potent force in the emergence of virus infections. Migration of humans and animals has been the pathway for disseminating virus diseases throughout history. In recent years, dengue virus has been identified as the most important travel-related, vector-borne virus disease. Other vector-borne virus infections, such as sandfly fever, Rift Valley fever, chikungunya fever and Japanese encephalitis, have been diagnosed in travelers returning from endemic areas. Crimean-Congo haemorrhagic fever may not only be imported by infected live stock, but also by travelers. Of rodent-borne virus infections, Lassa fever has been diagnosed occasionally in travelers returning from endemic areas. The potential impact of imported filoviruses is currently discussed.

  9. Suppressing Aedes albopictus, an Emerging Vector of Dengue and Chikungunya Viruses, by a Novel Combination of a Monomolecular Film and an Insect-Growth Regulator

    PubMed Central

    Nelder, Mark; Kesavaraju, Banugopan; Farajollahi, Ary; Healy, Sean; Unlu, Isik; Crepeau, Taryn; Ragavendran, Ashok; Fonseca, Dina; Gaugler, Randy

    2010-01-01

    The Asian tiger mosquito Aedes albopictus (Skuse) is rapidly increasing its global range and importance in transmission of chikungunya and dengue viruses. We tested pellet formulations of a monomolecular film (Agnique) and (S)-methoprene (Altosid) under laboratory and field conditions. In the laboratory, Agnique provided 80% control for 20 days, whereas Altosid, in combination with Agnique, provided 80% control for > 60 days. During field trials, the 1:1 pellet ratio of combined products provided > 95% control for at least 32 days and 50% control for at least 50 days. Altosid remained effective after a 107-day laboratory-induced drought, suggesting that the product serves as a means of control during drought conditions and against spring broods in temperate regions. Agnique and Altosid, when used in tandem for cryptic, difficult-to-treat locations, can provide long-term control of Ae. albopictus larvae and pupae. The possible additive or synergistic effects of the combined products deserve further investigation. PMID:20439963

  10. Host Immune Response to Mosquito-Transmitted Chikungunya Virus Differs from That Elicited by Needle Inoculated Virus

    PubMed Central

    Thangamani, Saravanan; Higgs, Stephen; Ziegler, Sarah; Vanlandingham, Dana; Tesh, Robert; Wikel, Stephen

    2010-01-01

    Background Mosquito-borne diseases are a worldwide public health threat. Mosquitoes transmit viruses or parasites during feeding, along with salivary proteins that modulate host responses to facilitate both blood feeding and pathogen transmission. Understanding these earliest events in mosquito transmission of arboviruses by mosquitoes is essential for development and assessment of rational vaccine and treatment strategies. In this report, we compared host immune responses to chikungunya virus (CHIKV) transmission by (1) mosquito bite, or (2) by needle inoculation. Methods and Findings Differential cytokine expression was measured using quantitative real-time RT-PCR, at sites of uninfected mosquito bites, CHIKV-infected mosquito bites, and needle-inoculated CHIKV. Both uninfected and CHIKV infected mosquitoes polarized host cytokine response to a TH2 profile. Compared to uninfected mosquito bites, expression of IL-4 induced by CHIKV-infected mosquitoes were 150 fold and 527.1 fold higher at 3 hours post feeding (hpf) and 6 hpf, respectively. A significant suppression of TH1 cytokines and TLR-3 was also observed. These significant differences may result from variation in the composition of uninfected and CHIKV-infected mosquito saliva. Needle injected CHIKV induced a robust interferon-γ, no detectable IL-4, and a significant up-regulation of TLR-3. Conclusions This report describes the first analysis of cutaneous cytokines in mice bitten by CHIKV–infected mosquitoes. Our data demonstrate contrasting immune activation in the response to CHIKV infection by mosquito bite or needle inoculation. The significant role of mosquito saliva in these earliest events of CHIKV transmission and infection are highlighted. PMID:20711354

  11. Genetic predisposition to chikungunya--a blood group study in chikungunya affected families.

    PubMed

    Lokireddy, Sudarsanareddy; Sarojamma, Vemula; Ramakrishna, Vadde

    2009-01-01

    Chikungunya fever is a viral disease transmitted to humans by the bite of CHIKV virus infected Aedes mosquitoes. During monsoon outbreak of chikungunya fever, we carried out the genetic predisposition to chikungunya in disease affected 100 families by doing blood group (ABO) tests by focusing on individuals who were likely to have a risk of chikungunya and identified the blood group involved in susceptibility/resistance to chikungunya. In the present study, based on blood group antigens, the individuals were kept in four groups - A (108), B (98), AB (20) and O (243). The result obtained was showed all Rh positive blood group individuals are susceptible to chikungunya fever. Among ABO group, the blood group O +ve individuals are more susceptible to chikungunya than other blood groups. No blood group with Rh negative was affected with chikungunya, it indicates Rh -ve more resistance to chikungunya.

  12. Chikungunya outbreak in Guangdong Province, China, 2010.

    PubMed

    Wu, De; Wu, Jie; Zhang, Qiaoli; Zhong, Haojie; Ke, Changwen; Deng, Xiaoling; Guan, Dawei; Li, Hui; Zhang, Yonghui; Zhou, Huiqiong; He, Jianfeng; Li, Linghui; Yang, Xingfen

    2012-03-01

    A disease outbreak with dengue-like symptoms was reported in Guangdong Province, China, in October 2010. Testing results confirmed that the pathogen causing the outbreak was chikungunya virus. Phylogenic analysis indicated that this virus was a member of the Indian Ocean clade of the East/Center/South African subgroup of chikungunya virus.

  13. High Rates of O’Nyong Nyong and Chikungunya Virus Transmission in Coastal Kenya

    PubMed Central

    LaBeaud, A. Desiree; Banda, Tamara; Brichard, Julie; Muchiri, Eric M.; Mungai, Peter L.; Mutuku, Francis M.; Borland, Erin; Gildengorin, Ginny; Pfeil, Sarah; Teng, Crystal Y.; Long, Kristin; Heise, Mark; Powers, Ann M.; Kitron, Uriel; King, Charles H.

    2015-01-01

    Background Chikungunya virus (CHIKV) and o’nyong nyong virus (ONNV) are mosquito-borne alphaviruses endemic in East Africa that cause acute febrile illness and arthritis. The objectives of this study were to measure the seroprevalence of CHIKV and ONNV in coastal Kenya and link it to demographics and other risk factors. Methodology Demographic and exposure questionnaires were administered to 1,848 participants recruited from two village clusters (Milalani-Nganja and Vuga) in 2009. Sera were tested for alphavirus exposure using standardized CHIKV IgG ELISA protocols and confirmed with plaque reduction neutralization tests (PRNT). Logistic regression models were used to determine the variables associated with seropositivity. Weighted K test for global clustering of houses with alphavirus positive participants was performed for distance ranges of 50–1,000 meters, and G* statistic and kernel density mapping were used to identify locations of higher seroprevalence. Principal Findings 486 (26%) participants were seropositive by IgG ELISA. Of 443 PRNT confirmed positives, 25 samples (6%) were CHIKV+, 250 samples (56%) were ONNV+, and 168 samples (38%) had high titers for both. Age was significantly associated with seropositivity (OR 1.01 per year, 95% C.I. 1.00–1.01); however, younger adults were more likely to be seropositive than older adults. Males were less likely to be seropositive (p<0.05; OR 0.79, 95% C.I. 0.64–0.97). Adults who owned a bicycle (p<0.05; OR 1.37, 95% C.I. 1.00–1.85) or motor vehicle (p<0.05; OR 4.64, 95% C.I. 1.19–18.05) were more likely to be seropositive. Spatial analysis demonstrated hotspots of transmission within each village and clustering among local households in Milalani-Nganja, peaking at the 200–500m range. Conclusions/Significance Alphavirus exposure, particularly ONNV exposure, is common in coastal Kenya with ongoing interepidemic transmission of both ONNV and CHIKV. Women and adults were more likely to be seropositive

  14. Chikungunya and dengue virus infections during pregnancy: seroprevalence, seroincidence and maternal-fetal transmission, southern Thailand, 2009-2010.

    PubMed

    Laoprasopwattana, K; Suntharasaj, T; Petmanee, P; Suddeaugrai, O; Geater, A

    2016-01-01

    Limited information is available on the seroprevalence of chikungunya virus (CHIKV) infection and maternal-fetal transmission incidence of CHIKV and dengue virus (DENV) infections during the 2008-2009 CHIKV outbreak in southern Thailand. A community-based post-epidemic seroprevalence study was conducted in parturient women admitted to the Thepa District Hospital in Songkhla Province, Thailand, for delivery from November 2009 to May 2010. The women were tested for chikungunya (CHIK) IgM/IgG and dengue (DEN) IgM/IgG. Cord blood samples were also tested for CHIK IgM or DEN IgM in women who tested positive for CHIK IgM or DEN IgM, respectively. The seroprevalence of CHIKV infection (CHIK IgM or IgG positive) was 227/319 (71·2%) with pre-outbreak seroprevalence (IgM-/IgG+) of 43·6% and the seroprevalence of DENV infection was 288/319 (90·3%). Complications during pregnancy, newborn outcomes and congenital anomalies were not different in those who had recent, remote or no CHIKV infections. None of the newborns whose mothers were CHIK or DEN IgM positive had cord blood positive for both CHIK and DEN IgM. In conclusion, both CHIKV and DENV are endemic in southern Thailand; during the recent CHIKV outbreak CHIK seroprevalence increased from 43·6% to 71·2%.

  15. Infection pattern and transmission potential of chikungunya virus in two New World laboratory-adapted Aedes aegypti strains

    PubMed Central

    Dong, Shengzhang; Kantor, Asher M.; Lin, Jingyi; Passarelli, A. Lorena; Clem, Rollie J.; Franz, Alexander W. E.

    2016-01-01

    Chikungunya virus (CHIKV) is an emerging mosquito-borne virus belonging to the Togaviridae, which is transmitted to humans by Aedes aegypti and Ae. albopictus. We describe the infection pattern of CHIKV in two New World Ae. aegypti strains, HWE and ORL. Both mosquito strains were susceptible to the virus but showed different infection patterns in midguts and salivary glands. Even though acquisition of a bloodmeal showed moderate levels of apoptosis in midgut tissue, there was no obvious additional CHIKV-induced apoptosis detectable during midgut infection. Analysis of expression of apoptosis-related genes suggested that CHIKV infection dampens rather than promotes apoptosis in the mosquito midgut. In both mosquito strains, the virus was present in saliva within two days post-oral infection. HWE and ORL mosquitoes exhibited no salivary gland infection barrier; however, only 60% (HWE) to 65% (ORL) of the females had released the virus in their saliva at one week post-oral acquisition, suggesting a salivary gland escape barrier. CHIKV induced an apoptotic response in salivary glands of HWE and ORL mosquitoes, demonstrating that the virus caused pathology in its natural vector. PMID:27102548

  16. Encephalitis Caused by Chikungunya Virus in a Traveler from the Kingdom of Tonga

    PubMed Central

    Nelson, Joanna; Waggoner, Jesse J.; Sahoo, Malaya K.; Grant, Philip M.

    2014-01-01

    Febrile travelers from countries with unique endemic pathogens pose a significant diagnostic challenge. In this report, we describe the case of a Tongan man presenting with fever, rash, and altered mental status. The diagnosis of Chikungunya encephalitis was made using a laboratory-developed real-time RT-PCR and serologic testing. PMID:24958800

  17. A perspective on targeting non-structural proteins to combat neglected tropical diseases: Dengue, West Nile and Chikungunya viruses.

    PubMed

    Bhakat, Soumendranath; Karubiu, Wilson; Jayaprakash, Venkatesan; Soliman, Mahmoud E S

    2014-11-24

    Neglected tropical diseases are major causes of fatality in poverty stricken regions across Africa, Asia and some part of America. The combined potential health risk associated with arthropod-borne viruses (arboviruses); Dengue virus (DENV), West Nile Virus (WNV) and Chikungunya Virus (CHIKV) is immense. These arboviruses are either emerging or re-emerging in many regions with recent documented outbreaks in the United States. Despite several recent evidences of emergence, currently there are no approved drugs or vaccines available to counter these diseases. Non-structural proteins encoded by these RNA viruses are essential for their replication and maturation and thus may offer ideal targets for developing antiviral drugs. In recent years, several protease inhibitors have been sourced from plant extract, synthesis, computer aided drug design and high throughput screening as well as through drug reposition based approaches to target the non-structural proteins. The protease inhibitors have shown different levels of inhibition and may thus provide template to develop selective and potent drugs against these devastating arboviruses. This review seeks to shed light on the design and development of antiviral drugs against DENV, WNV and CHIKV to date. To the best of our knowledge, this review provides the first comprehensive update on the development of protease inhibitors targeting non-structural proteins of three most devastating arboviruses, DENV, WNV and CHIKV.

  18. Evaluation of Simultaneous Transmission of Chikungunya Virus and Dengue Virus Type 2 in Infected Aedes aegypti and Aedes albopictus (Diptera: Culicidae)

    PubMed Central

    Nuckols, J. T.; Huang, Y.-J. S.; Higgs, S.; Miller, A. L.; Pyles, R. B.; Spratt, H. m.; Horne, K. M.; Vanlandingham, D. L.

    2015-01-01

    The simultaneous transmission of chikungunya virus (CHIKV) and dengue viruses (DENV) has been a major public health concern because of their sympatric distribution and shared mosquito vectors. Groups of Aedes aegypti (L.) and Aedes albopictus (Skuse) were orally infected with 1.5 × 105 PFU/ml of CHIKV and 3.2 × 106 FFU/ml of DENV-2 simultaneously or separately in inverse orders and evaluated for dissemination and transmission by qRT-PCR. Simultaneous dissemination of both viruses was detected for all groups in Ae. aegypti and Ae. albopictus while cotransmission of CHIKV and DENV-2 only occurred at low rates after sequential but not simultaneous infection. PMID:26334820

  19. Evaluation of Simultaneous Transmission of Chikungunya Virus and Dengue Virus Type 2 in Infected Aedes aegypti and Aedes albopictus (Diptera: Culicidae).

    PubMed

    Nuckols, J T; Huang, Y-J S; Higgs, S; Miller, A L; Pyles, R B; Spratt, H M; Horne, K M; Vanlandingham, D L

    2015-05-01

    The simultaneous transmission of chikungunya virus (CHIKV) and dengue viruses (DENV) has been a major public health concern because of their sympatric distribution and shared mosquito vectors. Groups of Aedes aegypti (L.) and Aedes albopictus (Skuse) were orally infected with 1.5 × 10(5) PFU/ml of CHIKV and 3.2 × 10(6) FFU/ml of DENV-2 simultaneously or separately in inverse orders and evaluated for dissemination and transmission by qRT-PCR. Simultaneous dissemination of both viruses was detected for all groups in Ae. aegypti and Ae. albopictus while cotransmission of CHIKV and DENV-2 only occurred at low rates after sequential but not simultaneous infection.

  20. Development and evaluation of a one-step SYBR-Green I-based real-time RT-PCR assay for the detection and quantification of Chikungunya virus in human, monkey and mosquito samples.

    PubMed

    Ummul Haninah, A; Vasan, S S; Ravindran, T; Chandru, A; Lee, H L; Shamala Devi, S

    2010-12-01

    This paper reports the development of a one-step SYBR-Green I-based realtime RT-PCR assay for the detection and quantification of Chikungunya virus (CHIKV) in human, monkey and mosquito samples by targeting the E1 structural gene. A preliminary evaluation of this assay has been successfully completed using 71 samples, consisting of a panel of negative control sera, sera from healthy individuals, sera from patients with acute disease from which CHIKV had been isolated, as well as monkey sera and adult mosquito samples obtained during the chikungunya fever outbreak in Malaysia in 2008. The assay was found to be 100-fold more sensitive than the conventional RT-PCR with a detection limit of 4.12x10(0) RNA copies/μl. The specificity of the assay was tested against other related viruses such as Dengue (serotypes 1-4), Japanese encephalitis, Herpes Simplex, Parainfluenza, Sindbis, Ross River, Yellow fever and West Nile viruses. The sensitivity, specificity and efficiency of this assay were 100%, 100% and 96.8% respectively. This study on early diagnostics is of importance to all endemic countries, especially Malaysia, which has been facing increasingly frequent and bigger outbreaks due to this virus since 1999.

  1. Development of a simple indirect enzyme-linked immunosorbent assay for the detection of immunoglobulin M antibody in serum from patients following an outbreak of chikungunya virus infection in Yangon, Myanmar.

    PubMed

    Thein, S; La Linn, M; Aaskov, J; Aung, M M; Aye, M; Zaw, A; Myint, A

    1992-01-01

    During 1984, 1548 children were admitted to the Yangon [Rangoon] Children's Hospital in Myanmar [Burma] with haemorrhagic fever. No evidence of recent dengue infection was found in 577 of the 803 children from whom paired sera were obtained, raising the possibility of reappearance of Chikungunya virus infection in Myanmar. An enzyme-linked immunosorbent assay (ELISA) for the detection of anti-Chikungunya virus immunoglobulin M (IgM) antibody was prepared and standardized using only reagents which are commercially available or which could be prepared without the use of sophisticated equipment. While there was 90% agreement between haemagglutination inhibition (HI) tests and the IgM ELISA in the diagnosis of acute Chikungunya virus infections, 12 additional patients with stationary anti-Chikungunya virus HI antibody titres could be identified as having acute Chikungunya infections using the ELISA. Furthermore, the ELISA could identify twice as many patients (31/103) at the time of admission to hospital as the HI test (15/103). There was no false positive IgM reaction with the ELISA which could be attributed to the presence of rheumatoid factor. Using the test, 103 of a sample of 163 children who presented to the Yangon Children's Hospital with fever/haemorrhagic fever were diagnosed as Chikungunya patients, 4 had possible dual Chikungunya and dengue infections, 16 had dengue, 30 had neither Chikungunya nor dengue infections, and a definitive diagnosis could not be made for 10 patients. Routine use of the ELISA would alert authorities to future outbreaks of Chikungunya virus infection and avoid admission to hospital of patients with a non-life-threatening viral disease.

  2. Emergence and clinical insights into the pathology of Chikungunya virus infection.

    PubMed

    Jaffar-Bandjee, Marie Christine; Ramful, Duksha; Gauzere, Bernard Alex; Hoarau, Jean Jacques; Krejbich-Trotot, Pascale; Robin, Stephanie; Ribera, Anne; Selambarom, Jimmy; Gasque, Philippe

    2010-09-01

    Major epidemics of Chikungunya have re-emerged with millions of cases worldwide. What was once largely a tropical disease in poorer countries is now recognized as a major global health issue. The disease is perpetuated by the alphavirus Chikungunya, and is transmitted by Aedes mosquitoes. The infection is highly symptomatic, with fever, skin rash and incapacitating arthralgia, which can evolve to chronic arthritis and rheumatism in elderly patients. Mother-to-child transmission, encephalitis, Guillain-Barré syndrome and deaths have been noted. In this article, we will highlight the epidemiological, clinical, virological and immunological aspects of the disease and mention the therapies that have been used during recent epidemics. Novel prevention measures to control the mosquito and a new vaccine are highly warranted.

  3. Seroprevalence of Asian Lineage Chikungunya Virus Infection on Saint Martin Island, 7 Months after the 2013 Emergence

    PubMed Central

    Gay, Noellie; Rousset, Dominique; Huc, Patricia; Matheus, Séverine; Ledrans, Martine; Rosine, Jacques; Cassadou, Sylvie; Noël, Harold

    2016-01-01

    At the end of 2013, chikungunya virus (CHIKV) emerged in Saint Martin Island, Caribbean. The Asian lineage was identified. Seven months after this introduction, the seroprevalence was 16.9% in the population of Saint Martin and 39.0% of infections remained asymptomatic. This moderate attack rate and the apparent limited size of the outbreak in Saint Martin could be explained by control measures involved to lower the exposure of the inhabitants. Other drivers such as climatic factors and population genetic factors should be explored. The substantial rate of asymptomatic infections recorded points to a potential source of infection that can both spread in new geographic areas and maintain an inconspicuous endemic circulation in the Americas. PMID:26643536

  4. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    PubMed

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-01

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease.

  5. Clinical and histopathological features of fatal cases with dengue and chikungunya virus co-infection in Colombia, 2014 to 2015.

    PubMed

    Mercado, Marcela; Acosta-Reyes, Jorge; Parra, Edgar; Pardo, Lissethe; Rico, Angélica; Campo, Alfonso; Navarro, Edgar; Viasus, Diego

    2016-06-01

    We report clinical features and histopathological findings in fatal cases with dengue (DENV) and chikungunya (CHIKV) co-infection identified at the Colombian National Institute of Health between September 2014 and October 2015. Seven such cases were documented. Dengue serotype 2 virus was identified in six cases. All patients were adults and comorbidities were present in four. Fever, arthralgia or myalgia was present in all cases. The frequency of rash, haemorrhage, oedema, and gastrointestinal symptoms was variable. Laboratory findings such as thrombocytopenia, renal failure, and leukocyte count were also inconsistent between cases. Post-mortem tissue examination documented focal hepatocellular coagulative necrosis in three cases, incipient acute pericarditis in one and tubulointerstitial nephritis in one. This study provides evidence of mortality in patients with DENV and CHIKV co-infection. Fatal cases were characterised by variable clinical and laboratory features. Evaluation of histopathology of autopsy tissues provided evidence of the pathological consequences of the disease. PMID:27277216

  6. Chikungunya, a paradigm of neglected tropical disease that emerged to be a new health global risk.

    PubMed

    Rougeron, Virginie; Sam, I-Ching; Caron, Mélanie; Nkoghe, Dieudonné; Leroy, Eric; Roques, Pierre

    2015-03-01

    Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV.

  7. Chikungunya, a paradigm of neglected tropical disease that emerged to be a new health global risk.

    PubMed

    Rougeron, Virginie; Sam, I-Ching; Caron, Mélanie; Nkoghe, Dieudonné; Leroy, Eric; Roques, Pierre

    2015-03-01

    Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family that causes chronic and incapacitating arthralgia in human populations. Since its discovery in 1952, CHIKV was responsible for sporadic and infrequent outbreaks. However, since 2005, global Chikungunya outbreaks have occurred, inducing some fatalities and associated with severe and chronic morbidity. Chikungunya is thus considered as an important re-emerging public health problem in both tropical and temperate countries, where the distribution of the Aedes mosquito vectors continues to expand. This review highlights the most recent advances in our knowledge and understanding of the epidemiology, biology, treatment and vaccination strategies of CHIKV. PMID:25453326

  8. A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis

    PubMed Central

    Lam, Shirley; Nyo, Min; Phuektes, Patchara; Yew, Chow Wenn; Tan, Yee Joo; Chu, Justin Jang Hann

    2015-01-01

    Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating and persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate and characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based and murine model. To evaluate their antigenicity and neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, and reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues and histopathology of the limb muscles were evaluated. Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia and protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate and similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design. PMID:26305993

  9. A potent neutralizing IgM mAb targeting the N218 epitope on E2 protein protects against Chikungunya virus pathogenesis.

    PubMed

    Lam, Shirley; Nyo, Min; Phuektes, Patchara; Yew, Chow Wenn; Tan, Yee Joo; Chu, Justin Jang Hann

    2015-01-01

    Chikungunya virus (CHIKV) is a medically important human viral pathogen that causes Chikungunya fever accompanied with debilitating and persistent joint pain. Host-elicited or passively-transferred monoclonal antibodies (mAb) are essential mediators of CHIKV clearance. Therefore, this study aimed to generate and characterize a panel of mAbs for their neutralization efficacy against CHIKV infection in a cell-based and murine model. To evaluate their antigenicity and neutralization profile, indirect enzyme-linked immunosorbent assay (ELISA), an immunofluorescence assay (IFA) and a plaque reduction neutralization test were performed on mAbs of IgM isotype. CHIKV escape mutants against mAb 3E7b neutralization were generated, and reverse genetics techniques were then used to create an infectious CHIKV clone with a single mutation. 3E7b was also administered to neonate mice prior or after CHIKV infection. The survival rate, CHIKV burden in tissues and histopathology of the limb muscles were evaluated. Both IgM 3E7b and 8A2c bind strongly to native CHIKV surface and potently neutralize CHIKV replication. Further analyses of 3E7b binding and neutralization of CHIKV single-mutant clones revealed that N218 of CHIKV E2 protein is a potent neutralizing epitope. In a pre-binding neutralization assay, 3E7b blocks CHIKV attachment to permissive cells, possibly by binding to the surface-accessible E2-N218 residue. Prophylactic administration of 3E7b to neonate mice markedly reduced viremia and protected against CHIKV pathogenesis in various mice tissues. Given therapeutically at 4 h post-infection, 3E7b conferred 100% survival rate and similarly reduced CHIKV load in most mice tissues except the limb muscles. Collectively, these findings highlight the usefulness of 3E7b for future prophylactic or epitope-based vaccine design.

  10. Protection against Chikungunya virus induced arthralgia following prophylactic treatment with adenovirus vectored interferon (mDEF201).

    PubMed

    Dagley, Ashley; Ennis, Jane; Turner, Jeffrey D; Rood, Kerry A; Van Wettere, Arnaud J; Gowen, Brian B; Julander, Justin G

    2014-08-01

    Recent outbreaks of Chikungunya virus (CHIKV) infection have resulted in millions of cases of disease with significant morbidity. No approved antiviral treatments exist for the prevention or treatment of this viral disease. Infection with CHIKV results in a high rate of symptomatic disease that primarily includes a debilitating arthralgia. To model this cardinal disease manifestation, adult DBA/1J mice were challenged with CHIKV by footpad injection. Viremia and hind limb virus titers increased ∼100-fold while spleen virus increased >1000-fold within 1day post-virus infection (dpi). Footpad swelling was measured over a 10-day period, with peak swelling observed between 6 and 7dpi. Histology of the hind leg at the site of virus challenge showed evidence of myositis and synovitis starting on 5dpi. Cytokine profiling of the hind limb at the site of inoculation revealed a biphasic inflammatory response represented by an increase in IL-6, MCP-1, IFN-γ, MIP-1α, RANTES, and IL-17. To investigate the prophylactic capacity of IFN, mice were treated with mDEF201, an adenovirus-vectored IFN-α. Intranasal administration of a single 10(7)pfu/ml dose of mDEF201 administered 21days to 24h prior to infection, significantly reduced footpad swelling, virus titers in the hind leg and spleen, and several inflammatory cytokines. Efficacy was not observed when treatment was initiated 24h after virus challenge. This arthralgia model of CHIKV recapitulates relevant disease features commonly observed in human disease making it applicable to preclinical testing of therapies that target both viral replication and the associated joint disease.

  11. A Field-Deployable Reverse Transcription Recombinase Polymerase Amplification Assay for Rapid Detection of the Chikungunya Virus

    PubMed Central

    Faye, Oumar; Prüger, Pauline; Kaiser, Marco; Thaloengsok, Sasikanya; Ubol, Sukathida; Sakuntabhai, Anavaj; Leparc-Goffart, Isabelle; Hufert, Frank T.; Sall, Amadou A.; Weidmann, Manfred; Niedrig, Matthias

    2016-01-01

    Background Chikungunya virus (CHIKV) is a mosquito-borne virus currently transmitted in about 60 countries. CHIKV causes acute flu-like symptoms and in many cases prolonged musculoskeletal and joint pain. Detection of the infection is mostly done using RT-RCR or ELISA, which are not suitable for point-of-care diagnosis. Methodology/Principal Findings In this study, a reverse transcription recombinase polymerase amplification (RT-RPA) assay for the detection of the CHIKV was developed. The assay sensitivity, specificity, and cross-reactivity were tested. CHIKV RT-RPA assay detected down to 80 genome copies/reaction in a maximum of 15 minutes. It successfully identified 18 isolates representing the three CHIKV genotypes. No cross-reactivity was detected to other alphaviruses and arboviruses except O'nyong'nyong virus, which could be differentiated by a modified RPA primer pair. Seventy-eight samples were screened both by RT-RPA and real-time RT-PCR. The diagnostic sensitivity and specificity of the CHIKV RT-RPA assay were determined at 100%. Conclusions/Significance The developed RT-RPA assay represents a promising method for the molecular detection of CHIKV at point of need. PMID:27685649

  12. High Incidence of Chikungunya Virus and Frequency of Viremic Blood Donations during Epidemic, Puerto Rico, USA, 2014

    PubMed Central

    Brès, Vanessa; Lu, Kai; Liss, Nathan M.; Brambilla, Donald J.; Ryff, Kyle R.; Bruhn, Roberta; Velez, Edwin; Ocampo, Derrek; Linnen, Jeffrey M.; Latoni, Gerardo; Petersen, Lyle R.; Williamson, Phillip C.; Busch, Michael P.

    2016-01-01

    Chikungunya virus (CHIKV) caused large epidemics throughout the Caribbean in 2014. We conducted nucleic acid amplification testing (NAAT) for CHIKV RNA (n = 29,695) and serologic testing for IgG against CHIKV (n = 1,232) in archived blood donor samples collected during and after an epidemic in Puerto Rico in 2014. NAAT yields peaked in October with 2.1% of donations positive for CHIKV RNA. A total of 14% of NAAT-reactive donations posed a high risk for virus transmission by transfusion because of high virus RNA copy numbers (104–109 RNA copies/mL) and a lack of specific IgM and IgG responses. Testing of minipools of 16 donations would not have detected 62.5% of RNA-positive donations detectable by individual donor testing, including individual donations without IgM and IgG. Serosurveys before and after the epidemic demonstrated that nearly 25% of blood donors in Puerto Rico acquired CHIKV infections and seroconverted during the epidemic. PMID:27070192

  13. Exposure of Epitope Residues on the Outer Face of the Chikungunya Virus Envelope Trimer Determines Antibody Neutralizing Efficacy

    PubMed Central

    Fong, Rachel H.; Banik, Soma S. R.; Mattia, Kimberly; Barnes, Trevor; Tucker, David; Liss, Nathan; Lu, Kai; Selvarajah, Suganya; Srinivasan, Surabhi; Mabila, Manu; Miller, Adam; Muench, Marcus O.; Michault, Alain; Rucker, Joseph B.; Paes, Cheryl; Simmons, Graham; Kahle, Kristen M.

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a reemerging alphavirus that causes a debilitating arthritic disease and infects millions of people and for which no specific treatment is available. Like many alphaviruses, the structural targets on CHIKV that elicit a protective humoral immune response in humans are poorly defined. Here we used phage display against virus-like particles (VLPs) to isolate seven human monoclonal antibodies (MAbs) against the CHIKV envelope glycoproteins E2 and E1. One MAb, IM-CKV063, was highly neutralizing (50% inhibitory concentration, 7.4 ng/ml), demonstrated high-affinity binding (320 pM), and was capable of therapeutic and prophylactic protection in multiple animal models up to 24 h postexposure. Epitope mapping using a comprehensive shotgun mutagenesis library of 910 mutants with E2/E1 alanine mutations demonstrated that IM-CKV063 binds to an intersubunit conformational epitope on domain A, a functionally important region of E2. MAbs against the highly conserved fusion loop have not previously been reported but were also isolated in our studies. Fusion loop MAbs were broadly cross-reactive against diverse alphaviruses but were nonneutralizing. Fusion loop MAb reactivity was affected by temperature and reactivity conditions, suggesting that the fusion loop is hidden in infectious virions. Visualization of the binding sites of 15 different MAbs on the structure of E2/E1 revealed that all epitopes are located at the membrane-distal region of the E2/E1 spike. Interestingly, epitopes on the exposed topmost and outer surfaces of the E2/E1 trimer structure were neutralizing, whereas epitopes facing the interior of the trimer were not, providing a rationale for vaccine design and therapeutic MAb development using the intact CHIKV E2/E1 trimer. IMPORTANCE CHIKV is the most important alphavirus affecting humans, resulting in a chronic arthritic condition that can persist for months or years. In recent years, millions of people have been infected

  14. Investigation Into an Outbreak of Dengue-like Illness in Pernambuco, Brazil, Revealed a Cocirculation of Zika, Chikungunya, and Dengue Virus Type 1.

