A Global Overview of the Chikungunya Virus Problem

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A Global Overview of the Chikungunya Virus Problem Ann M. Powers, Ph.D. Division of Vector-Borne Infectious Diseases Centers for Disease Control and Prevention

Chikungunya Virus Family Togaviridae,, genus Alphavirus Enveloped, single stranded RNA virus Plus-sense, sense, unsegmented genome of 11.5-11.8 11.8 kilobases First isolated from human serum during outbreak in Tanganyika - 1953 Distinct biological and transmission patterns between African and Asian strains Classical clinical presentation Fever Severe joint pain Rash (maculopapular( maculopapular)

Sylvatic CHIK Transmission Cycle Aedes furcifer, Aedes africanus chimpanzees, monkeys, baboons chimpanzees, monkeys, baboons Aedes furcifer, Aedes africanus

Urban CHIK Transmission Cycle Aedes aegypti Aedes albopictus Aedes aegypti Aedes albopictus

Distribution of CHIKV prior to 1999

Recent Outbreaks of CHIKV 2007 2005 2004 2006-2009 2008-2009 1999-2000 2005 2005-2006 1999, 2001-2003, 2007-2008

Re-emergence emergence of CHIKV: 2004-2006 2006

April, 2008 Timeline First cases identified in East Africa April, 2004 April, 2005 April, 2006 April, 2007

Kenya SUDAN ETHIOPIA UGANDA SOMALIA Nairobi Lamu Island Mombasa Indian ocean

Lamu Island Outbreak July 2004, unusual increase of malaria cases Severity of joint pains unusual 91% blood smears negative for Malaria Out of 10 sera, IgM Ab to CHIK detected in 3 sera

Early Findings At least 1300 suspected cases counted IgM ELISAs negative for Dengue, Yellow Fever, West Nile, RVF, and Sindbis CHIK infection diagnosis by IgM ELISA (60 cases) Virus isolation (22 cases) CHIK confirmed by genomic sequencing No deaths reported

Magnitude of Outbreak The attack rate was 75%. 13,500 persons (95% CI 12,458-14328) 14328) infected. (Lamu population=18,000) 86% of cases hospitalized/ stayed home in bed for a mean of 7 days ( range 1-901 ).

Nature of Virus Central / East African genotype Less than 3% divergent at nucleotide level from closest historical relative 0.001 substitutions/site 65 IND73- IND63- MH5 IND65- WB1 IND71- AP7 IND65- CH1 IND73-B- IND73-B- MH7 IND63-V- 731460 731463 IND65-M- 635865 IND71-M- 654957 713423 IND01-Y- 100 32330171 IND65-N- 654129 IND73-B- 731468 IND63- MY06- WB2 BP37437 MY06- BP34198 MY06- BP37348MY98- IND06- MALh0198 AP6 IND06- AP4 IND05- KA1 IND06- MH2 IND06- MS1 IND06- MH3 88 98 89 92 TA53-ND- ROSS IND73-B- PO731460 IND06- MS2 IND00- MH4 UG82-MD- AG41855 CAR??- CAR256 SA76- SA76- SAH2123 AR18211 TH88-SP- 644188 IN85-AI- PH85-B- TH78-BK- PHH15483 RSU1TH62-181/25 3412/78 (vaccine 181/25 strain) IND63-C- Gibbs63263 TH75-BK- 1455/75 TH95-BK- C039295 TH96-PP- SV0451/96 IND06- KA3 HK06-92111512 REU06-LR2006 REU06- OPY3 REU06- IMT6382 REU06-LR2006 IMT6466 OPY1 REU05- KEN04- reu223 COM05- KPA15 COM25 COM05- COM05- COMJ COM125 REU06- KEN04- IMTAAI72 LAMU33REU06- REU06-LR2006 CQI187 OPY2 DRC00- DRC00-1725 100 CAR96- ChikRCA DRC00-1719 DRC00-1718 027 DRC00-007 DRC00-1720 DRC00-1730 KARIUKI et al., 2008. JOURNAL OF GENERAL VIROLOGY. 89

April, 2007 April, 2008 Timeline Virus moves to Comoros April, 2005 April, 2006 First cases identified in East Africa First cases identified in East Africa April, 2004

Comoros Island Outbreak

Comoros Island Outbreak Suspected Dengue outbreak reported in February 2005. 25 Sera analyzed All negative for Dengue 9 positive for IgM CHIK Antibodies 6 positive for CHIK by PCR

1-May 8-May 15-May 22-May 29-May 24-Apr 800 700 600 500 400 300 200 100 0 Epidemic curve Epidemic curve Investigation started 30-Jan 6-Feb 13-Feb 20-Feb 27-Feb 6-Mar 13-Mar 20-Mar 27-Mar 3-Apr 10-Apr 17-Apr 23-Jan Week ending 16-Jan 9-Jan 2-Jan Number of cases

Antibody Testing Results (N=331) IgG IgM IgG or IgM Positive 89 (27%) 198 (60%) 209 (63%) Negative 242 (73%) 133 (40%) 122 (37%)

