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Sample records for a226v mutant chikungunya

  1. Chikungunya

    MedlinePlus

    ... risk factor for chikungunya. The disease occurs in Africa, Asia and the Indian subcontinent. In 2007, disease transmission was reported for the first time in Europe, in a localized outbreak in ...

  2. Chikungunya

    MedlinePlus

    ... 7 days after being bitten by an infected mosquito. The most common symptoms are fever and joint ... way to prevent chikungunya infection is to avoid mosquito bites: Use insect repellent Wear clothes that cover ...

  3. Chikungunya.

    PubMed

    Horwood, P F; Buchy, P

    2015-08-01

    Chikungunya is an acute viral disease characterised by fever and painful arthralgia. The arthritic symptoms associated with chikungunya can be debilitating and may persist for months or even years in some patients. Severe neurological complications such as encephalitis have also been reported during recent large outbreaks. The disease is caused by chikungunya virus (CHIKV), a mosquito-borne alphavirus from the Togaviridae family, which has recently emerged to become one of the most important exotic viral threats worldwide. Chikungunya is endemic throughout Africa, and over the past decade, it has also spread throughout the Indian Ocean, Asia, the South Pacific, southern Europe, the Caribbean and Central America. The rapid emergence of CHIKV has been linked to expansion of the mosquito vector species, Aedes aegypti and Ae. albopictus, throughout most tropical and subtropical regions of the world. Furthermore, mutations in some strains of CHIKV have been associated with increased transmissibility of the virus. The lack of a commercial vaccine and the failure of vector control strategies to limit the expansion of chikungunya have prompted the need for further options to prevent the spread of this disease.

  4. Chikungunya Virus

    MedlinePlus

    ... is key! Prevent Infection. Use mosquito repellent. Chikungunya Virus Distribution Chikungunya in the U.S. What's New Surveillance ... Clinical Challenge For Travelers CDC Travelers' Health Chikungunya Virus Home Prevention Transmission Symptoms & Treatment Geographic Distribution Chikungunya ...

  5. 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

  6. Entomologic and Virologic Investigation of Chikungunya, Singapore

    PubMed Central

    Tan, Li-Kiang; Tan, Cheong-Huat; Tan, Sharon S.Y.; Hapuarachchi, Hapuarachchige C.; Pok, Kwoon-Yong; Lai, Yee-Ling; Lam-Phua, Sai-Gek; Bucht, Göran; Lin, Raymond T.P.; Leo, Yee-Sin; Tan, Boon-Hian; Han, Hwi-Kwang; Ooi, Peng-Lim S; James, Lyn; Khoo, Seow-Poh

    2009-01-01

    Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas. PMID:19751586

  7. [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.

  8. Molecular characterization of Chikungunya virus isolates from clinical samples and adult Aedes albopictus mosquitoes emerged from larvae from Kerala, South India.

    PubMed

    Niyas, Kudukkil P; Abraham, Rachy; Unnikrishnan, Ramakrishnan Nair; Mathew, Thomas; Nair, Sajith; Manakkadan, Anoop; Issac, Aneesh; Sreekumar, Easwaran

    2010-08-13

    Chikungunya virus (CHIKV), an arthritogenic alphavirus, is transmitted to humans by infected Aedes (Ae.) aegypti and Ae.albopictus mosquitoes. In the study, reverse-transcription PCR (RT PCR) and virus isolation detected CHIKV in patient samples and also in adult Ae.albopictus mosquitoes that was derived from larvae collected during a chikungunya (CHIK) outbreak in Kerala in 2009. The CHIKV strains involved in the outbreak were the East, Central and South African (ECSA) genotype that had the E1 A226V mutation. The viral strains from the mosquitoes and CHIK patients from the same area showed a close relationship based on phylogenetic analysis. Genetic characterization by partial sequencing of non-structural protein 2 (nsP2; 378 bp), envelope E1 (505 bp) and E2 (428 bp) identified one critical mutation in the E2 protein coding region of these CHIKV strains. This novel, non-conservative mutation, L210Q, consistently present in both human and mosquito-derived samples studied, was within the region of the E2 protein (amino acids E2 200-220) that determines mosquito cell infectivity in many alpha viruses. Our results show the involvement of Ae. albopictus in this outbreak in Kerala and appearance of CHIKV with novel genetic changes. Detection of virus in adult mosquitoes, emerged in the laboratory from larvae, also points to the possibility of transovarial transmission (TOT) of mutant CHIKV strains in mosquitoes.

  9. Chikungunya virus

    MedlinePlus

    ... 7 days after being bitten by an infected mosquito. The disease is easily spread. Most people who ... and birdbaths. If sleeping outside, sleep under a mosquito net. If you get chikungunya, try to avoid ...

  10. 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

  11. Re-emergence of Chikungunya virus in South-east Asia: virological evidence from Sri Lanka and Singapore.

    PubMed

    Hapuarachchi, H C; Bandara, K B A T; Sumanadasa, S D M; Hapugoda, M D; Lai, Yee-Ling; Lee, Kim-Sung; Tan, Li-Kiang; Lin, Raymond T P; Ng, Lisa F P; Bucht, Göran; Abeyewickreme, Wimaladharma; Ng, Lee-Ching

    2010-04-01

    Chikungunya fever swept across many South and South-east Asian countries, following extensive outbreaks in the Indian Ocean Islands in 2005. However, molecular epidemiological data to explain the recent spread and evolution of Chikungunya virus (CHIKV) in the Asian region are still limited. This study describes the genetic Characteristics and evolutionary relationships of CHIKV strains that emerged in Sri Lanka and Singapore during 2006-2008. The viruses isolated in Singapore also included those imported from the Maldives (n=1), India (n=2) and Malaysia (n=31). All analysed strains belonged to the East, Central and South African (ECSA) lineage and were evolutionarily more related to Indian than to Indian Ocean Islands strains. Unique genetic characteristics revealed five genetically distinct subpopulations of CHIKV in Sri Lanka and Singapore, which were likely to have emerged through multiple, independent introductions. The evolutionary network based on E1 gene sequences indicated the acquisition of an alanine to valine 226 substitution (E1-A226V) by virus strains of the Indian sublineage as a key evolutionary event that contributed to the transmission and spatial distribution of CHIKV in the region. The E1-A226V substitution was found in 95.7 % (133/139) of analysed isolates in 2008, highlighting the widespread establishment of mutated CHIKV strains in Sri Lanka, Singapore and Malaysia. As the E1-A226V substitution is known to enhance the transmissibility of CHIKV by Aedes albopictus mosquitoes, this observation has important implications for the design of vector control strategies to fight the virus in regions at risk of chikungunya fever.

  12. Genome Microevolution of Chikungunya Viruses Causing the Indian Ocean Outbreak

    PubMed Central

    Schuffenecker, Isabelle; Iteman, Isabelle; Michault, Alain; Murri, Séverine; Frangeul, Lionel; Vaney, Marie-Christine; Lavenir, Rachel; Pardigon, Nathalie; Reynes, Jean-Marc; Pettinelli, François; Biscornet, Leon; Diancourt, Laure; Michel, Stéphanie; Duquerroy, Stéphane; Guigon, Ghislaine; Frenkiel, Marie-Pascale; Bréhin, Anne-Claire; Cubito, Nadège; Desprès, Philippe; Kunst, Frank; Rey, Félix A; Zeller, Hervé; Brisse, Sylvain

    2006-01-01

    Background A chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis. Methods and Findings We report the nearly complete genome sequence of six selected viral isolates (isolated from five sera and one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, and Mayotte islands. Our results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, four of which were located in alphavirus-conserved positions of nsP2 (which contains helicase, protease, and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for membrane fusion and virion assembly. Change E1-A226V was absent in the initial strains but was observed in >90% of subsequent viral sequences from Réunion, denoting evolutionary success possibly due to adaptation to the mosquito vector. Conclusions The unique molecular features of the analyzed Indian Ocean

  13. pH-dependent entry of chikungunya virus into Aedes albopictus cells.

    PubMed

    Gay, Bernard; Bernard, Eric; Solignat, Maxime; Chazal, Nathalie; Devaux, Christian; Briant, Laurence

    2012-08-01

    The chikungunya virus (CHIKV) recently caused explosive outbreaks in Indian Ocean islands and India. During these episodes, the virus was mainly spread to humans through the bite of the mosquito Aedes albopictus. Concomitantly to the description of symptoms of an unexpected severity in infants and elderly patients, a viral genome microevolution has been highlighted, in particular consisting in the acquisition of an A226V mutation in the gene encoding envelope glycoprotein E1, which was later found to confer an increased fitness for A. albopictus. We previously decrypted the entry pathway used by CHIKV to infect human epithelial cells and showed that these mechanisms are modulated by the E1-A226V mutation. In this report we investigated the conditions for CHIKV entry into mosquito cells and we assessed the consequence of E1 gene mutation on these parameters. Our main findings indicate that CHIKV infection of A. albopictus cell lines is sensitive to Bafilomycin A1 and chloroquine and to membrane cholesterol depletion. The E1-226V mutated LR-OPY1 isolate collected during the 2005 outbreak in La Réunion replicated more efficiently than the 37997 African reference strain in C6/36 cells. Moreover, the LR-OPY1 strain displayed greater membrane cholesterol dependence and was more sensitive to inhibition of endosomal pH acidification. Finally, using electron microscopy, we imaged CHIKV entry into C6/36 cells. Our data support that CHIKV is endocyted into A. albopictus cells and requires membrane cholesterol as well as a low-pH environment for entry. These features are modulated in some extent by the A226V mutation in the E1 gene of the LR-OPY1 isolate. Altogether, our data provide information regarding the pathways used by CHIKV to infect A. albopictus cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Epistatic roles of E2 glycoprotein mutations in adaption of chikungunya virus to Aedes albopictus and Ae. aegypti mosquitoes.

    PubMed

    Tsetsarkin, Konstantin A; McGee, Charles E; Volk, Sara M; Vanlandingham, Dana L; Weaver, Scott C; Higgs, Stephen

    2009-08-31

    Between 2005 and 2007 Chikungunya virus (CHIKV) caused its largest outbreak/epidemic in documented history. An unusual feature of this epidemic is the involvement of Ae. albopictus as a principal vector. Previously we have demonstrated that a single mutation E1-A226V significantly changed the ability of the virus to infect and be transmitted by this vector when expressed in the background of well characterized CHIKV strains LR2006 OPY1 and 37997. However, in the current study we demonstrate that introduction of the E1-A226V mutation into the background of an infectious clone derived from the Ag41855 strain (isolated in Uganda in 1982) does not significantly increase infectivity for Ae. albopictus. In order to elucidate the genetic determinants that affect CHIKV sensitivity to the E1-A226V mutation in Ae. albopictus, the genomes of the LR2006 OPY1 and Ag41855 strains were used for construction of chimeric viruses and viruses with a specific combination of point mutations at selected positions. Based upon the midgut infection rates of the derived viruses in Ae. albopictus and Ae. aegypti mosquitoes, a critical role of the mutations at positions E2-60 and E2-211 on vector infection was revealed. The E2-G60D mutation was an important determinant of CHIKV infectivity for both Ae. albopictus and Ae. aegypti, but only moderately modulated the effect of the E1-A226V mutation in Ae. albopictus. However, the effect of the E2-I211T mutation with respect to mosquito infections was much more specific, strongly modifying the effect of the E1-A226V mutation in Ae. albopictus. In contrast, CHIKV infectivity for Ae. aegypti was not influenced by the E2-1211T mutation. The occurrence of the E2-60G and E2-211I residues among CHIKV isolates was analyzed, revealing a high prevalence of E2-211I among strains belonging to the Eastern/Central/South African (ECSA) clade. This suggests that the E2-211I might be important for adaptation of CHIKV to some particular conditions prevalent in

  15. 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.

  16. 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

  17. Chikungunya Virus, Southeastern France

    PubMed Central

    Caro, Valérie; Plumet, Sébastien; Thiberge, Jean-Michel; Souarès, Yvan; Failloux, Anna-Bella; Tolou, Hugues J.; Budelot, Michel; Cosserat, Didier; Leparc-Goffart, Isabelle; Desprès, Philippe

    2011-01-01

    In September 2010, autochthonous transmission of chikungunya virus was recorded in southeastern France, where the Aedes albopictus mosquito vector is present. Sequence analysis of the viral genomes of imported and autochthonous isolates indicated new features for the potential emergence and spread of the virus in Europe. PMID:21529410

  18. 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

  19. Perinatal chikungunya in twins

    PubMed Central

    Karthiga, Vikneswari; Kommu, Peter Prasanth Kumar; Krishnan, Lalitha

    2016-01-01

    We report a case of vertically transmitted chikungunya infection in heterozygous twin neonates presenting as seizures, encephalopathy, midfacial hyperpigmentation, anemia, and thrombocytopenia. This could be considered as a rare cause of neonatal seizure and identification would help in appropriate management. PMID:27857791

  20. 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.

  1. Genetic analysis of chikungunya viruses imported to mainland China in 2008.

    PubMed

    Zheng, Kui; Li, Jiandong; Zhang, Quanfu; Liang, Mifang; Li, Chuan; Lin, Miao; Huang, Jicheng; Li, Hua; Xiang, Dapeng; Wang, Ninlan; Hong, Ye; Huang, Li; Li, Xiaobo; Pan, Deguan; Song, Wei; Dai, Jun; Guo, Boxuan; Li, Dexin

    2010-01-18

    Chikungunya virus (CHIKV) has caused large outbreaks worldwide in recent years, especially on the islands of the Indian Ocean and India. The virus is transmitted by mosquitoes (Aedes aegypti), which are widespread in China, with an especially high population density in southern China. Analyses of full-length viral sequences revealed the acquisition of a single adaptive mutation providing a selective advantage for the transmission of CHIKV by this species. No outbreaks due to the local transmission of CHIKV have been reported in China, and no cases of importation were detected on mainland China before 2008. We followed the spread of imported CHIKV in southern China and analyzed the genetic character of the detected viruses to evaluate their potential for evolution. The importation of CHIKV to mainland China was first detected in 2008. The genomic sequences of four of the imported viruses were identified, and phylogenetic analysis demonstrated that the sequences were clustered in the Indian Ocean group; however, seven amino acid changes were detected in the nonstructural protein-coding region, and five amino acid changes were noted in the structural protein-coding regions. In particular, a novel substitution in E2 was detected (K252Q), which may impact the neurovirulence of CHIKV. The adaptive mutation A226V in E1 was observed in two imported cases of chikungunya disease. Laboratory-confirmed CHIKV infections among travelers visiting China in 2008 were presented, new mutations in the viral nucleic acids and proteins may represent adaptive mutations for human or mosquito hosts.

  2. 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

    2016-09-07

    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.

  3. 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.

  4. Sequential Adaptive Mutations Enhance Efficient Vector Switching by Chikungunya Virus and Its Epidemic Emergence

    PubMed Central

    Tsetsarkin, Konstantin A.; Weaver, Scott C.

    2011-01-01

    The adaptation of Chikungunya virus (CHIKV) to a new vector, the Aedes albopictus mosquito, is a major factor contributing to its ongoing re-emergence in a series of large-scale epidemics of arthritic disease in many parts of the world since 2004. Although the initial step of CHIKV adaptation to A. albopictus was determined to involve an A226V amino acid substitution in the E1 envelope glycoprotein that first arose in 2005, little attention has been paid to subsequent CHIKV evolution after this adaptive mutation was convergently selected in several geographic locations. To determine whether selection of second-step adaptive mutations in CHIKV or other arthropod-borne viruses occurs in nature, we tested the effect of an additional envelope glycoprotein amino acid change identified in Kerala, India in 2009. This substitution, E2-L210Q, caused a significant increase in the ability of CHIKV to develop a disseminated infection in A. albopictus, but had no effect on CHIKV fitness in the alternative mosquito vector, A. aegypti, or in vertebrate cell lines. Using infectious viruses or virus-like replicon particles expressing the E2-210Q and E2-210L residues, we determined that E2-L210Q acts primarily at the level of infection of A. albopictus midgut epithelial cells. In addition, we observed that the initial adaptive substitution, E1-A226V, had a significantly stronger effect on CHIKV fitness in A. albopictus than E2-L210Q, thus explaining the observed time differences required for selective sweeps of these mutations in nature. These results indicate that the continuous CHIKV circulation in an A. albopictus-human cycle since 2005 has resulted in the selection of an additional, second-step mutation that may facilitate even more efficient virus circulation and persistence in endemic areas, further increasing the risk of more severe and expanded CHIK epidemics. PMID:22174678

  5. 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.

  6. [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.

  7. [The Chikungunya virus].

    PubMed

    Nakouné, E; Finance, C; Le Faou, A; Rihn, B

    2007-01-01

    Chikungunya virus (CHIKV), a member of the Alphavirus genus, represents a real public health problem in tropical regions of the Southeast Asia and Africa. It is transmitted to the man by Aedes mosquitoes and the illness, known as Chikungunya, is characterized by fever, eruptions and invalidating arthralgia. An increased surveillance in tropical and subtropical areas is necessary, as far as we have noticed recently the emergence of this new disease in regions where it had never existed before. The epidemic context is of a high importance for diagnosis. It is very important to know the clinical characteristics of the infection, to detect forms rarely or never described previously. Permanence of a highly technical core in specialized laboratories will allow, fast, specific and differential diagnosis. The knowledge of the epidemiological chain of transmission from reservoir, still unknown, to the host aims to protect populations by limiting the risks of exposure when it is possible. The only prevention measures available are individual protection against mosquitoes and antivectorial fight, in the absence of specific antiviral treatment and vaccine.

  8. Long-Lasting Immune Protection and Other Epidemiological Findings after Chikungunya Emergence in a Cambodian Rural Community, April 2012

    PubMed Central

    Duong, Veasna; Baisley, Kathy; Nguon, Kunthy; Chan, Siam; Huy, Rekol; Ly, Sovann; Sorn, Sopheak; Som, Leakhann; Buchy, Philippe; Tarantola, Arnaud

    2016-01-01

    The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3–4 weeks after the outbreak, and determined the sensitivity and specificity of case definitions and factors associated with infection by CHIKV. Self-reported clinical presentation consisted mostly of fever, rash and arthralgia. The presence of all three clinical signs or symptoms was identified as the most sensitive (67%) and specific (84%) self-reported diagnostic clinical indicator compared to biological confirmation by MAC-ELISA or RT-PCR used as a reference. Having an indoor occupation was associated with lower odds of infection compared with people who remained at home (adjOR 0.32, 95%CI 0.12–0.82). In contrast with findings from outbreaks in other settings, persons aged above 40 years were less at risk of CHIKV infection, likely reflecting immune protection acquired when Chikungunya circulated in Cambodia before the Khmer Rouge regime in 1975. In view of the very particular history of Cambodia, our epidemiological data from Trapeang Roka are the first to support the persistence of CHIKV antibodies over a period of 40 years. PMID:26752630

  9. Long-Lasting Immune Protection and Other Epidemiological Findings after Chikungunya Emergence in a Cambodian Rural Community, April 2012.

    PubMed

    Galatas, Beatriz; Ly, Sowath; Duong, Veasna; Baisley, Kathy; Nguon, Kunthy; Chan, Siam; Huy, Rekol; Ly, Sovann; Sorn, Sopheak; Som, Leakhann; Buchy, Philippe; Tarantola, Arnaud

    2016-01-01

    The East/Central/South African genotype of Chikungunya virus with the E1-A226V mutation emerged in 2011 in Cambodia and spread in 2012. An outbreak of 190 cases was documented in Trapeang Roka, a rural village. We surveyed 425 village residents within 3-4 weeks after the outbreak, and determined the sensitivity and specificity of case definitions and factors associated with infection by CHIKV. Self-reported clinical presentation consisted mostly of fever, rash and arthralgia. The presence of all three clinical signs or symptoms was identified as the most sensitive (67%) and specific (84%) self-reported diagnostic clinical indicator compared to biological confirmation by MAC-ELISA or RT-PCR used as a reference. Having an indoor occupation was associated with lower odds of infection compared with people who remained at home (adjOR 0.32, 95%CI 0.12-0.82). In contrast with findings from outbreaks in other settings, persons aged above 40 years were less at risk of CHIKV infection, likely reflecting immune protection acquired when Chikungunya circulated in Cambodia before the Khmer Rouge regime in 1975. In view of the very particular history of Cambodia, our epidemiological data from Trapeang Roka are the first to support the persistence of CHIKV antibodies over a period of 40 years.

  10. Genetic characterization of 2006-2008 isolates of Chikungunya virus from Kerala, South India, by whole genome sequence analysis.

    PubMed

    Sreekumar, E; Issac, Aneesh; Nair, Sajith; Hariharan, Ramkumar; Janki, M B; Arathy, D S; Regu, R; Mathew, Thomas; Anoop, M; Niyas, K P; Pillai, M R

    2010-02-01

    Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified and they were predominant in the 2007 and 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 and 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S and E2 K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120; 2008 RGCB355) by full-genome analysis, and also in 13 of the 31 additional samples (42%), obtained from various parts of the state, by sequencing the corresponding genomic regions. These mutations showed 100% co-occurrence in all these samples. In phylogenetic analysis, formation of a new genetic clade by these isolates within the East, Central and South African (ECSA) genotypes was observed. Homology modeling followed by mapping revealed that at least 20 of the identified mutations fall into functionally significant domains of the viral proteins and are predicted to affect protein structure. Eighteen of the identified mutations in structural proteins, including the E2 K252Q change, are predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK virus with novel genetic changes were present in the severe Chikungunya outbreaks in 2007 and 2008 in South India.

  11. First Report of the East-Central South African Genotype of Chikungunya Virus in Rio de Janeiro, Brazil

    PubMed Central

    Souza, Thiara Manuele Alves; Azeredo, Elzinandes Leal; Badolato-Corrêa, Jessica; Damasco, Paulo Vieira; Santos, Carla; Petitinga-Paiva, Fabienne; Nunes, Priscila Conrado Guerra; Barbosa, Luciana Santos; Cipitelli, Márcio Costa; Chouin-Carneiro, Thais; Faria, Nieli Rodrigues Costa; Nogueira, Rita Maria Ribeiro; de Bruycker-Nogueira, Fernanda; dos Santos, Flavia Barreto

    2017-01-01

    Background: Chikungunya virus (CHIKV) is an arbovirus that causes an acute febrile syndrome with a severe and debilitating arthralgia. In Brazil, the Asian and East-Central South African (ECSA) genotypes are circulating in the north and northeast of the country, respectively. In 2015, the first autochthonous cases in Rio de Janeiro, Brazil were reported but until now the circulating strains have not been characterized. Therefore, we aimed here to perform the molecular characterization and phylogenetic analysis of CHIKV strains circulating in the 2016 outbreak occurred in the municipality of Rio de Janeiro. Methods: The cases analyzed in this study were collected at a private Hospital, from April 2016 to May 2016, during the chikungunya outbreak in Rio de Janeiro, Brazil. All cases were submitted to the Real Time RT-PCR for CHIKV genome detection and to anti-CHIKV IgM ELISA. Chikungunya infection was laboratorially confirmed by at least one diagnostic method and, randomly selected positive cases (n=10), were partially sequenced (CHIKV E1 gene) and analyzed. Results: The results showed that all the samples grouped in ECSA genotype branch and the molecular characterization of the fragment did not reveal the A226V mutation in the Rio de Janeiro strains analyzed, but a K211T amino acid substitution was observed for the first time in all samples and a V156A substitution in two of ten samples. Conclusions: Phylogenetic analysis and molecular characterization reveals the circulation of the ECSA genotype of CHIKV in the city of Rio de Janeiro, Brazil and two amino acids substitutions (K211T and V156A) exclusive to the CHIKV strains obtained during the 2016 epidemic, were reported. PMID:28286701

  12. 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.

  13. 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.

  14. Cytokines in Acute Chikungunya

    PubMed Central

    Venugopalan, Anuradha; Ghorpade, Ravi P.; Chopra, Arvind

    2014-01-01

    Introduction Acute chikungunya (CHIKV) is predominantly an acute onset of excruciatingly painful, self-limiting musculoskeletal (MSK) arbovirus illness and this was further reported by us during the 2006 Indian epidemic [Chopra et al. Epidemiol Infect 2012]. Selected serum cytokines profile in subjects within one month of onset of illness is being presented. Methods Out of 509 clinical CHIKV cases (43% population) identified during a rural population survey, 225 subjects consented blood investigations. 132 examined within 30 days of febrile onset are the study cohort. Anti-CHIKV IgM and IgG antibodies tested by immunochromatography and indirect immunofluorescence respectively. Interferons (IFN)-α, -β and -γ, Interferon Gamma-Induced Protein-10 (CXCL-10/IP-10), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6), Interleukin-13 (IL-13), Monocyte Chemoattractant Protein-1 (MCP-1), Interleukin–4 (IL-4) and Interleukin–10 (IL-10) performed by ELISA. Samples collected from neighboring community a year prior to the epidemic used as healthy controls. Results Seropositivity for anti-CHIKV IgM and IgG was 65% and 52% respectively. IFN-α, IFN-β, IFN-γ, CXCL10/IP-10 and IL-1β showed intense response in early acute phase. Cytokines (particularly TNF-α, MCP-1, IL-4, IL-6 and IL-10) was maximum in extended symptomatic phase and remained elevated in recovered subjects. Higher (p<0.05) IFN and IL-4 seen in patients seropositive for anti-CHIKV IgG. Elderly cases (≥65 years) showed elevated cytokines (except IFN) and anti-CHIKV antibodies near similar to younger subjects. Significant correlations (p<0.05) found between cytokines and clinical features (fatigue, low back ache, myalgia) and anti-CHIKV antibodies. Conclusion An intense cytokine milieu was evident in the early and immediate persistent symptomatic phase and in recovered subjects. Early persistent IgM and lower IgG to anti-CHKV and intense Th2 cytokine phenotype seem to be

  15. Epidemiology of Chikungunya in the Americas.

    PubMed

    Yactayo, Sergio; Staples, J Erin; Millot, Véronique; Cibrelus, Laurence; Ramon-Pardo, Pilar

    2016-12-15

    Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya. © 2016 World Health Organization; licensee Oxford Journals.

  16. Epidemiology of Chikungunya in the Americas

    PubMed Central

    Yactayo, Sergio; Staples, J. Erin; Millot, Véronique; Cibrelus, Laurence; Ramon-Pardo, Pilar

    2016-01-01

    Chikungunya virus (CHIKV) emerged in the Americas in late 2013 to cause substantial acute and chronic morbidity. About 1.1 million cases of chikungunya were reported within a year, including severe cases and deaths. The burden of chikungunya is unclear owing to inadequate disease surveillance and underdiagnosis. Virus evolution, globalization, and climate change may further CHIKV spread. No approved vaccine or antiviral therapeutics exist. Early detection and appropriate management could reduce the burden of severe atypical and chronic arthritic disease. Improved surveillance and risk assessment are needed to mitigate the impact of chikungunya. PMID:27920170

  17. Ophthalmologic aspects of chikungunya infection.

    PubMed

    Martínez-Pulgarín, Dayron F; Chowdhury, Fazle Rabbi; Villamil-Gomez, Wilmer E; Rodriguez-Morales, Alfonso J; Blohm, Gabriela M; Paniz-Mondolfi, Alberto E

    Chikungunya fever, a viral disease epidemic in some parts of the world is newly introduced in the Americas. This is of considerable international concern, with a growing incidence owing to developing urbanization, tourism, and trade. Ocular manifestations of chikungunya fever are not frequent, but of great relevance. Common manifestations include conjunctivitis, optic neuritis, iridocyclitis, episcleritis, retinitis and uveitis. Diagnostic and monitoring investigations would include optical coherence tomography, fundus fluorescein and indocyanine green angiography, visual field analysis, and electrophysiologic tests. There have been no prospective, randomized therapeutic trials, and it is unclear if the disease is self-limiting or if treatment is actually beneficial. Prognosis varies, ranging from full resolution to permanent vision loss despite intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Antiviral Perspectives for Chikungunya Virus

    PubMed Central

    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. PMID:24955364

  19. Dengue and Chikungunya Vector Control Pocket Guide

    USDA-ARS?s Scientific Manuscript database

    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 ...

  20. Mapping recent chikungunya activity in the Americas

    USDA-ARS?s Scientific Manuscript database

    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....

  1. 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.

  2. Transplacental Chikungunya Virus Antibody Kinetics, Thailand

    PubMed Central

    Endy, Timothy P.; Simasathien, Sriluck; Kerdpanich, Angkool; Polprasert, Napuschon; Aree, Chanchai; Vaughn, David W.; Nisalak, Ananda

    2006-01-01

    Antibodies to chikungunya virus were detected by hemagglutination-inhibition assay in 33.6% of 2,000 infants' cord sera at delivery. Follow-up of 24 seropositive infants showed that the half-life of antibody persistence was 35.5 days. Chikungunya virus infection is common in Thailand, and routine use of diagnostic assays is needed. PMID:17283634

  3. 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."

  4. Vertical transmission of Indian Ocean Lineage of chikungunya virus in Aedes aegypti and Aedes albopictus mosquitoes.

    PubMed

    Chompoosri, Jakkrawarn; Thavara, Usavadee; Tawatsin, Apiwat; Boonserm, Rungfar; Phumee, Atchara; Sangkitporn, Somchai; Siriyasatien, Padet

    2016-04-23

    The re-emergence of chikungunya (CHIK) fever in Thailand has been caused by a novel lineage of chikungunya virus (CHIKV) termed the Indian Ocean Lineage (IOL). The Aedes albopictus mosquito is thought to be a primary vector of CHIK fever in Thailand, whereas Ae. aegypti acts as a secondary vector of the virus. The vertical transmission is believed to be a primary means to maintain CHIKV in nature and may be associated with an increased risk of outbreak. Therefore, the goal of this study was to analyze the potential of these two Thai mosquito species to transmit the virus vertically and to determine the number of successive mosquito generations for the virus transmission. Two-hundred-and-fifty female Ae. aegypti and Ae. albopictus mosquitoes were artificially fed a mixture of human blood and CHIKV IOL. Mosquito larvae and adults were sampled and screened for CHIKV by one-step qRT-PCR. LLC-MK2 cell line was used to isolate CHIKV in the mosquitoes each generation. The virus isolate was identified by immunocytochemical staining and was confirmed by sequencing. Both mosquito species fed on human blood without CHIKV and uninfected LLC-MK2 cells were used as controls. Aedes aegypti and Ae. albopictus mosquitoes were able to transmit CHIKV vertically to F5 and F6 progenies, respectively. The virus isolated from the two mosquito species caused cytopathic effect in LLC-MK2 cells by 2 days post-infection and immunocytochemical staining showed the reaction between CHIKV IOL antigen and specific monoclonal antibody in the infected cells. DNA sequence confirmed the virus transmitted vertically as CHIKV IOL with E1-A226V mutation. No CHIKV infection was observed in both mosquito species and LLC-MK2 cells from control groups. The study demonstrated that Ae. aegypti and Ae. albopictus mosquitoes from Thailand are capable of transmitting CHIKV IOL vertically in the laboratory. Our results showed that Ae. albopictus is more susceptible and has a greater ability to transmit the virus

  5. 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

  6. Characterization of Reemerging Chikungunya Virus

    PubMed Central

    Sourisseau, Marion; Schilte, Clémentine; Casartelli, Nicoletta; Trouillet, Céline; Guivel-Benhassine, Florence; Rudnicka, Dominika; Sol-Foulon, Nathalie; Roux, Karin Le; Prevost, Marie-Christine; Fsihi, Hafida; Frenkiel, Marie-Pascale; Blanchet, Fabien; Afonso, Philippe V; Ceccaldi, Pierre-Emmanuel; Ozden, Simona; Gessain, Antoine; Schuffenecker, Isabelle; Verhasselt, Bruno; Zamborlini, Alessia; Saïb, Ali; Rey, Felix A; Arenzana-Seisdedos, Fernando; Desprès, Philippe; Michault, Alain; Albert, Matthew L; Schwartz, Olivier

    2007-01-01

    An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host. PMID:17604450

  7. 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.

  8. 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 ...

  9. Chikungunya and the eye: a review

    PubMed Central

    2013-01-01

    Chikungunya is a self-limited, systemic viral infection that has been a major health problem since the past few years. Ocular manifestations of the disease have become more prevalent in the recent years. Currently, there is neither a specific treatment nor vaccine available for chikungunya fever. This review highlights the current understanding on the pathogenesis, systemic changes with an emphasis on ocular findings, laboratory investigations, and prevention and treatment of this disease. PMID:23514031

  10. CHIKUNGUNYA - A SERIOUS THREAT FOR PUBLIC HEALTH.

    PubMed

    Hrnjaković Cvjetković, Ivana B; Cvjetković, Dejan; Patić, Aleksandra; Nikolić, Nataša; Stefan Mikić, Sandra; Milošević, Vesna

    2015-01-01

    Chikungunya is a contagious disease caused by Chikungunya virus, an arbovirus from the Togaviridae family. This infection is mostly spread by mosquitoes from the genus Aedes, especially Aedes albopiclus, which have spread from Asia to America and Europe including some countries surrounding Serbia. EPIDEMIOLOGIC FEATURES: The outbreak of epidemics has been reported in Philippines, Sumatra, Java, Indonesia, West Africa region (from Senegal to Cameroon), Congo, Nigeria, Angola, Uganda, Guinea, Malawi, Central African Republic, Burundi, South Africa and India. At the beginning of the 21st century, large outbreaks were recorded on the island of Réunion. During 2006, 1.400.000 cases of chikungunya infection were recorded in India. Local transmission of infection in continental Europe was reported from Northeast Italy (254 suspected and 78 laboratory confirmed cases in Emilia-Romagna region) and France (two cases in 2010). From December 2013 to June 2014, 5.294 confirmed cases and more than 180.000 suspected cases of chikungunya were reported in the Caribbean. The disease presents suddenly with fever, rush and arthralgia. In general, chikungunya is a mild self - limited disease. Less often, it may be presented with signs of meningoencephalitis or fulminant hepatitis, sometimes with fatal outcome. Fast developing international traffic and booming tourism as well as the vector spreading from its homeland make chikungunya a real threat to our country.

  11. Neurologic Manifestation of Chikungunya Virus.

    PubMed

    Brizzi, Kate

    2017-02-01

    Chikungunya virus (CHIKV) is a RNA arbovirus that typically causes fevers and arthralgias, but reports of neurologic findings have become increasingly common. This article reviews our current understanding of CHIKV-associated neurologic manifestations. In the last 5 years, CHIKV endemicity has spread to the Americas and the number of cases of CHIKV-related disease has dramatically increased. Evidence suggests increasing neurovirulence of the virus, particularly among the critically ill. The spectrum of neurologic manifestations of the disease includes encephalitis, myelitis, and Guillain-Barre syndrome, but isolated reports of cranial neuropathies and cognitive deficits associated with recent infection also are reported. Though neurologic symptoms associated with CHIKV remain relatively uncommon, their frequency appears to be increasing. Clinicians treating patients with neurologic symptoms from CHIKV endemic areas should be aware of the growing association between CHIKV and neurologic sequelae to help guide diagnostics. Research into the optimal treatment of the disease is needed to inform treatment practices.

  12. MUCOCUTANEOUS MANIFESTATIONS OF CHIKUNGUNYA FEVER

    PubMed Central

    Bandyopadhyay, Debabrata; Ghosh, Sudip Kumar

    2010-01-01

    Chikungunya fever (CF) is an arboviral acute febrile illness transmitted by the bite of infected Aedes mosquitoes. After a quiescence of more than three decades, CF has recently re-emerged as a major public health problem of global scale. CF is characterized by an acute onset of high fever associated with a severe disabling arthritis often accompanied by prominent mucocutaneous manifestations. The disease is usually self-limiting, but the joint symptoms and some of the cutaneous features may persist after the defervescence. A wide range of mucocutaneous changes has been described to occur in association with CF during the current epidemic. Besides a morbilliform erythema, hyperpigmentation, xerosis, excoriated papules, aphthous-like ulcers, vesiculobullous and lichenoid eruptions, and exacerbation of pre-existing or quiescent dermatoses had been observed frequently. These unusual features may help in the clinical differential diagnosis of acute viral exanthems mimicking CF. PMID:20418982

  13. Chikungunya

    MedlinePlus

    ... About PAHO Help and Services Integrity and Conflict Management System (ICMS) Doing Business with PAHO Employment Internships Privacy Policy Events Contacts Resources  PAHO/WHO Collaborating Centers IRIS Institutional Repository for Information Sharing Virtual Campus for Public Health Complete news ...

  14. Chikungunya Fever in Los Angeles, California

    PubMed Central

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

    2014-01-01

    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. PMID:25493131

  15. 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.

  16. Development of Vaccines for Chikungunya Fever.

    PubMed

    Erasmus, Jesse H; Rossi, Shannan L; Weaver, Scott C

    2016-12-15

    Chikungunya fever, an acute and often chronic arthralgic disease caused by the mosquito-borne chikungunya virus (CHIKV), has reemerged since 2004 to cause millions of cases. Because CHIKV exhibits limited antigenic diversity and is not known to be capable of reinfection, a vaccine could serve to both prevent disease and diminish human amplification during epidemic circulation. Here, we review the many promising vaccine platforms and candidates developed for CHIKV since the 1970s, including several in late preclinical or clinical development. We discuss the advantages and limitations of each, as well as the commercial and regulatory challenges to bringing a vaccine to market.

  17. The medicinal chemistry of Chikungunya virus.

    PubMed

    da Silva-Júnior, Edeildo F; Leoncini, Giovanni O; Rodrigues, Érica E S; Aquino, Thiago M; Araújo-Júnior, João X

    2017-08-15

    Arthropod-borne viruses (arboviruses) are an important threat to human and animal health globally. Among these, zoonotic diseases account for billions of cases of human illness and millions of deaths every year, representing an increasing public health problem. Chikungunya virus belongs to the genus Alphavirus of the family Togariridae, and is transmitted mainly by the bite of female mosquitoes of the Aedes aegypti and/or A. albopictus species. The focus of this review will be on the medicinal chemistry of Chikungunya virus, including synthetic and natural products, as well as rationally designed compounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. 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.

  19. 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.

  20. Chikungunya virus infection: an overview.

    PubMed

    Caglioti, Claudia; Lalle, Eleonora; Castilletti, Concetta; Carletti, Fabrizio; Capobianchi, Maria Rosaria; Bordi, Licia

    2013-07-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus belonging to the Togaviridae family, first isolated in Tanzania in 1952. The main vectors are mosquitoes from the Aedes species. Recently, the establishment of an envelope mutation increased infectivity for A. albopictus. CHIKV has recently re-emerged causing millions of infections in countries around the Indian Ocean characterized by climate conditions favourable to high vector density. Importation of human cases to European regions with high density of suitable arthropod vectors (such as A. albopictus) may trigger autochthonous outbreaks. The clinical signs of CHIKV infection include non-specific flu-like symptoms, and a characteristic rash accompanied by joint pain that may last for a long time after the resolution of the infection. The death rate is not particularly high, but excess mortality has been observed in concomitance with large CHIKV outbreaks. Deregulation of innate defense mechanisms, such as cytokine inflammatory response, may participate in the main clinical signs of CHIKV infection, and the establishment of persistent (chronic) disease. There is no specific therapy, and prevention is the main countermeasure. Prevention is based on insect control and in avoiding mosquito bites in endemic countries. Diagnosis is based on the detection of virus by molecular methods or by virus culture on the first days of infection, and by detection of an immune response in later stages. CHIKV infection must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. Differential diagnosis should take into account the cross-reactivity with other viruses from the same antigenic complex (i.e. O'nyong-nyong virus).

  1. 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. Copyright © 2014 Meason, Paterson. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

  2. Chikungunya in Europe: What’s next?

    USDA-ARS?s Scientific Manuscript database

    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...

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

    PubMed

    Montero, Antonio

    2015-08-07

    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.

  4. Chronic arthritis in chikungunya virus infection.

    PubMed

    Mateo, Lourdes; Roure, Silvia

    2017-07-24

    Chikungunya virus infection causes arthralgia and arthritis in the acute phase of the disease but, in more than half of the cases, musculoskeletal manifestations can be prolonged over time and, in some cases, become chronic. Although polyarthralgia is the most frequent chronic manifestation, forms with polyarthritis, tenosynovitis and enthesopathy are also common. To analyze the clinical characteristics of patients with persistent articular manifestations after infection with the Chikungunya virus. Report of 3 cases of chronic arthritis after infection with chikungunya virus diagnosed at outpatient care in a university hospital of Catalonia, all of them imported after exposure in areas of epidemic infection between 2013-2015. All three patients had inflammatory joint pain for more than one year after acute disease (3, 2 and 1 years, respectively). In all cases, it appeared as polyarthritis with involvement of small joints of hands and feet (pseudorheumatoid arthritis-like). Laboratory tests showed a slight elevation of acute phase reactants, and analyses for immune markers were negative. Two of the patients required treatment with glucocorticoids and hydroxychloroquine. The course led to slow clinical improvement, but only one of them came to be completely asymptomatic. In the differential diagnosis of chronic polyarthritis, Chikungunya virus disease should also be considered in areas in which it is not endemic. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  5. 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.

  6. Reemergence of Chikungunya Virus in Cambodia

    PubMed Central

    Duong, Veasna; Andries, Anne-Claire; Ngan, Chantha; Sok, Touch; Richner, Beat; Asgari-Jirhandeh, Nima; Bjorge, Steve; Huy, Rekol; Ly, Sovann; Laurent, Denis; Hok, Bunheng; Roces, Maria Concepcion; Ong, Sivuth; Char, Meng Chuor; Deubel, Vincent; Tarantola, Arnaud

    2012-01-01

    Chikungunya virus (CHIKV), probably Asian genotype, was first detected in Cambodia in 1961. Despite no evidence of acute or recent CHIKV infections since 2000, real-time reverse transcription PCR of serum collected in 2011 detected CHIKV, East Central South African genotype. Spatiotemporal patterns and phylogenetic clustering indicate that the virus probably originated in Thailand. PMID:23171736

  7. Case Series: Chikungunya and Dengue at a Forward Operating Location

    DTIC Science & Technology

    2015-05-01

    ABSTRACT Chikungunya virus is a mosquito borne arbovirus in the genus Alphavirus. In humans, infection with chikungunya virus causes a painful but...SUBJECT TERMS Chikungunya, dengue, mosquitoes 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT SAR 18. NUMBER OF PAGES 3... mosquitoes around the lodging area. Patient 5 On 27 November 2014, a 24-year-old patient presented at the clinic with a fever of 102.6°F (39.2°C). His

  8. Chikungunya virus and prospects for a vaccine

    PubMed Central

    Weaver, Scott C; Osorio, Jorge E; Livengood, Jill A; Chen, Rubing; Stinchcomb, Dan T

    2013-01-01

    In 2004, chikungunya virus (CHIKV) re-emerged from East Africa to cause devastating epidemics of debilitating and often chronic arthralgia that have affected millions of people in the Indian Ocean Basin and Asia. More limited epidemics initiated by travelers subsequently occurred in Italy and France, as well as human cases exported to most regions of the world, including the Americas where CHIKV could become endemic. Because CHIKV circulates during epidemics in an urban mosquito–human cycle, control of transmission relies on mosquito abatement, which is rarely effective. Furthermore, there is no antiviral treatment for CHIKV infection and no licensed vaccine to prevent disease. Here, we discuss the challenges to the development of a safe, effective and affordable chikungunya vaccine and recent progress toward this goal. PMID:23151166

  9. 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.

  10. 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.

  11. A nonhuman primate model of chikungunya disease

    PubMed Central

    Higgs, Stephen; Ziegler, Sarah A.

    2010-01-01

    Chikungunya disease is a severely debilitating, mosquito-borne, viral illness that has reached epidemic proportions in Africa, Asia, and the islands of the Indian Ocean. A mutation enhancing the ability of the chikungunya virus (CHIKV) to infect and be transmitted by Aedes albopictus has increased the geographical range at risk for infection due to the continuing global spread of this mosquito. Research into disease pathogenesis, vaccine development, and therapeutic design has been hindered by the lack of appropriate animal models of this disease. The meticulous study reported in this issue of the JCI by Labadie et al. is one of the first reports describing CHIKV infection of adult immunocompetent nonhuman primates. Using traditional and modern molecular and immunological approaches, the authors demonstrate that macaques infected with CHIKV are a good model of human CHIKV infection and also show that persistent arthralgia in humans may be caused by persistent CHIKV infection of macrophages. PMID:20179348

  12. 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

  13. Antiviral activity of silymarin against chikungunya virus

    PubMed Central

    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

    2015-01-01

    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. PMID:26078201

  14. Spatial and temporal distribution of chikungunya activity in the Americas

    USDA-ARS?s Scientific Manuscript database

    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....

  15. Complete genome sequence of chikungunya virus isolated in the Philippines.

    PubMed

    Kawashima, Kent D; Suarez, Lady-Anne C; Labayo, Hannah Karen M; Liles, Veni R; Salvoza, Noel C; Klinzing, David C; Daroy, Maria Luisa G; Matias, Ronald R; Natividad, Filipinas F

    2014-06-26

    Chikungunya virus is an alphavirus of the Togaviridae family, which causes a febrile illness with arthralgia in humans. We report here on the complete genome sequence of chikungunya virus strain CHIKV-13-112A isolated from a patient in the Philippines who was suspected to have dengue virus. Phylogenetic analysis revealed that the strain is of the Asian genotype.

  16. Complete Genome Sequence of Chikungunya Virus Isolated in the Philippines

    PubMed Central

    Kawashima, Kent D.; Suarez, Lady-Anne C.; Labayo, Hannah Karen M.; Liles, Veni R.; Salvoza, Noel C.; Klinzing, David C.; Natividad, Filipinas F.

    2014-01-01

    Chikungunya virus is an alphavirus of the Togaviridae family, which causes a febrile illness with arthralgia in humans. We report here on the complete genome sequence of chikungunya virus strain CHIKV-13-112A isolated from a patient in the Philippines who was suspected to have dengue virus. Phylogenetic analysis revealed that the strain is of the Asian genotype. PMID:24970822

  17. Evaluating the effectiveness of localized control strategies to curtail chikungunya

    PubMed Central

    Ndeffo-Mbah, Martial L.; Durham, David P.; Skrip, Laura A.; Nsoesie, Elaine O.; Brownstein, John S.; Fish, Durland; Galvani, Alison P.

    2016-01-01

    Chikungunya, a re-emerging arbovirus transmitted to humans by Aedes aegypti and Ae. albopictus mosquitoes, causes debilitating disease characterized by an acute febrile phase and chronic joint pain. Chikungunya has recently spread to the island of St. Martin and subsequently throughout the Americas. The disease is now affecting 42 countries and territories throughout the Americas. While chikungunya is mainly a tropical disease, the recent introduction and subsequent spread of Ae. albopictus into temperate regions has increased the threat of chikungunya outbreaks beyond the tropics. Given that there are currently no vaccines or treatments for chikungunya, vector control remains the primary measure to curtail transmission. To investigate the effectiveness of a containment strategy that combines disease surveillance, localized vector control and transmission reduction measures, we developed a model of chikungunya transmission dynamics within a large residential neighborhood, explicitly accounting for human and mosquito movement. Our findings indicate that prompt targeted vector control efforts combined with measures to reduce transmission from symptomatic cases to mosquitoes may be highly effective approaches for controlling outbreaks of chikungunya, provided that sufficient detection of chikungunya cases can be achieved. PMID:27045523

  18. Chikungunya Fever in Traveler from Angola to Japan, 2016.

    PubMed

    Takaya, Saho; Kutsuna, Satoshi; Nakayama, Eri; Taniguchi, Satoshi; Tajima, Shigeru; Katanami, Yuichi; Yamamoto, Kei; Takeshita, Nozomi; Hayakawa, Kayoko; Kato, Yasuyuki; Kanagawa, Shuzo; Ohmagari, Norio

    2017-01-01

    Simultaneous circulation of multiple arboviruses presents diagnostic challenges. In May 2016, chikungunya fever was diagnosed in a traveler from Angola to Japan. Travel history, incubation period, and phylogenetic analysis indicated probable infection acquisition in Angola, where a yellow fever outbreak is ongoing. Thus, local transmission of chikungunya virus probably also occurs in Angola.

  19. Chikungunya Fever in Traveler from Angola to Japan, 2016

    PubMed Central

    Nakayama, Eri; Taniguchi, Satoshi; Tajima, Shigeru; Katanami, Yuichi; Yamamoto, Kei; Takeshita, Nozomi; Hayakawa, Kayoko; Kato, Yasuyuki; Kanagawa, Shuzo; Ohmagari, Norio

    2017-01-01

    Simultaneous circulation of multiple arboviruses presents diagnostic challenges. In May 2016, chikungunya fever was diagnosed in a traveler from Angola to Japan. Travel history, incubation period, and phylogenetic analysis indicated probable infection acquisition in Angola, where a yellow fever outbreak is ongoing. Thus, local transmission of chikungunya virus probably also occurs in Angola. PMID:27983938

  20. Imported Chikungunya Virus Strains, Taiwan, 2006–2014

    PubMed Central

    Yang, Cheng-Fen; Su, Chien-Ling; Hsu, Tung-Chien; Chang, Shu-Fen; Lin, Chien-Chou

    2016-01-01

    We identified 78 imported chikungunya cases in Taiwan during 2006–2014. Sixty-six (84.6%) cases were initially suspected to be dengue, which indicates the necessity for laboratory diagnostics in differentiation between dengue and chikungunya. Results also emphasize the need for active surveillance of febrile illness at points of entry. PMID:27767908

  1. Surveillance for Chikungunya and Dengue During the First Year of Chikungunya Virus Circulation in Puerto Rico.

    PubMed

    Sharp, Tyler M; Ryff, Kyle R; Alvarado, Luisa; Shieh, Wun-Ju; Zaki, Sherif R; Margolis, Harold S; Rivera-Garcia, Brenda

    2016-12-15

    After chikungunya virus (CHIKV) transmission was detected in Puerto Rico in May 2014, multiple surveillance systems were used to describe epidemiologic trends and CHIKV-associated disease. Of 28 327 cases reported via passive surveillance, 6472 were tested for evidence of CHIKV infection, and results for 4399 (68%) were positive. Of 250 participants in household cluster investigations, 70 (28%) had evidence of recent CHIKV infection. Enhanced surveillance for chikungunya at 2 hospitals identified 1566 patients who tested positive for CHIKV, of whom 10.9% were hospitalized. Enhanced surveillance for fatal cases enabled identification of 31 cases in which CHIKV was detected in blood or tissue specimens. All surveillance systems detected a peak incidence of chikungunya in September 2014 and continued circulation in 2015. Concomitant surveillance for dengue demonstrated low incidence, which had decreased before CHIKV was introduced. Multifaceted chikungunya surveillance in Puerto Rico resolved gaps in traditional passive surveillance and enabled a holistic description of the spectrum of disease associated with CHIKV infection. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Acute Macular Neuroretinopathy Associated With Chikungunya Fever.