    PubMed

    Pessôa, Rodrigo; Patriota, João Veras; Lourdes de Souza, Maria de; Felix, Alvina Clara; Mamede, Nubia; Sanabani, Sabri S

    2016-03-01

    In April 2015, an outbreak of dengue-like illness occurred in Tuparetama, a small city in the northeast region of Brazil; this outbreak was characterized by its fast expansion. An investigation was initiated to identify the viral etiologies and advise the health authorities on implementing control measures to contain the outbreak. This is the first report of this outbreak in the northeast, even though a few cases were documented earlier in a neighboring city.Plasma samples were obtained from 77 suspected dengue patients attending the main hospital in the city. Laboratory assays, such as real-time reverse transcription polymerase chain reaction, virus cDNA sequencing, and enzyme-linked immunosorbent assay, were employed to identify the infecting virus and molecular phylogenetic analysis was performed to define the circulating viral genotypes.RNA of Zika virus (ZIKV) and Dengue virus (DENV) or IgM antibodies (Abs) to DENV or chikungunya (CHIKV) were detected in 40 of the 77 plasma samples (51.9%). DENV was found in 9 patients (11.7%), ZIKV was found in 31 patients (40.2%), CHIKV in 1 patient (1.3%), and coinfection of DENV and ZIKV was detected in 2 patients (2.6%). The phylogenetic analysis of 2 available partial DENV and 14 ZIKV sequences revealed the identities of genotype 1 and the Asiatic lineage, respectively.Consistent with recent reports from the same region, our results showed that the ongoing outbreak is caused by ZIKV, DENV, and CHIKV. This emphasizes the need for a routine and differential diagnosis of arboviruses in patients with dengue-like illness. Coordinated efforts are necessary to contain the outbreak. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies.

  15. Investigation Into an Outbreak of Dengue-like Illness in Pernambuco, Brazil, Revealed a Cocirculation of Zika, Chikungunya, and Dengue Virus Type 1

    PubMed Central

    Pessôa, Rodrigo; Patriota, João Veras; de Lourdes de Souza, Maria; Felix, Alvina Clara; Mamede, Nubia; Sanabani, Sabri S.

    2016-01-01

    Abstract In April 2015, an outbreak of dengue-like illness occurred in Tuparetama, a small city in the northeast region of Brazil; this outbreak was characterized by its fast expansion. An investigation was initiated to identify the viral etiologies and advise the health authorities on implementing control measures to contain the outbreak. This is the first report of this outbreak in the northeast, even though a few cases were documented earlier in a neighboring city. Plasma samples were obtained from 77 suspected dengue patients attending the main hospital in the city. Laboratory assays, such as real-time reverse transcription polymerase chain reaction, virus cDNA sequencing, and enzyme-linked immunosorbent assay, were employed to identify the infecting virus and molecular phylogenetic analysis was performed to define the circulating viral genotypes. RNA of Zika virus (ZIKV) and Dengue virus (DENV) or IgM antibodies (Abs) to DENV or chikungunya (CHIKV) were detected in 40 of the 77 plasma samples (51.9%). DENV was found in 9 patients (11.7%), ZIKV was found in 31 patients (40.2%), CHIKV in 1 patient (1.3%), and coinfection of DENV and ZIKV was detected in 2 patients (2.6%). The phylogenetic analysis of 2 available partial DENV and 14 ZIKV sequences revealed the identities of genotype 1 and the Asiatic lineage, respectively. Consistent with recent reports from the same region, our results showed that the ongoing outbreak is caused by ZIKV, DENV, and CHIKV. This emphasizes the need for a routine and differential diagnosis of arboviruses in patients with dengue-like illness. Coordinated efforts are necessary to contain the outbreak. Continued surveillance will be important to assess the effectiveness of current and future prevention strategies. PMID:27015222

  16. A polarized cell model for Chikungunya virus infection: entry and egress of virus occurs at the apical domain of polarized cells.

    PubMed

    Lim, Pei Jin; Chu, Justin Jang Hann

    2014-02-01

    Chikungunya virus (CHIKV) has resulted in several outbreaks in the past six decades. The clinical symptoms of Chikungunya infection include fever, skin rash, arthralgia, and an increasing incidence of encephalitis. The re-emergence of CHIKV with more severe pathogenesis highlights its potential threat on our human health. In this study, polarized HBMEC, polarized Vero C1008 and non-polarized Vero cells grown on cell culture inserts were infected with CHIKV apically or basolaterally. Plaque assays, viral binding assays and immunofluorescence assays demonstrated apical entry and release of CHIKV in polarized HBMEC and Vero C1008. Drug treatment studies were performed to elucidate both host cell and viral factors involved in the sorting and release of CHIKV at the apical domain of polarized cells. Disruption of host cell myosin II, microtubule and microfilament networks did not disrupt the polarized release of CHIKV. However, treatment with tunicamycin resulted in a bi-directional release of CHIKV, suggesting that N-glycans of CHIKV envelope glycoproteins could serve as apical sorting signals. PMID:24587455

  17. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection

    PubMed Central

    Delang, L.; Li, C.; Tas, A.; Quérat, G.; Albulescu, I. C.; De Burghgraeve, T.; Guerrero, N. A. Segura; Gigante, A.; Piorkowski, G.; Decroly, E.; Jochmans, D.; Canard, B.; Snijder, E. J.; Pérez-Pérez, M. J.; van Hemert, M. J.; Coutard, B.; Leyssen, P.; Neyts, J.

    2016-01-01

    The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections. PMID:27545976

  18. The viral capping enzyme nsP1: a novel target for the inhibition of chikungunya virus infection.

    PubMed

    Delang, L; Li, C; Tas, A; Quérat, G; Albulescu, I C; De Burghgraeve, T; Guerrero, N A Segura; Gigante, A; Piorkowski, G; Decroly, E; Jochmans, D; Canard, B; Snijder, E J; Pérez-Pérez, M J; van Hemert, M J; Coutard, B; Leyssen, P; Neyts, J

    2016-01-01

    The chikungunya virus (CHIKV) has become a substantial global health threat due to its massive re-emergence, the considerable disease burden and the lack of vaccines or therapeutics. We discovered a novel class of small molecules ([1,2,3]triazolo[4,5-d]pyrimidin-7(6H)-ones) with potent in vitro activity against CHIKV isolates from different geographical regions. Drug-resistant variants were selected and these carried a P34S substitution in non-structural protein 1 (nsP1), the main enzyme involved in alphavirus RNA capping. Biochemical assays using nsP1 of the related Venezuelan equine encephalitis virus revealed that the compounds specifically inhibit the guanylylation of nsP1. This is, to the best of our knowledge, the first report demonstrating that the alphavirus capping machinery is an excellent antiviral drug target. Considering the lack of options to treat CHIKV infections, this series of compounds with their unique (alphavirus-specific) target offers promise for the development of therapy for CHIKV infections. PMID:27545976

  19. Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff.

    PubMed

    White, Laura K; Sali, Tina; Alvarado, David; Gatti, Evelina; Pierre, Philippe; Streblow, Daniel; Defilippis, Victor R

    2011-01-01

    Chikungunya virus (CHIKV) is an arthritogenic mosquito-transmitted alphavirus that is undergoing reemergence in areas around the Indian Ocean. Despite the current and potential danger posed by this virus, we know surprisingly little about the induction and evasion of CHIKV-associated antiviral immune responses. With this in mind we investigated innate immune reactions to CHIKV in human fibroblasts, a demonstrable in vivo target of virus replication and spread. We show that CHIKV infection leads to activation of the transcription factor interferon regulatory factor 3 (IRF3) and subsequent transcription of IRF3-dependent antiviral genes, including beta interferon (IFN-β). IRF3 activation occurs by way of a virus-induced innate immune signaling pathway that includes the adaptor molecule interferon promoter stimulator 1 (IPS-1). Despite strong transcriptional upregulation of these genes, however, translation of the corresponding proteins is not observed. We further demonstrate that translation of cellular (but not viral) genes is blocked during infection and that although CHIKV is found to trigger inactivation of the translational molecule eukaryotic initiation factor subunit 2α by way of the double-stranded RNA sensor protein kinase R, this response is not required for the block to protein synthesis. Furthermore, overall diminution of cellular RNA synthesis is also observed in the presence of CHIKV and transcription of IRF3-dependent antiviral genes appears specifically blocked late in infection. We hypothesize that the observed absence of IFN-β and antiviral proteins during infection results from an evasion mechanism exhibited by CHIKV that is dependent on widespread shutoff of cellular protein synthesis and a targeted block to late synthesis of antiviral mRNA transcripts.

  20. Chikungunya fever presenting with protracted severe pruritus.

    PubMed

    Cunha, Burke A; Leonichev, Victoria B; Raza, Muhammad

    2016-01-01

    Travelers returning from the tropics often present with rash/fever. Those with rash/fever and myalgias/arthralgias are most likely due to chikungunya fever, dengue fever, or Zika virus. In these arthropod viral transmitted infections, the rash may be pruritic. The case presented here is that of chikungunya fever remarkable for the intensity and duration of her pruritis.

  1. Dengue and Chikungunya Vector Control Pocket Guide

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This technical guide consolidates information and procedures for surveillance and control of mosquitoes that transmit dengue and chikungunya viruses. The guide focuses on mosquitoes that transmit dengue but also makes reference to chikungunya and yellow fever because the pathogens that cause these ...

  2. Chikungunya fever presenting with protracted severe pruritus.

    PubMed

    Cunha, Burke A; Leonichev, Victoria B; Raza, Muhammad

    2016-01-01

    Travelers returning from the tropics often present with rash/fever. Those with rash/fever and myalgias/arthralgias are most likely due to chikungunya fever, dengue fever, or Zika virus. In these arthropod viral transmitted infections, the rash may be pruritic. The case presented here is that of chikungunya fever remarkable for the intensity and duration of her pruritis. PMID:27679755

  3. Short Report: A Comparative Study of Clinical Features between Monotypic and Dual Infection Cases with Chikungunya Virus and Dengue Virus in West Bengal, India

    PubMed Central

    Sarkar, Arindam; Mukhopadhyay, Bansi B.; Chatterjee, Shyamalendu

    2012-01-01

    Chikungunya virus (CHIKV) and dengue virus (DENV) are circulating individually in the state of West Bengal, India. However, after 1965 the dual-infection caused by both viruses had not been recorded until 2010. In 2010, an investigation of the febrile cases was carried out to confirm the involvement of both viruses simultaneously. A total of 550 blood samples were tested for the detection of immunoglobulin M (IgM) antibody against both CHIKV and DENV. Serology by the enzyme-linked immunosorbent assay method confirmed that 131 (23.8%) and 104 (18.9%) patients had IgM antibody against CHIKV and DENV, respectively, whereas 68 (12.4%) had IgM antibodies against both CHIKV and DENV. Fever, joint pain, rashes, headache, myalgia, and nausea/vomiting are the common features in the case of both monotypic and dual-infection. Severe arthralgia and swelling of joints were common only in CHIKV-positive cases and abdominal pain was mainly associated with DENV infection. Diarrhea was reported only by the dual-infected patients (16.2%). PMID:22492160

  4. A comparative study of clinical features between monotypic and dual infection cases with Chikungunya virus and dengue virus in West Bengal, India.

    PubMed

    Taraphdar, Debjani; Sarkar, Arindam; Mukhopadhyay, Bansi B; Chatterjee, Shyamalendu

    2012-04-01

    Chikungunya virus (CHIKV) and dengue virus (DENV) are circulating individually in the state of West Bengal, India. However, after 1965 the dual-infection caused by both viruses had not been recorded until 2010. In 2010, an investigation of the febrile cases was carried out to confirm the involvement of both viruses simultaneously. A total of 550 blood samples were tested for the detection of immunoglobulin M (IgM) antibody against both CHIKV and DENV. Serology by the enzyme-linked immunosorbent assay method confirmed that 131 (23.8%) and 104 (18.9%) patients had IgM antibody against CHIKV and DENV, respectively, whereas 68 (12.4%) had IgM antibodies against both CHIKV and DENV. Fever, joint pain, rashes, headache, myalgia, and nausea/vomiting are the common features in the case of both monotypic and dual-infection. Severe arthralgia and swelling of joints were common only in CHIKV-positive cases and abdominal pain was mainly associated with DENV infection. Diarrhea was reported only by the dual-infected patients (16.2%).

  5. Comparing dengue and chikungunya emergence and endemic transmission in A. aegypti and A. albopictus.

    PubMed

    Manore, Carrie A; Hickmann, Kyle S; Xu, Sen; Wearing, Helen J; Hyman, James M

    2014-09-01

    Chikungunya and dengue are re-emerging mosquito-borne infectious diseases that are of increasing concern as human travel and expanding mosquito ranges increase the risk of spread. We seek to understand the differences in transient and endemic behavior of chikungunya and dengue; risk of emergence for different virus-vector assemblages; and the role that virus evolution plays in disease dynamics and risk. To address these questions, we adapt a mathematical mosquito-borne disease model to chikungunya and dengue in Aedes aegypti and Aedes albopictus mosquitoes. We derive analytical threshold conditions and important dimensionless parameters for virus transmission; perform sensitivity analysis on quantities of interest such as the basic reproduction number, endemic equilibrium, and first epidemic peak; and compute distributions for the quantities of interest across parameter ranges. We found that chikungunya and dengue exhibit different transient dynamics and long-term endemic levels. While the order of most sensitive parameters is preserved across vector-virus combinations, the magnitude of sensitivity is different across scenarios, indicating that risk of invasion or an outbreak can change with vector-virus assemblages. We found that the dengue - A. aegypti and new Rèunion strain of chikungunya - A. albopictus systems represent the highest risk across the range of parameters considered. These results inform future experimental and field research efforts and point toward effective mitigation strategies adapted to each disease. PMID:24801860

  6. Comparing dengue and chikungunya emergence and endemic transmission in A. aegypti and A. albopictus.

    PubMed

    Manore, Carrie A; Hickmann, Kyle S; Xu, Sen; Wearing, Helen J; Hyman, James M

    2014-09-01

    Chikungunya and dengue are re-emerging mosquito-borne infectious diseases that are of increasing concern as human travel and expanding mosquito ranges increase the risk of spread. We seek to understand the differences in transient and endemic behavior of chikungunya and dengue; risk of emergence for different virus-vector assemblages; and the role that virus evolution plays in disease dynamics and risk. To address these questions, we adapt a mathematical mosquito-borne disease model to chikungunya and dengue in Aedes aegypti and Aedes albopictus mosquitoes. We derive analytical threshold conditions and important dimensionless parameters for virus transmission; perform sensitivity analysis on quantities of interest such as the basic reproduction number, endemic equilibrium, and first epidemic peak; and compute distributions for the quantities of interest across parameter ranges. We found that chikungunya and dengue exhibit different transient dynamics and long-term endemic levels. While the order of most sensitive parameters is preserved across vector-virus combinations, the magnitude of sensitivity is different across scenarios, indicating that risk of invasion or an outbreak can change with vector-virus assemblages. We found that the dengue - A. aegypti and new Rèunion strain of chikungunya - A. albopictus systems represent the highest risk across the range of parameters considered. These results inform future experimental and field research efforts and point toward effective mitigation strategies adapted to each disease.

  7. Comparing dengue and chikungunya emergence and endemic transmission in A. aegypti and A. albopictus

    PubMed Central

    Manore, Carrie A.; Hickmann, Kyle S.; Xu, Sen; Wearing, Helen J.; Hyman, James M.

    2014-01-01

    Chikungunya and dengue are re-emerging mosquito-borne infectious diseases that are of increasing concern as human travel and expanding mosquito ranges increase the risk of spread. We seek to understand the differences in transient and endemic behavior of chikungunya and dengue; risk of emergence for different virus-vector assemblages; and the role that virus evolution plays in disease dynamics and risk. To address these questions, we adapt a mathematical mosquito-borne disease model to chikungunya and dengue in Aedes aegypti and Aedes albopictus mosquitoes. We derive analytical threshold conditions and important dimensionless parameters for virus transmission; perform sensitivity analysis on quantities of interest such as the basic reproduction number, endemic equilibrium, and first epidemic peak; and compute distributions for the quantities of interest across parameter ranges. We found that chikungunya and dengue exhibit different transient dynamics and long-term endemic levels. While the order of most sensitive parameters is preserved across vector-virus combinations, the magnitude of sensitivity is different across scenarios, indicating that risk of invasion or an outbreak can change with vector-virus assemblages. We found that the dengue-A. aegypti and new Rèunion strain of chikungunya-A. albopictus systems represent the highest risk across the range of parameters considered. These results inform future experimental and field research efforts and point toward effective mitigation strategies adapted to each disease. PMID:24801860

  8. Neurovirulence comparison of chikungunya virus isolates of the Asian and East/Central/South African genotypes from Malaysia.

    PubMed

    Chiam, Chun Wei; Chan, Yoke Fun; Ong, Kien Chai; Wong, Kum Thong; Sam, I-Ching

    2015-11-01

    Chikungunya virus (CHIKV), an alphavirus of the family Togaviridae, causes fever, polyarthritis and rash. There are three genotypes: West African, Asian and East/Central/South African (ECSA). The latter two genotypes have caused global outbreaks in recent years. Recent ECSA CHIKV outbreaks have been associated with severe neurological disease, but it is not known if different CHIKV genotypes are associated with different neurovirulence. In this study, the neurovirulence of Asian (MY/06/37348) and ECSA (MY/08/065) strains of CHIKV isolated in Malaysia were compared. Intracerebral inoculation of either virus into suckling mice was followed by virus titration, histopathology and gene expression analysis of the harvested brains. Both strains of CHIKV replicated similarly, yet mice infected with MY/06/37348 showed higher mortality. Histopathology findings showed that both CHIKV strains spread within the brain (where CHIKV antigen was localized to astrocytes and neurons) and beyond to skeletal muscle. In MY/06/37348-infected mice, apoptosis, which is associated with neurovirulence in alphaviruses, was observed earlier in brains. Comparison of gene expression showed that a pro-apoptotic gene (eIF2αK2) was upregulated at higher levels in MY/06/37348-infected mice, while genes involved in anti-apoptosis (BIRC3), antiviral responses and central nervous system protection (including CD40, IL-10RA, MyD88 and PYCARD) were upregulated more highly in MY/08/065-infected mice. In conclusion, the higher mortality observed following MY/06/37348 infection in mice is due not to higher viral replication in the brain, but to differentially expressed genes involved in host immune responses. These findings may help to identify therapeutic strategies and biomarkers for neurological CHIKV infections.

  9. Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus.

    PubMed

    Abraham, Rachy; Manakkadan, Anoop; Mudaliar, Prashant; Joseph, Iype; Sivakumar, Krishnankutty Chandrika; Nair, Radhakrishnan Reghunathan; Sreekumar, Easwaran

    2016-01-01

    Cosmopolitan genotypes of Chikungunya virus caused the large-scale febrile disease outbreaks in the last decade in Asian and African continents. Molecular analyses of these strains had revealed significant genetic diversification and occurrence of novel mosquito-adaptive mutations. In the present study we looked into whether the genetic diversification has implications in the infectivity phenotype. A detailed sequence and phylogenetic analyses of these virus strains of Indian Ocean lineage from Kerala, South India from the years 2008 to 2013 identified three distinct genetic clades (I, II and III), which had presence of clade-specific amino acid changes. The E2 envelope protein of the strains from the years 2012 to 2013 had a K252Q or a novel K252H change. This site is reported to affect mosquito cell infectivity. Most of these strains also had the E2 G82R mutation, a mutation previously identified to increase mammalian cell infectivity, and a novel mutation E2 N72S. Positive selection was identified in four sites in the envelope proteins (E1 K211E, A226V and V291I; E2 K252Q/H). In infectivity analysis, we found that strains from clade III had enhanced cytopathogenicity in HEK293 and Vero cells than by strains representing other two clades. These two strains formed smaller sized plaques and had distinctly higher viral protein expression, infectious virus production and apoptosis induction in HEK293 cells. They had novel mutations R171Q in the nsP1; I539S in nsP2; N409T in nsP3; and N72S in E2. Our study identifies a correlation between phylogenetic clade diversification and differences in mammalian cell infectivity phenotype among Cosmopolitan genotype CHIKV strains.

  10. A Sensitive and Robust High-Throughput Screening Assay for Inhibitors of the Chikungunya Virus nsP1 Capping Enzyme

    PubMed Central

    Bullard-Feibelman, Kristen M.; Fuller, Benjamin P.; Geiss, Brian J.

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus that causes severe and debilitating disease symptoms. Alarmingly, transmission rates of CHIKV have increased dramatically over the last decade resulting in 1.7 million suspected cases in the Western hemisphere alone. There are currently no antivirals for treatment of CHIKV infection and novel anti-alphaviral compounds are badly needed. nsP1 is the alphavirus protein responsible for the methyltransferase and guanylyltransferase activities necessary for formation of the 5’ type 0 cap structure added to newly formed viral RNA. Formation of this cap depends on nsP1 binding GTP and transferring a methylated GMP to nascent viral RNA. We have developed a fluorescence polarization-based assay that monitors displacement of a fluorescently-labeled GTP analog in real time. Determining the relative affinities of 15 GTP analogs for nsP1 GTP revealed important structural aspects of GTP that will inform identification of inhibitors able to outcompete GTP for the nsP1 binding site. Validation of the assay for HTS was completed and a secondary orthogonal assay that measures guanylation activity was developed in order to evaluate hits from future drug screens. This platform provides an avenue for identification of potent nsP1 inhibitors, which would potentially provide compounds capable of treating disease caused by CHIKV infection. PMID:27427769

  11. Antiviral Phosphorodiamidate Morpholino Oligomers are Protective against Chikungunya Virus Infection on Cell-based and Murine Models.

    PubMed

    Lam, Shirley; Chen, Huixin; Chen, Caiyun Karen; Min, Nyo; Chu, Justin Jang Hann

    2015-07-30

    Chikungunya virus (CHIKV) infection in human is associated with debilitating and persistent arthralgia and arthritis. Currently, there is no specific vaccine or effective antiviral available. Anti-CHIKV Phosphorodiamidate Morpholino Oligomer (CPMO) was evaluated for its antiviral efficacy and cytotoxcity in human cells and neonate murine model. Two CPMOs were designed to block translation initiation of a highly conserved sequence in CHIKV non-structural and structural polyprotein, respectively. Pre-treatment of HeLa cells with CPMO1 significantly suppressed CHIKV titre, CHIKV E2 protein expression and prevented CHIKV-induced CPE. CPMO1 activity was also CHIKV-specific as shown by the lack of cross-reactivity against SINV or DENV replication. When administered prophylactically in neonate mice, 15 μg/g CPMO1v conferred 100% survival against CHIKV disease. In parallel, these mice demonstrated significant reduction in viremia and viral load in various tissues. Immunohistological examination of skeletal muscles and liver of CPMO1v-treated mice also showed healthy tissue morphology, in contrast to evident manifestation of CHIKV pathogenesis in PBS- or scrambled sCPMO1v-treated groups. Taken together, our findings highlight for the first time that CPMO1v has strong protective effect against CHIKV infection. This warrants future development of morpholino as an alternative antiviral agent to address CHIKV infection in clinical applications.

  12. Stress Granule Components G3BP1 and G3BP2 Play a Proviral Role Early in Chikungunya Virus Replication

    PubMed Central

    Scholte, Florine E. M.; Tas, Ali; Albulescu, Irina C.; Žusinaite, Eva; Merits, Andres; Snijder, Eric J.

    2015-01-01

    ABSTRACT Stress granules (SGs) are protein-mRNA aggregates that are formed in response to environmental stresses, resulting in translational inhibition. SGs are generally believed to play an antiviral role and are manipulated by many viruses, including various alphaviruses. GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1) is a key component and commonly used marker of SGs. Its homolog G3BP2 is a less extensively studied SG component. Here, we demonstrate that Chikungunya virus (CHIKV) infection induces cytoplasmic G3BP1- and G3BP2-containing granules that differ from bona fide SGs in terms of morphology, composition, and behavior. For several Old World alphaviruses it has been shown that nonstructural protein 3 (nsP3) interacts with G3BPs, presumably to inhibit SG formation, and we have confirmed this interaction in CHIKV-infected cells. Surprisingly, CHIKV also relied on G3BPs for efficient replication, as simultaneous depletion of G3BP1 and G3BP2 reduced viral RNA levels, CHIKV protein expression, and viral progeny titers. The G3BPs colocalized with CHIKV nsP2 and nsP3 in cytoplasmic foci, but no colocalization with nsP1, nsP4, or dsRNA was observed. Furthermore, G3BPs could not be detected in a cellular fraction enriched for CHIKV replication/transcription complexes, suggesting that they are not directly involved in CHIKV RNA synthesis. Depletion of G3BPs did not affect viral entry, translation of incoming genomes, or nonstructural polyprotein processing but resulted in severely reduced levels of negative-stranded (and consequently also positive-stranded) RNA. This suggests a role for the G3BPs in the switch from translation to genome amplification, although the exact mechanism by which they act remains to be explored. IMPORTANCE Chikungunya virus (CHIKV) causes a severe polyarthritis that has affected millions of people since its reemergence in 2004. The lack of approved vaccines or therapeutic options and the ongoing explosive outbreak in the

  13. Rapid and Real-Time Detection of Chikungunya Virus by Reverse Transcription Loop-Mediated Isothermal Amplification Assay▿

    PubMed Central

    Parida, M. M.; Santhosh, S. R.; Dash, P. K.; Tripathi, N. K.; Lakshmi, V.; Mamidi, N.; Shrivastva, A.; Gupta, N.; Saxena, P.; Babu, J. Pradeep; Rao, P. V. Lakshmana; Morita, Kouichi

    2007-01-01

    The standardization and validation of a one-step, single-tube, accelerated, quantitative reverse transcription (RT) loop-mediated isothermal amplification (RT-LAMP) assay targeting the E1 gene for the rapid and real-time detection of Chikungunya virus (CHIKV) are reported. A linear relationship between the amount of template and time of positivity value over a range of 2 × 108 to 2 × 102 copies was obtained. The feasibility of CHIKV RT-LAMP for clinical diagnosis was validated with patient serum samples from an ongoing epidemic in Southern India. Optimal assay conditions with zero background were established for the detection of low levels of CHIKV in acute-phase patient serum samples. The comparative evaluation of the RT-LAMP assay with acute-phase patient serum samples demonstrated exceptionally higher sensitivity by correctly identifying 21 additional positive borderline cases that were missed by conventional RT-PCR (P < 0.0001) with a detection limit of 20 copies. The quantification of virus load in patient serum samples was also determined from the standard curve based on their time of positivity and was found to be in the range of 2 × 108 to 2 × 101 copies. In addition, the field applicability of the RT-LAMP assay was also demonstrated by standardizing SYBR Green I-based RT-LAMP wherein the amplification was carried out in a water bath at 63°C for 60 min, which was followed by monitoring gene amplification with the naked eye through color changes. These findings demonstrated that the RT-LAMP assay is a valuable tool for rapid, real-time detection as well as quantification of CHIKV in acute-phase serum samples without requiring any sophisticated equipment and has potential usefulness for clinical diagnosis and surveillance of CHIKV in developing countries. PMID:17135444

  14. Chikungunya: a review.

    PubMed

    Jain, Manisha; Rai, Sumit; Chakravarti, Anita

    2008-04-01

    The Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus, which causes epidemics of fever, rash and polyarthralgia in Africa and Asia. First isolated in 1953 in Tanzania, CHIKV has caused numerous well-documented outbreaks and epidemics in both Africa and South-East Asia. The epidemic of Chikungunya fever that affected the population of La Reunion at Christmas in 2005 will be remembered as the most serious public health crises in the island's history. A widely circulating mutant CHIKV is a possible explanation for the epidemiological pattern of the disease in this region. In this review, we have tried to give the latest information about the present outbreak and have tried to analyse the possible reasons for the same.

  15. A case of ADEM following Chikungunya fever.

    PubMed

    Maity, Pranab; Roy, Pinaki; Basu, Arindam; Das, Biman; Ghosh, U S

    2014-05-01

    Chikungunya most often is a self-limiting febrile illness with polyarthritis and the virus is not known to be neurotropic. We are reporting a case of chikugunya fever presenting as acute demyelinating encephalomyelitis(ADEM) which is very rare.

  16. Chikungunya: Information for the General Public

    MedlinePlus

    ... 7 days after being bitten by an infected mosquito • The most common symptoms are fever and severe ... to prevent chikungunya virus infection or disease • Reduce mosquito exposure o Use air conditioning or window/door ...

  17. Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

    PubMed Central

    Chua, Chong-Long; Sam, I-Ching; Merits, Andres; Chan, Yoke-Fun

    2016-01-01

    Background Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood. Methodology/Principal Findings We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008–2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes. Conclusion/Significance Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued

  18. Identification of Novel Compounds Inhibiting Chikungunya Virus-Induced Cell Death by High Throughput Screening of a Kinase Inhibitor Library

    PubMed Central

    Gomes, Rafael G. B.; da Silva, Camila T.; Taniguchi, Juliana B.; No, Joo Hwan; Lombardot, Benoit; Schwartz, Olivier; Hansen, Michael A. E.; Freitas-Junior, Lucio H.

