Les maladies vectorielles: le regard de l'entomologiste Anna-Bella FAILLOUX Arboviruses and Insect Vectors Department of Virology Medical entomology: a discipline focused upon arthropods that impact human health 1877: Patrick Manson Wuchereria bancro-i transmi;ed by the mosquito Culex pipiens 1939: Paul Hermann Müller DDT (Nobel Price 1948) 1877 MANSON : Wuchereria bancro-i in the mosquito Cx. pipiens fa4gans 1881 FINLAY : Ae. aegyp4, vector of yellow fever? 1897 ROSS : Plasmodium oocysts in Anopheles mosquitoes 1898 SIMOND : Experimental transmission of Yersinia pes8s by fleas 1899 BANCROFT : Transmission W. bancro-i by Culex GRASSI & coll : Transmission of malaria by Anopheles 1900 REED & coll : Transmission of yellow fever by Ae. aegyp4 1903 BRUCE & NAVARRO : Transmission of Trypanosoma by Glossina flies 1909 NICOLLE : Transmission of typhus fever by lice CHAGAS : Transmission of Trypanosoma cruzi by Triatoma megista. 1916 CLELAND & coll : Transmission of dengue virus by Aedes aegyp4 1926 BLACKLOCK : Transmission of Onchocerca volvulus by black flies 1939 MULLER : InsecMcidal properMes of DDT Les arthropodes vecteurs Phyllum Class Order Family Diseases Ixodidae (hard Wcks) RickeBsiosis, Tularemia, Ixodida Lyme disease Argasidae (so cks) Borreliosis Arachnids Siphonaptera Pulicidae (fleas) Plague, RickeBsiosis Phthiraptera Pediculidae (lice) Borreliosis, Bartonella, RickeBsioses Hemiptera Reduviidae (bugs) Chagas Arthropods Simulidae (black flies) Onchocerciasis Insects (river blindness) Tabanidae (horse flies) Loa Loa filariasis (eye worm) Diptera Psychodidae (sandflies) Leishmaniasis Glossinidae (tsetse fly) African trypanomiasis (sleeping sickness) Culicidae (mosquito) Fontaine & Almeras (2011) 4/61 IntroducMon Family: Culicidae Anopheles Aedes Culex Malaria Dengue Japanese encephaliWs 300 millions cases/yr 50 millions cases/yr 50 000 cases/yr 1 million deaths/yr 20 000 deaths/yr 10 000 deaths/yr Yellow fever St Louis encephaliWs 200 000 cases/yr 50 000 cases/yr 30 000 deaths/yr West Nile 3 630 cases in 2007 in U.S. Fontaine & Almeras (2011) Chiffres de l’OMS et du CDC, cartes: Roberts, L., 2002, 5/61 Science , photo: vectorbase.org Developmental cycle Mean duraMon: 8 - 12 days Terrestrial 4 stages AquaMc From www.cdc.gov/dengue/entomologyEcology/m_lifecycle.html. Urdane_a-Marquez and Failloux. Infect Genet Evol (2011) Gonotrophic cycle Unique mang Blood feeding Eggs Gonotrophic cycle 1st 2nd 3rd 4th 5th 6th Blood-meals 1 2 3 4 5 6 0 2 4 6 8 10 12 3-4 weeks Several months Arboviruses 80 families of viruses 4000 virus species 500-600 arboviruses described 265 transmi;ed by mosquitoes 100 pathogen to humans Most are RNA virus (except African swine plague, dsDNA, Asfarviridae) Enveloped virus Dengue Fièvre jaune West-Nile Zika Fièvre de la Vallée du Rii Chikungunya First detecMons DEN ZIK YF WN CHIK Flavivirus / DEN: dengue; YF: Yellow fever; WN: West-Nile; ZIK: Zika Alphavirus / CHIK: Chikungunya Worldwide expansion CC WN DEN WN CHIK DEN DEN DEN ZIK DEN CHIK CHIK WN CHIK DEN ZIK DEN DEN CHIK YF CHIK CHIK CHIK DEN ZIK YF ZIK DEN DEN ZIK CHIK DEN CHIK ZIK CHIK DEN Flavivirus / DEN: dengue; YF: Yellow fever; WN: West-Nile; ZIK: Zika Alphavirus / CHIK: Chikungunya The basic reproducMve number (R0) n Ø ma² . p . b . c . 