    PubMed

    Pang, Claudine E; Navajas, Eduardo V; Warner, Simon J; Heisler, Morgan; Sarunic, Marinko V

    2016-06-01

    A 47-year-old man with recent travel to the Caribbean was admitted with acute febrileillness associated with arthralgia and skin rash followed by sudden onset of bilateral visual field defects. Funduscopy revealed subtle bilateral paracentral dark lesions nasal to the fovea best seen on near infrared imaging as hyporeflective, wedge-shaped, paracentral macular lesions. Spectral-domain optical coherence tomography (SD-OCT) through the lesions revealed hyperreflective bands at the level of the outer plexiform layer and outer nuclear layer (ONL), with concomitant attenuation of the underlying external limiting membrane (ELM), ellipsoid zone (EZ), and interdigitation zone (IZ). Neither fluorescein angiography nor speckle variance OCT angiography (sv-OCTA) showed any defects in retinal circulation. Work up revealed positive Immunoglobulin M for Chikungunya virus (CHIKV). Six months later, the patient had persistent scotomas, although reduced in size. SD-OCT showed subtle ONL thinning and restoration of the ELM, although EZ and IZ remained disrupted. Chikungunya fever may manifest as bilateral acute macular neuroretinopathy (AMN). Clinicians should be aware of possible systemic associations of AMN. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:596-599.]. Copyright 2016, SLACK Incorporated.

  3. 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

  4. 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.

  5. [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.

  6. 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.

  7. Drought-associated chikungunya emergence along coastal East Africa.

    PubMed

    Chretien, Jean-Paul; Anyamba, Assaf; Bedno, Sheryl A; Breiman, Robert F; Sang, Rosemary; Sergon, Kibet; Powers, Ann M; Onyango, Clayton O; Small, Jennifer; Tucker, Compton J; Linthicum, Kenneth J

    2007-03-01

    Epidemics of chikungunya fever, an Aedes spp.-borne viral disease, affected hundreds of thousands of people in western Indian Ocean islands and India during 2005-2006. The initial outbreaks occurred in coastal Kenya (Lamu, then Mombasa) in 2004. We investigated eco-climatic conditions associated with chikungunya fever emergence along coastal Kenya using epidemiologic investigations and satellite data. Unusually dry, warm conditions preceded the outbreaks, including the driest since 1998 for some of the coastal regions. Infrequent replenishment of domestic water stores and elevated temperatures may have facilitated Chikungunya virus transmission. These results suggest that drought-affected populations may be at heightened risk for chikungunya fever, and underscore the need for safe water storage during drought relief operations.

  8. 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.

  9. Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation.

    PubMed

    Inglis, Fiona M; Lee, Kim M; Chiu, Kevin B; Purcell, Olivia M; Didier, Peter J; Russell-Lodrigue, Kasi; Weaver, Scott C; Roy, Chad J; MacLean, Andrew G

    2016-04-01

    Chikungunya, "that which bends up" in the Makonde dialect, is an emerging global health threat, with increasing incidence of neurological complications. Until 2013, Chikungunya infection had been largely restricted to East Africa and the Indian Ocean, with cases within the USA reported to be from foreign travel. However, in 2014, over 1 million suspected cases were reported in the Americas, and a recently infected human could serve as an unwitting reservoir for the virus resulting in an epidemic in the continental USA. Chikungunya infection is increasingly being associated with neurological sequelae. In this study, we sought to understand the role of astrocytes in the neuropathogenesis of Chikungunya infection. Even after virus has been cleared form the circulation, astrocytes were activated with regard to TLR2 expression. In addition, white matter astrocytes were hypertrophic, with increased arbor volume in gray matter astrocytes. Combined, these would alter the number and distribution of synapses that each astrocyte would be capable of forming. These results provide the first evidence that Chikungunya infection induces morphometric and innate immune activation of astrocytes in vivo. Perturbed glia-neuron signaling could be a major driving factor in the development of Chikungunya-associated neuropathology.

  10. Severe Chikungunya infection in Northern Mozambique: a case report.

    PubMed

    Aly, Mussa Manuel; Ali, Sadia; Muianga, Argentina Felisbela; Monteiro, Vanessa; Gallego, Jorge Galano; Weyer, Jacqueline; Falk, Kerstin I; Paweska, Janusz Tadeusz; Cliff, Julie; Gudo, Eduardo Samo

    2017-02-08

    Although Chikungunya virus has rapidly expanded to several countries in sub-Saharan Africa, little attention has been paid to its control and management. Until recently, Chikungunya has been regarded as a benign and self-limiting disease. In this report we describe the first case of severe Chikungunya disease in an adult patient in Pemba, Mozambique. A previously healthy 40 year old male of Makonde ethnicity with no known past medical history and resident in Pemba for the past 11 years presented with a severe febrile illness. Despite administration of broad spectrum intravenous antibiotics the patient rapidly deteriorated and became comatose while developing anaemia, thrombocytopenia and later, melaena. Laboratory testing revealed IgM antibodies against Chikungunya virus. Malaria tests were consistently negative. This report suggests that Chikungunya might cause unsuspected severe disease in febrile patients in Mozambique and provides insights for the improvement of national protocols for management of febrile patients in Mozambique. We recommend that clinicians should consider Chikungunya in the differential diagnosis of febrile illness in locations where Aedes aegypti mosquitos are abundant.

  11. Thiazolidone derivatives as inhibitors of chikungunya virus.

    PubMed

    Jadav, Surender Singh; Sinha, Barij Nayan; Hilgenfeld, Rolf; Pastorino, Boris; de Lamballerie, Xavier; Jayaprakash, Venkatesan

    2015-01-07

    A series of arylalkylidene derivatives of 1,3-thiazolidin-4-one (1-20) were synthesized and tested for their antiviral activity against chikungunya virus (LR2006_OPY1) in Vero cell culture by CPE reduction assay. Five compounds (7-9, 16 and 19) were identified to have anti-ChikV activity at lower micro molar concentration. The compounds 7, 8, 9, 16 and 19 inhibited the virus at 0.42, 4.2, 3.6, 40.1 and 6.8 μM concentrations respectively. Molecular docking simulation has been carried out using the available X-ray crystal structure of the ChikV nsp2 protease, in order to elucidate the possible mechanism of action. Interaction of ligands with ChikV nsp2 protease (PDB Code: 3TRK) suggested the possible mechanism of protease inhibition to act as potent anti-ChikV agents.

  12. Mapping interactions of Chikungunya virus nonstructural proteins.

    PubMed

    Sreejith, R; Rana, Jyoti; Dudha, Namrata; Kumar, Kapila; Gabrani, Reema; Sharma, Sanjeev K; Gupta, Amita; Vrati, Sudhanshu; Chaudhary, Vijay K; Gupta, Sanjay

    2012-10-01

    The four nonstructural proteins (nsPs1-4) of Chikungunya virus (CHIKV) play important roles involving enzymatic activities and specific interactions with both viral and host components, during different stages of viral pathogenesis. Elucidation of the presence and/or absence of interactions among nsPs in a systematic manner is thus of scientific interest. In the current study, each pair-wise combination among the four nonstructural proteins of CHIKV was systematically analyzed for possible interactions. Six novel protein interactions were identified for CHIKV, using systems such as yeast two-hybrid, GST pull down and ELISA, three of which have not been previously reported for the genus Alphavirus. These interactions form a network of organized associations that suggest the spatial arrangement of nonstructural proteins in the late replicase complex. The study identified novel interactions as well as concurred with previously described associations in related alphaviruses.

  13. Chikungunya in the Americas: Recommendations and Conclusions.

    PubMed

    Graham, Barney S; Repik, Patricia M; Yactayo, Sergio

    2016-12-15

    Discovered in 1953, chikungunya virus (CHIKV) circulated in Africa and Southeast Asia, with periodic outbreaks, for many years. Highly efficient transmission following a genetic mutation of the virus in 2005 caused its global spread. Associated with significant morbidity, CHIKV creates a large public health burden, and despite various efforts, there are currently no licensed vaccines nor specific treatments. To garner a better understanding of the virus, identify gaps in knowledge, and guide the development of more-effective interventions, the World Health Organization and National Institute of Allergy and Infectious Diseases assembled global experts for discussion and review. Herein described are the outcomes. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  14. 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.

  15. A study of the outbreak of Chikungunya fever.

    PubMed

    Patil, Supriya Satish; Patil, Satish R; Durgawale, P M; Patil, A G

    2013-06-01

    Chikungunya fever occurred in an epidemic form in the state of Maharashtra after a gap of about 32 years. Many cases with symptoms which were suggestive of Chikungunya fever were reported from the village Kasegaon, Dist Sangli, Maharashtra, India. Hence, this study was done to assess the magnitude of the outbreak and to identify the possible socio-environmental factors which are responsible for Chikungunya fever. This cross sectional study was carried out at Kasegaon by a team from the Krishna Institute of Medical Sciences, Karad, Maharashtra, in collaboration with the Primary Health Centre, Kasegaon, Distt. Sangli. The Chikungunya prevalence was 9.6%. There were 154 clinically suspected Chikungunya fever cases. Of these, 54.5% were males and 45.5% were females. About 72.7% of the cases were in the age range of 11-50 years, which is the active age group. The main symptoms were an acute onset of fever with joint pain (100%). Multiple joints were involved in (89.6%) cases. The mean duration of the fever was 3 days (range 1-10 days). About 40.3% people preferred to consult a government health facility. In the affected area, 83.1% people were aware of Chikungunya fever. Only few (1.1%) knew the vectors which were responsible for the Chikungunya transmission. Among the people in the affected area, 33.1% had knowledge on insecticide spraying, 23.2% had knowledge on the use of mosquito nets and repellents, 12.5% had knowledge on source reduction and 0.8% had knowledge on larvicides.

  16. A study of the outbreak of Chikungunya fever

    PubMed Central

    Patil, Supriya Satish; Patil, Satish R.; Durgawale, P.M.; Patil, A.G.

    2013-01-01

    Background and Objectives: Chikungunya fever occurred in an epidemic form in the state of Maharashtra after a gap of about 32 years. Many cases with symptoms which were suggestive of Chikungunya fever were reported from the village Kasegaon, Dist Sangli, Maharashtra, India. Hence, this study was done to assess the magnitude of the outbreak and to identify the possible socio-environmental factors which are responsible for Chikungunya fever. Material and Methods: This cross sectional study was carried out at Kasegaon by a team from the Krishna Institute of Medical Sciences, Karad, Maharashtra, in collaboration with the Primary Health Centre, Kasegaon, Distt. Sangli. Results and Conclusion: The Chikungunya prevalence was 9.6%. There were 154 clinically suspected Chikungunya fever cases. Of these, 54.5% were males and 45.5% were females. About 72.7% of the cases were in the age range of 11-50 years, which is the active age group. The main symptoms were an acute onset of fever with joint pain (100%). Multiple joints were involved in (89.6%) cases. The mean duration of the fever was 3 days (range 1-10 days). About 40.3% people preferred to consult a government health facility. In the affected area, 83.1% people were aware of Chikungunya fever. Only few (1.1%) knew the vectors which were responsible for the Chikungunya transmission. Among the people in the affected area, 33.1% had knowledge on insecticide spraying, 23.2% had knowledge on the use of mosquito nets and repellents, 12.5% had knowledge on source reduction and 0.8% had knowledge on larvicides. PMID:23905103

  17. Retrospective study of chikungunya outbreak in urban areas of India

    PubMed Central

    Nagpal, B.N.; Saxena, Rekha; Srivastava, Aruna; Singh, Neeru; Ghosh, S.K.; Sharma, S.K.; Kumar, Ashwani; Kumar, Hemant; Sharma, Alok Suman; Chand, S.K.; Ojha, V.P.; Mohanty, S.S.; Mohanty, A.K.; Dasgupta, R.K.; Dhillon, G.P.S.; Dash, A.P.

    2012-01-01

    Background & objectives: A retrospective study on chikungunya outbreak in India in five States viz. Delhi, Madhya Pradesh, Orissa, Maharashtra and Kerala was conducted in 2007-2008 to know the distribution and determinants of chikungunya fever outbreak in India. Methods: On the basis of high and low incidence of chikungunya fever, two districts from each State and two wards from the selected district were taken for random selection of 1000 households from 10 districts and 5 States. Semi-structured questionnaires were administered to individuals, patients, qualified health professionals and to stakeholders for collecting information. Results: The educational background and occupation of the respondents showed variations across the study States. Only in high incidence ward of Maharashtra, water storage period for 3-6 days and emptying, drying of water containers on weekly basis was noted. The study through knowledge, attitude, belief, practice (KABP) obtained individual's perception of chikungunya fever, its prevention and control. Patients’ expenditure on treatment was mainly recorded less than Rs 500 across study States. Health facility survey obtained an overview of the capacity of local health facilities. Stakeholders’ perception regarding chikungunya fever was also noted. Interpretation & Conclusions: The study revealed differences in awareness of chikungunya, cause of the disease, vector responsible, mode of transmission, biting time and elimination of breeding of mosquitoes statistically significant among high and low incidence wards of all the States. Expenditure on treatment was independent of economically active status and loss of man-days across all the States. Education and occupation did not have any relation with emptying/drying of water containers in high incidence wards. Strengthening of surveillance, information, education and communication (IEC) activities along with case management facilities may be provided by the State health department for

  18. Investigation of chikungunya fever outbreak in Laguna, Philippines, 2012.

    PubMed

    Ballera, Julius Erving; Zapanta, Ma Justina; de los Reyes, Vikki Carr; Sucaldito, Ma Nemia; Tayag, Enrique

    2015-01-01

    In July 2012, the Philippines National Epidemiology Center received a report of a suspected chikungunya fever outbreak in San Pablo City, Laguna Province, the first chikungunya cases reported from the city since surveillance started in 2007. We conducted an outbreak investigation to identify risk factors associated with chikungunya. A case was defined as any resident of Concepcion Village in San Pablo City who had fever of at least two days duration and either joint pains or rash between 23 June and 6 August 2012. Cases were ascertained by conducting house-to-house canvassing and medical records review. An unmatched case-control study was conducted and analysed using a multivariate logistic regression. An environmental investigation was conducted by observing water and sanitation practices, and 100 households were surveyed to determine House and Breteau Indices. Human serum samples were collected for confirmation for chikungunya IgM through enzyme-linked immunosorbent assay. There were 98 cases identified. Multivariate analysis revealed that having a chikungunya case in the household (adjusted odds ratio [aOR]: 6.2; 95% confidence interval [CI]: 3.0-12.9) and disposing of garbage haphazardly (aOR: 2.7; 95% CI: 1.4-5.4) were associated with illness. House and Breteau Indices were 27% and 28%, respectively. Fifty-eight of 84 (69%) serum samples were positive for chikungunya IgM. It was not surprising that having a chikungunya case in a household was associated with illness in this outbreak. However, haphazard garbage disposal is not an established risk factor for the disease, although this could be linked to increased breeding sites for mosquitoes.

  19. Investigation of chikungunya fever outbreak in Laguna, Philippines, 2012

    PubMed Central

    Zapanta, Ma Justina; de los Reyes, Vikki Carr; Sucaldito, Ma Nemia; Tayag, Enrique

    2015-01-01

    Background In July 2012, the Philippines National Epidemiology Center received a report of a suspected chikungunya fever outbreak in San Pablo City, Laguna Province, the first chikungunya cases reported from the city since surveillance started in 2007. We conducted an outbreak investigation to identify risk factors associated with chikungunya. Methods A case was defined as any resident of Concepcion Village in San Pablo City who had fever of at least two days duration and either joint pains or rash between 23 June and 6 August 2012. Cases were ascertained by conducting house-to-house canvassing and medical records review. An unmatched case-control study was conducted and analysed using a multivariate logistic regression. An environmental investigation was conducted by observing water and sanitation practices, and 100 households were surveyed to determine House and Breteau Indices. Human serum samples were collected for confirmation for chikungunya IgM through enzyme-linked immunosorbent assay. Results There were 98 cases identified. Multivariate analysis revealed that having a chikungunya case in the household (adjusted odds ratio [aOR]: 6.2; 95% confidence interval [CI]: 3.0–12.9) and disposing of garbage haphazardly (aOR: 2.7; 95% CI: 1.4–5.4) were associated with illness. House and Breteau Indices were 27% and 28%, respectively. Fifty-eight of 84 (69%) serum samples were positive for chikungunya IgM. Conclusion It was not surprising that having a chikungunya case in a household was associated with illness in this outbreak. However, haphazard garbage disposal is not an established risk factor for the disease, although this could be linked to increased breeding sites for mosquitoes. PMID:26668759

  20. 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

  1. Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission

    PubMed Central

    Mangala Prasad, Vidya; Wang, Cheng-I; Akahata, Wataru; Ng, Lisa F. P.

    2015-01-01

    ABSTRACT Chikungunya virus is a positive-stranded RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 and 5F10) were determined using cryo-electron microscopy and X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface and block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain and lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 and therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur. IMPORTANCE Alphaviral infections are transmitted mainly by mosquitoes. Chikungunya virus (CHIKV), which belongs to the Alphavirus genus, has a wide distribution in the Old World that has expanded in recent years into the Americas. There are currently no vaccines or drugs against alphaviral infections. Therefore, a better understanding of CHIKV and its associated neutralizing antibodies will aid in the development of effective treatments. PMID:26537684

  2. Preventing dengue and chikungunya fever among international travelers.

    PubMed

    Tither, Pauline Herold

    2014-11-01

    To describe the vulnerability of U.S. travelers in tropical and subtropical regions of the world to dengue and chikungunya fever, to provide practical recommendations to avoid these mosquito-borne diseases, and to offer a communication tool as an aid for pretravel health consultations. Medical, epidemiological, and entomological research articles and reviews, and reports from government agencies. Dengue and chikungunya fever have growing public health impact around the world. International travelers return to the United States infected with these diseases. Mosquito bite avoidance is the only way to prevent dengue and chikungunya fever. Informed travelers have many options for simple and practical measures to lessen the risk of mosquito bites. A message map can be used as a communication tool for pretravel counseling on the prevention of dengue and chikungunya fever within the time frame of an office visit. In a pretravel health consultation, a nurse practitioner can promote travelers' health and prevent dengue, chikungunya fever, and other mosquito-borne diseases by counseling on the risk of these diseases and giving practical recommendations for prevention using a message map. ©2014 American Association of Nurse Practitioners.

  3. 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.

  4. Detection of Chikungunya Virus Antigen by a Novel Rapid Immunochromatographic Test

    PubMed Central

    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

    2014-01-01

    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. PMID:25411170

  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. Preparedness for Threat of Chikungunya in the Pacific

    PubMed Central

    Hoy, Damian; Horwood, Paul F.; Ropa, Berry; Hancock, Thane; Guillaumot, Laurent; Rickart, Keith; Frison, Pascal; Pavlin, Boris; Souares, Yvan

    2014-01-01

    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. PMID:25062306

  7. Chikungunya Pathogenesis: From the Clinics to the Bench.

    PubMed

    Gasque, Philippe; Bandjee, Marie Christine Jaffar; Reyes, Marcela Mercado; Viasus, Diego

    2016-12-15

    Chikungunya alphavirus has caused large epidemics worldwide and leads to acute incapacitating polyarthralgia. The inflammatory reaction over several days will drive robust innate and humoral responses essential to control the infection. Critically, fatal cases and mother-to-child transmission have also been described. Chikungunya can give rise to chronic musculoskeletal diseases, which can last for months to years, particularly in elderly individuals, and occasionally leads to seronegative rheumatoid arthritis-like pathologies. Histopathological studies of patient biopsy specimens and animal models have revealed that chikungunya virus can hide in tissue sanctuaries, and ongoing research should help to decipher the inflammatory mechanisms of tissue injuries. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. Chikungunya Fever Presenting as Life Threatening Thrombotic Thrombocytopenic Purpura.

    PubMed

    Kumar, Vimal; Jain, Rujul; Kumar, Arvind; Nischal, Neeraj; Jorwal, Pankaj; Soneja, Manish; Arava, Sudheer; Wig, Naveet

    2017-07-01

    It is well known for Chikungunya fever to present as myriad of skin rash along with usual joint pain and fever, but probably this is the first case report of Chikungunya fever presenting as severe life threatening thrombotic microangiopathy, thrombotic thrombocytopenic purpura leading to multiple areas of skin necrosis, peripheral digital gangrene, haemolytic anemia, renal failure and severe thrombocytopenia with bleeding. This complication was most likely due to inhibitor autoantibody formation against ADAMTS13 triggered by chikungunya virus leading to thrombotic thrombocytopenic purpura. Patient was treated with plasmapheresis and other supportive careto which she responded. Her symptoms subsided, and she is symptom free and leading normal life in her follow up visits. © Journal of the Association of Physicians of India 2011.

  9. Chikungunya Virus in North-Eastern Italy: A Seroprevalence Survey

    PubMed Central

    Moro, Maria Luisa; Gagliotti, Carlo; Silvi, Giuliano; Angelini, Raffaella; Sambri, Vittorio; Rezza, Giovanni; Massimiliani, Erika; Mattivi, Andrea; Grilli, Elisa; Finarelli, Alba Carola; Spataro, Nadir; Pierro, Anna Maria; Seyler, Thomas; Macini, Pierluigi

    2010-01-01

    After an outbreak of Chikungunya infection in Emilia-Romagna Region (North-eastern Italy), a survey was performed to estimate the seroprevalence of antibody to Chikungunya virus and the proportion of asymptomatic infections, to identify factors associated with infection, and evaluate the performance of the surveillance system. The method used was a survey on a random sample of residents of the village with the largest number of reported cases. The prevalence was 10.2% (33 of 325), being higher in older people and males, and lower when window screens and insect repellents were used. Only 18% of infected persons were fully asymptomatic, 85% of the 27 symptomatic confirmed cases satisfied the surveillance case definition, and 63% of the persons meeting the criteria for suspect case were identified by the active surveillance system. This study provides basic parameters for modeling the transmission potential of outbreaks and planning control measures for Chikungunya infection in temperate settings. PMID:20207883

  10. Homeopathic drug therapy. Homeopathy in Chikungunya Fever and Post-Chikungunya Chronic Arthritis: an observational study.

    PubMed

    Wadhwani, Gyandas G

    2013-07-01

    To observe the effect of homeopathic therapy in Chikungunya Fever (CF) and in Post-Chikungunya Chronic Arthritis (PCCA) in a primary health care setting. A prospective observational study was conducted at Delhi Government Homeopathic Dispensary, Aali Village, New Delhi, India, for a period of 6 months, from 1st October 2010 to 31st March 2011. 126 patients (75 CF, 51 PCCA) were enrolled based on predefined inclusion criteria. A single homeopathic medicine was prescribed for each patient after case taking with the help of Materia Medica and/or Repertory. Results were evaluated on the basis of visual analogue scale and symptom scores. Complete recovery was seen in 84.5% CF cases in a mean time of 6.8 days. 90% cases of PCCA recovered completely in a mean time of 32.5 days. Homeopathic therapy may be effective in CF and PCCA. A randomized controlled trial should be considered. Copyright © 2013 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.

  11. Detection of chikungunya virus in saliva and urine.

    PubMed

    Musso, Didier; Teissier, Anita; Rouault, Eline; Teururai, Sylviane; de Pina, Jean-Jacques; Nhan, Tu-Xuan

    2016-06-16

    Saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (CHIKV). We investigated the use of saliva and urine for molecular detection of CHIKV during the French Polynesian outbreak. During the French Polynesian chikungunya outbreak (2014-2015), we collected the same day blood and saliva samples from 60 patients with probable chikungunya (47 during the 1st week post symptoms onset and 13 after), urine was available for 39 of them. All samples were tested using a CHIKV reverse-transcription PCR. Forty eight patients had confirmed chikungunya. For confirmed chikungunya presenting during the 1st week post symptoms onset, CHIKV RNA was detected from 86.1 % (31/36) of blood, 58.3 % (21/36) of saliva and 8.3 % (2/24) of urine. Detection rate of CHIKV RNA was significantly higher in blood compared to saliva. For confirmed chikungunya presenting after the 1st week post symptoms onset, CHIKV RNA was detected from 8.3 % (1/12) of blood, 8.3 % (1/12) of saliva and 0 % (0/8) of urine. In contrast to Zika virus (ZIKV), saliva did not increased the detection rate of CHIKV RNA during the 1st week post symptoms onset. In contrast to ZIKV, dengue virus and West Nile virus, urine did not enlarged the window of detection of CHIKV RNA after the 1st week post symptoms onset. Saliva can be used for molecular detection of CHIKV during the 1st week post symptoms onset only if blood is impossible to collect but with a lower sensitivity compared to blood.

  12. [Chikungunya and urban sprawl on Reunion Island].

    PubMed

    Aoustin, T

    2012-03-01

    The proportion of unsanitary housing in French overseas departments is much higher than in mainland France. Reunion Island is no exception to this fact. Between 80 and 90% of housing in Reunion Island was built by squatters with no legal claim or deed to the property. This has resulted in uncontrolled urban sprawl with living conditions reminiscent of those in developing countries. The absence of adequate drainage systems for sewage and rain water and the lack of properly organized garbage disposal that characterizes these sprawl areas constitutes a particularly favorable breeding ground for vector-borne diseases, especially chikungunya. Thus, implementing measures to control this type of settlement and to relocate of people out of existing sprawl areas constitutes a significant tool to control this epidemiological risk. Up to now, public officials have shown a clear reluctance to intervene in sprawl areas despite good knowledge of their location. On June 26th of this year, a law containing provisions relative to the control of urban sprawl and unsanitary housing in overseas departments and territories will come into effect. This law should provide public officials with the legal basis that has up until now been lacking to take action. Persistence in the "wait-and-see" attitude could lead to condemnation by French or European courts.

  13. Prophylaxis and therapy for Chikungunya virus infection.

    PubMed

    Couderc, Thérèse; Khandoudi, Nassirah; Grandadam, Marc; Visse, Catherine; Gangneux, Nicolas; Bagot, Sébastien; Prost, Jean-François; Lecuit, Marc

    2009-08-15

    Chikungunya virus (CHIKV) is a recently reemerged arbovirus responsible for a massive outbreak of infection in the Indian Ocean region and India that has a very significant potential to spread globally because of the worldwide distribution of its mosquito vectors. CHIKV induces a usually self-limited disease in humans that is characterized by fever, arthralgia, myalgia, and rash; however, cases of severe CHIKV infection have recently been described, particularly in adults with underlying condition and neonates born to viremic mothers. Human polyvalent immunoglobulins were purified from plasma samples obtained from donors in the convalescent phase of CHIKV infection, and the preventive and curative effects of these immunoglobulins were investigated in 2 mouse models of CHIKV infection that we developed. CHIKV immunoglobulins contain anti-CHIKV antibodies and exhibit a high in vitro neutralizing activity and a powerful prophylactic and therapeutic efficacy against CHIKV infection in vivo, including in the neonate. Administration of CHIKV immunoglobulins may constitute a safe and efficacious prevention strategy and treatment for individuals exposed to CHIKV who are at risk of severe infection, such as neonates born to viremic mothers and adults with underlying conditions. These results provide a proof-of-concept for purifying human immunoglobulins from plasma samples from patients in the convalescent phase of an emerging infectious disease for which neither prevention nor treatment is available.

  14. 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.

  15. 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.

  16. Activity of andrographolide against chikungunya virus infection

    PubMed Central

    Wintachai, Phitchayapak; Kaur, Parveen; Lee, Regina Ching Hua; Ramphan, Suwipa; Kuadkitkan, Atichat; Wikan, Nitwara; Ubol, Sukathida; Roytrakul, Sittiruk; Chu, Justin Jang Hann; Smith, Duncan R.

    2015-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus that has recently engendered large epidemics around the world. There is no specific antiviral for treatment of patients infected with CHIKV, and development of compounds with significant anti-CHIKV activity that can be further developed to a practical therapy is urgently required. Andrographolide is derived from Andrographis paniculata, a herb traditionally used to treat a number of conditions including infections. This study sought to determine the potential of andrographolide as an inhibitor of CHIKV infection. Andrographolide showed good inhibition of CHIKV infection and reduced virus production by approximately 3log10 with a 50% effective concentration (EC50) of 77 μM without cytotoxicity. Time-of-addition and RNA transfection studies showed that andrographolide affected CHIKV replication and the activity of andrographolide was shown to be cell type independent. This study suggests that andrographolide has the potential to be developed further as an anti-CHIKV therapeutic agent. PMID:26384169

  17. Wolbachia modulates Chikungunya replication in Aedes albopictus.

    PubMed

    Mousson, L; Martin, E; Zouache, K; Madec, Y; Mavingui, P; Failloux, A B

    2010-05-01

    The Aedes albopictus mosquito has been involved as the principal vector of recent major outbreaks due to the chikungunya virus (CHIKV). The species is naturally infected by two strains of Wolbachia (wAlbA and wAlbB). Wolbachia infections are thought to have spread by manipulating the reproduction of their hosts; cytoplasmic incompatibility is the mechanism used by Wolbachia to invade natural populations of many insects including Ae. albopictus. Here, we report a study on the effects of removing Wolbachia from Ae. albopictus on CHIKV replication and examine the consequences of CHIKV infection on some life-history traits (survival and reproduction) of Wolbachia-free Ae. albopictus. We found that Wolbachia-free mosquitoes maintained a highly heterogeneous CHIKV replication compared to Wolbachia-infected individuals. In Wolbachia-infected Ae. albopictus, the regular increase of CHIKV followed by a steady viral load from day 4 post-infection onwards was concomitant with a decline in Wolbachia density. This profile was also detected when examining the two key organs for viral transmission, the midgut and the salivary glands. Moreover, Wolbachia-free Ae. albopictus was not altered in life-history traits such as survival, oviposition and hatching characteristics whether infected or not with CHIKV. We found that Wolbachia is not essential for viral replication, its presence could lead to optimize replication from day 4 post-infection onwards, coinciding with a decrease in Wolbachia density. Wolbachia may regulate viral replication in Ae. albopictus, with consequences on survival and reproduction.

  18. Mathematical modeling of Chikungunya fever control

    NASA Astrophysics Data System (ADS)

    Hincapié-Palacio, Doracelly; Ospina, Juan

    2015-05-01

    Chikungunya fever is a global concern due to the occurrence of large outbreaks, the presence of persistent arthropathy and its rapid expansion throughout various continents. Globalization and climate change have contributed to the expansion of the geographical areas where mosquitoes Aedes aegypti and Aedes albopictus (Stegomyia) remain. It is necessary to improve the techniques of vector control in the presence of large outbreaks in The American Region. We derive measures of disease control, using a mathematical model of mosquito-human interaction, by means of three scenarios: a) a single vector b) two vectors, c) two vectors and human and non-human reservoirs. The basic reproductive number and critical control measures were deduced by using computer algebra with Maple (Maplesoft Inc, Ontario Canada). Control measures were simulated with parameter values obtained from published data. According to the number of households in high risk areas, the goals of effective vector control to reduce the likelihood of mosquito-human transmission would be established. Besides the two vectors, if presence of other non-human reservoirs were reported, the monthly target of effective elimination of the vector would be approximately double compared to the presence of a single vector. The model shows the need to periodically evaluate the effectiveness of vector control measures.

  19. Monoclonal Antibodies as Prophylactic and Therapeutic Agents Against Chikungunya Virus.

    PubMed

    Clayton, April M

    2016-12-15

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that is responsible for considerable epidemics worldwide and recently emerged in the Americas in 2013. CHIKV may cause long-lasting arthralgia after acute infection. With currently no licensed vaccines or antivirals, the design of effective therapies to prevent or treat CHIKV infection is of utmost importance and will be facilitated by increased understanding of the dynamics of chikungunya. In this article, monoclonal antibodies against CHIKV as viable prophylactic and therapeutic agents will be discussed. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Chikungunya virus capsid protein contains nuclear import and export signals

    PubMed Central

    2013-01-01

    Background Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. Methods EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. Results Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. Conclusions We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via

  1. Chikungunya virus capsid protein contains nuclear import and export signals.

    PubMed

    Thomas, Saijo; Rai, Jagdish; John, Lijo; Schaefer, Stephan; Pützer, Brigitte M; Herchenröder, Ottmar

    2013-08-28

    Chikungunya virus (CHIKV) is an alphavirus of the Togaviridae family. After autoproteolytic cleavage, the CHIKV capsid protein (CP) is involved in RNA binding and assembly of the viral particle. The monomeric CP is approximately 30 kDa in size and is small enough for passive transport through nuclear pores. Some alphaviruses are found to harbor nuclear localization signals (NLS) and transport of these proteins between cellular compartments was shown to be energy dependent. The active nuclear import of cytoplasmic proteins is mediated by karyopherins and their export by exportins. As nuclear and cytoplasmic trafficking may play a role in the life cycle of CHIKV, we have sought to identify nuclear localization and nuclear export signals in CHIKV CP in a virus-free system. EGFP-fusion proteins of CHIKV CP and mutants thereof were created and used to monitor their intracellular localization. Binding of cellular proteins was confirmed in pull-down assays with purified CP using co-immuoprecipitation. Nuclear localization was demonstrated in a virus-free system using fluorescence microscopy. Here we show that CHIKV CP is a nuclear-cytoplasmic shuttling protein with an active NLS that binds to karyopherin α (Karα) for its nuclear translocation. We also found that the Karα4 C-terminal NLS binding site is sufficient for this interaction. We further demonstrate that CHIKV CP interacts directly with the export receptor CRM1 to transport this viral protein out of the nucleus via a nuclear export signal (NES). The CHIKV CP NES was mapped between amino acids 143 and 155 of CP. Deduced from in silico analyses we found that the NES has a mode of binding similar to the snurportin-1 CRM1 complex. We were able to show that in a virus-free system that the CHIKV capsid protein contains both, a NLS and a NES, and that it is actively transported between the cytoplasma and the nucleus. We conclude that CHIKV CP has the ability to shuttle via interaction with karyopherins for its

  2. Clinical Forms of Chikungunya in Gabon, 2010

    PubMed Central

    Caron, Mélanie; Grard, Gilda; Mombo, Illich; Bikié, Branly; Paupy, Christophe; Becquart, Pierre; Bisvigou, Ulrich; Leroy, Eric Maurice

    2012-01-01

    Background Chikungunya virus (CHIKV) has caused multiple outbreaks in tropical and temperate areas worldwide, but the clinical and biological features of this disease are poorly described, particularly in Africa. We report a prospective study of clinical and biological features during an outbreak that occurred in Franceville, Gabon in 2010. Methodology/Principal Findings We collected, in suspect cases (individuals presenting with at least one of the following symptoms or signs: fever, arthralgias, myalgias, headaches, rash, fatigue, nausea, vomiting, diarrhea, bleeding, or jaundice), blood samples, demographic and clinical characteristics and outcome. Hematological and biochemical tests, blood smears for malaria parasites and quantitative PCR for CHIKV then dengue virus were performed. CHIKV+ patients with concomitant malaria and/or dengue were excluded from the study. From May to July 2010, data on 270 laboratory-confirmed CHIK patients were recorded. Fever and arthralgias were reported by respectively 85% and 90% of patients, while myalgias, rash and hemorrhage were noted in 73%, 42% and 2% of patients. The patients were grouped into 4 clinical categories depending on the existence of fever and/or joint pain. On this basis, mixed forms accounted for 78.5% of cases, arthralgic forms 12.6%, febrile forms 6.7% and unusual forms (without fever and arthralgias) 2.2%. No cases of organ failure or death were reported. Elevated liver enzyme and creatinine levels, anemia and lymphocytopenia were the predominant biological abnormalities, and lymphocytopenia was more severe in patients with high viral loads (p = 0.01). Conclusions/Significance During CHIK epidemics, some patients may not have classical symptoms. The existence of unusual forms and the absence of severe forms of CHIK call for surveillance to detect any change in pathogenicity. PMID:22348166

  3. 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.

  4. Molecular Characterization of Chikungunya Virus, Philippines, 2011–2013

    PubMed Central

    Sy, Ava Kristy; Saito-Obata, Mariko; Medado, Inez Andrea; Tohma, Kentaro; Dapat, Clyde; Segubre-Mercado, Edelwisa; Tandoc, Amado; Lupisan, Socorro

    2016-01-01

    During 2011–2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines. PMID:27088593

  5. Co-infections with Chikungunya and Dengue Viruses, Guatemala, 2015

    PubMed Central

    Signor, Leticia del Carmen Castillo; Williams, Christopher; Donis, Evelin; Cuevas, Luis E.; Adams, Emily R.

    2016-01-01

    We screened serum samples referred to the national reference laboratory in Guatemala that were positive for chikungunya or dengue viruses in June 2015. Co-infection with both viruses was detected by reverse transcription PCR in 46 (32%) of 144 samples. Specimens should be tested for both arboviruses to detect co-infections. PMID:27767914

  6. Pharmacologic management of pain in patients with Chikungunya: a guideline.

    PubMed

    Brito, Carlos Alexandre Antunes de; Sohsten, Ana Karla Arraes von; Leitão, Clezio Cordeiro de Sá; Brito, Rita de Cássia Coelho Moraes de; Valadares, Lilian David De Azevedo; Fonte, Caroline Araújo Magnata da; Mesquita, Zelina Barbosa de; Cunha, Rivaldo Venâncio; Luz, Kleber; Leão, Helena Maria Carneiro; Brito, Cecília Moraes de; Frutuoso, Lívia Carla Vinhal

    2016-01-01

    From the arrival of Chikungunya virus in the Americas in 2013 until March 2016, approximately two million cases of the disease have been reported. In Brazil, the virus was identified in 2014 and thousands of people have been affected. The disease has high attack rates, infecting 50% of a population within a few months. Approximately 50% of infected people develop chronic symptoms lasting for months or years. Joint involvement is the main clinical manifestation of Chikungunya. It is characterized by swelling and intense pain that is poorly responsive to analgesics, both in the acute and chronic phase of the disease. This significantly compromises quality of life and may have immeasurable psychosocial and economic repercussions, constituting therefore, a serious public health problem requiring a targeted approach. Physicians are often not familiar with how to approach the management of pain, frequently prescribing limited analgesics, such as dipyrone, in sub-therapeutic doses. In addition, there are few published studies or guidelines on the approach to the treatment of pain in patients with Chikungunya. Some groups of specialists from different fields have thus developed a protocol for the pharmacologic treatment of Chikungunya-associated acute and chronic joint pain; this will be presented in this review.

  7. 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

  8. Molecular Characterization of Chikungunya Virus, Philippines, 2011-2013.

    PubMed

    Sy, Ava Kristy; Saito-Obata, Mariko; Medado, Inez Andrea; Tohma, Kentaro; Dapat, Clyde; Segubre-Mercado, Edelwisa; Tandoc, Amado; Lupisan, Socorro; Oshitani, Hitoshi

    2016-05-01

    During 2011-2013, a nationwide outbreak of chikungunya virus infection occurred in the Philippines. The Asian genotype was identified as the predominant genotype; sporadic cases of the East/Central/South African genotype were detected in Mindanao. Further monitoring is needed to define the transmission pattern of this virus in the Philippines.

  9. Evaluation of Commercially Available Serologic Diagnostic Tests for Chikungunya Virus

    PubMed Central

    Flusin, Olivier; Panella, Amanda; Tenebray, Bernard; Lanciotti, Robert; Leparc-Goffart, Isabelle

    2014-01-01

    Chikungunya virus (CHIKV) is present or emerging in dengue virus–endemic areas. Infections caused by these viruses share some common signs/symptoms, but prognosis, patient care, and persistent symptoms differ. Thus, accurate diagnostic methods are essential for differentiating the infections. We evaluated 4 CHIKV serologic diagnostic tests, 2 of which showed poor sensitivity and specificity. PMID:25418184

  10. 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.

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

    USDA-ARS?s Scientific Manuscript database

    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. 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

  13. Measuring Haitian children's exposure to chikungunya, dengue and malaria

    PubMed Central

    Moss, Delynn M; Feeser, Karla R; Streit, Thomas G; Chang, Gwong-Jen J; Whitney, Matthew; Russell, Brandy J; Johnson, Barbara W; Basile, Alison J; Goodman, Christin H; Barry, Amanda K; Lammie, Patrick J

    2016-01-01

    Abstract Objective To differentiate exposure to the newly introduced chikungunya virus from exposure to endemic dengue virus and other pathogens in Haiti. Methods We used a multiplex bead assay to detect immunoglobulin G (IgG) responses to a recombinant chikungunya virus antigen, two dengue virus-like particles and three recombinant Plasmodium falciparum antigens. Most (217) of the blood samples investigated were collected longitudinally, from each of 61 children, between 2011 and 2014 but another 127 were collected from a cross-sectional sample of children in 2014. Findings Of the samples from the longitudinal cohort, none of the 153 collected between 2011 and 2013 but 78.7% (48/61) of those collected in 2014 were positive for IgG responses to the chikungunya virus antigen. In the cross-sectional sample, such responses were detected in 96 (75.6%) of the children and occurred at similar prevalence across all age groups. In the same sample, responses to malarial antigen were only detected in eight children (6.3%) but the prevalence of IgG responses to dengue virus antigens was 60.6% (77/127) overall and increased steadily with age. Spatial analysis indicated that the prevalence of IgG responses to the chikungunya virus and one of the dengue virus-like particles decreased as the sampling site moved away from the city of Léogâne and towards the ocean. Conclusion Serological evidence indicates that there had been a rapid and intense dissemination of chikungunya virus in Haiti. The multiplex bead assay appears to be an appropriate serological platform to monitor the seroprevalence of multiple pathogens simultaneously. PMID:27821884

  14. US Military contributions to the global response to pandemic chikungunya.

    PubMed

    Hoke, Charles H; Pace-Templeton, Judy; Pittman, Phillip; Malinoski, Frank J; Gibbs, Paul; Ulderich, Tracy; Mathers, Michelle; Fogtman, Beverly; Glass, Pamela; Vaughn, David W

    2012-10-19

    Chikungunya virus, transmitted by mosquitoes to man, causes an acute illness characterized by fever, rash and striking joint symptoms. US Military investigators developed, manufactured at The Salk Institute-Government Services Division (TSI-GSD), and tested the live, attenuated Chikungunya Vaccine TSI-GSD-218. The manufacturing facility stopped production in 1994. The Chikungunya Vaccine TSI-GSD-218 development effort was terminated in 1998, and materials were archived. In 2005, an alarming outbreak of chikungunya disease began in Africa and spread to islands in the Indian Ocean and throughout much of Asia. Abrupt epidemics with high attack rates and serious, even fatal, complications were reported, and travelers carried the virus to Europe and the Americas. In response to urgent requests, the US Military offered assistance by providing non-exclusive access to the previously stored vaccine production seed materials, bulk vaccine, regulatory documentation, and reports of previous clinical trials. Five companies requested technology transfers. This experience provides lessons about epidemiological unpredictability, preparedness, vaccine manufacturing, the potential global importance of vaccine seed materials and the advisability of a global strategic plan. Consideration should be given to banking of vaccine production seeds, cell substrates, and manufacturing instructions. In view of the manufacturability, attenuation, and immunogenicity of Chikungunya Vaccine TSI-GSD-218, authorities may wish to consider this product as a possible candidate itself, as a comparator vaccine to improve upon, as a seed for inactivated vaccine, or as a source of virus or antigen for neutralization assays or immunoassays. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence.

    PubMed

    McPherson, Robert Lyle; Abraham, Rachy; Sreekumar, Easwaran; Ong, Shao-En; Cheng, Shang-Jung; Baxter, Victoria K; Kistemaker, Hans A V; Filippov, Dmitri V; Griffin, Diane E; Leung, Anthony K L

    2017-02-14

    Chikungunya virus (CHIKV), an Old World alphavirus, is transmitted to humans by infected mosquitoes and causes acute rash and arthritis, occasionally complicated by neurologic disease and chronic arthritis. One determinant of alphavirus virulence is nonstructural protein 3 (nsP3) that contains a highly conserved MacroD-type macrodomain at the N terminus, but the roles of nsP3 and the macrodomain in virulence have not been defined. Macrodomain is a conserved protein fold found in several plus-strand RNA viruses that binds to the small molecule ADP-ribose. Prototype MacroD-type macrodomains also hydrolyze derivative linkages on the distal ribose ring. Here, we demonstrated that the CHIKV nsP3 macrodomain is able to hydrolyze ADP-ribose groups from mono(ADP-ribosyl)ated proteins. Using mass spectrometry, we unambiguously defined its substrate specificity as mono(ADP-ribosyl)ated aspartate and glutamate but not lysine residues. Mutant viruses lacking hydrolase activity were unable to replicate in mammalian BHK-21 cells or mosquito Aedes albopictus cells and rapidly reverted catalytically inactivating mutations. Mutants with reduced enzymatic activity had slower replication in mammalian neuronal cells and reduced virulence in 2-day-old mice. Therefore, nsP3 mono(ADP-ribosyl)hydrolase activity is critical for CHIKV replication in both vertebrate hosts and insect vectors, and for virulence in mice.

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

    PubMed Central

    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. PMID:24637708

  17. 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.

  18. Outbreak of chikungunya in Johor Bahru, Malaysia: clinical and laboratory features of hospitalized patients.

    PubMed

    Chew, L P; Chua, H H

    2009-09-01

    In 2008, an outbreak of chikungunya infection occurred in Johor. We performed a retrospective review of all laboratory confirmed adult chikungunya cases admitted to Hospital Sultanah Aminah, Johor Bahru from April to August 2008, looking into clinical and laboratory features. A total of 18 laboratory confirmed cases of chikungunya were identified with patients presenting with fever, joint pain, rash and vomiting. Haemorrhagic signs were not seen. Lymphopenia, neutropenia, thrombocytopenia, raised liver enzymes and deranged coagulation profile were the prominent laboratory findings. We hope this study can help guide physician making a diagnosis of chikungunya against other arborviruses infection.

  19. The Range of Neurological Complications in Chikungunya Fever.

    PubMed

    Cerny, T; Schwarz, M; Schwarz, U; Lemant, J; Gérardin, P; Keller, E

    2017-05-25

    Chikungunya fever is a globally spreading mosquito-borne disease that shows an unexpected neurovirulence. Even though the neurological complications have been a major cause of intensive care unit admission and death, to date, there is no systematic analysis of their spectrum available. To review evidence of neurological manifestations in Chikungunya fever and map their epidemiology, clinical spectrum, pathomechanisms, diagnostics, therapies and outcomes. Case report and systematic review of the literature followed established guidelines. All cases found were assessed using a 5-step clinical diagnostic algorithm assigning categories A-C, category A representing the highest level of quality. Only A and B cases were considered for further analysis. After general analysis, cases were clustered according to geospatial criteria for subgroup analysis. Thirty-six of 1196 studies were included, yielding 130 cases. Nine were ranked as category A (diagnosis of Neuro-Chikungunya probable), 55 as B (plausible), and 51 as C (disputable). In 15 cases, alternative diagnoses were more likely. Patient age distribution was bimodal with a mean of 49 years and a second peak in infants. Fifty percent of the cases occurred in patients <45 years with no reported comorbidity. Frequent diagnoses were encephalitis, optic neuropathy, neuroretinitis, and Guillain-Barré syndrome. Neurologic conditions showing characteristics of a direct viral pathomechanism showed a peak in infants and a second one in elder patients, and complications and neurologic sequelae were more frequent in these groups. Autoimmune-mediated conditions appeared mainly in patients over 20 years and tended to show longer latencies and better outcomes. Geospatial subgrouping of case reports from either India or Réunion revealed diverging phenotypic trends (Réunion: 88% direct viral vs. India: 81% autoimmune). Direct viral forms of Neuro-Chikungunya seem to occur particularly in infants and elderly patients, while

  20. Dengue, Zika and Chikungunya: Emerging Arboviruses in the New World.

    PubMed

    Patterson, Jessica; Sammon, Maura; Garg, Manish

    2016-11-01

    The arboviruses that cause dengue, chikungunya, and Zika illnesses have rapidly expanded across the globe in recent years, with large-scale outbreaks occurring in Western Hemisphere territories in close proximity to the United States (U.S.). In March 2016, the Centers for Disease Control and Protection (CDC) expanded its vector surveillance maps for A. aegypti and A. albopictus, the mosquito vectors for these arboviruses. They have now been shown to inhabit a larger portion of the U.S., including the heavily populated northeast corridor. Emergency physicians need to further familiarize themselves with these diseases, which have classically been considered only in returning travelers but may soon be encountered in the U.S. even in the absence of travel. In this paper, we discuss the presentation and treatment of dengue, Zika, and chikungunya, as well as special challenges presented to the emergency physician in evaluating a patient with a suspected arbovirus infection.

  1. Chikungunya virus isolation using simplified cell culture technique in Mauritius.

    PubMed

    Pyndiah, M N; Pursem, V; Meetoo, G; Daby, S; Ramuth, V; Bhinkah, P; Chuttoo, R; Paratian, U

    2012-03-01

    During the chikungunya outbreak of 2005 - 2006, the only laboratory facilities available in Mauritius were virus isolation in cell culture tubes and serology. The laboratory was submerged with large numbers of blood samples. Comparative isolation was made in human embryonic lung (HEL) and VERO cells grown in 96-well plate. Culture on HEL cells was found to be more sensitive and presence of cytopathic effect (CPE) was observed earlier than in VERO cells. Out of the 18 300 blood samples inoculated on HEL, 11 165 were positive. This virus isolation method was of great help for the surveillance and control of the vectors. In cases of an outbreak a cheap, rapid and simple method of isolating chikungunya virus is described.

  2. 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.

  3. Dengue, Zika and Chikungunya: Emerging Arboviruses in the New World

    PubMed Central

    Patterson, Jessica; Sammon, Maura; Garg, Manish

    2016-01-01

    The arboviruses that cause dengue, chikungunya, and Zika illnesses have rapidly expanded across the globe in recent years, with large-scale outbreaks occurring in Western Hemisphere territories in close proximity to the United States (U.S.). In March 2016, the Centers for Disease Control and Protection (CDC) expanded its vector surveillance maps for A. aegypti and A. albopictus, the mosquito vectors for these arboviruses. They have now been shown to inhabit a larger portion of the U.S., including the heavily populated northeast corridor. Emergency physicians need to further familiarize themselves with these diseases, which have classically been considered only in returning travelers but may soon be encountered in the U.S. even in the absence of travel. In this paper, we discuss the presentation and treatment of dengue, Zika, and chikungunya, as well as special challenges presented to the emergency physician in evaluating a patient with a suspected arbovirus infection. PMID:27833670

  4. Seroprevalence of Chikungunya Virus in a Rural Community in Brazil.

    PubMed

    Cunha, Rivaldo V; Trinta, Karen S; Montalbano, Camila A; Sucupira, Michel V F; de Lima, Maricelia M; Marques, Erenilde; Romanholi, Izilyanne H; Croda, Julio

    2017-01-01

    The emergence of the Chikungunya virus (CHIKV) is currently expanding. In 2015, 38,332 cases of Chikungunya were reported to the Brazilian epidemiological surveillance system. Eighteen months after notification of the first case in the city of Feira de Santana, we conducted the first serosurvey to define the magnitude of transmission in a rural community in Brazil. The serosurvey was conducted in a random sample of 450 residences in the Chapada district, located 100 kilometers from Feira de Santana. We administered questionnaires and tested 120 sera from Chapada district residents for CHIKV IgM- and IgG-specific antibodies. An individual with CHIKV infection was defined as any person with CHIKV IgM or IgG antibodies detected in the serum. One Hundred cases of Chikungunya were reported after prolonged rainfall, which reinforced the relationship between the rainfall index and CHIKV transmission. Eighteen months after the start of the outbreak, we identified a seroprevalence of 20% (95% CI, 15.4-35%). CHIKV IgG- and IgM-specific antibodies were detected in 22/120 (18.3%) and 6/120 (5.0%) individuals, respectively. Among seropositive patients, 13/24 (54.2%) reported fever and joint pain over the previous two years (p<0.01). The rate of symptomatic CHIKV infection was 40.7%. We identified a moderate seroprevalence of Chikungunya in the Chapada district, and in half of the confirmed CHIKV infections, patients reported arthralgia and fever over the previous two years.