    2013-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne arthrogenic alphavirus that causes acute febrile illness in humans accompanied by joint pains and in many cases, persistent arthralgia lasting weeks to years. The re-emergence of CHIKV has resulted in numerous outbreaks in the eastern hemisphere, and threatens to expand in the foreseeable future. Unfortunately, no effective treatment is currently available. The present study reports the use of resazurin in a cell-based high-throughput assay, and an image-based high-content assay to identify and characterize inhibitors of CHIKV-infection in vitro. CHIKV is a highly cytopathic virus that rapidly kills infected cells. Thus, cell viability of HuH-7 cells infected with CHIKV in the presence of compounds was determined by measuring metabolic reduction of resazurin to identify inhibitors of CHIKV-associated cell death. A kinase inhibitor library of 4,000 compounds was screened against CHIKV infection of HuH-7 cells using the resazurin reduction assay, and the cell toxicity was also measured in non-infected cells. Seventy-two compounds showing ≥50% inhibition property against CHIKV at 10 µM were selected as primary hits. Four compounds having a benzofuran core scaffold (CND0335, CND0364, CND0366 and CND0415), one pyrrolopyridine (CND0545) and one thiazol-carboxamide (CND3514) inhibited CHIKV-associated cell death in a dose-dependent manner, with EC50 values between 2.2 µM and 7.1 µM. Based on image analysis, these 6 hit compounds did not inhibit CHIKV replication in the host cell. However, CHIKV-infected cells manifested less prominent apoptotic blebs typical of CHIKV cytopathic effect compared with the control infection. Moreover, treatment with these compounds reduced viral titers in the medium of CHIKV-infected cells by up to 100-fold. In conclusion, this cell-based high-throughput screening assay using resazurin, combined with the image-based high content assay approach identified compounds against CHIKV having a novel

  19. A Novel 2006 Indian Outbreak Strain of Chikungunya Virus Exhibits Different Pattern of Infection as Compared to Prototype Strain

    PubMed Central

    Das, Indrani; Nayak, Tapas K.; Kumar, Sameer; Chhatai, Jagamohan; Chattopadhyay, Subhasis; Suryawanshi, Amol R.; Chattopadhyay, Soma

    2014-01-01

    Background The recent re-emergence of Chikungunya virus (CHIKV) in India after 32 years and its worldwide epidemics with unprecedented magnitude raised a great public health concern. Methods and Findings In this study, a biological comparison was carried out between a novel 2006 Indian CHIKV outbreak strain, DRDE-06 and the prototype strain S-27 in mammalian cells in order to understand their differential infection pattern. Results showed that S-27 produced maximum number of progenies (2.43E+06 PFU/ml) at 20 to 24 hours post infection whereas DRDE-06 produced more than double number of progenies around 8 hours post infection in mammalian cells. Moreover, the observation of cytopathic effect, detection of viral proteins and viral proliferation assay confirmed the remarkably faster and significantly higher replication efficiency of DRDE-06. Moreover, our mutational analysis of whole genome of DRDE-06 revealed the presence of nineteen mutations as compared to S-27, whereas the analysis of 273 global isolates showed the consistent presence of fifteen out of nineteen mutations in almost all outbreak isolates. Further analysis revealed that ∼46% of recent outbreak strains including DRDE-06 do not contain the E1-A226V mutation which was earlier shown to be associated with the adaptation of CHIKV in a new vector species, Aedes albopictus. Conclusions A novel 2006 Indian CHIKV outbreak strain, DRDE-06 exhibits different pattern of infection as compared to prototype strain, S-27. This might be associated to some specific mutations observed in genome wide mutational analysis in DRDE-06 which emphasizes the need of future experimental investigation. PMID:24465661

  20. ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

    PubMed Central

    Rohatgi, Anjali; Monte, Kristen J.; Michault, Alain; Arenzana-Seisdedos, Fernando; Vanlandingham, Dana L.; Higgs, Stephen; Fontanet, Arnaud

    2011-01-01

    Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection. PMID:22028657

  1. Versatile Trans-Replication Systems for Chikungunya Virus Allow Functional Analysis and Tagging of Every Replicase Protein

    PubMed Central

    Utt, Age; Quirin, Tania; Saul, Sirle; Hellström, Kirsi; Ahola, Tero; Merits, Andres

    2016-01-01

    Chikungunya virus (CHIKV; genus Alphavirus, family Togaviridae) has recently caused several major outbreaks affecting millions of people. There are no licensed vaccines or antivirals, and the knowledge of the molecular biology of CHIKV, crucial for development of efficient antiviral strategies, remains fragmentary. CHIKV has a 12 kb positive-strand RNA genome, which is translated to yield a nonstructural (ns) or replicase polyprotein. CHIKV structural proteins are expressed from a subgenomic RNA synthesized in infected cells. Here we have developed CHIKV trans-replication systems, where replicase expression and RNA replication are uncoupled. Bacteriophage T7 RNA polymerase or cellular RNA polymerase II were used for production of mRNAs for CHIKV ns polyprotein and template RNAs, which are recognized by CHIKV replicase and encode for reporter proteins. CHIKV replicase efficiently amplified such RNA templates and synthesized large amounts of subgenomic RNA in several cell lines. This system was used to create tagged versions of ns proteins including nsP1 fused with enhanced green fluorescent protein and nsP4 with an immunological tag. Analysis of these constructs and a matching set of replicon vectors revealed that the replicases containing tagged ns proteins were functional and maintained their subcellular localizations. When cells were co-transfected with constructs expressing template RNA and wild type or tagged versions of CHIKV replicases, formation of characteristic replicase complexes (spherules) was observed. Analysis of mutations associated with noncytotoxic phenotype in CHIKV replicons showed that a low level of RNA replication is not a pre-requisite for reduced cytotoxicity. The CHIKV trans-replicase does not suffer from genetic instability and represents an efficient, sensitive and reliable tool for studies of different aspects of CHIKV RNA replication process. PMID:26963103

  2. High rates of co-infection of Dengue and Chikungunya virus in Odisha and Maharashtra, India during 2013.

    PubMed

    Saswat, Tanuja; Kumar, Abhishek; Kumar, Sameer; Mamidi, Prabhudutta; Muduli, Sagarika; Debata, Nagen Kumar; Pal, Niladri Shekhar; Pratheek, B M; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-10-01

    Dengue viral (DENV) infection is endemic in different parts of India and because of similar primary signs and symptoms, Chikungunya virus (CHIKV) is mostly undiagnosed. Hence, we investigated 204 suspected Dengue cases in a hospital based cross-sectional study in Odisha, India in 2013. It was observed that 50 samples were positive for DENV only, 28 were positive for CHIKV only and interestingly, 28 patients were co-infected with both DENV and CHIKV. Additionally, a total of 18 confirmed Dengue samples from Maharashtra, India were screened for CHIKV and out of those, 15 were co-infected. All CHIKV strains were of East Central South African (ECSA) type and serotype 2 (genotype IV) was predominant in the DENV samples. Additionally, Dengue serotype 1 and 3 were also detected during this time. Further, sequence analysis of E1 gene of CHIKV strains revealed that two substitution mutations (M269V and D284E) were observed in almost 50% strains and they were from co-infected patients. Similarly, sequence analysis of C-prM gene showed the presence of five substitution mutations, (G70S, L72F, N90S, S93N and I150L) in all serotype 1 and two consistent mutations (A101V and V112A) in serotype 2 Dengue samples. Together, it appears that a significantly high number of dengue patients (43, 44.8%) were co-infected with DENV and CHIKV during this study. This emphasizes the need of a routine diagnosis of CHIKV along with DENV for febrile patients. This will be useful in early and proper recognition of infecting pathogen to study the correlation of clinical symptoms with single or co-infection which will ultimately help to implement proper patient care in future.

  3. Chikungunya fever outbreak, Bhutan, 2012.

    PubMed

    Wangchuk, Sonam; Chinnawirotpisan, Piyawan; Dorji, Tshering; Tobgay, Tashi; Dorji, Tandin; Yoon, In-Kyu; Fernandez, Stefan

    2013-10-01

    In 2012, chikungunya virus (CHIKV) was reported for the first time in Bhutan. IgM ELISA results were positive for 36/210 patient samples; PCR was positive for 32/81. Phylogenetic analyses confirmed that Bhutan CHIKV belongs to the East/Central/South African genotype. Appropriate responses to future outbreaks require a system of surveillance and improved laboratory capacity.

  4. Association of Oligoadenylate Synthetase Gene Cluster and DC-SIGN (CD209) Gene Polymorphisms with Clinical Symptoms in Chikungunya Virus Infection.

    PubMed

    Chaaithanya, Itta Krishna; Muruganandam, Nagarajan; Surya, Palani; Anwesh, Maile; Alagarasu, Kalichamy; Vijayachari, Paluru

    2016-01-01

    Biology and pathogenesis of chikungunya virus (CHIKV) are not clearly established. Host factors play an important role in determining the progression and severity of the disease. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) and OAS1 (rs1131454 and rs10774671), OAS2 (rs15895 and rs1732778), and OAS3 (rs2285932 and rs2072136) genes were investigated in 100 patients with CHIKV infection and 101 healthy controls to find out the association of these polymorphisms with CHIKV infection. To evaluate the association of OAS and CD209 gene polymorphisms with the presence or absence of disease symptoms in CHIKV-infected patients. DNA was extracted and typed using polymerase chain reaction followed by restriction fragment length polymorphism methods. Results revealed that the allele and genotype frequencies of OAS1, OAS3, and OAS2 gene polymorphisms were not different between healthy controls and CHIKV patients. The frequency of CD209 gene G/G genotype of rs4804803 was significantly higher in CHIKV patients compared to healthy controls (p = 0.046). The present study suggests that rs4804803 GG genotype of CD209 gene is associated with susceptibility to CHIKV infection. To conclude, the present preliminary study suggests that OAS gene cluster and CD209 gene polymorphisms influence the risk of developing clinical symptoms in CHIKV-infected patients. Further follow-up studies with a large number of samples are needed to assess the role of these genes in association with post-sequela symptoms observed in CHIKV patients. A detailed research is required in these directions to understand the biology behind CHIKV infection and disease severity.

  5. [The chikungunya epidemic in the Caribbean: implications for travellers and physicians].

    PubMed

    Cleton, Natalie B; Reusken, Chantal B E M; van Gorp, Eric C M

    2014-01-01

    In 2013, the first autochthonous cases of the chikungunya virus (CHIKV) were reported on the Caribbean island of Saint Martin. The chikungunya virus has since become endemic in the Caribbean due to autochthonous transmission. In the presence of fever and joint symptoms in any traveller returning from the Caribbean, CHIKV should be considered. Although symptoms resemble those of dengue fever, the course of chikungunya is milder. Chikungunya much more commonly causes chronic joint pain. Laboratory tests for the chikungunya virus may give false positive results due to cross reactions with closely related viruses, so taking a full disease and travel history from the patient is necessary in order to interpret these test results correctly. There is no specific treatment for the chikungunya virus. A correct diagnosis can prevent unnecessary additional tests and unjustified treatment. The chikungunya virus can be prevented by the use of insect-repelling substances, nets and air-conditioning.

  6. The Chikungunya Epidemic: A look at five cases

    PubMed Central

    Shiferaw, Bethel; Lam, Paul; Tuthill, Summer; Choudhry, Hira; Syed, Sarah; Ahmed, Shadab; Yasmin, Tabassum

    2015-01-01

    Chikungunya is an infection caused by the Chikungunya virus and transmitted by the bite of infected mosquito. The most common symptoms of Chikungunya virus infection are fever, joint pain or rash. Chikungunya virus outbreaks had been identified in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. In late 2013, the first local transmission of Chikungunya virus in the Americas was identified in Caribbean countries and territories. Chikungunya virus disease became a nationally notifiable condition in 2015. There is a threat that Chikungunya will continue to spread to new areas in the Americas. We describe 5 patients who presented to our hospital with Chikungunya infection, shortly after returning from endemic areas. Fever and travel history to endemic areas were documented in all of our cases. Skin rash, arthralgia and contact history were also reported by these patients. Persons with suspected Chikungunya infection should be counseled to avoid mosquito bites during illness to decrease the risk of local transmission. The transmitting mosquitos are present in the US, and limiting the viral spread is essential. In this report, we describe the clinical presentation, risk factors and laboratory tests of each patient, and attempt to ensure awareness on the risk of potential spread of the disease. PMID:26793467

  7. Chikungunya fever from Malaysia.

    PubMed

    Yamamoto, Kouta; Matumoto, Kentaro; Lim, Chang-Kweng; Moi, Meng Ling; Kotaki, Akira; Takasaki, Tomohiko

    2010-01-01

    An adult Malaysian woman returned to Japan from Kuala Lumpur and had onset of dengue fever-like symptoms including high fever, malaise and arthritis in early January 2009. Serum obtained on the following day was tested at the National Institute of Infectious Diseases in Tokyo, where it was determined to be positive for chikungunya virus (CHIKV) RNA. IgM antibody against CHIKV was negative on January 6 and sero-converted to be positive on January 14, confirming a recent CHIKV infection. Except for arthralgia, all her symptoms resolved uneventfully within 10 days.

  8. Dengue and chikungunya: long-distance spread and outbreaks in naïve areas.

    PubMed

    Rezza, Giovanni

    2014-12-01

    Mosquito-borne virus infections, such as dengue and chikungunya, are continuously expanding their geographical range. The dengue virus, which is known to be a common cause of febrile illness in tropical areas of the Old World, is now widespread in the Americas. In most affected areas, all the four dengue virus serotypes have circulated. Recently, small clusters of dengue have been identified also in Southern Europe during the hot season. The chikungunya virus, initially restricted to Central Africa, where is a common cause of sporadic cases or small outbreaks, and Asia, where it is used to cause large epidemics, has recently invaded new territories. After ravaging Indian Ocean Islands and the Indian subcontinent, CHIKV caused an outbreak in north-eastern Italy. Recently, chikungunya has reached the Caribbean, causing for the first time a large epidemic on the American continent. Although Aedes aegypti is the main vector of both viruses, Aedes albopictus, the Asian 'Tiger' mosquito, is now playing an increasingly important role, contributing to their spread in temperate climate areas. Hereby, we focus the attention on outbreaks of dengue and chikungunya occurring in previously disease-free areas and discuss factors associated with the long-distance spread of the vector-borne infections, such as mutations increasing viral fitness, climate change, urbanization, and globalization of humans and vectors. PMID:25491436

  9. Dengue and chikungunya: long-distance spread and outbreaks in naïve areas.

    PubMed

    Rezza, Giovanni

    2014-12-01

    Mosquito-borne virus infections, such as dengue and chikungunya, are continuously expanding their geographical range. The dengue virus, which is known to be a common cause of febrile illness in tropical areas of the Old World, is now widespread in the Americas. In most affected areas, all the four dengue virus serotypes have circulated. Recently, small clusters of dengue have been identified also in Southern Europe during the hot season. The chikungunya virus, initially restricted to Central Africa, where is a common cause of sporadic cases or small outbreaks, and Asia, where it is used to cause large epidemics, has recently invaded new territories. After ravaging Indian Ocean Islands and the Indian subcontinent, CHIKV caused an outbreak in north-eastern Italy. Recently, chikungunya has reached the Caribbean, causing for the first time a large epidemic on the American continent. Although Aedes aegypti is the main vector of both viruses, Aedes albopictus, the Asian 'Tiger' mosquito, is now playing an increasingly important role, contributing to their spread in temperate climate areas. Hereby, we focus the attention on outbreaks of dengue and chikungunya occurring in previously disease-free areas and discuss factors associated with the long-distance spread of the vector-borne infections, such as mutations increasing viral fitness, climate change, urbanization, and globalization of humans and vectors.

  10. [Imported Zika virus infection in the Netherlands].

    PubMed

    von Eije, Karin J; Schinkel, Janke; van den Kerkhof, J H C T Hans; Schreuder, Imke; de Jong, Menno D; Grobusch, Martin P; Goorhuis, Abraham

    2015-01-01

    Since mid-2015, a rapidly expanding outbreak of Zika virus infection is spreading across Latin America and the Caribbean. Although Zika virus infection usually causes only mild disease, the World Health Organization has declared the epidemiological association with the occurrence of congenital microcephaly and neurological complications a 'Public Health Emergency of International Concern' and urged the international community to mount a coordinated international response aimed to protect people at risk, especially pregnant women. In December 2015, the first case of imported Zika virus infection in the Netherlands was diagnosed in a returned traveler from Surinam. To date, more than 20 cases have been reported in The Netherlands, all imported from Surinam. We describe the epidemiology, clinical aspects, diagnostic challenges and the existing evidence to date that link Zika virus infection to complications.

  11. [[Virus-like particle-based immunoglobulin M capture enzyme-linked immunosorbent assay for the detection of IgM antibodies against Chikungunya virus].

    PubMed

    Li, Jian-dong; Zhang, Quan-fu; Zhang, Shuo; Li, Chuan; Liu, Qin-zhi; Liang, Mi-fang; Li, De-xin

    2014-11-01

    To establish a MacELISA method for the detection of IgM antibodies against Chikungunya virus (CHIKV), we prepared virus like particle (VLP) antigens of CHIKV using the whole structural protein C-E3-E2-6K-E1 encoding gene with a baculovirus expression system in Sf9 insect cells. The VLPs were purified and used to immunize Kunming mice. Then, polyclonal antibodies were purified from the samples of ascites with a protein G HiTrap SP column and labeled with horseradish peroxidase. A MacELISA method for the detection of IgM antibodies against CHIKV was assembled with goat anti-human IgM antibody, VLP antigens and an enzyme-labeled polyclonal antibody. The results were evaluated with a serum panel containing serum samples from laboratory-confirmed CHIK, HFRS patients, healthy donors, and commercially available CHIKV IgM as a quality control. It was shown that the MacELISA had a specificity of 99% (99/100), the coefficients of variation (CoV) within a plate were <10%, and the CoV of different ELISA plates in terms of the plate variation coefficient was <15%. A comparative analysis was performed to compare the current method against a commercial CHIKV IgM antibody detection kit for IIFA-IgM. The detection limit of MacELISA was significantly lower than that of the IIFA-IgM commercial kit (P< 0.0001). Here, we demonstrate that the VLP-based MacELISA is a promising tool for the early diagnosis and epidemiological investigation of CHIKV infection, with a high level of sensitivity and specificity for the detection of IgM antibodies against CHIKV.

  12. Construction of an infectious Chikungunya virus cDNA clone and stable insertion of mCherry reporter genes at two different sites.

    PubMed

    Kümmerer, Beate Mareike; Grywna, Klaus; Gläsker, Sabine; Wieseler, Janett; Drosten, Christian

    2012-09-01

    Chikungunya virus (CHIKV) has caused massive epidemics in the Indian Ocean region since 2005. It belongs to the genus Alphavirus and possesses a positive-stranded RNA genome of nearly 12 kb in size. To produce genetically modified viruses for the study of various aspects of the CHIKV life cycle, a reverse genetic system is needed. We report the generation of a T7 RNA polymerase-driven infectious cDNA clone of CHIKV. Electroporation of in vitro-transcribed RNA resulted in the recovery of a recombinant virus with growth characteristics comparable to the parental strain. Using the established cDNA clone, the red fluorescent marker gene mCherry was introduced into two different sites within the CHIKV nsP3 gene. Both constructs allowed the rescue of stable fluorescent reporter viruses with growth characteristics similar to the wild-type virus. The latter reporter viruses represent valuable tools for easy follow-up of replicating CHIKV useful in several applications of CHIKV research. PMID:22673932

  13. Inhibition of chikungunya virus by picolinate that targets viral capsid protein.

    PubMed

    Sharma, Rajesh; Fatma, Benazir; Saha, Amrita; Bajpai, Sailesh; Sistla, Srinivas; Dash, Paban Kumar; Parida, Manmohan; Kumar, Pravindra; Tomar, Shailly

    2016-11-01

    The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1×10(-7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases.

  14. Inhibition of chikungunya virus by picolinate that targets viral capsid protein.

    PubMed

    Sharma, Rajesh; Fatma, Benazir; Saha, Amrita; Bajpai, Sailesh; Sistla, Srinivas; Dash, Paban Kumar; Parida, Manmohan; Kumar, Pravindra; Tomar, Shailly

    2016-11-01

    The protein-protein interactions (PPIs) of the transmembrane glycoprotein E2 with the hydrophobic pocket on the surface of capsid protein (CP) plays a critical role in alphavirus life cycle. Dioxane based derivatives targeting PPIs have been reported to possess antiviral activity against Sindbis Virus (SINV), the prototype alphavirus. In this study, the binding of picolinic acid (PCA) to the conserved hydrophobic pocket of capsid protein was analyzed by molecular docking, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR) and fluorescence spectroscopy. The binding constant KD obtained for PCA was 2.1×10(-7)M. Additionally, PCA significantly inhibited CHIKV replication in infected Vero cells, decreasing viral mRNA and viral load as assessed by qRT-PCR and plaque reduction assay, respectively. This study is suggestive of the potential of pyridine ring compounds as antivirals against alphaviruses and may serve as the basis for the development of PCA based drugs against alphaviral diseases. PMID:27614702

  15. Use of Household Cluster Investigations to Identify Factors Associated with Chikungunya Virus Infection and Frequency of Case Reporting in Puerto Rico

    PubMed Central

    Bloch, Danielle; Roth, Nicole M.; Caraballo, Elba V.; Muñoz-Jordan, Jorge; Hunsperger, Elizabeth; Rivera, Aidsa; Pérez-Padilla, Janice; Rivera Garcia, Brenda

    2016-01-01

    Background Chikungunya virus (CHIKV) is transmitted by Aedes species mosquitoes and is the cause of an acute febrile illness characterized by potentially debilitating arthralgia. After emerging in the Caribbean in late 2013, the first locally-acquired case reported to public health authorities in Puerto Rico occurred in May 2014. During June–August 2014, household-based cluster investigations were conducted to identify factors associated with infection, development of disease, and case reporting. Methodology/Principal Findings Residents of households within a 50-meter radius of the residence of laboratory-positive chikungunya cases that had been reported to Puerto Rico Department of Health (PRDH) were offered participation in the investigation. Participants provided a serum specimen and answered a questionnaire that collected information on demographic factors, household characteristics, recent illnesses, healthcare seeking behaviors, and clinical diagnoses. Current CHIKV infection was identified by rRT-PCR, and recent CHIKV infection was defined by detection of either anti-CHIKV IgM or IgG antibody. Among 250 participants, 74 (30%) had evidence of CHIKV infection, including 12 (5%) with current and 62 (25%) with recent CHIKV infection. All specimens from patients with CHIKV infection that were collected within four days, two weeks, and three weeks of illness onset were positive by RT-PCR, IgM ELISA, and IgG ELISA, respectively. Reporting an acute illness in the prior three months was strongly associated with CHIKV infection (adjusted odds ratio [aOR] = 21.6, 95% confidence interval [CI]: 9.24–50.3). Use of air conditioning (aOR = 0.50, 95% CI = 0.3–0.9) and citronella candles (aOR = 0.4, 95% CI = 0.1–0.9) were associated with protection from CHIKV infection. Multivariable analysis indicated that arthralgia (aOR = 51.8, 95% CI = 3.8–700.8) and skin rash (aOR = 14.2, 95% CI = 2.4–84.7) were strongly associated with CHIKV infection. Hierarchical cluster

  16. Differential Phosphatidylinositol-3-Kinase-Akt-mTOR Activation by Semliki Forest and Chikungunya Viruses Is Dependent on nsP3 and Connected to Replication Complex Internalization

    PubMed Central

    Biasiotto, Roberta; Eng, Kai; Neuvonen, Maarit; Götte, Benjamin; Rheinemann, Lara; Mutso, Margit; Utt, Age; Varghese, Finny; Balistreri, Giuseppe; Merits, Andres; Ahola, Tero; McInerney, Gerald M.

    2015-01-01

    ABSTRACT Many viruses affect or exploit the phosphatidylinositol-3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) pathway, a crucial prosurvival signaling cascade. We report that this pathway was strongly activated in cells upon infection with the Old World alphavirus Semliki Forest virus (SFV), even under conditions of complete nutrient starvation. We mapped this activation to the hyperphosphorylated/acidic domain in the C-terminal tail of SFV nonstructural protein nsP3. Viruses with a deletion of this domain (SFV-Δ50) but not of other regions in nsP3 displayed a clearly delayed and reduced capacity of Akt stimulation. Ectopic expression of the nsP3 of SFV wild type (nsP3-wt), but not nsP3-Δ50, equipped with a membrane anchor was sufficient to activate Akt. We linked PI3K-Akt-mTOR stimulation to the intracellular dynamics of viral replication complexes, which are formed at the plasma membrane and subsequently internalized in a process blocked by the PI3K inhibitor wortmannin. Replication complex internalization was observed upon infection of cells with SFV-wt and SFV mutants with deletions in nsP3 but not with SFV-Δ50, where replication complexes were typically accumulated at the cell periphery. In cells infected with the closely related chikungunya virus (CHIKV), the PI3K-Akt-mTOR pathway was only moderately activated. Replication complexes of CHIKV were predominantly located at the cell periphery. Exchanging the hypervariable C-terminal tail of nsP3 between SFV and CHIKV induced the phenotype of strong PI3K-Akt-mTOR activation and replication complex internalization in CHIKV. In conclusion, infection with SFV but not CHIKV boosts PI3K-Akt-mTOR through the hyperphosphorylated/acidic domain of nsP3 to drive replication complex internalization. IMPORTANCE SFV and CHIKV are very similar in terms of molecular and cell biology, e.g., regarding replication and molecular interactions, but are strikingly different regarding pathology: CHIKV is a relevant human

  17. Do we need a vaccine against chikungunya?

    PubMed

    Rezza, Giovanni

    2015-06-01

    During the last decade, the chikungunya (CHIKV) virus has expanded its range of activity, conquering new territories and becoming an important global health threat. In particular, the challenge represented by the recent emergence of CHIKV in the Americas has strengthened the need of a safe and effective vaccine. Although research on vaccines against CHIKV has been slow, a few vaccine candidates have been tested over the years. Inactivated and attenuated vaccine candidates have shown promising results in phase I/II trials, and engineered vaccines have proven to be safe and immunogenic in mouse and/or non-human primate models. Recently, a vaccine based on virus-like particles (VLP) has been successfully tested in a phase I trial. However, large phase I/II controlled trials, which are needed in order to provide evidence of vaccine efficacy, may be planned only under certain conditions. First, they should be conducted during epidemic periods, when a large number of cases occur, in order to ensure an adequate study power. Second, they are expensive and investments returns are not always guaranteed. To overcome this problem, public/private partnership and government support, the identification of target population groups for vaccination and the commitment of donor agencies are key factors for supporting both the development and the availability of vaccines against neglected tropical diseases like chikungunya.

  18. Do we need a vaccine against chikungunya?

    PubMed Central

    Rezza, Giovanni

    2015-01-01

    During the last decade, the chikungunya (CHIKV) virus has expanded its range of activity, conquering new territories and becoming an important global health threat. In particular, the challenge represented by the recent emergence of CHIKV in the Americas has strengthened the need of a safe and effective vaccine. Although research on vaccines against CHIKV has been slow, a few vaccine candidates have been tested over the years. Inactivated and attenuated vaccine candidates have shown promising results in phase I/II trials, and engineered vaccines have proven to be safe and immunogenic in mouse and/or non-human primate models. Recently, a vaccine based on virus-like particles (VLP) has been successfully tested in a phase I trial. However, large phase I/II controlled trials, which are needed in order to provide evidence of vaccine efficacy, may be planned only under certain conditions. First, they should be conducted during epidemic periods, when a large number of cases occur, in order to ensure an adequate study power. Second, they are expensive and investments returns are not always guaranteed. To overcome this problem, public/private partnership and government support, the identification of target population groups for vaccination and the commitment of donor agencies are key factors for supporting both the development and the availability of vaccines against neglected tropical diseases like chikungunya. PMID:25971340

  19. Do we need a vaccine against chikungunya?

    PubMed

    Rezza, Giovanni

    2015-06-01

    During the last decade, the chikungunya (CHIKV) virus has expanded its range of activity, conquering new territories and becoming an important global health threat. In particular, the challenge represented by the recent emergence of CHIKV in the Americas has strengthened the need of a safe and effective vaccine. Although research on vaccines against CHIKV has been slow, a few vaccine candidates have been tested over the years. Inactivated and attenuated vaccine candidates have shown promising results in phase I/II trials, and engineered vaccines have proven to be safe and immunogenic in mouse and/or non-human primate models. Recently, a vaccine based on virus-like particles (VLP) has been successfully tested in a phase I trial. However, large phase I/II controlled trials, which are needed in order to provide evidence of vaccine efficacy, may be planned only under certain conditions. First, they should be conducted during epidemic periods, when a large number of cases occur, in order to ensure an adequate study power. Second, they are expensive and investments returns are not always guaranteed. To overcome this problem, public/private partnership and government support, the identification of target population groups for vaccination and the commitment of donor agencies are key factors for supporting both the development and the availability of vaccines against neglected tropical diseases like chikungunya. PMID:25971340

  20. Imported tropical virus infections in Germany.

    PubMed

    Schmitz, H; Emmerich, P; ter Meulen, J

    1996-01-01

    Our routine tests for tropical viruses document that several hundreds of Dengue fever cases are imported into Germany every year. In contrast, hemorrhagic fever cases are rarely diagnosed in Germany. Our investigations suggest that this low number is due to the different living conditions of the local population in the tropics compared with that of travellers from Europe or North America. Improved methods for detecting Dengue virus infections, e.g. three different antibody tests and the reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of viral RNA, have been developed.

  1. Bats: Important Reservoir Hosts of Emerging Viruses

    PubMed Central

    Calisher, Charles H.; Childs, James E.; Field, Hume E.; Holmes, Kathryn V.; Schountz, Tony

    2006-01-01

    Bats (order Chiroptera, suborders Megachiroptera [“flying foxes”] and Microchiroptera) are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimized and many of their populations and species are at risk, even threatened or endangered. Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviors, ability to echolocate, virus susceptibility) make them exquisitely suitable hosts of viruses and other disease agents. Bats of certain species are well recognized as being capable of transmitting rabies virus, but recent observations of outbreaks and epidemics of newly recognized human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. This paper summarizes information regarding chiropteran characteristics and information regarding 66 viruses that have been isolated from bats. From these summaries, it is clear that we do not know enough about bat biology; we are doing too little in terms of bat conservation; and there remain a multitude of questions regarding the role of bats in disease emergence. PMID:16847084

  2. Pan-European Chikungunya surveillance: designing risk stratified surveillance zones

    PubMed Central

    Tilston, Natasha; Skelly, Chris; Weinstein, Phil

    2009-01-01

    The first documented transmission of Chikungunya within Europe took place in Italy during the summer of 2007. Chikungunya, a viral infection affecting millions of people across Africa and Asia, can be debilitating and no prophylactic treatment exists. Although imported cases are reported frequently across Europe, 2007 was the first confirmed European outbreak and available evidence suggests that Aedes albopictus was the vector responsible and the index case was a visitor from India. This paper proposed pan-European surveillance zones for Chikungunya, based on the climatic conditions necessary for vector activity and viral transmission. Pan-European surveillance provides the best hope for an early-warning of outbreaks, because national boundaries do not play a role in defining the risk of this new vector borne disease threat. A review of climates, where Chikungunya has been active, was used to inform the delineation of three pan-European surveillance zones. These vary in size each month across the June-September period of greatest risk. The zones stretch across southern Europe from Portugal to Turkey. Although the focus of this study was to define the geography of potential surveillance zones based on the climatic limits on the vector and virus, a preliminary examination of inward bound airline passengers was also undertaken. This indicated that France and Italy are likely to be at greater risk due to the number of visitors they receive from Chikungunya active regions, principally viraemic visitors from India. Therefore this study represents a first attempt at creating risk stratified surveillance zones, which we believe could be usefully refined with the use of higher resolution climate data and more complete air travel data. PMID:19878588

  3. Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate.

    PubMed

    Saraswat, Shweta; Athmaram, T N; Parida, Manmohan; Agarwal, Ankita; Saha, Amrita; Dash, Paban Kumar

    2016-07-01

    Chikungunya virus (CHIKV) has emerged as a global health concern due to its recent spread in both old and new world. So far, no CHIKV specific drug or vaccine is licensed for human use. In this study, we report production of Chikungunya virus like particles (CHIK-VLPs) using novel yeast expression system (Pichia pastoris) and its evaluation as vaccine candidate. The gene encoding structural polyprotein of CHIKV from a recent epidemic strain was cloned into yeast expression system. The multicopy integrants were processed for expression of CHIK-VLPs. The VLPs were purified and confirmed through electron microscopic analysis for their morphological identity with CHIKV. The in vitro and in vivo evaluation of CHIK-VLPs as vaccine candidate was determined in Balb/c mice. Induction of both humoral and cellular immune response was observed with different doses of CHIK-VLPs. The humoral immune response was studied through different techniques like enzyme linked immunosorbent assay, IgG Isotyping and plaque reduction neutralization test. CHIK-VLPs were found to elicit high titer of antibodies that are able to recognize native CHIKV. Higher level of IgG2a and IgG1 subtypes was identified suggestive of balanced Th1/Th2 response. Both in vitro and in vivo neutralization activity of CHIK-VLPs antibodies was observed even with low concentration, which shows its high specificity and neutralizing activity against two different CHIKV strains. Neonatal mice receiving anti-CHIK-VLPs antibodies were protected from CHIKV challenge. Induction of cellular immune response was confirmed through higher level of TNF-α, IL-10 and substantial level of IL-2, IL-4 and IFN-γ indicating a balanced response. This is the first report, where CHIK-VLPs has been expressed by Pichia pastoris and evaluated for neutralizing activity against CHIKV. These promising results indicate the utility of CHIK-VLPs as a promising vaccine candidate against emerging CHIKV. PMID:27399001

  4. Chikungunya Virus Infections Among Patients with Dengue-Like Illness at a Tertiary Care Hospital in the Philippines, 2012-2013.

