1. Yellow fever: threat to Asia Jack Woodall PhD Institute of Medical Biochemistry Federal University of Rio de Janeiro Brazil ASIA Jack Woodall PhD Institute of Medical Biochemistry Federal University of Rio de Janeiro Brazil (retired)

2. YF endemic zones Paraguay (border region) added in 2008

3. Imported Yellow fever Americas USA1999 (California ex Venezuela) fatal ϯ Unvaccinated tourist Urban YF vector mosquito Aedes aegypti does NOT occur in California USA 2002 (Texas ex Brazil) fatal ϯ Unvaccinated tourist fishing on Amazon Urban YF vector mosquito Aedes aegypti occurs in Texas… But case was hospitalized in USA in March, before mosquito season, therefore no epidemic possible USA1999 (California ex Venezuela) fatal ϯ Unvaccinated tourist Urban YF vector mosquito Aedes aegypti does NOT occur in California USA 2002 (Texas ex Brazil) fatal ϯ Unvaccinated tourist fishing on Amazon Urban YF vector mosquito Aedes aegypti occurs in Texas… But case was hospitalized in USA in March, before mosquito season, therefore no epidemic possible

4. Imported Yellow fever Europe Germany 1999 (ex Côte d'Ivoire) fatal ϯ Netherlands 2000 (ex Suriname) survived Belgium 2001 (ex Gambia) fatal ϯ Unvaccinated tourists Urban YF vector mosquito Aedes aegypti occurs only in Spain, Portugal, & southernmost parts of Italy & Greece So, imported cases of YF into these more northern parts of Europe did not result in epidemics.

5. If  USA & Europe, why not Asia? All of tropical Asia is infested with the urban yellow fever mosquito, Aedes aegypti

6. Dengue worldwide 2013

7. Aedes albopictus problem “We conclude that the Houston (USA) strain of Ae. albopictus is a competent vector of yellow fever virus and can serve as bridging vector between the jungle yellow fever cycle and the urban cycle in New World ecosystems.” (Miller BR, Mitchell CJ, Ballinger ME. 1989) [It could therefore also transmit YF in Asia]

8. Map 3. Ae. albopictus: global spread Source: Landcare Research, Keys to the Mosquitoes of New Zealand (2004)

9. Yellow fever 1 Jan. 2012 - 28 Feb. 2013 AFRICA Cameroon Chad * Congo Republic Ghana Nigeria * Senegal Sierra Leone Sudan * Uganda AMERICAS Bolivia * Peru * * 2013

10. Yellow fever in capital cities with international airports AFRICA, 2010 Abidjan, Côte d’Ivoire SOUTH AMERICA, 2008 Asuncion, Paraguay

12. Travel times (including connections) Nearest points: Abidjan – Pakistan Total airport  airport 23hrs Furthest points: Asuncion – Jakarta Total airport  airport 35hrs

13. W hy hasn’t YF broken out in Asia yet? 1. Cross-immunity theory the Asian population is protected by cross- immunity, because so many have had dengue? BUT neither dengue nor Japanese encephalitis patients produce neutralising antibodies to YF –Ref: Makino Y et al. Studies on serological cross- reaction in sequential flavivirus infections. Microbiol Immunol. 1994;38(12):951-5

14. W hy hasn’t YF broken out in Asia yet? 2. Vector competence theory Asian Aedes aegypti mosquitoes are not as competent as the vectors of YF in Africa & South America? BUT lab tests show this does not matter - Ref: Miller BR, Monath TP, Tabachnick WJ, Ezike VI.Miller BRMonath TPTabachnick WJEzike VI Trop Med Parasitol. 1989 Dec;40(4):396-9. Epidemic yellow fever caused by an incompetent mosquito vector.

15. Diagnosis & Surveillance situation Nobody in Asia is expecting to see a case of YF jaundice hemorrhagic –therefore a case of high fever with jaundice and hemorrhagic symptoms will be put down to DHF, hepatitis or something else, but NOT YF –no lab test for YF will be requested Probably only the national reference lab will have reagents –preferably the rapid PCR test for YF YF is probably not a reportable disease –although it should be because of the new IHR

16. Vaccine situation (1) Stocks: existing world stocks are INSUFFICIENT to counter a major epidemic in Asia Supply: production CANNOT be ramped up fast enough to provide protection to all of Asia Distribution: vaccine requires a cold chain. Cold chains exist in Asian countries BUT are only adequate to handle enough vaccine for the childhood cohort

17. Vaccine situation (2) Application : a crash program of mass training and mobilization of vaccinators is beyond the capacity of many Asian countries Adverse effects : one or two deaths due to the vaccine (inevitable during mass campaigns) are sufficient to shut down a vaccination program Cultural resistance : some Asian countries may resist vaccination (as happened recently with polio vaccination in West Africa).

18. Vector control situation Existing vector control programs in Asia are failing to control dengue Temporary use of DDT could help (legal in India) BUT a crash program of training & deployment of spray workers would take time AND experience has shown that householders find spray obnoxious and close up their houses when sprayers pass -- protecting the mosquitoes inside!

19. Health care situation There is NO specific therapy for YF In hospitals: Stocks of antiviral drugs will soon be exhausted In rural areas: Stocks of intravenous fluids will soon be exhausted [ Fortunately, YF is not transmitted by fomites, because stocks of disposable syringes, needles, etc. will run out – and they will be re-used, spreading hepatitis & HIV]

20. Containment situation Populace will flee –when plague broke out in Surat, India in 1994, 400 000 people (1/5 of the population) fled the city Some reached New Delhi & even Pakistan –potentially spreading the infection

21. Population (x1000) at risk for YF in Asia* - more than 2.5 billion Bangladesh 150 494Malaysia 28 859 Bhutan 783Nepal 30 486 Cambodia 14 305Pakistan Papua N.G. 176 745 7 014 China at risk** Macau SAR Hong Kong SAR 336 891 550 7 122 Philippines Singapore Sri Lanka 94 852 5 188 21 045 India1 241 492Thailand 69 519 Indonesia 242 326Viet Nam 88 792 Laos 6 288(Yemen 24 800) Myanmar 48 337 TOTAL2 595 056 * UNDP Population estimates (2011) rounded **very rough estimate (approx. 25% of pop.)

22. CONCLUSION WHY hasn’t YF broken out in Asia yet? We don’t know! BUT because of fast airline through routes, the risk is higher than it has ever been IF YF does break out, there will be insufficient vaccine and inadequate vector control With up to 2.6 billion people exposed And a CFR of up to 50%, MILLIONS WOULD DIE!

23. YF contingency plan? We have had over 5 years to worry about avian flu There is now a plethora of plans in many countries to combat its spread We have had decades to think about YF invading Asia Is there even ONE contingency plan for that?

24. GREATER THE RISK OF YELLOW FEVER INTRODUCTION INTO ASIA IS GREATER THAN AT ANY TIME IN HISTORY! What are we doing about it?