  5. Status of research and development of vaccines for chikungunya.

    PubMed

    Smalley, Claire; Erasmus, Jesse H; Chesson, Charles B; Beasley, David W C

    2016-06-03

    Chikungunya virus (CHIKV) is an arthritogenic alphavirus that during the last decade has significantly expanded its geographical range and caused large outbreaks of human disease around the world. Although mortality rates associated with CHIKV outbreaks are low, acute and chronic illnesses caused by CHIKV represent a significant burden of disease largely affecting low and middle income countries. This report summarizes the current status of vaccine development for CHIKV. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  6. Seroprevalence of Chikungunya Virus in a Rural Community in Brazil

    PubMed Central

    Cunha, Rivaldo V.; Trinta, Karen S.; Montalbano, Camila A.; Sucupira, Michel V. F.; de Lima, Maricelia M.; Marques, Erenilde; Romanholi, Izilyanne H.

    2017-01-01

    Background The emergence of the Chikungunya virus (CHIKV) is currently expanding. In 2015, 38,332 cases of Chikungunya were reported to the Brazilian epidemiological surveillance system. Eighteen months after notification of the first case in the city of Feira de Santana, we conducted the first serosurvey to define the magnitude of transmission in a rural community in Brazil. Methodology/Main findings The serosurvey was conducted in a random sample of 450 residences in the Chapada district, located 100 kilometers from Feira de Santana. We administered questionnaires and tested 120 sera from Chapada district residents for CHIKV IgM- and IgG-specific antibodies. An individual with CHIKV infection was defined as any person with CHIKV IgM or IgG antibodies detected in the serum. One Hundred cases of Chikungunya were reported after prolonged rainfall, which reinforced the relationship between the rainfall index and CHIKV transmission. Eighteen months after the start of the outbreak, we identified a seroprevalence of 20% (95% CI, 15.4–35%). CHIKV IgG- and IgM-specific antibodies were detected in 22/120 (18.3%) and 6/120 (5.0%) individuals, respectively. Among seropositive patients, 13/24 (54.2%) reported fever and joint pain over the previous two years (p<0.01). The rate of symptomatic CHIKV infection was 40.7%. Conclusions/Significance We identified a moderate seroprevalence of Chikungunya in the Chapada district, and in half of the confirmed CHIKV infections, patients reported arthralgia and fever over the previous two years. PMID:28107342

  7. Animal Models of Chikungunya Virus Infection and Disease.

    PubMed

    Haese, Nicole N; Broeckel, Rebecca M; Hawman, David W; Heise, Mark T; Morrison, Thomas E; Streblow, Daniel N

    2016-12-15

    Chikungunya virus (CHIKV) is a reemerging alphavirus that causes acute febrile illness and severe joint pain in humans. Although acute symptoms often resolve within a few days, chronic joint and muscle pain can be long lasting. In the last decade, CHIKV has caused widespread outbreaks of unprecedented scale in the Americas, Asia, and the Indian Ocean island regions. Despite these outbreaks and the continued expansion of CHIKV into new areas, mechanisms of chikungunya pathogenesis and disease are not well understood. Experimental animal models are indispensable to the field of CHIKV research. The most commonly used experimental animal models of CHIKV infection are mice and nonhuman primates; each model has its advantages for studying different aspects of CHIKV disease. This review will provide an overview of animal models used to study CHIKV infection and disease and major advances in our understanding of chikungunya obtained from studies performed in these models. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  8. [First case of chikungunya fever in Hermosillo, Sonora, Mexico].

    PubMed

    Martínez-Medina, Miguel Ángel; Cañedo-Dorame, Ismael Antonio

    2017-01-01

    The Chikungunya is an arbovirus first described during a 1952 outbreak of febrile exantematic disease in southern Tanganyika (now Tanzania). It is a virus within the alphavirus genus of the Togaviridae family, it is usually transmitted to humans by Aedes mosquitoes. Typically, the disease manifests as acute onset of fever and joint pains. This study describes the clinical characteristics the first imported case infected with chikungunya fever (CHIK) in Hermosillo, Sonora, Mexico. We report the case of a 30 years old man seen in our emergency department due to fever, polyarthralgia, rash and headache. This patient has been in Tapachula, Chiapas, a jungle area in southern México, and he returned from a 45 days trip before the onset his symptoms. The chikungunya viral infection (CHIK) was diagnosed by RT-PCR procedure. Paracetamol therapy was administered and his clinical course was self-limited. We concluded that with the increase of mosquito´s habitat by global warming and frequent traveling, CHIK reemerged and showed global distribution recently. This disease must be suspected in patients with compatible clinical symptoms returning from epidemic/endemic areas. CHIK must be diagnosed on the basis of clinical, epidemiological and laboratory criteria.

  9. 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.

  10. [Chikungunya: a challenge for the Dominican Republic's health services].

    PubMed

    Moya, José; Pimentel, Raquel; Puello, José

    2014-11-01

    The Region of the Americas has been affected since December 2013 by a chikungunya epidemic for the first time. Although the first cases were recorded in the French Caribbean, the epidemic quickly spread to the Dominican Republic due to trade and people movements. The Dominican Republic, which shares the island of Hispaniola with Haiti, has a population of 10 million. This article contains information from a range of different publications and official documents about the chikungunya virus infection and epidemic. These papers were extremely helpful for guiding the response to the epidemic in the Dominican Republic and may also be useful for enhancing knowledge of the virus and responses among health workers elsewhere in the region. Particular attention is drawn to the important research undertaken in countries and territories affected by the epidemic in the Indian Ocean area. This is the case, for example, of the island of La Réunion, where the epidemic had an attack rate of more than 30% between 2005 and 2007. Researchers were able to identify risk groups, severe and atypical forms of the infection, cases of vertical transmission, chronic disease causing recurrent pain over three years, and directly- or indirectly-related deaths from the virus. Given its high attack rate, the chikungunya virus has emerged as an exceptional challenge for health ministries and calls for appropriate organized responses from the health services, prioritization of care for risk groups and patients exhibiting severe forms of the disease, and effective social communication and intersectoral actions.

  11. 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.

  12. Notes from the field: Transmission of chikungunya virus in the continental United States--Florida, 2014.

    PubMed

    Kendrick, Katherine; Stanek, Danielle; Blackmore, Carina

    2014-12-05

    On June 27, 2014, the Florida Department of Health in Miami-Dade County was notified by the Florida Poison Information Center Network of a patient with travel to Southeast Asia who was suspected of having chikungunya virus infection. After further investigation and additional testing, it was determined that the patient had not recently traveled to an endemic area, and this case was confirmed as the first locally acquired chikungunya case in the continental United States. Since the first case of locally acquired chikungunya virus infection in the Americas was reported on the Caribbean island of St. Martin in December 2013, the United States has seen an increase in chikungunya cases among travelers returning from areas where chikungunya has become endemic, particularly the Caribbean and South America. Compared with other states, Florida has seen an especially large number of chikungunya fever cases. During January 1-October 14, 2014, a total of 272 imported cases were reported in Florida, compared with 1,110 reported in the other 47 contiguous states. In addition, 11 locally acquired chikungunya cases have been identified. The recent spread of the virus and the presence of competent mosquito vectors provide the conditions for transmission of chikungunya virus in Florida.

  13. Chikungunya: acute fever, rash and debilitating arthralgias in a returning traveler from Haiti.

    PubMed

    Anderson, Kathryn B; Pureza, Vincent; Walker, Patricia F

    2014-01-01

    The following case report details a case of chikungunya fever in a returning traveler from Haiti. The report highlights the clinical presentation and natural history of the disease, and emphasizes that chikungunya has become established in the western hemisphere, with a resultant need for heightened provider awareness.

  14. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014.

    PubMed

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume; Hoen, Bruno

    2016-05-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection.

  15. Severe Sepsis and Septic Shock Associated with Chikungunya Virus Infection, Guadeloupe, 2014

    PubMed Central

    Rollé, Amélie; Schepers, Kinda; Cassadou, Sylvie; Curlier, Elodie; Madeux, Benjamin; Hermann-Storck, Cécile; Fabre, Isabelle; Lamaury, Isabelle; Tressières, Benoit; Thiery, Guillaume

    2016-01-01

    During a 2014 outbreak, 450 patients with confirmed chikungunya virus infection were admitted to the University Hospital of Pointe-à-Pitre, Guadeloupe. Of these, 110 were nonpregnant adults; 42 had severe disease, and of those, 25 had severe sepsis or septic shock and 12 died. Severe sepsis may be a rare complication of chikungunya virus infection. PMID:27088710

  16. Complete Genome Sequences of 15 Chikungunya Virus Isolates from Puerto Rico.

    PubMed

    Sanders, Wes A; Long, Kristin; Rivera, Brenda; Vincent, Heather A; Heise, Mark T; Rodriguez-Orengo, Jose F; Moorman, Nathaniel J

    2017-07-06

    Here, we report the complete genome sequences of 15 chikungunya virus strains isolated from human plasma from infected patients in Puerto Rico. The results show that currently circulating chikungunya strains in Puerto Rico are closely related. Copyright © 2017 Sanders et al.

  17. Chikungunya in Singapore: imported cases among travelers visiting friends and relatives.

    PubMed

    Lim, Poh Lian; Oh, Helen May-Lin; Ooi, Eng Eong

    2009-01-01

    Chikungunya infections were detected in Singapore among returning travelers who had visited friends and relatives (VFR) in India and Malaysia. These sporadic imported cases occurred over a year before the 2008 chikungunya outbreaks in Singapore, demonstrating the potential for introducing this emerging viral infection into new areas via VFR travel.

  18. Chikungunya virus infection with severe neurologic manifestations: report of four fatal cases.

    PubMed

    Sá, Priscilla Karen de Oliveira; Nunes, Michaela de Miranda; Leite, Ingrid Ramalho; Campelo, Maria das Graças Loureiro das Chagas; Leão, Cláudia Ferreira Ribeiro; Souza, Joelma Rodrigues de; Castellano, Lúcio Roberto; Fernandes, Ana Isabel Vieira

    2017-01-01

    Here, we present four patients with confirmed Chikungunya virus infection showing atypical neurologic manifestations and death. This case series includes patients ranging in age from five to 92 years, with or without comorbidities. This report is important, as very few cases in the literature reporting death due to atypical Chikungunya virus infection are available.

  19. Assessing the threat of chikungunya virus emergence in Australia.

    PubMed

    Viennet, Elvina; Knope, Katrina; Faddy, Helen M; Williams, Craig R; Harley, David

    2013-06-30

    Chikungunya virus (CHIKV) is a major threat to Australia given the distribution of competent vectors, and the large number of travellers returning from endemic regions. We describe current knowledge of CHIKV importations into Australia, and quantify reported viraemic cases, with the aim of facilitating the formulation of public health policy and ensuring maintenance of blood safety. Cases reported to the National Notifiable Disease Surveillance System (NNDSS) from 2002 to 2012 were analysed by place, month of acquisition, and place of residence. Rates of chikungunya importation were estimated based on reported cases and on the numbers of short-term movements. Between 2002 and 2012, there were 168 cases of chikungunya virus (CHIKV) imported into Australia. Victoria and New South Wales had the largest number of notifications. The main sources were Indonesia, India and Malaysia. The number of cases increased from 2008 to reach a peak in 2010 (n=64; 40%). Although Indonesia accounted for the majority of CHIKV notifications in Australia, travel from India had the highest CHIKV importation rate (number of imported cases per 100,000 travellers). The Australian population is increasingly at risk from CHIKV. Arrivals from endemic countries have increased concurrently with vector incursions via imported goods, as well as via local movement from the Torres Strait to North Queensland ports. An outbreak of CHIKV could have a significant impact on health, the safety of the blood supply and on tourism. Case and vector surveillance as well as population health responses are crucial for minimising any potential impact of CHIKV establishment in Australia. This work is copyright. Apart from any use as permitted under the Copyright Act 1968, no part may be reproduced by any process without prior written permission from the Commonwealth. Requests and inquiries concerning reproduction and rights should be addressed to the Commonwealth Copyright Administration, Attorney General

  20. 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

  1. Autochthonous Chikungunya Transmission and Extreme Climate Events in Southern France

    PubMed Central

    Roiz, David; Boussès, Philippe; Simard, Frédéric; Paupy, Christophe; Fontenille, Didier

    2015-01-01

    Background Extreme precipitation events are increasing as a result of ongoing global warming, but controversy surrounds the relationship between flooding and mosquito-borne diseases. A common view among the scientific community and public health officers is that heavy rainfalls have a flushing effect on breeding sites, which negatively affects vector populations, thereby diminishing disease transmission. During 2014 in Montpellier, France, there were at least 11 autochthonous cases of chikungunya caused by the invasive tiger mosquito Aedes albopictus in the vicinity of an imported case. We show that an extreme rainfall event increased and extended the abundance of the disease vector Ae. albopictus, hence the period of autochthonous transmission of chikungunya. Methodology/Principal Findings We report results from close monitoring of the adult and egg population of the chikungunya vector Ae. albopictus through weekly sampling over the entire mosquito breeding season, which revealed an unexpected pattern. Statistical analysis of the seasonal dynamics of female abundance in relation to climatic factors showed that these relationships changed after the heavy rainfall event. Before the inundations, accumulated temperatures are the most important variable predicting Ae. albopictus seasonal dynamics. However, after the inundations, accumulated rainfall over the 4 weeks prior to capture predicts the seasonal dynamics of this species and extension of the transmission period. Conclusions/Significance Our empirical data suggests that heavy rainfall events did increase the risk of arbovirus transmission in Southern France in 2014 by favouring a rapid rise in abundance of vector mosquitoes. Further studies should now confirm these results in different ecological contexts, so that the impact of global change and extreme climatic events on mosquito population dynamics and the risk of disease transmission can be adequately understood. PMID:26079620

  2. An Outbreak of Chikungunya in Rural Bangladesh, 2011

    PubMed Central

    Khatun, Selina; Chakraborty, Apurba; Rahman, Mahmudur; Nasreen Banu, Nuzhat; Rahman, Mohammad Mostafizur; Hasan, S. M. Murshid; Luby, Stephen P.; Gurley, Emily S.

    2015-01-01

    Background The first identified Chikungunya outbreak occurred in Bangladesh in 2008. In late October 2011, a local health official from Dohar Sub-district, Dhaka District, reported an outbreak of undiagnosed fever and joint pain. We investigated the outbreak to confirm the etiology, describe the clinical presentation, and identify associated vectors. Methodology During November 2–21, 2011, we conducted house-to-house surveys to identify suspected cases, defined as any inhabitant of Char Kushai village with fever followed by joint pain in the extremities with onset since August 15, 2011. We collected blood specimens and clinical histories from self-selected suspected cases using a structured questionnaire. Blood samples were tested for IgM antibodies against Chikungunya virus. The village was divided into nine segments and we collected mosquito larvae from water containers in seven randomly selected houses in each segment. We calculated the Breteau index for the village and identified the mosquito species. Results The attack rate was 29% (1105/3840) and 29% of households surveyed had at least one suspected case: 15% had ≥3. The attack rate was 38% (606/1589) in adult women and 25% in adult men (320/1287). Among the 1105 suspected case-patients, 245 self-selected for testing and 80% of those (196/245) had IgM antibodies. In addition to fever and joint pain, 76% (148/196) of confirmed cases had rash and 38%(75/196) had long-lasting joint pain. The village Breteau index was 35 per 100 and 89%(449/504) of hatched mosquitoes were Aedes albopictus. Conclusion The evidence suggests that this outbreak was due to Chikungunya. The high attack rate suggests that the infection was new to this area, and the increased risk among adult women suggests that risk of transmission may have been higher around households. Chikungunya is an emerging infection in Bangladesh and current surveillance and prevention strategies are insufficient to mount an effective public health response

  3. [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.

  4. 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.

  5. [Physiopathology of chronic arthritis following chikungunya infection in man].

    PubMed

    Hoarau, G

    2012-03-01

    This article relates the problems initially encountered by an elected official of the French Republic in drawing the attention of authorities to the ravages of the chikungunya epidemic that occurred on Reunion Island in 2005-2006. Due to inadequate medical knowledge, the benign reputation of the disease, and slow reaction of authorities, the virus affected more than one third of the population. A great deal of further study will be needed to understand this public health crisis and to transform the lessons learned into a decisive breakthrough that will doubtless be of equal benefit for mainland France.

  6. Emerging alphaviruses in the Americas: Chikungunya and Mayaro.

    PubMed

    Figueiredo, Mario Luis Garcia de; Figueiredo, Luiz Tadeu Moraes

    2014-01-01

    Chikungunya virus (CHIKV) and Mayaro virus (MAYV) are emergent arthropod-borne viruses that produce outbreaks of acute febrile illness with arthropathy. Despite their different continental origins, CHIKV and MAYV are closely related and are components of the Semliki Forest Complex of the Alphavirus (Togaviridae). MAYV and, more recently, CHIKV, which are both transmitted by Aedes mosquitoes, have resulted in severe public health problems in the Americas, including Brazil. In this review, we present aspects of the pathogenesis, clinical presentation and treatment of febrile illnesses produced by CHIKV and MAYV. We also discuss the epidemiological aspects and effects related to the prophylaxis of infections by both viruses.

  7. Trigocherrierin A, a potent inhibitor of chikungunya virus replication.

    PubMed

    Bourjot, Mélanie; Leyssen, Pieter; Neyts, Johan; Dumontet, Vincent; Litaudon, Marc

    2014-03-24

    Trigocherrierin A (1) and trigocherriolide E (2), two new daphnane diterpenoid orthoesters (DDOs), and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A-C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV) replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC₅₀ = 0.6 ± 0.1 µM, SI = 71.7).

  8. 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.

  9. Chikungunya viruses that escape monoclonal antibody therapy are clinically attenuated, stable, and not purified in mosquitoes.

    PubMed

    Pal, Pankaj; Fox, Julie M; Hawman, David W; Huang, Yan-Jang S; Messaoudi, Ilhem; Kreklywich, Craig; Denton, Michael; Legasse, Alfred W; Smith, Patricia P; Johnson, Syd; Axthelm, Michael K; Vanlandingham, Dana L; Streblow, Daniel N; Higgs, Stephen; Morrison, Thomas E; Diamond, Michael S

    2014-08-01

    Chikungunya virus (CHIKV) is a reemerging mosquito-transmitted alphavirus that causes epidemics of debilitating polyarthritis in humans. A prior study identified two anti-CHIKV monoclonal antibodies ([MAbs] CHK-152 and CHK-166) against the E2 and E1 structural proteins, which had therapeutic efficacy in immunocompetent and immunocompromised mice. Combination MAb therapy was required as administration of a single MAb resulted in the rapid selection of neutralization escape variants and treatment failure in mice. Here, we initially evaluated the efficacy of combination MAb therapy in a nonhuman primate model of CHIKV infection. Treatment of rhesus macaques with CHK-152 and CHK-166 reduced viral spread and infection in distant tissue sites and also neutralized reservoirs of infectious virus. Escape viruses were not detected in the residual viral RNA present in tissues and organs of rhesus macaques. To evaluate the possible significance of MAb resistance, we engineered neutralization escape variant viruses (E1-K61T, E2-D59N, and the double mutant E1-K61T E2-D59N) that conferred resistance to CHK-152 and CHK-166 and tested them for fitness in mosquito cells, mammalian cells, mice, and Aedes albopictus mosquitoes. In both cell culture and mosquitoes, the mutant viruses grew equivalently and did not revert to wild-type (WT) sequence. All escape variants showed evidence of mild clinical attenuation, with decreased musculoskeletal disease at early times after infection in WT mice and a prolonged survival time in immunocompromised Ifnar1(-/-) mice. Unexpectedly, this was not associated with decreased infectivity, and consensus sequencing from tissues revealed no evidence of reversion or compensatory mutations. Competition studies with CHIKV WT also revealed no fitness compromise of the double mutant (E1-K61T E2-D59N) neutralization escape variant in WT mice. Collectively, our study suggests that neutralization escape viruses selected during combination MAb therapy with CHK

  10. Chikungunya Viruses That Escape Monoclonal Antibody Therapy Are Clinically Attenuated, Stable, and Not Purified in Mosquitoes

    PubMed Central

    Pal, Pankaj; Fox, Julie M.; Hawman, David W.; Huang, Yan-Jang S.; Messaoudi, Ilhem; Kreklywich, Craig; Denton, Michael; Legasse, Alfred W.; Smith, Patricia P.; Johnson, Syd; Axthelm, Michael K.; Vanlandingham, Dana L.; Streblow, Daniel N.; Higgs, Stephen; Morrison, Thomas E.

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) is a reemerging mosquito-transmitted alphavirus that causes epidemics of debilitating polyarthritis in humans. A prior study identified two anti-CHIKV monoclonal antibodies ([MAbs] CHK-152 and CHK-166) against the E2 and E1 structural proteins, which had therapeutic efficacy in immunocompetent and immunocompromised mice. Combination MAb therapy was required as administration of a single MAb resulted in the rapid selection of neutralization escape variants and treatment failure in mice. Here, we initially evaluated the efficacy of combination MAb therapy in a nonhuman primate model of CHIKV infection. Treatment of rhesus macaques with CHK-152 and CHK-166 reduced viral spread and infection in distant tissue sites and also neutralized reservoirs of infectious virus. Escape viruses were not detected in the residual viral RNA present in tissues and organs of rhesus macaques. To evaluate the possible significance of MAb resistance, we engineered neutralization escape variant viruses (E1-K61T, E2-D59N, and the double mutant E1-K61T E2-D59N) that conferred resistance to CHK-152 and CHK-166 and tested them for fitness in mosquito cells, mammalian cells, mice, and Aedes albopictus mosquitoes. In both cell culture and mosquitoes, the mutant viruses grew equivalently and did not revert to wild-type (WT) sequence. All escape variants showed evidence of mild clinical attenuation, with decreased musculoskeletal disease at early times after infection in WT mice and a prolonged survival time in immunocompromised Ifnar1−/− mice. Unexpectedly, this was not associated with decreased infectivity, and consensus sequencing from tissues revealed no evidence of reversion or compensatory mutations. Competition studies with CHIKV WT also revealed no fitness compromise of the double mutant (E1-K61T E2-D59N) neutralization escape variant in WT mice. Collectively, our study suggests that neutralization escape viruses selected during combination MAb therapy

  11. Chikungunya Virus Infection: An Update on Joint Manifestations and Management

    PubMed Central

    Krutikov, Maria; Manson, Jessica

    2016-01-01

    The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to previously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection. PMID:27824550

  12. [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.

  13. 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.

  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. 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

  16. Chikungunya virus: is this the next emerging disease threat to the americas?

    PubMed

    Girimont, Trina M

    2014-12-01

    Chikungunya fever is a mosquito-borne infection for which no cure or vaccine is available. It made its first appearance in the Americas in December 2013. Seven months later, two locally acquired cases of the disease emerged in the United States. The emergence of chikungunya fever cases in the Americas emphasizes the need for sustained vector control, clear public health information, and disease awareness and surveillance. Copyright 2014, SLACK Incorporated.

  17. Structure-function relationship of Chikungunya nsP2 protease: A comparative study with papain.

    PubMed

    Ramakrishnan, Chandrasekaran; Kutumbarao, Nidamarthi H V; Suhitha, Sivasubramanian; Velmurugan, Devadasan

    2016-11-07

    Chikungunya virus is a growing human pathogen transmitted by mosquito bite. It causes fever, chills, nausea, vomiting, joint pain, headache, and swelling in the joints. Its replication and propagation depend on the protease activity of the Chikungunya virus-nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into individual functional units. The N-terminal segment of papain is structurally identical with the Chikungunya virus-nsP2 protease. Hence, molecular dynamics simulations were performed to compare molecular mechanism of these proteases. The Chikungunya virus-snP2 protease shows more conformational changes and adopts an alternate conformation. However, N-terminal segment of these two proteases has identical active site scaffold with the conserved catalytic diad. Hence, some of the non-peptide inhibitors of papain were used for induced fit docking at the active site of the nsP2 to assess the binding mode. In addition, the peptides that connect different domains/protein in Chikungunya virus poly-protein were also subjected for docking. The overall results suggest that the active site scaffold is the same in both the proteases and a possibility exists to experimentally assess the efficacy of some of the papain inhibitors to inhibit the Chikungunya virus-nsP2.

  18. IL-1β, IL-6, and RANTES as Biomarkers of Chikungunya Severity

    PubMed Central

    Sun, Yong-Jiang; Kwek, Dyan J. C.; Lim, Poh-Lian; Dimatatac, Frederico; Ng, Lee-Ching; Ooi, Eng-Eong; Choo, Khar-Heng; Her, Zhisheng; Kourilsky, Philippe; Leo, Yee-Sin

    2009-01-01

    Background Little is known about the immunopathogenesis of Chikungunya virus. Circulating levels of immune mediators and growth factors were analyzed from patients infected during the first Singaporean Chikungunya fever outbreak in early 2008 to establish biomarkers associated with infection and/or disease severity. Methods and Findings Adult patients with laboratory-confirmed Chikungunya fever infection, who were referred to the Communicable Disease Centre/Tan Tock Seng Hospital during the period from January to February 2008, were included in this retrospective study. Plasma fractions were analyzed using a multiplex-microbead immunoassay. Among the patients, the most common clinical features were fever (100%), arthralgia (90%), rash (50%) and conjunctivitis (40%). Profiles of 30 cytokines, chemokines, and growth factors were able to discriminate the clinical forms of Chikungunya from healthy controls, with patients classified as non-severe and severe disease. Levels of 8 plasma cytokines and 4 growth factors were significantly elevated. Statistical analysis showed that an increase in IL-1β, IL-6 and a decrease in RANTES were associated with disease severity. Conclusions This is the first comprehensive report on the production of cytokines, chemokines, and growth factors during acute Chikungunya virus infection. Using these biomarkers, we were able to distinguish between mild disease and more severe forms of Chikungunya fever, thus enabling the identification of patients with poor prognosis and monitoring of the disease. PMID:19156204

  19. Chikungunya Viral Fitness Measures within the Vector and Subsequent Transmission Potential

    PubMed Central

    Christofferson, Rebecca C.; Chisenhall, Daniel M.; Wearing, Helen J.; Mores, Christopher N.

    2014-01-01

    Given the recent emergence of chikungunya in the Americas, the accuracy of forecasting and prediction of chikungunya transmission potential in the U.S. requires urgent assessment. The La Reunion-associated sub-lineage of chikungunya (with a valine substitution in the envelope protein) was shown to increase viral fitness in the secondary vector, Ae. albopictus. Subsequently, a majority of experimental and modeling efforts focused on this combination of a sub-lineage of the East-Central-South African genotype (ECSA-V) – Ae. albopictus, despite the Asian genotype being the etiologic agent of recent chikungunya outbreaks world-wide. We explore a collection of data to investigate relative transmission efficiencies of the three major genotypes/sub-lineages of chikungunya and found difference in the extrinsic incubation periods to be largely overstated. However, there is strong evidence supporting the role of Ae. albopictus in the expansion of chikungunya that our R0 calculations cannot attribute to fitness increases in one vector over another. This suggests other ecological factors associated with the Ae. albopictus-ECSA-V cycle may drive transmission intensity differences. With the apparent bias in literature, however, we are less prepared to evaluate transmission where Ae. aegypti plays a significant role. Holistic investigations of CHIKV transmission cycle(s) will allow for more complete assessment of transmission risk in areas affected by either or both competent vectors. PMID:25310016

  20. Mosquito Cellular Factors and Functions in Mediating the Infectious entry of Chikungunya Virus

    PubMed Central

    Lee, Regina Ching Hua; Hapuarachchi, Hapuarachchige Chanditha; Chen, Karen Caiyun; Hussain, Khairunnisa' Mohamed; Chen, Huixin; Low, Swee Ling; Ng, Lee Ching; Lin, Raymond; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2013-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus responsible for recent epidemics in the Asia Pacific regions. A customized gene expression microarray of 18,760 transcripts known to target Aedes mosquito genome was used to identify host genes that are differentially regulated during the infectious entry process of CHIKV infection on C6/36 mosquito cells. Several genes such as epsin I (EPN1), epidermal growth factor receptor pathway substrate 15 (EPS15) and Huntingtin interacting protein I (HIP1) were identified to be differentially expressed during CHIKV infection and known to be involved in clathrin-mediated endocytosis (CME). Transmission electron microscopy analyses further revealed the presence of CHIKV particles within invaginations of the plasma membrane, resembling clathrin-coated pits. Characterization of vesicles involved in the endocytic trafficking processes of CHIKV revealed the translocation of the virus particles to the early endosomes and subsequently to the late endosomes and lysosomes. Treatment with receptor-mediated endocytosis inhibitor, monodansylcadaverine and clathrin-associated drug inhibitors, chlorpromazine and dynasore inhibited CHIKV entry, whereas no inhibition was observed with caveolin-related drug inhibitors. Inhibition of CHIKV entry upon treatment with low-endosomal pH inhibitors indicated that low pH is essential for viral entry processes. CHIKV entry by clathrin-mediated endocytosis was validated via overexpression of a dominant-negative mutant of Eps15, in which infectious entry was reduced, while siRNA-based knockdown of genes associated with CME, low endosomal pH and RAB trafficking proteins exhibited significant levels of CHIKV inhibition. This study revealed, for the first time, that the infectious entry of CHIKV into mosquito cells is mediated by the clathrin-dependent endocytic pathway. PMID:23409203

  1. Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.

    PubMed

    Das, Trina; Jaffar-Bandjee, Marie Christine; Hoarau, Jean Jacques; Krejbich Trotot, Pascale; Denizot, Melanie; Lee-Pat-Yuen, Ghislaine; Sahoo, Renubala; Guiraud, Pascale; Ramful, Duksha; Robin, Stephanie; Alessandri, Jean Luc; Gauzere, Bernard Alex; Gasque, Philippe

    2010-06-01

    Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy.

  2. Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies.

    PubMed

    Silva, Laurie A; Dermody, Terence S

    2017-03-01

    Chikungunya virus (CHIKV), a reemerging arbovirus, causes a crippling musculoskeletal inflammatory disease in humans characterized by fever, polyarthralgia, myalgia, rash, and headache. CHIKV is transmitted by Aedes species of mosquitoes and is capable of an epidemic, urban transmission cycle with high rates of infection. Since 2004, CHIKV has spread to new areas, causing disease on a global scale, and the potential for CHIKV epidemics remains high. Although CHIKV has caused millions of cases of disease and significant economic burden in affected areas, no licensed vaccines or antiviral therapies are available. In this Review, we describe CHIKV epidemiology, replication cycle, pathogenesis and host immune responses, and prospects for effective vaccines and highlight important questions for future research.

  3. Chikungunya fever. Rheumatic manifestations of an emerging disease in Europe.

    PubMed

    Horcada, M Loreto; Díaz-Calderón, Carlos; Garrido, Laura

    2015-01-01

    Chikungunya fever is a viral disease caused by an alphavirus belonging to the Togaviridae family, transmitted by several species of Aedes mosquitoes: Aedes aegypti and Aedes albopictus (A. albopictus). It is endemic in Africa and Asia with recurrent outbreaks. It is an emerging disease and cases in Europe transmitted by A. albopictus have been established in Mediterranean areas. The first autochthonous cases detected on the Caribbean islands suppose a serious threat of spreading disease to America, which so far has been disease free. Clinical symptoms begin abruptly with fever, skin rash and polyarthritis. Although mortality is low, a high percentage of patients develop a chronic phase defined by persistent arthritis for months or even years. A severe immune response is responsible for joint inflammation. The absence of specific treatment and lack of vaccine requires detailed studies about its immunopathogenesis in order to determine the most appropriate target.

  4. Concentration of Rift Valley Fever and Chikungunya Viruses by Precipitation

    PubMed Central

    Klein, Frederick; Mahlandt, Bill G.; Cockey, Ralph R.; Lincoln, Ralph E.

    1970-01-01

    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. PMID:5494763

  5. 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

  6. 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.

  7. Bovine lactoferrin activity against Chikungunya and Zika viruses.

    PubMed

    Carvalho, Carlos A M; Casseb, Samir M M; Gonçalves, Rafael B; Silva, Eliana V P; Gomes, Andre M O; Vasconcelos, Pedro F C

    2017-07-01

    Chikungunya (CHIKV) and Zika (ZIKV) viruses are arboviruses which have recently broken their sylvatic isolation and gone on to spread rampantly among humans in some urban areas of the world, especially in Latin America. Given the lack of effective interventions against such viruses, the aim of this work was to evaluate the antiviral potential of bovine lactoferrin (bLf) in their infections. Through viability, plaque, immunofluorescence and nucleic acid quantification assays, our data show that bLf exerts a dose-dependent strong inhibitory effect on the infection of Vero cells by the aforementioned arboviruses, reducing their infection efficiency by up to nearly 80 %, with no expressive cytotoxicity, and that such antiviral activity occurs at the levels of input and output of virus particles. These findings reveal that bLf antimicrobial properties are extendable to CHIKV and ZIKV, underlining a generic inhibition mechanism that can be explored to develop a potential strategy against their infections.

  8. 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.

  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. Design and Validation of Novel Chikungunya Virus Protease Inhibitors.

    PubMed

    Das, Pratyush Kumar; Puusepp, Laura; Varghese, Finny S; Utt, Age; Ahola, Tero; Kananovich, Dzmitry G; Lopp, Margus; Merits, Andres; Karelson, Mati

    2016-12-01

    Chikungunya virus (CHIKV; genus Alphavirus) is the causative agent of chikungunya fever. CHIKV replication can be inhibited by some broad-spectrum antiviral compounds; in contrast, there is very little information about compounds specifically inhibiting the enzymatic activities of CHIKV replication proteins. These proteins are translated in the form of a nonstructural (ns) P1234 polyprotein precursor from the CHIKV positive-strand RNA genome. Active forms of replicase enzymes are generated using the autoproteolytic activity of nsP2. The available three-dimensional (3D) structure of nsP2 protease has made it a target for in silico drug design; however, there is thus far little evidence that the designed compounds indeed inhibit the protease activity of nsP2 and/or suppress CHIKV replication. In this study, a set of 12 compounds, predicted to interact with the active center of nsP2 protease, was designed using target-based modeling. The majority of these compounds were shown to inhibit the ability of nsP2 to process recombinant protein and synthetic peptide substrates. Furthermore, all compounds found to be active in these cell-free assays also suppressed CHIKV replication in cell culture, the 50% effective concentration (EC50) of the most potent inhibitor being ∼1.5 μM. Analysis of stereoisomers of one compound revealed that inhibition of both the nsP2 protease activity and CHIKV replication depended on the conformation of the inhibitor. Combining the data obtained from different assays also indicates that some of the analyzed compounds may suppress CHIKV replication using more than one mechanism.

  11. Next generation sequencing of DNA-launched Chikungunya vaccine virus

    SciTech Connect

    Hidajat, Rachmat; Nickols, Brian; Forrester, Naomi; Tretyakova, Irina; Weaver, Scott; Pushko, Peter

    2016-03-15

    Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3′ untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. - Highlights: • Chikungunya virus (CHIKV) is an emerging pandemic threat. • In vivo DNA-launched attenuated CHIKV is a novel vaccine technology. • DNA-launched virus was sequenced using HiSeq2000 and compared to the 181/25 virus. • DNA-launched virus has lower frequency of SNPs at E2-12 and E2-82 attenuation loci.

  12. Evidence for Endemic Chikungunya Virus Infections in Bandung, Indonesia

    PubMed Central

    Kosasih, Herman; de Mast, Quirijn; Widjaja, Susana; Sudjana, Primal; Antonjaya, Ungke; Ma'roef, Chairin; Riswari, Silvita Fitri; Porter, Kevin R.; Burgess, Timothy H.; Alisjahbana, Bachti; van der Ven, Andre; Williams, Maya

    2013-01-01

    Chikungunya virus (CHIKV) is known to cause sporadic or explosive outbreaks. However, little is known about the endemic transmission of CHIKV. To ascertain the endemic occurrence of CHIKV transmission, we tested blood samples from patients with a non-dengue febrile illness who participated in a prospective cohort study of factory workers in Bandung, Indonesia. From August 2000 to June 2004, and September 2006 to April 2008, 1901 febrile episodes occurred and 231 (12.2%) dengue cases were identified. The remaining febrile cases were evaluated for possible CHIKV infection by measuring anti-CHIKV IgM and IgG antibodies in acute and convalescent samples. Acute samples of serologically positive cases were subsequently tested for the presence of CHIKV RNA by RT-PCR and/or virus isolation. A total of 135 (7.1%) CHIKV infections were identified, providing an incidence rate of 10.1/1,000 person years. CHIKV infections were identified all year round and tended to increase during the rainy season (January to March). Severe illness was not found and severe arthralgia was not a prominently reported symptom. Serial post-illness samples from nine cases were tested to obtain a kinetic picture of IgM and IgG anti-CHIKV antibodies. Anti-CHIKV IgM antibodies were persistently detected in high titers for approximately one year. Three patients demonstrated evidence of possible sequential CHIKV infections. The high incidence rate and continuous chikungunya cases in this adult cohort suggests that CHIKV is endemically transmitted in Bandung. Further characterization of the circulating strains and surveillance in larger areas are needed to better understand CHIKV epidemiology in Indonesia. PMID:24205417

  13. 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

  14. 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.

  15. Risk perceptions, attitudes, and knowledge of chikungunya among the public and health professionals: a systematic review.

    PubMed

    Corrin, Tricia; Waddell, Lisa; Greig, Judy; Young, Ian; Hierlihy, Catherine; Mascarenhas, Mariola

    2017-01-01

    Recently, attention to chikungunya has increased due to its spread into previously non-endemic areas. Since there is no available treatment or vaccine, most intervention strategies focus on mosquito bite prevention and mosquito control, which require community involvement to be successful. Thus, our objective was to systematically review the global primary literature on the risk perceptions, attitudes, and knowledge of chikungunya among the public and health professionals to inform future research and improve our understanding on which intervention strategies are likely to be successful. Potentially relevant articles were identified through a standardized systematic review (SR) process consisting of the following steps: comprehensive search strategy in seven databases (Scopus, PubMed, CINAHL, CAB, LILACS, Agricola, and Cochrane) and a grey literature search of public health organizations, relevance screening, risk of bias assessment, and data extraction. Two independent reviewers performed each step. Reporting of this SR follows PRISMA reporting guidelines. Thirty-seven relevant articles were identified. The majority of the articles were published since 2011 (83.8%) and reported on studies conducted in Asia (48.7%) and the Indian Ocean Islands (24.3%). The results were separated into four categories: general knowledge and perceptions on chikungunya; perceptions on the risk and severity of chikungunya; knowledge of chikungunya-harboring vectors and transmission; and knowledge, perceptions, and attitudes on mitigation practices. Overall, the systematic review found that risk perceptions, attitudes, and knowledge of chikungunya among the public and health professionals vary across populations and countries and knowledge is higher in areas that have experienced an outbreak. The results suggest that most of the affected populations in this study do not understand mosquito borne diseases or chikungunya and are therefore less likely to protect themselves from mosquito

  16. 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

    2015-07-16

    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.

  17. 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

  18. 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

  19. 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

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

    PubMed

    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.

  1. Outbreak of chikungunya due to virus of Central/East African genotype in Malaysia.

    PubMed

    Noridah, O; Paranthaman, V; Nayar, S K; Masliza, M; Ranjit, K; Norizah, I; Chem, Y K; Mustafa, B; Kumarasamy, V; Chua, K B

    2007-10-01

    Chikungunya is an acute febrile illness caused by an alphavirus which is transmitted by infective Aedes mosquitoes. Two previous outbreaks of chikungunya in Malaysia were due to chikungunya virus of Asian genotype. The present outbreak involved two adjoining areas in the suburb of Ipoh city within the Kinta district of Perak, a state in the northern part of Peninsular Malaysia. Thirty seven residents in the main outbreak area and two patients in the secondary area were laboratory confirmed to be infected with the virus. The index case was a 44-year Indian man who visited Paramakudi, Tamil Naidu, India on 21st November 2006 and returned home on 30th of November 2006, and subsequently developed high fever and joint pain on the 3rd of December 2006. A number of chikungunya virus isolates were isolated from both patients and Aedes albopictus mosquitoes in the affected areas. Molecular study showed that the chikungunya virus causing the Kinta outbreak was of the Central/East African genotype which occurred for the first time in Malaysia.

  2. Chikungunya virus disease outbreak in Yap State, Federated States of Micronesia

    PubMed Central

    Pastula, Daniel M.; Hancock, W. Thane; Bel, Martin; Biggs, Holly; Marfel, Maria; Lanciotti, Robert; Laven, Janeen; Chen, Tai-Ho; Staples, J. Erin; Fischer, Marc

    2017-01-01

    Background Chikungunya virus is a mosquito-borne alphavirus which causes an acute febrile illness associated with polyarthralgia. Beginning in August 2013, clinicians from the Yap State Department of Health in the Federated States of Micronesia (FSM) identified an unusual cluster of illness which was subsequently confirmed to be chikungunya virus disease. Chikungunya virus disease previously had not been recognized in FSM. Methodology/Principal findings Information from patients presenting to healthcare facilities was collected and analyzed. During August 11, 2013, to August 10, 2014, a total of 1,761 clinical cases were reported for an attack rate of 155 clinical cases per 1,000 population. Among residents of Yap Main Island, 3% were hospitalized. There were no deaths. The outbreak began on Yap Main Island and rapidly spread throughout Yap Main Island and to three neighboring islands. Conclusions/Significance Chikungunya virus can cause explosive outbreaks with substantial morbidity. Given the increasing globalization of chikungunya virus, strong surveillance systems and access to laboratory testing are essential to detect outbreaks. PMID:28248978

  3. Chikungunya virus: recent advances in epidemiology, host pathogen interaction and vaccine strategies.

    PubMed

    Deeba, Farah; Islam, Asimul; Kazim, Syed Naqui; Naqvi, Irshad Hussain; Broor, Shobha; Ahmed, Anwar; Parveen, Shama

    2016-04-01

    The Chikungunya virus is a re-emerging alphavirus that belongs to the family Togaviridae. The symptoms include fever, rashes, nausea and joint pain that may last for months. The laboratory diagnosis of the infection is based on the serologic assays, virus isolation and molecular methods. The pathogenesis of the Chikungunya viral infection is not completely understood. Some of the recent investigations have provided information on replication of the virus in various cells and organs. In addition, some recent reports have indicated that the severity of the disease is correlated with the viral load and cytokines. The Chikungunya virus infection re-emerged as an explosive epidemic during 2004-09 affecting millions of people in the Indian Ocean. Subsequent global attention was given to research on this viral pathogen due to its broad area of geographical distribution during this epidemic. Chikungunya viral infection has become a challenge for the public health system because of the absence of a vaccine as well as antiviral drugs. A number of potential vaccine candidates have been tested on humans and animal models during clinical and preclinical trials. In this review, we mainly discuss the host-pathogen relationship, epidemiology and recent advances in the development of drugs and vaccines for the Chikungunya viral infection.

  4. Chikungunya in the region of the Americas. A challenge for rheumatologists and health care systems.

    PubMed

    Pineda, Carlos; Muñoz-Louis, Roberto; Caballero-Uribe, Carlo V; Viasus, Diego

    2016-10-01

    At the end of 2013, the Pan American Health Organization issued an epidemiological alert due to the detection of the first local cases of Chikungunya in the Americas. By August 2015, autochthonous transmissions were detected in 33 countries and territories of the Americas. Latin America has reported nearly one million cases; only Colombia has issued a report of >200,000 cases during the first 4 months of 2015. In some Latin American and Caribbean countries, Chikungunya becomes a major public health problem. The disease commonly exhibits a self-limited course of arthritis, usually lasting for a few days or that may be prolonged to weeks; however, in 10-60 % of cases, joint pain may become chronic and persist for up to 3-5 years. Human-caused environmental changes, such as climate change, the globalization of international exchange, and disordered urban growth, are some factors that aid in its emergence and dissemination. Outbreaks of Chikungunya comprise a challenge for health care systems and rheumatologists because of the high attack rate on the population and the anticipated development of post-Chikungunya chronic rheumatism. This review emphasizes the rheumatologic clinical manifestations reported in the American continent and highlights the challenges that health care systems face in the absence of an effective vaccine and specific treatment to fight Chikungunya.

  5. 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. Copyright (c) 2010 Elsevier. Published by Elsevier B.V. All rights reserved.

  6. Emergence of chikungunya virus in Indian subcontinent after 32 years: A review.

    PubMed

    Lahariya, Chandrakant; Pradhan, S K

    2006-12-01

    An outbreak of chikungunya virus is currently ongoing in many countries in Indian Ocean since January 2005. The current outbreak appears to be the most severe and one of the biggest outbreaks caused by this virus. India, where this virus was last reported in 1973, is also amongst affected countries. Chikungunya virus has affected millions of the people in Africa and Southeast Asia, since it was first reported in 1952 in Tanzania. Even then, natural history of this disease is not fully understood. The intra-outbreak studies, point towards recent changes in the viral genome facilitating the rapid spread and enhanced pathogenecity. The available published scientific literature on chikungunya virus was searched to understand the natural history of this disease, reasons for the current outbreak and the causes behind re-emergence of the virus in India. The paucity of the scientific information on various epidemiological aspects of chikungunya virus threatens off an epidemic as control of spread of virus might be difficult in the absence of appropriate knowledge. There is an immediate need of the research on chikungunya virus, for an effective vaccine besides strengthening the existing diagnostic laboratory facilities. The current outbreak can also be taken as a lesson for establishment of a system for continuous surveillance of diseases, considered disappeared from the countries. The re-emergence and epidemics are unpredictable phenomena but the impact of such events can be ameliorated by appropriate knowledge and by being in the right state of preparedness.

  7. 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.

  8. 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

  9. The 2005-2007 Chikungunya epidemic in Réunion: ambiguous etiologies, memories, and meaning-making.

    PubMed

    Jansen, Karine Aasgaard

    2013-01-01

    From March 2005 to April 2007 the French overseas department and Indian Ocean island of Réunion was significantly affected by an epidemic of chikungunya. Chikungunya is a vector-spread disease (by the aedes albopictus mosquito) that leads to painful rheumatic symptoms. The disease infected approximately one third of the island's total population of 802,000 inhabitants (Rallu 2009 ). This article is a discussion of local etiological accounts of chikungunya. The primary topic raised by informants was whether chikungunya was a vector- or air-borne disease. Even though informants had access to substantial biomedical information concerning the disease and its transmission, some were convinced by it and others were not. In order to make meaning of the disease, the Réunionese drew on various types of medical knowledge from different health sectors simultaneously. To understand people's experiences with chikungunya, we must account for all of their etiological explanations.

  10. [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.

  11. Clinical Features and Neurologic Complications of Children Hospitalized With Chikungunya Virus in Honduras.

    PubMed

    Samra, José A; Hagood, Nancy L; Summer, Andrea; Medina, Marco T; Holden, Kenton R

    2017-07-01

    The first case of Chikungunya virus in Honduras was identified in 2014. The virus has spread widely across Honduras via the Aedes aegypti mosquito, leading to an outbreak of Chikungunya virus (CHIKV) in 2015 that significantly impacted children. A retrospective chart review of 235 children diagnosed with CHIKV and admitted to the National Autonomous University of Honduras Hospital Escuela (Hospital Escuela) in Tegucigalpa, Honduras, was accomplished with patients who were assessed for clinical features and neurologic complications. Of 235 children admitted to Hospital Escuela with CHIKV, the majority had symptoms of fever, generalized erythematous rash, and irritability. Fourteen percent had clinical arthritis. Ten percent of patients had seizures. Six percent had meningoencephalitis. There were 2 childhood deaths during the course of this study, one from meningoencephalitis and another from myocarditis. Chikungunya virus can cause severe complications in children, the majority of which impact the central nervous system.

  12. Chikungunya Virus Sequences across the First Epidemic in Nicaragua, 2014–2015

    PubMed Central

    Wang, Chunling; Saborio, Saira; Gresh, Lionel; Eswarappa, Meghana; Wu, Diane; Fire, Andrew; Parameswaran, Poornima; Balmaseda, Angel; Harris, Eva

    2016-01-01

    Chikungunya is caused by the mosquito-borne arthrogenic alphavirus, chikungunya virus (CHIKV). Chikungunya was introduced into the Americas in late 2013 and Nicaragua in mid-2014. Here, we sequenced five imported and 30 autochthonous Nicaraguan CHIKV from cases identified in the first epidemic in the country between August 2014 and April 2015. One full-length and two partial genomic sequences were obtained by deep sequencing; Sanger methodology yielded 33 E1 sequences from five imported and 28 autochthonous cases. Phylogenetic analysis indicates that Nicaraguan CHIKV all belonged to the Asian genotype, Caribbean clade. Moreover, E1 gene sequences revealed accumulation of mutations in later months of the epidemic, including four silent mutations in 11 autochthonous cases and three non-synonymous mutations in three autochthonous cases. No mutations contributing to increased transmissibility by Aedes albopictus were identified in the E1 gene. This represents the most comprehensive set of CHIKV sequences available from the Americas to date. PMID:26643533

  13. Genital Aphthous Ulcers and a Case of Suspected Chikungunya: A Short Clinical Case.

    PubMed

    Martinez-Díaz, Frances A

    2017-09-01

    Genital aphthous ulcers can result from multiple conditions including febrile syndromes. Chikungunya infection manifests mainly as fever accompanied by polyarthralgia and pruritic rash. Nevertheless, healthcare providers should be alert to additional presentations. This is the case of a young woman presenting with painful genital ulcers after a three day prodome of fever and polyarthralgia. As a suspected case of Chikungunya infection and a clinical diagnosis of aphthae, treatment with oral prednisone for two weeks produced complete resolution of ulcers with no scarring. It is important to recognize that genital aphthous ulcers can develop in a febrile presentation such as that with Chikungunya. Although sexually transmitted diseases should be ruled out as a more common diagnosis in cases of genital lesions, knowledge about this unusual dermatological presentation would represent not only adequate prompt treatment but will minimize equivocal diagnosis as a sexually transmitted disease.

  14. Dengue and Chikungunya fever among viral diseases in outpatient febrile children in Kilosa district hospital, Tanzania.

    PubMed

    Chipwaza, Beatrice; Mugasa, Joseph P; Selemani, Majige; Amuri, Mbaraka; Mosha, Fausta; Ngatunga, Steve D; Gwakisa, Paul S

    2014-11-01

    Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2-13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35-3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of febrile patients is recommended.

  15. Local and regional spread of chikungunya fever in the Americas

    PubMed Central

    Cauchemez, S; Ledrans, M; Poletto, C; Quenel, P; De Valk, H; Colizza, V; Boelle, PY

    2015-01-01

    Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act. PMID:25060573

  16. Chikungunya Virus Vaccines: Viral Vector-Based Approaches.

    PubMed

    Ramsauer, Katrin; Tangy, Frédéric

    2016-12-15

    In 2013, a major chikungunya virus (CHIKV) epidemic reached the Americas. In the past 2 years, >1.7 million people have been infected. In light of the current epidemic, with millions of people in North and South America at risk, efforts to rapidly develop effective vaccines have increased. Here, we focus on CHIKV vaccines that use viral-vector technologies. This group of vaccine candidates shares an ability to potently induce humoral and cellular immune responses by use of highly attenuated and safe vaccine backbones. So far, well-described vectors such as modified vaccinia virus Ankara, complex adenovirus, vesicular stomatitis virus, alphavirus-based chimeras, and measles vaccine Schwarz strain (MV/Schw) have been described as potential vaccines. We summarize here the recent data on these experimental vaccines, with a focus on the preclinical and clinical activities on the MV/Schw-based candidate, which is the first CHIKV-vectored vaccine that has completed a clinical trial. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  17. 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

    2015-07-23

    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.