    PubMed

    Velasco, John Mark; Valderama, Maria Theresa; Lopez, Maria Nila; Chua, Domingo; Latog, Rene; Roque, Vito; Corpuz, June; Klungthong, Chonticha; Rodpradit, Prinyada; Hussem, Kittinun; Poolpanichupatam, Yongyuth; Macareo, Louis; Fernandez, Stefan; Yoon, In-Kyu

    2015-12-01

    Chikungunya virus (CHIKV) often co-circulates with dengue virus (DENV). A cross-sectional surveillance study was conducted at a tertiary hospital in Manila, Philippines, to describe the prevalence and characteristics of DENV and CHIKV infections among patients seeking care for dengue-like illness. Acute blood samples from patients ≥ 6 months of age clinically diagnosed with dengue from November 2012 to December 2013 underwent reverse transcription polymerase chain reaction (RT-PCR) to detect DENV and CHIKV RNA. A total of 118 patients with clinically diagnosed dengue (age range = 1-89 years, mean = 22 years; male-to-female ratio = 1.51) were tested by DENV RT-PCR; 40 (34%) were DENV PCR-positive (age range = 1-45 years, mean = 17 years). All DENV serotypes were detected: 11 (28%) DENV-1, 6 (15%) DENV-2, 6 (15%) DENV-3, and 17 (42%) DENV-4. Of 112 patients clinically diagnosed with dengue and tested by CHIKV RT-PCR, 11 (10%) were CHIKV PCR-positive (age range = 2-47 years, mean = 20.3 years). No coinfections were detected. Presenting signs/symptoms did not differ between DENV- and CHIKV-positive cases. Sequencing of envelope 1 gene from two CHIKV PCR-positive samples showed Asian genotype. This study highlights the potential for misdiagnosis of medically attended CHIKV infections as DENV infection and the difficulty in clinically differentiating dengue and chikungunya based on presenting signs/symptoms alone. This underscores the necessity for diagnostic laboratory tests to distinguish CHIKV infections in the background of actively co-circulating DENV.

  5. Expression and Characterization of Yeast Derived Chikungunya Virus Like Particles (CHIK-VLPs) and Its Evaluation as a Potential Vaccine Candidate

    PubMed Central

    Saraswat, Shweta; Athmaram, T. N.; Parida, Manmohan; Agarwal, Ankita; Saha, Amrita; Dash, Paban Kumar

    2016-01-01

    Chikungunya virus (CHIKV) has emerged as a global health concern due to its recent spread in both old and new world. So far, no CHIKV specific drug or vaccine is licensed for human use. In this study, we report production of Chikungunya virus like particles (CHIK-VLPs) using novel yeast expression system (Pichia pastoris) and its evaluation as vaccine candidate. The gene encoding structural polyprotein of CHIKV from a recent epidemic strain was cloned into yeast expression system. The multicopy integrants were processed for expression of CHIK-VLPs. The VLPs were purified and confirmed through electron microscopic analysis for their morphological identity with CHIKV. The in vitro and in vivo evaluation of CHIK-VLPs as vaccine candidate was determined in Balb/c mice. Induction of both humoral and cellular immune response was observed with different doses of CHIK-VLPs. The humoral immune response was studied through different techniques like enzyme linked immunosorbent assay, IgG Isotyping and plaque reduction neutralization test. CHIK-VLPs were found to elicit high titer of antibodies that are able to recognize native CHIKV. Higher level of IgG2a and IgG1 subtypes was identified suggestive of balanced Th1/Th2 response. Both in vitro and in vivo neutralization activity of CHIK-VLPs antibodies was observed even with low concentration, which shows its high specificity and neutralizing activity against two different CHIKV strains. Neonatal mice receiving anti-CHIK-VLPs antibodies were protected from CHIKV challenge. Induction of cellular immune response was confirmed through higher level of TNF-α, IL-10 and substantial level of IL-2, IL-4 and IFN-γ indicating a balanced response. This is the first report, where CHIK-VLPs has been expressed by Pichia pastoris and evaluated for neutralizing activity against CHIKV. These promising results indicate the utility of CHIK-VLPs as a promising vaccine candidate against emerging CHIKV. PMID:27399001

  6. First report of chikungunya from the Maldives.

    PubMed

    Yoosuf, Abdul Azeez; Shiham, Ibrahim; Mohamed, Ahmed Jamsheed; Ali, Geela; Luna, J M; Pandav, R; Gongal, G N; Nisaluk, Ananda; Jarman, Richard G; Gibbons, Robert V

    2009-02-01

    An outbreak, characterised by fever, arthralgia and myalgia, in Malé and other islands of the Maldives began in December 2006. The illness was suspected as being due to chikungunya virus based on clinical symptoms and the prevailing chikungunya epidemic in the Indian Ocean region. The Department of Public Health initiated an investigation and collected blood samples from 67 patients; 21% were IgM-positive for chikungunya and 96% were PCR-positive. Six percent were positive for dengue by enzyme immunosorbent assay and 4% had evidence of dual infection. This is the first time that chikungunya fever has been confirmed in the Maldives. A total of 11,879 suspected and confirmed cases affecting 61% of inhabited islands (attack rate ranging from 0% to 72% on individual islands) were reported by the end of the epidemic in April 2007.

  7. Importance of Viruses in Acute Otitis Media

    PubMed Central

    Nokso-Koivisto, Johanna; Marom, Tal; Chonmaitree, Tasnee

    2015-01-01

    Purpose of review Acute otitis media (AOM) occurs as a complication of viral upper respiratory tract infection (URI). Bacterial otopathogens and respiratory viruses interact and play important roles in AOM development. Better understanding of viral and bacterial interactions may lead to innovative ways to lessen the burden of this common childhood disease. Recent findings There has been increasing evidence that AOM occurs during URI, even in the absence of nasopharyngeal bacterial colonization. Among the types of viruses associated with AOM, respiratory syncytial virus continues to be the most commonly detected. It is still unclear whether viral load plays an important role in AOM development, but symptomatic URI (as opposed to asymptomatic viral infection) is crucial. Widespread use of bacterial and viral vaccines in young children, including pneumococcal conjugate and influenza vaccines, has led to the reduction in otitis media-related health care use between 2001 and 2011. There has been no new vaccine against respiratory viruses other than influenza. Summary Progress has been made towards reduction of the burden of AOM in the last decade. Success in reducing AOM incidence will rely mainly on prevention of nasopharyngeal otopathogen colonization, as well as reduction in the incidence of viral URI. PMID:25514574

  8. Fatal leptospirosis and chikungunya co-infection: Do not forget leptospirosis during chikungunya outbreaks.

    PubMed

    Nhan, Tu-Xuan; Bonnieux, Eric; Rovery, Clarisse; De Pina, Jean-Jacques; Musso, Didier

    2016-01-01

    In endemic areas, leptospirosis can be missed by erroneous clinical or laboratory diagnosis of arboviroses or co-infections with arboviruses and an increase in mortality due to leptospirosis has already been reported during arboviruses outbreaks. During the French Polynesian chikungunya virus outbreak in 2014-2015, two leptospirosis and chikungunya co-infections were reported, one of which was fatal. Diagnosis of leptospiroses was delayed in the context of chikungunya outbreak. In the context of arbovirus outbreak, the risk of misdiagnosis of leptospirosis is maximum and clinicians should initiate early antibiotic therapy if leptospirosis is suspected. A delayed diagnosis of leptospirosis can be responsible for fatal outcome. Leptospirosis should be considered even if dengue or chikungunya virus infections are confirmed by reference molecular testing. PMID:27413690

  9. Inhibition of Chikungunya Virus Replication by 1-[(2-Methylbenzimidazol-1-yl) Methyl]-2-Oxo-Indolin-3-ylidene] Amino] Thiourea(MBZM-N-IBT)

    PubMed Central

    Mishra, Priyadarsee; Kumar, Abhishek; Mamidi, Prabhudutta; Kumar, Sameer; Basantray, Itishree; Saswat, Tanuja; Das, Indrani; Nayak, Tapas Kumar; Chattopadhyay, Subhasis; Subudhi, Bharat Bhusan; Chattopadhyay, Soma

    2016-01-01

    Chikungunya virus (CHIKV) infection is one of the most challenging human Arboviral infections with global significance and without any specific antiviral. In this investigation, 1-[(2-methylbenzimidazol-1-yl) methyl]-2-oxo-indolin-3-ylidene] amino] thiourea (MBZM-N-IBT) was synthesised as a molecular hybrid of 2-methyl benzimidazole and isatin-β-thiosemicarbazone and its anti-CHIKV property was evaluated. The release of infectious virus particles was calculated by plaque assay, expression profile of viral RNA was estimated by RT-PCR and viral protein profiles were assessed by Western blot and FACS analyses. The safety index of MBZM-N-IBT was found to be >21. The CHIKV infectious viral particle formation was abrogated around 76.02% by MBZM-N-IBT during infection in mammalian system and the viral RNA synthesis was reduced by 65.53% and 23.71% for nsP2 and E1 respectively. Surprisingly, the viral protein levels were reduced by 97% for both nsP2 and E2. In the time-of-addition experiment it abrogated viral infection at early as well as late phase of viral life cycle, which indicates about multiple mechanisms for its anti-CHIKV action. In silico analysis justified development of MBZM-N-IBT with good affinities for potential target proteins of CHIKV and related virus. With predictions of good drug-likeness property, it shows potential of a drug candidate which needs further experimental validation. PMID:26843462

  10. False positive dengue NS1 antigen test in a traveller with an acute Zika virus infection imported into Switzerland.

    PubMed

    Gyurech, Danielle; Schilling, Julian; Schmidt-Chanasit, Jonas; Cassinotti, Pascal; Kaeppeli, Franz; Dobec, Marinko

    2016-01-01

    We report the first case of an acute Zika virus infection imported into Switzerland by a traveller returning from Canoa Quebrada, Ceará state, in the north-eastern part of Brazil. Due to a false positive dengue virus NS1 antigen test, IgG antibody seroconversion and a suggestive clinical picture,an acute dengue fever was initially considered. However, because of lack of specific IgM-antibodies, stationary IgG antibody titre and a negative dengue virus PCR test result, a dengue virus infection was excluded and a cross-reaction with other, causative flaviviruses was postulated. Based on recent reports of Zika fever cases in the north-eastern parts of Brazil, an acute Zika virus infection was suspected. Because of a lack of commercially available Zika virus diagnostic tests, the case was confirmed in the WHO reference laboratory. As the clinical presentation of Zika virus infection can be confused with dengue fever and chikungunya fever, and because of possible public health implications, all patients returning from affected areas should be additionally tested for Zika virus. This case illustrates the urgent medical need for a broadly available assay capable of differentiating Zika from Dengue infections.

  11. Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases.

    PubMed

    Sahadeo, Nikita; Mohammed, Hamish; Allicock, Orchid M; Auguste, Albert J; Widen, Steven G; Badal, Kimberly; Pulchan, Krishna; Foster, Jerome E; Weaver, Scott C; Carrington, Christine V F

    2015-11-01

    Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson's χ2 and student's t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson's χ2 and Fisher's exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28-16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever--aOR: 0.56 [0.40-0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71-0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which

  12. Molecular Characterisation of Chikungunya Virus Infections in Trinidad and Comparison of Clinical and Laboratory Features with Dengue and Other Acute Febrile Cases.

    PubMed

    Sahadeo, Nikita; Mohammed, Hamish; Allicock, Orchid M; Auguste, Albert J; Widen, Steven G; Badal, Kimberly; Pulchan, Krishna; Foster, Jerome E; Weaver, Scott C; Carrington, Christine V F

    2015-11-01

    Local transmission of Chikungunya virus (CHIKV) was first documented in Trinidad and Tobago (T&T) in July 2014 preceding a large epidemic. At initial presentation, it is difficult to distinguish chikungunya fever (CHIKF) from other acute undifferentiated febrile illnesses (AUFIs), including life-threatening dengue disease. We characterised and compared dengue virus (DENV) and CHIKV infections in 158 patients presenting with suspected dengue fever (DF) and CHIKF at a major hospital in T&T, and performed phylogenetic analyses on CHIKV genomic sequences recovered from 8 individuals. The characteristics of patients with and without PCR-confirmed CHIKV were compared using Pearson's χ2 and student's t-tests, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were determined using logistic regression. We then compared signs and symptoms of people with RT-qPCR-confirmed CHIKV and DENV infections using the Mann-Whitney U, Pearson's χ2 and Fisher's exact tests. Among the 158 persons there were 8 (6%) RT-qPCR-confirmed DENV and 30 (22%) RT-qPCR-confirmed CHIKV infections. Phylogenetic analyses showed that the CHIKV strains belonged to the Asian genotype and were most closely related to a British Virgin Islands strain isolated at the beginning of the 2013/14 outbreak in the Americas. Compared to persons who were RT-qPCR-negative for CHIKV, RT-qPCR-positive individuals were significantly more likely to have joint pain (aOR: 4.52 [95% CI: 1.28-16.00]), less likely to be interviewed at a later stage of illness (days post onset of fever--aOR: 0.56 [0.40-0.78]) and had a lower white blood cell count (aOR: 0.83 [0.71-0.96]). Among the 38 patients with RT-qPCR-confirmed CHIKV or DENV, there were no significant differences in symptomatic presentation. However when individuals with serological evidence of recent DENV or CHIKV infection were included in the analyses, there were key differences in clinical presentation between CHIKF and other AUFIs including DF, which

  13. Chikungunya Outbreaks Caused by African Genotype, India

    PubMed Central

    Yergolkar, Prasanna N.; Tandale, Babasaheb V.; Arankalle, Vidya A.; Sathe, Padmakar S.; Gandhe, Swati S.; Gokhle, Mangesh D.; Jacob, George P.; Hundekar, Supriya L.

    2006-01-01

    Chikungunya fever is reported in India after 32 years. Immunoglobulin M antibodies and virus isolation confirmed the cause. Phylogenic analysis based on partial sequences of NS4 and E1 genes showed that all earlier isolates (1963–1973) were Asian genotype, whereas the current and Yawat (2000) isolates were African genotype. PMID:17176577

  14. Salivary Transmission of the Chikungunya Arbovirus.

    PubMed

    Rolph, Michael S; Zaid, Ali; Mahalingam, Suresh

    2016-02-01

    The emergence of Chikungunya virus (CHIKV) has prompted a re-think of how preventative solutions should be approached since recent studies support the notion of salivary transmission. With the threat of significant health and economic burden, new control strategies aimed at limiting salivary transmission are needed to avoid further outbreaks.

  15. Chikungunya in Europe: What’s next?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In August 2004, Kenyan health authorities and partners identified chikungunya virus as the cause of a febrile epidemic in humans in a coastal island city. This epidemic spread to Indian Ocean islands and India, where it continues and more than 1 million cases are suspected. Rezza and colleagues des...

  16. Case reports of neuro-Chikungunya in southern Thailand.

    PubMed

    Chusri, Sarunyou; Siripaitoon, Pisud; Hirunpat, Siriporn; Silpapojakul, Khachornsakdi

    2011-08-01

    There has been a recent increase in reports of neurologic complications as major causes of morbidity and mortality in chikungunya virus infection. As a part of 2004-2009 global outbreaks, an unprecedented large chikungunya epidemic occurred in Southern Thailand during 2008-2009 in which 49,069 cases were reported. During this period, we encountered two patients with meningoencephalitis and another patient with myeloneuropathy among 1,018 cases diagnosed as chikungunya in our hospital. The clinical pictures are presented and the key points are used to recognize and differentiate chikungunya from Japanese encephalitis virus, dengue virus, and herpesvirus infections, which are more common causes of meningoencephalitis and myelitis in this region.

  17. Chikungunya infection in DoD healthcare beneficiaries following the 2013 introduction of the virus into the Western Hemisphere, 1 January 2014 to 28 February 2015.

    PubMed

    Writer, James V; Hurt, Lee

    2015-10-01

    The introduction and rapid spread of chikungunya virus (CHIKV) into the Western Hemisphere after December 2013 pose a potentially significant risk to Department of Defense (DoD) personnel, operations, and the military healthcare system. This report describes the DoD experience with CHIKV between January 2014 and February 2015 using case reports in the Defense Medical Surveillance System's (DMSS) Reportable Medical Events database and the Navy and Marine Corps Public Health Center's laboratory test results database. Case finding identified 157 confirmed cases; of these, 118 (75.2%) were either active or reserve component service members and 39 (24.8%) were other beneficiaries. Exposure locations were known for 117 (74.5%) of all cases, and of these, 113 (96.6%) reported likely exposures in the Western Hemisphere; 85 (75.2%) of those cases occurred in Puerto Rico. Although historical data on CHIKV in DoD populations are scant, introduction of CHIKV into the Western Hemisphere with ongoing transmission appears to have resulted in a significant increase in the number of cases among DoD healthcare beneficiary populations. PMID:26505074

  18. Differences in response of primary human myoblasts to infection with recent epidemic strains of Chikungunya virus isolated from patients with and without myalgia.

    PubMed

    Lohachanakul, Jindarat; Phuklia, Weerawat; Thannagith, Montri; Thongsakulprasert, Tipparat; Smith, Duncan R; Ubol, Sukathida

    2015-05-01

    In addition to fever, rash, and arthralgia/arthritis, myalgia is another dominant symptom in Chikungunya virus (CHIKV) infection. How CHIKV induces myalgia is unclear. To better understand the viral factors involved in CHIKV-induced myalgia, CHIKVs were isolated from patients with and without myalgia designated myalgia-CHIKV and mild-CHIKV, respectively. The response of myoblasts to infection by the two groups of clinical isolates of CHIKV was investigated. Both groups of CHIKV replicated well in primary human myoblasts. However, the myalgia-CHIKVs replicated to a higher titer and caused the death of infected myoblast more rapidly than the mild-CHIKVs. CHIKV-infected myoblasts increased production of four out of five inflammatory cytokines examined (MCP-1, IP-10, MIP-1α, and IL-8) in comparison to mock-infected cells. Comparison between the myoblast inflammatory cytokine responses showed that myalgia-CHIKVs were stronger activators of cytokines than mild-CHIKVs. This means that recent epidemic strains of CHIKV exhibited different degrees of myoblast permissiveness as evidenced by differences in the ability to replicate and to stimulate inflammatory responses in myoblasts. This data suggest that the myopathic syndrome in recent epidemics is dependent upon the strain of CHIKV.

  19. Vector Competence of Aedes aegypti and Aedes vittatus (Diptera: Culicidae) from Senegal and Cape Verde Archipelago for West African Lineages of Chikungunya Virus

    PubMed Central

    Diagne, Cheikh T.; Faye, Oumar; Guerbois, Mathilde; Knight, Rachel; Diallo, Diawo; Faye, Ousmane; Ba, Yamar; Dia, Ibrahima; Faye, Ousmane; Weaver, Scott C.; Sall, Amadou A.; Diallo, Mawlouth

    2014-01-01

    To assess the risk of emergence of chikungunya virus (CHIKV) in West Africa, vector competence of wild-type, urban, and non-urban Aedes aegypti and Ae. vittatus from Senegal and Cape Verde for CHIKV was investigated. Mosquitoes were fed orally with CHIKV isolates from mosquitoes (ArD30237), bats (CS13-288), and humans (HD180738). After 5, 10, and 15 days of incubation following an infectious blood meal, presence of CHIKV RNA was determined in bodies, legs/wings, and saliva using real-time reverse transcription–polymerase chain reaction. Aedes vittatus showed high susceptibility (50–100%) and early dissemination and transmission of all CHIKV strains tested. Aedes aegypti exhibited infection rates ranging from 0% to 50%. Aedes aegypti from Cape Verde and Kedougou, but not those from Dakar, showed the potential to transmit CHIKV in saliva. Analysis of biology and competence showed relatively high infective survival rates for Ae. vittatus and Ae. aegypti from Cape Verde, suggesting their efficient vector capacity in West Africa. PMID:25002293

  20. Evaluating Liquid and Granular Bacillus thuringiensis var. israelensis Broadcast Applications for Controlling Vectors of Dengue and Chikungunya Viruses in Artificial Containers and Tree Holes.

    PubMed

    Harwood, James F; Farooq, Muhammad; Turnwall, Brent T; Richardson, Alec G

    2015-07-01

    The principal vectors of chikungunya and dengue viruses typically oviposit in water-filled artificial and natural containers, including tree holes. Despite the risk these and similar tree hole-inhabiting mosquitoes present to global public health, surprisingly few studies have been conducted to determine an efficient method of applying larvicides specifically to tree holes. The Stihl SR 450, a backpack sprayer commonly utilized during military and civilian vector control operations, may be suitable for controlling larval tree-hole mosquitoes, as it is capable of delivering broadcast applications of granular and liquid dispersible formulations of Bacillus thuringiensis var. israelensis (Bti) to a large area relatively quickly. We compared the application effectiveness of two granular (AllPro Sustain MGB and VectoBac GR) and two liquid (Aquabac XT and VectoBac WDG) formulations of Bti in containers placed on bare ground, placed beneath vegetative cover, and hung 1.5 or 3 m above the ground to simulate tree holes. Aedes aegypti (L.) larval mortality and Bti droplet and granule density data (when appropriate) were recorded for each formulation. Overall, granular formulations of Bti resulted in higher mortality rates in the simulated tree-hole habitats, whereas applications of granular and liquid formulations resulted in similar levels of larval mortality in containers placed on the ground in the open and beneath vegetation. PMID:26335473

  1. Vector competence of Aedes aegypti and Aedes vittatus (Diptera: Culicidae) from Senegal and Cape Verde archipelago for West African lineages of chikungunya virus.

    PubMed

    Diagne, Cheikh T; Faye, Oumar; Guerbois, Mathilde; Knight, Rachel; Diallo, Diawo; Faye, Ousmane; Ba, Yamar; Dia, Ibrahima; Faye, Ousmane; Weaver, Scott C; Sall, Amadou A; Diallo, Mawlouth

    2014-09-01

    To assess the risk of emergence of chikungunya virus (CHIKV) in West Africa, vector competence of wild-type, urban, and non-urban Aedes aegypti and Ae. vittatus from Senegal and Cape Verde for CHIKV was investigated. Mosquitoes were fed orally with CHIKV isolates from mosquitoes (ArD30237), bats (CS13-288), and humans (HD180738). After 5, 10, and 15 days of incubation following an infectious blood meal, presence of CHIKV RNA was determined in bodies, legs/wings, and saliva using real-time reverse transcription-polymerase chain reaction. Aedes vittatus showed high susceptibility (50-100%) and early dissemination and transmission of all CHIKV strains tested. Aedes aegypti exhibited infection rates ranging from 0% to 50%. Aedes aegypti from Cape Verde and Kedougou, but not those from Dakar, showed the potential to transmit CHIKV in saliva. Analysis of biology and competence showed relatively high infective survival rates for Ae. vittatus and Ae. aegypti from Cape Verde, suggesting their efficient vector capacity in West Africa. PMID:25002293

  2. Development of 2, 7-Diamino-1, 8-Naphthyridine (DANP) Anchored Hairpin Primers for RT-PCR Detection of Chikungunya Virus Infection.

    PubMed

    Chen, Huixin; Parimelalagan, Mariya; Takei, Fumie; Hapuarachchi, Hapuarachchige Chanditha; Koay, Evelyn Siew-Chuan; Ng, Lee Ching; Ho, Phui San; Nakatani, Kazuhiko; Chu, Justin Jang Hann

    2016-08-01

    A molecular diagnostic platform with DANP-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of Chikungunya virus (CHIKV) with high sensitivity and specificity. The molecule 2, 7-diamino-1, 8-naphthyridine (DANP) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. Thus, by measuring the decline in fluorescence emitted from DANP-primer complexes after PCR reaction, we could monitor the PCR progress. By adapting this property of DANP, we have previously developed the first generation DANP-coupled hairpin RT-PCR assay. In the current study, we improved the assay performance by conjugating the DANP molecule covalently onto the hairpin primer to fix the DANP/primer ratio at 1:1; and adjusting the excitation emission wavelength to 365/430 nm to minimize the background signal and a 'turn-on' system is achieved. After optimizing the PCR cycle number to 30, we not only shortened the total assay turnaround time to 60 minutes, but also further reduced the background fluorescence. The detection limit of our assay was 0.001 PFU per reaction. The DANP-anchored hairpin primer, targeting nsP2 gene of CHIKV genome, is highly specific to CHIKV, having no cross-reactivity to a panel of other RNA viruses tested. In conclusion, we report here a molecular diagnostic assay that is sensitive, specific, rapid and cost effective for CHIKV detection and can be performed where no real time PCR instrumentation is required. Our results from patient samples indicated 93.62% sensitivity and 100% specificity of this method, ensuring that it can be a useful tool for rapid detection of CHIKV for outbreaks in many parts of the world. PMID:27571201

  3. Development of 2, 7-Diamino-1, 8-Naphthyridine (DANP) Anchored Hairpin Primers for RT-PCR Detection of Chikungunya Virus Infection

    PubMed Central

    Chen, Huixin; Parimelalagan, Mariya; Takei, Fumie; Hapuarachchi, Hapuarachchige Chanditha; Koay, Evelyn Siew-Chuan; Ng, Lee Ching; Ho, Phui San; Nakatani, Kazuhiko; Chu, Justin Jang Hann

    2016-01-01

    A molecular diagnostic platform with DANP-anchored hairpin primer was developed and evaluated for the rapid and cost-effective detection of Chikungunya virus (CHIKV) with high sensitivity and specificity. The molecule 2, 7-diamino-1, 8-naphthyridine (DANP) binds to a cytosine-bulge and emits fluorescence at 450 nm when it is excited by 400 nm light. Thus, by measuring the decline in fluorescence emitted from DANP—primer complexes after PCR reaction, we could monitor the PCR progress. By adapting this property of DANP, we have previously developed the first generation DANP-coupled hairpin RT-PCR assay. In the current study, we improved the assay performance by conjugating the DANP molecule covalently onto the hairpin primer to fix the DANP/primer ratio at 1:1; and adjusting the excitation emission wavelength to 365/430 nm to minimize the background signal and a ‘turn-on’ system is achieved. After optimizing the PCR cycle number to 30, we not only shortened the total assay turnaround time to 60 minutes, but also further reduced the background fluorescence. The detection limit of our assay was 0.001 PFU per reaction. The DANP-anchored hairpin primer, targeting nsP2 gene of CHIKV genome, is highly specific to CHIKV, having no cross-reactivity to a panel of other RNA viruses tested. In conclusion, we report here a molecular diagnostic assay that is sensitive, specific, rapid and cost effective for CHIKV detection and can be performed where no real time PCR instrumentation is required. Our results from patient samples indicated 93.62% sensitivity and 100% specificity of this method, ensuring that it can be a useful tool for rapid detection of CHIKV for outbreaks in many parts of the world. PMID:27571201

  4. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    PubMed

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection. PMID:26280524

  5. Development of novel antibodies against non-structural proteins nsP1, nsP3 and nsP4 of chikungunya virus: potential use in basic research.

    PubMed

    Kumar, Sameer; Mamidi, Prabhudutta; Kumar, Abhishek; Basantray, Itishree; Bramha, Umarani; Dixit, Anshuman; Maiti, Prasanta Kumar; Singh, Sujay; Suryawanshi, Amol Ratnakar; Chattopadhyay, Subhasis; Chattopadhyay, Soma

    2015-11-01

    Chikungunya virus (CHIKV) has reemerged recently as an important pathogen, causing several large epidemics worldwide. This necessitates the development of better reagents to understand its biology and to establish effective and safe control measures. The present study describes the development and characterization of polyclonal antibodies (pAbs) against synthetic peptides of CHIKV non-structural proteins (nsPs; nsP1, nsP3 and nsP4). The reactivity of these pAbs was demonstrated by ELISA and Western blot. Additionally, in vitro infection studies in a mammalian system confirmed that these pAbs are highly sensitive and specific for CHIKV nsPs, as these proteins were detected very early during viral replication. Homology analysis of the selected epitope sequences revealed that they are conserved among all of the CHIKV strains of different genotypes, while comparison with other alphavirus sequences showed that none of them are 100% identical to the epitope sequences (except Onyong-nyong and Igbo Ora viruses, which show 100% identity to the nsP4 epitope). Interestingly, two different forms of CHIKV nsP1 and three different forms of nsP3 were detected in Western blot analysis during infection; however, further experimental investigations are required to confirm their identity. Also, the use of these antibodies demonstrated faster and enhanced expression profiles of all CHIKV nsPs in 2006 Indian outbreak strains when compared to the CHIKV prototype strain, suggesting the epidemic potential of the 2006 isolate. Accordingly, it can be suggested that the pAbs reported in this study can be used as sensitive and specific tools for experimental investigations of CHIKV replication and infection.

  6. [The tropical disease Chikungunya fever has come to Europe].

    PubMed

    Dogan, Ayse Dudu Altintas; Bunes, Kristin; Skarphédinsson, Sigurdur

    2013-06-10

    Chikungunya fever is an acute febrile illness associated with severe, often debilitating polyarthralgias. The disease is caused by the Chikungunya virus (CHIKV), an arthropod-borne virus that is transmitted to humans primarily via the bite of an infected mosquito. Since a re-emergence of CHIKV in 2004 in the Indian Ocean islands, the virus has spread into novel locations such as Europe. In Italy, an outbreak occurred in 2007. A mutation in CHIKV (E1-A226V) appears to improve virus survival in Ae. albopictus and also increase its virulence. Further attention should be given the disease since it is emerging in Europe.

  7. Arthropod-borne virus antibodies in sera of residents of Kainji Lake Basin, Nigeria 1980.

    PubMed

    Adekolu-John, E O; Fagbami, A H

    1983-01-01

    A survey for haemagglutination-inhibiting arthropod-borne virus antibody was carried out in the Kainji Lake area of Nigeria. Of 267 persons tested, 139 (52%) and 158 (59%) had alphavirus and flavivirus group HI antibody, respectively. The prevalence of antibody to individual virus antigen is as follows: Chikungunya, 45%; Semliki Forest, 25%; Sindbis, 33%, Yellow fever, 31%, Dengue type 2, 46%; and Zika 56%. The presence of high antibody rates to Chikungunya, Dengue type 2 and Yellow fever viruses is of public health significance. These viruses have been identified as the most important arthropod-borne viruses causing human infections in Nigeria.

  8. A study of Chikungunya outbreak in Delhi.

    PubMed

    Chakravarti, Anita; Malik, Sonia; Tiwari, Sayani; Ashraf, Anzar

    2011-12-01

    Chikungunya virus, an alphavirus belonging to the Togaviridae family, caused large scale outbreaks in several parts of southern, western and eastern India in 2006. We report Chikungunya outbreak in Delhi in 2010. This study was conducted in the virology laboratory of Maulana Azad Medical College and associated Lok Nayak Hospital, Delhi from August 2010 to February 2011. Serum samples of 324 patients presenting with fever, arthralgia, myalgia, rash etc. were tested for anti-Chikungunya IgM antibody using MAC ELISA. 148/324 (45.6%) samples were positive for anti Chikungunya IgM antibody. More females were affected compared to males (1: 1.34). The most common age group affected was 31-40 year. Characteristically, paediatric age group was least affected with cases in children accounting for only 3.3%. The number of cases increased with increasing age group. The commonest clinical presentation was arthralgia (100%) followed by fever (88%). Complications such as bleeding manifestations and encephalitis were seen in 2.7% patients. This report confirms emergence and establishment of CHIKV in the northern region of India, which is also endemic for dengue viruses. There is an urgent need for early and aggressive vector control and containment measures for risk reduction.

  9. Chikungunya outbreak in Montpellier, France, September to October 2014.

    PubMed

    Delisle, E; Rousseau, C; Broche, B; Leparc-Goffart, I; L'Ambert, G; Cochet, A; Prat, C; Foulongne, V; Ferre, J B; Catelinois, O; Flusin, O; Tchernonog, E; Moussion, I E; Wiegandt, A; Septfons, A; Mendy, A; Moyano, M B; Laporte, L; Maurel, J; Jourdain, F; Reynes, J; Paty, M C; Golliot, F

    2015-04-30

    In October 2014, an outbreak of 12 autochthonous chikungunya cases, 11 confirmed and 1 probable, was detected in a district of Montpellier, a town in the south of France colonised by the vector Aedes albopictus since 2010. A case returning from Cameroon living in the affected district was identified as the primary case. The epidemiological investigations and the repeated vector control treatments performed in the area and around places frequented by cases helped to contain the outbreak. In 2014, the chikungunya and dengue surveillance system in mainland France was challenged by numerous imported cases due to the chikungunya epidemic ongoing in the Caribbean Islands. This first significant outbreak of chikungunya in Europe since the 2007 Italian epidemic, however, was due to an East Central South African (ECSA) strain, imported by a traveller returning from West Africa. Important lessons were learned from this episode, which reminds us that the threat of a chikungunya epidemic in southern Europe is real.