Magnitude of Outbreak Attack rate of infection was 63% 214,830 persons (95% CI 196,757-233,244 persons) infected on Island. 79% of cases hospitalized/ stayed at home in bed, mean = 6 days (range 1-301 days)

Nature of Virus Central / East African genotype Virtually identical to isolates from Mombasa and Lamu 0.001 changes REU06 LR2006 OPY1 COM05 - COM125 KEN04 KPA15 COM05 - COM25 COM05 - COMJ IND06-80422 KEN04 - LAMU33 TA53 - S27 KARIUKI et al., 2008. JOURNAL OF GENERAL VIROLOGY. 89

Species Method Sex Number pools + Pools MIR A.aegypti Asp Male 60 8 0 - A. aegypti Asp Female 65 11 2 30.8 A. aegypti HLC Male 392 34 0 - A. aegypti HLC Female 944 81 2 (1*) 2.1 A. simpsoni HLC Female 65 6 0 - A. bromeli HLC Female 10 1 0 - A. vittatus Asp Female 1 1 0 - A. simpsoni HLC Female 41 3 0 - Specie Method Sex Number pools + Pools MIR Aedes. sp Asp Female 42 4 2 47.6 Culex HLC Female 74 5 0 - Culex Asp Female 354 16 1 2.8 Culex Asp/ HLC Males 189 9 0 -

Timeline Virus identified in nearby Reunion April, 2005 April, 2006 April, 2007 April, 2008 PLoS Med. 2006, 3:1058-70 Virus moves to Comoros Virus moves to Comoros First cases identified in East Africa First cases identified in East Africa April, 2004

La Reunion Outbreak First cases: March 2005 Major increase in cases during summer rainy season (mid-december April, 2006) Total number of cases estimated at 244,000

Timeline Epidemic peaks in La Reunion: 40,000 cases/wk Cases identified in Virus identified in nearby Reunion Virus identified in nearby Reunion Mauritius, Seychelles, Madagascar, Maldives April, 2008 April, 2007 April, 2006 April, 2005 Virus moves to Comoros Virus moves to Comoros First cases identified in East Africa First cases identified in East Africa April, 2004

La Reunion changing patterns? New, virulent genotype? Neurological involvement Intrauterine transmission (?) /neonatal disease CHIKV-associated deaths (underlying conditions) Transmission by alternate vector (?)

Possible increase in virulence? PLoS Med. 2006, 3:1058-70

Aedes albopictus as a vector of CHIKV

Timeline Outbreaks occur in India, Malaysia, Sri Lanka, Indonesia Institute Pasteur CHIKV research Science reports Several Indian Ocean islands Epidemic peaks in La Reunion April, 2008 April, 2007 April, 2006 Virus identified in nearby Reunion Virus identified in nearby Reunion April, 2005 Virus moves to Comoros Virus moves to Comoros First cases identified in East Africa First cases identified in East Africa April, 2004

Movement to Asia

India outbreaks 13 states affected in 2005-2006 2006 after 32 year interepidemic period Estimated 1.3 million cases Introduction of the Central/East African genotype into Asia

Imported Cases of CHIKV Canada Hong Kong UK Belgium Czech Republic Germany Norway Switzerland Australia France Italy Corsica Sri Lanka Singapore USA Spain Japan Taiwan

CHIKV in Italy Outbreak resurges in India A V: albopictus April, 2008 April, 2007 Outbreak explodes in India Outbreak explodes in India Timeline Imported cases documented Outbreaks occur in India, Malaysia, Sri Lanka, Indonesia Institute Pasteur CHIKV research Science reports Several Indian Ocean islands Epidemic peaks in La Reunion April, 2006 Virus identified in nearby Reunion Virus identified in nearby Reunion April, 2005 Virus moves to Comoros Virus moves to Comoros First cases identified in East Africa First cases identified in East Africa April, 2004

Confirmed cases of CHIKV in Italy

Movement to Italy

Italian Outbreaks

Outbreaks continue in SE Asia, India Outbreaks continue in SE Asia, India CHIKV in Italy CHIKV in Italy Outbreak resurges in India A V: albopictus April, 2008 April, 2007 Outbreak explodes in India Outbreak explodes in India Timeline Imported cases documented Outbreaks occur in India, Malaysia, Sri Lanka, Indonesia Institute Pasteur CHIKV research Science reports Several Indian Ocean islands Epidemic peaks in La Reunion April, 2006 Virus identified in nearby Reunion Virus identified in nearby Reunion April, 2005 Virus moves to Comoros Virus moves to Comoros First cases identified in East Africa First cases identified in East Africa April, 2004

Timeline Continued & renewed activity in Thailand, India, Malaysia, La Reunion. Outbreaks continue in SE Asia, India Outbreaks continue in SE Asia, India????? April, 2011 April, 2010 April, 2009 Outbreaks continue in SE Asia, India Outbreaks continue in SE Asia, India April, 2008

Factors Affecting Emergence/Outbreaks???

Factors Affecting Emergence/Outbreaks Environmental/ecological conditions Abundance of mosquito egg laying habitats Completely naïve pop Alternate vector(s), new ecological niches involved Viral genetics / mutations

Gracias!