L’Epidemiologia di Chikungunya e Dengue in Italia Maria Grazia Ciufolini Dipartimento di Malattie Infettive, Parassitarie ed Immuno-mediate Istituto Superiore di Sanità, Roma Cervia 9- 10 maggio 2011 “ Malattie emergenti trasmesse da vettori: il rischio da zanzare Aedes” Arbovirus: ARthropod BOrne Viruses Arboviruses are viruses which are maintained in nature principally, or to an important extent, through biological transmission between susceptible vertebrate hosts by hematophagous arthropods: they multiply and produce viremia in vertebrates, multiply in the tissues of arthropods, and are passed to new vertebrates by the bites of arthropods after a period of extrinsic incubation. W.H.O. 1967 DENV and CHIKV: epidemiological features Dengue (DENV) and chikungunya viruses (CHIKV) are ARthropod BOrne Viruses which share similar epidemiological features. Both viruses are endemic in the tropics and are transmitted to humans through the bite of infected Aedes mosquitoes. During recent years, the incidence of both dengue and chikungunya fever has risen worldwide. There is no vaccine available for either virus and prevention relies entirely on mosquito control and personal protection. Countries of acquisition and countries of importation of dengue and chikungunya cases reported by EuroTravNet core sites in 2008 and the overlapping area of habitation of Aedes albopictus. Field et al. BMCInfectious Diseases 2010, 10:330 http://www.biomedcentral.com/14712334/10/330 Comparison of the Clinical Features of Chikungunya Fever and Dengue Fever J. Erin Staples,et.al Clinical Infectious Diseases 2009; 49:942–8 Dengue: viruses characteristics Family Transmission Flaviviridae: Flavivirus Aedes mosquitoes Viral Particles Icosohedral core, 40-60 nm Structural Proteins C, M, E Genome Single stranded positive sense RNA Dengue Virus: Dengue 1 Dengue 2 Dengue 3 Dengue 4 Geographic distribution: Tropical regions (epidemic during the rainy season) Public health impact: High morbidity (estimated 50–100 million annual cases of DEN and tens-of-thousands of cases of the more severe and sometimes fatal DHF/DSS syndromes) during epidemics. Immunity: There is no cross-protective immunity in humans Dengue: the viruses Infection of one of the four DENV serotypes provides lifelong immunity to that serotype, but not to the others Each of the four serotypes can cause a spectrum of diseases ranging from a clinically inapparent infection to a potentially lethal disease Within each DENV serotype different genotypes has been found on the basis of sequence data from the E gene Selected genotypes of virus within serotypes, have a greater epidemic potential and virulence Dengue: viral cycles FOREST RURAL/SUB-URBAN Aedes aegypti Mosquito Aedes Mosquito Aedes TOT TOT Human Human Primati TOT? Aedes aegypti Mosquito Aedes Mosquito Aedes AFRICA Aedes (Diceromya) Aedes (Stegomyia) URBAN Ae. albopictus Ae. polynesiensis Ae. aegypti Ae. albopictus Ae. aegypti Ae. mediovittatus Ae. polynesiensis ASIA Aedes (Finlaya) Aedes (Stegomyia) AMERICA Aedes spp. Aedes spp. Dengue: replication and transmission of virus 1. The virus is transmitted to man through the saliva of mosquitoes 2. The virus replicates in target organs n o 3. 4. The virus infects the limphocytes and lymphocit tissues The virus is released into the blood circulation q p Dengue: replication and transmission of virus (2) 5. A second mosquito ingests the virus from the blood 6. The virus replicates in the intestine and later reaches the saliva glands s t r 7. The virus replicates in the saliva glands Dengue fever (DF): clinical characteristics Incubation period: 3-14 days, usually 4-7 days High Fever Headaches Muscular pains and articulation problems Nausea / vomiting Esanthema Hemorrhagic manifestations Dengue haemorrhagic fever DHF DHF I Fever, trombocitopenia , haemoconcentration Positive “Tourniquet” test and or easy bruising. DHF II All DHF I criteria + spontaneous bleeding DHF III All DHF I /II criteria + one of the following : 1. Rapid/weak pulse and narrow pulse pressure 2. Hypotension with cold , clammy skin and restlessness DHF IV All DHF I /II criteria +undetectable blood pressure or pulse DHF/DSS: risk factors Strain of virus Previous infection with heterotypic DENV Age Genetic background of the person Dengue is seldom recognized as an important disease in Europe. DF has been diagnosed in increasing proportions of febrile travellers returning from the tropics, ranging from 2% in the early 1990s to 16% more recently. Due to the non-specific and self-limiting nature of milder infections, these figures are likely to