NEW MICROBIOLOGICA 36 211 227 2013 Chikungunya virus infection an overview Claudia Caglioti Eleonora Lalle Concetta Castilletti Fabrizio Carletti Maria Rosaria Capobianchi Licia Bordi Laboratory of Virology L Spallanzani National Institute for Infectious Diseases Rome Italy SUMMARY 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 KEY WORDS CHIKV Arbovirus Virus dissemination Immunopathogenesis Geographic distribution Diagnosis Treatment and prevention Received May 26 2013 INTRODUCTION Chikungunya virus CHIKV an arbovirus transmitted by mosquito vectors is an alphavirus belonging to the Togaviridae family Alphaviruses are small spherical enveloped viruses with a 6070 nm diameter The genome is a single strand RNA molecule of positive polarity encoding four non structural nsP1 4 and three structural proteins C E1 E2 Viral replication is initiated by attachment of the viral envelope to host cell re Corresponding author Maria Rosaria Capobianchi Laboratory of Virology Padiglione Baglivi National Institute for Infectious Diseases INMI L Spallanzani Via Portuense 292 00149 Rome Italy E mail maria capobianchi inmi it Accepted May 30 2013 ceptors Strauss and Strauss 1994 followed by clathrin mediated endocytosis of the attached particle Lee et al 2013 low pH mediated membrane fusion and delivery of the viral nucleocapsid into the cytoplasm Sorisseau et al 2007 To date no CHIKV interacting protein has been characterized but in a very recent study Wintachai et al identified prohibitin as CHIKV binding protein expressed by microglial cells Wintachai et al 2012 The replication cycle is fast taking around 4 hours Alphaviruses are sensitive to dissecation and to temperatures above 58 C Strauss and Strauss 1994 Khan et al 2002 About 30 species of arthropod borne viruses are included in the alphavirus genus antigenically classified into 7 complexes These viruses are widely distributed throughout the world with the exception of Antarctica Besides CHIKV several arthropod transmitted alphaviruses cause human disease characterized by similar clinical presentation Barmah Forest 212 C Caglioti E Lalle C Castilletti F Carletti M R Capobianchi L Bordi BFV and Ross River viruses RRV Oceania O nyong nyong ONNV and Semliki Forest viruses SFV Africa Mayaro South America Sindbis SINV and Sindbis like viruses Africa Asia Scandinavia and Russia Taubiz et al 2007 Chikungunya fever CHIKF derives its name from Makonde a language spoken in south Tanzania and means that which bends up referring to the posture of patients afflicted with severe joint pain characterizing this infection First isolated in Tanzania in 1952 Robinson 1955 CHIKV attracted worldwide attention when it caused a massive outbreak in the Indian Ocean islands Enserik 2006 Since 1952 CHIKV has caused a number of epidemics both in Africa and in Southeast Asia many of them involving hundreds of thousands of people After a few years of relative dormancy in La R union Island CHIKV transmission has restarted renewing concerns about the possibility of renewed autochthonous transmission in Mediterranean countries GEOGRAPHIC DISTRIBUTION CHIKF has an epidemiological pattern with both sporadic and epidemics cases in West Africa from Senegal to Cameroun and in many other African countries Democratic Republic of Congo Nigeria Angola Uganda Guinea Malawi Central African Republic Burundi and South Africa Moreover many epidemics occurred in Asia Burma Thailand Cambodia Vietnam India Sri Lanka Timor Indonesia and the Philippines in the 1960s and in the 1990s Pialoux et al 2007 Jain et al 2008 Major epidemics appear and disappear cyclically usually with an inter epidemic period ranging from 7 to 20 years The huge outbreak that increased concern about CHIKV started in Kenya in 2004 where the seroprevalence rates reached 75 in Lamu island Pialoux et al 2007 before reaching the Comores Seychelles and Mauritius islands The virus reached La R union island in March April 2005 probably FIGURE 1 Geographic distribution of CHIKV shown in the most recent map May 2012 retrieved from the CDC website http www cdc gov chikungunya map index html last accessed May 2013 Chikungunya overview as a result of importation of cases among immigrants from the Comores and rapidly spread to several countries in the Indian Ocean and India Enserik 2006 Mavalankar et al 2007 Compared to earlier outbreaks this episode was massive occurred in highly medicalized areas such as La R union and had very significant economic and social impact Since the beginning of the outbreak in the Indian Ocean region more than 1 000 imported CHIKV cases have been detected among European and American travellers returning from the affected areas Fusco et al 2006 Taubiz et al 2007 giving rise in 2007 to the first autochthonous human to mosquito tohuman transmission European outbreak in Italy
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