  10. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil.

  11. First Imported Case of Zika Virus Infection into Korea.

    PubMed

    Jang, Hee-Chang; Park, Wan Beom; Kim, Uh Jin; Chun, June Young; Choi, Su-Jin; Choe, Pyoeng Gyun; Jung, Sook-In; Jee, Youngmee; Kim, Nam-Joong; Choi, Eun Hwa; Oh, Myoung-Don

    2016-07-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  12. First Imported Case of Zika Virus Infection into Korea

    PubMed Central

    Jee, Youngmee

    2016-01-01

    Since Zika virus has been spreading rapidly in the Americas from 2015, the outbreak of Zika virus infection becomes a global health emergency because it can cause neurological complications and adverse fetal outcome including microcephaly. Here, we report clinical manifestations and virus isolation findings from a case of Zika virus infection imported from Brazil. The patient, 43-year-old Korean man, developed fever, myalgia, eyeball pain, and maculopapular rash, but not neurological manifestations. Zika virus was isolated from his semen, and reverse-transcriptase PCR was positive for the virus in the blood, urine, and saliva on the 7th day of the illness but was negative on the 21st day. He recovered spontaneously without any neurological complications. He is the first case of Zika virus infection in Korea imported from Brazil. PMID:27366020

  13. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis

    PubMed Central

    Goupil, Brad A.; McNulty, Margaret A.; Martin, Matthew J.; McCracken, Michael K.; Christofferson, Rebecca C.; Mores, Christopher N.

    2016-01-01

    Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains. PMID:27182740

  14. Novel Lesions of Bones and Joints Associated with Chikungunya Virus Infection in Two Mouse Models of Disease: New Insights into Disease Pathogenesis.

    PubMed

    Goupil, Brad A; McNulty, Margaret A; Martin, Matthew J; McCracken, Michael K; Christofferson, Rebecca C; Mores, Christopher N

    2016-01-01

    Chikungunya virus is an arbovirus spread predominantly by Aedes aegypti and Ae. albopictus mosquitoes, and causes debilitating arthralgia and arthritis. While these are common manifestations during acute infection and it has been suggested they can recur in patients chronically, gaps in knowledge regarding the pathogenesis still exist. Two established mouse models were utilized (adult IRF 3/7 -/- -/- and wild-type C57BL/6J mice) to evaluate disease manifestations in bones and joints at various timepoints. Novel lesions in C57BL/6J mice consisted of periostitis (91%) and foci of cartilage of necrosis (50% of mice at 21 DPI). Additionally, at 21 DPI, 50% and 75% of mice exhibited periosteal bone proliferation affecting the metatarsal bones, apparent via histology and μCT, respectively. μCT analysis did not reveal any alterations in trabecular bone volume measurements in C57BL/6J mice. Novel lesions demonstrated in IRF 3/7 -/- -/- mice at 5 DPI included focal regions of cartilage necrosis (20%), periosteal necrosis (66%), and multifocal ischemic bone marrow necrosis (100%). Contralateral feet in 100% of mice of both strains had similar, though milder lesions. Additionally, comparison of control IRF 3/7 -/- -/- and wild-type C57BL/6J mice demonstrated differences in cortical bone. These experiments demonstrate novel manifestations of disease similar to those occurring in humans, adding insight into disease pathogenesis, and representing new potential targets for therapeutic interventions. Additionally, results demonstrate the utility of μCT in studies of bone and joint pathology and illustrate differences in bone dynamics between mouse strains.

  15. Effectiveness of Ultra-Low Volume Nighttime Applications of an Adulticide against Diurnal Aedes albopictus, a Critical Vector of Dengue and Chikungunya Viruses

    PubMed Central

    Farajollahi, Ary; Healy, Sean P.; Unlu, Isik; Gaugler, Randy; Fonseca, Dina M.

    2012-01-01

    Aedes albopictus, the Asian tiger mosquito, continues expanding its geographic range and involvement in mosquito-borne diseases such as chikungunya and dengue. Vector control programs rarely attempt to suppress this diurnal species with an ultra-low volume (ULV) adulticide because for maximum efficacy applications are conducted at night. During 2009–2011 we performed experimental nighttime applications of a novel adulticide (DUET®) against field populations of Ae. albopictus within an urban site composed of approximately 1,000 parcels (home and yard) in northeastern USA. Dual applications at mid label rate of the adulticide spaced one or two days apart accomplished significantly higher control (85.0±5.4% average reduction) than single full rate applications (73.0±5.4%). Our results demonstrate that nighttime ULV adulticiding is effective in reducing Ae. albopictus abundance and highlight its potential for use as part of integrated pest management programs and during disease epidemics when reducing human illness is of paramount importance. PMID:23145115

  16. Effectiveness of ultra-low volume nighttime applications of an adulticide against diurnal Aedes albopictus, a critical vector of dengue and chikungunya viruses.

    PubMed

    Farajollahi, Ary; Healy, Sean P; Unlu, Isik; Gaugler, Randy; Fonseca, Dina M

    2012-01-01

    Aedes albopictus, the Asian tiger mosquito, continues expanding its geographic range and involvement in mosquito-borne diseases such as chikungunya and dengue. Vector control programs rarely attempt to suppress this diurnal species with an ultra-low volume (ULV) adulticide because for maximum efficacy applications are conducted at night. During 2009-2011 we performed experimental nighttime applications of a novel adulticide (DUET®) against field populations of Ae. albopictus within an urban site composed of approximately 1,000 parcels (home and yard) in northeastern USA. Dual applications at mid label rate of the adulticide spaced one or two days apart accomplished significantly higher control (85.0 ± 5.4% average reduction) than single full rate applications (73.0 ± 5.4%). Our results demonstrate that nighttime ULV adulticiding is effective in reducing Ae. albopictus abundance and highlight its potential for use as part of integrated pest management programs and during disease epidemics when reducing human illness is of paramount importance.

  17. High Rate of Subclinical Chikungunya Virus Infection and Association of Neutralizing Antibody with Protection in a Prospective Cohort in The Philippines

    PubMed Central

    Yoon, In-Kyu; Alera, Maria Theresa; Lago, Catherine B.; Tac-An, Ilya A.; Villa, Daisy; Fernandez, Stefan; Thaisomboonsuk, Butsaya; Klungthong, Chonticha; Levy, Jens W.; Velasco, John Mark; Roque, Vito G.; Salje, Henrik; Macareo, Louis R.; Hermann, Laura L.; Nisalak, Ananda; Srikiatkhachorn, Anon

    2015-01-01

    Background Chikungunya virus (CHIKV) is a globally re-emerging arbovirus for which previous studies have indicated the majority of infections result in symptomatic febrile illness. We sought to characterize the proportion of subclinical and symptomatic CHIKV infections in a prospective cohort study in a country with known CHIKV circulation. Methods/Findings A prospective longitudinal cohort of subjects ≥6 months old underwent community-based active surveillance for acute febrile illness in Cebu City, Philippines from 2012-13. Subjects with fever history were clinically evaluated at acute, 2, 5, and 8 day visits, and at a 3-week convalescent visit. Blood was collected at the acute and 3-week convalescent visits. Symptomatic CHIKV infections were identified by positive CHIKV PCR in acute blood samples and/or CHIKV IgM/IgG ELISA seroconversion in paired acute/convalescent samples. Enrollment and 12-month blood samples underwent plaque reduction neutralization test (PRNT) using CHIKV attenuated strain 181/clone25. Subclinical CHIKV infections were identified by ≥8-fold rise from a baseline enrollment PRNT titer <10 without symptomatic infection detected during the intervening surveillance period. Selected CHIKV PCR-positive samples underwent viral isolation and envelope protein-1 gene sequencing. Of 853 subjects who completed all study procedures at 12 months, 19 symptomatic infections (2.19 per 100 person-years) and 87 subclinical infections (10.03 per 100 person-years) occurred. The ratio of subclinical-to-symptomatic infections was 4.6:1 varying with age from 2:1 in 6 month-5 year olds to 12:1 in those >50 years old. Baseline CHIKV PRNT titer ≥10 was associated with 100% (95%CI: 46.1, 100.0) protection from symptomatic CHIKV infection. Phylogenetic analysis demonstrated Asian genotype closely related to strains from Asia and the Caribbean. Conclusions Subclinical infections accounted for a majority of total CHIKV infections. A positive baseline CHIKV PRNT

  18. [Dengue and chikungunya acquired during travel in the tropics].

    PubMed

    van Aart, Carola J C; Braks, Marieta A H; Hautvast, Jeannine L A; de Mast, Quirijn; Tostmann, Alma

    2015-01-01

    The global incidence of dengue and chikungunya has greatly increased over recent decades, partly due to the increase of geographic distribution of both vectors. These infections are endemic to the tropics and subtropics, however autochthonous transmission and outbreaks have been described in non-endemic areas. Currently, there is a large chikungunya outbreak in the western hemisphere which started in the Caribbean. Chikungunya had not previously been endemic to this region. Both arboviral infections are important causes of fever in Dutch travellers returning from tropical destinations. The clinical presentations of dengue and chikungunya overlap; both are characterised by high fever and arthralgia. Bleeding and plasma leakage are potentially life-threatening complications of dengue, while persistent arthralgia typifies chikungunya. The prevention of mosquito bites, by using protective clothing and insect repellents, is the only way to prevent infection. No vaccine is yet available.

  19. [Dengue and chikungunya acquired during travel in the tropics].

    PubMed

    van Aart, Carola J C; Braks, Marieta A H; Hautvast, Jeannine L A; de Mast, Quirijn; Tostmann, Alma

    2015-01-01

    The global incidence of dengue and chikungunya has greatly increased over recent decades, partly due to the increase of geographic distribution of both vectors. These infections are endemic to the tropics and subtropics, however autochthonous transmission and outbreaks have been described in non-endemic areas. Currently, there is a large chikungunya outbreak in the western hemisphere which started in the Caribbean. Chikungunya had not previously been endemic to this region. Both arboviral infections are important causes of fever in Dutch travellers returning from tropical destinations. The clinical presentations of dengue and chikungunya overlap; both are characterised by high fever and arthralgia. Bleeding and plasma leakage are potentially life-threatening complications of dengue, while persistent arthralgia typifies chikungunya. The prevention of mosquito bites, by using protective clothing and insect repellents, is the only way to prevent infection. No vaccine is yet available. PMID:25784059

  20. Chikungunya fever presenting with acute optic neuropathy.

    PubMed

    Mohite, Abhijit Anand; Agius-Fernandez, Adriana

    2015-07-28

    Chikungunya fever is a vector borne virus that typically causes a self-limiting systemic illness with fever, skin rash and joint aches 2 weeks after infection. We present the case of a 69-year-old woman presenting with an acute unilateral optic neuropathy as a delayed complication of Chikungunya virus (CHIKV) infection contracted during a recent trip to the West Indies. She presented to our ophthalmology department with acute painless visual field loss in the right eye and a recent flu-like illness. She was found to have a right relative afferent pupillary defect (RAPD) with unilateral optic disc swelling. Serology confirmed recent CHIKV infection. Treatment with intravenous methylprednisolone was delayed while awaiting MRI scans and serology results. At 5-month follow-up, there was a persistent right RAPD and marked optic atrophy with a corresponding inferior scotoma in the visual field.

  1. Laboratory-confirmed dengue fever and chikungunya fever cases at the Narita Airport Quarantine Station in 2013.

    PubMed

    Furuichi, Mieko; Makie, Toshio; Honma, Yasuko; Isoda, Takayoshi; Miyake, Satoru

    2015-01-01

    Fourteen patients were laboratory-confirmed cases of imported infectious diseases at the Narita Airport Quarantine Station in 2013. Blood tests were performed on 283 subjects suspected of having imported infectious diseases. Of these, 11 were diagnosed as having dengue fever (dengue) and 3 as having chikungunya fever (chikungunya) using real-time RT-PCR. The possible countries from which dengue virus infections were contracted were Thailand, Laos, Sri Lanka, and some other countries in Southeast Asia and South Asia. The 3 chikungunya cases were also diagnosed in individuals that returned from Southeast Asia. Most of the patients with dengue had a fever of over 38℃. The other symptoms were generalized fatigue, dull headache, pain behind the eyes, arthralgia, and digestive symptoms. Four of the patients were unaware of any mosquito bites. The information obtained from the confirmed cases showed that it is important to consider both the destination to which individuals travelled and the clinical symptoms, regardless of whether the subjects were aware of mosquito bites. The detection rate of chikungunya at the Quarantine Station was higher than that of dengue in all reported cases in Japan.

  2. Chikungunya and dengue autochthonous cases in Europe, 2007-2012.

    PubMed

    Tomasello, Danilo; Schlagenhauf, Patricia

    2013-01-01

    A large number of autochthonous cases of dengue fever (2237) and chikungunya fever (231) occurred in Europe (Italy, France, Croatia, Madeira) during the period covered by our analysis (2007-2012). In all dengue outbreaks, the circulating strain, identified by means of molecular analysis, was the DENV-1 strain. Dengue and chikungunya are infectious diseases that often result in hospitalizations and are associated with high public health costs. The dengue epidemic on the island of Madeira resulted in 122 hospitalizations. Only one death (from chikungunya) occurred but long-term sequelae were described after the chikungunya outbreak in Emilia-Romagna, Italy. Vector control is key to reducing the impact of these diseases. During the chikungunya outbreak in Italy and the dengue outbreak in Madeira, appropriate measures for the control of mosquitoes (Aedes aegypti and Aedes albopictus) were effectively implemented. The effectiveness of these measures (reducing the number of breeding sites, application of pesticides and insecticides, public health education) was shown in the context of these real-life outbreaks. All the pre-requisites for autochthonous transmission of both dengue virus and chikungunya virus (vectors, viremic returned travellers, climatic conditions) are present in Europe. Constant surveillance is imperative.

  3. [Paediatric features of Dengue and Chikungunya fevers].

    PubMed

    Gérardin, P

    2010-01-01

    Dengue (Df) and Chikungunya fever (Cf) arbovirosis are booming in the world, because of the plasticity of their pathogens, mutant RNA viruses making the acquisition of sustainable herd immunity and vaccination difficult in humans, and the plasticity of their vectors, the female mosquitoes of the genus Aedes (Stegomya), capable of adapting to different environments. This review summarizes the viral life cycle and epidemiology of these arboviruses, pathogenesis and pediatric aspects of their clinical forms and the basic principles of their treatment and prevention.

  4. Chikungunya Virus–Vector Interactions

    PubMed Central

    Coffey, Lark L.; Failloux, Anna-Bella; Weaver, Scott C.

    2014-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya fever, a severe, debilitating disease that often produces chronic arthralgia. Since 2004, CHIKV has emerged in Africa, Indian Ocean islands, Asia, Europe, and the Americas, causing millions of human infections. Central to understanding CHIKV emergence is knowledge of the natural ecology of transmission and vector infection dynamics. This review presents current understanding of CHIKV infection dynamics in mosquito vectors and its relationship to human disease emergence. The following topics are reviewed: CHIKV infection and vector life history traits including transmission cycles, genetic origins, distribution, emergence and spread, dispersal, vector competence, vector immunity and microbial interactions, and co-infection by CHIKV and other arboviruses. The genetics of vector susceptibility and host range changes, population heterogeneity and selection for the fittest viral genomes, dual host cycling and its impact on CHIKV adaptation, viral bottlenecks and intrahost diversity, and adaptive constraints on CHIKV evolution are also discussed. The potential for CHIKV re-emergence and expansion into new areas and prospects for prevention via vector control are also briefly reviewed. PMID:25421891

  5. Risk Factors for the Presence of Chikungunya and Dengue Vectors (Aedes aegypti and Aedes albopictus), Their Altitudinal Distribution and Climatic Determinants of Their Abundance in Central Nepal

    PubMed Central

    Dhimal, Meghnath; Gautam, Ishan; Joshi, Hari Datt; O’Hara, Robert B.; Ahrens, Bodo; Kuch, Ulrich

    2015-01-01

    Background The presence of the recently introduced primary dengue virus vector mosquito Aedes aegypti in Nepal, in association with the likely indigenous secondary vector Aedes albopictus, raises public health concerns. Chikungunya fever cases have also been reported in Nepal, and the virus causing this disease is also transmitted by these mosquito species. Here we report the results of a study on the risk factors for the presence of chikungunya and dengue virus vectors, their elevational ceiling of distribution, and climatic determinants of their abundance in central Nepal. Methodology/Principal Findings We collected immature stages of mosquitoes during six monthly cross-sectional surveys covering six administrative districts along an altitudinal transect in central Nepal that extended from Birgunj (80 m above sea level [asl]) to Dhunche (highest altitude sampled: 2,100 m asl). The dengue vectors Ae. aegypti and Ae. albopictus were commonly found up to 1,350 m asl in Kathmandu valley and were present but rarely found from 1,750 to 2,100 m asl in Dhunche. The lymphatic filariasis vector Culex quinquefasciatus was commonly found throughout the study transect. Physiographic region, month of collection, collection station and container type were significant predictors of the occurrence and co-occurrence of Ae. aegypti and Ae. albopictus. The climatic variables rainfall, temperature, and relative humidity were significant predictors of chikungunya and dengue virus vectors abundance. Conclusions/Significance We conclude that chikungunya and dengue virus vectors have already established their populations up to the High Mountain region of Nepal and that this may be attributed to the environmental and climate change that has been observed over the decades in Nepal. The rapid expansion of the distribution of these important disease vectors in the High Mountain region, previously considered to be non-endemic for dengue and chikungunya fever, calls for urgent actions to

  6. Epidemiological features of dengue and chikungunya infections in Burma.

    PubMed

    Thaung, U; Ming, C K; Swe, T; Thein, S

    1975-06-01

    A serological survey for antibody to dengue and chikungunya was carried out in all 14 divisions and states and 2 border towns in Burma during 1973-74. Dengue HI antibody prevalence rate of less than 10% was observed in Arakan and Shan States, 10 to 30% in the Irrawaddy, Pegu, Mandalay Divisions and Kachin, Mon and Karen States, 31 to 60% in Sagaing Division, and over 60% in Rangoon, Magwe and Tenasserim Divisions. Similarly, chikungunya HI antibody prevalence rate of less than 10% was observed in Arakan State, 10 to 30% in the Irrawaddy, Pegu, Mandalay and Sagaing Divisions and Kachin State, 31 to 60% in Rangoon Division and Mon State. Both dengue and chikungunya antibodies were detected where Aedes aegypti mosquitoes were prevalent but the antibody prevalent rates were not directly proportional to the premises index. No HI antibody to dengue nor chikungunya was detected in Aedes aegypti free hilly areas, Chin and Kayah States, but was detected in the Shan State, Dengue and chikungunya infections were observed both in rural and urban populations. Dengue and chikungunya infections affected all socioeconomic classes in Rangoon equally but in Mandalay high socioeconomic class was nearly 3 times less affected than lower socioeconomic class. The infrequencies of dengue and chikungunya infections were observed to be 2 to 3 times higher in residents of Rangoon City than those of other towns. In Rangoon the antibody prevalence rates to dengue increased progressively with age while in other towns no appreciable increase in rates with age was observed. Both sexes were equally affected. This study provides strong circumstantial evidence that dengue and chikungunya viruses are highly and widely distributed throughout Burma, and that new outbreaks of haemorrhagic fever could occur in previously free areas following introduction of dengue viruses into populations previously exposed to one type of dengue.

  7. Imported dengue virus infections in German tourists.

    PubMed

    Schwarz, T F; Jäger, G; Gilch, S

    1995-10-01

    Dengue viruses (DEN) are increasingly becoming endemic and epidemic in tropical and subtropical countries. In this study, 17 serologically confirmed clinical cases of DEN infection diagnosed in German tourists over the period from May 1993 until May 1994 are presented. Thirteen out of 17 (76.5%) infections occurred in southeast Asia (Thailand 58.9%), and 4/17 (23.5%) in Central and South America. All sera screened by means of the indirect immunofluorescence assay (IIFA) were positive for anti-DEN IgM. Acute infection was confirmed by demonstrating anti-DEN IgM using a "mu-capture assay". Sixteen out of 17 (94.1%) of patients presenting with fever upon admission were positive for anti-DEN IgG, with titres of > or = 128 in the IIFA. This report indicates the rising significance of DEN as a travel-associated infection in German tourists.

  8. Neurocognitive Outcome of Children Exposed to Perinatal Mother-to-Child Chikungunya Virus Infection: The CHIMERE Cohort Study on Reunion Island

    PubMed Central

    Ramful, Duksha; Boumahni, Brahim; Bintner, Marc; Alessandri, Jean-Luc; Carbonnier, Magali; Tiran-Rajaoefera, Isabelle; Beullier, Gilles; Boya, Irénée; Noormahomed, Tahir; Okoï, Jocelyn; Rollot, Olivier; Cotte, Liliane; Jaffar-Bandjee, Marie-Christine; Michault, Alain; Favier, François; Kaminski, Monique; Fourmaintraux, Alain; Fritel, Xavier

    2014-01-01

    Background Little is known about the neurocognitive outcome in children exposed to perinatal mother-to-child Chikungunya virus (p-CHIKV) infection. Methods The CHIMERE ambispective cohort study compared the neurocognitive function of 33 p-CHIKV-infected children (all but one enrolled retrospectively) at around two years of age with 135 uninfected peers (all enrolled prospectively). Psychomotor development was assessed using the revised Brunet-Lezine scale, examiners blinded to infectious status. Development quotients (DQ) with subscores covering movement/posture, coordination, language, sociability skills were calculated. Predictors of global neurodevelopmental delay (GND, DQ≤85), were investigated using multivariate Poisson regression modeling. Neuroradiologic follow-up using magnetic resonance imaging (MRI) scans was proposed for most of the children with severe forms. Results The mean DQ score was 86.3 (95%CI: 81.0–91.5) in infected children compared to 100.2 (95%CI: 98.0–102.5) in uninfected peers (P<0.001). Fifty-one percent (n = 17) of infected children had a GND compared to 15% (n = 21) of uninfected children (P<0.001). Specific neurocognitive delays in p-CHIKV-infected children were as follows: coordination and language (57%), sociability (36%), movement/posture (27%). After adjustment for maternal social situation, small for gestational age, and head circumference, p-CHIKV infection was found associated with GND (incidence rate ratio: 2.79, 95%CI: 1.45–5.34). Further adjustments on gestational age or breastfeeding did not change the independent effect of CHIKV infection on neurocognitive outcome. The mean DQ of p-CHIKV-infected children was lower in severe encephalopathic children than in non-severe children (77.6 versus 91.2, P<0.001). Of the 12 cases of CHIKV neonatal encephalopathy, five developed a microcephaly (head circumference <−2 standard deviations) and four matched the definition of cerebral palsy. MRI scans showed severe

  9. High Seroprevalence of Chikungunya Virus Antibodies Among Pregnant Women Living in an Urban Area in Benin, West Africa

    PubMed Central

    Bacci, Anastasia; Marchi, Serena; Fievet, Nadine; Massougbodji, Achille; Perrin, Renè Xavier; Chippaux, Jean-Philippe; Sambri, Vittorio; Landini, Maria Paola; Varani, Stefania; Rossini, Giada

    2015-01-01

    The aim of this study was to investigate the seroprevalence of antichikungunya virus (anti-CHIKV) antibodies in pregnant women living in an urban area of Benin (West Africa). Results were obtained by screening sera collected in 2006 and 2007 with enzyme-linked immunosorbent assay (ELISA) for anti-CHIKV immunoglobulin G (IgG) and IgM. Positive results were confirmed by indirect immunofluorescence test and microneutralization assay. We found that a large proportion (36.1%) of pregnant women living in Cotonou had specific IgG against CHIKV, indicating a high seroprevalence of the infection in urban southern Benin, whereas no active cases of CHIKV infection were detected. PMID:25940198

  10. Chikungunya: A Potentially Emerging Epidemic?

    PubMed Central

    Thiboutot, Michelle M.; Kannan, Senthil; Kawalekar, Omkar U.; Shedlock, Devon J.; Khan, Amir S.; Sarangan, Gopalsamy; Srikanth, Padma; Weiner, David B.; Muthumani, Karuppiah

    2010-01-01

    Chikungunya virus is a mosquito-borne emerging pathogen that has a major health impact in humans and causes fever disease, headache, rash, nausea, vomiting, myalgia, and arthralgia. Indigenous to tropical Africa, recent large outbreaks have been reported in parts of South East Asia and several of its neighboring islands in 2005–07 and in Europe in 2007. Furthermore, positive cases have been confirmed in the United States in travelers returning from known outbreak areas. Currently, there is no vaccine or antiviral treatment. With the threat of an emerging global pandemic, the peculiar problems associated with the more immediate and seasonal epidemics warrant the development of an effective vaccine. In this review, we summarize the evidence supporting these concepts. PMID:20436958

  11. [A case of Chikungunya fever in the Primorye Territory].

    PubMed

    Simakova, A I; Popov, A F; Sokotun, S A; Sokotun, O A; Petukhova, S A

    2014-01-01

    The authors analyze a case of Chikungunya fever imported to Vladivostok. The disease was severe and resulted in disability in a female patient for more than 6 months. There were difficulties in its differential diagnosis with rheumatic diseases.

  12. Reappearance of chikungunya, formerly called dengue, in the Americas.

    PubMed

    Halstead, Scott B

    2015-04-01

    After an absence of ≈200 years, chikungunya returned to the American tropics in 2013. The virus is maintained in a complex African zoonotic cycle but escapes into an urban cycle at 40- to 50-year intervals, causing global pandemics. In 1823, classical chikungunya, a viral exanthem in humans, occurred on Zanzibar, and in 1827, it arrived in the Caribbean and spread to North and South America. In Zanzibar, the disease was known as kidenga pepo, Swahili for a sudden cramp-like seizure caused by an evil spirit; in Cuba, it was known as dengue, a Spanish homonym of denga. During the eighteenth century, dengue (present-day chikungunya) was distinguished from breakbone fever (present-day dengue), another febrile exanthem. In the twentieth century, experiments resulted in the recovery and naming of present-day dengue viruses. In 1952, chikungunya virus was recovered during an outbreak in Tanzania, but by then, the virus had lost its original name to present-day dengue viruses.

  13. Reappearance of Chikungunya, Formerly Called Dengue, in the Americas

    PubMed Central

    2015-01-01

    After an absence of ≈200 years, chikungunya returned to the American tropics in 2013. The virus is maintained in a complex African zoonotic cycle but escapes into an urban cycle at 40- to 50-year intervals, causing global pandemics. In 1823, classical chikungunya, a viral exanthem in humans, occurred on Zanzibar, and in 1827, it arrived in the Caribbean and spread to North and South America. In Zanzibar, the disease was known as kidenga pepo, Swahili for a sudden cramp-like seizure caused by an evil spirit; in Cuba, it was known as dengue, a Spanish homonym of denga. During the eighteenth century, dengue (present-day chikungunya) was distinguished from breakbone fever (present-day dengue), another febrile exanthem. In the twentieth century, experiments resulted in the recovery and naming of present-day dengue viruses. In 1952, chikungunya virus was recovered during an outbreak in Tanzania, but by then, the virus had lost its original name to present-day dengue viruses. PMID:25816211

  14. The Hidden Burden of Dengue and Chikungunya in Chennai, India

    PubMed Central

    Rodríguez-Barraquer, Isabel; Solomon, Sunil S.; Kuganantham, Periaswamy; Srikrishnan, Aylur Kailasom; Vasudevan, Canjeevaram K.; Iqbal, Syed H.; Balakrishnan, Pachamuthu; Solomon, Suniti; Mehta, Shruti H.; Cummings, Derek A. T.

    2015-01-01

    Background Dengue and chikungunya are rapidly expanding viruses transmitted by mosquitoes of the genus Aedes. Few epidemiological studies have examined the extent of transmission of these infections in South India despite an increase in the number of reported cases, and a high suitability for transmission. Methods and findings We conducted a household-based seroprevalence survey among 1010 individuals aged 5-40 years living in fifty randomly selected spatial locations in Chennai, Tamil Nadu. Participants were asked to provide a venous blood sample and to complete a brief questionnaire with basic demographic and daily activity information. Previous exposure to dengue and chikungunya was determined using IgG indirect ELISA (Panbio) and IgG ELISA (Novatec), respectively. We used this data to estimate key transmission parameters (force of infection and basic reproductive number) and to explore factors associated with seropositivity. While only 1% of participants reported history of dengue and 20% of chikungunya, we found that 93% (95%CI 89-95%) of participants were seropositive to dengue virus, and 44% (95%CI 37-50%) to chikungunya. Age-specific seroprevalence was consistent with long-tem, endemic circulation of dengue and suggestive of epidemic chikungunya transmission. Seropositivity to dengue and chikungunya were significantly correlated, even after adjusting for individual and household factors. We estimate that 23% of the susceptible population gets infected by dengue each year, corresponding to approximately 228,000 infections. This transmission intensity is significantly higher than that estimated in known hyperendemic settings in Southeast Asia and the Americas. Conclusions These results provide unprecedented insight into the very high transmission potential of dengue and chikungunya in Chennai and underscore the need for enhanced surveillance and control methods. PMID:26181441

  15. Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy.

    PubMed

    Thiberville, Simon-Djamel; Moyen, Nanikaly; Dupuis-Maguiraga, Laurence; Nougairede, Antoine; Gould, Ernest A; Roques, Pierre; de Lamballerie, Xavier

    2013-09-01

    Chikungunya virus (CHIKV) is the aetiological agent of the mosquito-borne disease chikungunya fever, a debilitating arthritic disease that, during the past 7years, has caused immeasurable morbidity and some mortality in humans, including newborn babies, following its emergence and dispersal out of Africa to the Indian Ocean islands and Asia. Since the first reports of its existence in Africa in the 1950s, more than 1500 scientific publications on the different aspects of the disease and its causative agent have been produced. Analysis of these publications shows that, following a number of studies in the 1960s and 1970s, and in the absence of autochthonous cases in developed countries, the interest of the scientific community remained low. However, in 2005 chikungunya fever unexpectedly re-emerged in the form of devastating epidemics in and around the Indian Ocean. These outbreaks were associated with mutations in the viral genome that facilitated the replication of the virus in Aedes albopictus mosquitoes. Since then, nearly 1000 publications on chikungunya fever have been referenced in the PubMed database. This article provides a comprehensive review of chikungunya fever and CHIKV, including clinical data, epidemiological reports, therapeutic aspects and data relating to animal models for in vivo laboratory studies. It includes Supplementary Tables of all WHO outbreak bulletins, ProMED Mail alerts, viral sequences available on GenBank, and PubMed reports of clinical cases and seroprevalence studies.

  16. Epidemiology of Chikungunya infection on Reunion Island, Mayotte, and neighboring countries.

    PubMed

    Renault, P; Balleydier, E; D'Ortenzio, E; Bâville, M; Filleul, L

    2012-03-01

    Since 2004, the frequency of chikungunya virus infections has been increasing in Africa, Indian Ocean islands, and Asia. The epidemic began on the Kenyan coast, and reached the Comoros at the end of 2004 before spreading to the South-western Indian Ocean islands (SWIOI) in 2005 and especially in 2006. The epidemic then spread to Asia where epidemic foci are still active today. This increase also affected temperate zone countries where imported cases were reported, and indigenous transmission was reported in Italy in 2007, and in France (Var) in 2010. This review provides an update on the knowledge gained from monitoring chikungunya infections in SWIOI. Despite significant differences in design and performance, the implementation of surveillance systems has allowed describing the evolution of epidemic waves in the affected areas. Synchronous epidemic waves were observed in SWIOI, despite the differences between the preventive measures locally implemented. Between 2005 and 2007, all SWIOI were in inter-epidemic situation, except for Madagascar where a persistent virus circulation in an endemic-epidemic pattern was observed. In 2009, and in 2010, two moderate indigenous outbreaks were identified on the Reunion Island by the inter-epidemic surveillance system. Strains analyses demonstrated a reintroduction of the virus from Madagascar. These limited outbreaks should be a reminder of the vulnerability of SWIOI to arbovirosis, since the entomological indexes for competent vectors are high and the virus keeps on circulating more or less actively in the area.

