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)

YF endemic zones

Paraguay (border region) added in 2008

Imported Yellow feverAmericas

• 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

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.

If USA & Europe, why not Asia?

All of tropical Asia is infested with the urban yellow fever mosquito,

Aedes aegypti

Dengue worldwide 2013

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]

Map 3. Ae. albopictus: global spread

Source: Landcare Research, Keys to the Mosquitoes of New Zealand (2004)

Yellow fever 1 Jan. 2012 - 28 Feb. 2013

AFRICA• Cameroon• Chad *• Congo Republic• Ghana• Nigeria *• Senegal• Sierra Leone• Sudan *• Uganda

AMERICAS• Bolivia *• Peru *

* 2013

Yellow fever in capital citieswith international airports

AFRICA, 2010

Abidjan, Côte d’Ivoire

SOUTH AMERICA, 2008

Asuncion, Paraguay

Travel times (including connections)

Nearest points:

• Abidjan – Pakistan

• Total airport airport 23hrs

Furthest points:

• Asuncion – Jakarta

• Total airport airport 35hrs

Why 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

Why 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.

Trop Med Parasitol. 1989 Dec;40(4):396-9. Epidemic yellow fever caused by an incompetent mosquito vector.

Diagnosis & Surveillance situation

• Nobody in Asia is expecting to see a case of YF– therefore a case of high fever with jaundicejaundice and

hemorrhagichemorrhagic 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

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

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).

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!

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]

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

Population (x1000) at risk for YF in Asia*- more than 2.5 billion

Bangladesh 150 494 Malaysia 28 859

Bhutan 783 Nepal 30 486

Cambodia 14 305 Pakistan

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

India 1 241 492 Thailand 69 519

Indonesia 242 326 Viet Nam 88 792

Laos 6 288 (Yemen 24 800)

Myanmar 48 337 TOTAL 2 595 056

*UNDP Population estimates (2011) rounded **very rough estimate (approx. 25% of pop.)

CONCLUSIONWHY 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!MILLIONS WOULD DIE!

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?

THE RISK OF YELLOW FEVER

INTRODUCTION INTO

ASIA IS GREATERGREATER

THAN AT ANY TIME IN HISTORY!

What are we doing about it?