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

    PubMed Central

    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

  19. 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.

  20. Local and regional spread of chikungunya fever in the Americas.

    PubMed

    Cauchemez, S; Ledrans, M; Poletto, C; Quenel, P; de Valk, H; Colizza, V; Boëlle, P Y

    2014-07-17

    Chikungunya fever (CHIKV), a viral disease transmitted by mosquitoes, is currently affecting several areas in the Caribbean. The vector is found in the Americas from southern Florida to Brazil, and the Caribbean is a highly connected region in terms of population movements. There is therefore a significant risk for the epidemic to quickly expand to a wide area in the Americas. Here, we describe the spread of CHIKV in the first three areas to report cases and between areas in the region. Local transmission of CHIKV in the Caribbean is very effective, the mean number of cases generated by a human case ranging from two to four. There is a strong spatial signature in the regional epidemic, with the risk of transmission between areas estimated to be inversely proportional to the distance rather than driven by air transportation. So far, this simple distance-based model has successfully predicted observed patterns of spread. The spatial structure allows ranking areas according to their risk of invasion. This characterisation may help national and international agencies to optimise resource allocation for monitoring and control and encourage areas with elevated risks to act.

  1. Next Generation Sequencing of DNA-Launched Chikungunya Vaccine Virus

    PubMed Central

    Hidajat, Rachmat; Nickols, Brian; Forrester, Naomi; Tretyakova, Irina; Weaver, Scott; Pushko, Peter

    2016-01-01

    Chikungunya virus (CHIKV) represents a pandemic threat with no approved vaccine available. Recently, we described a novel vaccination strategy based on iDNA® infectious clone designed to launch a live-attenuated CHIKV vaccine from plasmid DNA in vitro or in vivo. As a proof of concept, we prepared iDNA plasmid pCHIKV-7 encoding the full-length cDNA of the 181/25 vaccine. The DNA-launched CHIKV-7 virus was prepared and compared to the 181/25 virus. Illumina HiSeq2000 sequencing revealed that with the exception of the 3’ untranslated region, CHIKV-7 viral RNA consistently showed a lower frequency of single-nucleotide polymorphisms than the 181/25 RNA including at the E2-12 and E2-82 residues previously identified as attenuating mutations. In the CHIKV-7, frequencies of reversions at E2-12 and E2-82 were 0.064% and 0.086%, while in the 181/25, frequencies were 0.179% and 0.133%, respectively. We conclude that the DNA-launched virus has a reduced probability of reversion mutations, thereby enhancing vaccine safety. PMID:26855330

  2. Attenuated and vectored vaccines protect nonhuman primates against Chikungunya virus

    PubMed Central

    Ljungberg, Karl; Kümmerer, Beate M.; Gosse, Leslie; Dereuddre-Bosquet, Nathalie; Tchitchek, Nicolas; Hallengärd, David; García-Arriaza, Juan; Meinke, Andreas; Esteban, Mariano; Merits, Andres

    2017-01-01

    Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this virus is a serious threat to public health, but at present, there is no vaccine against this debilitating disease. We have recently developed a number of vaccine candidates, and here we have evaluated 3 of them in a nonhuman primate model. A single immunization with an attenuated strain of CHIKV (Δ5nsP3), a homologous prime-boost immunization with a DNA-launched RNA replicon encoding CHIKV envelope proteins (DREP-E), and a DREP-E prime followed by a recombinant modified vaccinia virus Ankara encoding CHIKV capsid and envelope (MVA-CE) boost all induced protection against WT CHIKV infection. The attenuated Δ5nsP3 virus proved to be safe and did not show any clinical signs typically associated with WT CHIKV infections such as fever, skin rash, lymphopenia, or joint swelling. These vaccines are based on an East/Central/South African strain of Indian Ocean lineage, but they also generated neutralizing antibodies against an isolate of the Asian genotype that now is rapidly spreading across the Americas. These results form the basis for clinical development of an efficacious CHIKV vaccine that generates both humoral and cellular immunity with long-term immunological memory. PMID:28352649

  3. Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases.

    PubMed

    Weaver, Scott C; Charlier, Caroline; Vasilakis, Nikos; Lecuit, Marc

    2017-08-28

    Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms. Expected final online publication date for the Annual Review of Medicine Volume 69 is January 29, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  4. 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.

  5. 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.

  6. Evidence of acute rickettsioses among patients presumed to have chikungunya fever during the chikungunya outbreak in Sri Lanka.

    PubMed

    Premaratna, R; Halambarachchige, L P; Nanayakkara, D M; Chandrasena, T G A N; Rajapakse, R P V J; Bandara, N K B K R G W; de Silva, H J

    2011-12-01

    Chikungunya fever (CGF) and rickettsioses are known to cause acute onset febrile illnesses associated with severe arthritis. Rickettsial arthritis is curable with the use of appropriate anti-rickettsial antibiotics, however the arthritis of CGF tends to have a prolonged course leading to protracted disability. The aim of this study was to investigate the contribution of CGF and rickettsioses to cases of fever and arthritis during a presumed CGF outbreak in Sri Lanka. Fifty-eight consecutive patients with presumed CGF were further investigated to determine the occurrence of rickettsioses among them, and to identify differences in clinical, hematological, and biochemical parameters between the two diseases. Nearly a third of the patients had serological evidence of rickettsioses accounting for their illness. The presence of a late onset major joint arthropathy sparing the small joints of the hands and feet, and the occurrence of a late onset discrete maculopapular rash over the trunk and extremities, suggested rickettsioses over CGF. White blood cell count, erythrocyte sedimentation rate, C-reactive protein, and liver function tests were not helpful in differentiating rickettsioses from CGF. Patients with rickettsioses and arthritis who received an empirical course of doxycycline recovered faster than those who did not receive specific treatment. The establishment of rapid diagnostic methods able to differentiate the etiological agents of fever and arthritis, such as CGF and rickettsioses, would be beneficial in endemic settings. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Mutation of the N-Terminal Region of Chikungunya Virus Capsid Protein: Implications for Vaccine Design.

    PubMed

    Taylor, Adam; Liu, Xiang; Zaid, Ali; Goh, Lucas Y H; Hobson-Peters, Jody; Hall, Roy A; Merits, Andres; Mahalingam, Suresh

    2017-02-21

    Mosquito-transmitted chikungunya virus (CHIKV) is an arthritogenic alphavirus of the Togaviridae family responsible for frequent outbreaks of arthritic disease in humans. Capsid protein, a structural protein encoded by the CHIKV RNA genome, is able to translocate to the host cell nucleolus. In encephalitic alphaviruses, nuclear translocation induces host cell transcriptional shutoff; however, the role of capsid protein nucleolar localization in arthritogenic alphaviruses remains unclear. Using recombinant enhanced green fluorescent protein (EGFP)-tagged expression constructs and CHIKV infectious clones, we describe a nucleolar localization sequence (NoLS) in the N-terminal region of capsid protein, previously uncharacterized in CHIKV. Mutation of the NoLS by site-directed mutagenesis reduced efficiency of nuclear import of CHIKV capsid protein. In the virus, mutation of the capsid protein NoLS (CHIKV-NoLS) attenuated replication in mammalian and mosquito cells, producing a small-plaque phenotype. Attenuation of CHIKV-NoLS is likely due to disruption of the viral replication cycle downstream of viral RNA synthesis. In mice, CHIKV-NoLS infection caused no disease signs compared to wild-type CHIKV (CHIKV-WT)-infected mice; lack of disease signs correlated with significantly reduced viremia and decreased expression of proinflammatory factors. Mice immunized with CHIKV-NoLS, challenged with CHIKV-WT at 30 days postimmunization, develop no disease signs and no detectable viremia. Serum from CHIKV-NoLS-immunized mice is able to efficiently neutralize CHIKV infection in vitro Additionally, CHIKV-NoLS-immunized mice challenged with the related alphavirus Ross River virus showed reduced early and peak viremia postchallenge, indicating a cross-protective effect. The high degree of CHIKV-NoLS attenuation may improve CHIKV antiviral and rational vaccine design.IMPORTANCE CHIKV is a mosquito-borne pathogen capable of causing explosive epidemics of incapacitating joint pain

  8. Saccharomyces cerevisiae aldolase mutants.

    PubMed Central

    Lobo, Z

    1984-01-01

    Six mutants lacking the glycolytic enzyme fructose 1,6-bisphosphate aldolase have been isolated in the yeast Saccharomyces cerevisiae by inositol starvation. The mutants grown on gluconeogenic substrates, such as glycerol or alcohol, and show growth inhibition by glucose and related sugars. The mutations are recessive, segregate as one gene in crosses, and fall in a single complementation group. All of the mutants synthesize an antigen cross-reacting to the antibody raised against yeast aldolase. The aldolase activity in various mutant alleles measured as fructose 1,6-bisphosphate cleavage is between 1 to 2% and as condensation of triose phosphates to fructose 1,6-bisphosphate is 2 to 5% that of the wild-type. The mutants accumulate fructose 1,6-bisphosphate from glucose during glycolysis and dihydroxyacetone phosphate during gluconeogenesis. This suggests that the aldolase activity is absent in vivo. PMID:6384192

  9. A recombinant measles vaccine expressing chikungunya virus-like particles is strongly immunogenic and protects mice from lethal challenge with chikungunya virus.

    PubMed

    Brandler, Samantha; Ruffié, Claude; Combredet, Chantal; Brault, Jean-Baptiste; Najburg, Valérie; Prevost, Marie-Christine; Habel, André; Tauber, Erich; Desprès, Philippe; Tangy, Frédéric

    2013-08-12

    Chikungunya virus (CHIKV), a mosquito-transmitted alphavirus, recently reemerged in the Indian Ocean, India and Southeast Asia, causing millions of cases of severe polyarthralgia. No specific treatment to prevent disease or vaccine to limit epidemics is currently available. Here we describe a recombinant live-attenuated measles vaccine (MV) expressing CHIKV virus-like particles comprising capsid and envelope structural proteins from the recent CHIKV strain La Reunion. Immunization of mice susceptible to measles virus induced high titers of CHIKV antibodies that neutralized several primary isolates. Specific cellular immune responses were also elicited. A single immunization with this vaccine candidate protected all mice from a lethal CHIKV challenge, and passive transfer of immune sera conferred protection to naïve mice. Measles vaccine is one of the safest and most effective human vaccines. A recombinant MV-CHIKV virus could make a safe and effective vaccine against chikungunya that deserves to be further tested in human trials.

  10. 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

    2014-07-17

    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.

  11. 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

    2014-12-05

    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

  12. 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

  13. 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.

  14. High Level of Vector Competence of Aedes aegypti and Aedes albopictus from Ten American Countries as a Crucial Factor in the Spread of Chikungunya Virus

    PubMed Central

    Vega-Rúa, Anubis; Zouache, Karima; Girod, Romain

    2014-01-01

    ABSTRACT Chikungunya virus (CHIKV) causes a major public health problem. In 2004, CHIKV began an unprecedented global expansion and has been responsible for epidemics in Africa, Asia, islands in the Indian Ocean region, and surprisingly, in temperate regions, such as Europe. Intriguingly, no local transmission of chikungunya virus (CHIKV) had been reported in the Americas until recently, despite the presence of vectors and annually reported imported cases. Here, we assessed the vector competence of 35 American Aedes aegypti and Aedes albopictus mosquito populations for three CHIKV genotypes. We also compared the number of viral particles of different CHIKV strains in mosquito saliva at two different times postinfection. Primarily, viral dissemination rates were high for all mosquito populations irrespective of the tested CHIKV isolate. In contrast, differences in transmission efficiency (TE) were underlined in populations of both species through the Americas, suggesting the role of salivary glands in selecting CHIKV for highly efficient transmission. Nonetheless, both mosquito species were capable of transmitting all three CHIKV genotypes, and TE reached alarming rates as high as 83.3% and 96.7% in A. aegypti and A. albopictus populations, respectively. A. albopictus better transmitted the epidemic mutant strain CHIKV_0621 of the East-Central-South African (ECSA) genotype than did A. aegypti, whereas the latter species was more capable of transmitting the original ECSA CHIKV_115 strain and also the Asian genotype CHIKV_NC. Therefore, a high risk of establishment and spread of CHIKV throughout the tropical, subtropical, and even temperate regions of the Americas is more real than ever. IMPORTANCE Until recently, the Americas had never reported chikungunya (CHIK) autochthonous transmission despite its global expansion beginning in 2004. Large regions of the continent are highly infested with Aedes aegypti and Aedes albopictus mosquitoes, and millions of dengue (DEN

  15. 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

  16. Analysis of coevolution in nonstructural proteins of chikungunya virus.

    PubMed

    Jain, Jaspreet; Mathur, Kalika; Shrinet, Jatin; Bhatnagar, Raj K; Sunil, Sujatha

    2016-06-02

    RNA viruses are characterized by high rate of mutations mainly due to the lack of proofreading repair activities associated with its RNA-dependent RNA-polymerase (RdRp). In case of arboviruses, this phenomenon has lead to the existence of mixed population of genomic variants within the host called quasi-species. The stability of strains within the quasi-species lies on mutations that are positively selected which in turn depend on whether these mutations are beneficial in either or both hosts. Coevolution of amino acids (aa) is one phenomenon that leads to establishment of favorable traits in viruses and leading to their fitness. Fourteen CHIKV clinical samples collected over three years were subjected to RT-PCR, the four non-structural genes amplified and subjected to various genetic analyses. Coevolution analysis showed 30 aa pairs coevolving in nsP1, 23 aa pairs coevolving in nsP2, 239 in nsP3 and 46 aa coevolving pairs in nsP4 when each non-structural protein was considered independently. Further analysis showed that 705 amino acids pairs of the non-structural polyproteins coevolved together with a correlation coefficient of ≥0.5. Functional relevance of these coevolving amino acids in all the nonstructural proteins of CHIKV were predicted using Eukaryotic Linear Motifs (ELMs) of human. The present study was undertaken to study co-evolving amino acids in the non-structural proteins of chikungunya virus (CHIKV), an important arbovirus. It was observed that several amino acids residues were coevolving and shared common functions.

  17. Replication cycle of chikungunya: A re-emerging arbovirus

    PubMed Central

    Solignat, Maxime; Gay, Bernard; Higgs, Stephen; Briant, Laurence; Devaux, Christian

    2010-01-01

    Arboviruses (or arthropod-borne viruses), represent a threat for the new century. The 2005–2006 year unprecedented epidemics of chikungunya virus (CHIKV) in the French Reunion Island in the Indian Ocean, followed by several outbreaks in other parts of the world such as India, have attracted the attention of clinicians, scientists, and state authorities about the risks linked to this re-emerging mosquito-borne virus. CHIKV, which belongs to the Alphaviruses genus, was not previously regarded as a highly pathogenic arbovirus. However, this opinion was challenged by the death of several CHIKV-infected persons in Reunion Island. The epidemic episode began in December 2005 and four months later the seroprevalence survey report indicated that 236,000 persons, more than 30% of Reunion Island population, had been infected with CHIKV, among which 0.4–0.5% of cases were fatal. Since the epidemic peak, the infection case number has continued to increase to almost 40% of the population, with a total of more than 250 fatalities. Although information available on CHIKV is growing quite rapidly, we are still far from understanding the strategies required for the ecologic success of this virus, virus replication, its interactions with its vertebrate hosts and arthropod vectors, and its genetic evolution. In this paper, we summarize the current knowledge of CHIKV genomic organization, cell tropism, and the virus replication cycle, and evaluate the possibility to predict its future evolution. Such understanding may be applied in order to anticipate future epidemics and reduce the incidence by development and application of, for example, vaccination and antiviral therapy. PMID:19732931

  18. Emergence and potential for spread of Chikungunya virus in Brazil.

    PubMed

    Nunes, Marcio Roberto Teixeira; Faria, Nuno Rodrigues; de Vasconcelos, Janaina Mota; Golding, Nick; Kraemer, Moritz U G; de Oliveira, Layanna Freitas; Azevedo, Raimunda do Socorro da Silva; da Silva, Daisy Elaine Andrade; da Silva, Eliana Vieira Pinto; da Silva, Sandro Patroca; Carvalho, Valéria Lima; Coelho, Giovanini Evelim; Cruz, Ana Cecília Ribeiro; Rodrigues, Sueli Guerreiro; Vianez, Joao Lídio da Silva Gonçalves; Nunes, Bruno Tardelli Diniz; Cardoso, Jedson Ferreira; Tesh, Robert B; Hay, Simon I; Pybus, Oliver G; Vasconcelos, Pedro Fernando da Costa

    2015-04-30

    In December 2013, an outbreak of Chikungunya virus (CHIKV) caused by the Asian genotype was notified in the Caribbean. The outbreak has since spread to 38 regions in the Americas. By September 2014, the first autochthonous CHIKV infections were confirmed in Oiapoque, North Brazil, and in Feira de Santana, Northeast Brazil. We compiled epidemiological and clinical data on suspected CHIKV cases in Brazil and polymerase-chain-reaction-based diagnostic was conducted on 68 serum samples from patients with symptom onset between April and September 2014. Two imported and four autochthonous cases were selected for virus propagation, RNA isolation, full-length genome sequencing, and phylogenetic analysis. We then followed CDC/PAHO guidelines to estimate the risk of establishment of CHIKV in Brazilian municipalities. We detected 41 CHIKV importations and 27 autochthonous cases in Brazil. Epidemiological and phylogenetic analyses indicated local transmission of the Asian CHIKV genotype in Oiapoque. Unexpectedly, we also discovered that the ECSA genotype is circulating in Feira de Santana. The presumed index case of the ECSA genotype was an individual who had recently returned from Angola and developed symptoms in Feira de Santana. We estimate that, if CHIKV becomes established in Brazil, transmission could occur in 94% of municipalities in the country and provide maps of the risk of importation of each strain of CHIKV in Brazil. The etiological strains associated with the early-phase CHIKV outbreaks in Brazil belong to the Asian and ECSA genotypes. Continued surveillance and vector mitigation strategies are needed to reduce the future public health impact of CHIKV in the Americas.

  19. Chikungunya Virus Infection and Diabetes Mellitus: A Double Negative Impact

    PubMed Central

    Jean-Baptiste, Eddy; von Oettingen, Julia; Larco, Philippe; Raphaël, Frédérica; Larco, Nancy Charles; Cauvin, Marie Marcelle; Charles, René

    2016-01-01

    The impact of chikungunya virus (CHIKV) infection on diabetic patients (DPs) has not been described. We aimed to compare clinical features of CHIKV infection in DPs and nondiabetic patients (NDPs), and to evaluate its effects on glycemic control among DPs. We recorded clinical information and, in DPs, glycemic control. Forty-six DPs and 53 NDPs aged ≥ 20 years living in Haiti, with acute CHIKV infection, were studied. Diabetes duration was 7.1 ± 6.1 years. The most common acute CHIKV clinical manifestations were arthralgia (100.0% DPs and 98.1% NDPs, P = 1.000) and fever (86.9% DPs and 90.5% NDPs, P = 0.750). In DPs as compared with NDPs, arthralgia was more intense (mean pain score of 6.0/10 ± 2.2 versus 5.1/10 ± 2.0, P = 0.04) and took longer to improve (8.2 ± 3.0 versus 3.5 ± 2.5 days, P < 0.0001). Severe arthralgia was more prevalent (58.7% versus 20.8%, P = 0.0002), as was myalgia (80.4% versus 50.9%, P = 0.003), and fever lasted longer (5.1 ± 1.8 versus 3.7 ± 1.7 days, P = 0.0002). Among DPs, median fasting capillary glucose before versus after disease onset was 132.5 and 167.5 mg/dL (P < 0.001), corresponding to a median increase of 26.8% (interquartile range: 14.4–50.1%). Antidiabetic medication was titrated up in 41.3%. In summary, among DPs, CHIKV infection has a significant negative impact on glycemic control and, compared with NDPs, results in greater morbidity. Close clinical and glycemic observation is recommended in DPs with CHIKV infection. PMID:27729569

  20. 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

  1. Nowcasting the spread of chikungunya virus in the Americas.

    PubMed

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

    2014-01-01

    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. 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. 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.

  2. 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

    2016-07-06

    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. © The American Society of Tropical Medicine and Hygiene.

  3. Chikungunya virus transmission between Aedes albopictus and laboratory mice.

    PubMed

    Hugo, Leon E; Prow, Natalie A; Tang, Bing; Devine, Greg; Suhrbier, Andreas

    2016-10-19

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus associated with epidemics of acute and chronic arthritic disease in humans. Aedes albopictus has emerged as an important new natural vector for CHIKV transmission; however, mouse models for studying transmission have not been developed. Aedes albopictus mosquitoes were infected with CHIKV via membrane feeding and by using infected adult wild-type C57BL/6 mice. Paraffin sections of infected mosquitoes were analysed by immunofluorescent antibody staining using an anti-CHIKV antibody. CHIKV-infected mosquitoes were used to infect adult C57BL/6 and interferon response factor 3 and 7 deficient (IRF3/7(-/-)) mice. Feeding mosquitoes on blood meals with CHIKV titres > 5 log10CCID50/ml, either by membrane feeding or feeding on infected mice, resulted in  ≥ 50 % of mosquitoes becoming infected. However, CHIKV titres in blood meals  ≥ 7 log10CCID50/ml were required before salivary glands showed significant levels of immunofluorescent staining with an anti-CHIKV antibody. Mosquitoes fed on blood meals of 7.5 (but not 5.9) log10CCID50/ml were able efficiently to transmit virus to adult C57BL/6 and IRF3/7(-/-) mice, with the latter mice showing overt signs of arthritis post-infection. The results provide a simple in vivo model for studying transmission of CHIKV from mosquitoes to mammals and also argue against a resistance barrier to CHIKV infection in adult mice.

  4. Chikungunya virus outbreak in Sint Maarten, 2013-2014.

    PubMed

    Henry, Maria; Francis, Lorraine; Asin, Virginia; Polson-Edwards, Karen; Olowokure, Babatunde

    2017-08-21

    This report describes the outbreak of chikungunya virus (CHIKV) in Sint Maarten, a constituent country of Kingdom of the Netherlands comprising the southern part of the Caribbean island of Saint Martin, from 22 December 2013 (first reported case) through 5 December 2014. The outbreak was first reported by the French overseas collectivity of Saint-Martin in the northern part of the island-the first site in the Americas to report autochthonous transmission of CHIKV. By 5 December 2014, Sint Maarten had reported a total of 658 cases-an overall attack rate of 1.76%. Actual prevalence may have been higher, as some cases may have been misdiagnosed as dengue. Fever and arthralgia affected 71% and 69% of reported cases respectively. Of the 390 laboratory-confirmed cases, 61% were female and the majority were 20-59 years old (mean: 42; range: 4-92). The spread of CHIKV to Sint Maarten was inevitable given the ease of movement of people, and the vector, island-wide. Continuing their history of collaboration, the French and Dutch parts of the island coordinated efforts for prevention and control of the disease. These included a formal agreement to exchange epidemiological information on a regular basis and provide alerts in a timely manner; collaboration among personnel through joint island-wide planning of mosquito control activities, especially along borders; notification of all island visitors, upon their arrival at airports and seaports, of preventative measures to avoid being bitten by mosquitoes; dissemination of educational materials to the public; and island-wide public awareness campaigns, particularly in densely populated areas, for both residents and visitors. The information provided in this report could help increase understanding of the epidemiological characteristics of CHIKV and guide other countries dealing with vector-borne epidemics.

  5. A Combination of Doxycycline and Ribavirin Alleviated Chikungunya Infection

    PubMed Central

    Rothan, Hussin A.; Bahrani, Hirbod; Mohamed, Zulqarnain; Teoh, Teow Chong; Shankar, Esaki M.; Rahman, Noorsaadah A.; Yusof, Rohana

    2015-01-01

    Lack of vaccine and effective antiviral drugs against chikungunya virus (CHIKV) outbreaks have led to significant impact on health care in the developing world. Here, we evaluated the antiviral effects of tetracycline (TETRA) derivatives and other common antiviral agents against CHIKV. Our results showed that within the TETRA derivatives group, Doxycycline (DOXY) exhibited the highest inhibitory effect against CHIKV replication in Vero cells. On the other hand, in the antiviral group Ribavirin (RIBA) showed higher inhibitory effects against CHIKV replication compared to Aciclovir (ACIC). Interestingly, RIBA inhibitory effects were also higher than all but DOXY within the TETRA derivatives group. Docking studies of DOXY to viral cysteine protease and E2 envelope protein showed non-competitive interaction with docking energy of -6.6±0.1 and -6.4±0.1 kcal/mol respectively. The 50% effective concentration (EC50) of DOXY and RIBA was determined to be 10.95±2.12 μM and 15.51±1.62 μM respectively, while DOXY+RIBA (1:1 combination) showed an EC50 of 4.52±1.42 μM. When compared, DOXY showed higher inhibition of viral infectivity and entry than RIBA. In contrast however, RIBA showed higher inhibition against viral replication in target cells compared to DOXY. Assays using mice as animal models revealed that DOXY+RIBA effectively inhibited CHIKV replication and attenuated its infectivity in vivo. Further experimental and clinical studies are warranted to investigate their potential application for clinical intervention of CHIKV disease. PMID:25970853

  6. Psychiatric Morbidity in Patients with Chikungunya Fever: First Report from India.

    PubMed

    Bhatia, M S; Gautam, Priyanka; Jhanjee, Anurag

    2015-10-01

    Chikungunya fever is an acute illness caused by an arbovirus and has various complications like neurological, psychological, dermatological and even multi organ failure. Psychiatric co-morbidity is not very well studied till now. This is the first report from India. Aim of the study was to assess the psychiatric morbidity during or after the onset of Chikungunya fever. Patients referred from Medicine department with confirmed diagnosis of Chikungunya fever were recruited, after taking informed consent. Patient's socio-demographic characteristics were noted and Psychiatric co-morbidity was assessed by complete history taking and mental status examination, using WHO International Classification of Diseases, 10(th) edition (ICD -10) of Mental and Behavioural Disorders, Diagnostic criteria for research. The age range of the study group was found to be 23-48 years. Fourteen (70%) were males and 6 (30%) were females. Five (25%) patients were diagnosed with depressive disorder, 3 (15%) patients had Generalized Anxiety Disorder (GAD), 2 (10%) patients GAD with Panic attacks, 1(5%) patients phobic disorder (claustrophobia), 3 (15%) patients Somatoform Disorder, 3 (15%), Neurasthenia (Fatigue Syndrome), etc. Two (10%) patients presented with vague somatic complaints which did not fit into any of the diagnostic category. Chikungunya fever can result in significant psychiatric morbidity, mainly in the form of depressive episode, anxiety disorder and even long persisting illnesses like somato-form disorders. Further research is required to know about the phenomenology or the neurobiology of the psychiatric disorders occurring in the course of this illness.

  7. Envelope specific T cell responses & cytokine profiles in chikungunya patients hospitalized with different clinical presentations

    PubMed Central

    Tripathy, Anuradha S.; Tandale, Babasaheb V.; Balaji, Saravana S.; Hundekar, Supriya L.; Ramdasi, Ashwini Y.; Arankalle, Vidya A.

    2015-01-01

    Background & objectives: Since the 2006 massive outbreaks, chikungunya (CHIK) is a major public health concern in India. The aim of this study was to assess envelope specific immune responses in patients with chikungunya infection. Methods: This study included 46 hospitalized patients with chikungunya virus infection (encephalitis, n=22, other systemic involvement, OSI, n=12, classical, n=12) and six controls from Ahmedabad city, Gujarat, India. T cell responses and the levels of Th1, pro/ anti-inflammatory cytokines against the CHIK virus envelope antigens were assessed by lymphocyte proliferation assay and by cytometric bead array in flow cytometry, respectively. Results: Lymphoproliferative response was uniform among the patients. Comparisons of cytokines revealed significantly higher levels of interleukin (IL)-4 and IL-5 in encephalitis, OSI and classical patients versus controls. The levels of tumour necrosis factor (TNF)-α were higher in classical patients categories compared to the controls. Interferon (IFN)-γ levels were lower in encephalitis patients versus control. Interpretation & conclusions: Our findings showed recognition of T cell epitopes on the envelope region of chikungunya virus by all patient categories. Lower level of IFN-γ may be associated with the severity of disease in these patients. PMID:25900956

  8. Impact of Chikungunya virus infection on oral health status: an observational study.

    PubMed

    Katti, Roopa; Shahapur, P R; Udapudi, K L

    2011-01-01

    Chikungunya fever outbreak started in December 2005 in India when the country experienced more than 13 lakhs of Chikungunya infected cases. We undertook this study to describe the impact of Chikungunya virus infection on oral health. The confirmed seropositive patients were included for the study (N = 97). Oral hygiene index simplified, gingival index, plaque index were recorded. Of the 181 tested, 97 were confirmed seropositive for chikungunya infection. Pain and bleeding gums were seen in 55% of the subjects. Of them, 29.1% had poor oral hygiene, 42.27% had severe gingivitis, and 27.84% had severe plaque deposits. Severe gingivitis was observed in patients with chronic disease, this association was statistically significant (χ2 = 6.417, P = 0.040). Our findings showed that about more than half of the tested patients suffered severe pain and bleeding in the oral cavity thereby causing discomfort in chewing. About 1/3 patients had severe gingivitis and foul breath which caused discomfort in carrying out their day-to-day activities.

  9. 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

  10. Analytical and clinical performance of a Chikungunya qRT-PCR for Central and South America.

    PubMed

    Edwards, Thomas; Del Carmen Castillo Signor, Leticia; Williams, Christopher; Larcher, Clément; Espinel, Mauricio; Theaker, Jane; Donis, Evelin; Cuevas, Luis E; Adams, Emily R

    2017-09-01

    Chikungunya was introduced into the Americas in 2015 causing a pandemic across the continent. Testing during the acute phase of infection relies on qRT-PCR, but available assays have a number of limitations. A qRT-PCR assay specific to the chikungunya E1 gene was designed using sequence data from contemporary strains. A probit analysis established the 95% limit of detection as 19.6 copies per reaction. We compared the assay with a US Centers for Disease Control (CDC) chikungunya qRT-PCR as the reference standard. The assay had a sensitivity and specificity of 98.4% and 100% in 90 samples retrospectively collected in Guatemala. In a further 74 febrile samples prospectively collected in Ecuador and Guatemala the test had a sensitivity and specificity of 100% and 98.4%, respectively. Sequencing the nsp4 gene of the discordant positive sample indicated the presence of chikungunya RNA, and mismatches to the primer binding sites of the CDC assay. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Dengue and chikungunya: long-distance spread and outbreaks in naïve areas

    PubMed Central

    Rezza, Giovanni

    2014-01-01

    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

  12. 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

  13. 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.

  14. 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

  15. Spread of Chikungunya Virus East/Central/South African Genotype in Northeast Brazil.

    PubMed

    Charlys da Costa, Antonio; Thézé, Julien; Komninakis, Shirley Cavalcante Vasconcelos; Sanz-Duro, Rodrigo Lopes; Felinto, Marta Rejane Lemos; Moura, Lúcia Cristina Corrêa; Barroso, Ivoneide Moreira de Oliveira; Santos, Lucineide Eliziario Correia; Nunes, Mardjane Alves de Lemos; Moura, Adriana Avila; Lourenço, José; Deng, Xutao; Delwart, Eric L; Guimarães, Maria Raquel Dos Anjos Silva; Pybus, Oliver G; Sabino, Ester C; Faria, Nuno R

    2017-10-01

    We investigated an outbreak of exanthematous illness in Maceió by using molecular surveillance; 76% of samples tested positive for chikungunya virus. Genetic analysis of 23 newly generated genomes identified the East/Central/South African genotype, suggesting that this lineage has persisted since mid-2014 in Brazil and may spread in the Americas and beyond.

  16. Experimental Vaccine for Mosquito-Borne Chikungunya Virus Rates Well in Clinical Study | FNLCR

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya virus, which spread to the U.S. this year, appears to be safe and well-tolerated while offering protection against the virus, according to the results of a first-in-human clinical trial. The vacc

  17. 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.

  18. Surveillance for West Nile, Dengue, and Chikungunya Virus Infections, Veneto Region, Italy, 2010

    PubMed Central

    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

    2012-01-01

    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 PMID:22469230

  19. Persistent Arthralgia Associated with Chikungunya Virus Outbreak, US Virgin Islands, December 2014-February 2016.

    PubMed

    Feldstein, Leora R; Rowhani-Rahbar, Ali; Staples, J Erin; Weaver, Marcia R; Halloran, M Elizabeth; Ellis, Esther M

    2017-04-01

    After the 2014-2015 outbreak of chikungunya virus in the US Virgin Islands, we compared the prevalence of persistent arthralgia among case-patients and controls. Prevalence was higher in case-patients than controls 6 and 12 months after disease onset. Continued vaccine research to prevent acute illness and long-term sequelae is essential.

  20. Persistent Arthralgia Associated with Chikungunya Virus Outbreak, US Virgin Islands, December 2014–February 2016

    PubMed Central

    Rowhani-Rahbar, Ali; Staples, J. Erin; Weaver, Marcia R.; Halloran, M. Elizabeth; Ellis, Esther M.

    2017-01-01

    After the 2014–2015 outbreak of chikungunya virus in the US Virgin Islands, we compared the prevalence of persistent arthralgia among case-patients and controls. Prevalence was higher in case-patients than controls 6 and 12 months after disease onset. Continued vaccine research to prevent acute illness and long-term sequelae is essential. PMID:28322703

  1. 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.

  2. 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.

  3. Nasal Skin Necrosis: An Unexpected New Finding in Severe Chikungunya Fever.

    PubMed

    Torres, Jaime R; Córdova, Leopoldo G; Saravia, Víctor; Arvelaez, Joanne; Castro, Julio S

    2016-01-01

    Three adult Venezuelan patients with virologically confirmed Chikungunya fever, who developed extensive acute nasal skin necrosis early in the course of a life-threatening illness characterized by shock and multiple organ dysfunction syndrome, are discussed. One patient survived and fully recovered. Nasal necrosis has not previously been associated with the disease.

  4. A case of consecutive infection with Zika virus and Chikungunya virus in Bora Bora, French Polynesia.

    PubMed

    Kutsuna, Satoshi; Kato, Yasuyuki; Nakayama, Eri; Taniguchi, Satoshi; Takasaki, Tomohiko; Yamamoto, Kei; Takeshita, Nozomi; Hayakawa, Kayoko; Kanagawa, Shuzo; Ohmagari, Norio

    2017-02-01

    Chikungunya fever (CHIK) and Zika virus (ZIKV) infection have similar endemic areas and clinical manifestations. We report a case of CHIK at 1 year after a ZIKV infection in Bora Bora (French Polynesia), which we diagnosed based on IgM to the CHIK virus and neutralizing antibodies to ZIKV.

  5. Zika, dengue, and chikungunya co-infection in a pregnant woman from Colombia.

    PubMed

    Villamil-Gómez, Wilmer E; Rodríguez-Morales, Alfonso J; Uribe-García, Ana María; González-Arismendy, Edgardo; Castellanos, Jaime E; Calvo, Eliana P; Álvarez-Mon, Melchor; Musso, Didier

    2016-10-01

    The clinical findings of a pregnant woman from Colombia with a triple co-infection caused by dengue, chikungunya, and Zika viruses are described. Weekly obstetric ultrasounds from 14.6 to 29 weeks of gestation were normal. She remains under follow-up and management according to the standard guidelines for the management of Zika virus-infected pregnant women.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26196378

  7. [Confirmed Dengue, Chikungunya and Zika Cases during the Period 2014 to 2016 in Barcelona, Spain].

    PubMed

    González, Roser; Camprubí, Esteve; Fernández, Lidia; Millet, Joan Pau; Peracho, Víctor; Gorrindo, Pilar; Avellanés, Ingrid; Romero, Arancha; Caylà, Joan A

    2017-03-07

    Arbovirus infections are a group of diseases whose incidence is increasing and that entail an important problem for public health. The aim of this study was to describe detected cases of arbovirosis in Barcelona, and surveillance and control actions performed in order to reduce the risk of transmission. Descriptive cross-sectional study of confirmed dengue, chikungunya and Zika cases in Barcelona during 2014-2016 (1st trimester). Suspected cases detected in the city were notified to the Epidemiology Department of the Barcelona Public Health Agency, where an epidemiological survey is undertaken and, if appropriate, Urban Pests Surveillance and Control Department is contacted. They perform an entomological inspection and implement control and monitoring actions. We collected sociodemographical, epidemiological, clinical and entomological variables. In 2014, 50 chikungunya and 20 dengue cases were detected; 25 entomological inspections were carried out in residences and 38 in the street. In 2015, 47 chikungunya, 51 dengue and 2 Zika cases were detected; 27 inspections were carried out in residences and 80 in the street. In 2016, 17 chikungunya, 52 dengue and 48 Zika cases were detected; 50 inspections were carried out in residences and 103 in the street. No autochtonous case was detected. We observed an increasing incidence of arbovirosis cases during the 3-year study period. There was a progressive intensification of vector surveillance and control actions (inspections, sample collection…).

  8. Entomological study of chikungunya infections in the State of Kelantan, Malaysia

    PubMed Central

    Rozilawati, H.; Faudzi, A.Y.; Rahidah, A.A. Siti; Azlina, A.H. Nor; Abdullah, A.G.; Amal, N.M.; Mansor, H. Wan; Hani, H.; Apandi, Y.; Noor, Faezah; Norziyana; Nazni, W.A.; Zairi, J.; Lee, H.L.

    2011-01-01

    Background & objectives: Chikungunya infection has become a public health threat in Malaysia since the 2008 nationwide outbreaks. Aedes albopictus Skuse has been identified as the chikungunya vector in Johor State during the outbreaks. In 2009, several outbreaks had been reported in the State of Kelantan. Entomological studies were conducted in Kelantan in four districts, namely Jeli, Tumpat, Pasir Mas and Tanah Merah to identify the vector responsible for the virus transmission. Methods: CHIKV cases records were obtained from State Health Department, Kelantan and localities involved were identified. Larva survey was conducted to collect the immature mosquito stages. Modified aspirators were used to collect the adult mosquitoes. All samples on dry ice were transferred to laboratory and the presence of the virus was detected using reverse transcriptase PCR. Results: A total of 1,245 mosquito larvae were collected during larval survey and 2,019 adult mosquitoes were collected using aspirator. From these collections, 640 mosquito pools were tested for the presence of CHIKV by RT-PCR but none found positive. Ae. albopictus was the most abundant mosquito collected, followed by Culex sp., Armigeres sp. and Anopheles sp. A total of 2, 814 artificial containers were inspected during the study. Interpretation & conclusions: Since none of the mosquito samples was found to be positive for chikungunya virus, the vector(s) of chikungunya virus in these localities could not be identified. PMID:21727669

  9. Entomological study of chikungunya infections in the State of Kelantan, Malaysia.

    PubMed

    Rozilawati, H; Faudzi, A Y; Rahidah, A A Siti; Azlina, A H Nor; Abdullah, A G; Amal, N M; Mansor, H Wan; Hani, H; Apandi, Y; Noor, Faezah; Norziyana; Nazni, W A; Zairi, J; Lee, H L

    2011-06-01

    Chikungunya infection has become a public health threat in Malaysia since the 2008 nationwide outbreaks. Aedes albopictus Skuse has been identified as the chikungunya vector in Johor State during the outbreaks. In 2009, several outbreaks had been reported in the State of Kelantan. Entomological studies were conducted in Kelantan in four districts, namely Jeli, Tumpat, Pasir Mas and Tanah Merah to identify the vector responsible for the virus transmission. CHIKV cases records were obtained from State Health Department, Kelantan and localities involved were identified. Larva survey was conducted to collect the immature mosquito stages. Modified aspirators were used to collect the adult mosquitoes. All samples on dry ice were transferred to laboratory and the presence of the virus was detected using reverse transcriptase PCR. A total of 1,245 mosquito larvae were collected during larval survey and 2,019 adult mosquitoes were collected using aspirator. From these collections, 640 mosquito pools were tested for the presence of CHIKV by RT-PCR but none found positive. Ae. albopictus was the most abundant mosquito collected, followed by Culex sp., Armigeres sp. and Anopheles sp. A total of 2, 814 artificial containers were inspected during the study. Since none of the mosquito samples was found to be positive for chikungunya virus, the vector(s) of chikungunya virus in these localities could not be identified.

  10. 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.

  11. Ocular involvement associated with an epidemic outbreak of chikungunya virus infection.

    PubMed

    Lalitha, Prajna; Rathinam, Sivakumar; Banushree, Krishnadas; Maheshkumar, Shanmugam; Vijayakumar, Rajendran; Sathe, Padmakar

    2007-10-01

    To study the range of ocular symptoms in a cohort of patients with chikungunya infection. Retrospective, observational case series. Patients attending a tertiary eye care hospital in South India were included in the study. We included adult patients with serologically confirmed chikungunya virus infection who received clinical care at the Aravind Eye Hospital, Madurai, South India. They were assessed for demographic characteristics, ocular symptoms, laboratory parameters, and chikungunya virus infection severity. Patients underwent a complete ophthalmologic examination that included visual acuity, slit-lamp examination, and indirect funduscopic examination. Visual outcome at the end of three months was the main outcome measure. The charts of 37 patients were analyzed based on the clinical picture and the serologic results. Forty patients were included as controls and tested negative. There were 21 males and 16 females with a mean age of 44.17 years. The main ocular symptoms included granulomatous and nongranulomatous anterior uveitis, optic neuritis retrobulbar neuritis, and dendritic lesions. Of the 26 patients who were followed up for three months, the visual acuity improved in 11 patients (42.3%), remained the same in 12 patients (46.15%), and worsened in three patients (11.5%). The main ocular manifestation associated with the recent epidemic outbreak of chikungunya virus infection in South India included granulomatous and nongranulomatous anterior uveitis, optic neuritis, retrobulbar neuritis, and dendritic lesions. The visual prognosis generally was good, with most patients recovering good vision. Further studies are needed to understand the pathogenesis of this disease.

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25061762

  13. Leidos Biomed Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR Staging

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  14. Frederick National Lab Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  15. [Septic shock secondary to non-congenital chikungunya fever in a young infant: A clinical case].

    PubMed

    Méndez-Domínguez, Nina; Achach-Asaf, Jorge Augusto; Basso-García, Luis Manuel; Quiñones-Pacheco, Yazmín Berenice; Gómez-Carro, Salvador

    2016-01-01

    A chikungunya outbreak took place in the State of Yucatan starting in the second half of 2015 OBJECTIVE: To analyse the clinical course of a case of chikungunya in a previously healthy infant, providing practical evidence to guide future diagnoses and treatment during outbreak seasons in endemic areas Clinical manifestation started with a sudden onset of fever and a diffuse macular-papillary erythema, originally treated in the community with non-steroidal anti-inflammatory drugs. Two days later, the fever relapsed with hypoactivity, severe thrombocytopenia and neutropenia (without lymphopenia), respiratory distress, liver dysfunction, sepsis, followed by septic shock with a fatal outcome. IgM test was positive to chikungunya, while her mother tested negative. Pseudomonas aeruginosa was isolated from the blood culture possible due to contamination, without ruling out the possibility of a mixed origin sepsis. Chikungunya is a disease in which the manifestations in neonates and young infants can be severe, and even fatal. It is important to suspect it in this age group at risk of vector contact, in the presence of fever without apparent source of infection and cutaneous manifestations. It is important to use the antipyretics cautiously, considering the possibility of aggravating the underlying infection, and the potential hepatic and haematological damage. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. Activities of proteasome and m-calpain are essential for Chikungunya virus replication.

    PubMed

    Karpe, Yogesh A; Pingale, Kunal D; Kanade, Gayatri D

    2016-10-01

    Replication of many viruses is dependent on the ubiquitin proteasome system. The present study demonstrates that Chikungunya virus replication increases proteasome activity and induces unfolded protein response (UPR) in cultured cells. Further, it was seen that the virus replication was dependent on the activities of proteasomes and m-calpain. Proteasome inhibition induced accumulation of polyubiquitinated proteins and earlier visualization of UPR.

  17. 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.

  18. Long-term sequelae of chikungunya virus disease: A systematic review.

    PubMed

    van Aalst, Mariëlle; Nelen, Charlotte Marieke; Goorhuis, Abraham; Stijnis, Cornelis; Grobusch, Martin Peter

    The acute phase of chikungunya is well documented; less so are its long-term effects. This systematic literature review provides an overview of the currently available data. We performed an electronic search in PubMed/Medline and checked reference lists. We included studies in English on long-term sequelae of chikungunya in adults and on long-term sequelae of congenital infection from 2000 to 2016. Case reports, reviews and studies with a follow-up shorter than 6 weeks were excluded. In total, 37 studies were included; with follow-up periods ranging from 1.5 to 72 months. Most studies were questionnaire-based studies only, in which clinical diagnoses such as arthritis, alopecia and depression were mostly recorded without professional verification. Persisting arthralgia/arthritis (arthralgia/joint stiffness plus joint swelling) was the most frequent problem encountered. Further frequently mentioned sequelae were alopecia and depression. Quality of life was reduced in many for months to years after the acute phase of chikungunya. Female gender, older age, some co-morbidities and the severity of the acute phase were associated with persistent arthralgia. Congenital infection was associated with neurocognitive dysfunctioning in early childhood. Chikungunya leads to (self-perceived) long-term sequelae in a considerable proportion of patients, impacting significantly on quality of life. Long-term chikungunya sequelae must be taken into account when dealing with this disease because of its important effect on public and individual health. Prospective large-scale, long-term studies with objective assessment of signs and symptoms attributed to the disease are needed to optimally quantify and qualify these problems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Viremic profiles in asymptomatic and symptomatic chikungunya fever: a blood transfusion threat?

    PubMed

    Appassakij, Hatsadee; Khuntikij, Paiwon; Kemapunmanus, Marisa; Wutthanarungsan, Rochana; Silpapojakul, Khachornsakdi

    2013-10-01

    The presence of a chikungunya virus (CHIKV) outbreak could have an impact on transfusion safety when there are a large number of infected persons during an epidemic. Serosurveys have found that 3% to 28% of infected persons remain asymptomatic and are potential disseminators of transfusion-associated chikungunya. However, the viremic profiles of asymptomatic chikungunya patients, the major determinant of the transfusion risk, are unknown. Data on CHIKV viremic profiles were obtained from a case-control study carried out in a chikungunya-affected area during the 2009 epidemic in Songkhla, Thailand. CHIKV-infected individuals were classified based on a combination of the patient's history and clinical and laboratory findings. There were 134 laboratory-proven CHIKV-infected cases, of whom 122 (91.0%) were symptomatic and 12 (9.0%) were asymptomatic. The viremic levels in the symptomatic infected individuals peaked on the first 3 days and lasted up to 8 days as defined by viral isolates. CHIKV genomic products were detected as late as Day 17 of illness. The viral loads observed in the symptomatic individuals (median, 5.6 × 10(5) plaque-forming units per milliliter [pfu/mL]; range, 1.3 × 10(1) -2.9 × 10(8) pfu/mL) were higher than but not significantly different from those observed in the viremic asymptomatic individuals (median, 3.4 × 10(3) pfu/mL; range, 8.4 × 10(1) -2.9 × 10(5) pfu/mL [p = 0.22, Wilcoxon test]). CHIKV infection is highly symptomatic and is associated with high-titred viremia. The viremic levels in asymptomatic CHIKV-infected individuals were in the range known to be capable of transmitting the disease to experimental animals. Asymptomatic CHIKV viremia individuals could be potential disseminators of transfusion-associated chikungunya. © 2012 American Association of Blood Banks.

  20. Chikungunya Infection in Hospitalized Febrile Infants Younger Than 3 Months of Age.

    PubMed

    Elenga, Narcisse; Folin, Marion; Vandamme, Yves-Marie; Cuadro-Alvarez, Emma; Long, Laurence; Njuieyon, Falucar; Martin, Elise; Kom-Tchameni, Rémi; Defo, Antoine; Herinantenaina Razafindrakoto, Sitraka; Mrsic, Yajaira; Couppie, Pierre; Nacher, Mathieu; Dufour, Julie

    2017-08-01

    Fever in infants younger than 3 months is generally a cause for concern because of the risk for a serious bacterial infection. The aim of this study was to describe clinical and biologic features of Chikungunya infection in infants <3 months of age hospitalized in Cayenne Hospital during the 2014-2015 outbreak. We performed a preliminary retrospective study followed by a prospective study from March 2014 to February 2015. All infants younger than 3 months presenting with fever and hospitalized in Cayenne Hospital were included. The main diagnostic criteria were fever and positive Chikungunya polymerase chain reaction. One hundred and twenty infants were hospitalized with fever. The mean age was 46 days (standard deviation ± 22 days). The mean hospitalization duration was 7.4 days (standard deviation ± 6.1 days). Chikungunya infection was diagnosed in 26 children. The most important clinical findings were high [80.8% (77.5-84)] and prolonged fever [76.9% (73.4-80.4)], irritability [96.2% (94.5-97.7)] and skin rash [69.2% (65.4-73)]. Half of the infants presented edema of the extremities (hands and feet principally). However, in 15% of infants, Chikungunya infection was associated with a serious bacterial infection. Infants who presented with irritability, high fever and elevated PCT were at high risk for Chikungunya: OR 39 (9.2-243; P < .001), with a specificity of 96.7% and a negative predictive value of 89.4%. The area of the receiver operating characteristic curve was 0.96. Our results confirm that Chikunguyna infection is a cause of high fever in infants younger than 3 months. Our data should be confirmed by larger studies.