  17. The invaders: phylogeography of dengue and chikungunya viruses Aedes vectors, on the South West islands of the Indian Ocean.

    PubMed

    Delatte, H; Bagny, L; Brengue, C; Bouetard, A; Paupy, C; Fontenille, D

    2011-10-01

    to spread quickly are of high importance of arbovirus transmission and the epidemicity of the associated diseases in these islands.

  18. Clinical Profile of Chikungunya Patients during the Epidemic of 2007 in Kerala, India

    PubMed Central

    Vijayakumar, Krishna Pillai; Nair Anish, Thekkumkara Surendran; George, Biju; Lawrence, Tony; Muthukkutty, Sujina C; Ramachandran, Reshmi

    2011-01-01

    Background: The association of the present Chikungunya pandemic with a mutation in the Chik virus is already established in many parts of the world, including Kerala. Kerala was one of the worst-affected states of India in the Chikungunya epidemic of 2006–2007. It is important to discuss the clinical features of patients affected by Chikungunya fever in the context of this change in the epidemiology of the disease. Aim: This study tries to analyze the clinical picture of the Chikungunya patients in Kerala during the epidemic of 2007. Setting and Design: A cross-sectional survey was carried out in five of the most affected districts in Kerala, India. Materials and Methods: A two-stage cluster sampling technique was used to collect the information. Ten clusters each were selected from all the five districts, and the size of the clusters were 18 houses each. A structured interview schedule was used for data collection. Diagnosis based on clinical signs and symptoms was the major case-finding strategy. Results and Conclusion: Of the 3623 residents in the surveyed households, 1913 (52.8%) had Chikungunya clinically. Most of the affected were in the adult age group (73.4%). Swelling of the joints was seen in 69.9% of the patients, followed by headache (64.1%) and itching (50.3%). The knee joint was the most common joint affected (52%). The number of patients with persistence of any of the symptoms even after 1 month of illness was 1388 (72.6%). Taking bed rest till the relief of joint pain was found to be a protective factor for the persistence of the symptoms. Recurrence of symptoms with a period of disease-free interval was complained by 669 (35.0%) people. Older age (>40 years), a presentation of high-grade fever with shivering, involvement of the small joints of the hand, presence of rashes or joint swelling during the first week of fever and fever lasting for more than 1 week were the significant risk factors for recurrence of symptoms predicted by a binary

  19. THE BURDEN OF DENGUE AND CHIKUNGUNYA WORLDWIDE: IMPLICATIONS FOR THE SOUTHERN UNITED STATES AND CALIFORNIA

    PubMed Central

    Fredericks, Anthony C.; Fernandez-Sesma, Ana

    2015-01-01

    Dengue virus (DENV) spreads to humans through the bite of an infected Aedes aegypti or Aedes albopictus mosquito and is a growing public health threat to both industrialized and developing nations worldwide. Outbreaks of autochthonous dengue in the United States occurred extensively in the past but over the past three decades have again taken place in Florida, Hawai’i, and Texas as well as in American Samoa, Guam, Northern Mariana Islands, Puerto Rico, and the US Virgin Islands. As the Aedes vectors spread worldwide it is anticipated that DENV as well as other viruses also transmitted by these vectors, such as Chikungunya virus (CHKV), will invade new areas of the world, including the US. In this review, we describe the current burden of dengue disease worldwide and the potential introduction of DENV and CHKV into different areas of the US. Of these areas, the state of California saw the arrival and spread of the Aedes aegypti vector beginning in 2013. This invasion presents a developing situation when considering the state’s number of imported dengue cases and proximity to northern Mexico as well as the rising specter of chikungunya in the Western hemisphere. The distribution of Aedes vectors in California as well as a discussion of several factors contributing to the risk of dengue importation are discussed and evaluated. PMID:25960096

  20. Preparedness for threat of chikungunya in the pacific.

    PubMed

    Roth, Adam; Hoy, Damian; Horwood, Paul F; Ropa, Berry; Hancock, Thane; Guillaumot, Laurent; Rickart, Keith; Frison, Pascal; Pavlin, Boris; Souares, Yvan

    2014-08-01

    Chikungunya virus (CHIKV) caused significant outbreaks of illness during 2005-2007 in the Indian Ocean region. Chikungunya outbreaks have also occurred in the Pacific region, including in Papua New Guinea in 2012; New Caledonia in April 2013; and Yap State, Federated States of Micronesia, in August 2013. CHIKV is a threat in the Pacific, and the risk for further spread is high, given several similarities between the Pacific and Indian Ocean chikungunya outbreaks. Island health care systems have difficulties coping with high caseloads, which highlights the need for early multidisciplinary preparedness. The Pacific Public Health Surveillance Network has developed several strategies focusing on surveillance, case management, vector control, laboratory confirmation, and communication. The management of this CHIKV threat will likely have broad implications for global public health.

  1. Outbreak of chikungunya fever, Dakshina Kannada District, South India, 2008.

    PubMed

    Manimunda, Sathya P; Sugunan, Attayur P; Rai, Subhodh K; Vijayachari, Paluru; Shriram, Ananganallur N; Sharma, Sameer; Muruganandam, Nagarajan; Chaitanya, Itta K; Guruprasad, Dev R; Sudeep, Anakkathil B

    2010-10-01

    The outbreak of chikungunya fever that surfaced in India during late 2005 has affected more than 1.56 million people, spread to more than 17 states/union territories, and is still ongoing. Many of these areas are dengue- and leptospirosis-endemic settings. We carried out a cross-sectional survey in one such chikungunya-affected location in Dakshina Kannada District of Karnataka State to estimate the magnitude of the epidemic and the proportion of chikungunya virus (CHIKV) infections that remained clinically inapparent. The seropositivity for CHIKV infection was 62.2%, and the attack rate of confirmed CHIK fever was 58.3%. The proportion of inapparent CHIKV infection was 6.3%. The increasing trend in the seropositivity and attack rate of CHIKV infection with age group was statistically significant. The present study is an indicator of the magnitude of the ongoing outbreak of CHIKV infection in India that started during 2005-2006.

  2. [First case of chikungunya diagnosed in the Netherlands].

    PubMed

    Hassing, R J; Heijstek, M W; van Beek, Y; van Doornum, G J J; Overbosch, D

    2008-01-12

    A 52-year-old man was seen in the Diagnostic Centre for Tropical Diseases of the Havenziekenhuis, Rotterdam, presenting with arthralgia, fever and exanthema following a stay in Mauritius. Infection with the Dengue virus infection is a common diagnosis for this combination of complaints, but nowadays chikungunya should also be considered. This is particularly the case when a patient has visited a country in or around the Indian Ocean. Risk areas are La Réunion and Mauritius, where, in February 2005 and April 2005 respectively, epidemics broke out. Chikungunya is a viral infection. The causative virus is an Alpha virus, transmitted by mosquitoes. The symptoms include arthralgia, myalgia, diffuse maculopapular rash, fever and headache. In contrast to dengue, chikungunya is not associated with haemorrhagic diathesis. Treatment takes place in response to the symptoms, since there is no targeted therapy available. The main preventive measure is to prevent mosquito bites. The disease is not deadly and healing is spontaneous. To our knowledge this is the first case of chikungunya diagnosed in the Netherlands during this epidemic. The disease has recently been reported in Italy, where native mosquitoes transmit it.

  3. The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition.

    PubMed

    Goh, Lucas Y H; Hobson-Peters, Jody; Prow, Natalie A; Baker, Kelly; Piyasena, Thisun B H; Taylor, Carmel T; Rana, Ashok; Hastie, Marcus L; Gorman, Jeff J; Hall, Roy A

    2015-06-08

    Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1-35 and 140-210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP.

  4. The Chikungunya Virus Capsid Protein Contains Linear B Cell Epitopes in the N- and C-Terminal Regions that are Dependent on an Intact C-Terminus for Antibody Recognition

    PubMed Central

    Goh, Lucas Y. H.; Hobson-Peters, Jody; Prow, Natalie A.; Baker, Kelly; Piyasena, Thisun B. H.; Taylor, Carmel T.; Rana, Ashok; Hastie, Marcus L.; Gorman, Jeff J.; Hall, Roy A.

    2015-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne agent that causes severe arthritic disease in humans and is considered a serious health threat in areas where competent mosquito vectors are prevalent. CHIKV has recently been responsible for several millions of cases of disease, involving over 40 countries. The recent re-emergence of CHIKV and its potential threat to human health has stimulated interest in better understanding of the biology and pathogenesis of the virus, and requirement for improved treatment, prevention and control measures. In this study, we mapped the binding sites of a panel of eleven monoclonal antibodies (mAbs) previously generated towards the capsid protein (CP) of CHIKV. Using N- and C-terminally truncated recombinant forms of the CHIKV CP, two putative binding regions, between residues 1–35 and 140–210, were identified. Competitive binding also revealed that five of the CP-specific mAbs recognized a series of overlapping epitopes in the latter domain. We also identified a smaller, N-terminally truncated product of native CP that may represent an alternative translation product of the CHIKV 26S RNA and have potential functional significance during CHIKV replication. Our data also provides evidence that the C-terminus of CP is required for authentic antigenic structure of CP. This study shows that these anti-CP mAbs will be valuable research tools for further investigating the structure and function of the CHIKV CP. PMID:26061335

  5. Interferon-alpha/beta deficiency greatly exacerbates arthritogenic disease in mice infected with wild-type chikungunya virus but not with the cell culture-adapted live-attenuated 181/25 vaccine candidate

    PubMed Central

    Gardner, Christina L.; Burke, Crystal W.; Higgs, Stephen T.; Klimstra, William B.; Ryman, Kate D.

    2012-01-01

    In humans, chikungunya virus (CHIKV) infection causes fever, rash, and acute and persisting polyarthalgia/arthritis associated with joint swelling. We report a new CHIKV disease model in adult mice that distinguishes the wild-type CHIKV-LR strain from the live-attenuated vaccine strain (CHIKV-181/25). Although eight-week old normal mice inoculated in the hind footpad developed no hind limb swelling with either virus, CHIKV-LR replicated in musculoskeletal tissues and caused detectable inflammation. In mice deficient in STAT1-dependent interferon (IFN) responses, CHIKV-LR caused significant swelling of the inoculated and contralateral limbs and dramatic inflammatory lesions, while CHIKV-181/25 vaccine and another arthritogenic alphavirus, Sindbis, failed to induce swelling. IFN responses suppressed CHIKV-LR and CHIKV-181/25 replication equally in dendritic cells in vitro whereas macrophages were refractory to infection independently of STAT1-mediated IFN responses. Glycosaminoglycan (GAG) binding may be a CHIKV vaccine attenuation mechanism as CHIKV-LR infectivity was not dependent upon GAG, while CHIKV-181/25 was highly dependent. PMID:22305131

  6. Imported dengue virus serotype 1 from Madeira to Finland 2012.

    PubMed

    Huhtamo, E; Korhonen, Em; Vapalahti, O

    2013-01-01

    Imported dengue cases originating from the Madeiran outbreak are increasingly reported. In 2012 five Finnish travellers returning from Madeira were diagnosed with dengue fever. Viral sequence data was obtained from two patients. The partial C-preM sequences (399 and 396 bp respectively) were found similar to that of an autochthonous case from Madeira. The partial E-gene sequence (933 bp) which was identical among the two patients grouped phylogenetically with South American strains of dengue virus serotype 1.

  7. Development of a consensus microarray method for identification of some highly pathogenic viruses.

    PubMed

    Xiao-Ping, Kang; Yong-Qiang, Li; Qing-Ge, Sun; Hong, Liu; Qing-Yu, Zhu; Yin-Hui, Yang

    2009-11-01

    Some highly pathogenic viruses, such as Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Hanta virus, SARS-CoV, and H5N1 avian influenza virus can cause severe infectious diseases. However, the consensus method for detecting these viruses has not been well established. A rapid and sensitive microarray approach for detection of these viruses and a panel of specific probes covering nine genera and 16 virus species were designed. 70-mer oligonucleotides were used at the genus level and 50-mer oligonucleotides were at the species level, respectively. To decrease the interference of the host genome in hybridization, the consensus genus primers were designed and used to reverse transcribe only virus genome. The synthesis of the second strand was carried out with a random primer sequence (5'-GTTTCCCAGTAGGTCTCNNNNNNNN-3'). The amplified products were labeled and processed for microarray analyses. This microarray-based method used the highly conserved consensus primers to synthesize specifically the virus cDNA and could identify effectively Chikungunya virus, Japanese encephalitis virus, Yellow fever virus, Dengue virus, Tick borne encephalitis virus, and H5N1 avian influenza virus. Using this method, one unknown virus isolated from pig brain in Shanxi Province, China was identified. This method may have an important potential application for the diagnosis of virus infection.

  8. [Chikungunya in children].

    PubMed

    Mac Donald-Ottevanger, M Sigrid; Gravenberch-Ramnandanlall, Charleen I; Zijlmans, C W R Wilco

    2015-01-01

    Chikungunya is a rapidly spreading infectious disease throughout the Caribbean, reaching epidemic proportions in Suriname, with more than 1200 registered cases in 2014. Similar to dengue, classic symptoms are high fever, rash and arthralgia. However, the presentation differs in adults and children. At the Academic Hospital Paramaribo in Suriname, three children had different presentations of chikungunya. An 11-year-old girl was referred to the paediatric centre with acute-onset fever of 40.5ºC, painful knees and a rash on face and arms. Koplik spots were visible on the inside of her mouth. A 13-year-old boy attended the ER with acute-onset fever and a state of reduced consciousness. Physical examination revealed hypotension, tachycardia and fever. No rash was observed. A 2.5-month-old baby with fever, vomiting, diarrhoea and a rash was brought to the ER. She was agitated and had signs of meningism. The symptoms resolved quickly in all patients after rehydration and pain medication.

  9. Computational Approach Towards Exploring Potential Anti-Chikungunya Activity of Selected Flavonoids

    PubMed Central

    Seyedi, Seyedeh Somayeh; Shukri, Munirah; Hassandarvish, Pouya; Oo, Adrian; Muthu, Shankar Esaki; Abubakar, Sazaly; Zandi, Keivan

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes chikungunya infection in humans. Despite the widespread distribution of CHIKV, no antiviral medication or vaccine is available against this virus. Therefore, it is crucial to find an effective compound to combat CHIKV. We aimed to predict the possible interactions between non-structural protein 3 (nsP) of CHIKV as one of the most important viral elements in CHIKV intracellular replication and 3 potential flavonoids using a computational approach. The 3-dimensional structure of nsP3 was retrieved from the Protein Data Bank, prepared and, using AutoDock Vina, docked with baicalin, naringenin and quercetagetin as ligands. The first-rated ligand with the strongest binding affinity towards the targeted protein was determined based on the minimum binding energy. Further analysis was conducted to identify both the active site of the protein that reacts with the tested ligands and all of the existing intermolecular bonds. Compared to the other ligands, baicalin was identified as the most potential inhibitor of viral activity by showing the best binding affinity (−9.8 kcal/mol). Baicalin can be considered a good candidate for further evaluation as a potentially efficient antiviral against CHIKV. PMID:27071308

  10. Chikungunya outbreak in Al-Hudaydah, Yemen, 2011: epidemiological characterization and key lessons learned for early detection and control.

    PubMed

    Malik, Mamunur Rahman; Mnzava, Abraham; Mohareb, Emad; Zayed, Alia; Al Kohlani, Abdulhakeem; Thabet, Ahmed A K; El Bushra, Hassan

    2014-09-01

    Little is known about the occurrence of chikungunya fever in the Eastern Mediterranean Region of the World Health Organization (WHO). In January 2011, the Ministry of Public Health and Population (MoPH&P) of Yemen reported to WHO an increasing number of "dengue-like" acute febrile illnesses of unknown origin from one of its coastal governorates. An epidemiological investigation was conducted in Al-Hudaydah governorate between 23 and 26 January 2011 by a joint team of WHO, the MoPH&P of Yemen and the U.S. Naval Medical Research Unit (NAMRU-3) in Cairo, Egypt. The investigation led to the detection of an outbreak of chikungunya in Yemen which was the first time ever from any of the 22 countries in the Eastern Mediterranean Region of WHO. Appropriate public health control measures were strengthened following the investigation, and the outbreak was contained. This paper provides a short description of the outbreak and its epidemiological characteristics and highlights the important lessons that were learned for early detection and control of chikungunya in countries where competent vectors for transmission of the virus exist.

  11. Importance of mosquito "quasispecies" in selecting an epidemic arthropod-borne virus.

    PubMed

    Vazeille, Marie; Zouache, Karima; Vega-Rúa, Anubis; Thiberge, Jean-Michel; Caro, Valérie; Yébakima, André; Mousson, Laurence; Piorkowski, Géraldine; Dauga, Catherine; Vaney, Marie-Christine; Manni, Mosè; Gasperi, Giuliano; de Lamballerie, Xavier; Failloux, Anna-Bella

    2016-07-07

    Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Réunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1-A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Réunion.

  12. Importance of mosquito “quasispecies” in selecting an epidemic arthropod-borne virus

    PubMed Central

    Vazeille, Marie; Zouache, Karima; Vega-Rúa, Anubis; Thiberge, Jean-Michel; Caro, Valérie; Yébakima, André; Mousson, Laurence; Piorkowski, Géraldine; Dauga, Catherine; Vaney, Marie-Christine; Manni, Mosè; Gasperi, Giuliano; de Lamballerie, Xavier; Failloux, Anna-Bella

    2016-01-01

    Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Réunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1-A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Réunion. PMID:27383735

  13. Importance of mosquito "quasispecies" in selecting an epidemic arthropod-borne virus.

    PubMed

    Vazeille, Marie; Zouache, Karima; Vega-Rúa, Anubis; Thiberge, Jean-Michel; Caro, Valérie; Yébakima, André; Mousson, Laurence; Piorkowski, Géraldine; Dauga, Catherine; Vaney, Marie-Christine; Manni, Mosè; Gasperi, Giuliano; de Lamballerie, Xavier; Failloux, Anna-Bella

    2016-01-01

    Most arthropod-borne viruses (arboviruses), perpetuated by alternation between a vertebrate host and an insect vector, are likely to emerge through minor genetic changes enabling the virus to adapt to new hosts. In the past decade, chikungunya virus (CHIKV; Alphavirus, Togaviridae) has emerged on La Réunion Island following the selection of a unique substitution in the CHIKV E1 envelope glycoprotein (E1-A226V) of an East-Central-South African (ECSA) genotype conferring a higher transmission rate by the mosquito Aedes albopictus. Assumed to have occurred independently on at least four separate occasions, this evolutionary convergence was suspected to be responsible for CHIKV worldwide expansion. However, assumptions on CHIKV emergence were mainly based on viral genetic changes and the role of the mosquito population quasispecies remained unexplored. Here we show that the nature of the vector population is pivotal in selecting the epidemic CHIKV. We demonstrate using microsatellites mosquito genotyping that Ae. albopictus populations are genetically differentiated, contributing to explain their differential ability to select the E1-226V mutation. Aedes albopictus, newly introduced in Congo coinciding with the first CHIKV outbreak, was not able to select the substitution E1-A226V nor to preferentially transmit a CHIKV clone harboring the E1-226V as did Ae. albopictus from La Réunion. PMID:27383735

  14. Zika virus infection in a traveller returning to Europe from Brazil, March 2015.

    PubMed

    Zammarchi, L; Tappe, D; Fortuna, C; Remoli, M E; Günther, S; Venturi, G; Bartoloni, A; Schmidt-Chanasit, J

    2015-06-11

    We report a case of laboratory-confirmed Zika virus infection imported into Europe from the Americas. The patient developed fever, rash, and oedema of hands and feet after returning to Italy from Brazil in late March 2015. The case highlights that, together with chikungunya virus and dengue virus, three major arboviruses are now co-circulating in Brazil. These arboviruses represent a burden for the healthcare systems in Brazil and other countries where competent mosquito vectors are present.

  15. Zoonotic viruses associated with illegally imported wildlife products

    USGS Publications Warehouse

    Smith, Kristine M.; Anthony, Simon J.; Switzer, William M.; Epstein, Jonathan H.; Seimon, Tracie; Jia, Hongwei; Sanchez, Maria D.; Huynh, Thanh Thao; Galland, G. Gale; Shapiro, Sheryl E.; Sleeman, Jonathan M.; McAloose, Denise; Stuchin, Margot; Amato, George; Kolokotronis, Sergios-Orestis; Lipkin, W. Ian; Karesh, William B.; Daszak, Peter; Marano, Nina

    2012-01-01

    The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.

  16. Zoonotic Viruses Associated with Illegally Imported Wildlife Products

    PubMed Central

    Switzer, William M.; Epstein, Jonathan H.; Seimon, Tracie; Jia, Hongwei; Sanchez, Maria D.; Huynh, Thanh Thao; Galland, G. Gale; Shapiro, Sheryl E.; Sleeman, Jonathan M.; McAloose, Denise; Stuchin, Margot; Amato, George; Kolokotronis, Sergios-Orestis; Lipkin, W. Ian; Karesh, William B.; Daszak, Peter; Marano, Nina

    2012-01-01

    The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence. PMID:22253731

  17. Zoonotic viruses associated with illegally imported wildlife products.

    PubMed

    Smith, Kristine M; Anthony, Simon J; Switzer, William M; Epstein, Jonathan H; Seimon, Tracie; Jia, Hongwei; Sanchez, Maria D; Huynh, Thanh Thao; Galland, G Gale; Shapiro, Sheryl E; Sleeman, Jonathan M; McAloose, Denise; Stuchin, Margot; Amato, George; Kolokotronis, Sergios-Orestis; Lipkin, W Ian; Karesh, William B; Daszak, Peter; Marano, Nina

    2012-01-01

    The global trade in wildlife has historically contributed to the emergence and spread of infectious diseases. The United States is the world's largest importer of wildlife and wildlife products, yet minimal pathogen surveillance has precluded assessment of the health risks posed by this practice. This report details the findings of a pilot project to establish surveillance methodology for zoonotic agents in confiscated wildlife products. Initial findings from samples collected at several international airports identified parts originating from nonhuman primate (NHP) and rodent species, including baboon, chimpanzee, mangabey, guenon, green monkey, cane rat and rat. Pathogen screening identified retroviruses (simian foamy virus) and/or herpesviruses (cytomegalovirus and lymphocryptovirus) in the NHP samples. These results are the first demonstration that illegal bushmeat importation into the United States could act as a conduit for pathogen spread, and suggest that implementation of disease surveillance of the wildlife trade will help facilitate prevention of disease emergence.

  18. Estimated Zika virus importations to Europe by travellers from Brazil

    PubMed Central

    Massad, Eduardo; Tan, Ser-Han; Khan, Kamran; Wilder-Smith, Annelies

    2016-01-01

    Background Given the interconnectivity of Brazil with the rest of the world, Zika virus (ZIKV) infections have the potential to spread rapidly around the world via viremic travellers. The extent of spread depends on the travel volume and the endemicity in the exporting country. In the absence of reliable surveillance data, we did mathematical modelling to estimate the number of importations of ZIKV from Brazil into Europe. Design We applied a previously developed mathematical model on importations of dengue to estimate the number of ZIKV importations into Europe, based on the travel volume, the probability of being infected at the time of travel, the population size of Brazil, and the estimated incidence of ZIKV infections. Results Our model estimated between 508 and 1,778 imported infections into Europe in 2016, of which we would expect between 116 and 355 symptomatic Zika infections; with the highest number of importations being into France, Portugal and Italy. Conclusions Our model identified high-risk countries in Europe. Such data can assist policymakers and public health professionals in estimating the extent of importations in order to prepare for the scale up of laboratory diagnostic assays and estimate the occurrence of Guillain–Barré Syndrome, potential sexual transmission, and infants with congenital ZIKV syndrome. PMID:27193266

  19. [New vector control measures implemented between 2005 and 2011 on Reunion Island: lessons learned from chikungunya epidemic].

    PubMed

    Bâville, M; Dehecq, J S; Reilhes, O; Margueron, T; Polycarpe, D; Filleul, L

    2012-03-01

    A major chikungunya outbreak concerned 38% of people living in Reunion Island in 2005-2006. Chikungunya is an arthropod-born-virus disease conveyed by mosquitoes called Aedes albopictus. The health agency in Indian Ocean is responsible for vector control. Previously, in the early 40s, vector control concerned only malaria prophylaxis in La Réunion. Then, during the chikungunya outbreak, a new vector control team was installed and learned from this epidemic. The lessons drawn from chikungunya outbreak in La Réunion are about global executive management and organization linked the local partners and population. The lessons also concern technical topics such as the need of scientific research about vectors and vector-control methods. Finally, the regional cooperation in Indian Ocean (Réunion, Maurice, Seychelles, Comoros, Madagascar) has to be developed to share epidemiologic and entomologic data in order to prevent new chikungunya or dengue outbreak.

  20. Chikungunya Fever Presenting as a Systemic Disease with Fever. Arthritis and Rash: Our Experience in Israel.

    PubMed

    Tanay, Amir

    2016-01-01

    Chikungunya fever (CHIK-F) has been increasingly documented among Western travelers returning from areas with chikungunya virus transmission, which are also popular tourist sites. We present three Israeli travelers who developed fever, maculopapular rash and long-standing arthralgias while visiting northern Indian states not known to be involved in the chikungunya fever epidemic. We also present an epidemiological review of the chikungunya epidemic over the past decades. Rare systemic manifestations of this disorder, like catastrophic antiphospholipid syndrome (CAPS) and adult-onset Still's syndrome, are discussed. The present era of international travel poses a new diagnostic and epidemiologic challenge that demands increased awareness to the possibility of an exotic tropical infectious disease.

  1. Dissemination and transmission of the E1-226V variant of chikungunya virus in Aedes albopictus are controlled at the midgut barrier level.

    PubMed

    Arias-Goeta, Camilo; Mousson, Laurence; Rougeon, François; Failloux, Anna-Bella

    2013-01-01

    Emergence of arboviruses could result from their ability to exploit new environments, for example a new host. This ability is facilitated by the high mutation rate occurring during viral genome replication. The last emergence of chikungunya in the Indian Ocean region corroborates this statement since a single viral mutation at the position 226 on the E1 glycoprotein (E1-A226V) was associated with enhanced transmission by the mosquito Aedes albopictus in regions where the major mosquito vector, Aedes aegypti, is absent.We used direct competition assays in vivo to dissect out the mechanisms underlying the selection of E1-226V by Ae. albopictus. When the original variant E1-226A and the newly emerged E1-226V were provided in the same blood-meal at equal titers to both species of mosquitoes, we found that the proportion of both variants was drastically different in the two mosquito species. Following ingestion of the infectious blood-meal, the E1-226V variant was preferentially selected in Ae. albopictus, whereas the E1-226A variant was sometimes favored in Ae. aegypti. Interestingly, when the two variants were introduced into the mosquitoes by intrathoracic inoculations, E1-226V was no longer favored for dissemination and transmission in Ae. albopictus, showing that the midgut barrier plays a key role in E1-226V selection.This study sheds light on the role of the midgut barrier in the selection of novel arbovirus emerging variants. We also bring new insight into how the pre-existing variant E1-226V was selected among other viral variants including E1-226A. Indeed the E1-226V variant present at low levels in natural viral populations could rapidly emerge after being selected in Ae. albopictus at the midgut barrier level. PMID:23437397

  2. Chikungunya in Thailand: a re-emerging disease?

    PubMed

    Thaikruea, L; Charearnsook, O; Reanphumkarnkit, S; Dissomboon, P; Phonjan, R; Ratchbud, S; Kounsang, Y; Buranapiyawong, D

    1997-06-01

    The first reported case of chikungunya virus diagnosed by serology in Thailand was in 1960 and the last one was in 1991. The disease surveillance system does not specifically include chikungunya cases and the signs and symptoms are similar to these of dengue fever/dengue hemorrhagic fever (DF/DHF), rubella, and fever of unknown origin (FUO); thus cases might often be reported under those diagnoses. During the rainy season of 1995 (Jun-Aug), there were at least 2 reported chikungunya outbreaks which might indicate that it is a re-emerging disease in Thailand. However, there is still limited information and knowledge on some aspects of this disease such as clinical manifestations, subclinical cases, duration of illness, complications, transmission, immunity, and reservoirs. Thus, the objectives of this paper are to describe the epidemiology of chikungunya infection based on outbreak investigations carried out in Khon Kaen (July 1991), Nakorn Si Thammarat (July 1995), and Nong Khai Provinces (August 1995). All three outbreaks occurred during the rainy season. The three most common clinical manifestations were fever with severe althralgia with maculopapular rash. Both sexes and all age groups were affected. Serological results were positive for IgM, with four-fold rises in paired sera, and viral isolation in Nakorn Si Thammarat and Nong Khai. Only in Nong Khai was hemagglutinin inhibition conducted and the results were positive. No deaths were reported. The outbreaks occurred in rural villages and all three larval indices (BI, HI, CI) were very high. The possible vectors in these outbreaks were Aedes aegypti and Aedes albopictus. In the Nong Khai outbreak, blood specimens were taken at the 3-5th day after onset and therefore the proportion of positive results was low. IgM antibody of follow-up cases declined within 3 months, villagers from all three areas with outbreaks mentioned that they had no previous experience of this disease. This suggests that chikungunya

  3. Chikungunya as a Cause of Acute Febrile Illness in Southern Sri Lanka

    PubMed Central

    Reller, Megan E.; Akoroda, Ufuoma; Nagahawatte, Ajith; Devasiri, Vasantha; Kodikaarachchi, Wasantha; Strouse, John J.; Chua, Robert; Hou, Yan'an; Chow, Angelia; Sessions, October M.; Østbye, Truls; Gubler, Duane J.; Woods, Christopher W.; Bodinayake, Champica

    2013-01-01

    Background Chikungunya virus (CHIKV) re-emerged in Sri Lanka in late 2006 after a 40-year hiatus. We sought to identify and characterize acute chikungunya infection (CHIK) in patients presenting with acute undifferentiated febrile illness in unstudied rural and semi-urban southern Sri Lanka in 2007. Methodology/Principal Findings We enrolled febrile patients ≥ 2 years of age, collected uniform epidemiologic and clinical data, and obtained serum samples for serology, virus isolation, and real-time reverse-transcriptase PCR (RT-PCR). Serology on paired acute and convalescent samples identified acute chikungunya infection in 3.5% (28/797) patients without acute dengue virus (DENV) infection, 64.3% (18/28) of which were confirmed by viral isolation and/or real-time RT-PCR. No CHIKV/DENV co-infections were detected among 54 patients with confirmed acute DENV. Sequencing of the E1 coding region of six temporally distinct CHIKV isolates (April through October 2007) showed that all isolates posessed the E1-226A residue and were most closely related to Sri Lankan and Indian isolates from the same time period. Except for more frequent and persistent musculoskeletal symptoms, acute chikungunya infections mimicked DENV and other acute febrile illnesses. Only 12/797 (1.5%) patients had serological evidence of past chikungunya infection. Conclusions/Significance Our findings suggest CHIKV is a prominent cause of non-specific acute febrile illness in southern Sri Lanka. PMID:24312651

  4. Cutaneous manifestations of chikungunya fever.

    PubMed

    Seetharam, K A; Sridevi, K; Vidyasagar, P

    2012-01-01

    Chikungunya fever, a re-emerging RNA viral infection produces different cutaneous manifestations in children compared to adults. 52 children with chikungunya fever, confirmed by positive IgM antibody test were seen during 2009-2010. Pigmentary lesions were common (27/52) followed by vesiculobullous lesions (16/52) and maculopapular lesions (14/52). Vesiculobullous lesions were most common in infants, although rarely reported in adults. Psoriasis was exacerbated in 4 children resulting in more severe forms. In 2 children, guttate psoriasis was observed for the first time.