be an underestimation caused by underreporting. Diagnosis of imported diseases Samples Serum (20°C) to be provided with notices about morbidity and epidemiologic data about the patients Positive: •RT-PCR positive •Serologic tests (seroconversion, IgM positivity, four-fold rise of antibody titer) Past infections: •RT-PCR negative •IgG positive •IgM negative Indetermined: just one serum sample and negative RTPCR and negligible titer Negative: •RT-PCR negative •Negative serologic results Casi importati di Dengue in Italia CHIK 120 100 80 60 40 20 0 Positive 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Pregressed Undetermined Negative Casi importati di Dengue in Italia CHIK 120 100 80 60 40 20 0 Positive 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 Pregressed Undetermined Dengue importata: distribuzione regionale Negative Dengue Importata: origine geografica Virus CHIK Famiglia Togaviridae Genere Alphavirus Trasmissione: zanzare Aedes Virus a RNA a singolo filamento, con envelope. Chikungunya •Alphavirus genus (Togaviridae (Togaviridae family) •Identified in the Newala District, Tanzania, in 1952 •Transmitted by Aedes spp mosquitoes •Endemic in several areas of Africa •Recurrent epidemics in Asia Life cycle of Chikungunya virus in Africa showing the interconnection between the sylvatic cycle on the left and the urban cycle on the right Michelle M. Thiboutotet al, April 2010 CHIK: la distribuzione nell’Oceano Indiano (2006) India: >1.000.000 di casi sospetti Comore: >5.000 casi sospetti nel 2005 Malesia: 20.000 casi sospetti Seychelles: >8.800 casi sospetti Mauritius: 6.000 casi sospetti Mayotte: 6.000 casi sospetti Madagascar: numerosi casi sospetti La Réunion: 266.000 casi sospetti dal 2005 Lancet, 1 dicembre 2007 Ravenna Epidemic 21 June : A healthy man from Kerala, India, arrives at the Milan airport. He goes to his home at Forlimpopoli. 23 June : He goes to visit his cousin, living in Castiglione di Cervia. That evening he develops a high fever. 4 July: The cousin also develops a high fever, with pains in joints and a rash. In the next few days the whole family falls sick. The illness spreads to Castiglione di Cervia and Castiglione di Ravenna. In the second half of August the epidemic reaches a peak. Epidemic Curve by Presumed Place of Infection 12 11 10 9 Other location Cervia Castiglione di Cervia and Castiglione di Ravenna 8 No. of cases 7 6 5 4 3 2 1 0 23-Jun 30-Jun 7-Jul 14-Jul 21-Jul 28-Jul 4-Aug 11-Aug 18-Aug 25-Aug 1-Sep 8-Sep 15-Sep •The 2005-2006 outbreak in the Indian Ocean was associated with a CHIKV strain with a mutation in the envelope protein gene (E1A226V) •This single amino acid substitution appeared to influence vector specificity increasing CHIKV fitness in Aedes albopictus Vazeille M, PLOS One, Nov 2007 Konstantin A, PLOS Pathogens, Dec 2007 Phylogenetic analysis of the partial nucleotide sequence (1011 nucleotides) nucleotides) of the E1 gene of CHIKV strains identified in Italy and in different parts of the world CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/1 CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/3 CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/2 CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/6 CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/4 CHIKs/ CHIKs/Ravenna.ITA/34 Ravenna.ITA/34--07/7 INDIND-0606-RJ1 Central/East Central/East African genotype INDIND-0606-TN1 INDIND-0606-AP3 100 INDIND-0606-MH2 INDIND-0606-KA15 85 Mauritius D570/06 LR2006 OPY1OPY1-Reunion INDIND-0000-MH4 Tanzania-S27. ECSA 96 TanzaniaTanzaniaTanzania-strain Ross IND-6363-WB1 (Kolkata) Asian 100 IND- Asian genotype INDIND-7373-MH5 (Barsi (Barsi)) Asian 100 Nigeria 64 WA Senegal -83 WA 37997 0.005 West African genotype CHIK: le epidemie Tilston, Skelly and Weinstein,, 2009 Imported cases of CHIK in Italy 120 N° of cases 100 80 60 40 20 0 2006 2007 Positive 2008 Negative 2009 2010 CHIK importata: provenienza delle richieste di diagnosi CHIK importata: origine geografica Conclusions •Recurrence of Chikungunya and introduction of other viruses (Dengue?) cannot be excluded • Sustainment of the epidemics beyond the warm season is unlikely in absence of dramatic climate change, (due to lack of transovarial transmission) •Improvement of diagnostic capacity and effective surveillance and control of exotic vectorborne infections is needed in preparedness plans in the EU Many thanks to Loredana Nicoletti Antonella Marchi Cristiano Fiorentini Fabio Magurano Claudia Fortuna Eleonora Benedetti Paola Bucci Maria Elena Remoli Melissa Baggieri Giovanni Rezza Thank you for your attention