  1. Cardiovascular involvement and manifestations of systemic Chikungunya virus infection: A systematic review

    PubMed Central

    Alvarez, María Fernanda; Bolívar-Mejía, Adrián; Rodriguez-Morales, Alfonso J.; Ramirez-Vallejo, Eduardo

    2017-01-01

    Background: In the last three years, chikungunya virus disease has been spreading, affecting particularly the Americas, producing more than two million cases. In this setting, not only new disease-related epidemiological patterns have been found, but also new clinical findings have been reported by different research groups. These include findings on the cardiovascular system, including clinical, electrocardiographic and echocardiographic alterations. No previous systemic reviews have been found in major databases about it. Methods: We performed a systematic review looking for reports about cardiovascular compromise during chikungunya disease. Cardiac compromise is not so common in isolated episodes; but countries where chikungunya virus is an epidemic should be well informed about this condition. We used 6 bibliographical databases as resources: Medline/Pubmed, Embase, ScienceDirect, ClinicalKey, Ovid and SciELO. Dengue reports on cardiovascular compromise were included as well, to compare both arbovirus’ organic compromises. Articles that delved mainly into the rheumatic articular and cutaneous complications were not considered, as they were not in line with the purpose of this study. The type of articles included were reviews, meta-analyses, case-controls, cohort studies, case reports and case series. This systematic review does not reach or performed a meta-analysis. Results: Originally based on 737 articles, our reviewed selected 40 articles with 54.2% at least mentioning CHIKV cardiovascular compromise within the systemic compromise. Cardiovascular manifestations can be considered common and have been reported in France, India, Sri Lanka, Malaysia, Colombia, Venezuela and USA, including mainly, but no limited to: hypotension, shock and circulatory collapse, Raynaud phenomenon, arrhythmias, murmurs, myocarditis, dilated cardiomyopathy, congestive insufficiency, heart failure and altered function profile (Troponins, CPK). Conclusions: Physicians should be

  2. Unusual pattern of chikungunya virus epidemic in the Americas, the Panamanian experience

    PubMed Central

    Denis, Bernardino; Barahona de Mosca, Itza; Rodriguez, Dennys; Cedeño, Israel; Arauz, Dimelza; González, Publio; Cerezo, Lizbeth; Moreno, Lourdes; García, Lourdes; Sáenz, Lisseth E.; Atencio, María Aneth; Rojas-Fermin, Eddy; Vizcaino, Fernando; Perez, Nicolas; Moreno, Brechla; López-Vergès, Sandra; Valderrama, Anayansi; Armién, Blas

    2017-01-01

    Background Chikungunya virus (CHIKV) typically causes explosive epidemics of fever, rash and polyarthralgia after its introduction into naïve populations. Since its introduction in Panama in May of 2014, few autochthonous cases have been reported; most of them were found within limited outbreaks in Panama City in 2014 and Puerto Obaldia town, near the Caribbean border with Colombia in 2015. In order to confirm that Panama had few CHIKV cases compared with neighboring countries, we perform an epidemiological analysis of chikungunya cases reported from May 2014 to July 2015. Moreover, to understand this paucity of confirmed CHIKV cases, a vectorial analysis in the counties where these cases were reported was performed. Methods Chikungunya cases were identified at medical centers and notified to health authorities. Sera samples were analyzed at Gorgas Memorial Institute for viral RNA and CHIKV-specific antibody detection. Results A total of 413 suspected cases of CHIKV infections were reported, with incidence rates of 0.5 and 0.7 per 100,000 inhabitants in 2014 and 2015, respectively. During this period, 38.6% of CHIKV cases were autochthonous with rash and polyarthralgia as predominant symptoms. CHIKV and DENV incidence ratios were 1:306 and 1:34, respectively. A phylogenetic analysis of E1/E2 genomic segment indicates that the outbreak strains belong to the Asian genotype and cluster together with CHIKV isolates from other American countries during the same period. Statistical analysis of the National Vector Control program at the district level shows low and medium vector infestation level for most of the counties with CHIKV cases. This index was lower than for neighboring countries. Conclusions Previous training of clinical, laboratory and vector workers allowed a good caption and detection of the chikungunya cases and fast intervention. It is possible that low/medium vector infestation level could explain in part the paucity of chikungunya infections in Panama

  3. Chikungunya virus: an update on the biology and pathogenesis of this emerging pathogen.

    PubMed

    Burt, Felicity J; Chen, Weiqiang; Miner, Jonathan J; Lenschow, Deborah J; Merits, Andres; Schnettler, Esther; Kohl, Alain; Rudd, Penny A; Taylor, Adam; Herrero, Lara J; Zaid, Ali; Ng, Lisa F P; Mahalingam, Suresh

    2017-04-01

    Re-emergence of chikungunya virus, a mosquito-transmitted pathogen, is of serious public health concern. In the past 15 years, after decades of infrequent, sporadic outbreaks, the virus has caused major epidemic outbreaks in Africa, Asia, the Indian Ocean, and more recently the Caribbean and the Americas. Chikungunya virus is mainly transmitted by Aedes aegypti mosquitoes in tropical and subtropical regions, but the potential exists for further spread because of genetic adaptation of the virus to Aedes albopictus, a species that thrives in temperate regions. Chikungunya virus represents a substantial health burden to affected populations, with symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. The inflammatory response coincides with raised levels of immune mediators and infiltration of immune cells into infected joints and surrounding tissues. Animal models have provided insights into disease pathology and immune responses. Although host innate and adaptive responses have a role in viral clearance and protection, they can also contribute to virus-induced immune pathology. Understanding the mechanisms of host immune responses is essential for the development of treatments and vaccines. Inhibitory compounds targeting key inflammatory pathways, as well as attenuated virus vaccines, have shown some success in animal models, including an attenuated vaccine strain based on an isolate from La Reunion incorporating an internal ribosome entry sequence that prevents the virus from infecting mosquitoes and a vaccine based on virus-like particles expressing envelope proteins. However, immune correlates of protection, as well as the safety of prophylactic and therapeutic candidates, are important to consider for their application in chikungunya infections. In this Review, we provide an update on chikungunya virus with regard to its epidemiology, molecular virology, virus-host interactions

  4. Diagnosis of Chikungunya dominated co-infection with dengue during an outbreak in south India (2010 and 2012).

    PubMed

    Venkatasubramani, K; Paramasivan, R; Thenmozhi, V; Dhananjeyan, K J; Balaji, T; Leo, S Victor Jerald

    2015-07-01

    Following a report of dengue outbreak from January 2010 to 2012 in the Tirunelveli, Theni, Dharmapuri and Thiruvallur districts of Tamil Nadu state, India, an investigation was carried out. The study was to demonstrate the probable presence of Chikungunya viral antibodies in patients clinically suspected of dengue fever. Out of 331 samples analysed, dengue viral antibodies were observed in 14.8% (n = 49) of patients, while 16.6% (n = 55) were positive for Chikungunya viral specific IgM antibodies. In the four districts surveyed, patients found positive for Chikungunya were found to be higher than dengue. The clinician should consider Chikungunya in the differential diagnosis of dengue-like infection appearing in the community.

  5. 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].

  6. 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.

  7. Concurrent outbreaks of Chikungunya and Dengue fever in Kandy, Sri Lanka, 2006-07: a comparative analysis of clinical and laboratory features.

    PubMed

    Kularatne, S A M; Gihan, M C; Weerasinghe, S C; Gunasena, S

    2009-07-01

    To compare the clinical and laboratory features of confirmed cases of Chikungunya and Dengue fever; to validate the clinical diagnosis based on serology. Cases with a clinical diagnosis of Chikungunya and Dengue fever were recruited for seroconfirmation during a concurrent epidemic in 2006-07, at the General Hospital, Peradeniya, Sri Lanka. Of 54 patients with fever, serology confirmed 21 with Chikungunya infection, 20 with Dengue infection, and three co-infections, with sensitivity of the clinical diagnosis of 92% for Chikungunya fever and 95% for Dengue fever. The mean age of patients with Chikungunya fever was 45 years (range 21-74 years), and patients with Dengue fever was 30 years (range 15-63 years) (p = 0.005). Sixteen (70%) of Chikungunya fever patients were females, while 15 (71%) of those with Dengue fever were males (p = 0.007). Arthralgia was common to both groups (p = 0.155), while headache and a bleeding tendency were observed more in patients with Dengue fever. Twelve (57%) Chikungunya cases had acute arthritis compared with none in the Dengue group (p = 0.001), lasting mean 6 days (range 1-14 days). They developed chronic arthritic disability (range 1-6 months). Leucopenia was common to both Chikungunya and Dengue fever patients. However, thrombocytopenia was more pronounced in the Dengue patients (mean (SD) platelet count 75 (34)x10(9)/l) than in the Chikungunya patients (117 (70)x10(9)/l) (p = 0.001). In the Chikungunya group there was a positive correlation between duration of the illness and the platelet count (r = 0.181, p = 0.194), but the Dengue group showed a negative correlation (r = -0.309, p<0.001). Most of the clinical and laboratory features of patients with Chikungunya and Dengue fever are similar. Arthritis is the pathognomonic sign in patients with Chikungunya fever.

  8. PDGFRA-mutant syndrome.

    PubMed

    Ricci, Riccardo; Martini, Maurizio; Cenci, Tonia; Carbone, Arnaldo; Lanza, Paola; Biondi, Alberto; Rindi, Guido; Cassano, Alessandra; Larghi, Alberto; Persiani, Roberto; Larocca, Luigi M

    2015-07-01

    Germline PDGFRA mutations cause multiple heterogeneous gastrointestinal mesenchymal tumors. In its familial form this disease, which was formerly termed intestinal neurofibromatosis/neurofibromatosis 3b (INF/NF3b), has been included among familial gastrointestinal stromal tumors (GISTs) because of its genotype, described when GIST was the only known PDGFRA-mutant gastrointestinal tumor. Shortly afterwards, however, inflammatory fibroid polyps also revealed PDGFRA mutations. Subsequently, gastrointestinal CD34+ 'fibrous tumors' of uncertain classification were described in a germline PDGFRA-mutant context. Our aim was to characterize the syndrome produced by germline PDGFRA mutations and establish diagnostic criteria and management strategies for this hitherto puzzling disease. We studied a kindred displaying multiple gastrointestinal mesenchymal tumors, comparing it with published families/individuals with possible analogous conditions. We identified a novel inherited PDGFRA mutation (P653L), constituting the third reported example of familial PDGFRA mutation. In adult mutants we detected inflammatory fibroid polyps, gastric GISTs and gastrointestinal fibrous tumors of uncertain nosology. We demonstrate that the syndrome formerly defined as INF/NF3b (exemplified by the family reported herein) is simplistically considered a form of familial GIST, because inflammatory fibroid polyps often prevail. Fibrous tumors appear variants of inflammatory fibroid polyps. 'INF/NF3b' and 'familial GIST' are misleading terms which we propose changing to 'PDGFRA-mutant syndrome'. In this condition, unlike KIT-dependent familial GIST syndromes, if present, GISTs are stomach-restricted and diffuse Cajal cell hyperplasia is not observed. This restriction of GISTs to the stomach in PDGFRA-mutant syndrome: (i) focuses oncological concern on gastric masses, as inflammatory fibroid polyps are benign; (ii) supports a selective role of gastric environment for PDGFRA mutations to elicit GISTs

  9. Inhibitors of alphavirus entry and replication identified with a stable Chikungunya replicon cell line and virus-based assays.

    PubMed

    Pohjala, Leena; Utt, Age; Varjak, Margus; Lulla, Aleksei; Merits, Andres; Ahola, Tero; Tammela, Päivi

    2011-01-01

    Chikungunya virus (CHIKV), an alphavirus, has recently caused epidemic outbreaks and is therefore considered a re-emerging pathogen for which no effective treatment is available. In this study, a CHIKV replicon containing the virus replicase proteins together with puromycin acetyltransferase, EGFP and Renilla luciferase marker genes was constructed. The replicon was transfected into BHK cells to yield a stable cell line. A non-cytopathic phenotype was achieved by a Pro718 to Gly substitution and a five amino acid insertion within non-structural protein 2 (nsP2), obtained through selection for stable growth. Characterization of the replicon cell line by Northern blotting analysis revealed reduced levels of viral RNA synthesis. The CHIKV replicon cell line was validated for antiviral screening in 96-well format and used for a focused screen of 356 compounds (natural compounds and clinically approved drugs). The 5,7-dihydroxyflavones apigenin, chrysin, naringenin and silybin were found to suppress activities of EGFP and Rluc marker genes expressed by the CHIKV replicon. In a concomitant screen against Semliki Forest virus (SFV), their anti-alphaviral activity was confirmed and several additional inhibitors of SFV with IC₅₀ values between 0.4 and 24 µM were identified. Chlorpromazine and five other compounds with a 10H-phenothiazinyl structure were shown to inhibit SFV entry using a novel entry assay based on a temperature-sensitive SFV mutant. These compounds also reduced SFV and Sindbis virus-induced cytopathic effect and inhibited SFV virion production in virus yield experiments. Finally, antiviral effects of selected compounds were confirmed using infectious CHIKV. In summary, the presented approach for discovering alphaviral inhibitors enabled us to identify potential lead structures for the development of alphavirus entry and replication phase inhibitors as well as demonstrated the usefulness of CHIKV replicon and SFV as biosafe surrogate models for anti

  10. Chikungunya Infection in India: Results of a Prospective Hospital Based Multi-Centric Study

    PubMed Central

    Ray, Pratima; Ratagiri, Vinod H.; Kabra, Sushil K.; Lodha, Rakesh; Sharma, Sumit; Sharma, B. S.; Kalaivani, Mani; Wig, Naveet

    2012-01-01

    Background Chikungunya (CHIKV) has recently seen a re-emergence in India with high morbidity. However, the epidemiology and disease burden remain largely undetermined. A prospective multi-centric study was conducted to evaluate clinical, epidemiological and virological features of chikugunya infection in patients with acute febrile illness from various geographical regions of India. Methods and Findings A total of 540 patients with fever of up to 7days duration were enrolled at Karnataka Institute of Medical Sciences (KIMS), Karnataka (South); Sawai Man Singh Medical College (SMS) Rajasthan (West), and All India Institute of Medical Sciences (AIIMS) New Delhi (North) from June 2008 to May 2009. Serum specimens were screened for chikungunya infection concurrently through RT-PCR and serology (IgM). Phylogenetic analysis was performed using Bioedit and Mega2 programs. Chikungunya infection was detected in 25.37% patients by RT-PCR and/or IgM-ELISA. Highest cases were detected in south (49.36%) followed by west (16.28%) and north (0.56%) India. A difference in proportion of positives by RT-PCR/ELISA with regard to duration of fever was observed (p<0.05). Rashes, joint pain/swelling, abdominal pain and vomiting was frequently observed among chikungunya confirmed cases (p<0.05). Adults were affected more than children. Anti-CHIK antibodies (IgM) were detected for more than 60days of fever onset. Phylogenetic analysis based on E1 gene from KIMS patients (n = 15) revealed ∼99% homology clustering with Central/East African genotype. An amino acid change from lysine to glutamine at position 132 of E1 gene was frequently observed among strains infecting children. Conclusions The study documented re-emergence of chikungunya in high frequencies and severe morbidity in south and west India but rare in north. The study emphasizes the need for continuous surveillance for disease burden using multiple diagnostic tests and also warrants the need for an appropriate molecular

  11. Dengue and Chikungunya Fever among Viral Diseases in Outpatient Febrile Children in Kilosa District Hospital, Tanzania

    PubMed Central

    Chipwaza, Beatrice; Mugasa, Joseph P.; Selemani, Majige; Amuri, Mbaraka; Mosha, Fausta; Ngatunga, Steve D.; Gwakisa, Paul S.

    2014-01-01

    Introduction Viral etiologies of fever, including dengue, Chikungunya, influenza, rota and adeno viruses, cause major disease burden in tropical and subtropical countries. The lack of diagnostic facilities in developing countries leads to failure to estimate the true burden of such illnesses, and generally the diseases are underreported. These diseases may have similar symptoms with other causes of acute febrile illnesses including malaria and hence clinical diagnosis without laboratory tests can be difficult. This study aimed to identify viral etiologies as a cause of fever in children and their co-infections with malaria. Methods A cross sectional study was conducted for 6 months at Kilosa district hospital, Tanzania. The participants were febrile children aged 2–13 years presented at the outpatient department. Diagnostic tests such as IgM and IgG ELISA, and PCR were used. Results A total of 364 patients were enrolled, of these 83(22.8%) had malaria parasites, 76 (20.9%) had presumptive acute dengue infection and among those, 29(38.2%) were confirmed cases. Dengue was more likely to occur in children ≥ 5 years than in <5 years (OR 2.28, 95% CI: 1.35–3.86). Presumptive acute Chikungunya infection was identified in 17(4.7%) of patients. We observed no presenting symptoms that distinguished patients with Chikungunya infection from those with dengue infection or malaria. Co-infections between malaria and Chikungunya, malaria and dengue fever as well as Chikungunya and dengue were detected. Most patients with Chikungunya and dengue infections were treated with antibacterials. Furthermore, our results revealed that 5(5.2%) of patients had influenza virus while 5(12.8%) had rotavirus and 2(5.1%) had adenovirus. Conclusion Our results suggest that even though viral diseases are a major public health concern, they are not given due recognition as a cause of fever in febrile patients. Emphasis on laboratory diagnostic tests for proper diagnosis and management of

  12. [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

  13. Brassinosteroid Mutants of Crops.

    PubMed

    Bishop, Gerard J.

    2003-12-01

    Plant steroid hormones, brassinosteroids (BRs), were originally isolated from extracts of pollen because of their growth-promoting properties and their potential use for enhancing crop production. Mutants in the biosynthesis, metabolism, and signaling of brassinolide (BL), the most bioactive BR, are important resources in helping to establish BRs' essential role in plant growth and development. The dark green and distinctive dwarf phenotype of BR-related mutants identified in pea, tomato, and rice highlights the importance of BRs in crops. These mutants are helping to elucidate both the conserved and the unique features of BR biosynthesis and signaling. Such insights are providing the key knowledge and understanding that will enable the development of strategies towards the production of crops with enhanced qualities.

  14. Emerging Causes of Arbovirus Encephalitis in North America: Powassan, Chikungunya, and Zika Viruses.

    PubMed

    Doughty, Christopher T; Yawetz, Sigal; Lyons, Jennifer

    2017-02-01

    Arboviruses are arthropod-borne viruses transmitted by the bite of mosquitoes, ticks, or other arthropods. Arboviruses are a common and an increasing cause of human illness in North America. Powassan virus, Chikungunya virus, and Zika virus are arboviruses that have all recently emerged as increasing causes of neurologic illness. Powassan virus almost exclusively causes encephalitis, but cases are rare, sporadic, and restricted to portions of North America and Russia. Chikungunya virus has spread widely across the world, causing millions of infections. Encephalitis is a rare manifestation of illness but is more common and severe in neonates and older adults. Zika virus has recently spread through much of the Americas and has been associated mostly with microcephaly and other congenital neurologic complications. Encephalitis occurring in infected adults has also been recently reported. This review will discuss the neuropathogenesis of these viruses, their transmission and geographic distribution, the spectrum of their neurologic manifestations, and the appropriate method of diagnosis.

  15. 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.

  16. 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.

  17. [Chikungunya fever in Mexico: confirmed case and notes on the epidemiologic response].

    PubMed

    Rivera-Ávila, Roberto Carlos

    2014-01-01

    Chikungunya fever (CHIK) is a viral disease transmitted to human beings by the same vector as dengue -the Aedes mosquito. Besides fever and severe pain in the joints, it produces other symptoms such as myalgias, headache, nausea, fatigue and exanthema. There is no specific treatment for it; the therapeutic management of patients focuses on symptom relief. Historically, outbreaks of large proportions have been reported; even since 2010 it was considered to be a potential emerging epidemic. In 2013 it was introduced into the islands of the Caribbean, and it has recently been reported in the American continent. This paper describes the first confirmed case of chikungunya in Mexico -in the municipality of Tlajomulco de Zúñiga, Jalisco, in May, 2014-, which was imported from the Caribbean island of Antigua and Barbuda by a 39 year-old woman.

  18. Detection of Wolbachia in Aedes albopictus and Their Effects on Chikungunya Virus

    PubMed Central

    Ahmad, Noor Afizah; Vythilingam, Indra; Lim, Yvonne A. L.; Zabari, Nur Zatil Aqmar M.; Lee, Han Lim

    2017-01-01

    Wolbachia-based vector control strategies have been proposed as a means to augment the currently existing measures for controlling dengue and chikungunya vectors. Prior to utilizing Wolbachia as a novel vector control strategy, it is crucial to understand the Wolbachia–mosquito interactions. In this study, field surveys were conducted to screen for the infection status of Wolbachia in field-collected Aedes albopictus. The effects of Wolbachia in its native host toward the replication and dissemination of chikungunya virus (CHIKV) was also studied. The prevalence of Wolbachia-infected field-collected Ae. albopictus was estimated to be 98.6% (N = 142) for females and 95.1% (N = 102) for males in the population studied. The Ae. albopictus were naturally infected with both wAlbA and wAlbB strains. We also found that the native Wolbachia has no impact on CHIKV infection and minimal effect on CHIKV dissemination to secondary organs. PMID:27920393

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26416113

  20. Chikungunya fever: Atypical and lethal cases in the Western hemisphere: A Venezuelan experience.

    PubMed

    Torres, Jaime R; Leopoldo Códova G; Castro, Julio S; Rodríguez, Libsen; Saravia, Víctor; Arvelaez, Joanne; Ríos-Fabra, Antonio; Longhi, María A; Marcano, Melania

    2015-01-01

    A large epidemic of Chikungunya fever currently affects the Caribbean, Central and South America. Despite a high number of reported cases, little is known on the occurrence of severe clinical complications. We describe four Venezuelan patients with a severe and/or lethal course who exhibit unusual manifestations of the disease. Case 1 describes a 75 year-old man with rapid onset of septic shock and multi-organ failure. Cases 2 and 3 describe two patients with rapid aggressive clinical course who developed shock, severe purpuric lesions and a distinct area large of necrosis in the nasal region. Case 4 depicts a splenectomized woman with shock, generalized purpuric lesions, bullous dermatosis and acronecrosis of an upper limb. Chikungunya fever in the Western hemisphere may also associate with atypical and severe manifestations. Some patients experience a life-threatening, aggressive clinical course, with rapid deterioration and death due to multisystem failure.

  1. [Chikungunya, an emerging viral disease. Proposal of an algorithm for its clinical management].

    PubMed

    Palacios-Martínez, D; Díaz-Alonso, R A; Arce-Segura, L J; Díaz-Vera, E

    2015-01-01

    Chikungunya fever (CHIK) is an emerging viral disease. It is caused by the Chikungunya virus, an alphavirus from the Togaviridae family. It is transmitted to humans by the bite of infected mosquitoes, mainly Aedes aegypti and Aedes albopictus. They are also involved in the transmission of dengue, malaria, etc. CHIK is now endemic in any region of Africa and Southeast-Asia. Cases of CHIK have been reported in America, the Caribbean, and Europe (France, Italy and Spain). There are reservoirs of these mosquitoes in some regions of Spain (Catalonia, Alicante, Murcia and Balearic islands). CHIK is characterized by a sudden high and debilitating fever, and severe or disabling symmetrical arthralgia. It tends to improve in days or weeks. There are severe and chronic forms of CHIK. There is no specific treatment or prophylaxis for CHIK. An algorithm is proposed for the clinical management of CHIK based in the latest guidelines.

  2. 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.

  3. [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.

  4. Evaluation of three commercially-available chikungunya virus immunoglobulin G immunoassays.

    PubMed

    De Salazar, Pablo M; Valadere, Anne Marie; Goodman, Christin H; Johnson, Barbara W

    2017-08-21

    The emergence of chikungunya virus in the Americas means the affected population is at risk of developing severe, chronic, rheumatologic disease, even months after acute infection. Accurate diagnostic methods for past infections are essential for differential diagnosis and consequence management. This study evaluated three commercially-available chikungunya Immunoglobulin G immunoassays by comparing them to an in-house Enzyme-Linked ImmunoSorbent Assay conducted by the Centers for Disease Control and Prevention (Atlanta, Georgia, United States). Results showed sensitivity and specificity values ranging from 92.8% - 100% and 81.8% - 90.9%, respectively, with a significant number of false-positives ranging from 12.5% - 22%. These findings demonstrate the importance of evaluating commercial kits, especially regarding emerging infectious diseases whose medium and long-term impact on the population is unclear.

  5. Dengue infection in the nervous system: lessons learned for Zika and Chikungunya.

    PubMed

    Puccioni-Sohler, Marzia; Roveroni, Natalia; Rosadas, Carolina; Ferry, Fernando; Peralta, Jose Mauro; Tanuri, Amilcar

    2017-02-01

    Dengue, Zika and Chikungunya are emerging arboviruses and important causes of acute febrile disease in tropical areas. Although dengue does not represent a new condition, a geographic expansion over time has occurred with the appearance of severe neurological complications. Neglect has allowed the propagation of the vector (Aedes spp), which is also responsible for the transmission of other infections such as Zika and Chikungunya throughout the world. The increased number of infected individuals has contributed to the rise of neurological manifestations including encephalitis, myelitis, meningitis, Guillain-Barré syndrome and congenital malformations such as microcephaly. In this narrative review, we characterize the impact of the geographic expansion of the vector on the appearance of neurological complications, and highlight the lack of highly accurate laboratory tests for nervous system infections. This represents a challenge for public health in the world, considering the high number of travelers and people living in endemic areas.

  6. Surveillance of deaths caused by arboviruses in Brazil: from dengue to chikungunya

    PubMed Central

    Cavalcanti, Luciano Pamplona de Góes; Freitas, André Ricardo Ribas; Brasil, Patrícia; da Cunha, Rivaldo Venâncio

    2017-01-01

    Did death occur DUE TO dengue, or in a patient WITH dengue virus infection? It seems a matter of semantics, but in fact, it underscores how challenging it is to distinguish whether the disease contributed to death, or was itself the underlying cause of death. Can a death be attributed to chikungunya virus, when some deaths occur after the acute phase? Did the virus decompensate the underlying diseases, leading to death? Did prolonged hospitalisation lead to infection, resulting in the patient’s progression to death? Were there iatrogenic complications during patient care? The dengue question, for which there has not yet been a definitive response, resurfaces prominently under the chikungunya surveillance scenario. We are facing an epidemic of a disease that seems to be more lethal than previously thought. The major challenge ahead is to investigate deaths suspected of occurring due to arbovirus infections and to understand the role of each infection in the unfavourable outcome. PMID:28767985

  7. A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs

    PubMed Central

    Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F.; Lecuit, Marc

    2016-01-01

    Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310

  8. Mutant fatty acid desaturase

    DOEpatents

    Shanklin, John; Cahoon, Edgar B.

    2004-02-03

    The present invention relates to a method for producing mutants of a fatty acid desaturase having a substantially increased activity towards fatty acid substrates with chains containing fewer than 18 carbons relative to an unmutagenized precursor desaturase having an 18 carbon atom chain length substrate specificity. The method involves inducing one or more mutations in the nucleic acid sequence encoding the precursor desaturase, transforming the mutated sequence into an unsaturated fatty acid auxotroph cell such as MH13 E. coli, culturing the cells in the absence of supplemental unsaturated fatty acids, thereby selecting for recipient cells which have received and which express a mutant fatty acid desaturase with an elevated specificity for fatty acid substrates having chain lengths of less than 18 carbon atoms. A variety of mutants having 16 or fewer carbon atom chain length substrate specificities are produced by this method. Mutant desaturases produced by this method can be introduced via expression vectors into prokaryotic and eukaryotic cells and can also be used in the production of transgenic plants which may be used to produce specific fatty acid products.

  9. Long-term persistence of Chikungunya virus neutralizing antibodies in human populations of North Eastern Thailand.

    PubMed

    Nitatpattana, Narong; Kanjanopas, Kobkan; Yoksan, Sutee; Satimai, Wichai; Vongba, Narong; Langdatsuwan, Sasiporn; Nakgoi, Khajornpong; Ratchakum, Supot; Wauquier, Nadia; Souris, Marc; Auewarakul, Prasert; Gonzalez, Jean-Paul

    2014-10-21

    Chikungunya virus (CHIKV) outbreak recurrences in Thailand are unpredictable and separated by unexplained and often long silent epidemiological periods that can last for several years. These silent periods could be explained in part by the fact that infection with one CHIKV strain confers lasting natural immunity, even against other CHIKV strains. In this study we evaluated the persistence of CHIKV-specific neutralizing antibodies in the population of Chumpae District, Khon Kaen Province, nineteen years after a CHIKV outbreak occurred in the same area in 1991. Overall 39% (44/111) of 111 former patients had neutralizing antibodies reacting against CHIKV ECSA strain. Consistently high titers of neutralizing antibodies were found in 75% (33/44) of all positively-reacting sera, 70% of which (23/33) were collected from individuals amongst the >60 years old age group. Although the prevalence found in Pong Haeng village (70%) was significantly higher than the prevalence detected in the Nong Thum village (14%), control study villages without known previous Chikungunya epidemics had a high Chikungunya neutralizing antibody prevalence (65%). More than one-third of the pre-exposed population had persisting natural immunity that was more likely boosted by recent and repetitive exposure to the emerging ECSA CHIKV in Thailand. Also, Chikungunya virus appears to largely circulate in the country with a great variability appears between villages or area probably associated with the vector abundance and efficiency. Altogether these results show a potential for a lifelong immunity against CHIKV. Given the rapid spread of the highly pathogenic ECSA strain in Southern Thailand, the development of CHIK vaccine is strongly recommended.

  10. Chikungunya Virus-associated Long-term Arthralgia: A 36-month Prospective Longitudinal Study

    PubMed Central

    Madec, Yoann; Carpentier, Florence; Kassab, Somar; Albert, Matthew L.; Lecuit, Marc; Michault, Alain

    2013-01-01

    Background Arthritogenic alphaviruses, including Chikungunya virus (CHIKV), are responsible for acute fever and arthralgia, but can also lead to chronic symptoms. In 2006, a Chikungunya outbreak occurred in La Réunion Island, during which we constituted a prospective cohort of viremic patients (n = 180) and defined the clinical and biological features of acute infection. Individuals were followed as part of a longitudinal study to investigate in details the long-term outcome of Chikungunya. Methodology/Principal Findings Patients were submitted to clinical investigations 4, 6, 14 and 36 months after presentation with acute CHIKV infection. At 36 months, 22 patients with arthralgia and 20 patients without arthralgia were randomly selected from the cohort and consented for blood sampling. During the 3 years following acute infection, 60% of patients had experienced symptoms of arthralgia, with most reporting episodic relapse and recovery periods. Long-term arthralgias were typically polyarthralgia (70%), that were usually symmetrical (90%) and highly incapacitating (77%). They were often associated with local swelling (63%), asthenia (77%) or depression (56%). The age over 35 years and the presence of arthralgia 4 months after the disease onset are risk factors of long-term arthralgia. Patients with long-term arthralgia did not display biological markers typically found in autoimmune or rheumatoid diseases. These data helped define the features of CHIKV-associated chronic arthralgia and permitted an estimation of the economic burden associated with arthralgia. Conclusions/Significance This study demonstrates that chronic arthralgia is a frequent complication of acute Chikungunya disease and suggests that it results from a local rather than systemic inflammation. PMID:23556021

  11. Performance of the RealStar Chikungunya Virus Real-Time Reverse Transcription-PCR Kit▿

    PubMed Central

    Panning, Marcus; Hess, Markus; Fischer, Waldemar; Grywna, Klaus; Pfeffer, Martin; Drosten, Christian

    2009-01-01

    A novel commercial Chikungunya virus real-time reverse transcription-PCR (RT-PCR) kit was evaluated on a comprehensive panel of original patient samples. The assay was 100% sensitive and specific in comparison to a published real-time RT-PCR. Viral loads from both assays were highly correlated. The kit proved to be suitable for routine use in patient care. PMID:19625474

  12. Autochthonous Transmission of East/Central/South African Genotype Chikungunya Virus, Brazil.

    PubMed

    Cunha, Marcela S; Cruz, Nádia V G; Schnellrath, Laila C; Medaglia, Maria Luiza Gomes; Casotto, Michele E; Albano, Rodolpho M; Costa, Luciana J; Damaso, Clarissa R

    2017-10-01

    We isolated East/Central/South African genotype chikungunya virus during the 2016 epidemic in Rio de Janeiro, Brazil. Genome sequencing revealed unique mutations in the nonstructural protein 4 (NSP4-A481D) and envelope protein 1 (E1-K211T). Moreover, all Brazil East/Central/South isolates shared the exclusive mutations E1-M407L and E2-A103T.

  13. 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.

  14. A large-scale stochastic spatiotemporal model for Aedes albopictus-borne chikungunya epidemiology

    PubMed Central

    Chandra, Nastassya L.; Proestos, Yiannis; Lelieveld, Jos; Christophides, George K.; Parham, Paul E.

    2017-01-01

    Chikungunya is a viral disease transmitted to humans primarily via the bites of infected Aedes mosquitoes. The virus caused a major epidemic in the Indian Ocean in 2004, affecting millions of inhabitants, while cases have also been observed in Europe since 2007. We developed a stochastic spatiotemporal model of Aedes albopictus-borne chikungunya transmission based on our recently developed environmentally-driven vector population dynamics model. We designed an integrated modelling framework incorporating large-scale gridded climate datasets to investigate disease outbreaks on Reunion Island and in Italy. We performed Bayesian parameter inference on the surveillance data, and investigated the validity and applicability of the underlying biological assumptions. The model successfully represents the outbreak and measures of containment in Italy, suggesting wider applicability in Europe. In its current configuration, the model implies two different viral strains, thus two different outbreaks, for the two-stage Reunion Island epidemic. Characterisation of the posterior distributions indicates a possible relationship between the second larger outbreak on Reunion Island and the Italian outbreak. The model suggests that vector control measures, with different modes of operation, are most effective when applied in combination: adult vector intervention has a high impact but is short-lived, larval intervention has a low impact but is long-lasting, and quarantining infected territories, if applied strictly, is effective in preventing large epidemics. We present a novel approach in analysing chikungunya outbreaks globally using a single environmentally-driven mathematical model. Our study represents a significant step towards developing a globally applicable Ae. albopictus-borne chikungunya transmission model, and introduces a guideline for extending such models to other vector-borne diseases. PMID:28362820

  15. Virus Isolation and Preparation of Sucrose-Banded Chikungunya Virus Samples for Transmission Electron Microscopy.

    PubMed

    Lim, Chang-Kweng

    2016-01-01

    Virus isolation and purification is an invaluable technique in virology to detect and characterize viruses. This chapter describes a large-scale Chikungunya virus (CHIKV) propagation and purification methods by using discontinuous sucrose gradient, and sample preparation for transmission electron microscopy. Sucrose-banding yields large quantities of high-titer (10(10) pfu/ml) CHIKV stocks. Such stocks are stable for years when stored at -70 °C.

  16. Investigation of twenty selected medicinal plants from Malaysia for anti-Chikungunya virus activity.

    PubMed

    Chan, Yik Sin; Khoo, Kong Soo; Sit, Nam Weng Weng

    2016-09-01

    Chikungunya virus is a reemerging arbovirus transmitted mainly by Aedes mosquitoes. As there are no specific treatments available, Chikungunya virus infection is a significant public health problem. This study investigated 120 extracts from selected medicinal plants for anti-Chikungunya virus activity. The plant materials were subjected to sequential solvent extraction to obtain six different extracts for each plant. The cytotoxicity and antiviral activity of each extract were examined using African monkey kidney epithelial (Vero) cells. The ethanol, methanol and chloroform extracts of Tradescantia spathacea (Commelinaceae) leaves showed the strongest cytopathic effect inhibition on Vero cells, resulting in cell viabilities of 92.6% ± 1.0% (512 μg/ml), 91.5% ± 1.7% (512 μg/ml) and 88.8% ± 2.4% (80 μg/ml) respectively. However, quantitative RT-PCR analysis revealed that the chloroform extract of Rhapis excelsa (Arecaceae) leaves resulted in the highest percentage of reduction of viral load (98.1%), followed by the ethyl acetate extract of Vernonia amygdalina (Compositae) leaves (95.5%). The corresponding 50% effective concentrations (EC50) and selectivity indices for these two extracts were 29.9 ± 0.9 and 32.4 ± 1.3 μg/ml, and 5.4 and 5.1 respectively. Rhapis excelsa and Vernonia amygdalina could be sources of anti-Chikungunya virus agents. [Int Microbiol 19(3):175-182 (2016)]. Copyright© by the Spanish Society for Microbiology and Institute for Catalan Studies.

  17. Sequential Chikungunya and Zika Virus Infections in a Traveler from Honduras.

    PubMed

    Norman, Francesca F; Chamorro, Sandra; Vázquez, Ana; Sánchez-Seco, María-Paz; Pérez-Molina, José-Antonio; Monge-Maillo, Begoña; Vivancos, María-Jesús; Rodríguez-Dominguez, Mario; Galán, Juan-Carlos; de Ory, Fernando; López-Vélez, Rogelio

    2016-11-02

    Zika virus (ZIKV) and chikungunya virus (CHIKV) are currently circulating in overlapping areas in the American continents and may both be transmitted by Aedes spp. mosquitoes. The first documented case, to the authors' knowledge, of sequential CHIKV and ZIKV infections diagnosed in a nonendemic area in a returning traveler is reported. The implications for heightened clinical surveillance for these infections and specific patient recommendations are emphasized. © The American Society of Tropical Medicine and Hygiene.

  18. Plant expression systems, a budding way to confront chikungunya and Zika in developing countries?

    PubMed Central

    Cardona-Ospina, Jaime A.; Sepúlveda-Arias, Juan C.; Mancilla, L.; Gutierrez-López, Luis G.

    2016-01-01

    Plant expression systems could be used as biofactories of heterologous proteins that have the potential to be used with biopharmaceutical aims and vaccine design. This technology is scalable, safe and cost-effective and it has been previously proposed as an option for vaccine and protein pharmaceutical development in developing countries. Here we present a proposal of how plant expression systems could be used to address Zika and chikungunya outbreaks through development of vaccines and rapid diagnostic kits. PMID:27781090

  19. Plant expression systems, a budding way to confront chikungunya and Zika in developing countries?

    PubMed

    Cardona-Ospina, Jaime A; Sepúlveda-Arias, Juan C; Mancilla, L; Gutierrez-López, Luis G

    2016-01-01

    Plant expression systems could be used as biofactories of heterologous proteins that have the potential to be used with biopharmaceutical aims and vaccine design. This technology is scalable, safe and cost-effective and it has been previously proposed as an option for vaccine and protein pharmaceutical development in developing countries. Here we present a proposal of how plant expression systems could be used to address Zika and chikungunya outbreaks through development of vaccines and rapid diagnostic kits.

  20. Imported Chikungunya fever case in Greece in June 2014 and public health response

    PubMed Central

    Pervanidou, Danai; Papadopoulou, Elpida; Kavatha, Dimitra; Baka, Agoritsa; Koliopoulos, George; Badieritakis, Evangelos; Michaelakis, Antonios; Gavana, Elpida; Patsoula, Eleni; Tsimpos, Ioannis; Gioksari, Thalia; Kyriazopoulou, Evdoxia; Vakali, Annita; Pavli, Androula; Maltezou, Helena C.; Georgakopoulou, Theano; Hadjichristodoulou, Christos; Kremastinou, Jenny; Papa, Anna

    2016-01-01

    We report about the first imported case of Chikungunya fever in Greece in a Greek traveler returning from the Dominican Republic and the associated public health response. We investigated the case and performed focused epidemiological and entomological investigation in all areas the patient visited during the infectious period, to identify the targeted interventions needed. Entomological investigation revealed the occurrence of the competent vector Aedes albopictus (Diptera: Culicidae) in the environment surrounding the hospital where the patient was admitted and in her workplace. All captured mosquitoes tested negative for Chikungunya virus. We further conducted clinical and laboratory examination of the patient’s co-travelers, gave advice on appropriate personal preventive measures against mosquito bites to the patient and co-travelers and on vector control, and raised awareness among health professionals throughout Greece. The risk of introduction and local transmission of Chikungunya and other arboviruses in Greece and other European countries is present, as the competent vector exists in many parts of Europe. Public health professionals, travel medicine specialists and clinicians should maintain awareness regarding this possibility of importation of arbovirus cases in order to provide the appropriate advice, seek the prompt diagnosis, and implement appropriate interventions. Mobilization of various stakeholders will lead to enhanced epidemiological and entomological surveillance that will allow for improved risk assessment in each area. PMID:27159571

  1. Clinical Attack Rate of Chikungunya in a Cohort of Nicaraguan Children

    PubMed Central

    Balmaseda, Angel; Gordon, Aubree; Gresh, Lionel; Ojeda, Sergio; Saborio, Saira; Tellez, Yolanda; Sanchez, Nery; Kuan, Guillermina; Harris, Eva

    2016-01-01

    Chikungunya virus (CHIKV) was recently introduced into the Americas. In Nicaragua, the first endogenous transmission of CHIKV was recognized in September 2014. We used an ongoing dengue cohort study of children aged 2–14 years in Managua, Nicaragua, to document the attack rate of symptomatic chikungunya in a presumably naive population. From September 2014 through March 2015, the overall clinical attack rate of laboratory-confirmed CHIKV infection was 2.9% (95% confidence interval [CI]: 2.3%, 3.4%). The attack rate was greater in children ≥ 8 years of age (4.1%; 95% CI: 3.2%, 5.1%) than in those < 8 years of age (1.5%; 95% CI: 0.9%, 2.1%). The mean age of CHIKV cases presenting with typical chikungunya symptoms was 9.8 years, compared with 7.8 years for cases presenting with undifferentiated fever (P = 0.04). Our data suggest that the clinical attack rate in children may underestimate the true burden of disease as some children, especially young children, may experience more atypical symptoms (e.g., undifferentiated fever). PMID:26643531

  2. First report of naturally infected Aedes aegypti with chikungunya virus genotype ECSA in the Americas.

    PubMed

    Costa-da-Silva, André Luis; Ioshino, Rafaella Sayuri; Petersen, Vivian; Lima, Antonio Fernando; Cunha, Marielton Dos Passos; Wiley, Michael R; Ladner, Jason T; Prieto, Karla; Palacios, Gustavo; Costa, Danuza Duarte; Suesdek, Lincoln; Zanotto, Paolo Marinho de Andrade; Capurro, Margareth Lara

    2017-06-01

    The worldwide expansion of new emergent arboviruses such as Chikungunya and Zika reinforces the importance in understanding the role of mosquito species in spreading these pathogens in affected regions. This knowledge is essential for developing effective programs based on species specificity to avoid the establishment of endemic transmission cycles sustained by the identified local vectors. Although the first autochthonous transmission of Chikungunya virus was described in 2014 in the north of Brazil, the main outbreaks were reported in 2015 and 2016 in the northeast of Brazil. During 5 days of February 2016, we collected mosquitoes in homes of 6 neighborhoods of Aracaju city, the capital of Sergipe state. Four mosquito species were identified but Culex quinquefasciatus and Aedes aegypti were the most abundant. Field-caught mosquitoes were tested for Chikungunya (CHIKV), Zika (ZIKV) and Dengue viruses (DENV) by qRT-PCR and one CHIKV-infected Ae. aegypti female was detected. The complete sequence of CHIKV genome was obtained from this sample and phylogenetic analysis revealed that this isolate belongs to the East-Central-South-African (ECSA) genotype. Our study describes the first identification of a naturally CHIKV-infected Ae. aegypti in Brazil and the first report of a CHIKV from ECSA genotype identified in this species in the Americas. These findings support the notion of Ae. aegypti being a vector involved in CHIKV outbreaks in northeast of Brazil.

  3. Waiting for chikungunya fever in Argentina: spatio-temporal risk maps

    PubMed Central

    Carbajo, Aníbal E; Vezzani, Darío

    2015-01-01

    Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegypti in half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya by Ae. aegypti in the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable. PMID:25946252

  4. Clinical Attack Rate of Chikungunya in a Cohort of Nicaraguan Children.

    PubMed

    Balmaseda, Angel; Gordon, Aubree; Gresh, Lionel; Ojeda, Sergio; Saborio, Saira; Tellez, Yolanda; Sanchez, Nery; Kuan, Guillermina; Harris, Eva

    2016-02-01

    Chikungunya virus (CHIKV) was recently introduced into the Americas. In Nicaragua, the first endogenous transmission of CHIKV was recognized in September 2014. We used an ongoing dengue cohort study of children aged 2-14 years in Managua, Nicaragua, to document the attack rate of symptomatic chikungunya in a presumably naive population. From September 2014 through March 2015, the overall clinical attack rate of laboratory-confirmed CHIKV infection was 2.9% (95% confidence interval [CI]: 2.3%, 3.4%). The attack rate was greater in children ≥ 8 years of age (4.1%; 95% CI: 3.2%, 5.1%) than in those < 8 years of age (1.5%; 95% CI: 0.9%, 2.1%). The mean age of CHIKV cases presenting with typical chikungunya symptoms was 9.8 years, compared with 7.8 years for cases presenting with undifferentiated fever (P = 0.04). Our data suggest that the clinical attack rate in children may underestimate the true burden of disease as some children, especially young children, may experience more atypical symptoms (e.g., undifferentiated fever).

  5. 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.

  6. 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

  7. Waiting for chikungunya fever in Argentina: spatio-temporal risk maps.

    PubMed

    Carbajo, Aníbal E; Vezzani, Darío

    2015-04-01

    Chikungunya virus (CHIKV) transmission has been detected in America in 2013 and recently reached south up to Bolivia, Brazil and Paraguay, bordering countries of Argentina. The presence of the mosquito Aedes aegypti in half of the country together with the regional context drove us to make a rapid assessment of transmission risk. Temperature thresholds for vector breeding and for virus transmission, together with adult activity from the literature, were mapped on a monthly basis to estimate risk. Transmission of chikungunya by Ae. aegypti in the world was seen at monthly mean temperatures from 21-34ºC, with the majority occurring between 26-28ºC. In Argentina temperatures above 21ºC are observed since September in the northeast, expanding south until January and retreating back to the northeast in April. The maximum area under risk encompasses more than half the country and around 32 million inhabitants. Vector adult activity was registered where monthly means temperatures exceeded 13ºC, in the northeast all over the year and in the northern half from September-May. The models herein proposed show that conditions for transmission are already present. Considering the regional context and the historic inability to control dengue in the region, chikungunya fever illness seems unavoidable.

  8. Relative risk estimation of Chikungunya disease in Malaysia: An analysis based on Poisson-gamma model

    NASA Astrophysics Data System (ADS)

    Samat, N. A.; Ma'arof, S. H. Mohd Imam

    2015-05-01

    Disease mapping is a method to display the geographical distribution of disease occurrence, which generally involves the usage and interpretation of a map to show the incidence of certain diseases. Relative risk (RR) estimation is one of the most important issues in disease mapping. This paper begins by providing a brief overview of Chikungunya disease. This is followed by a review of the classical model used in disease mapping, based on the standardized morbidity ratio (SMR), which we then apply to our Chikungunya data. We then fit an extension of the classical model, which we refer to as a Poisson-Gamma model, when prior distributions for the relative risks are assumed known. Both results are displayed and compared using maps and we reveal a smoother map with fewer extremes values of estimated relative risk. The extensions of this paper will consider other methods that are relevant to overcome the drawbacks of the existing methods, in order to inform and direct government strategy for monitoring and controlling Chikungunya disease.

  9. 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

    2016-09-08

    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.

  10. Imported Chikungunya fever case in Greece in June 2014 and public health response.

    PubMed

    Tsiodras, Sotirios; Pervanidou, Danai; Papadopoulou, Elpida; Kavatha, Dimitra; Baka, Agoritsa; Koliopoulos, George; Badieritakis, Evangelos; Michaelakis, Antonios; Gavana, Elpida; Patsoula, Eleni; Tsimpos, Ioannis; Gioksari, Thalia; Kyriazopoulou, Evdoxia; Vakali, Annita; Pavli, Androula; Maltezou, Helena C; Georgakopoulou, Theano; Hadjichristodoulou, Christos; Kremastinou, Jenny; Papa, Anna

    2016-03-01

    We report about the first imported case of Chikungunya fever in Greece in a Greek traveler returning from the Dominican Republic and the associated public health response. We investigated the case and performed focused epidemiological and entomological investigation in all areas the patient visited during the infectious period, to identify the targeted interventions needed. Entomological investigation revealed the occurrence of the competent vector Aedes albopictus (Diptera: Culicidae) in the environment surrounding the hospital where the patient was admitted and in her workplace. All captured mosquitoes tested negative for Chikungunya virus. We further conducted clinical and laboratory examination of the patient's co-travelers, gave advice on appropriate personal preventive measures against mosquito bites to the patient and co-travelers and on vector control, and raised awareness among health professionals throughout Greece. The risk of introduction and local transmission of Chikungunya and other arboviruses in Greece and other European countries is present, as the competent vector exists in many parts of Europe. Public health professionals, travel medicine specialists and clinicians should maintain awareness regarding this possibility of importation of arbovirus cases in order to provide the appropriate advice, seek the prompt diagnosis, and implement appropriate interventions. Mobilization of various stakeholders will lead to enhanced epidemiological and entomological surveillance that will allow for improved risk assessment in each area.

  11. [Chikungunya seroprevalence and clinical case rate in Nicaragua, 2014-2015].

    PubMed

    2017-08-21

    Estimate seroprevalence, clinical case rate, and proportion of subclinical infections from chikungunya. A cross-sectional study was conducted in October 2015 at 39 sites distributed across Nicaragua. Demographic and clinical information was compiled through a personal survey. Blood samples were collected to detect chikungunya antibodies using the ELISA inhibition method developed by Nicaragua's National Diagnostic and Reference Center. Results were analyzed using generalized linear models and multilevel Poisson models. A total of 11 722 participants aged >2 years were enrolled and 11 280 samples were processed. National seroprevalence was 32.8% (95% CI [95% confidence interval]: 31.9-33.6), with a clinical case rate of 26.5% (95% CI: 25.7-27.3) and a proportion of subclinical infections of 19.1% (95% CI: 17.8-20.4). Seroprevalence varied among the 39 sites and was greater at sites with higher vector infestation indices. Individually, seroprevalence was higher in participants aged >11 years. Since its introduction, this is the first study on chikungunya seroprevalence in continental Latin America to determine national prevalence, clinical case rate, and proportion of subclinical infections. The study model, employing broad community participation and leadership by the Ministry of Health of Nicaragua, can be an example for conducting similar studies in the region.

  12. Acquired auditory neuropathy spectrum disorder after an attack of chikungunya: case study.

    PubMed

    Prabhu, Prashanth

    2016-01-01

    Auditory neuropathy spectrum disorder (ANSD) is a retrocochlear disorder in which the cochlear functioning is normal but the transmission in the auditory neural pathway is affected. The present study reports of a 14-year-old teenager with acquired ANSD after an attack of chikungunya. He reported symptoms of difficulty in understanding speech, tinnitus and vertigo when exposed to loud sounds. The audiological characteristics suggested auditory neuropathy spectrum disorder with raising audiogram configuration. The results of tinnitus evaluation showed low-pitched tinnitus and it was persistent causing significant handicap to him based on self report tinnitus handicap questionnaire results. The results of depression, anxiety and stress scale also suggested symptoms of mild depression and anxiety. Chikungunya virus is suspected to be neurotropic in nature which can damage auditory nerve cells and may have caused ANSD. The result also shows presence of tullio's phenomenon and absence of cervical vestibular evoked myogenic potentials suggesting damage to the vestibular neuronal system. The possible pathophysiology of chikungunya virus causing ANSD and vestibular symptoms needs to be explored further in future studies.

  13. Epidemic outbreak of Chikungunya in two neighboring towns in the Colombian Caribbean: a survival analysis.

    PubMed

    Oviedo-Pastrana, Misael; Méndez, Nelson; Mattar, Salim; Arrieta, Germán; Gomezcaceres, Luty

    2017-01-01

    The first autochthonous Chikungunya virus transmission in Colombia was reported in September 2014. Three months later, every town in the Caribbean region was affected, including the bordering towns of Ovejas and Corozal, in the department of Sucre. The objective of the study was to analyze and compare the temporal dynamics of the outbreak of Chikungunya in two towns of the department of Sucre. Households with suspicious cases with clinical symptomatology for Chikungunya were enrolled. In each house an epidemiological questionnaire was applied to collect economic and social information and methods for vector control. The study analyzed data collected between 09/01/2014 and 01/31/2015; 458 families in Corozal and 516 families in Ovejas were identified with Chikungunya cases. Estimated attack rates were 10,621 cases and 1640 cases per 100,000 inhabitants, in Ovejas and Corozal, respectively. The 75-day survival curve was 27.2% lower (0.632, CI = 0.614-0.651) in Ovejas than in Corozal (0.904, CI = 0.891-0.917). After 120 days, both curves showed a stable horizontal slope, close to a survival probability of 0.54, indicating the end of the epidemic period. The log-rank test (X(2) = 94.6, 1fd, p-value = 0.000) showed the improved survival of Chikungunya in the town of Corozal. The relative risk between the two towns was 0.863 (CI = 0.809-0.921; p-value < 0.001). The dynamics of the temporal distribution of CHIKV could be influenced by socioeconomic and preventable risk factors. Poor socioeconomic conditions such as the lack and poor efficiency of water supply and waste collection services could be determining factors in the proliferation of CHIKV. The survival analysis proved to be a suitable method for studying the presentation of CHIKV and can be applied to other prevalent vector-borne diseases such as the ZIKA and Dengue.