  5. Chikungunya virus–induced autophagy delays caspase-dependent cell death

    PubMed Central

    Joubert, Pierre-Emmanuel; Werneke, Scott W.; de la Calle, Claire; Guivel-Benhassine, Florence; Giodini, Alessandra; Peduto, Lucie; Levine, Beth; Schwartz, Olivier; Lenschow, Deborah J.

    2012-01-01

    Autophagy is an important survival pathway and can participate in the host response to infection. Studying Chikungunya virus (CHIKV), the causative agent of a major epidemic in India, Southeast Asia, and southern Europe, we reveal a novel mechanism by which autophagy limits cell death and mortality after infection. We use biochemical studies and single cell multispectral assays to demonstrate that direct infection triggers both apoptosis and autophagy. CHIKV-induced autophagy is mediated by the independent induction of endoplasmic reticulum and oxidative stress pathways. These cellular responses delay apoptotic cell death by inducing the IRE1α–XBP-1 pathway in conjunction with ROS-mediated mTOR inhibition. Silencing of autophagy genes resulted in enhanced intrinsic and extrinsic apoptosis, favoring viral propagation in cultured cells. Providing in vivo evidence for the relevance of our findings, Atg16LHM mice, which display reduced levels of autophagy, exhibited increased lethality and showed a higher sensitivity to CHIKV-induced apoptosis. Based on kinetic studies and the observation that features of apoptosis and autophagy were mutually exclusive, we conclude that autophagy inhibits caspase-dependent cell death but is ultimately overwhelmed by viral replication. Our study suggests that inducers of autophagy may limit the pathogenesis of acute Chikungunya disease. PMID:22508836

  6. Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.

    PubMed

    Tilak, Rina; Ray, Sougat; Tilak, V W; Mukherji, Sandip

    2016-04-01

    Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever.

  7. Dengue, chikungunya … and the missing entity - Zika fever: A new emerging threat.

    PubMed

    Tilak, Rina; Ray, Sougat; Tilak, V W; Mukherji, Sandip

    2016-04-01

    Zika virus (ZIKV), a relative newcomer from the flavivirus group that includes dengue, Japanese encepahalitis and yellow fever, is one of the emerging pathogens that is fast transcending geographical boundaries. It is a vector-borne disease transmitted by the same Aedes aegypti and Aedes albopictus, which cause dengue and chikungunya. In addition to the vector-mediated transmission of Zika fever, probable human-to-human transmission through exchange of body fluids, including sexual and perinatal transmission and through blood transfusion, makes containment of this new entity more challenging. Moreover, a high index of suspicion by an astute physician is necessary for diagnosis of Zika fever in view of the similarity of symptoms with dengue and chikungunya, especially in areas, where these two diseases are already endemic. Zika, till recently, has had minimal impact, but its true potential is unfolding with increasing detection of congenital malformities, Guillain-Barré syndrome and other neurological and autoimmune syndromes in patients with recent history of ZIKV infection, or when mothers get infected with Zika during first or second trimester of pregnancy. The association, however, needs to be established, nonetheless it is important that we keep a close vigil on this emerging vector borne disease - the 'ZIKA' fever. PMID:27257326

  8. Increase in cases of Guillain-Barré syndrome during a Chikungunya outbreak, French Polynesia, 2014 to 2015.

    PubMed

    Oehler, Erwan; Fournier, Emmanuel; Leparc-Goffart, Isabelle; Larre, Philippe; Cubizolle, Stéphanie; Sookhareea, Chantal; Lastère, Stéphane; Ghawche, Frédéric

    2015-01-01

    During the recent chikungunya fever outbreak in French Polynesia in October 2014 to March 2015, we observed an abnormally high number of patients with neurological deficit. Clinical presentation and complementary exams were suggestive of Guillain-Barré syndrome (GBS) for nine patients. All nine had a recent dengue-like syndrome and tested positive for chikungunya virus (CHIKV) in serology or RT-PCR. GBS incidence was increased four- to nine-fold during this period, suggesting a link to CHIKV infection.

  9. [Chikungunya emergency in Emilia-Romagna: learning through experience].

    PubMed

    Angelini, Paola; Finarelli, Alba Carola; Silvi, Giuliano; Borrini, Bianca Maria; Frasca, Gabriella; Mattivi, Andrea; Massimiliani, Erika; Po, Claudio; Angelini, Raffaella; Venturelli, Claudio; Macini, Pierluigi

    2008-01-01

    This paper summarizes the Emilia-Romagna strategy to face the 2007 emergency, caused by a Chikungunya epidemic outbreak with local virus transmission by Ae. albopictus. The paper describes the trend of epidemic and the interventions adopted to face toward the event. The first cases were in Ravenna and Cervia and then the outbreak spread toward other areas: the Provinces of Forlì-Cesena, Rimini and Bologna. Last case was notified 2007 28th September; Health Ministry declared over the outbreak on 2007 20th November. Emilia-Romagna Region did not consider over the trouble and prepared a Plan for the fight against the asian tiger mosquito and the prevention of Chikungunya and Dengue fever for 2008, activating an health surveillance system and optimizing the entomological control of the territory.

  10. Complete Genome Sequence of Zika Virus from the First Imported Case in Mainland China

    PubMed Central

    Liu, Lin; Wu, Wei; Zhao, Xiang; Xiong, Ying; Zhang, Shuo; Liu, Xiaoqing; Qu, Jing; Li, Jiandong; Nei, Kai; Shu, Yuelong; Hu, Guoliang

    2016-01-01

    The first case of Zika virus infection was identified in a Chinese traveler returning from Venezuela in February 2016. This report describes the complete genome sequence of Zika virus from the first imported case in China. The genome sequence analysis showed that the Zika virus isolated in this case belongs to the Asian lineage. PMID:27103718

  11. Complete Genome Sequence of Zika Virus from the First Imported Case in Mainland China.

    PubMed

    Liu, Lin; Wu, Wei; Zhao, Xiang; Xiong, Ying; Zhang, Shuo; Liu, Xiaoqing; Qu, Jing; Li, Jiandong; Nei, Kai; Liang, Mifang; Shu, Yuelong; Hu, Guoliang; Ma, Xuejun; Li, Dexin

    2016-01-01

    The first case of Zika virus infection was identified in a Chinese traveler returning from Venezuela in February 2016. This report describes the complete genome sequence of Zika virus from the first imported case in China. The genome sequence analysis showed that the Zika virus isolated in this case belongs to the Asian lineage.

  12. Chikungunya: a paradigm of emergence and globalization of vector-borne diseases.

    PubMed

    Simon, Fabrice; Savini, Hélène; Parola, Philippe

    2008-11-01

    Chikungunya (CHIK) fever is a tropical arboviral disease responsible for acute polyarthritis which can last for weeks to months. In 2007, the chikungunya virus (CHIKV) reached Europe. Since the beginning of this outbreak, several million cases of chikungunya virus disease have occurred in autochthonous populations and in travelers who were diagnosed after they returned home from epidemic areas. CHIKV, usually transmitted by Aedes aegypti mosquitoes, has now been repeatedly associated with a new vector, Aedes albopictus (the "Asian tiger mosquito"), which has spread into tropical areas previously occupied predominantly by A aegypti, and has dispersed worldwide. Because CHIKV could spread throughout the world, all physicians should be prepared to encounter this arboviral infection, which represents a paradigm for emerging arboviral infections. In this article, the authors review different aspects of this reemerging and fascinating disease, focusing on clinical aspects and lessons from the recent large-scale outbreaks.

  13. Updates on chikungunya epidemiology, clinical disease, and diagnostics.

    PubMed

    Sam, I-Ching; Kümmerer, Beate M; Chan, Yoke-Fun; Roques, Pierre; Drosten, Christian; AbuBakar, Sazaly

    2015-04-01

    Chikungunya virus (CHIKV) is an Aedes-borne alphavirus, historically found in Africa and Asia, where it caused sporadic outbreaks. In 2004, CHIKV reemerged in East Africa and spread globally to cause epidemics, including, for the first time, autochthonous transmission in Europe, the Middle East, and Oceania. The epidemic strains were of the East/Central/South African genotype. Strains of the Asian genotype of CHIKV continued to cause outbreaks in Asia and spread to Oceania and, in 2013, to the Americas. Acute disease, mainly comprising fever, rash, and arthralgia, was previously regarded as self-limiting; however, there is growing evidence of severe but rare manifestations, such as neurological disease. Furthermore, CHIKV appears to cause a significant burden of long-term morbidity due to persistent arthralgia. Diagnostic assays have advanced greatly in recent years, although there remains a need for simple, accurate, and affordable tests for the developing countries where CHIKV is most prevalent. This review focuses on recent important work on the epidemiology, clinical disease and diagnostics of CHIKV.

  14. [Important aspects of virus safety of advanced therapy medicinal products].

    PubMed

    Blümel, J; Stühler, A

    2010-01-01

    Virus safety of advanced therapy medicinal products is a particular challenge. These products may consist of whole cells and the manufacture of these is performed using various human or animal-derived starting materials and reagents. Therefore, extensive testing of donors and of established cell banks is required. Furthermore, the virus safety of reagents such as bovine sera, porcine trypsin, and growth factors needs to be considered. Whenever possible, manufacturing steps for inactivation or removal of viruses should be introduced. However, it is not possible to introduce such steps for cell-based medicinal products as the activity and viability of cells will be compromised. Only in the production of small and stable non-enveloped viral gene vectors is it conceivable to implement steps to selectively inactivate or remove potential contaminating enveloped viruses.

  15. Chikungunya outbreak in Garo Hills, Meghalaya: An epidemiological perspective

    PubMed Central

    Khan, Siraj Ahmed; Dutta, Prafulla; Topno, Rashmee; Borah, Jani; Chowdhury, Purvita; Mahanta, Jagadish

    2015-01-01

    Background & objectives: Chikungunya (CHIK) fever is a mosquito-borne disease caused by chikungunya virus (CHIKV). Chikungunya infection was first reported from India in 1963 from Kolkata. We report the serological and molecular evidence of an outbreak of chikungunya in northeast India that occurred in Tura, a hilly and forested terrain in Garo Hills district of Meghalaya. Methods: Blood samples (3 ml) collected from hospitalized patients during the outbreak were tested for IgM antibodies against CHIKV and followed up four months later. A repeat survey was carried out in the same area after four months from where cases had been reported. Blood samples were also collected from people with history of fever and body ache in the last four months. Persons showing IgM positivity against CHIKV in the repeat survey were followed up one and a half years later. All samples were also processed by RT-PCR assay for CHIK Envelope (E) 1 gene. Immature mosquitoes were collected, link reared and identified with standard keys. Virus incrimination studies were done on Aedes aegypti and Ae. albopictus mosquitoes collected during the survey. Results: Fever, headache and joint pain were the primary clinical presentations. Twenty three (35.93 %) of 64 samples reported during the outbreak were IgM positive for CHIK. Three samples showed PCR amplification. All these were IgM positive. The sequenced E1 gene revealed that the strains belonged to East Central South African (ECSA) genotype. Interpretation & conclusions: Field survey done after four months revealed that some individuals still had joint pain associated with episodes of headache and fever. It could be inferred that these persons might have contracted infection during the CHIK outbreak four months ago or during the intervening period which caused persistence of sequelae. ECSA genotype was found to be involved in the outbreak. Aedes albopictus was the predominant mosquito species collected during the outbreak. PMID:26139776

  16. Chikungunya Outbreak, South India, 2006

    PubMed Central

    Kaur, Prabhdeep; Ponniah, Manickam; Murhekar, Manoj V.; Ramachandran, Vidya; Ramachandran, Ramakrishnan; Raju, Hari Kishan; Perumal, Vanamail; Mishra, Akhilesh C.

    2008-01-01

    We investigated chikungunya outbreaks in South India and observed a high attack rate, particularly among adults and women. Transmission was facilitated by Aedes aegypti mosquitoes in peridomestic water containers, as indicated by a high Breteau index. We recommended vector control measures and health education to promote safe water storage practices. PMID:18826830

  17. Importance of respiratory viruses in acute otitis media.

    PubMed

    Heikkinen, Terho; Chonmaitree, Tasnee

    2003-04-01

    Acute otitis media is usually considered a simple bacterial infection that is treated with antibiotics. However, ample evidence derived from studies ranging from animal experiments to extensive clinical trials supports a crucial role for respiratory viruses in the etiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory mucosa initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. The pathogenesis of acute otitis media involves a complex interplay between viruses, bacteria, and the host's inflammatory response. In a substantial number of children, viruses can be found in the middle-ear fluid either alone or together with bacteria, and recent studies indicate that at least some viruses actively invade the middle ear. Viruses appear to enhance the inflammatory process in the middle ear, and they may significantly impair the resolution of otitis media. Prevention of the predisposing viral infection by vaccination against the major viruses would probably be the most effective way to prevent acute otitis media. Alternatively, early treatment of the viral infection with specific antiviral agents would also be effective in reducing the occurrence of acute otitis media.

  18. EPIDEMIOLOGY, CLINICAL MANIFESTATIONS, AND DIAGNOSIS OF CHIKUNGUNYA FEVER: LESSONS LEARNED FROM THE RE-EMERGING EPIDEMIC

    PubMed Central

    Mohan, Alladi; Kiran, DHN; Manohar, I Chiranjeevi; Kumar, D Prabath

    2010-01-01

    Chikungunya fever, caused by “Chikungunya virus,” is an arbovirus disease transmitted by the bite of infected mosquitoes belonging to the genus Aedes. Chikungunya fever epidemics have been reported from several countries around the world. The disease that was silent for nearly 32 years re-emerged in the October 2005 outbreak in India that is still ongoing. The incubation period ranges from 3 to 12 days. The onset is usually abrupt and the acute stage is characterized by sudden onset with high-grade fever, severe arthralgias, myalgias, and skin rash. Swollen tender joints and crippling arthritis are usually evident. In the chronic stage, relapses that include sensation of fever, asthenia, exacerbation of arthralgias, inflammatory polyarthritis, and stiffness may be evident. Neurological, ocular, and mucocutaneous manifestations have also been described. Chronic arthritis may develop in about 15% of the patients. Viral culture is the gold standard for the diagnosis of Chikungunya fever. Reverse transcription polymerase chain reaction and real-time loop-mediated isothermal amplification have also been found to be useful. Serodiagnostic methods for the detection of immunoglobulin M and immunoglobulin G antibodies against Chikungunya virus are more frequently used. Chikungunya is a self-limiting disease; however, severe manifestations such as meningoencephalitis, fulminant hepatitis, and bleeding manifestations may sometimes be life-threatening. Treatment is symptomatic and supportive. Prevention by educating the community and public health officials, vector control measures appear to be the best approach at controlling Chikungunya fever as no commercially available vaccine is available for public use in India for this condition presently. PMID:20418981

  19. Epidemiology, clinical manifestations, and diagnosis of Chikungunya fever: lessons learned from the re-emerging epidemic.

    PubMed

    Mohan, Alladi; Kiran, D H N; Manohar, I Chiranjeevi; Kumar, D Prabath

    2010-01-01

    Chikungunya fever, caused by "Chikungunya virus," is an arbovirus disease transmitted by the bite of infected mosquitoes belonging to the genus Aedes. Chikungunya fever epidemics have been reported from several countries around the world. The disease that was silent for nearly 32 years re-emerged in the October 2005 outbreak in India that is still ongoing. The incubation period ranges from 3 to 12 days. The onset is usually abrupt and the acute stage is characterized by sudden onset with high-grade fever, severe arthralgias, myalgias, and skin rash. Swollen tender joints and crippling arthritis are usually evident. In the chronic stage, relapses that include sensation of fever, asthenia, exacerbation of arthralgias, inflammatory polyarthritis, and stiffness may be evident. Neurological, ocular, and mucocutaneous manifestations have also been described. Chronic arthritis may develop in about 15% of the patients. Viral culture is the gold standard for the diagnosis of Chikungunya fever. Reverse transcription polymerase chain reaction and real-time loop-mediated isothermal amplification have also been found to be useful. Serodiagnostic methods for the detection of immunoglobulin M and immunoglobulin G antibodies against Chikungunya virus are more frequently used. Chikungunya is a self-limiting disease; however, severe manifestations such as meningoencephalitis, fulminant hepatitis, and bleeding manifestations may sometimes be life-threatening. Treatment is symptomatic and supportive. Prevention by educating the community and public health officials, vector control measures appear to be the best approach at controlling Chikungunya fever as no commercially available vaccine is available for public use in India for this condition presently.

  20. Two novel epistatic mutations (E1:K211E and E2:V264A) in structural proteins of Chikungunya virus enhance fitness in Aedes aegypti.

    PubMed

    Agarwal, Ankita; Sharma, Ajay Kumar; Sukumaran, D; Parida, Manmohan; Dash, Paban Kumar

    2016-10-01

    Expansion of CHIKV outbreaks with appearance of novel mutations are reported from many parts of the world. Two novel mutations viz. E1:K211E and E2:V264A in background of E1:226A are recently identified from Aedes aegypti dominated areas of India. In this study, the role of these mutations in modulation of infectivity, dissemination and transmission by two different Aedes species was studied. Mutations were sequentially constructed in CHIKV genome and female Ae. aegypti and Aedes albopictus mosquitoes were orally infected with eight different CHIKV mutants. Double mutant virus containing E1:K211E and E2:V264A mutations in background of E1:226A revealed remarkably higher fitness for Ae. aegypti, as indicated by significant increase in virus infectivity (13 fold), dissemination (15 fold) and transmission (62 fold) compared to parental E1:226A virus. These results indicate that adaptive mutations in CHIKV are leading to efficient CHIKV circulation in Ae. aegypti endemic areas, contributing and sustaining the major CHIKV outbreaks. PMID:27423270

  1. Isolation of Zika Virus Imported from Tonga into Australia

    PubMed Central

    Pyke, Alyssa T.; Moore, Peter R.; Hall-Mendelin, Sonja; McMahon, Jamie L.; Harrower, Bruce J; Constantino, Tanya R; van den Hurk, Andrew F

    2016-01-01

    Introduction: The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016. Methods: A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine. Results: A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage. Discussion: This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region. PMID:27679739

  2. Isolation of Zika Virus Imported from Tonga into Australia

    PubMed Central

    Pyke, Alyssa T.; Moore, Peter R.; Hall-Mendelin, Sonja; McMahon, Jamie L.; Harrower, Bruce J; Constantino, Tanya R; van den Hurk, Andrew F

    2016-01-01

    Introduction: The globally emergent Zika virus (ZIKV) is a threat to Australia, given the number of imported cases from epidemic regions and the presence of competent mosquito vectors. We report the isolation of ZIKV from a female traveler who recently returned from Tonga to Brisbane, Queensland, Australia in 2016. Methods: A specific TaqMan real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) assay was used to detect ZIKV in serum and urine samples. Conventional cell culture techniques and suckling mice were employed in an attempt to isolate ZIKV from serum and urine. Results: A ZIKV isolate (TS17-2016) was recovered from the serum sample after one passage in suckling mouse brains and harvested 11 days post inoculation. Phylogenetic analysis of complete envelope (E) gene sequences demonstrated TS17-2016 shared 99.9% nucleotide identity with other contemporary sequences from Tonga 2016, Brazil 2015 and French Polynesia 2013 within the Asian lineage. Discussion: This is the first known report of successful isolation of ZIKV from a human clinical sample in Australia and the first from a traveler from Tonga. This study highlights the potential difficulties in isolating ZIKV from acute clinical samples using conventional cell culture techniques, particularly in non-endemic countries like Australia where access to samples of sufficient viral load is limited. The successful isolation of TS17-2016 will be essential for continued investigations of ZIKV transmission and pathogenicity and will enable the advancement of new preventative control measures extremely relevant to the Australian and Pacific region.

  3. Increasing importance of viruses in acute otitis media.

    PubMed

    Heikkinen, T; Chonmaitree, T

    2000-04-01

    Acute otitis media is generally considered a simple bacterial infection that can be effectively treated with antibiotics. However, despite the extensive use of broad-spectrum antibiotics, poor clinical response to treatment of acute otitis media is common in children. Numerous studies ranging from animal experiments to extensive clinical studies have clearly demonstrated that respiratory viruses play a crucial role in the aetiology and pathogenesis of acute otitis media. Viral infection of the upper respiratory tract initiates the whole cascade of events that finally leads to the development of acute otitis media as a complication. Respiratory viruses induce a release of inflammatory mediators in the nasopharynx, increase bacterial colonization and adherence, and have a suppressive effect on the host's immune defense. Recent data indicate that at least some types of viruses actively invade the middle ear. Viruses also seem to enhance the inflammatory process in the middle ear and impair the outcome of the disease. Vaccines against the major viruses predisposing to acute otitis media hold a great promise for the prevention of this disease. Major advances in the management of acute otitis media will require further research into the mechanisms of viral infection, viral-bacterial interaction and the host inflammatory response during viral infection.

  4. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored.

  5. First case of imported Zika virus infection in Spain.

    PubMed

    Bachiller-Luque, Pablo; Domínguez-Gil González, Marta; Álvarez-Manzanares, Jesús; Vázquez, Ana; De Ory, Fernando; Sánchez-Seco Fariñas, M Paz

    2016-04-01

    We report a case of Zika virus (ZIKV) infection in a patient with diarrhea, fever, synovitis, non-purulent conjunctivitis, and with discreet retro-orbital pain, after returning from Colombia in January 2016. The patient referred several mosquito bites. Presence of ZIKV was detected by PCR (polymerase chain reaction) in plasma. Rapid microbiological diagnosis of ZIKV infection is needed in European countries with circulation of its vector, in order to avoid autochthonous circulation. The recent association of ZIKV infection with abortion and microcephaly, and a Guillain-Barré syndrome highlights the need for laboratory differentiation of ZIKV from other virus infection. Women with potential risk for Zika virus infection who are pregnant or planning to become pregnant must mention that fact during prenatal visits in order to be evaluated and properly monitored. PMID:26994814

  6. Bats and their virome: an important source of emerging viruses capable of infecting humans.

    PubMed

    Smith, Ina; Wang, Lin-Fa

    2013-02-01

    Bats are being increasingly recognized as an important reservoir of zoonotic viruses of different families, including SARS coronavirus, Nipah virus, Hendra virus and Ebola virus. Several recent studies hypothesized that bats, an ancient group of flying mammals, are the major reservoir of several important RNA virus families from which other mammalian viruses of livestock and humans were derived. Although this hypothesis needs further investigation, the premise that bats carry a large number of viruses is commonly accepted. The question of whether bats have unique biological features making them ideal reservoir hosts has been the subject of several recent reviews. In this review, we will focus on the public health implications of bat derived zoonotic viral disease outbreaks, examine the drivers and risk factors of past disease outbreaks and outline research directions for better control of future disease events.

  7. Zika virus and the risk of imported infection in returned travelers: Implications for clinical care.

    PubMed

    Goorhuis, Abraham; von Eije, Karin J; Douma, Renée A; Rijnberg, Noor; van Vugt, Michele; Stijnis, Cornelis; Grobusch, Martin P

    2016-01-01

    Since late 2015, an unprecedented outbreak of Zika virus is spreading quickly across Southern America. The large size of the current outbreak in The Americas will also result in an increase in Zika virus infections among travelers returning from endemic areas. We report five cases of imported Zika virus infection to The Netherlands. Although the clinical course is usually mild, establishing the diagnosis is important, mainly because of the association with congenital microcephaly and the possibility of sexual transmission.

  8. In silico analysis of MHC-I restricted epitopes of Chikungunya virus proteins: Implication in understanding anti-CHIKV CD8(+) T cell response and advancement of epitope based immunotherapy for CHIKV infection.

    PubMed

    Pratheek, B M; Suryawanshi, Amol R; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2015-04-01

    Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus, responsible for acute febrile infection. The high morbidity and socio-economic loss associated with the recent CHIKV epidemics worldwide have raised a great public health concern and emphasize the need to study the immunological basis of CHIKV infection to control the disease. MHC-I restricted CD8(+) T cell response represent one of the major anti-viral immune responses. Accordingly, it is essential to have a detailed understanding towards CHIKV specific MHC-I restricted immunogenic epitopes for anti-viral CD8(+) CTL immunogenicity. In the present study, a computational approach was used to predict the conserved MHC-I epitopes for mouse haplotypes (H2-Db and H2-Dd) and some alleles of the major HLA-I supertypes (HLA-A2, -A3, -A24, -B7, -B15) of all CHIKV proteins. Further, an in-depth computational analysis was carried out to validate the selected epitopes for their nature of conservation in different global CHIKV isolates to assess their binding affinities to the appropriate site of respective MHC-I molecules and to predict anti-CHIKV CD8(+) CTL immunogenicity. Our analyses resulted in fifteen highly conserved epitopes for H2-Db and H2-Dd and fifty epitopes for different HLA-I supertypes. Out of these, the MHC-I epitopes VLLPNVHTL and MTPERVTRL were found to have highest predictable CTL immunogenicities and least binding energies for H2-Db and H2-Dd, whereas, for HLA-I, the epitope FLTLFVNTL was with the highest population coverage, CTL immunogenicity and least binding energy. Hence, our study has identified MHC-I restricted epitopes that may help in the advancement of MHC-I restricted epitope based anti-CHIKV immune responses against this infection and this will be useful towards the development of epitope based anti-CHIKV immunotherapy in the future. However, further experimental investigations for cross validation and evaluation are warranted to establish the ability of epitopes to induce CD8(+) T cell

  9. In silico analysis of MHC-I restricted epitopes of Chikungunya virus proteins: Implication in understanding anti-CHIKV CD8(+) T cell response and advancement of epitope based immunotherapy for CHIKV infection.

    PubMed

    Pratheek, B M; Suryawanshi, Amol R; Chattopadhyay, Soma; Chattopadhyay, Subhasis

    2015-04-01

    Chikungunya virus (CHIKV) is a mosquito-borne Alphavirus, responsible for acute febrile infection. The high morbidity and socio-economic loss associated with the recent CHIKV epidemics worldwide have raised a great public health concern and emphasize the need to study the immunological basis of CHIKV infection to control the disease. MHC-I restricted CD8(+) T cell response represent one of the major anti-viral immune responses. Accordingly, it is essential to have a detailed understanding towards CHIKV specific MHC-I restricted immunogenic epitopes for anti-viral CD8(+) CTL immunogenicity. In the present study, a computational approach was used to predict the conserved MHC-I epitopes for mouse haplotypes (H2-Db and H2-Dd) and some alleles of the major HLA-I supertypes (HLA-A2, -A3, -A24, -B7, -B15) of all CHIKV proteins. Further, an in-depth computational analysis was carried out to validate the selected epitopes for their nature of conservation in different global CHIKV isolates to assess their binding affinities to the appropriate site of respective MHC-I molecules and to predict anti-CHIKV CD8(+) CTL immunogenicity. Our analyses resulted in fifteen highly conserved epitopes for H2-Db and H2-Dd and fifty epitopes for different HLA-I supertypes. Out of these, the MHC-I epitopes VLLPNVHTL and MTPERVTRL were found to have highest predictable CTL immunogenicities and least binding energies for H2-Db and H2-Dd, whereas, for HLA-I, the epitope FLTLFVNTL was with the highest population coverage, CTL immunogenicity and least binding energy. Hence, our study has identified MHC-I restricted epitopes that may help in the advancement of MHC-I restricted epitope based anti-CHIKV immune responses against this infection and this will be useful towards the development of epitope based anti-CHIKV immunotherapy in the future. However, further experimental investigations for cross validation and evaluation are warranted to establish the ability of epitopes to induce CD8(+) T cell

  10. Entomological Investigation and Control of a Chikungunya Cluster in Singapore

    PubMed Central

    Tan, Cheong Huat; Wong, Pei Sze Jeslyn; Li, Mei Zhi Irene; Tan, Siok Yin Sharon; Lee, Tze Kwang Caleb; Pang, Sook Cheng; Lam-Phua, Sai Gek; Maideen, Nasir; Png, Ah Bah; Koou, Sin Ying; Lu, Deng

    2011-01-01

    Abstract In August 2008, a team from the National Environmental Agency conducted an entomological investigation of a chikungunya cluster in Singapore, with the primary aim of identifying the vector responsible for the outbreak and to assess the vector control operation. A total of 173 adult mosquitoes were caught using both the sweep-net method and the BG Sentinel Traps in and around the affected workers' quarters. Of these, 120 (69.4%) were Aedes albopictus and the rest were Culex quinquefasciatus. More than 2700 Ae. albopictus larvae were also collected from 33 breeding habitats detected. No Aedes aegypti was found. During the preintervention period, 6 (8.4%) out of 71 adult female Ae. albopictus were found positive for the chikungunya virus (CHIKV). Vector control measures resulted in a 90% reduction of adult Ae. albopictus caught by BG Sentinel Traps. Postintervention surveillance revealed the presence of CHIKV-positive mosquitoes. These findings led to continued intensive vector control operation in the affected area that further reduced vector population and interrupted the transmission of the disease. The E1 gene sequence of the CHIKV was identical to those of CHIKV isolated from human chikungunya cases working in the affected area, and contained the A226V mutation. The incrimination of Ae. albopictus as a major vector involved in the transmission of A226V CHIKV had led to the revision of chikungunya control strategy in Singapore. This study suggests the benefit of a vector control program that includes the evaluation of control measures in conjunction to virological surveillance in vector population. PMID:21395419

  11. Human antibody response to Aedes albopictus salivary proteins: a potential biomarker to evaluate the efficacy of vector control in an area of Chikungunya and Dengue Virus transmission.

    PubMed

    Doucoure, Souleymane; Mouchet, François; Cornelie, Sylvie; Drame, Papa Makhtar; D'Ortenzio, Eric; DeHecq, Jean Sébastien; Remoue, Franck

    2014-01-01

    Aedes borne viruses represent public health problems in southern countries and threat to emerge in the developed world. Their control is currently based on vector population control. Much effort is being devoted to develop new tools to control such arbovirus. Recent findings suggest that the evaluation of human antibody (Ab) response to arthropod salivary proteins is relevant to measuring the level of human exposure to mosquito bites. Using an immunoepidemiological approach, the present study aimed to assess the usefulness of the salivary biomarker for measuring the efficacy of Ae. albopictus control strategies in La Reunion urban area. The antisaliva Ab response of adult humans exposed to Ae. albopictus was evaluated before and after vector control measures. Our results showed a significant correlation between antisaliva Ab response and the level of exposure to vectors bites. The decrease of Ae. albopictus density has been detected by this biomarker two weeks after the implementation of control measures, suggesting its potential usefulness for evaluating control strategies in a short time period. The identification of species specific salivary proteins/peptides should improve the use of this biomarker. PMID:24822216

  12. Simple Clinical and Laboratory Predictors of Chikungunya versus Dengue Infections in Adults

    PubMed Central

    Lee, Vernon J.; Chow, Angela; Zheng, Xiaohui; Carrasco, Luis R.; Cook, Alex R.; Lye, David C.; Ng, Lee-Ching; Leo, Yee-Sin

    2012-01-01

    Background Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF), is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. Methods We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR) with 917 dengue RT-PCR-positive adult patients (including 55 with DHF). We compared dengue fever (DF), DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. Findings At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF), nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118×109/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100×109/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. Interpretation There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management. PMID:23029573

  13. Mapping recent chikungunya activity in the Americas

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To better understand chikungunya activity in the America we mapped recent chikungunya activity in the Americas. This activity is needed to better understand that the relationships between climatic factors and disease outbreak patters are critical to the design and constructing of predictive models....