1 R0 = r R0 < 1 -ln. p m: Vector density a: Human biWng rate p: Daily survival rate of mosquitoes n: Extrinsic Incubaon Period b: Vector competence c: Transmission efficiency from an infected human to a mosquito 1/r: Human infecWous period R0 = 2 R0 = 3 ………. Vectorial system The mosquito is not a needle! Pathogen protozoans helminths viruses Host Vector Humans mosquitoes animals sandflies cks.. Transmission is possible All mosquitoes are not able to transmit all viruses RVF CHIK DEN + - - Culex pipiens - + + Aedes albopictus - + + Aedes aegyp4 Vector competence 2. Wings/Legs/Heads Disseminaon rate 3. Saliva 1. Midgut Transmission rate Extrinsic incubaon period (EIP) InfecMon rate Extrinsic incubaon period (EIP) Vector competence EIP according to T° Once infected, she remains infected all her life Unique mang Blood-meal 1st 2nd 3rd 4th 5th 6th Blood-meals 0 2 4 6 8 10 12 3-4 weeks Several months 4 days Extrinsic incubaon period Infected female Chikungunya Togaviridae - Alphavirus Coffey et al. Future Microbiol (2013) Aedes albopictus CHIK in the world 1952 E1-226V Zouache and Failloux. Curr Opin Insect Sci (2015) Two transmission cycles Aedes furcifer Aedes luteocephalus Aedes taylori Aedes aegypti Aedes africanus Aedes albopictus Sylvac cycle Epidemic cycle Country Year Vector Genotype E1-226 (A or V) Kenya 2004 AA ECSA A Comoros 2005 AA ECSA A La Réunion 2005 AL ECSA/IOL V Seychelles 2005 AL ECSA/IOL V MauriWus 2006 AL ECSA/IOL V Mayo;e 2006 AA - AL ECSA/IOL V Madagascar 2006 AL ECSA/IOL V India 2006 AA - AL ECSA/IOL V Sri Lanka 2006 AA - AL ECSA/IOL V Maldives 2006 AA - AL ECSA/IOL V Cameroon 2006 AL ECSA/IOL V Aedes albopictus Equatorial 2006 AL ECSA/IOL V Guinea Gabon 2007 AL ECSA/IOL V Italy 2007 AL ECSA/IOL V Singapore 2008 AA - AL ECSA/IOL V Malaysia 2008 AA - AL ECSA/IOL V Thailand 2008 AA - AL ECSA/IOL V France 2010 AL ECSA/IOL A Kraemer et al. eLife (2015) China 2010 AL ECSA/IOL V Cambodia 2011 AA - AL ECSA/IOL V Congo 2011 AL ECSA/IOL V Bhutan 2012 AA - AL ECSA/IOL A Aedes albopictus (Skuse, 1894) Colonizes wide range of habitats - Urban, suburban, rural areas, forests - Natural and arWficial breeding sites Nave from Asia Two main biological characterisMcs: • desiccated eggs • diapause during winter Aedes albopictus: an invasive species Europe 1979: Albania 1990: Italy 1999: France 2001: Serbia, Montenegro 2003: Switzerland, Greece, Israel 2004: Belgium, Spain 2005: Netherlands, Slovenia, Croaa, Bosnia, Herzegovia 2007: Germany 2009: Malta 2012: Czech Republic Americas 1983: Trinidad 1985: USA 1986: Brazil 1988: Mexico 1995: Cuba, Guatemala, Honduras, El Salvador Africa 1997: Bolivia 1991: Nigeria, South Africa 1998: ArgenWna, Colombia, Paraguay 2000: Cameroon 2002: Panama 2001: Guinea 2003: Nicaragua 2006: Gabon A new CHIK mutant A V Schuffenecker et al. PLoS Med (2006) Enhanced replicaon in Aedes albopictus Vazeille et al. PLoS ONE (2007) Saliva CHIKV-posive from day 2 Dubrulle et al. PLoS ONE (2009) Has Aedes albopictus contributed to select E1-226V? Kenya (2004) Aedes aegyp8 E1-226A La Reunion Aedes albopictus Mayo_e E1–226V Aedes aegyp8 Aedes albopictus High disseminaon of E1-226V in Aedes albopictus Aedes