  14. Recommendations of the Brazilian Society of Rheumatology for the diagnosis and treatment of chikungunya fever. Part 2 - Treatment.

    PubMed

    Marques, Claudia Diniz Lopes; Duarte, Angela Luzia Branco Pinto; Ranzolin, Aline; Dantas, Andrea Tavares; Cavalcanti, Nara Gualberto; Gonçalves, Rafaela Silva Guimarães; Junior, Laurindo Ferreira da Rocha; Valadares, Lilian David de Azevedo; Melo, Ana Karla Guedes de; Freire, Eutilia Andrade Medeiros; Teixeira, Roberto; Neto, Francisco Alves Bezerra; Medeiros, Marta Maria das Chagas; Carvalho, Jozélio Freire de; Santos, Mario Sergio F; Océa, Regina Adalva de L Couto; Levy, Roger A; Andrade, Carlos Augusto Ferreira de; Pinheiro, Geraldo da Rocha Castelar; Abreu, Mirhelen Mendes; Verztman, José Fernando; Merenlender, Selma; Ribeiro, Sandra Lucia Euzebio; Costa, Izaias Pereira da; Pileggi, Gecilmara; Trevisani, Virginia Fernandes Moça; Lopes, Max Igor Banks; Brito, Carlos; Figueiredo, Eduardo; Queiroga, Fabio; Feitosa, Tiago; Tenório, Angélica da Silva; Siqueira, Gisela Rocha de; Paiva, Renata; Vasconcelos, José Tupinambá Sousa; Christopoulos, Georges

    2017-01-01

    Chikungunya fever has become an important public health problem in countries where epidemics occur because half of the cases progress to chronic, persistent and debilitating arthritis. Literature data on specific therapies at the various phases of arthropathy caused by chikungunya virus (CHIKV) infection are limited, lacking quality randomized trials assessing the efficacies of different therapies. There are a few studies on the treatment of musculoskeletal manifestations of chikungunya fever, but these studies have important methodological limitations. The data currently available preclude conclusions favorable or contrary to specific therapies, or an adequate comparison between the different drugs used. The objective of this study was to develop recommendations for the treatment of chikungunya fever in Brazil. A literature review was performed via evidence-based selection of articles in the databases Medline, SciELO, PubMed and Embase and conference proceedings abstracts, in addition to expert opinions to support decision-making in defining recommendations. The Delphi method was used to define the degrees of agreement in 2 face-to-face meetings and several online voting rounds. This study is part 2 of the Recommendations of the Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia - SBR) for the Diagnosis and Treatment of chikungunya fever and specifically addresses treatment. Copyright © 2017. Published by Elsevier Editora Ltda.

  15. Estimating and mapping the incidence of dengue and chikungunya in Honduras during 2015 using Geographic Information Systems (GIS).

    PubMed

    Zambrano, Lysien I; Sierra, Manuel; Lara, Bredy; Rodríguez-Núñez, Iván; Medina, Marco T; Lozada-Riascos, Carlos O; Rodríguez-Morales, Alfonso J

    Geographical information systems (GIS) use for development of epidemiological maps in dengue has been extensively used, however not in other emerging arboviral diseases, nor in Central America. Surveillance cases data (2015) were used to estimate annual incidence rates of dengue and chikungunya (cases/100,000 pop) to develop the first maps in the departments and municipalities of Honduras. The GIS software used was Kosmo Desktop 3.0RC1(®). Four thematic maps were developed according departments, municipalities, diseases incidence rates. A total of 19,289 cases of dengue and 85,386 of chikungunya were reported (median, 726 cases/week for dengue and 1460 for chikungunya). Highest peaks were observed at weeks 25th and 27th, respectively. There was association between progression by weeks (p<0.0001). The cumulated crude national rate was estimated in 224.9 cases/100,000 pop for dengue and 995.6 for chikungunya. The incidence rates ratio between chikungunya and dengue is 4.42 (ranging in municipalities from 0.0 up to 893.0 [San Vicente Centenario]). Burden of both arboviral diseases is concentrated in capital Central District (>37%, both). Use of GIS-based epidemiological maps allow to guide decisions-taking for prevention and control of diseases that still represents significant issues in the region and the country, but also in emerging conditions. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  16. Impaired NK cell functionality and increased TNF-α production as biomarkers of chronic chikungunya arthritis and rheumatoid arthritis.

    PubMed

    Thanapati, Subrat; Ganu, Mohini; Giri, Prashant; Kulkarni, Shruti; Sharma, Meenal; Babar, Prasad; Ganu, Ashok; Tripathy, Anuradha S

    2017-04-01

    The chronic chikungunya arthritis symptoms closely mimic the rheumatoid arthritis (RA) symptoms, thus making it difficult to distinguish between these two clinical entities. The current comparative study characterizes NK (CD3(-)CD56(+)) and NK-like T (CD3(+)CD56(+)) cell responses in patients with chronic chikungunya arthritis and RA. Phenotype and functions of NK and NK-like T cells repertoire were assessed in 56 chronic chikungunya arthritis, 26 RA patients and 82 controls using flow cytometry. TNF-α and IFN-γ-secreting NK-like T cells were high in both chronic arthritis patients than in controls. Percentage of TNF-α(+) NK cells was higher in RA patients than in controls. Percentage of perforin(+) NK cells was low in both chronic arthritis patient groups. Among the patient groups, expressions of perforin(+) and IFN-γ(+) NK-like T cells were higher in RA. Overall, our data show reduced frequency of NK-like T cells, lower expression of perforin(+) NK, higher expression of TNF-α(+) NK-like T and IFN-γ(+) NK-like T cells as the markers of chronic arthritic diseases. In the absence of any specific treatment for chronic chikungunya induced arthritis and promising results of anti-TNF-α therapy against RA, current data may form the basis for future in vivo studies and has scope as possible therapeutics against chikungunya.

  17. Prevalence and characteristics of dengue and chikungunya infections among acute febrile patients in Nong Khai Province, Thailand.

    PubMed

    Lertanekawattana, Sujet; Anantapreecha, Surapee; Jiraphongsa, Chuleeporn; Duan-ngern, Pawinee; Potjalongsin, Sathit; Wiittayabamrung, Wisanu; Daroon, Pamol; Techolarn, Meta

    2013-09-01

    We conducted a cross sectional study at three hospitals of Nong Khai Province, Thailand to determine the prevalence and characteristics of dengue and chikungunya infection among patients who sought care. The study population was acute febrile patients who visited these hospitals during 1 August -31 October, 2010 who were aged 2-60 years and had clinical symptoms compatible with the case definition. Dengue and chikungunya cases were confirmed by an ELISA IgM titer or RT-PCR. We also reviewed surveillance data of dengue and chikungunya infections from 2003-2009. Of the 200 participants recruited into the study, 103 patients (51.5%) were confirmed to have acute dengue infection; dengue serotype 2 was the most prevalence serotype. The ages of confirmed dengue cases ranged from 2-37 years old. The distribution of cases showed that dengue morbidity tended to be clustered in adjacent areas, particularly in Mueang District. Only a small proportion of the patients uses mosquito repellant and had screens on their windows. One patient (0.5%) had laboratory confirmed chikungunya infection. She was from Rattanawapi District, an area where no chikungunya had been reported before. Since the disease varies by age and geographic location, increased awareness of health care workers and public health officers about the diseases in the area is needed for early detection of cases and to promote early prevention and control measures.

  18. 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."

  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. The zebrafish early arrest mutants.

    PubMed

    Kane, D A; Maischein, H M; Brand, M; van Eeden, F J; Furutani-Seiki, M; Granato, M; Haffter, P; Hammerschmidt, M; Heisenberg, C P; Jiang, Y J; Kelsh, R N; Mullins, M C; Odenthal, J; Warga, R M; Nüsslein-Volhard, C

    1996-12-01

    This report describes mutants of the zebrafish having phenotypes causing a general arrest in early morphogenesis. These mutants identify a group of loci making up about 20% of the loci identified by mutants with visible morphological phenotypes within the first day of development. There are 12 Class I mutants, which fall into 5 complementation groups and have cells that lyse before morphological defects are observed. Mutants at three loci, speed bump, ogre and zombie, display abnormal nuclei. The 8 Class II mutants, which fall into 6 complementation groups, arrest development before cell lysis is observed. These mutants seemingly stop development in the late segmentation stages, and maintain a body shape similar to a 20 hour embryo. Mutations in speed bump, ogre, zombie, specter, poltergeist and troll were tested for cell lethality by transplanting mutant cells into wild-type hosts. With poltergeist, transplanted mutant cells all survive. The remainder of the mutants tested were autonomously but conditionally lethal: mutant cells, most of which lyse, sometimes survive to become notochord, muscles, or, in rare cases, large neurons, all cell types which become postmitotic in the gastrula. Some of the genes of the early arrest group may be necessary for progression though the cell cycle; if so, the survival of early differentiating cells may be based on having their terminal mitosis before the zygotic requirement for these genes.

  1. Hyperferritinemic syndrome: Still's disease and catastrophic antiphospholipid syndrome triggered by fulminant Chikungunya infection: a case report of two patients.

    PubMed

    Betancur, Juan-Felipe; Navarro, Erika-Paola; Echeverry, Alex; Moncada, Pablo A; Cañas, Carlos A; Tobón, Gabriel J

    2015-11-01

    There are four medical conditions characterized by high levels of ferritin, the macrophage activation syndrome (MAS), adult onset Still' s disease (AOSD), catastrophic antiphospholipid syndrome (CAPS), and septic shock, that share similar clinical and laboratory features, suggesting a common pathogenic mechanism. This common syndrome entity is termed "the hyperferritinemic syndrome." Here, we describe two different cases of hyperferritinemic syndrome triggered by Chikungunya fever virus infection: a 21-year-old female with SLE and a 32-year-old male patient who developed AOSD after the coinfection of dengue and Chikungunya viruses.

  2. [Lessons learned in the control of Aedes aegypti to address dengue and the emergency of chikungunya in Iquitos, Peru].

    PubMed

    Vilcarromero, Stalin; Casanova, Wilma; Ampuero, Julia S; Ramal-Asayag, Cesar; Siles, Crystyan; Díaz, Gloria; Durand, Salomón; Celis-Salinas, Juan C; Astete, Helvio; Rojas, Percy; Vásquez-La Torre, Gabriela; Marín, Johan; Bazán, Isabel; Alegre, Yuri; Morrison, Amy C; Rodriguez-Ferrucci, Hugo

    2015-01-01

    Dengue has affected Iquitos since 1990 causing outbreaks of major impact on public health and for this reason great efforts have been made for its temporal control. Currently, with the expansion of the chikungunya virus in the Americas and the threat of the emergence of the virus in Iquitos, we reflect on lessons learned by way of the activities undertaken in the area of vector control; epidemiological surveillance, diagnosis and clinical management during periods of outbreaks of dengue, in a way that will allow us to better face the threat of an outbreak of chikungunya virus in the largest city in the Peruvian Amazon.

  3. Comprehensive proteomic analysis of white blood cells from chikungunya fever patients of different severities.

    PubMed

    Wikan, Nitwara; Khongwichit, Sarawut; Phuklia, Weerawat; Ubol, Sukathida; Thonsakulprasert, Tipparat; Thannagith, Montri; Tanramluk, Duangrudee; Paemanee, Atchara; Kittisenachai, Suthathip; Roytrakul, Sittiruk; Smith, Duncan R

    2014-04-11

    Chikungunya fever (CHIKF) is a recently re-emerged mosquito transmitted viral disease caused by the chikungunya virus (CHIKV), an Alphavirus belonging to the family Togaviridae. Infection of humans with CHIKV can result in CHIKF of variable severity, although the factors mediating disease severity remain poorly defined. White blood cells were isolated from blood samples collected during the 2009-2010 CHIKF outbreak in Thailand. Clinical presentation and viral load data were used to classify samples into three groups, namely non chikungunya fever (non-CHIKF), mild CHIKF, and severe CHIKF. Five samples from each group were analyzed for protein expression by GeLC-MS/MS. CHIKV proteins (structural and non-structural) were found only in CHIKF samples. A total of 3505 human proteins were identified, with 68 proteins only present in non-CHIKF samples. A total of 240 proteins were found only in CHIKF samples, of which 65 and 46 were found only in mild and severe CHIKF samples respectively. Proteins with altered expression mapped predominantly to cellular signaling pathways (including toll-like receptor and PI3K-Akt signaling) although many other processes showed altered expression as a result of CHIKV infection. Expression of proteins consistent with the activation of the inflammasome was detected, and quantitation of (pro)-caspase 1 at the protein and RNA levels showed an association with disease severity. This study confirms the infection of at least a component of white blood cells by CHIKV, and shows that CHIKV infection results in activation of the inflammasome in a manner that is associated with disease severity.

  4. 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

  5. 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

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

    PubMed

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

    2016-05-01

    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. 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. 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. 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 is no Ae. aegypti.

  7. Comprehensive proteomic analysis of white blood cells from chikungunya fever patients of different severities

    PubMed Central

    2014-01-01

    Background Chikungunya fever (CHIKF) is a recently re-emerged mosquito transmitted viral disease caused by the chikungunya virus (CHIKV), an Alphavirus belonging to the family Togaviridae. Infection of humans with CHIKV can result in CHIKF of variable severity, although the factors mediating disease severity remain poorly defined. Methods White blood cells were isolated from blood samples collected during the 2009-2010 CHIKF outbreak in Thailand. Clinical presentation and viral load data were used to classify samples into three groups, namely non chikungunya fever (non-CHIKF), mild CHIKF, and severe CHIKF. Five samples from each group were analyzed for protein expression by GeLC-MS/MS. Results CHIKV proteins (structural and non-structural) were found only in CHIKF samples. A total of 3505 human proteins were identified, with 68 proteins only present in non-CHIKF samples. A total of 240 proteins were found only in CHIKF samples, of which 65 and 46 were found only in mild and severe CHIKF samples respectively. Proteins with altered expression mapped predominantly to cellular signaling pathways (including toll-like receptor and PI3K-Akt signaling) although many other processes showed altered expression as a result of CHIKV infection. Expression of proteins consistent with the activation of the inflammasome was detected, and quantitation of (pro)-caspase 1 at the protein and RNA levels showed an association with disease severity. Conclusions This study confirms the infection of at least a component of white blood cells by CHIKV, and shows that CHIKV infection results in activation of the inflammasome in a manner that is associated with disease severity. PMID:24721947

  8. Outbreak of Chikungunya virus in the north Caribbean area of Colombia: clinical presentation and phylogenetic analysis.

    PubMed

    Mattar, Salim; Miranda, Jorge; Pinzon, Hernando; Tique, Vanesa; Bolanos, Amada; Aponte, Jose; Arrieta, German; Gonzalez, Marco; Barrios, Katerine; Contreras, Hector; Alvarez, Jaime; Aleman, Ader

    2015-10-29

    The Caribbean area of Colombia has been severely affected by a Chikungunya virus (CHIKV) outbreak since 2014. The study was carried out on 100 patients during a fever outbreak from August to September 2014 in two small rural villages in the northern Caribbean area of Colombia. The molecular assays performed by reverse transcription polymerase chain reaction (RT-PCR) on acute patient sera were collected within one to five days of the appearance of symptoms. Sequence analyses were carried out based on phylogenetic analyses of genes NS1 and E2. For serological assays, 49 (49%) patients at ≥ 6 days of disease onset were tested with NovaLisa Chikungunya IgG/IgM µ-capture enzyme-linked immunosorbent assay (ELISA). The main signs or symptoms associated with Chikungunya infection were arthralgia of the lower limbs (96%), fever (91%), arthralgia of the upper limbs (85%), rash (64%), and headache (57%). Ninety-four percent (46/49) of patients were positive for either IgM or IgG; the remaining three (6%) patients were seronegative. Viral loads were detected in 25 patients. Based on phylogenetic analysis of NS1 and E2, the characterization of the Colombian CHIKV indicated that it was a strain closely related to the British Virgin Islands strain and to the Asian genotype. This study shows the phylogenetic and clinical description of CHIKV in Colombia. The main symptoms shown were: arthralgia, fever, and rash. CHIKV sequences detected in Colombian patients were within the Asian genotype and closely related to the British Virgin Islands strain.

  9. [Aedes albopictus, vector of chikungunya and dengue viruses in Reunion Island: biology and control].

    PubMed

    Delatte, H; Paupy, C; Dehecq, J S; Thiria, J; Failloux, A B; Fontenille, D

    2008-03-01

    Chikungunya virus (CHIKV) and dengue virus (DENV) are mosquito-borne viruses transmitted by the Aedes genus. Dengue is considered as the most important arbovirus disease throughout the World. Chikungunya, known from epidemics in continental Africa and Asia, has up to now been poorly studied. It has been recently responsible for the severe 2004-2007 epidemic reported in the Indian Ocean (IO), which has caused several serious health and economic problems. This unprecedented epidemic of the IO has shown severe health troubles with morbidity and death associated, which had never been observed before. The two major vectors of those arboviruses in the IO area are Aedes aegypti and Aedes albopictus. The latest is considered as the main vector in most of the islands of the area, especially in Reunion Island. Ae. albopictus showed strong ecological plasticity. Small disposable containers were the principal urban breeding sites, and preferred natural developmental sites were bamboo stumps and rock holes in peri-urban and gully areas. The virus has been isolated from field collected Ae. albopictus females, and in two out of 500 pools of larvae, demonstrating vertical transmission. Experimental works showed that both Ae. albopictus and Ae. aegypti from west IO islands are efficient vectors of dengue and chikungunya viruses. Since 2006 and all along the epidemic of CHIKV, measures for the control of larvae (temephos then Bacillus thuringiensis) and adults (fenitrothion, then deltamethrine) of Ae. albopictus where applied along with individual and collective actions (by the use of repellents, and removal of breeding sites around houses) in Reunion Island. In order to prevent such epidemics, a preventive plan for arboviruses upsurge is ongoing processed. This plan would allow a quicker response to the threat and adapt it according to the virus and its specific vector.

  10. Phylogenetic analysis of Chikungunya virus in Colombia: Evidence of purifying selection in the E1 gene.

    PubMed

    Laiton-Donato, Katherine; Usme-Ciro, José A; Rico, Angélica; Pardo, Lissethe; Martínez, Camilo; Salas, Daniela; Ardila, Susanne; Páez, Andrés

    2015-10-23

    Chikungunya virus (CHIKV) is a single-stranded positive sense RNA virus that belongs to the Alphavirus genus of the family Togaviridae. Its genome is 11.8 kb in length, and three genotypes have been identified worldwide: Asian, East/Central/South African (ECSA) and West African. Chikungunya fever is an acute febrile disease transmitted by Aedes spp. that usually presents with polyarthralgia and cutaneous eruption. Following introduction of the virus to the Americas in 2013, the first cases in Colombia occurred in September of 2014, and they reached a cumulative total of 399,932 cases by June of 2015.  To identify the genotype or genotypes responsible for the current epidemic in Colombia and to describe the genetic variability of the virus in the country.  Serum samples from patients presenting with symptoms compatible with Chikungunya fever during 2014-2015 were selected for the study. RT-PCR products of the E1 gene from these samples were used for sequencing and subsequent phylogenetic and adaptive evolution analyses.  The study identified only the presence of the Asian genotype in Colombia. Comparing the Colombian sequences with other sequences from the Americas revealed an average of 0.001 base substitutions per site, with 99.7% and 99.9% nucleotide identity and 99.9% amino acid identity. The adaptive evolution analysis indicated that the E1 gene is under strong purifying selection.  The first epidemic of Chikunguya fever in Colombia was caused by the circulation of the virus Asian genotype. Further genotypic surveillance of the virus in Colombia is required to detect possible changes in its epidemiology, fitness and pathogenicity.

  11. [Atypical mucocutaneous manifestations in neonates and infants with chikungunya fever in the municipalities of Cúcuta, Los Patios and Villa del Rosario, Norte de Santander, Colombia, 2014].

    PubMed

    Muñoz, Claudia Marcela; Castillo, José Orlando; Salas, Daniela; Valderrama, Milena Alexandra; Rangel, Claudia Teresa; Vargas, Heiddy Patricia; Silva, Diana Carolina

    2016-09-01

    Atypical clinical manifestations have been observed in newborns and infants suffering from fever caused by the chikungunya virus. Objective: To describe the cases of fever caused by the chikungunya virus in newborns and infants with atypical mucocutaneous lesions. Materials and methods: We reviewed the clinical records, as well as lab tests and histopathological results, of newborns and infants diagnosed with Chikungunya virus and atypical mucocutaneous lesions in three regional hospitals. Results: Out of 18 suspected cases of chikungunya virus in newborns and infants, 11 were positive and presented atypical mucocutaneous manifestations. Six of the eleven confirmed cases corresponded to children under five months of age. The most common symptoms were fever, skin rash, irritability, and diarrhea. Three of the patients were infected with both dengue and chikungunya viruses. The ulcers occurred in the scalp, abdomen, genital and perianal region. We report mucocutaneous manifestations in newborns and infants diagnosed with fever caused by the chikungunya virus in Colombia. The rapid development of ulcers is most likely due to the immune response to the virus. Special attention should be given to pregnant women presenting symptoms of chikungunya virus infection prior to delivery, and their offspring should be followed-up in order to monitor possible complications.

  12. Congenital and perinatal complications of chikungunya fever: a Latin American experience.

    PubMed

    Torres, Jaime R; Falleiros-Arlant, Luiza H; Dueñas, Lourdes; Pleitez-Navarrete, Jorge; Salgado, Doris M; Castillo, José Brea-Del

    2016-10-01

    During the years 2014 and 2015, the Region of the Americas underwent a devastating epidemic of chikungunya virus (CHIKV) of the Asian genotype, resulting in millions of affected individuals. However, epidemiological and clinical information on this experience is scarce. Prior knowledge of congenital and neonatal illness caused by CHIKV is limited and almost exclusively based on data obtained from a single outbreak of the East/Central/South African (ECSA) genotype. The effect of chikungunya fever (CHIKF) on pregnancy outcomes and its consequences for infants born to infected mothers at the peak of the epidemic wave in Latin America are reviewed herein. Epidemiological and clinical data on maternal and neonatal infections were collected prospectively and analyzed. One hundred sixty-nine symptomatic newborns with CHIKF seen at four large regional maternity hospitals in three different Central and South American countries were evaluated prospectively. The outcomes of pregnancies in symptomatic infected mothers at two of these clinical centers were also analyzed. The observed vertical transmission rate ranged between 27.7% and 48.29%. The incidence of congenital disease was unrelated to the use of cesarean section or natural delivery. The case fatality rate (CFR) at the only center that reported deaths was 5.3%. The most common clinical manifestations included fever, irritability, rash, hyperalgesia syndrome, diffuse limb edema, meningoencephalitis, and bullous dermatitis. Severe complications included meningoencephalitis, myocarditis, seizures, and acute respiratory failure. Leukocytosis with neutrophilia and normal or increased platelets was a common finding, and in those with signs of meningeal involvement, moderate lymphocytic pleocytosis with normal glucose and protein levels was typical. This study presents the largest number of symptomatic neonates with CHIKF analyzed so far in any region and is the first involving infection with the Asian genotype of CHIKV

  13. Mayaro fever in an HIV-infected patient suspected of having Chikungunya fever.

    PubMed

    Estofolete, Cássia Fernanda; Mota, Mânlio Tasso Oliveira; Vedovello, Danila; Góngora, Delzi Vinha Nunes de; Maia, Irineu Luiz; Nogueira, Maurício Lacerda

    2016-01-01

    Arboviruses impose a serious threat to public health services. We report a case of a patient returning from a work trip to the Amazon basin with myalgia, arthralgia, fever, and headache. During this travel, the patient visited riverside communities. Both dengue and Chikungunya fevers were first suspected, tested for, and excluded. Mayaro fever was then confirmed by reverse transcription polymerase chain reaction followed by next-generation sequencing and phylogenetic reconstruction. The increased awareness of physicians and consequent detection of Mayaro virus in this case was only possible due a previous surveillance program with specific health personnel training about these neglected arboviruses.

  14. Chikungunya fever: an emerging viral infection threatening North America and Europe.

    PubMed

    Handler, Marc Z; Handler, Nancy S; Stephany, Matthew P; Handler, Glenn A; Schwartz, Robert A

    2017-02-01

    Since the beginning of the twenty-first century, there has been a rapid rise in the number of cases of chikungunya. Initially limited to islands of the southwestern Indian Ocean, the virus has spread across Africa and into the islands of the Caribbean. Cutaneous symptoms include a morbilliform eruption, hyperpigmented macules, and aphthae-like ulcers. Patients often also experience fever and joint pain. We review the methods for diagnosis, treatment, and prevention of this increasingly prevalent virus now emerging more commonly in Europe and North America. © 2016 The International Society of Dermatology.

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

    PubMed

    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

    2013-06-01

    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.

  16. [Chikungunya crisis on Reunion Island. Media coverage and conflicting public information].

    PubMed

    Idelson, B

    2012-03-01

    The purpose of this article is to analyze media coverage of the health crisis created by the chikungunya epidemic on Reunion Island in 2005/2006. In reaction to nformation provided to the public, the media overstated the sanitary risk. Analysis of the press corpus corresponding to that period reveals an exaggerated account of the epidemic aimed at echoing the genuine distress expressed by victims and their family. Based on the feedback principle, the article suggests a relationship between this situation and information provided to the public about the crisis.

  17. Low Seroprevalence Indicates Vulnerability of Eastern and Central Sudan to Infection with Chikungunya Virus.

    PubMed

    Adam, Awadalkareem; Seidahmed, Osama M E; Weber, Christopher; Schnierle, Barbara; Schmidt-Chanasit, Jonas; Reiche, Sven; Jassoy, Christian

    2016-04-01

    Outbreaks of infections with chikungunya virus (CHIKV) have previously been reported from Sudan but the prevalence in the general population is unknown. We investigated the seroprevalence of CHIKV infection in 379 serum samples from patients with fever in the outpatient clinics of three hospitals in eastern and central Sudan. The seroprevalence was 1.8%, indicating that CHIKV infections are rare in these parts of Sudan. As the vector Aedes aegypti is endemic in this area, the population is at risk for a CHIKV epidemic.

  18. Identification of Chikungunya virus strains circulating in Kelantan, Malaysia in 2009.

    PubMed

    Apandi, Y; Lau, S K; Izmawati, N; Amal, N M; Faudzi, Y; Mansor, Wan; Hani, M H; Zainah, S

    2010-11-01

    Malaysia experienced its first outbreak of chikungunya virus (CHIKV) infection in late 1998 in Klang District in Selangor; six years later the virus re-emerged in the state of Perak. All the CHIKV isolates in 1988 and 2006 shared high sequence similarities and belonged to the Asian genotype. In 2007 and 2008 CHIKV infection again reemerged but the genotype was the Central/East African genotype. This strain was found to be similar to the strains causing outbreaks in the India Ocean. In 2009, the strains circulating in Malaysia, including the state of Kelantan, based on the partial E1 gene, also belong to the Central/East African genotype.

  19. [Coverage of the chikungunya epidemic on Reunion Island in 2006 by the French healthcare system].

    PubMed

    Lagacherie, P

    2012-03-01

    The chikungunya epidemic that occurred on Reunion Island between 2005 and 2006 was covered by the French health insurance system. This coverage involved a major increase in the number of paid sick leave days and prescription drug refunds in the first quarter of 2006. Special governmental measures such as full reimbursement of certain medications and waiving of the waiting period for sick leave in case of relapse greatly reduced the impact of the epidemic. Five years after, the database of the health insurance systems indicates a low incidence of chronic forms. Only cases managed on an outpatient basis were included in this study.

  20. 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.

  1. Potential Antivirals: Natural Products Targeting Replication Enzymes of Dengue and Chikungunya Viruses.

    PubMed

    Oliveira, Ana Flávia Costa da Silveira; Teixeira, Róbson Ricardo; Oliveira, André Silva de; Souza, Ana Paula Martins de; Silva, Milene Lopes da; Paula, Sérgio Oliveira de

    2017-03-22

    Dengue virus (DENV) and chikungunya virus (CHIKV) are reemergent arboviruses that are transmitted by mosquitoes of the Aedes genus. During the last several decades, these viruses have been responsible for millions of cases of infection and thousands of deaths worldwide. Therefore, several investigations were conducted over the past few years to find antiviral compounds for the treatment of DENV and CHIKV infections. One attractive strategy is the screening of compounds that target enzymes involved in the replication of both DENV and CHIKV. In this review, we describe advances in the evaluation of natural products targeting the enzymes involved in the replication of these viruses.

  2. ECB deacylase mutants

    DOEpatents

    Arnold, Frances H.; Shao, Zhixin; Zhao, Huimin; Giver, Lorraine J.

    2002-01-01

    A method for in vitro mutagenesis and recombination of polynucleotide sequences based on polymerase-catalyzed extension of primer oligonucleotides is disclosed. The method involves priming template polynucleotide(s) with random-sequences or defined-sequence primers to generate a pool of short DNA fragments with a low level of point mutations. The DNA fragments are subjected to denaturization followed by annealing and further enzyme-catalyzed DNA polymerization. This procedure is repeated a sufficient number of times to produce full-length genes which comprise mutants of the original template polynucleotides. These genes can be further amplified by the polymerase chain reaction and cloned into a vector for expression of the encoded proteins.

  3. 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

  4. 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.

  5. 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.

  6. [The ideation of the Emilia-Romagna surveillance system for arbovirosis following the experience from the Chikungunya outbreak 2007].

    PubMed

    Angelini, Paola; Mattivi, Andrea; Cagarelli, Roberto; Bellini, Romeo; Finarelli, Alba Carola

    2014-01-01

    Since 2008 the Emilia-Romagna Regional public health authority activated a regional Plan for arbovirosis surveillance and control, focused on Chikungunya, Dengue and West Nile. The Plan integrates sanitary, entomological and veterinary surveillance allowing a prompt adoption of efficient measures, aiming at the prevention and reduction of arbovirosis transmission risk. Following the 2007 Chikungunya outbreak, no autochthonous Chikungunya or Dengue cases has been registered, while an increase of confirmed imported cases of Dengue and Chikungunya has been observed. The integrated surveillance system allowed a prompt, appropriate and efficient intervention in 98.2% of imported suspected cases. The humanWNND (West Nile Neuroinvasive Disease) surveillance reported confirmed cases in 2008, 2009 and then in 2013 and 2014. In all cases the entomological and ornithological surveillance detected WNV circulation well in advance respect to the appearance of the first human case. The integration of information provided by different surveillance sources allows to evaluate, even through the vector index (VI) calculation, the risk of transmission, to optimize preventive measures on blood, tissues and organs donation and to implement further measures of vector fight.

  7. 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

  8. Complete Genome Sequences of Two Chikungunya Viruses Isolated in the Central African Republic in the 1970s and 1980s

    PubMed Central

    Desdouits, Marion; Nakouné, Emmanuel; Gessain, Antoine; Kazanji, Mirdad; Berthet, Nicolas

    2017-01-01

    ABSTRACT Some arboviruses threaten human global health with potentially explosive emergence. Analysis of whole-genome sequences of decades-old isolates might contribute to the understanding of the complex dynamics which drive their circulation and emergence. Here, we report the whole-genome sequences of two Chikungunya viruses isolated in the Central African Republic in the 1970s and 1980s. PMID:28254965

  9. Ultrasound of ankles in the diagnosis of complications of chikungunya fever.

    PubMed

    Mogami, Roberto; Vaz, João Luiz Pereira; Chagas, Yêdda de Fátima Barcelos; Torezani, Rodrigo Sperling; Vieira, André de Almeida; Koifman, Ana Célia Baptista; Barbosa, Yasmin Baptista; de Abreu, Mirhelen Mendes

    2017-01-01

    To describe the main ultrasound findings of chikungunya fever in the ankle. This was a cross-sectional observational study involving 52 patients referred to the Hospital Universitário Pedro Ernesto and presenting with clinical and biochemical evidence of chikungunya fever. The examinations were performed by a radiologist with more than 20 years of experience in ultrasound. The predominant gender was female (in 88.5%), and the mean age was 58.4 years. The majority (61.5%) of the patients came from the northern part of the city of Rio de Janeiro, and 46.2% were using corticosteroids to treat inflammatory symptoms. The most common alterations observed by ultrasound were joint effusion (in 69.2%), tenosynovitis (in 59.6%), cellulitis (in 46.2%), Kager's fat pad thickening (in 29.9%), myositis (of the soleus or flexor hallucis longus muscle) (in 17.3%), retrocalcaneal bursitis (in 5.8%), tendon ruptures (in 3.8%), and increased vascular flow on power Doppler (in 3.8%). Signs of synovitis and tenosynovitis were the main ultrasound findings in a predominantly female population with a mean age of 58.4 years. Further studies are needed in order to define the role of ultrasound in the follow-up of such patients.

  10. 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

  11. Transmission risk of two chikungunya lineages by invasive mosquito vectors from Florida and the Dominican Republic.

    PubMed

    Alto, Barry W; Wiggins, Keenan; Eastmond, Bradley; Velez, Daniel; Lounibos, L Philip; Lord, Cynthia C

    2017-07-01

    Between 2014 and 2016 more than 3,800 imported human cases of chikungunya fever in Florida highlight the high risk for local transmission. To examine the potential for sustained local transmission of chikungunya virus (CHIKV) in Florida we tested whether local populations of Aedes aegypti and Aedes albopictus show differences in susceptibility to infection and transmission to two emergent lineages of CHIKV, Indian Ocean (IOC) and Asian genotypes (AC) in laboratory experiments. All examined populations of Ae. aegypti and Ae. albopictus mosquitoes displayed susceptibility to infection, rapid viral dissemination into the hemocoel, and transmission for both emergent lineages of CHIKV. Aedes albopictus had higher disseminated infection and transmission of IOC sooner after ingesting CHIKV infected blood than Ae. aegypti. Aedes aegypti had higher disseminated infection and transmission later during infection with AC than Ae. albopictus. Viral dissemination and transmission of AC declined during the extrinsic incubation period, suggesting that transmission risk declines with length of infection. Interestingly, the reduction in transmission of AC was less in Ae. aegypti than Ae. albopictus, suggesting that older Ae. aegypti females are relatively more competent vectors than similar aged Ae. albopictus females. Aedes aegypti originating from the Dominican Republic had viral dissemination and transmission rates for IOC and AC strains that were lower than for Florida vectors. We identified small-scale geographic variation in vector competence among Ae. aegypti and Ae. albopictus that may contribute to regional differences in risk of CHIKV transmission in Florida.

  12. A novel DANP-coupled hairpin RT-PCR for rapid detection of Chikungunya virus.

    PubMed

    Chen, Huixin; Takei, Fumie; Koay, Evelyn Siew-Chuan; Nakatani, Kazuhiko; Chu, Justin Jang Hann

    2013-03-01

    Chikungunya has re-emerged as an important arboviral infection of global health significance. Because of lack of a vaccine and effective treatment, rapid diagnosis plays an important role in early clinical management of patients. In this study, we have developed a novel molecular diagnostic platform that ensures a rapid and cost-effective one-step RT-PCR assay, with high sensitivity and specificity, for the early detection of the Chikungunya virus (CHIKV). It uses 2,7-diamino-1,8-naphthyridine derivative (DANP)-labeled cytosine-bulge hairpin primers to amplify the nsP2 region of the CHIKV genome, followed by measurement of the fluorescence emitted from DANP-primer complexes after PCRs. The detection limit of our assay was 0.01 plaque-forming units per reaction of CHIKV. Furthermore, the HP-nsP2 primers were highly specific in detecting CHIKV, without any cross-reactivity with the panel of RNA viruses validated in this study. The feasibility of the DANP-coupled hairpin RT-PCR for clinical diagnosis was evaluated using clinical serum samples from CHIKV-infected patients, and the specificity and sensitivity were 100% (95% CI, 80.0% to 100%) and 95.5% (95% CI, 75.1% to 99.8%), respectively. These findings confirmed its potential as a point-of-care clinical molecular diagnostic assay for CHIKV in acute-phase patient serum samples.

  13. 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

  14. Retrospective seroepidemiological study of chikungunya infection in South Asia, Southeast Asia and the Pacific region.

    PubMed

    Ngwe Tun, M M; Inoue, S; Thant, K Z; Talemaitoga, N; Aryati, A; Dimaano, E M; Matias, R R; Buerano, C C; Natividad, F F; Abeyewickreme, W; Thuy, N T T; Mai, L T Q; Hasebe, F; Hayasaka, D; Morita, K

    2016-08-01

    Chikungunya virus (CHIKV) and Ross River virus (RRV) of the genus Alphavirus, family Togaviridae are mainly transmitted by Aedes mosquitoes and the symptoms they cause in patients are similar to dengue. A chikungunya (CHIK) outbreak re-emerged in several Asian countries during 2005-2006. This study aimed to clarify the prevalence of CHIKV infection in suspected dengue patients in six countries in South Asia and Southeast Asia. Seven hundred forty-eight serum samples were from dengue-suspected patients in South Asia and Southeast Asia, and 52 were from patients in Fiji. The samples were analysed by CHIKV IgM capture ELISA, CHIKV IgG indirect ELISA and focus reduction neutralization test against CHIKV or RRV. CHIK-confirmed cases in South Asia, particularly Myanmar and Sri Lanka, were 4·6%, and 6·1%, respectively; and in Southeast Asia, particularly Indonesia, the Philippines and Vietnam, were 27·4%, 26·8% and 25·0%, respectively. It suggests that CHIK was widely spread in these five countries in Asia. In Fiji, no CHIK cases were confirmed; however, RRV-confirmed cases represented 53·6% of suspected dengue cases. It suggests that RRV is being maintained or occasionally entering from neighbouring countries and should be considered when determining a causative agent for dengue-like illness in Fiji.

  15. Production of a Chikungunya Vaccine Using a CHO Cell and Attenuated Viral-Based Platform Technology.

    PubMed

    Eldi, Preethi; Cooper, Tamara H; Liu, Liang; Prow, Natalie A; Diener, Kerrilyn R; Howley, Paul M; Suhrbier, Andreas; Hayball, John D

    2017-10-04

    Vaccinia-based systems have been extensively explored for the development of recombinant vaccines. Herein we describe an innovative vaccinia virus (VACV)-derived vaccine platform technology termed Sementis Copenhagen Vector (SCV), which was rendered multiplication-defective by targeted deletion of the essential viral assembly gene D13L. A SCV cell substrate line was developed for SCV vaccine production by engineering CHO cells to express D13 and the VACV host-range factor CP77, because CHO cells are routinely used for manufacture of biologics. To illustrate the utility of the platform technology, a SCV vaccine against chikungunya virus (SCV-CHIK) was developed and shown to be multiplication-defective in a range of human cell lines and in immunocompromised mice. A single vaccination of mice with SCV-CHIK induced antibody responses specific for chikungunya virus (CHIKV) that were similar to those raised following vaccination with a replication-competent VACV-CHIK and able to neutralize CHIKV. Vaccination also provided protection against CHIKV challenge, preventing both viremia and arthritis. Moreover, SCV retained capacity as an effective mouse smallpox vaccine. In summary, SCV represents a new and safe vaccine platform technology that can be manufactured in modified CHO cells, with pre-clinical evaluation illustrating utility for CHIKV vaccine design and construction. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Reconstruction of 60 Years of Chikungunya Epidemiology in the Philippines Demonstrates Episodic and Focal Transmission.

    PubMed

    Salje, Henrik; Cauchemez, Simon; Alera, Maria Theresa; Rodriguez-Barraquer, Isabel; Thaisomboonsuk, Butsaya; Srikiatkhachorn, Anon; Lago, Catherine B; Villa, Daisy; Klungthong, Chonticha; Tac-An, Ilya A; Fernandez, Stefan; Velasco, John Mark; Roque, Vito G; Nisalak, Ananda; Macareo, Louis R; Levy, Jens W; Cummings, Derek; Yoon, In-Kyu

    2016-02-15

    Proper understanding of the long-term epidemiology of chikungunya has been hampered by poor surveillance. Outbreak years are unpredictable and cases often misdiagnosed. Here we analyzed age-specific data from 2 serological studies (from 1973 and 2012) in Cebu, Philippines, to reconstruct both the annual probability of infection and population-level immunity over a 60-year period (1952-2012). We also explored whether seroconversions during 2012-2013 were spatially clustered. Our models identified 4 discrete outbreaks separated by an average delay of 17 years. On average, 23% (95% confidence interval [CI], 16%-37%) of the susceptible population was infected per outbreak, with >50% of the entire population remaining susceptible at any point. Participants who seroconverted during 2012-2013 were clustered at distances of <230 m, suggesting focal transmission. Large-scale outbreaks of chikungunya did not result in sustained multiyear transmission. Nevertheless, we estimate that >350 000 infections were missed by surveillance systems. Serological studies could supplement surveillance to provide important insights on pathogen circulation. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

  17. Management and Treatment of Dengue and Chikungunya - Natural Products to the Rescue.

    PubMed

    Suroowan, Shanoo; Mahomoodally, Fawzi; Ragoo, Luxcha

    2016-01-01

    Neglected tropical diseases (NTDs) flourish mostly in impoverished developing nations of the world. It is estimated that NTDs plague up to 1 billion people every year thereby inducing a massive economic and health burden worldwide. Following explosive outbreaks mostly in Asia, Latin America, Europe and the Indian Ocean, two common NTDs namely, Chikungunya and Dengue both transmitted by an infected mosquito vector principally Aedes aegypti have emerged as a major public health threat. Given the limitations of conventional medicine in specifically targeting the Chikungunya and Dengue virus (CHIKV and DENV), natural products present an interesting avenue to explore in the quest of developing novel anti; mosquito, CHIKV and DENV agents. In this endeavor, a number of plant extracts, isolated phytochemicals, essential oils and seaweeds have shown promising larvicidal and insecticidal activity against some mosquito vectors as well as anti CHIKV and DENV activity invitro. Other natural products that have depicted good potential against these diseases include; the symbiotic bacterial genus Wolbachia which can largely reduce the life span and infectivity of mosquito vectors and the marine Cyanobacterium Trichodesmium erythraeum which has shown anti- CHIKV activity at minimal cytotoxic level. The impetus of modern drug discovery approaches such as high throughput screening, drug repositioning, synthesis and computer-aided drug design will undeniably enhance the process of developing more stable lead molecules from natural products which have shown promising antiviral activity in-vitro.

  18. [Emerging infectious diseases: the example of the Indian Ocean chikungunya outbreak (2005-2006)].

    PubMed

    Flahault, Antoine

    2007-01-01

    Factors known to trigger the emergence or re-emergence of infectious diseases include globalisation, population growth, migration, international trade, urbanisation, forest destruction, climate change, loss of biodiversity, poverty, famine and war. Epidemics not only lead to disastrous loss of human life but may also have catastrophic economic, political and social consequences. Outbreaks may rapidly jeopardize industry, trade or tourism in countries that are unprepared. Dengue is currently spreading throughout the tropics, while another arbovirus, chikungunya, infected 30 to 75% of the population in some parts of the Indian Ocean region between 2005 and 2006. Chikungunya is now spreading through India, where more than a million people have so far been infected. This viral disease can cause lasting disability, and the first deaths were recently reported in La Réunion and Mayotte. All countries are at risk from emerging or re-emerging diseases, but the consequences are far worse in poor countries. Microbial pathogens and wild mammals, birds and arthropods do not respect man-made borders. There is still time to act against this threat of emerging and re-emerging infectious diseases, through prevention, anticipation, monitoring and research.

  19. Reconstruction of 60 Years of Chikungunya Epidemiology in the Philippines Demonstrates Episodic and Focal Transmission

    PubMed Central

    Salje, Henrik; Cauchemez, Simon; Alera, Maria Theresa; Rodriguez-Barraquer, Isabel; Thaisomboonsuk, Butsaya; Srikiatkhachorn, Anon; Lago, Catherine B.; Villa, Daisy; Klungthong, Chonticha; Tac-An, Ilya A.; Fernandez, Stefan; Velasco, John Mark; Roque, Vito G.; Nisalak, Ananda; Macareo, Louis R.; Levy, Jens W.; Cummings, Derek; Yoon, In-Kyu

    2016-01-01

    Proper understanding of the long-term epidemiology of chikungunya has been hampered by poor surveillance. Outbreak years are unpredictable and cases often misdiagnosed. Here we analyzed age-specific data from 2 serological studies (from 1973 and 2012) in Cebu, Philippines, to reconstruct both the annual probability of infection and population-level immunity over a 60-year period (1952–2012). We also explored whether seroconversions during 2012–2013 were spatially clustered. Our models identified 4 discrete outbreaks separated by an average delay of 17 years. On average, 23% (95% confidence interval [CI], 16%–37%) of the susceptible population was infected per outbreak, with >50% of the entire population remaining susceptible at any point. Participants who seroconverted during 2012–2013 were clustered at distances of <230 m, suggesting focal transmission. Large-scale outbreaks of chikungunya did not result in sustained multiyear transmission. Nevertheless, we estimate that >350 000 infections were missed by surveillance systems. Serological studies could supplement surveillance to provide important insights on pathogen circulation. PMID:26410592

  20. 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

    2016-05-16

    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.

  1. A chikungunya fever vaccine utilizing an insect-specific virus platform.

    PubMed

    Erasmus, Jesse H; Auguste, Albert J; Kaelber, Jason T; Luo, Huanle; Rossi, Shannan L; Fenton, Karla; Leal, Grace; Kim, Dal Y; Chiu, Wah; Wang, Tian; Frolov, Ilya; Nasar, Farooq; Weaver, Scott C

    2017-02-01

    Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but have reduced safety when compared to inactivated vaccines. In contrast, the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya fever (CHIKF) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the chikungunya virus (CHIKV) structural proteins. The recombinant EILV/CHIKV was structurally identical at 10 Å to wild-type CHIKV, as determined by single-particle cryo-electron microscopy, and it mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery. Yet the recombinant virus remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 d) and long-lasting (>290 d) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology.

  2. 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

  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. Neutralization activity of patient sera collected during the 2008-2009 Chikungunya outbreak in Thailand.

    PubMed

    Kishishita, Natsuko; Sasayama, Mikiko; Takeda, Naokazu; Sa-Ngasang, Areerat; Anuegoonpipat, Atchareeya; Anantapreecha, Surapee

    2015-01-01

    Chikungunya virus (CHIKV) infection typically causes fever, rash, myalgia, and arthralgia and sometimes results in recurrent joint pain or, in severe cases, neurological disorders or death. How CHIKV infection leads to prolonged or severe symptoms is still not well understood. In this study, we examined the neutralization (NT) titer of 98 serum samples collected from patients during the 2008-2009 chikungunya outbreak in Thailand. While all serum samples showed neutralizing activity, virus was detected in 58% of the serum samples. When we analyzed a possible association between virus and antibody titers and the presence of typical symptoms of CHIKV infection, fever and joint pain, there was no significant association except that the number of patients with fever was over three times more than the number of those without fever when CHIKV was detectable in serum. This study indicates that although neutralizing antibody is critical to eliminate CHIKV, it appears not to be the main factor associated with clinical symptoms in some cases, so that other aspects of immune responses, such as those involving proinflammatory mediators and adaptive immune cells, should be considered altogether.

  5. 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.

  6. Chikungunya virus impacts the diversity of symbiotic bacteria in mosquito vector.

    PubMed

    Zouache, Karima; Michelland, Rory J; Failloux, Anna-Bella; Grundmann, Genevieve L; Mavingui, Patrick

    2012-05-01

    Mosquitoes transmit numerous arboviruses including dengue and chikungunya virus (CHIKV). In recent years, mosquito species Aedes albopictus has expanded in the Indian Ocean region and was the principal vector of chikungunya outbreaks in La Reunion and neighbouring islands in 2005 and 2006. Vector-associated bacteria have recently been found to interact with transmitted pathogens. For instance, Wolbachia modulates the replication of viruses or parasites. However, there has been no systematic evaluation of the diversity of the entire bacterial populations within mosquito individuals particularly in relation to virus invasion. Here, we investigated the effect of CHIKV infection on the whole bacterial community of Ae. albopictus. Taxonomic microarrays and quantitative PCR showed that members of Alpha- and Gammaproteobacteria phyla, as well as Bacteroidetes, responded to CHIKV infection. The abundance of bacteria from the Enterobacteriaceae family increased with CHIKV infection, whereas the abundance of known insect endosymbionts like Wolbachia and Blattabacterium decreased. Our results clearly link the pathogen propagation with changes in the dynamics of the bacterial community, suggesting that cooperation or competition occurs within the host, which may in turn affect the mosquito traits like vector competence.

  7. Transmission risk of two chikungunya lineages by invasive mosquito vectors from Florida and the Dominican Republic

    PubMed Central

    Wiggins, Keenan; Eastmond, Bradley; Velez, Daniel; Lounibos, L. Philip; Lord, Cynthia C.

    2017-01-01

    Between 2014 and 2016 more than 3,800 imported human cases of chikungunya fever in Florida highlight the high risk for local transmission. To examine the potential for sustained local transmission of chikungunya virus (CHIKV) in Florida we tested whether local populations of Aedes aegypti and Aedes albopictus show differences in susceptibility to infection and transmission to two emergent lineages of CHIKV, Indian Ocean (IOC) and Asian genotypes (AC) in laboratory experiments. All examined populations of Ae. aegypti and Ae. albopictus mosquitoes displayed susceptibility to infection, rapid viral dissemination into the hemocoel, and transmission for both emergent lineages of CHIKV. Aedes albopictus had higher disseminated infection and transmission of IOC sooner after ingesting CHIKV infected blood than Ae. aegypti. Aedes aegypti had higher disseminated infection and transmission later during infection with AC than Ae. albopictus. Viral dissemination and transmission of AC declined during the extrinsic incubation period, suggesting that transmission risk declines with length of infection. Interestingly, the reduction in transmission of AC was less in Ae. aegypti than Ae. albopictus, suggesting that older Ae. aegypti females are relatively more competent vectors than similar aged Ae. albopictus females. Aedes aegypti originating from the Dominican Republic had viral dissemination and transmission rates for IOC and AC strains that were lower than for Florida vectors. We identified small-scale geographic variation in vector competence among Ae. aegypti and Ae. albopictus that may contribute to regional differences in risk of CHIKV transmission in Florida. PMID:28749964

  8. 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.