  14. The lethal ovitrap: a response to the resurgence of dengue and chikungunya.

    PubMed

    Zeichner, Brian C; Debboun, Mustapha

    2011-01-01

    There has been a global resurgence in dengue fever since the 1960s and now more than one third of the world's population lives in dengue endemic areas. Chikungunya, another mosquito-borne disease, had been limited to sub-Saharan Africa and Southeast Asia, but recently spread to Italy and France, raising concerns that it could spread to many more countries in Europe and the Americas. There are currently no vaccines available to prevent infection with either virus and medical care is limited to symptomatic and supportive treatments. Suppression of the mosquito vector populations reduces disease transmission, however, the tools currently available to control the main vectors of dengue and chikungunya are inadequate. Larval control is very labor intensive and pesticide sprays do not adequately penetrate the microhabitats where adult mosquitoes are sequestered. The lethal ovitrap addresses these shortcomings by luring the potentially viremic female mosquitoes to an egg laying site where they are exposed to a toxic insecticide dose. It is a safe, environmentally sound, economical, and simple means of dengue and chikungunya vector control whose efficacy has been documented in 9 research papers. Management programs using the lethal ovitrap have been shown to halt dengue and chikungunya transmission. Efforts are underway to mass produce the lethal ovitrap under the registered trade name Trap-N-Kill which will ensure its availability to our armed forces deployed in dengue and chikungunya endemic areas. PMID:21805450

  15. Chikungunya: bending over the Americas and the rest of the world.

    PubMed

    Madariaga, Miguel; Ticona, Eduardo; Resurrecion, Cristhian

    2016-01-01

    Chikungunya is an arthropod-borne virus transmitted by Aedes mosquito bites. A viral mutation has allowed Aedes albopictus to become the preferred vector extending the geographic spread of the condition. The virus causes an acute febrile illness occasionally followed by a chronic rheumatic condition causing severe impairment. The diagnosis is usually confirmed with serology. No specific treatment is currently available. This article reviews the condition with emphasis on his dissemination in the Americas.

  16. Chikungunya cases identified through passive surveillance and household investigations--Puerto Rico, May 5-August 12, 2014.

    PubMed

    Sharp, Tyler M; Roth, Nicole M; Torres, Jomil; Ryff, Kyle R; Pérez Rodríguez, Nicole M; Mercado, Chanis; Pilar Diaz Padró, Maria Del; Ramos, Maria; Phillips, Raina; Lozier, Matthew; Arriola, Carmen S; Johansson, Michael; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Margolis, Harold S; García, Brenda Rivera

    2014-12-01

    Chikungunya and dengue are mosquito-borne, viral, acute febrile illnesses that can be difficult to distinguish clinically. Whereas dengue is endemic in many countries in the Caribbean and the Americas, the first locally acquired chikungunya case in the Western Hemisphere was reported from the Caribbean island of St. Martin in December 2013 and was soon followed by cases in many parts of the region. In January 2014, the Puerto Rico Department of Health (PRDH) and CDC initiated chikungunya surveillance by building on an existing passive dengue surveillance system. To assess the extent of chikungunya in Puerto Rico, the severity of illnesses, and the health care-seeking behaviors of residents, PRDH and CDC analyzed data from passive surveillance and investigations conducted around the households of laboratory-positive chikungunya patients. Passive surveillance indicated that the first locally acquired, laboratory-positive chikungunya case in Puerto Rico was in a patient with illness onset on May 5, 2014. By August 12, a total of 10,201 suspected chikungunya cases (282 per 100,000 residents) had been reported. Specimens from 2,910 suspected cases were tested, and 1,975 (68%) were positive for chikungunya virus (CHIKV) infection. Four deaths were reported. The household investigations found that, of 250 participants, 70 (28%) tested positive for current or recent CHIKV infection, including 59 (84%) who reported illness within the preceding 3 months. Of 25 laboratory-positive participants that sought medical care, five (20%) were diagnosed with chikungunya and two (8%) were reported to PRDH. These investigative efforts indicated that chikungunya cases were underrecognized and underreported, prompting PRDH to conduct information campaigns to increase knowledge of the disease among health care professionals and the public. PRDH and CDC recommended that health care providers manage suspected chikungunya cases as they do dengue because of the similarities in symptoms and

  17. Chikungunya cases identified through passive surveillance and household investigations--Puerto Rico, May 5-August 12, 2014.

    PubMed

    Sharp, Tyler M; Roth, Nicole M; Torres, Jomil; Ryff, Kyle R; Pérez Rodríguez, Nicole M; Mercado, Chanis; Pilar Diaz Padró, Maria Del; Ramos, Maria; Phillips, Raina; Lozier, Matthew; Arriola, Carmen S; Johansson, Michael; Hunsperger, Elizabeth; Muñoz-Jordán, Jorge L; Margolis, Harold S; García, Brenda Rivera

    2014-12-01

    Chikungunya and dengue are mosquito-borne, viral, acute febrile illnesses that can be difficult to distinguish clinically. Whereas dengue is endemic in many countries in the Caribbean and the Americas, the first locally acquired chikungunya case in the Western Hemisphere was reported from the Caribbean island of St. Martin in December 2013 and was soon followed by cases in many parts of the region. In January 2014, the Puerto Rico Department of Health (PRDH) and CDC initiated chikungunya surveillance by building on an existing passive dengue surveillance system. To assess the extent of chikungunya in Puerto Rico, the severity of illnesses, and the health care-seeking behaviors of residents, PRDH and CDC analyzed data from passive surveillance and investigations conducted around the households of laboratory-positive chikungunya patients. Passive surveillance indicated that the first locally acquired, laboratory-positive chikungunya case in Puerto Rico was in a patient with illness onset on May 5, 2014. By August 12, a total of 10,201 suspected chikungunya cases (282 per 100,000 residents) had been reported. Specimens from 2,910 suspected cases were tested, and 1,975 (68%) were positive for chikungunya virus (CHIKV) infection. Four deaths were reported. The household investigations found that, of 250 participants, 70 (28%) tested positive for current or recent CHIKV infection, including 59 (84%) who reported illness within the preceding 3 months. Of 25 laboratory-positive participants that sought medical care, five (20%) were diagnosed with chikungunya and two (8%) were reported to PRDH. These investigative efforts indicated that chikungunya cases were underrecognized and underreported, prompting PRDH to conduct information campaigns to increase knowledge of the disease among health care professionals and the public. PRDH and CDC recommended that health care providers manage suspected chikungunya cases as they do dengue because of the similarities in symptoms and

  18. Tropical food legumes: virus diseases of economic importance and their control.

    PubMed

    Hema, Masarapu; Sreenivasulu, Pothur; Patil, Basavaprabhu L; Kumar, P Lava; Reddy, Dodla V R

    2014-01-01

    Diverse array of food legume crops (Fabaceae: Papilionoideae) have been adopted worldwide for their protein-rich seed. Choice of legumes and their importance vary in different parts of the world. The economically important legumes are severely affected by a range of virus diseases causing significant economic losses due to reduction in grain production, poor quality seed, and costs incurred in phytosanitation and disease control. The majority of the viruses infecting legumes are vectored by insects, and several of them are also seed transmitted, thus assuming importance in the quarantine and in the epidemiology. This review is focused on the economically important viruses of soybean, groundnut, common bean, cowpea, pigeonpea, mungbean, urdbean, chickpea, pea, faba bean, and lentil and begomovirus diseases of three minor tropical food legumes (hyacinth bean, horse gram, and lima bean). Aspects included are geographic distribution, impact on crop growth and yields, virus characteristics, diagnosis of causal viruses, disease epidemiology, and options for control. Effectiveness of selection and planting with virus-free seed, phytosanitation, manipulation of crop cultural and agronomic practices, control of virus vectors and host plant resistance, and potential of transgenic resistance for legume virus disease control are discussed. PMID:25410108

  19. High concentrations of circulating interleukin-6 and monocyte chemotactic protein-1 with low concentrations of interleukin-8 were associated with severe chikungunya fever during the 2009-2010 outbreak in Thailand.

    PubMed

    Lohachanakul, Jindarat; Phuklia, Weerawat; Thannagith, Montri; Thonsakulprasert, Tipparat; Ubol, Sukathida

    2012-02-01

    The recent outbreak of Chikungunya virus in Thailand caused a rheumatic fever associated with considerable morbidity and fatalities. Thus, it is important to identify biomarker(s) of severe disease induced by this threatening arbovirus. Putative biomarkers in cases of chikungunya fever during an outbreak in the southern part of Thailand in 2009-2010 were identified. Sixty-two patients who had developed fever and myalgia, with or without arthralgia/arthritis, were enrolled and grouped into severe chikungunya fever (CHIKF) (n= 15), mild CHIKF (n= 20) and non-CHIKF (n= 27) to investigate circulating immunological mediators that might serve as markers of severity. Blood samples were taken at presentation (day 1) and 30 days later (day 30) and plasma concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-17, tumor necrosis factor-alpha, monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-1 and viral load were measured by ELISA. On day 1, severe CHIKF and mild CHIKF groups had viral loads of 10(8.5) and 10(8.3) of RNA copies/mL, respectively. At presentation, all CHIKF patients had circulating concentrations of IL-6 and MCP-1 higher than did non-CHIKF patients, whereas amongst the CHKF patients, the severe CHIKF patients had higher IL-6 concentrations than did mild CHIKF patients. Interestingly, severe CHIKF patients had significantly lower concentrations of circulating IL-8 than the other groups of patients, suggesting that high concentrations of IL-6 and MCP-1 with low concentrations of IL-8 may be a determinant of severe chikungunya virus infection.

  20. Chikungunya antibodies detected in non-human primates and rats in three Indian Ocean islands after the 2006 ChikV outbreak

    PubMed Central

    2014-01-01

    The role of terrestrial vertebrates in the epidemiology of chikungunya disease is poorly understood. We evaluated their exposure and amplification role during the 2006 chikungunya outbreak in the Indian Ocean. Blood samples were collected from 18 mammalian and reptile species from Reunion Island, Mauritius and Mayotte. Among the 1051 samples serologically tested for chikungunya virus (CHIKV), two crab-eating macaques (Macaca fascicularis) and two ship rats (Rattus rattus) proved to be exposed to CHIKV. CHIKV RNA was not detected in 791 analyzed sera. Our results confirm the preferential infection of simian primates and suggest that other vertebrates played a poor or no role in CHIKV transmission during the 2006 outbreak. PMID:24885529

  1. The haemagglutinin protein is an important determinant of measles virus tropism for dendritic cells in vitro.

    PubMed

    Ohgimoto, S; Ohgimoto, K; Niewiesk, S; Klagge, I M; Pfeuffer, J; Johnston, I C; Schneider-Schaulies, J; Weidmann, A; ter Meulen, V; Schneider-Schaulies, S

    2001-08-01

    Recombinant measles viruses (MV) in which the authentic glycoprotein genes encoding the fusion and the haemagglutinin (H) proteins of the Edmonston (ED) vaccine strains were swapped singly or doubly for the corresponding genes of a lymphotropic MV wild-type virus (strain WTF) were used previously to investigate MV tropism in cell lines in tissue culture. When these recombinants and their parental strains, the molecular ED-based clone (ED-tag) and WTF, were used to infect cotton rats, only viruses expressing the MV WTF H protein replicated in secondary lymphatic tissues and caused significant immunosuppression. In vitro, viruses containing the ED H protein revealed a tropism for human peripheral blood lymphocytes as documented by enhanced binding and virus production, whereas those containing the WTF H protein replicated well in monocyte-derived dendritic cells (Mo-DC). This did not correlate with more efficient binding of these viruses to DC, but with an enhancement of uptake, virus spread, accumulation of viral antigens and virus production. Thus, replacement of the ED H protein with WTF H protein was sufficient to confer the DC tropism of WTF to ED-tag in vitro. This study suggests that the MV H protein plays an important role in determining cell tropism to immune cells and this may play an important role in the induction of immunosuppression in vivo. PMID:11457989

  2. Chikungunya fever diagnosed among international travelers--United States, 2005-2006.

    PubMed

    2006-09-29

    Chikungunya virus (CHIKV) is an alphavirus indigenous to tropical Africa and Asia, where it is transmitted to humans by the bite of infected mosquitoes, usually of the genus Aedes. Chikungunya (CHIK) fever, the disease caused by CHIKV, was first recognized in epidemic form in East Africa during 1952-1953. The word "chikungunya" is thought to derive from description in local dialect of the contorted posture of patients afflicted with the severe joint pain associated with this disease. Because CHIK fever epidemics are sustained by human-mosquito-human transmission, the epidemic cycle is similar to those of dengue and urban yellow fever. Large outbreaks of CHIK fever have been reported recently on several islands in the Indian Ocean and in India. In 2006, CHIK fever cases also have been reported in travelers returning from known outbreak areas to Europe, Canada, the Caribbean (Martinique), and South America (French Guyana). During 2005-2006, 12 cases of CHIK fever were diagnosed serologically and virologically at CDC in travelers who arrived in the United States from areas known to be epidemic or endemic for CHIK fever. This report describes four of these cases and provides guidance to health-care providers. Clinicians should be alert for additional cases among travelers, and public health officials should be alert to evidence of local transmission of chikungunya virus (CHIKV), introduced through infection of local mosquitoes by a person with viremia.

  3. Imported Zika Virus Infection from the Cook Islands into Australia, 2014

    PubMed Central

    Pyke, Alyssa T.; Daly, Michelle T.; Cameron, Jane N.; Moore, Peter R.; Taylor, Carmel T.; Hewitson, Glen R.; Humphreys, Jan L.; Gair, Richard

    2014-01-01

    A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia. PMID:24944843

  4. Imported zika virus infection from the cook islands into australia, 2014.

    PubMed

    Pyke, Alyssa T; Daly, Michelle T; Cameron, Jane N; Moore, Peter R; Taylor, Carmel T; Hewitson, Glen R; Humphreys, Jan L; Gair, Richard

    2014-01-01

    A female resident of Townsville, Queensland, Australia has been diagnosed with Zika virus infection following a recent trip to the Cook Islands. An initial serum sample collected in March, 2014 was positive by two separate Zika virus TaqMan real-time RT-PCRs and a pan-Flavivirus RT-PCR. Nucleotide sequencing and phylogenetics of the complete Cook Islands Zika virus envelope gene revealed 99.1% homology with a previous Cambodia 2010 sequence within the Asian lineage. In addition, IgG and IgM antibody seroconversions were detected between paired acute and convalescent phase sera using recombinant Zika virus serology assays. This is the first known imported case of Zika virus infection into northern Queensland where the potential mosquito vector Aedes aegypti is present and only the second such reported case diagnosed within Australia.

  5. Virus decomposition provides an important contribution to benthic deep-sea ecosystem functioning.

    PubMed

    Dell'Anno, Antonio; Corinaldesi, Cinzia; Danovaro, Roberto

    2015-04-21

    Viruses are key biological agents of prokaryotic mortality in the world oceans, particularly in deep-sea ecosystems where nearly all of the prokaryotic C production is transformed into organic detritus. However, the extent to which the decomposition of viral particles (i.e., organic material of viral origin) influences the functioning of benthic deep-sea ecosystems remains completely unknown. Here, using various independent approaches, we show that in deep-sea sediments an important fraction of viruses, once they are released by cell lysis, undergo fast decomposition. Virus decomposition rates in deep-sea sediments are high even at abyssal depths and are controlled primarily by the extracellular enzymatic activities that hydrolyze the proteins of the viral capsids. We estimate that on a global scale the decomposition of benthic viruses releases ∼37-50 megatons of C per year and thus represents an important source of labile organic compounds in deep-sea ecosystems. Organic material released from decomposed viruses is equivalent to 3 ± 1%, 6 ± 2%, and 12 ± 3% of the input of photosynthetically produced C, N, and P supplied through particles sinking to bathyal/abyssal sediments. Our data indicate that the decomposition of viruses provides an important, previously ignored contribution to deep-sea ecosystem functioning and has an important role in nutrient cycling within the largest ecosystem of the biosphere.

  6. Virus decomposition provides an important contribution to benthic deep-sea ecosystem functioning

    PubMed Central

    Dell’Anno, Antonio; Corinaldesi, Cinzia

    2015-01-01

    Viruses are key biological agents of prokaryotic mortality in the world oceans, particularly in deep-sea ecosystems where nearly all of the prokaryotic C production is transformed into organic detritus. However, the extent to which the decomposition of viral particles (i.e., organic material of viral origin) influences the functioning of benthic deep-sea ecosystems remains completely unknown. Here, using various independent approaches, we show that in deep-sea sediments an important fraction of viruses, once they are released by cell lysis, undergo fast decomposition. Virus decomposition rates in deep-sea sediments are high even at abyssal depths and are controlled primarily by the extracellular enzymatic activities that hydrolyze the proteins of the viral capsids. We estimate that on a global scale the decomposition of benthic viruses releases ∼37–50 megatons of C per year and thus represents an important source of labile organic compounds in deep-sea ecosystems. Organic material released from decomposed viruses is equivalent to 3 ± 1%, 6 ± 2%, and 12 ± 3% of the input of photosynthetically produced C, N, and P supplied through particles sinking to bathyal/abyssal sediments. Our data indicate that the decomposition of viruses provides an important, previously ignored contribution to deep-sea ecosystem functioning and has an important role in nutrient cycling within the largest ecosystem of the biosphere. PMID:25848024

  7. Inflammation of the external ear in acute chikungunya infection: Experience from the outbreak in Johor Bahru, Malaysia, 2008.

    PubMed

    Javelle, Emilie; Tiong, Tee Hua; Leparc-Goffart, Isabelle; Savini, Hélène; Simon, Fabrice

    2014-04-01

    The re-emerging invalidating chikungunya disease has recently extended to temperate areas. Other alphaviruses can also present with febrile arthalgias. Dengue virus transmitted by the same species of mosquitoes may cocirculate, leading to dual infections and concurrent epidemics. Although these diseases share similar clinical features, their prognoses considerably differ. Prominent and prolonged articular disorders are more consistent with chikungunya virus, whereas haemorrhages make the gravity of dengue infection. Specific symptoms are required, especially when diagnostic tests are not available or performable at a large scale. Indeed, early clinical suspicion of a vector-borne disease is crucial to isolate the first cases in the course of an outbreak, and discrimination between arboviruses help to optimal management of patients. No specific chikungunya clinical sign has been yet reported. We highlight here the high prevalence (about 25%) of acute ear redness in infected people during the 2008 chikungunya outbreak in Jahor Bahru in Malaysia. Nine consenting patients are more precisely described. Ear chondritis could be sensitive diagnostic criterion of the acute stage of chikungunya, every physician - even in occidental non endemic areas - should be aware of.

  8. Twenty-four cases of imported zika virus infections diagnosed by molecular methods.

    PubMed

    Alejo-Cancho, Izaskun; Torner, Nuria; Oliveira, Inés; Martínez, Ana; Muñoz, José; Jane, Mireia; Gascón, Joaquim; Requena-Méndez, Ana; Vilella, Anna; Marcos, M Ángeles; Pinazo, María Jesús; Gonzalo, Verónica; Rodriguez, Natalia; Martínez, Miguel J

    2016-10-01

    Zika virus is an emerging flavivirus widely spreading through Latin America. Molecular diagnosis of the infection can be performed using serum, urine and saliva samples, although a well-defined diagnostic algorithm is not yet established. We describe a series of 24 cases of imported zika virus infection into Catalonia (northeastern Spain). Based on our findings, testing of paired serum and urine samples is recommended.

  9. [Chikungunya fever--expanded distribution of a re-emerging tropical infectious disease].

    PubMed

    Stock, Ingo

    2009-01-01

    Chikungunya fever has been originally distributed in several parts of Africa, South Asia and Southeast Asia. The disease is caused by Chikungunya virus, an enveloped, single-stranded ribonucleic acid virus of the alphavirus genus (family Togaviridae). In Asia, virus transmission to humans occurs predominantly by the bite of the female Aedes aegypti or Aedes albopictus mosquito. In rural Africa, other mosquito species are also implicated in virus transmission. Chikungunya fever is characterized by fever with sudden onset, headache, backache, myalgia, and rash as well as painful and long-lasting arthralgia, affecting primarily the peripheral joints. Joint pain frequently persists for two or more months. Treatment strategies are primarily supportive and symptomatic and comprise the continuous application of certain analgetics, i.e., paracetamol (acetaminophen) and several non-steroidal anti-inflammatory agents. Although there is no generally recommended specific antiviral therapy, the use of chloroquine, ribavirin and interferon-alpha might be useful. In 2005 and 2006, the largest epidemic of Chikungunya fever ever recorded has been occurred in the islands of the southwest Indian Ocean and in India. The epidemic affected at least 1.3 million cases in India alone. The most affected island was the French territory La Réunion, where approximately one third of the total population (266,000 of 770,000) suffered from the disease. Based on the extent of the epidemic and the busy tourism between India/the islands of the Indian Ocean and Europe, numerous cases have been reported in several European countries since 2005. In 2007, one of these travellers served as "index patient" for the first outbreak of Chikungunya fever in a temperate region. Between July and September 2007, more than 200 cases of infection with Chikungunya virus have been notified in a region of north eastern Italy. The first autochthonic outbreak in Europe has been associated with the presence of A

  10. First Chikungunya Outbreak in Suriname; Clinical and Epidemiological Features

    PubMed Central

    van Genderen, Farah T.; Krishnadath, Ingrid; Sno, Rachel; Grunberg, Meritha G.; Zijlmans, Wilco; Adhin, Malti R.

    2016-01-01

    Background In June 2014, Suriname faced the first Chikungunya outbreak. Since international reports mostly focus on hospitalized patients, the least affected group, a study was conducted to describe clinical characteristics of mainly outpatients including children. In addition, the cumulative incidence of this first epidemic was investigated. Methodology During August and September 2014, clinically suspected Chikungunya cases were included in a prospective follow-up study. Blood specimens were collected and tested for viral RNA presence. Detailed clinical information was gathered through multiple telephone surveys until day 180. In addition, a three stage household-based cluster with a cross-sectional design was conducted in October, December 2014 and March 2015 to assess the cumulative incidence. Principal Findings Sixty-eight percent of symptomatic patients tested positive for Chikungunya virus (CHIKV). Arthralgia and pain in the fingers were distinctive for viremic CHIKV infected patients. Viremic CHIKV infected children (≤12 years) characteristically displayed headache and vomiting, while arthralgia was less common at onset. The disease was cleared within seven days by 20% of the patients, while 22% of the viremic CHIKV infected patients, mostly women and elderly reported persistent arthralgia at day 180. The extrapolated cumulative CHIKV incidence in Paramaribo was 249 cases per 1000 persons, based on CHIKV self-reported cases in 53.1% of the households and 90.4% IgG detected in a subset of self-reported CHIKV+ persons. CHIKV peaked in the dry season and a drastic decrease in CHIKV patients coincided with a governmental campaign to reduce mosquito breeding sites. Conclusions/Significance This study revealed that persistent arthralgia was a concern, but occurred less frequently in an outpatient setting. The data support a less severe pathological outcome for Caribbean CHIKV infections. This study augments incidence data available for first outbreaks in the

  11. Chikungunya and dengue fever among hospitalized febrile patients in northern Tanzania.

    PubMed

    Hertz, Julian T; Munishi, O Michael; Ooi, Eng Eong; Howe, Shiqin; Lim, Wen Yan; Chow, Angelia; Morrissey, Anne B; Bartlett, John A; Onyango, Jecinta J; Maro, Venance P; Kinabo, Grace D; Saganda, Wilbrod; Gubler, Duane J; Crump, John A

    2012-01-01

    Consecutive febrile admissions were enrolled at two hospitals in Moshi, Tanzania. Confirmed acute Chikungunya virus (CHIKV), Dengue virus (DENV), and flavivirus infection were defined as a positive polymerase chain reaction (PCR) result. Presumptive acute DENV infection was defined as a positive anti-DENV immunoglobulin M (IgM) enzyme-linked immunsorbent assay (ELISA) result, and prior flavivirus exposure was defined as a positive anti-DENV IgG ELISA result. Among 870 participants, PCR testing was performed on 700 (80.5%). Of these, 55 (7.9%) had confirmed acute CHIKV infection, whereas no participants had confirmed acute DENV or flavivirus infection. Anti-DENV IgM serologic testing was performed for 747 (85.9%) participants, and of these 71 (9.5%) had presumptive acute DENV infection. Anti-DENV IgG serologic testing was performed for 751 (86.3%) participants, and of these 80 (10.7%) had prior flavivirus exposure. CHIKV infection was more common among infants and children than adults and adolescents (odds ratio [OR] 1.9, P = 0.026) and among HIV-infected patients with severe immunosuppression (OR 10.5, P = 0.007). CHIKV infection is an important but unrecognized cause of febrile illness in northern Tanzania. DENV or other closely related flaviviruses are likely also circulating.

  12. Isolation and characterization of Solenopsis invicta virus 3, a new positive-strand RNA virus infecting the red imported fire ant, Solenopsis invicta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We report the discovery of a new virus from the red imported fire ant, Solenopsis invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus identified from this ant species using the metagenomics approach. The single (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 wa...

  13. Infectious disease emergencies in returning travelers: special reference to malaria, dengue fever, and chikungunya.

    PubMed

    Wattal, Chand; Goel, Neeraj

    2012-11-01

    This review article discusses important infectious illnesses, namely malaria, dengue, and chikungunya, in travelers returning from endemic areas. Malaria and dengue are two of the most common systemic illnesses reported in returning travelers. Because chikungunya is gaining importance, it is also briefly discussed. The clinical significance of these diseases is mainly due to the possibility of sudden deterioration with high mortality in clinically healthy looking patients. The key clinical features, their diagnosis, and treatment algorithms are discussed in detail to help in early diagnosis and appropriate clinical management of such travelers presenting in emergency departments.

  14. The Virus-Host Interplay: Biogenesis of +RNA Replication Complexes

    PubMed Central

    Reid, Colleen R.; Airo, Adriana M.; Hobman, Tom C.

    2015-01-01

    Positive-strand RNA (+RNA) viruses are an important group of human and animal pathogens that have significant global health and economic impacts. Notable members include West Nile virus, Dengue virus, Chikungunya, Severe acute respiratory syndrome (SARS) Coronavirus and enteroviruses of the Picornaviridae family.Unfortunately, prophylactic and therapeutic treatments against these pathogens are limited. +RNA viruses have limited coding capacity and thus rely extensively on host factors for successful infection and propagation. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions. These viral replication complexes (VRCs) serve two main functions: To increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. This review summarizes current knowledge of critical host factors recruited to or demonstrated to be involved in the biogenesis and stabilization of +RNA virus VRCs. PMID:26287230

  15. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    NASA Astrophysics Data System (ADS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-01

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  16. Disease mapping based on stochastic SIR-SI model for Dengue and Chikungunya in Malaysia

    SciTech Connect

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2014-12-04

    This paper describes and demonstrates a method for relative risk estimation which is based on the stochastic SIR-SI vector-borne infectious disease transmission model specifically for Dengue and Chikungunya diseases in Malaysia. Firstly, the common compartmental model for vector-borne infectious disease transmission called the SIR-SI model (susceptible-infective-recovered for human populations; susceptible-infective for vector populations) is presented. This is followed by the explanations on the stochastic SIR-SI model which involve the Bayesian description. This stochastic model then is used in the relative risk formulation in order to obtain the posterior relative risk estimation. Then, this relative estimation model is demonstrated using Dengue and Chikungunya data of Malaysia. The viruses of these diseases are transmitted by the same type of female vector mosquito named Aedes Aegypti and Aedes Albopictus. Finally, the findings of the analysis of relative risk estimation for both Dengue and Chikungunya diseases are presented, compared and displayed in graphs and maps. The distribution from risk maps show the high and low risk area of Dengue and Chikungunya diseases occurrence. This map can be used as a tool for the prevention and control strategies for both diseases.

  17. [Technical guidelines for the prevention and treatment of chikungunya fever].

    PubMed

    Barrera-Cruz, Antonio; Díaz-Ramos, Rita Delia; Viniegra-Osorio, Arturo; Grajales-Muñiz, Concepción; Dávila-Torres, Javier

    2015-01-01

    Chikungunya fever is an emerging disease caused by an alphavirus belonging to the Togaviridae family, transmitted by the bite of Aedes genus species: Aedesaegypti and Aedesalbopictus. In 2013, PAHO/WHO received confirmation of the first cases of indigenous transmission of chikungunya in the Americas. This disease may be acute, subacute and chronic, affecting all age groups. Following an incubation period from three to seven days, the patient usually begins with a high fever (greater than 39 °C), arthralgia, back pain, headache, nausea, vomiting, arthritis, rash, and conjunctivitis (acute phase: 3-10 days). Most patients recover fully, but in some cases, joint involvement may persist chronically and cause discapacity and affect life quality. Serious complications are rare, however, attention must be focused on vulnerable populations (the elderly, children and pregnant women). So far, there is no specific antiviral treatment or effective vaccine, so it is giving priority symptomatic and supportive treatment for the acute phase and make an early diagnosis of atypical and severe forms, and to implement effective prevention and control measures. Given the eco-epidemiological conditions and distribution of vectors in the region of the Americas, the spread of the virus to other countries is likely, so that health professionals should be aware of and identify risk factors and major clinical manifestations, allow timely prevention and safe and effective treatment of this disease.

  18. Studies of hepatitis C virus in chimpanzees and their importance for vaccine development.

    PubMed

    Bukh, J; Forns, X; Emerson, S U; Purcell, R H

    2001-01-01

    Persistent infection with hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. Therefore, the development of vaccines to prevent HCV infection, or at least to prevent progression to chronicity, is a major goal. Potential HCV vaccine candidates include recombinant proteins, recombinant viruses, DNA constructs, synthetic peptides and virus-like particles. Various vaccine candidates have been shown to generate humoral and cellular immune responses in animals, primarily in mice. However, the efficacy of most vaccine candidates in protecting against HCV has not been tested because the chimpanzee, the only animal other than humans that is susceptible to HCV, is not readily available, requires special facilities, and is very expensive. The course of infection in chimpanzees is similar in its diversity to that in humans and detailed studies in this model are beginning to define the immune responses that can terminate HCV infection. Of relevance for vaccine evaluation was the titration in chimpanzees of different HCV variants to provide well-characterized challenge pools. In addition, monoclonal virus pools generated from chimpanzees infected with cloned viruses make it possible now to examine immunity to HCV without the confounding factor of antigenic diversity of the challenge virus (quasispecies). The vaccine trials performed in chimpanzees to date all have tested the efficacy of immunizations with various forms of the envelope proteins of HCV.

  19. Chikungunya

    MedlinePlus

    ... focused on relieving the symptoms. The proximity of mosquito breeding sites to human habitation is a significant ... bites of infected Aedes aegypti and Aedes albopictus mosquitos, both present in the Americas. After the bite ...

  20. Historical inability to control Aedes aegypti as a main contributor of fast dispersal of chikungunya outbreaks in Latin America.

    PubMed

    Fernández-Salas, Ildefonso; Danis-Lozano, Rogelio; Casas-Martínez, Mauricio; Ulloa, Armando; Bond, J Guillermo; Marina, Carlos F; Lopez-Ordóñez, Teresa; Elizondo-Quiroga, Armando; Torres-Monzón, Jorge A; Díaz-González, Esteban E

    2015-12-01

    The arrival of chikungunya fever (CHIKF) in Latin American countries has been expected to trigger epidemics and challenge health systems. Historically considered as dengue-endemic countries, abundant Aedes aegypti populations make this region highly vulnerable to chikungunya virus (CHIKV) circulation. This review describes the current dengue and CHIKF epidemiological situations, as well as the role of uncontrolled Ae. aegypti and Aedes albopictus vectors in spreading the emerging CHIKV. Comments are included relating to the vector competence of both species and failures of surveillance and vector control measures. Dengue endemicity is a reflection of these abundant and persistent Aedes populations that are now spreading CHIKV in the Americas. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World."