albopictus Aedes aegyp 100 100 80 80 60 60 40 40 20 20 Disseminated infection rate(%) 0 Disseminated infection rate(%) 0 4.5 5.5 6.5 7.5 8.5 4.5 5.5 6.5 7.5 8.5 Log10 PFU / mL Log10 PFU / mL E1-226A E1-226V E1-226A E1-226V MarMn et al. BMC Ecol (2010) E1-226V predominates in Aedes albopictus 100 80 60 Midgut 40 20 %CHIKVE1-226V 0 0 1 2 3 4 5 6 7 Day post-infection Aedes albopictus Aedes aegypti Saliva Arias-Goeta et al. PLoS ONE (2013) The midgut plays a key role Disseminaon 100 80 60 Blood-meal Inoculaon 40 % CHIKV E1-226V 20 0 Aedes albopictus ALPROV Aedes aegyp8 AAPT 100 Transmission 80 Blood-meal Inoculaon 60 40 % CHIKV E1-226V 20 Arias-Goeta et al. PLoS ONE (2013) 0 Aedes albopictus ALPROV Aedes aegyp8 AAPT AdaptaMon of CHIKV to Ae. albopictus E2-60: Modulates CHIKV infecWvity for both Ae. albopictus and Ae. aegyp8 Tsetsarkin et al. PLoS One (2009) E2-210,211: Interacts with cell receptors Voss et al. Nature (2010) E1-98: Modulates the kineWcs of the pH-dependent E1-226: Involved conformaonal changes and fusion reacWon in endosomal compartment of Ae. albopictus cells in viral entry via fusion with endosomal Tsetsarkin et al. PNAS (2011) membranes Tsetsarkin et al. Curr Opin Virol (2011) Chikungunya emerging in temperates regions Emergence of CHIK Expansion of Aedes albopictus Waldock et al. Pathogens and Global Health (2013) Aedes albopictus in Europe Medlock et al. VBZD (2012) 2007: CHIKV in Italy Emilia-Romagna 229 cases Tomasello & Schlagenhauf. Travel Med Inf Dis (2013) 2010: CHIKV in France AL-South of France Vega-Rua et al. PLoS ONE (2013) France Fréjus (2010) Paty et al. Euro Surveillance (2014) Lower transmission of CHIKV at 28°C 30 France, 2010 25 20 15 10 5 Mean temperature (°C) 0 J F M A M J J A S O N D Month AL South of France AL La Réunion 100 95 100 100 80 85,7 80 70 60 60 55 40 45 40 50 20 20 Transmission rate (%) Transmission rate (%) 0 0 20°C 28°C La Réunion E1-226V 20°C 28°C South of France E1-226A Zouache et al. Proc Biol Sci (2014) CHIK in America Weaver. PLoS Negl Trop Dis (2014) Leparc-Goffart et al. Lancet (2014) Saint-MarMn: Aedes aegyp8 more suscepble to the Asian CHIKV genotype? Vega-Rua et al. PLoS Negl Trop Dis (2015) Ae. albopictus? Florida (USA) Rio (Brazil) Vega-Rua et al. PLoS Negl Trop Dis (2015) Two clusters of Ae. albopictus Florida (USA) Tapachula (Mexico) Tyson (USA) Colon (Panama) Calcutta (Inde) North and Central Americas Brazzaville1 (Congo) Brazzaville2 (Congo) Manaus (Brazil) La Providence (La Réunion) Saint-André (La Réunion) Bar-Sur-Loup (France) Parnamirim (Brazil) Santarem (Brazil) Santos (Brazil) Misiones (Argentina) Rio de Janeiro (Brazil) South America 0.02 Collaboraons: M. Manni, A. Malacrida, G. Gasperi, C. Dauga Salivary glands of Ae. albopictus infected with CHIKV Salivary duct Acini (lobes) Acinar lobe (transverse secon) Vega-Rua et al. Viruses (2015) The threat of CHIKV in France Vega-Rua et al. PLoS Negl trop Dis (2015) CHIKV in France An ECSA genotype rather than an Asian genotype! 11 CHIK cases in October 2014 INVS (2014) Zika Flaviviridae - Flavivirus Source: ViralZone Aedes aegyp8 Zika forest Uganda, near Entebbe (1947) h;ps://en.wikipedia.org/wiki/Rhesus_macaque Rhesus monkey (Macacamula_a) Dick et al.