  9. Epidemiological Investigation of an Outbreak of Chikungunya in Hyderabad and Nalgonda Districts of Andhra Pradesh, India

    PubMed Central

    Jain, SK; Kadri, SM; Venkatesh, Srinivas; Lal, S; Katyal, RK

    2007-01-01

    After about three decades, Chikungunya infection has re-emerged in India and the first cases were reported in December, 2005. The outbreak has currently affected about 8 states in the country. Although known to be commonly non fatal, since the present outbreak involved a large population, it has been raised as an issue of public health concern and also attracted wide media attention. The clinico-epidemiological and entomological review of the Chikungunya outbreak situation in Hyderabad and Nalgonda Districts of Andhra Pradesh, which started in December 2005, revealed that it is under control. However, preventive efforts need to continue and disease surveillance for early detection of potential outbreaks further strengthening. Given the significantly high House Index, all the three study areas remain at significant risk of outbreaks in the future if appropriate control measures are not put in place. Community support and participation is also crucial for the prevention of future outbreaks and improving the health and well being of population in the districts. PMID:21475442

  10. How to explain the re-emergence of chikungunya infection in Reunion Island in 2010?

    PubMed

    Vilain, P; Larrieu, S; Renault, P; Baville, M; Filleul, L

    2012-08-01

    In March 2010, a new outbreak of chikungunya infection was detected in the west of Reunion Island. An investigation was launched to describe the incident cases occurrence and to raise hypotheses on factors that could explain the occurrence of this outbreak. All probable or confirmed cases detected by the surveillance system in the western area between March 1st and July 2nd, 2010 were included in the investigation. A standardized questionnaire was performed by phone, including sociodemographic, environmental and behaviour data. A total of 74 cases were described (i.e. response rate of 72%). They were mainly women (sex ratio M/F=0.7), all ages were represented. Most of them (76%) resided in a house; 31% had recently moved, including 22% from metropolitan France. They reported to have been more exposed to mosquitoes and to infected patients than during the major epidemic of 2005-2006. In addition, 41% reported to have reduced their protection against mosquitoes. The results suggest that several concomitant factors contributed to this outbreak: the reintroduction of the chikungunya virus in the island, the population characteristics and environmental factors.

  11. 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.

  12. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses

    PubMed Central

    Priye, Aashish; Bird, Sara W.; Light, Yooli K.; Ball, Cameron S.; Negrete, Oscar A.; Meagher, Robert J.

    2017-01-01

    Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. Here we demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable “LAMP box” supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. Our smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device’s utility for widespread clinical deployment. Together, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most. PMID:28317856

  13. A smartphone-based diagnostic platform for rapid detection of Zika, chikungunya, and dengue viruses.

    PubMed

    Priye, Aashish; Bird, Sara W; Light, Yooli K; Ball, Cameron S; Negrete, Oscar A; Meagher, Robert J

    2017-03-20

    Current multiplexed diagnostics for Zika, dengue, and chikungunya viruses are situated outside the intersection of affordability, high performance, and suitability for use at the point-of-care in resource-limited settings. Consequently, insufficient diagnostic capabilities are a key limitation facing current Zika outbreak management strategies. Here we demonstrate highly sensitive and specific detection of Zika, chikungunya, and dengue viruses by coupling reverse-transcription loop-mediated isothermal amplification (RT-LAMP) with our recently developed quenching of unincorporated amplification signal reporters (QUASR) technique. We conduct reactions in a simple, inexpensive and portable "LAMP box" supplemented with a consumer class smartphone. The entire assembly can be powered by a 5 V USB source such as a USB power bank or solar panel. Our smartphone employs a novel algorithm utilizing chromaticity to analyze fluorescence signals, which improves the discrimination of positive/negative signals by 5-fold when compared to detection with traditional RGB intensity sensors or the naked eye. The ability to detect ZIKV directly from crude human sample matrices (blood, urine, and saliva) demonstrates our device's utility for widespread clinical deployment. Together, these advances enable our system to host the key components necessary to expand the use of nucleic acid amplification-based detection assays towards point-of-care settings where they are needed most.

  14. Detection of Wolbachia in Aedes albopictus and Their Effects on Chikungunya Virus.

    PubMed

    Ahmad, Noor Afizah; Vythilingam, Indra; Lim, Yvonne A L; Zabari, Nur Zatil Aqmar M; Lee, Han Lim

    2017-01-11

    Wolbachia-based vector control strategies have been proposed as a means to augment the currently existing measures for controlling dengue and chikungunya vectors. Prior to utilizing Wolbachia as a novel vector control strategy, it is crucial to understand the Wolbachia-mosquito interactions. In this study, field surveys were conducted to screen for the infection status of Wolbachia in field-collected Aedes albopictus The effects of Wolbachia in its native host toward the replication and dissemination of chikungunya virus (CHIKV) was also studied. The prevalence of Wolbachia-infected field-collected Ae. albopictus was estimated to be 98.6% (N = 142) for females and 95.1% (N = 102) for males in the population studied. The Ae. albopictus were naturally infected with both wAlbA and wAlbB strains. We also found that the native Wolbachia has no impact on CHIKV infection and minimal effect on CHIKV dissemination to secondary organs. © The American Society of Tropical Medicine and Hygiene.

  15. Prevalence of dengue and chikungunya virus infections in north-eastern Tanzania: a cross sectional study among participants presenting with malaria-like symptoms.

    PubMed

    Kajeguka, Debora C; Kaaya, Robert D; Mwakalinga, Steven; Ndossi, Rogathe; Ndaro, Arnold; Chilongola, Jaffu O; Mosha, Franklin W; Schiøler, Karin L; Kavishe, Reginald A; Alifrangis, Michael

    2016-04-26

    In spite of increasing reports of dengue and chikungunya activity in Tanzania, limited research has been done to document the general epidemiology of dengue and chikungunya in the country. This study aimed at determining the sero-prevalence and prevalence of acute infections of dengue and chikungunya virus among participants presenting with malaria-like symptoms (fever, headache, rash, vomit, and joint pain) in three communities with distinct ecologies of north-eastern Tanzania. Cross sectional studies were conducted among 1100 participants (aged 2-70 years) presenting with malaria-like symptoms at health facilities at Bondo dispensary (Bondo, Tanga), Hai hospital (Hai, Kilimanjaro) and TPC hospital (Lower Moshi). Participants who were malaria negative using rapid diagnostic tests (mRDT) were screened for sero-positivity towards dengue and chikungunya Immunoglobulin G and M (IgG and IgM) using ELISA-based kits. Participants with specific symptoms defined as probable dengue and/or chikungunya by WHO (fever and various combinations of symptoms such as headache, rash, nausea/vomit, and joint pain) were further screened for acute dengue and chikungunya infections by PCR. Out of a total of 1100 participants recruited, 91.2 % (n = 1003) were malaria negative by mRDT. Out of these, few of the participants (<5 %) were dengue IgM or IgG positive. A total of 381 participants had fever out of which 8.7 % (33/381) met the defined criteria for probable dengue, though none (0 %) was confirmed to be acute cases. Chikungunya IgM positives among febrile participants were 12.9 % (49/381) while IgG positives were at 3.7 % (14/381). A total of 74.2 % (283/381) participants met the defined criteria for probable chikungunya and 4.2 % (11/263) were confirmed by PCR to be acute chikungunya cases. Further analyses revealed that headache and joint pain were significantly associated with chikungunya IgM seropositivity. In north-eastern Tanzania, mainly chikungunya virus appears

  16. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    NASA Astrophysics Data System (ADS)

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-11-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management.

  17. Serum metabolomics analysis of patients with chikungunya and dengue mono/co-infections reveals distinct metabolite signatures in the three disease conditions

    PubMed Central

    Shrinet, Jatin; Shastri, Jayanthi S.; Gaind, Rajni; Bhavesh, Neel Sarovar; Sunil, Sujatha

    2016-01-01

    Chikungunya and dengue are arboviral infections with overlapping clinical symptoms. A subset of chikungunya infection occurs also as co-infections with dengue, resulting in complications during diagnosis and patient management. The present study was undertaken to identify the global metabolome of patient sera infected with chikungunya as mono infections and with dengue as co-infections. Using nuclear magnetic resonance (NMR) spectroscopy, the metabolome of sera of three disease conditions, namely, chikungunya and dengue as mono-infections and when co-infected were ascertained and compared with healthy individuals. Further, the cohorts were analyzed on the basis of age, onset of fever and joint involvement. Here we show that many metabolites in the serum are significantly differentially regulated during chikungunya mono-infection as well as during chikungunya co-infection with dengue. We observed that glycine, serine, threonine, galactose and pyrimidine metabolisms are the most perturbed pathways in both mono and co-infection conditions. The affected pathways in our study correlate well with the clinical manifestation like fever, inflammation, energy deprivation and joint pain during the infections. These results may serve as a starting point for validations and identification of distinct biomolecules that could be exploited as biomarker candidates thereby helping in better patient management. PMID:27845374

  18. 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

  19. Longitudinal Analysis of Natural Killer Cells in Dengue Virus-Infected Patients in Comparison to Chikungunya and Chikungunya/Dengue Virus-Infected Patients

    PubMed Central

    Petitdemange, Caroline; Wauquier, Nadia; Devilliers, Hervé; Yssel, Hans; Mombo, Illich; Caron, Mélanie; Nkoghé, Dieudonné; Debré, Patrice; Leroy, Eric; Vieillard, Vincent

    2016-01-01

    Background Dengue virus (DENV) is the most prominent arbovirus worldwide, causing major epidemics in South-East Asia, South America and Africa. In 2010, a major DENV-2 outbreak occurred in Gabon with cases of patients co-infected with chikungunya virus (CHIKV). Although the innate immune response is thought to be of primordial importance in the development and outcome of arbovirus-associated pathologies, our knowledge of the role of natural killer (NK) cells during DENV-2 infection is in its infancy. Methodology We performed the first extensive comparative longitudinal characterization of NK cells in patients infected by DENV-2, CHIKV or both viruses. Hierarchical clustering and principal component analyses were performed to discriminate between CHIKV and DENV-2 infected patients. Principal Findings We observed that both activation and differentiation of NK cells are induced during the acute phase of infection by DENV-2 and CHIKV. Combinatorial analysis however, revealed that both arboviruses induced two different signatures of NK-cell responses, with CHIKV more associated with terminal differentiation, and DENV-2 with inhibitory KIRs. We show also that intracellular production of interferon-γ (IFN-γ) by NK cells is strongly stimulated in acute DENV-2 infection, compared to CHIKV. Conclusions/Significance Although specific differences were observed between CHIKV and DENV-2 infections, the significant remodeling of NK cell populations observed here suggests their potential roles in the control of both infections. PMID:26938618

  20. Point of sampling detection of Zika virus within a multiplexed kit capable of detecting dengue and chikungunya.

    PubMed

    Yaren, Ozlem; Alto, Barry W; Gangodkar, Priyanka V; Ranade, Shatakshi R; Patil, Kunal N; Bradley, Kevin M; Yang, Zunyi; Phadke, Nikhil; Benner, Steven A

    2017-04-20

    Zika, dengue, and chikungunya are three mosquito-borne viruses having overlapping transmission vectors. They cause diseases having similar symptoms in human patients, but requiring different immediate management steps. Therefore, rapid (< one hour) discrimination of these three viruses in patient samples and trapped mosquitoes is needed. The need for speed precludes any assay that requires complex up-front sample preparation, such as extraction of nucleic acids from the sample. Also precluded in robust point-of-sampling assays is downstream release of the amplicon mixture, as this risks contamination of future samples that will give false positives. Procedures are reported that directly test urine and plasma (for patient diagnostics) or crushed mosquito carcasses (for environmental surveillance). Carcasses are captured on paper samples carrying quaternary ammonium groups (Q-paper), which may be directly introduced into the assay. To avoid the time and instrumentation requirements of PCR, the procedure uses loop-mediated isothermal amplification (LAMP). Downstream detection is done in sealed tubes, with dTTP-dUTP mixtures in the LAMP with a thermolabile uracil DNA glycosylase (UDG); this offers a second mechanism to prevent forward contamination. Reverse transcription LAMP (RT-LAMP) reagents are distributed dry without requiring a continuous chain of refrigeration. The tests detect viral RNA in unprocessed urine and other biological samples, distinguishing Zika, chikungunya, and dengue in urine and in mosquitoes infected with live Zika and chikungunya viruses. The limits of detection (LODs) are ~0.71 pfu equivalent viral RNAs for Zika, ~1.22 pfu equivalent viral RNAs for dengue, and ~38 copies of chikungunya viral RNA. A handheld, battery-powered device with an orange filter was constructed to visualize the output. Preliminary data showed that this architecture, working with pre-prepared tubes holding lyophilized reagent/enzyme mixtures and shipped without a chain

  1. How Chikungunya Virus Virology Affects Its Epidemiology and Transmission: Implications for Influencing Public Health.

    PubMed

    Powers, Ann M

    2016-12-15

    Chikungunya virus has been causing a series of ongoing epidemics around the globe for the past 12 years. During that time, estimates indicate that >4 million cases occurred worldwide. Despite the magnitude of these outbreaks and the broad interest in understanding the virus and disease, significant gaps still exist in our knowledge base. An in-depth understanding of the basic virological elements that can affect the epidemiology of the agent is critical for future development of control and treatment products. This work describes how knowledge of various viral genetic and structural elements has begun to advance the development of vaccines and therapeutics and suggests that further knowledge is needed to provide additional options. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  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. A Case of Initially Undiagnosed Chikungunya Arthritis Developing into Chronic Phase in a Nonendemic Area

    PubMed Central

    Leung, Moon Ho

    2017-01-01

    This case report described a 40-year-old lady presented with fever, headache, arthralgia, myalgia, and impaired liver function after returning from the Philippines. Chikungunya virus (CHIKV) and dengue serology were negative. Eight weeks after initial presentation, she experienced inflammatory polyarthritis mimic rheumatoid arthritis. This time CHIKV-IgM was detected, together with a >4-fold rise of CHIKV-polyvalent-antibody titre. The first CHIKV-IgM negative sample was reexamined and was CHIKV-PCR positive. CHIKV infection was confirmed and diagnosis of CHIKV-related arthritis was made. A quarter of CHIKV infected individuals develop post-CHIKV rheumatisms that affect quality of life and may need treatment with Disease Modifying Antirheumatic Drugs. This case highlights the importance of considering CHIKV infection in patients present with symmetrical polyarthritis particularly after travel to endemic regions. Testing of both CHIKV acute and convalescent-phase serum for CHIKV antibodies and PCR is recommended in suspicious case. PMID:28408930

  4. Chikungunya Virus Glycoproteins Pseudotype with Lentiviral Vectors and Reveal a Broad Spectrum of Cellular Tropism

    PubMed Central

    Wang, Hua; Liu, Shuangchun; Yu, Lianhua; Sun, Lingfen; Qu, Ying

    2014-01-01

    Background Outbreaks of the Chikungunya virus (CHIKV) infection has been documented in over 40 countries, resulting in clinical symptoms characterized by fever and joint pain. Diagnosing CHIKV in a clinical lab setting is often omitted because of the high lab safety requirement. An infection system that mimics CHIKV infection will permit clinical evaluation of the production of neutralizing antibody for both disease diagnostics and treatment. Methodology/Principal Findings We generated a CHIKV construct expressing CHIKV structural proteins. This construct permits the production of CHIKV pseudo-viral particles with a luciferase reporter. The pseudo-virus was able to infect a wide range of cell lines. The pseudovirus could be neutralized by the addition of neutralizing antibodies from patients. Conclusions Taken together, we have developed a powerful system that can be handled at biosafety level 2 laboratories for evaluation of existence of CHIKV neutralizing antibodies. PMID:25333782

  5. 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

  6. 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

  7. Characterization of N-glycosylation profiles from mammalian and insect cell derived chikungunya VLP.

    PubMed

    Lancaster, Catherine; Pristatsky, Pavlo; Hoang, Van M; Casimiro, Danilo R; Schwartz, Richard M; Rustandi, Richard; Ha, Sha

    2016-10-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes severe arthralgia. The envelope of CHIKV is composed of 240 copies of two glycoproteins: E1 and E2. In this work, we have characterized the N-glycosylation patterns of CHIKV virus-like particles (VLPs), containing both E1 and E2 proteins, derived from mammalian and insect cells using hydrophilic interaction liquid chromatography (HILIC) with fluorescence (FL) and mass spectrometry (MS) detection. While HEK293 derived CHIKV VLPs contain oligomannose, hybrid and complex glycans, VLPs derived from SfBasic predominantly contain oligomannose glycans. This strong host dependence of N-glycosylation pattern resembles other alphaviruses such as SINV. The VLPs from HEK293 and SfBasic, with significantly different N-glycosylation profiles, are valuable reagents enabling future in-depth correlation studies between immunogenicity and glycosylation. In addition, the characterization tools presented here allow one to monitor glycosylation during vaccine process development and ensure process consistency.

  8. 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

  9. 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.

  10. A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection.

    PubMed

    Akahata, Wataru; Yang, Zhi-Yong; Andersen, Hanne; Sun, Siyang; Holdaway, Heather A; Kong, Wing-Pui; Lewis, Mark G; Higgs, Stephen; Rossmann, Michael G; Rao, Srinivas; Nabel, Gary J

    2010-03-01

    Chikungunya virus (CHIKV) has infected millions of people in Africa, Europe and Asia since this alphavirus reemerged from Kenya in 2004. The severity of the disease and the spread of this epidemic virus present a serious public health threat in the absence of vaccines or antiviral therapies. Here, we describe a new vaccine that protects against CHIKV infection of nonhuman primates. We show that selective expression of viral structural proteins gives rise to virus-like particles (VLPs) in vitro that resemble replication-competent alphaviruses. Immunization with these VLPs elicited neutralizing antibodies against envelope proteins from alternative CHIKV strains. Monkeys immunized with VLPs produced high-titer neutralizing antibodies that protected against viremia after high-dose challenge. We transferred these antibodies into immunodeficient mice, where they protected against subsequent lethal CHIKV challenge, indicating a humoral mechanism of protection. Immunization with alphavirus VLP vaccines represents a strategy to contain the spread of CHIKV and related pathogenic viruses in humans.

  11. [Chikungunya in the Dominican Republic: lessons learned in the first six months].

    PubMed

    Pimentel, Raquel; Skewes-Ramm, Ronald; Moya, José

    2014-11-01

    The chikungunya epidemic in the Dominican Republic began in February 2014. During the first six months 429 421 cases were recorded, representing 65% of all those notified to the Pan American Health Organization by 33 countries and territories of the Region of the Americas. This epidemic has spread quickly in the Dominican Republic, requiring a focused intersectoral response, led by the Ministry of Public Health and involving major efforts by the National Epidemiological System and the health services network. Given that the virus will affect thousands of people, this article seeks to describe the actions that have already been carried out, and to share the results and lessons learned during these first months with health ministries and professionals in the countries of the Region, in order to assist them to prepare an appropriate response to confront the epidemic effectively and efficiently.

  12. 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

  13. Chikungunya virus and West Nile virus infections imported into Belgium, 2007-2012.

    PubMed

    VAN DEN Bossche, D; Cnops, L; Meersman, K; Domingo, C; VAN Gompel, A; VAN Esbroeck, M

    2015-07-01

    Arboviral infections are emerging among tourists travelling to (sub)tropical regions. This study aims to describe the importation of chikungunya virus (CHIKV) and West Nile virus (WNV) into Belgium over a 6-year period from 2007 to 2012. Clinical samples were obtained from travellers presenting at the outpatient clinic of the Institute of Tropical Medicine (ITM), Antwerp, Belgium or submitted to the Central Laboratory for Clinical Biology of the ITM. Testing was performed by serology and/or by real-time reverse transcriptase-polymerase chain reaction. A total of 1288 returning travellers were investigated for CHIKV infection resulting in 34 confirmed and two probable diagnoses (2·80%). Out of 899 patients, four confirmed and one probable imported WNV infections were diagnosed (0·55%). No locally acquired cases have been registered in Belgium until now and the geographical origin of the imported infections reflects the global locations where the viruses are circulating.

  14. 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.

  15. 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.

  16. 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

  17. 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.

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

    PubMed Central

    Smith, Daniel E.; Beckham, J. David; Tyler, Kenneth L.

    2016-01-01

    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

  19. 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

  20. 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.

  1. [Chikungunya outbreak on Reunion Island in 2005/2006: role of hospital physicians in raising alert].

    PubMed

    Boisson, V; Cresta, M P; Thibault, L; Antok, E; Lemant, J; Gradel, A; André, H; Tixier, F; Winer, A

    2012-03-01

    The epidemic of chikungunya (CHIK) that swept through Reunion Island from late 2005 to mid 2006 affected 38.2% of the population, i.e., 300000 people. Although this outbreak took place in a French overseas department with high public health standards, failure to anticipate a large-scale epidemic associated with unprecedented severity and unexpectedly high mortality led to a major public health crisis. The purpose of this report is to provide a complete account of the experience of hospital intensive care physicians in addressing problems ranging from discovery of severe forms to management of a major health crisis. This report underlines the role of the head hospital physician and the necessity of mutual trust and collaboration with supervisory authorities.

  2. Tetrahymena mutants with short telomeres.

    PubMed Central

    Ahmed, S; Sheng, H; Niu, L; Henderson, E

    1998-01-01

    Telomere length is dynamic in many organisms. Genetic screens that identify mutants with altered telomere lengths are essential if we are to understand how telomere length is regulated in vivo. In Tetrahymena thermophila, telomeres become long at 30 degrees, and growth rate slows. A slow-growing culture with long telomeres is often overgrown by a variant cell type with short telomeres and a rapid-doubling rate. Here we show that this variant cell type with short telomeres is in fact a mutant with a genetic defect in telomere length regulation. One of these telomere growth inhibited forever (tgi) mutants was heterozygous for a telomerase RNA mutation, and this mutant telomerase RNA caused telomere shortening when overexpressed in wild-type cells. Several other tgi mutants were also likely to be heterozygous at their mutant loci, since they reverted to wild type when selective pressure for short telomeres was removed. These results illustrate that telomere length can regulate growth rate in Tetrahymena and that this phenomenon can be exploited to identify genes involved in telomere length regulation. PMID:9755196

  3. Chikungunya Fever Among Patients with Acute Febrile Illness Attending a Tertiary Care Hospital in Mumbai

    PubMed Central

    Galate, Lata Baswanna; Agrawal, Sachee R; Shastri, Jayanthi S; Londhey, Vikram

    2016-01-01

    Background: Chikungunya fever (CHIK) is an arboviral disease. Dengue fever (DENG) and CHIK are indistinguishable clinically and need to be differentiated by laboratory investigations. Purpose: This study aimed at estimating the seroprevalence of CHIK mono-infection and CHIK and DENG dual infection in suspected patients. We also analyzed the age, sex distribution, joint involvement, and relation of joint movement restriction with visual analog scale (VAS). Materials and Methods: Two hundred patients clinically suspected with DENG and CHIK were enrolled from a Tertiary Care Hospital in Mumbai from April 2012 to October 2013. The detailed history and examination findings were recorded. Serum samples were subjected to DENG and CHIK immunoglobulin G (IgM) enzyme-linked immunosorbent assay (ELISA). Results: The seroprevalence of CHIK was 12.5%. Mono-infection of CHIK was 3%, and CHIK and DENG dual infection was 9.5%. Most affected age group in CHIK cases was 46–60 years wherein female preponderance was seen. All 6 patients with CHIK mono-infection had fever and joint involvement; knee and elbow were the most commonly affected joints. All CHIK patients had VAS score of 6–10 with restricted joint movement. Of the patients with dual infection, the majorities were from 31 to 45 years with male preponderance; all had fever and joint pain mainly affecting knee and elbow. Of patients who had VAS score 6–10 in patients with dual infection, only 5.26% had restricted joint movement. Conclusion: IgM ELISA for Chikungunya infection should be included in the routine laboratory tests for acute febrile illness. PMID:27365916

  4. First reported chikungunya fever outbreak in the republic of Congo, 2011.

    PubMed

    Moyen, Nanikaly; Thiberville, Simon-Djamel; Pastorino, Boris; Nougairede, Antoine; Thirion, Laurence; Mombouli, Jean-Vivien; Dimi, Yannick; Leparc-Goffart, Isabelle; Capobianchi, Maria Rosaria; Lepfoundzou, Amelia Dzia; de Lamballerie, Xavier

    2014-01-01

    Chikungunya is an Aedes -borne disease characterised by febrile arthralgia and responsible for massive outbreaks. We present a prospective clinical cohort study and a retrospective serological study relating to a CHIK outbreak, in the Republic of Congo in 2011. We analysed 317 suspected cases, of which 308 (97.2%) lived in the city of Brazzaville (66.6% in the South area). Amongst them, 37 (11.7%) were CHIKV+ve patients (i.e., biologically confirmed by a real-time RT-PCR assay), of whom 36 (97.3%) had fever, 22 (66.7%) myalgia and 32 (86.5%) arthralgia. All tested negative for dengue. The distribution of incident cases within Brazzaville districts was compared with CHIKV seroprevalence before the outbreak (34.4% in 517 blood donors), providing evidence for previous circulation of CHIKV. We applied a CHIK clinical score to 126 patients recruited within the two first day of illness (including 28 CHIKV+ves (22.2%)) with sensitivity (78.6%) and specificity (72.4%) values comparing with those of the referent study in Reunion Island. The negative predictive value was high (92%), but the positive predictive value (45%) indicate poor potential contribution to medical practice to identify CHIKV+ve patients in low prevalence outbreaks. However, the score allowed a slightly more accurate follow-up of the evolution of the outbreak than the criterion "fever+arthralgia". The complete sequencing of a Congolase isolate (Brazza_MRS1) demonstrated belonging to the East/Central/South African lineage and was further used for producing a robust genome-scale CHIKV phylogenetic analysis. We describe the first Chikungunya outbreak declared in the Republic of Congo. The seroprevalence study conducted amongst blood donors before outbreak provided evidence for previous CHIKV circulation. We suggest that a more systematic survey of the entomological situation and of arbovirus circulation is necessary in Central Africa for better understanding the environmental, microbiological and

  5. 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.

  6. Mathematical studies on the sterile insect technique for the Chikungunya disease and Aedes albopictus.

    PubMed

    Dumont, Y; Tchuenche, J M

    2012-11-01

    Chikungunya is an arthropod-borne disease caused by the Asian tiger mosquito, Aedes albopictus. It can be an important burden to public health and a great cause of morbidity and, sometimes, mortality. Understanding if and when disease control measures should be taken is key to curtail its spread. Dumont and Chiroleu (Math Biosc Eng 7(2):315-348, 2010) showed that the use of chemical control tools such as adulticide and larvicide, and mechanical control, which consists of reducing the breeding sites, would have been useful to control the explosive 2006 epidemic in Réunion Island. Despite this, chemical control tools cannot be of long-time use, because they can induce mosquito resistance, and are detrimental to the biodiversity. It is therefore necessary to develop and test new control tools that are more sustainable, with the same efficacy (if possible). Mathematical models of sterile insect technique (SIT) to prevent, reduce, eliminate or stop an epidemic of Chikungunya are formulated and analysed. In particular, we propose a new model that considers pulsed periodic releases, which leads to a hybrid dynamical system. This pulsed SIT model is coupled with the human population at different epidemiological states in order to assess its efficacy. Numerical simulations for the pulsed SIT, using an appropriate numerical scheme are provided. Analytical and numerical results indicate that pulsed SIT with small and frequent releases can be an alternative to chemical control tools, but only if it is used or applied early after the beginning of the epidemic or as a preventive tool.

  7. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

    PubMed Central

    Kautz, Tiffany F.; Auguste, Albert J.; Erasmus, Jesse H.; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L.; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E.; Silfa, Jael; Bido, Franklin

    2016-01-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  8. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences.

    PubMed

    Sahadeo, N S D; Allicock, O M; De Salazar, P M; Auguste, A J; Widen, S; Olowokure, B; Gutierrez, C; Valadere, A M; Polson-Edwards, K; Weaver, S C; Carrington, C V F

    2017-01-01

    Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an 'Asian/American' lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 × 10(-4) substitutions per site per year (95% higher probability density, 2.9-7.9 × 10(-4)) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage.

  9. Comprehensive Genome Scale Phylogenetic Study Provides New Insights on the Global Expansion of Chikungunya Virus.

    PubMed

    Chen, Rubing; Puri, Vinita; Fedorova, Nadia; Lin, David; Hari, Kumar L; Jain, Ravi; Rodas, Juan David; Das, Suman R; Shabman, Reed S; Weaver, Scott C

    2016-12-01

    Since the India and Indian Ocean outbreaks of 2005 and 2006, the global distribution of chikungunya virus (CHIKV) and the locations of epidemics have dramatically shifted. First, the Indian Ocean lineage (IOL) caused sustained epidemics in India and has radiated to many other countries. Second, the Asian lineage has caused frequent outbreaks in the Pacific islands and in 2013 was introduced into the Caribbean, followed by rapid spread to nearly all of the neotropics. Further, CHIKV epidemics, as well as exported cases, have been reported in central Africa after a long period of perceived silence. To understand these changes and to anticipate the future of the virus, the exact distribution, genetic diversity, transmission routes, and future epidemic potential of CHIKV require further assessment. To do so, we conducted the most comprehensive phylogenetic analysis to date, examined CHIKV evolution and transmission, and explored distinct genetic factors associated with the emergence of the East/Central/South African (ECSA) lineage, the IOL, and the Asian lineage. Our results reveal contrasting evolutionary patterns among the lineages, with growing genetic diversities observed in each, and suggest that CHIKV will continue to be a major public health threat with the potential for further emergence and spread. Chikungunya fever is a reemerging infectious disease that is transmitted by Aedes mosquitoes and causes severe health and economic burdens in affected populations. Since the unprecedented Indian Ocean and Indian subcontinent outbreaks of 2005 and 2006, CHIKV has further expanded its geographic range, including to the Americas in 2013. Its evolution and transmission during and following these epidemics, as well as the recent evolution and spread of other lineages, require optimal assessment. Using newly obtained genome sequences, we provide a comprehensive update of the global distribution of CHIKV genetic diversity and analyze factors associated with recent

  10. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014.

    PubMed

    Langsjoen, Rose M; Rubinstein, Rebecca J; Kautz, Tiffany F; Auguste, Albert J; Erasmus, Jesse H; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E; Silfa, Jael; Bido, Franklin; Dacso, Matthew; Weaver, Scott C

    2016-12-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  11. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences

    PubMed Central

    Sahadeo, N. S. D.; Allicock, O. M.; De Salazar, P. M.; Auguste, A. J.; Widen, S.; Olowokure, B.; Gutierrez, C.; Valadere, A. M.; Polson-Edwards, K.; Weaver, S. C.

    2017-01-01

    Abstract Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an ‘Asian/American’ lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 × 10−4 substitutions per site per year (95% higher probability density, 2.9–7.9 × 10−4) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage. PMID:28480053

  12. Chikungunya Virus Infection of Cell Lines: Analysis of the East, Central and South African Lineage

    PubMed Central

    Wikan, Nitwara; Sakoonwatanyoo, Prirayapak; Ubol, Sukathida; Yoksan, Sutee; Smith, Duncan R.

    2012-01-01

    Chikungunya virus (CHIKV) is a re-emerging mosquito borne alphavirus that has caused large scale epidemics in the countries around the Indian Ocean, as well as leading to autochthonous transmission in some European countries. The transmission of the disease has been driven by the emergence of an African lineage of CHIKV with enhanced transmission and dissemination in Aedes mosquito hosts. Two main genotypes of this lineage have been circulating, characterized by the presence of a substitution of a valine for an alanine at position 226 of the E1 protein. The outbreak, numbering in millions of cases in the infected areas, has been associated with increasing numbers of cases with non-classical presentation including encephalitis and meningitis. This study sought to compare the original Ross strain with two isolates from the recent outbreak of chikungunya fever in respect of infectivity and the induction of apoptosis in eight mammalian cell lines and two insect cell lines, in addition to generating a comprehensive virus production profile for one of the newer isolates. Results showed that in mammalian cells there were few differences in either tropism or pathogenicity as assessed by induction of apoptosis with the exception of Hela cells were the recent valine isolate showed less infectivity. The Aedes albopictus C6/36 cell line was however significantly more permissive for both of the more recent isolates than the Ross strain. The results suggest that the increased infectivity seen in insect cells derives from an evolution of the CHIKV genome not solely associated with the E1:226 substitution. PMID:22299053

  13. Clinical manifestations of chikungunya among university professors and staff in Santo Domingo, the Dominican Republic.

    PubMed

    Zingman, Michael A; Paulino, Amarilis Then; Payano, Matilde Peguero

    2017-08-21

    To further characterize chikungunya virus infection and its associated clinical manifestations, using a sample of university professors and staff in Santo Domingo, the Dominican Republic. A cross-sectional study with quota sampling by department was performed to obtain a convenience sample of professors (n = 736) and staff (n = 499) at the Universidad Autónoma de Santo Domingo. Surveys were used to collect demographic and infection data during the fall term of 2014. Univariate and bivariate analyses were carried out to quantify infection and clinical manifestation prevalence and to assess relationships of these outcomes with age, sex, and acute phase duration. Of 1 236 participants, 49% reported infection (professors = 41%; staff = 61%). Of these, 53% also reported the presence of chronic effects, largely arthralgia (48%). Significant relationships were observed between reported infection and sex (P = 0.023), age (P < 0.001), and occupation (P < 0.001). More headache (P = 0.008) and edema (P < 0.001) in females, more headache (P = 0.005) in younger subjects, and more myalgia (P = 0.006) in those with longer acute symptoms were found. Additionally, more chronic arthralgia (P < 0.001; P = 0.003) and chronic edema (P < 0.001; P = 0.001) in females and older subjects, and more chronic myalgia (P = 0.041) and chronic edema (P = 0.037) in those with longer acute symptoms were observed. To the authors knowledge, this is the first population-based chikungunya prevalence study in the Dominican Republic, and the first to explore clinical manifestations in a university setting. The findings reflect results from studies following the 2005 - 2006 Reunion Island outbreak: prevalence of infection and chronic arthralgia, as well as associations with sex, age, and acute intensity. Longitudinal research can provide further insight into these effects.

  14. 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. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

  15. Recommendations of the Brazilian Society of Rheumatology for diagnosis and treatment of Chikungunya fever. Part 1 - Diagnosis and special situations.

    PubMed

    Marques, Claudia Diniz Lopes; Duarte, Angela Luzia Branco Pinto; Ranzolin, Aline; Dantas, Andrea Tavares; Cavalcanti, Nara Gualberto; Gonçalves, Rafaela Silva Guimarães; Rocha Junior, Laurindo Ferreira da; Valadares, Lilian David de Azevedo; Melo, Ana Karla Guedes de; Freire, Eutilia Andrade Medeiros; Teixeira, Roberto; Bezerra Neto, Francisco Alves; Medeiros, Marta Maria das Chagas; Carvalho, Jozélio Freire de; Santos, Mario Sergio F; Océa, Regina Adalva de L Couto; Levy, Roger A; Andrade, Carlos Augusto Ferreira de; Pinheiro, Geraldo da Rocha Castelar; Abreu, Mirhelen Mendes; Verztman, José Fernando; Merenlender, Selma; Ribeiro, Sandra Lucia Euzebio; Costa, Izaias Pereira da; Pileggi, Gecilmara; Trevisani, Virginia Fernandes Moça; Lopes, Max Igor Banks; Brito, Carlos; Figueiredo, Eduardo; Queiroga, Fabio; Feitosa, Tiago; Tenório, Angélica da Silva; Siqueira, Gisela Rocha de; Paiva, Renata; Vasconcelos, José Tupinambá Sousa; Christopoulos, Georges

    2017-01-01

    Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2. Copyright © 2017. Published by Elsevier Editora Ltda.

  16. Community context and sub-neighborhood scale detail to explain dengue, chikungunya and Zika patterns in Cali, Colombia.

    PubMed

    Krystosik, Amy R; Curtis, Andrew; Buritica, Paola; Ajayakumar, Jayakrishnan; Squires, Robert; Dávalos, Diana; Pacheco, Robinson; Bhatta, Madhav P; James, Mark A

    2017-01-01

    Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali's dengue patterns but lack the sub-neighborhood-scale detail investigated here. Spatial-video geonarratives (SVG) with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data. SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system. Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk.

  17. Potential of Aedes aegypti and Aedes albopictus populations in the Central African Republic to transmit enzootic chikungunya virus strains.

    PubMed

    Ngoagouni, Carine; Kamgang, Basile; Kazanji, Mirdad; Paupy, Christophe; Nakouné, Emmanuel

    2017-03-27

    Major chikungunya outbreaks have affected several Central African countries during the past decade. The chikungunya virus (CHIKV) was isolated from humans and sylvan mosquitoes in the Central African Republic (CAR) during the 1970 and 1980s but has not been found recently, despite the presence of Aedes albopictus since 2010. The risk of a massive chikungunya epidemic is therefore potentially high, as the human populations are immunologically naïve and because of the presence of the mosquito vector. In order to estimate the risk of a large outbreak, we assessed the vector competence of local Ae. aegypti and Ae. albopictus populations for ancient local strains of CHIKV in CAR. Mosquitoes were orally infected with the virus, and its presence in mosquito saliva was analysed 7 and 14 days post-infection (dpi) by quantitative reverse transcriptase polymerase chain reaction. The two species had similar infection rates at 7 and 14 days, and the dissemination rate of both vectors was ≥ 80% at 14 dpi. Only females followed up to 14 dpi had CHKV in their saliva. These results confirm the risk of transmission of enzootic CHIKV by anthropophilic vectors such as Ae. aegypti and Ae. albopictus.

  18. Community context and sub-neighborhood scale detail to explain dengue, chikungunya and Zika patterns in Cali, Colombia

    PubMed Central

    Curtis, Andrew; Buritica, Paola; Ajayakumar, Jayakrishnan; Squires, Robert; Dávalos, Diana; Pacheco, Robinson; Bhatta, Madhav P.; James, Mark A.

    2017-01-01

    Background Cali, Colombia has experienced chikungunya and Zika outbreaks and hypoendemic dengue. Studies have explained Cali’s dengue patterns but lack the sub-neighborhood-scale detail investigated here. Methods Spatial-video geonarratives (SVG) with Ministry of Health officials and Community Health Workers were collected in hotspots, providing perspective on perceptions of why dengue, chikungunya and Zika hotspots exist, impediments to control, and social outcomes. Using spatial video and Google Street View, sub-neighborhood features possibly contributing to incidence were mapped to create risk surfaces, later compared with dengue, chikungunya and Zika case data. Results SVG captured insights in 24 neighborhoods. Trash and water risks in Calipso were mapped using SVG results. Perceived risk factors included proximity to standing water, canals, poverty, invasions, localized violence and military migration. These risks overlapped case density maps and identified areas that are suitable for transmission but are possibly underreporting to the surveillance system. Conclusion Resulting risk maps with local context could be leveraged to increase vector-control efficiency- targeting key areas of environmental risk. PMID:28767730

  19. Molecular Characterisation of Clinical Isolates of Chikungunya Virus: A Study from Tertiary Care Hospitals in Southern India

    PubMed Central

    Peerapur, B.V.

    2016-01-01

    Introduction Indian ocean islands and India have experienced massive severe Chikungunya outbreak from 2005 up till now and then Chikungunya became epidemic in India. The mutations that occurred in E1 gene were responsible for increased infectivity, virulence and host adaptability. It is important to find out the genotype and its probable evolvement and novel mutations in the E1 gene reported during 2006-2009 from the current isolates, which may affect the local protein structure. Aim To perform Molecular diagnosis and Molecular Characterisation of Chikungunya virus isolates. Materials and Methods A total of 33 samples were included in the study. RNA was isolated from 33 serum samples and Real time PCR was carried out. Further, Nested PCR and E1 partial gene sequencing was performed. Phylogenetic analysis, mutational analysis and protein modelling studies were carried out. Results Out of 33 samples tested, 31 were found positive for CHIK RNA. Phylogenetic analysis showed that isolates belongs to ECSA genotype and E1K211E, E1M269V and E1D284E mutations were observed from all the isolates. Conclusion The isolates may have evolved from ECSA Reunion island strains and identified unique mutations in E1 gene were maintained. These mutations have not affected local protein structure. PMID:27134872

  20. Ubiquitin-Conjugating Enzyme E2 L3 is Downregulated by the Chikungunya Virus nsP2 Protease.

    PubMed

    Ramphan, Suwipa; Khongwichit, Sarawut; Saisawang, Chonticha; Kovanich, Duangnapa; Ketterman, Albert J; Ubol, Sukathida; Auewarakul, Prasert; Roytrakul, Sittiruk; Smith, Duncan R; Kuadkitkan, Atichat

    2017-10-04

    Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus that causes chikungunya fever in humans. The CHIKV nonstructural protein 2 (nsP2) is a multifunctional protein that additionally modulates the host cell to dampen the innate immune response and inhibit other cellular processes. To further investigate the interactions of nsP2 with host cells, the protease domain of CHIKV nsP2 (nsP2-pro) was transfected into Hela cells, and differential protein expression was detected by 2-dimension (2D) polyacrylamide gel electrophoresis. A total of 21 differentially regulated (6 upregulated, 15 downregulated) spots were observed, of which 5 were identified by mass spectrometry. The downregulation of one of the identified proteins, ubiquitin-conjugating enzyme E2 L3 (UBE2L3) was confirmed by western blotting of both nsP2-pro transfection and CHIKV natural infection, and the downregulation of UBE2L3 was additionally shown to require an enzymatically active nsP2 protease domain. Transfection of full length UBE2L3 into HEK293T/17 cells prior to CHIKV infection reduced levels of infection and E protein expression but did not alter RNA genome levels. These results suggest that UBE2L3 is a cellular target of the CHIKV nsP2 protease, and this possibly mediates the pathogenesis of chikungunya fever. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  1. The Chikungunya Epidemic on La Réunion Island in 2005–2006: A Cost-of-Illness Study

    PubMed Central

    Soumahoro, Man-Koumba; Boelle, Pierre-Yves; Gaüzere, Bernard-Alex; Atsou, Kokuvi; Pelat, Camille; Lambert, Bruno; La Ruche, Guy; Gastellu-Etchegorry, Marc; Renault, Philippe; Sarazin, Marianne; Yazdanpanah, Yazdan; Flahault, Antoine; Malvy, Denis; Hanslik, Thomas

    2011-01-01

    Background This study was conducted to assess the impact of chikungunya on health costs during the epidemic that occurred on La Réunion in 2005–2006. Methodology/Principal Findings From data collected from health agencies, the additional costs incurred by chikungunya in terms of consultations, drug consumption and absence from work were determined by a comparison with the expected costs outside the epidemic period. The cost of hospitalization was estimated from data provided by the national hospitalization database for short-term care by considering all hospital stays in which the ICD-10 code A92.0 appeared. A cost-of-illness study was conducted from the perspective of the third-party payer. Direct medical costs per outpatient and inpatient case were evaluated. The costs were estimated in Euros at 2006 values. Additional reimbursements for consultations with general practitioners and drugs were estimated as €12.4 million (range: €7.7 million–€17.1 million) and €5 million (€1.9 million–€8.1 million), respectively, while the cost of hospitalization for chikungunya was estimated to be €8.5 million (€5.8 million–€8.7 million). Productivity costs were estimated as €17.4 million (€6 million–€28.9 million). The medical cost of the chikungunya epidemic was estimated as €43.9 million, 60% due to direct medical costs and 40% to indirect costs (€26.5 million and €17.4 million, respectively). The direct medical cost was assessed as €90 for each outpatient and €2,000 for each inpatient. Conclusions/Significance The medical management of chikungunya during the epidemic on La Réunion Island was associated with an important economic burden. The estimated cost of the reported disease can be used to evaluate the cost/efficacy and cost/benefit ratios for prevention and control programmes of emerging arboviruses. PMID:21695162

  2. Enhanced production of Chikungunya virus-like particles using a high-pH adapted spodoptera frugiperda insect cell line.

    PubMed

    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

  3. The Antiviral Alkaloid Berberine Reduces Chikungunya Virus-Induced Mitogen-Activated Protein Kinase Signaling.

    PubMed

    Varghese, Finny S; Thaa, Bastian; Amrun, Siti Naqiah; Simarmata, Diane; Rausalu, Kai; Nyman, Tuula A; Merits, Andres; McInerney, Gerald M; Ng, Lisa F P; Ahola, Tero

    2016-11-01

    Chikungunya virus (CHIKV) has infected millions of people in the tropical and subtropical regions since its reemergence in the last decade. We recently identified the nontoxic plant alkaloid berberine as an antiviral substance against CHIKV in a high-throughput screen. Here, we show that berberine is effective in multiple cell types against a variety of CHIKV strains, also at a high multiplicity of infection, consolidating the potential of berberine as an antiviral drug. We excluded any effect of this compound on virus entry or on the activity of the viral replicase. A human phosphokinase array revealed that CHIKV infection specifically activated the major mitogen-activated protein kinase (MAPK) signaling pathways extracellular signal-related kinase (ERK), p38 and c-Jun NH2-terminal kinase (JNK). Upon treatment with berberine, this virus-induced MAPK activation was markedly reduced. Subsequent analyses with specific inhibitors of these kinases indicated that the ERK and JNK signaling cascades are important for the generation of progeny virions. In contrast to specific MAPK inhibitors, berberine lowered virus-induced activation of all major MAPK pathways and resulted in a stronger reduction in viral titers. Further, we assessed the in vivo efficacy of berberine in a mouse model and measured a significant reduction of CHIKV-induced inflammatory disease. In summary, we demonstrate the efficacy of berberine as a drug against CHIKV and highlight the importance of the MAPK signaling pathways in the alphavirus infectious cycle. Chikungunya virus (CHIKV) is a mosquito-borne virus that causes severe and persistent muscle and joint pain and has recently spread to the Americas. No licensed drug exists to counter this virus. In this study, we report that the alkaloid berberine is antiviral against different CHIKV strains and in multiple human cell lines. We demonstrate that berberine collectively reduced the virus-induced activation of cellular mitogen-activated protein kinase

  4. Bacteriorhodopsin mutants of Halobacterium sp. GRB. II. Characterization of mutants.

    PubMed

    Soppa, J; Otomo, J; Straub, J; Tittor, J; Meessen, S; Oesterhelt, D

    1989-08-05

    The bacterioopsin genes of Halobacterium sp. GRB (Ebert, K., Goebel, W., and Pfeifer, F. (1984) Mol. & Gen. Genet. 194, 91-97) wild type and 10 independent mutants of different phenotypes have been cloned and sequenced. The wild type gene has two conservative changes compared to the gene of Halobacterium halobium, so that the proteins of the two species are identical. Six different mutations at five different codons have been found, leading to the following amino acid changes compared to the wild type: Trp10----Cys (three cases), Tyr57----Asn, Asp85----Glu, Asp06----Asn (three cases), Asp96----Gly, Trp138----Arg. A first characterization of the mutant proteins is given, and their implications for models of bacteriorhodopsin structure and function are discussed.

  5. Mutant power: using mutant allele collections for yeast functional genomics

    PubMed Central

    Norman, Kaitlyn L.

    2016-01-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. PMID:26453908

  6. Mutant power: using mutant allele collections for yeast functional genomics.

    PubMed

    Norman, Kaitlyn L; Kumar, Anuj

    2016-03-01

    The budding yeast has long served as a model eukaryote for the functional genomic analysis of highly conserved signaling pathways, cellular processes and mechanisms underlying human disease. The collection of reagents available for genomics in yeast is extensive, encompassing a growing diversity of mutant collections beyond gene deletion sets in the standard wild-type S288C genetic background. We review here three main types of mutant allele collections: transposon mutagen collections, essential gene collections and overexpression libraries. Each collection provides unique and identifiable alleles that can be utilized in genome-wide, high-throughput studies. These genomic reagents are particularly informative in identifying synthetic phenotypes and functions associated with essential genes, including those modeled most effectively in complex genetic backgrounds. Several examples of genomic studies in filamentous/pseudohyphal backgrounds are provided here to illustrate this point. Additionally, the limitations of each approach are examined. Collectively, these mutant allele collections in Saccharomyces cerevisiae and the related pathogenic yeast Candida albicans promise insights toward an advanced understanding of eukaryotic molecular and cellular biology. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  7. Chikungunya virus susceptibility & variation in populations of Aedes aegypti (Diptera: Culicidae) mosquito from India.

    PubMed

    Gokhale, Mangesh D; Paingankar, Mandar S; Sudeep, Anakathil B; Parashar, Deepti

    2015-12-01

    Although having immense clinical relevance, yet only a few studies have been targeted to understand the chikungunya virus (CHIKV) susceptibility and growth in Aedes aegypti populations from India. This study was undertaken to investigate CHIKV susceptibility and growth kinetics in Ae. aegypti along with genetic heterogeneity of Ae. aegypti populations. Dose dependent CHIKV susceptibility and growth kinetic studies for three CHIKV strains reported from India were carried out in Ae. aegypti mosquito populations. The phenotypic variation and genetic heterogeneity in five Ae. aegypti populations were investigated using multivariate morphometrics and allozyme variation studies. The dissemination and growth kinetics studies of the three CHIKV strains showed no selective advantage for a particular strain of CHIKV in Ae. aegypti. At 100 per cent infection rate, five geographic Ae. aegypti populations showed differences in dissemination to three CHIKV strains. Morphometric studies revealed phenotypic variation in all the studied populations. The allelic frequencies, F statistics, and Nei's genetic identity values showed that genetic differences between the populations were small, but significant. The results obtained in this study suggest that genetic background of the vector strongly influences the CHIKV susceptibility in Ae. aegypti.

  8. A Systematic Meta-analysis of Immune Signatures in Patients With Acute Chikungunya Virus Infection

    PubMed Central

    Teng, Terk-Shin; Kam, Yiu-Wing; Lee, Bernett; Hapuarachchi, Hapuarachchige Chanditha; Wimal, Abeyewickreme; Ng, Lee-Ching; Ng, Lisa F. P.

    2015-01-01

    Background. Individuals infected with chikungunya virus (CHIKV) normally exhibit a variety of clinical manifestations during the acute phase of infection. However, studies in different patient cohorts have revealed that disease manifestations vary in frequency. Methods. Disease profiles between patients with acute CHIKV-infection and febrile patients without CHIKV were compared and examined to determine whether any clinical presentations were associated with the clinical outcome of CHIKV infection. Circulatory immune mediators profiles were then characterized and compared with data from 14 independent patient cohort studies. The particular immune mediator signature that defines acute CHIKV infection was determined. Results. Our findings revealed a specific pattern of clinical presentations of joint-specific arthralgia from this CHIKV cohort. More importantly, we identified an immune mediator signature dominated by proinflammatory cytokines, which include interferon α and γ and interleukin 2, 2R, 6, 7, 12, 15, 17, and 18, across different patient cohorts of CHIKV load associated with arthralgia. Conclusions. To our knowledge, this is the first study that associated levels of CHIKV load with arthralgia as an indicator of acute CHIKV infection. Importantly, our findings also revealed specific immune mediator signatures that can be used to better define CHIKV infection. PMID:25635123

  9. Clinical and Serological Insights from the Asian Lineage Chikungunya Outbreak in Grenada, 2014: An Observational Study.

    PubMed

    Macpherson, Calum; Noël, Trevor; Fields, Paul; Jungkind, Donald; Yearwood, Katherine; Simmons, Monika; Widjaja, Susana; Mitchell, George; Noel, Dolland; Bidaisee, Satesh; Myers, Todd E; LaBeaud, A Desiree

    2016-10-05

    Chikungunya virus (CHIKV) spread rapidly throughout the Caribbean region in 2014, and the first serologically confirmed case was seen in Grenada in July. This study investigated the outbreak of CHIKV in Grenada to identify the distinguishing clinical manifestations and the symptoms that corresponded the closest with serological test results. Sera were tested by IgM enzyme-linked immunosorbent assay and polymerase chain reaction to distinguish between cases positive or negative for CHIKV. Of 493 cases, 426 (86%) tested positive for CHIKV. The diagnostic decision rule, "Define as CHIKV positive a patient presenting with joint pain and any combination of fever, body pain, or rash," produced the closest agreement (85%) with the serological test results (Cohen's kappa, k = 0.289, P value < 0.001). When laboratory facilities are not available for diagnostic confirmation, syndromic surveillance using these four symptoms could be useful to define cases during a CHIKV outbreak when CHIKV is the predominant circulating arbovirus. © The American Society of Tropical Medicine and Hygiene.

  10. [A model for evaluation of key measures for control of chikungunya fever outbreak in China].

    PubMed

    Zhao, Jin; Liu, Ruchun; Chen, Shuilian; Chen, Tianmu

    2015-11-01

    To analyze the transmission pattern of Chikungunya (CHIK) fever in community and evaluate the effectiveness of mosquito control, case isolation and other key control measures by using ordinary differential equation (ODE) model. According to natural history of CHIK, an ODE model for the epidemiological analysis of CHIK outbreak was established. The key parameters of the model were obtained by fitting the model with reported outbreak data of the first CHIK outbreak in China. Then the outbreak characteristics without intervention, the effectiveness of mosquito control and case isolation were simulated. Without intervention, an imported case would cause an outbreak in a community with population of 11 000, and cumulative case number would exceed 941 when the total attack rate was 8.55%. The results of our simulation revealed that the effectiveness of case isolation was not perfect enough when it was implemented alone. Although the number of cases could be decreased by case isolation, the duration of outbreak would not be shortened. Differently, the effectiveness of mosquito control was remarkable. In addition, the earlier the measure was implemented, the better the effectiveness would be. The effectiveness of mosquito control plus case isolation was same with mosquito control. To control a CHIK outbreak, mosquito control is the most recommended measures. However, case isolation is also necessary as the supplementation of mosquito control.

  11. School-Based Health Education in Yucatan, Mexico about the Chikungunya Virus and Mosquito Illness Prevention.

    PubMed

    Choo, Monica Seungah; Blackwood, R Alexander

    2017-05-31

    The Chikungunya virus (CHIKV) has been rapidly spreading throughout Latin America, utilizing pre-existing vectors to infiltrate the immunologically naïve populations. With the current rise of the Zika Virus, there is an urgent need for more rigorous vector control efforts to prevent further Zika breakout. We designed a school-based education module on CHIKV and mosquito prevention and presented it to the local students of ages of 6-18 in a rural town called Sudzal in Yucatan, Mexico. We distributed questionnaires before and after education to test the students' knowledge of CHIKV and mosquito prevention. Chi-squared test was performed to determine the efficacy of the presentation in increasing their knowledge. The education presentation has proven to effectively educate the local residents in several critical methods of mosquito prevention, increasing the average test scores by 67% post-education. These include applying repellent, staying hydrated during recuperation, and cleaning indoor water containers to eliminate breeding sites (P<0.001). Furthermore, the questionnaire captured the residents' behavioral patterns regarding CHIKV and mosquito prevention and identified cultural, ecological, and socioeconomic factors hindering effective implementation of vector control.

  12. A phenotypic assay to identify Chikungunya virus inhibitors targeting the nonstructural protein nsP2.

    PubMed

    Lucas-Hourani, Marianne; Lupan, Alexandru; Desprès, Philippe; Thoret, Sylviane; Pamlard, Olivier; Dubois, Joëlle; Guillou, Catherine; Tangy, Frédéric; Vidalain, Pierre-Olivier; Munier-Lehmann, Hélène

    2013-02-01

    Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen responsible for an acute infection of abrupt onset, characterized by high fever, polyarthralgia, myalgia, headaches, chills, and rash. In 2006, CHIKV was responsible for an epidemic outbreak of unprecedented magnitude in the Indian Ocean, stressing the need for therapeutic approaches. Since then, we have acquired a better understanding of CHIKV biology, but we are still missing active molecules against this reemerging pathogen. We recently reported that the nonstructural nsP2 protein of CHIKV induces a transcriptional shutoff that allows the virus to block cellular antiviral response. This was demonstrated using various luciferase-based reporter gene assays, including a trans-reporter system where Gal4 DNA binding domain is fused to Fos transcription factor. Here, we turned this assay into a high-throughput screening system to identify small molecules targeting nsP2-mediated shutoff. Among 3040 molecules tested, we identified one natural compound that partially blocks nsP2 activity and inhibits CHIKV replication in vitro. This proof of concept suggests that similar functional assays could be developed to target other viral proteins mediating a cellular shutoff and identify innovative therapeutic molecules.

  13. Identification of chikungunya virus nsP2 protease inhibitors using structure-base approaches.

    PubMed

    Nguyen, Phuong T V; Yu, Haibo; Keller, Paul A

    2015-04-01

    The nsP2 protease of chikungunya virus (CHIKV) is one of the essential components of viral replication and it plays a crucial role in the cleavage of polyprotein precursors for the viral replication process. Therefore, it is gaining attention as a potential drug design target against CHIKV. Based on the recently determined crystal structure of the nsP2 protease of CHIKV, this study identified potential inhibitors of the virus using structure-based approaches with a combination of molecular docking, virtual screening and molecular dynamics (MD) simulations. The top hit compounds from database searching, using the NCI Diversity Set II, with targeting at five potential binding sites of the nsP2 protease, were identified by blind dockings and focused dockings. These complexes were then subjected to MD simulations to investigate the stability and flexibility of the complexes and to gain a more detailed insight into the interactions between the compounds and the enzyme. The hydrogen bonds and hydrophobic contacts were characterized for the complexes. Through structural alignment, the catalytic residues Cys1013 and His1083 were identified in the N-terminal region of the nsP2 protease. The absolute binding free energies were estimated by the linear interaction energy approach and compared with the binding affinities predicted with docking. The results provide valuable information for the development of inhibitors for CHIKV.

  14. Conformer and pharmacophore based identification of peptidomimetic inhibitors of chikungunya virus nsP2 protease.

    PubMed

    Dhindwal, Sonali; Kesari, Pooja; Singh, Harvijay; Kumar, Pravindra; Tomar, Shailly

    2016-12-02

    Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease. The interactions of the junction residues of nsP3/4 polyprotein in the active site of nsP2 protease have been mimicked to identify and design potential inhibitory molecules. Molecular docking of the nsP3/4 junction peptide in the active site of ChikV nsP2 protease provided the structural insight of the probable binding mode of nsP3/4 peptide and pigeonholed the molecular interactions critical for the substrate binding. Further, the shape and pharmacophoric properties of the viral nsP3/4 substrate peptide were taken into consideration and the mimetic molecules were identified and designed. The designed mimetic compounds were then analyzed by docking and their binding affinity was assessed by molecular dynamics simulations.

  15. Expression and biochemical characterization of nsP2 cysteine protease of Chikungunya virus.

    PubMed

    Pastorino, Boris A M; Peyrefitte, Christophe N; Almeras, Lionel; Grandadam, Marc; Rolland, Dominique; Tolou, Hugues J; Bessaud, Maël

    2008-02-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes epidemic fever, rash and polyarthralgia in Africa and Asia. Although it is known since the 1950s, new epidemiological and clinical features reported during the recent outbreak in the Indian Ocean can be regarded as the emergence of a new disease. Numerous severe forms of the infection have been described that put emphasis on the lack of efficient antiviral therapy. Among the virus-encoded enzymes, nsP2 constitutes an attractive target for the development of antiviral drugs. It is a multifunctional protein of approximately 90 kDa with a helicase motif in the N-terminal portion of the protein while the papain-like protease activity resides in the C-terminal portion. The nsP2 proteinase is an essential enzyme whose proteolytic activity is critical for virus replication. In this work, a recombinant CHIKV nsP2pro and a C-terminally truncated variant were expressed in Escherichia coli and purified by metal-chelate chromatography. The enzymatic properties of the proteinase were then determined using specific synthetic fluorogenic substrates. This study constitutes the first characterization of a recombinant CHIKV nsP2 cysteine protease, which may be useful for future drug screening.

  16. Photochemical inactivation of chikungunya virus in human apheresis platelet components by amotosalen and UVA light.

    PubMed

    Tsetsarkin, Konstantin A; Sampson-Johannes, Adam; Sawyer, Lynette; Kinsey, John; Higgs, Stephen; Vanlandingham, Dana L

    2013-06-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that recently re-emerged in Africa and rapidly spread into countries of the Indian Ocean basin and South-East Asia. The mean viremic blood donation risk for CHIKV on La Réunion reached 1.5% at the height of the 2005-2006 outbreaks, highlighting the need for development of safety measures to prevent transfusion-transmitted infections. We describe successful inactivation of CHIKV in human platelets and plasma using photochemical treatment with amotosalen and long wavelength UVA illumination. Platelet components in additive solution and plasma units were inoculated with two different strains of high titer CHIKV stock (6.0-8.0 logs/mL), and then treated with amotosalen and exposure to 1.0-3.0 J/cm² UVA. Based on in vitro assays of infectious virus pre- and post-treatment to identify endpoint dilutions where virus was not detectable, mean viral titers could effectively be reduced by > 6.4 ± 0.6 log₁₀ TCID₅₀/mL in platelets and ≥ 7.6 ± 1.4 logs in plasma, indicating this treatment has the capacity to prevent CHIKV transmission in human blood components collected from infected donors in or traveling from areas of CHIKV transmission.

  17. Molecular epidemiology of chikungunya virus in Malaysia since its first emergence in 1998.

    PubMed

    Chem, Y K; Zainah, S; Berendam, S J; Rogayah, T A R Tengku; Khairul, A H; Chua, K B

    2010-03-01

    Malaysia experienced the first outbreak of chikungunya (CHIK) in Klang in late 1998 due to CHIK virus of Asian genotype. The CHIK virus of Asian genotype reemerged causing outbreak in Bangan Panchor, Perak in March 2006. CHIK virus of Central/East African genotype was first detected from a patient who returned from India in August 2006. In December 2006, CHIK virus of Central/East African genotype was re-introduced into Malaysia from India and caused an outbreak in Kinta district, Perak but was successfully controlled following an early detection and institution of intensive vector control measures. In late April 2008, CHIK virus of Central/East African genotype was laboratory confirmed as the cause of CHIK outbreak in Johore which spread to other parts of Malaysia by August 2008. Phylogenetic analysis based on the 254-bp fragment of the virus envelope protein gene as the genetic marker showed that three different strains of CHIK virus of Central/East African genotype were introduced into Malaysia on three separate occasions from 2006 to 2008. The strain that was introduced into Johor state was responsible for its subsequent spread to other parts of Malaysia, inclusive of Sarawak.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. Nanopatch-targeted skin vaccination against West Nile Virus and Chikungunya virus in mice.

    PubMed

    Prow, Tarl W; Chen, Xianfeng; Prow, Natalie A; Fernando, Germain J P; Tan, Cindy S E; Raphael, Anthony P; Chang, David; Ruutu, Merja P; Jenkins, Derek W K; Pyke, Alyssa; Crichton, Michael L; Raphaelli, Kristin; Goh, Lucas Y H; Frazer, Ian H; Roberts, Michael S; Gardner, Joy; Khromykh, Alexander A; Suhrbier, Andreas; Hall, Roy A; Kendall, Mark A F

    2010-08-16

    The 'Nanopatch' (NP) comprises arrays of densely packed projections with a defined geometry and distribution designed to physically target vaccines directly to thousands of epidermal and dermal antigen presenting cells (APCs). These miniaturized arrays are two orders of magnitude smaller than standard needles-which deliver most vaccines-and are also much smaller than current microneedle arrays. The NP is dry-coated with antigen, adjuvant, and/or DNA payloads. After the NP was pressed onto mouse skin, a protein payload co-localized with 91.4 + or - 4.1 APC mm(-2) (or 2925 in total) representing 52% of the delivery sites within the NP contact area, agreeing well with a probability-based model used to guide the device design; it then substantially increases as the antigen diffuses in the skin to many more cells. APC co-localizing with protein payloads rapidly disappears from the application area, suggesting APC migration. The NP also delivers DNA payloads leading to cutaneous expression of encoded proteins within 24 h. The efficiency of NP immunization is demonstrated using an inactivated whole chikungunya virus vaccine and a DNA-delivered attenuated West Nile virus vaccine. The NP thus offers a needle-free, versatile, highly effective vaccine delivery system that is potentially inexpensive and simple to use.

  3. Chikungunya Virus Infection: First Detection of Imported and Autochthonous Cases in Panama

    PubMed Central

    Díaz, Yamilka; Carrera, Jean-Paul; Cerezo, Lizbeth; Arauz, Dimelza; Guerra, Ilka; Cisneros, Julio; Armién, Blas; Botello, Ana Margarita; Araúz, Ana Belén; Gonzalez, Vladimir; López, Yamileth; Moreno, Lourdes; López-Vergès, Sandra; Moreno, Brechla A.

    2015-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne pathogen that was only endemic in Africa and south Asia until 2005 and 2006, when the virus spread into the Indian Ocean islands, Europe, and Asia. Autochthonous CHIKV transmission in the Caribbean islands was reported in December of 2013. In Panama, two febrile cases were detected in May of 2014: one traveling from Haiti, and the other traveling from the Dominican Republic. After other imported cases were detected, the first autochthonous case was reported in August of the same year. We detected CHIKV viral RNA and isolated the virus from serum samples. The phylogenetic analysis of the two imported isolates and one autochthonous CHIKV isolate indicated that the viruses belong to the Asian lineage in the Caribbean clade and are related to viruses recently identified in Saint Martin island, British Virgin Islands, China, and the Philippines. Although the circulating CHIKV lineages in the Americas have not yet been described, our results suggest that the Asian lineage is circulating in most American countries reporting autochthonous infection. PMID:25601996

  4. Molecular Docking Studies to Explore Potential Binding Pockets and Inhibitors for Chikungunya Virus Envelope Glycoproteins.

    PubMed

    Nguyen, Phuong T V; Yu, Haibo; Keller, Paul A

    2017-03-11

    The chikungunya virus (CHIKV) envelope glycoproteins are considered important potential targets for anti-CHIKV drug discovery due to their crucial roles in virus attachment and virus entry. In this study, using two available crystal structures of the immature and mature forms of envelope glycoproteins, virtual screenings based on blind dockings and focused dockings were carried out to identify potential binding pockets and hit compounds for the virus. The chemical library database of compounds, NCI Diversity Set II, was used in these docking studies. In addition to reproducing previously reported examples, new binding pockets were identified, e.g., Pocket 2 in the 3N40, and Pocket 2 and Pocket 3 in the 3N42. Convergences in conformational sampling in docking using AutoDock Vina were evaluated. An analysis of docking results was carried out to understand interactions of the envelope glycoproteins complexes. Some key residues for interactions, for example Gly91 and His230, are identified as possessing important roles in the fusion process.

  5. The neutralizing role of IgM during early Chikungunya virus infection

    PubMed Central

    Chua, Chong-Long; Chiam, Chun-Wei; Chan, Yoke-Fun

    2017-01-01

    The antibody isotype IgM appears earlier than IgG, within days of onset of symptoms, and is important during the early stages of the adaptive immune response. Little is known about the functional role of IgM during infection with chikungunya virus (CHIKV), a recently reemerging arbovirus that has caused large global outbreaks. In this study, we studied antibody responses in 102 serum samples collected during CHIKV outbreaks in Malaysia. We described the neutralizing role of IgM at different times post-infection and examined the independent contributions of IgM and IgG towards the neutralizing capacity of human immune sera during the early phase of infection, including the differences in targets of neutralizing epitopes. Neutralizing IgM starts to appear as early as day 4 of symptoms, and their appearance from day 6 is associated with a reduction in viremia. IgM acts in a complementary manner with the early IgG, but plays the main neutralizing role up to a point between days 4 and 10 which varies between individuals. After this point, total neutralizing capacity is attributable almost entirely to the robust neutralizing IgG response. IgM preferentially binds and targets epitopes on the CHIKV surface E1-E2 glycoproteins, rather than individual E1 or E2. These findings provide insight into the early antibody responses to CHIKV, and have implications for design of diagnostic serological assays. PMID:28182795

  6. Unrecognized Emergence of Chikungunya Virus during a Zika Virus Outbreak in Salvador, Brazil

    PubMed Central

    Prates, Ana Paula P. B.; Paploski, Igor A. D.; Tauro, Laura B.; Silva, Monaise M. O.; Santana, Perla; Rego, Marta F. S.; Reis, Mitermayer G.; Kitron, Uriel

    2017-01-01

    Background Chikungunya virus (CHIKV) entered Brazil in 2014, causing a large outbreak in Feira de Santana, state of Bahia. Although cases have been recorded in Salvador, the capital of Bahia, located ~100 km of Feira de Santana, CHIKV transmission has not been perceived to occur epidemically, largely contrasting with the Zika virus (ZIKV) outbreak and ensuing complications reaching the city in 2015. Methodology/Principal Findings This study aimed to determine the intensity of CHIKV transmission in Salvador between November 2014 and April 2016. Results of all the CHIKV laboratory tests performed in the public sector were obtained and the frequency of positivity was analyzed by epidemiological week. Of the 2,736 tests analyzed, 456 (16.7%) were positive. An increasing in the positivity rate was observed, starting in January/2015, and peaking at 68% in August, shortly after the exanthematous illness outbreak attributed to ZIKV. Conclusions/Significance Public health authorities and health professionals did not immediately detect the increase in CHIKV cases, likely because all the attention was directed to the ZIKV outbreak and ensuing complications. It is important that regions in the world that harbor arbovirus vectors and did not experience intense ZIKV and CHIKV transmission be prepared for the potential co-emergence of these two viruses. PMID:28114414

  7. Zika and chikungunya: mosquito-borne viruses in a changing world.

    PubMed

    Shragai, Talya; Tesla, Blanka; Murdock, Courtney; Harrington, Laura C

    2017-07-01

    The reemergence and growing burden of mosquito-borne virus infections have incited public fear and growing research efforts to understand the mechanisms of infection-associated health outcomes and to provide better approaches for mosquito vector control. While efforts to develop therapeutics, vaccines, and novel genetic mosquito-control technologies are underway, many important underlying ecological questions remain that could significantly enhance our understanding and ability to predict and prevent transmission. Here, we review the current knowledge about the transmission ecology of two recent arbovirus invaders, the chikungunya and Zika viruses. We introduce the viruses and mosquito vectors, highlighting viral biology, historical routes of transmission, and viral mechanisms facilitating rapid global invasion. In addition, we review factors contributing to vector global invasiveness and transmission efficiency. We conclude with a discussion of how human-induced biotic and abiotic environmental changes facilitate mosquito-borne virus transmission, emphasizing critical gaps in understanding. These knowledge gaps are tremendous; much of our data on basic mosquito ecology in the field predate 1960, and the mosquitoes themselves, as well as the world they live in, have substantially changed. A concerted investment in understanding the basic ecology of these vectors, which serve as the main drivers of pathogen transmission in both wildlife and human populations, is now more important than ever. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  8. 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.

  9. The role of environmental variables on Aedes albopictus biology and chikungunya epidemiology

    PubMed Central

    Waldock, Joanna; Chandra, Nastassya L; Lelieveld, Jos; Proestos, Yiannis; Michael, Edwin; Christophides, George; Parham, Paul E

    2013-01-01

    Aedes albopictus is a vector of dengue and chikungunya viruses in the field, along with around 24 additional arboviruses under laboratory conditions. As an invasive mosquito species, Ae. albopictus has been expanding in geographical range over the past 20 years, although the poleward extent of mosquito populations is limited by winter temperatures. Nonetheless, population densities depend on environmental conditions and since global climate change projections indicate increasing temperatures and altered patterns of rainfall, geographic distributions of previously tropical mosquito species may change. Although mathematical models can provide explanatory insight into observed patterns of disease prevalence in terms of epidemiological and entomological processes, understanding how environmental variables affect transmission is possible only with reliable model parameterisation, which, in turn, is obtained only through a thorough understanding of the relationship between mosquito biology and environmental variables. Thus, in order to assess the impact of climate change on mosquito population distribution and regions threatened by vector-borne disease, a detailed understanding (through a synthesis of current knowledge) of the relationship between climate, mosquito biology, and disease transmission is required, but this process has not yet been undertaken for Ae. albopictus. In this review, the impact of temperature, rainfall, and relative humidity on Ae. albopictus development and survival are considered. Existing Ae. albopictus populations across Europe are mapped with current climatic conditions, considering whether estimates of climatic cutoffs for Ae. albopictus are accurate, and suggesting that environmental thresholds must be calibrated according to the scale and resolution of climate model outputs and mosquito presence data. PMID:23916332

  10. Zika and Chikungunya Virus Detection in Naturally Infected Aedes aegypti in Ecuador.

    PubMed

    Cevallos, Varsovia; Ponce, Patricio; Waggoner, Jesse J; Pinsky, Benjamin A; Coloma, Josefina; Quiroga, Cristina; Morales, Diego; Cárdenas, Maria José

    2017-10-02

    The wide and rapid spread of Chikungunya (CHIKV) and Zika (ZIKV) viruses represent a global public health problem, especially for tropical and subtropical environments. The early detection of CHIKV and ZIKV in mosquitoes may help to understand the dynamics of the diseases in high-risk areas, and to design data based epidemiological surveillance to activate the preparedness and response of the public health system and vector control programs. This study was done to detect ZIKV and CHIKV viruses in naturally infected fed female Aedes aegypti (L.) mosquitoes from active epidemic urban areas in Ecuador. Pools (n=193; 22 pools) and individuals (n=22) of field collected Ae. aegypti mosquitoes from high-risk arboviruses infection sites in Ecuador were analyzed for the presence of CHIKV and ZIKV using RT-PCR. Phylogenetic analysis demonstrated that both ZIKV and CHIKV viruses circulating in Ecuador correspond to the Asian lineages. Minimum infection rate (MIR) of CHIKV for Esmeraldas city was 2.3% and the maximum likelihood estimation (MLE) was 3.3%. The minimum infection rate (MIR) of ZIKV for Portoviejo city was 5.3% and for Manta city was 2.1%. Maximum likelihood estimation (MLE) for Portoviejo city was 6.9% and 2.6% for Manta city. Detection of arboviruses and infection rates in the arthropod vectors may help to predict an outbreak and serve as a warning tool in surveillance programs. Copyright © 2017. Published by Elsevier B.V.

  11. Emerging arboviruses in Rio Grande do Sul, Brazil: Chikungunya and Zika outbreaks, 2014-2016.

    PubMed

    Gregianini, Tatiana Schäffer; Ranieri, Tani; Favreto, Cátia; Nunes, Zenaida Marion Alves; Tumioto Giannini, Gabriela Luchiari; Sanberg, Nara Druck; da Rosa, Marilda Tereza Mar; da Veiga, Ana Beatriz Gorini

    2017-09-20

    The recent emergence of arboviruses such as Chikungunya virus (CHIKV) and Zika virus (ZIKV) in Brazil has posed a threat to human health and to the country's economy. Outbreaks occur mainly in tropical areas; however, increasing number of cases have been observed in Rio Grande do Sul (RS), the Southernmost state; therefore, surveillance of these arboviruses is essential for public health measures. In this study, we analyzed 1276 samples from patients with clinically suspected arboviral diseases between 2014 and 2016. Demographic and clinical data were collected and described; cases of microcephaly associated with congenital infection were analyzed. Results show that CHIKV and ZIKV entered RS in 2014 and 2015, respectively, with imported cases confirmed. Autochthonous infections occurred in 2016 for both viruses, with a total of 5 autochthonous cases for CHIKV and 44 for ZIKV. Most patients were older than 21 years; the main symptoms were fever, arthralgia, myalgia, and headache; rash, conjunctivitis, and pruritus were also reported in ZIKV cases. Three cases of congenital Zika syndrome were confirmed in our study, while another 20 cases of microcephaly associated with congenital infection were confirmed (10 positive for syphilis, 6 for toxoplasmosis and 4 for cytomegalovirus). Considering co-circulation of different arbovirus in RS, including Dengue virus, CHIKV, and ZIKV, and the presence of Aedes aegypti and Aedes albopictus in the area, surveillance of patients infected by these viruses contributes to the control and prevention of such diseases. Practical difficulties in diagnosing these infections are discussed. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Chikungunya virus susceptibility & variation in populations of Aedes aegypti (Diptera: Culicidae) mosquito from India

    PubMed Central

    Gokhale, Mangesh D.; Paingankar, Mandar S.; Sudeep, Anakathil B.; Parashar, Deepti

    2015-01-01

    Background & objectives: Although having immense clinical relevance, yet only a few studies have been targeted to understand the chikungunya virus (CHIKV) susceptibility and growth in Aedes aegypti populations from India. This study was undertaken to investigate CHIKV susceptibility and growth kinetics in Ae. aegypti along with genetic heterogeneity of Ae. aegypti populations. Methods: Dose dependent CHIKV susceptibility and growth kinetic studies for three CHIKV strains reported from India were carried out in Ae. aegypti mosquito populations. The phenotypic variation and genetic heterogeneity in five Ae. aegypti populations were investigated using multivariate morphometrics and allozyme variation studies. Results: The dissemination and growth kinetics studies of the three CHIKV strains showed no selective advantage for a particular strain of CHIKV in Ae. aegypti. At 100 per cent infection rate, five geographic Ae. aegypti populations showed differences in dissemination to three CHIKV strains. Morphometric studies revealed phenotypic variation in all the studied populations. The allelic frequencies, F statistics, and Nei's genetic identity values showed that genetic differences between the populations were small, but significant. Interpretation & conclusions: The results obtained in this study suggest that genetic background of the vector strongly influences the CHIKV susceptibility in Ae. aegypti. PMID:26905240

  13. Serological Evidence of Chikungunya Virus among Acute Febrile Patients in Southern Mozambique.

    PubMed

    Gudo, Eduardo Samo; Pinto, Gabriela; Vene, Sirkka; Mandlaze, Arcildo; Muianga, Argentina Felisbela; Cliff, Julie; Falk, Kerstin

    2015-01-01

    In the last two decades, chikungunya virus (CHIKV) has rapidly expanded to several geographical areas, causing frequent outbreaks in sub-Saharan Africa, South East Asia, South America, and Europe. Therefore, the disease remains heavily neglected in Mozambique, and no recent study has been conducted. Between January and September 2013, acute febrile patients with no other evident cause of fever and attending a health center in a suburban area of Maputo city, Mozambique, were consecutively invited to participate. Paired acute and convalescent serum samples were requested from each participant. Convalescent samples were initially screened for anti-CHIKV IgG using a commercial indirect immunofluorescence test, and if positive, the corresponding acute sample was screened using the same test. Four hundred patients were enrolled. The median age of study participants was 26 years (IQR: 21-33 years) and 57.5% (224/391) were female. Paired blood samples were obtained from 209 patients, of which 26.4% (55/208) were presented anti-CHIKV IgG antibodies in the convalescent sample. Seroconversion or a four-fold titer rise was confirmed in 9 (4.3%) patients. The results of this study strongly suggest that CHIKV is circulating in southern Mozambique. We recommend that CHIKV should be considered in the differential diagnosis of acute febrile illness in Mozambique and that systematic surveillance for CHIKV should be implemented.

  14. Differential Analysis of the Secretome of WRL68 Cells Infected with the Chikungunya Virus

    PubMed Central

    Thio, Christina Li-Ping; Yusof, Rohana; Ashrafzadeh, Ali; Bahari, Syareena; Abdul-Rahman, Puteri Shafinaz; Karsani, Saiful Anuar

    2015-01-01

    The Chikungunya virus (CHIKV) is an arthropod borne virus. In the last 50 years, it has been the cause of numerous outbreaks in tropical and temperate regions, worldwide. There is limited understanding regarding the underlying molecular mechanisms involved in CHIKV replication and how the virus interacts with its host. In the present study, comparative proteomics was used to identify secreted host proteins that changed in abundance in response to early CHIKV infection. Two-dimensional gel electrophoresis was used to analyse and compare the secretome profiles of WRL-68 cells infected with CHIKV against mock control WRL-68 cells. The analysis identified 25 regulated proteins in CHIKV infected cells. STRING network analysis was then used to predict biological processes that may be affected by these proteins. The processes predicted to be affected include signal transduction, cellular component and extracellular matrix (ECM) organization, regulation of cytokine stimulus and immune response. These results provide an initial view of CHIKV may affect the secretome of infected cells during early infection. The results presented here will compliment earlier results from the study of late host response. However, functional characterization will be necessary to further enhance our understanding of the roles played by these proteins in the early stages of CHIKV infection in humans. PMID:26083627

  15. A Chikungunya Fever Vaccine Utilizing an Insect-Specific Virus Platform

    PubMed Central

    Erasmus, Jesse H.; Auguste, Albert J.; Kaelber, Jason T.; Luo, Huanle; Rossi, Shannan L.; Fenton, Karla; Leal, Grace; Kim, Dal Y.; Chiu, Wah; Wang, Tian; Frolov, Ilya; Nasar, Farooq; Weaver, Scott C.

    2016-01-01

    Traditionally, vaccine development involves tradeoffs between immunogenicity and safety. Live-attenuated vaccines typically offer rapid and durable immunity but reduced safety, while the inability of inactivated vaccines to replicate enhances safety at the expense of immunogenicity, often necessitating multiple doses and boosters. To overcome these tradeoffs, we developed the insect-specific alphavirus, Eilat virus (EILV), as a vaccine platform. To address the chikungunya virus (CHIKV) pandemic, we used an EILV cDNA clone to design a chimeric virus containing the CHIKV structural proteins. The recombinant EILV/CHIKV virus was structurally identical at 10Å to wild-type CHIKV by single particle cryoelectron microscopy, mimicked the early stages of CHIKV replication in vertebrate cells from attachment and entry to viral RNA delivery, yet remained completely defective for productive replication, providing a high degree of safety. A single dose of EILV/CHIKV produced in mosquito cells elicited rapid (within 4 days) and long-lasting (>290 days) neutralizing antibodies that provided complete protection in two different mouse models. In nonhuman primates, EILV/CHIKV elicited rapid and robust immunity that protected against viremia and telemetrically-monitored fever. Our EILV platform represents the first structurally native application of an insect-specific virus in preclinical vaccine development and highlights the potential application of such viruses in vaccinology. PMID:27991917

  16. Unrecognized Emergence of Chikungunya Virus during a Zika Virus Outbreak in Salvador, Brazil.

    PubMed

    Cardoso, Cristiane W; Kikuti, Mariana; Prates, Ana Paula P B; Paploski, Igor A D; Tauro, Laura B; Silva, Monaise M O; Santana, Perla; Rego, Marta F S; Reis, Mitermayer G; Kitron, Uriel; Ribeiro, Guilherme S

    2017-01-01

    Chikungunya virus (CHIKV) entered Brazil in 2014, causing a large outbreak in Feira de Santana, state of Bahia. Although cases have been recorded in Salvador, the capital of Bahia, located ~100 km of Feira de Santana, CHIKV transmission has not been perceived to occur epidemically, largely contrasting with the Zika virus (ZIKV) outbreak and ensuing complications reaching the city in 2015. This study aimed to determine the intensity of CHIKV transmission in Salvador between November 2014 and April 2016. Results of all the CHIKV laboratory tests performed in the public sector were obtained and the frequency of positivity was analyzed by epidemiological week. Of the 2,736 tests analyzed, 456 (16.7%) were positive. An increasing in the positivity rate was observed, starting in January/2015, and peaking at 68% in August, shortly after the exanthematous illness outbreak attributed to ZIKV. Public health authorities and health professionals did not immediately detect the increase in CHIKV cases, likely because all the attention was directed to the ZIKV outbreak and ensuing complications. It is important that regions in the world that harbor arbovirus vectors and did not experience intense ZIKV and CHIKV transmission be prepared for the potential co-emergence of these two viruses.

  17. Estimating the burden of disease and the economic cost attributable to chikungunya, Colombia, 2014.

    PubMed

    Cardona-Ospina, Jaime A; Villamil-Gómez, Wilmer E; Jimenez-Canizales, Carlos E; Castañeda-Hernández, Diana M; Rodríguez-Morales, Alfonso J

    2015-12-01

    Chikungunya (CHIK) virus disease is expected to be a considerable cause of disability and economic burden in Latin America given its chronic sequelae, particularly its chronic inflammatory rheumatism. There have been no previous studies assessing CHIK costs and disability in Latin America. We calculated incidence rates for CHIK during the 2014 outbreak in Colombia using epidemiological data provided by the Colombian National Institute of Health, using demographic data from the National Administrative Department of Statistics. The burden of disease was estimated through disability adjusted life years (DALYs) lost and the costs were estimated based on the national recommendations for CHIK acute and chronic phase attention. There were a total of 106 592 cases, with incidence rates ranging from 0 to 1837.3 cases/100 000 population in different departments. An estimate was made of total DALYs lost of 40.44 to 45.14 lost/100 000 population. The 2014 outbreak estimated costs were at least US$73.6 million. Our estimates raise concerns about the effects of continued CHIK spread in Colombia and other Latin-American countries. The lack of transmission control for this disease and potential for spread means that there will be significant acute and chronic disability and related costs in the short and long term for Latin American health care systems. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Deciphering the host-pathogen protein interface in chikungunya virus-mediated sickness.

    PubMed

    Rana, Jyoti; Sreejith, R; Gulati, Sahil; Bharti, Isha; Jain, Surangna; Gupta, Sanjay

    2013-06-01

    Successful infection with chikungunya virus (CHIKV) depends largely on the ability of this virus to manipulate cellular processes in its favour through specific interactions with several host factors. The knowledge of virus-host interactions is of particular value for understanding the interface through which therapeutic strategies could be applied. In the current study, the authors have employed a computational method to study the protein interactions between CHIKV and both its human host and its mosquito vector. In this structure-based study, 2028 human and 86 mosquito proteins were predicted to interact with those of CHIKV through 3918 and 112 unique interactions, respectively. This approach could predict 40 % of the experimentally confirmed CHIKV-host interactions along with several novel interactions, suggesting the involvement of CHIKV in intracellular cell signaling, programmed cell death, and transcriptional and translational regulation. The data corresponded to those obtained in earlier studies for HIV and dengue viruses using the same methodology. This study provides a conservative set of potential interactions that can be employed for future experimental studies with a view to understanding CHIKV biology.

  19. The First Reported Outbreak of Chikungunya in the U.S. Virgin Islands, 2014-2015.

    PubMed

    Feldstein, Leora R; Ellis, Esther M; Rowhani-Rahbar, Ali; Halloran, M Elizabeth; Ellis, Brett R

    2016-10-05

    The chikungunya virus (CHIKV) epidemic in the Americas is of significant public health importance due to the lack of effective control and prevention strategies, severe disease morbidity among susceptible populations, and potential for persistent arthralgia and long-term impaired physical functionality. Using surveillance data of suspected CHIKV cases, we describe the first reported outbreak in the U.S. Virgin Islands. CHIKV incidence was highest among individuals aged 55-64 years (13.1 cases per 1,000 population) and lowest among individuals aged 0-14 years (1.8 cases per 1,000 population). Incidence was higher among women compared to men (6.6 and 5.0 cases per 1,000 population, respectively). More than half of reported laboratory-positive cases experienced fever lasting 2-7 days, chills/rigor, myalgia, anorexia, and headache. No clinical symptoms apart from the suspected case definition of fever ≥ 38°C and arthralgia were significantly associated with being a reported laboratory-positive case. These results contribute to our knowledge of demographic risk factors and clinical manifestations of CHIKV disease and may aid in mitigating future CHIKV outbreaks in the Caribbean. © The American Society of Tropical Medicine and Hygiene.

  20. The First Reported Outbreak of Chikungunya in the U.S. Virgin Islands, 2014–2015

    PubMed Central

    Feldstein, Leora R.; Ellis, Esther M.; Rowhani-Rahbar, Ali; Halloran, M. Elizabeth; Ellis, Brett R.

    2016-01-01

    The chikungunya virus (CHIKV) epidemic in the Americas is of significant public health importance due to the lack of effective control and prevention strategies, severe disease morbidity among susceptible populations, and potential for persistent arthralgia and long-term impaired physical functionality. Using surveillance data of suspected CHIKV cases, we describe the first reported outbreak in the U.S. Virgin Islands. CHIKV incidence was highest among individuals aged 55–64 years (13.1 cases per 1,000 population) and lowest among individuals aged 0–14 years (1.8 cases per 1,000 population). Incidence was higher among women compared to men (6.6 and 5.0 cases per 1,000 population, respectively). More than half of reported laboratory-positive cases experienced fever lasting 2–7 days, chills/rigor, myalgia, anorexia, and headache. No clinical symptoms apart from the suspected case definition of fever ≥ 38°C and arthralgia were significantly associated with being a reported laboratory-positive case. These results contribute to our knowledge of demographic risk factors and clinical manifestations of CHIKV disease and may aid in mitigating future CHIKV outbreaks in the Caribbean. PMID:27402523

  1. 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.

  2. Invasiveness of Aedes aegypti and Aedes albopictus and Vectorial Capacity for Chikungunya Virus.

    PubMed

    Lounibos, Leon Philip; Kramer, Laura D

    2016-12-15

    In this review, we highlight biological characteristics of Aedes aegypti and Aedes albopictus, 2 invasive mosquito species and primary vectors of chikungunya virus (CHIKV), that set the tone of these species' invasiveness, vector competence, and vectorial capacity (VC). The invasiveness of both species, as well as their public health threats as vectors, is enhanced by preference for human blood. Vector competence, characterized by the efficiency of an ingested arbovirus to replicate and become infectious in the mosquito, depends largely on vector and virus genetics, and most A. aegypti and A. albopictus populations thus far tested confer vector competence for CHIKV. VC, an entomological analog of the pathogen's basic reproductive rate (R0), is epidemiologically more important than vector competence but less frequently measured, owing to challenges in obtaining valid estimates of parameters such as vector survivorship and host feeding rates. Understanding the complexities of these factors will be pivotal in curbing CHIKV transmission. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Genomic evolution and phenotypic distinctions of Chikungunya viruses causing the Indian Ocean outbreak.

    PubMed

    Powers, Ann M

    2011-08-01

    In our current global community with the rapid movement of products and people across and between continents, the emergence of a human pathogen can have devastating consequences. One dramatic example of this has been the emergence of Chikungunya virus (CHIKV), which causes a severe, prolonged, and debilitating arthralgic disease. This virus emerged in a large outbreak on the east coast of Africa in 2004; over the subsequent seven years, CHIKV has spread across the Indian Ocean, the Indian subcontinent, Southeast Asia and even reached Europe, leaving more than two million people affected. Because CHIKV has a small genome, currently available tools to analyze complete viral genomes have provided scientists with unique opportunities to understand the epidemiology, pathogenesis and transmission of the virus. The most commonly used application of these cutting edge tools has been to track the movement of the virus over time and space. While this is an important concept for identifying areas that remain at risk for outbreaks, these postgenomic era tools can also be applied to the highly significant tasks of understanding how viral microevolutionary changes can affect both invertebrate transmission and vertebrate virulence. Significant alterations in the patterns of CHIKV movement have already been identified using microevolutionary studies. These approaches now need to be further expanded to aid in expanding vaccine, therapeutic and control options. This review will highlight some of the most significant recent research developments obtained using these cutting edge approaches for CHIKV.

  4. Characterization of Aedes aegypti Innate-Immune Pathways that Limit Chikungunya Virus Replication

    PubMed Central

    McFarlane, Melanie; Arias-Goeta, Camilo; Martin, Estelle; O'Hara, Zoe; Lulla, Aleksei; Mousson, Laurence; Rainey, Stephanie M.; Misbah, Suzana; Schnettler, Esther; Donald, Claire L.; Merits, Andres; Kohl, Alain; Failloux, Anna-Bella

    2014-01-01

    Replication of arboviruses in their arthropod vectors is controlled by innate immune responses. The RNA sequence-specific break down mechanism, RNA interference (RNAi), has been shown to be an important innate antiviral response in mosquitoes. In addition, immune signaling pathways have been reported to mediate arbovirus infections in mosquitoes; namely the JAK/STAT, immune deficiency (IMD) and Toll pathways. Very little is known about these pathways in response to chikungunya virus (CHIKV) infection, a mosquito-borne alphavirus (Togaviridae) transmitted by aedine species to humans resulting in a febrile and arthralgic disease. In this study, the contribution of several innate immune responses to control CHIKV replication was investigated. In vitro experiments identified the RNAi pathway as a key antiviral pathway. CHIKV was shown to repress the activity of the Toll signaling pathway in vitro but neither JAK/STAT, IMD nor Toll pathways were found to mediate antiviral activities. In vivo data further confirmed our in vitro identification of the vital role of RNAi in antiviral defence. Taken together these results indicate a complex interaction between CHIKV replication and mosquito innate immune responses and demonstrate similarities as well as differences in the control of alphaviruses and other arboviruses by mosquito immune pathways. PMID:25058001

  5. Characterization of Aedes aegypti innate-immune pathways that limit Chikungunya virus replication.

    PubMed

    McFarlane, Melanie; Arias-Goeta, Camilo; Martin, Estelle; O'Hara, Zoe; Lulla, Aleksei; Mousson, Laurence; Rainey, Stephanie M; Misbah, Suzana; Schnettler, Esther; Donald, Claire L; Merits, Andres; Kohl, Alain; Failloux, Anna-Bella

    2014-07-01

    Replication of arboviruses in their arthropod vectors is controlled by innate immune responses. The RNA sequence-specific break down mechanism, RNA interference (RNAi), has been shown to be an important innate antiviral response in mosquitoes. In addition, immune signaling pathways have been reported to mediate arbovirus infections in mosquitoes; namely the JAK/STAT, immune deficiency (IMD) and Toll pathways. Very little is known about these pathways in response to chikungunya virus (CHIKV) infection, a mosquito-borne alphavirus (Togaviridae) transmitted by aedine species to humans resulting in a febrile and arthralgic disease. In this study, the contribution of several innate immune responses to control CHIKV replication was investigated. In vitro experiments identified the RNAi pathway as a key antiviral pathway. CHIKV was shown to repress the activity of the Toll signaling pathway in vitro but neither JAK/STAT, IMD nor Toll pathways were found to mediate antiviral activities. In vivo data further confirmed our in vitro identification of the vital role of RNAi in antiviral defence. Taken together these results indicate a complex interaction between CHIKV replication and mosquito innate immune responses and demonstrate similarities as well as differences in the control of alphaviruses and other arboviruses by mosquito immune pathways.

  6. 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.

  7. Establishment of a Novel Primary Human Skeletal Myoblast Cellular Model for Chikungunya Virus Infection and Pathogenesis.

    PubMed

    Hussain, Khairunnisa' Mohamed; Lee, Regina Ching Hua; Ng, Mary Mah-Lee; Chu, Justin Jang Hann

    2016-02-19

    Chikungunya virus (CHIKV) is a re-emerging arbovirus known to cause chronic myalgia and arthralgia and is now considered endemic in countries across Asia and Africa. The tissue tropism of CHIKV infection in humans remains, however, ill-defined. Due to the fact that myositis is commonly observed in most patients infected with CHIKV, we sought to develop a clinically relevant cellular model to better understand the pathogenesis of CHIKV infection. In this study, primary human skeletal muscle myoblasts (HSMM) were established as a novel human primary cell line that is highly permissive to CHIKV infection, with maximal amounts of infectious virions observed at 16 hours post infection. Genome-wide microarray profiling analyses were subsequently performed to identify and map genes that are differentially expressed upon CHIKV infection. Infection of HSMM cells with CHIKV resulted in altered expressions of host genes involved in skeletal- and muscular-associated disorders, innate immune responses, cellular growth and death, host metabolism and virus replication. Together, this study has shown the establishment of a clinically relevant primary human cell model that paves the way for the further analysis of host factors and their involvement in the various stages of CHIKV replication cycle and viral pathogenesis.

  8. Cross-Inhibition of Chikungunya Virus Fusion and Infection by Alphavirus E1 Domain III Proteins

    PubMed Central

    Sánchez-San Martín, Claudia; Nanda, Soumya; Zheng, Yan; Fields, Whitney

    2013-01-01

    Alphaviruses are small enveloped RNA viruses that include important emerging human pathogens, such as chikungunya virus (CHIKV). These viruses infect cells via a low-pH-triggered membrane fusion reaction, making this step a potential target for antiviral therapies. The E1 fusion protein inserts into the target membrane, trimerizes, and refolds to a hairpin-like conformation in which the combination of E1 domain III (DIII) and the stem region (DIII-stem) pack against a core trimer composed of E1 domains I and II (DI/II). Addition of exogenous DIII proteins from Semliki Forest virus (SFV) has been shown to inhibit E1 hairpin formation and SFV fusion and infection. Here we produced and characterized DIII and DI/II proteins from CHIKV and SFV. Unlike SFV DIII, both core trimer binding and fusion inhibition by CHIKV DIII required the stem region. CHIKV DIII-stem and SFV DIII-stem showed efficient cross-inhibition of SFV, Sindbis virus, and CHIKV infections. We developed a fluorescence anisotropy-based assay for the binding of SFV DIII-stem to the core trimer and used it to demonstrate the relatively high affinity of this interaction (Kd [dissociation constant], ∼85 nM) and the importance of the stem region. Together, our results support the conserved nature of the key contacts of DIII-stem in the alphavirus E1 homotrimer and describe a sensitive and quantitative in vitro assay for this step in fusion protein refolding. PMID:23637415

  9. Seroprevalence of Antibodies against Chikungunya, Dengue, and Rift Valley Fever Viruses after Febrile Illness Outbreak, Madagascar

    PubMed Central

    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

    2012-01-01

    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. PMID:23092548

  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. Clinical Update on Dengue, Chikungunya, and Zika: What We Know at the Time of Article Submission.

    PubMed

    Liu, Liang E; Dehning, Meaghan; Phipps, Ashley; Swienton, Ray E; Harris, Curtis A; Klein, Kelly R

    2017-06-01

    Mosquito-borne diseases pose a threat to individual health and population health on both a local and a global level. The threat is even more exaggerated during disasters, whether manmade or environmental. With the recent Zika virus outbreak, it is important to highlight other infections that can mimic the Zika virus and to better understand what can be done as public health officials and health care providers. This article reviews the recent literature on the Zika virus as well as chikungunya virus and dengue virus. The present findings give a better understanding of the similarities and differences between the 3 infections in terms of their characteristics, clinical presentation, diagnosis methodology, and treatment and what can be done for prevention. Additionally, the article highlights a special population that has received much focus in the latest outbreak, the pregnant individual. Education and training are instrumental in controlling the outbreak, and early detection can be lifesaving. (Disaster Med Public Health Preparedness. 2017;11:290-299).

  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.

  13. Study of viremic profile in febrile specimens of chikungunya in Bandung, Indonesia.

    PubMed

    Riswari, S F; Ma'roef, C N; Djauhari, H; Kosasih, H; Perkasa, A; Yudhaputri, F A; Artika, I M; Williams, M; van der Ven, A; Myint, K S; Alisjahbana, B; Ledermann, J P; Powers, A M; Jaya, U A

    2016-01-01

    Data regarding the viremia profile of chikungunya virus (CHIKV) infected patients especially during the pre-febrile period is limited. To obtain virological kinetic data on CHIKV infections. A two-week community observation for dengue transmission was conducted in Bandung, Indonesia, from 2005 to 2009. Acute specimens from non-dengue febrile patients were screened by pan-alphavirus conventional RT-PCR. The positives were confirmed for CHIKV RNA by a specific RT-PCR followed by sequencing. Simultaneously these specimens were also cultured in Vero cells and tested for anti-CHIK IgM MAC-ELISA. All the available serial specimens,including the pre-febrile specimens, from confirmed CHIK cases, were tested by virus isolation, RT-PCR, qRT-PCR, and CHIK IgM ELISA. There were five laboratory confirmed CHIK cases identified and studied. Among these, viremia was determined to extend from as early as 6 days prior to until 13 days post fever onset. Quantitative RT-PCR showed viremia peaked at or near onset of illness. In this study, individuals were identified with viremia prior to fever onset and extending beyond the febrile phase. This extended viremic phase has the potential to impact transmission dynamics and thus the public health response to CHIK outbreaks. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

  14. 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

  15. Curcumin inhibits Zika and chikungunya virus infection by inhibiting cell binding.

    PubMed

    Mounce, Bryan C; Cesaro, Teresa; Carrau, Lucia; Vallet, Thomas; Vignuzzi, Marco

    2017-03-24

    Several compounds extracted from spices and herbs exhibit antiviral effects in vitro, suggesting potential pharmacological uses. Curcumin, a component of turmeric, has been used as a food additive and herbal supplement due to its potential medicinal properties. Previously, curcumin exhibited antiviral properties against several viruses, including dengue virus and hepatitis C virus, among others. Here, we describe the antiviral effect of curcumin on Zika and chikungunya viruses, two mosquito-borne outbreak viruses. Both viruses responded to treatment of cells with up to 5 μM curumin without impacting cellular viability. We observed that direct treatment of virus with curcumin reduced infectivity of virus in a dose- and time-dependent manner for these enveloped viruses, as well as vesicular stomatitis virus. In contrast, we found no change in infectivity for Coxsackievirus B3, a non-enveloped virus. Derivatives of curcumin also exhibited antiviral activity against enveloped viruses. Further examination revealed that curcumin interfered with the binding of the enveloped viruses to cells in a dose-dependent manner, though the integrity of the viral RNA was maintained. Together, these results expand the family of viruses sensitive to curcumin and provide a mechanism of action for curcumin's effect on these enveloped viruses.

  16. Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses

    PubMed Central

    Tong, Yigang

    2014-01-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment. PMID:24595095

  17. Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death.

    PubMed

    Staveness, Daryl; Abdelnabi, Rana; Schrier, Adam J; Loy, Brian A; Verma, Vishal A; DeChristopher, Brian A; Near, Katherine E; Neyts, Johan; Delang, Leen; Leyssen, Pieter; Wender, Paul A

    2016-04-22

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer's disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency and low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment.

  18. Simplified Bryostatin Analogues Protect Cells from Chikungunya Virus-Induced Cell Death

    PubMed Central

    2016-01-01

    Chikungunya virus (CHIKV) is a mosquito-borne alphavirus showing a recent resurgence and rapid spread worldwide. While vaccines are under development, there are currently no therapies to treat this disease, except for over-the-counter (OTC) analgesics, which alleviate the devastating arthritic and arthralgic symptoms. To identify novel inhibitors of the virus, analogues of the natural product bryostatin 1, a clinical lead for the treatment of cancer, Alzheimer’s disease, and HIV eradication, were investigated for in vitro antiviral activity and were found to be among the most potent inhibitors of CHIKV replication reported to date. Bryostatin-based therapeutic efforts and even recent anti-CHIKV strategies have centered on modulation of protein kinase C (PKC). Intriguingly, while the C ring of bryostatin primarily drives interactions with PKC, A- and B-ring functionality in these analogues has a significant effect on the observed cell-protective activity. Significantly, bryostatin 1 itself, a potent pan-PKC modulator, is inactive in these assays. These new findings indicate that the observed anti-CHIKV activity is not solely mediated by PKC modulation, suggesting possible as yet unidentified targets for CHIKV therapeutic intervention. The high potency and low toxicity of these bryologs make them promising new leads for the development of a CHIKV treatment. PMID:26900625

  19. Viremia in North American Mammals and Birds after Experimental Infection with Chikungunya Viruses

    PubMed Central

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

    2016-01-01

    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. PMID:26666699

  20. 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.