Yellow fever Global threat Jack Woodall Ph D

Yellow fever: Global threat Jack Woodall, Ph. D Institute of Medical Biochemistry Federal University of Rio de Janeiro, Brazil (retired) (Formerly CDC & WHO Geneva) Not me! ASTMH Annual Meeting, 16 Nov. 2013

YF endemic zones

Background • “Fears have long been held that if yellow fever were introduced to Asia it might spread widely and rapidly with – catastrophic human mortality and – subsequent establishment of a forest reservoir in primates or other animals – because of the presence of large populations of potential vector mosquitos (Aedes aegypti, A. albopictus). ”

Background (2) • “In 1954 a meeting of experts on yellow fever at Kuala Lumpur discussed the hazard of introduction of yellow fever to south and south-east Asia. “Trials of yellow fever vaccination in Malayan volunteers were subsequently carried out with the assistance of United Kingdom Colonial Development and Welfare. ” (Gordon-Smith CE, Turner LH, Armitage P. 1962)

Last Yellow fever epidemics USA Sailing-ship era • 1905 New Orleans, Louisiana, 8, 399 cases) & Pensacola, Florida • 1911 last indigenous case http: //www. gideononline. com

Last Yellow fever epidemics EUROPE Sailing-ship era 1861 France (St Nazaire) 44 cases, 24 deaths 1828 Gibraltar (UK) 1500 deaths

Yellow fever, imported cases, 1999 -present Airline era Netherlands 2000 Surinam

What has changed in the last 10 years? • Yellow fever in emerging phase Yellow fever

Yellow fever in emerging phase 2013 AFRICA • WHO warning about urbanization in West Africa 2005 • Sudan & 5 more African outbreaks 2012 -13: one ongoing TODAY

WEST AFRICA URBANIZATION WHO ALERT • Date: 2005 • Source: WHO Global Alert and Response (GAR) • http: //www. who. int/csr/disease/yellowfev/urbanoutbreaks/en/ • Increased risk of urban yellow fever outbreaks • The risk of large and uncontrollable outbreaks in urban areas in Africa is more likely than ever. • Accelerated urbanization has concentrated a nonimmune population in settings where, high vector and population density, the main factors contributing to increased virus transmission are present.

YELLOW FEVER – SUDAN (KORDOFAN) • • Date: 14 Nov 2013 Source: Radio Dabanga (Hilversum) http: //allafrica. com/stories/201311151118. html According to the Sudanese Ministry of Health, between 3 Oct and 5 Nov [2013], a total of 22 suspected yellow fever cases, resulting in 7 deaths, occurred in West & South Kordofan, CFR 36. 3%, OCHA reports in its latest Humanitarian Bulletin. 45 000 people to be vaccinated. -Communicated by : Pro. MED-mail <promed@promedmail. org>

Yellow fever in emerging phase 2013 SOUTH AMERICA Peru 2013 Bolivia 2013 Brazil 2012 (monkey deaths) Source: Pro. MED <http: //www. promedmail. org/>

Yellow fever – Brazil: CDC Alert • Yellow Fever in Brazil -- Outbreak Alert 2013 Because an outbreak of yellow fever was found in areas of Brazil outside of the reported yellow fever risk areas… Travelers should follow “enhanced precautions” for that risk area [Rio Grande do Sul & SW Sao Paulo states] by receiving the yellow fever vaccine. • Source: CDC <http: //wwwnc. cdc. gov/travel/notices#travel-noticedefinitions>

Yellow fever in South America increasing since 2008 • Source: Pro. MED http: //promedmail. org/direct. php? id=20080401. 1206 • The last outbreak of jungle yellow fever reported was in Corrientes in 1966 -- 47 years ago • Source: PAHO report <http: //promedmail. org/direct. php? id=171703> Paraguay Brazil ARGENTINA Misiones • 2008: Ministry of Health confirmed Corrientes 5 cases of jungle yellow fever in Misiones Province Uruguay

Yellow fever in South America increasing since 2008 BRAZIL • Outbreaks of YF -- typically occurring in Brazil every 7 years -- have become more frequent • YF has progressed to areas previously considered free – in Rio Grande do Sul (free since 1966) – & SW Sao Paulo state • These 2 areas previously posed no risk for YF, but between November 2008 and April 2009 they recorded 43 infections, with 16 deaths. • Source: O Estado de Sao Paulo, 21 May 2009 [in Portuguese] via Pro. MED <http: //promedmail. org/direct. php? id=204930> [in English]

What has changed in the last 10 years? • Yellow fever in emerging phase Yellow fever • Dengue continues its worldwide spread

* Map 2. Madeira (PT) 2005 *range of Aedes aegypti

Dengue, Madeira (PT) 2012 -13 • The island of Madeira, Portugal, experienced an outbreak of dengue, which began in October 2012, and saw an overall total of 2, 170 cases of dengue fever through April 2013 [no deaths] • DEN-1 was identified with probable Central or South American origin. (Alves MJ, et al. 2012) Origin Venezuela (Annelise Wilder-Smith at ASTMH Annual Meeting, Washington DC 14 Nov 2013) 2 cases imported since from Angola (Pro. MED 3 June 2013 Dengue/DHF update (46): Asia, Africa)

Dengue, imported into Europe, 2012 Madeira 2012

Dengue in Europe • A large number of autochthonous cases of dengue fever (2237) occurred in Europe (Italy, France, Croatia, Madeira) during the period covered by our analysis (2007 -2012) (Tomasello D, Schlagenhauf P. 2013)

Beavis to Butthead Where dengue goes, YELLOW FEVER can follow… …anywhere the mosquito vectors are found!

But if USA & Europe, why not Asia? All of tropical Asia is infested with the yellow fever vector mosquito, Aedes aegypti

Why hasn’t YF broken out in Asia? • If YF cases have occasionally been imported into the USA & Europe • Cases must also have occasionally been imported into Asia • But there have been no such records in medical history

Why hasn’t YF broken out in Asia? Cross-immunity theory • Asian population protected by broad crossimmunity, because of dengue, Japanese encephalitis & other flavivirus infections

Why hasn’t YF broken out in Asia? BUT neither dengue nor Japanese encephalitis patients produce neutralising antibodies to YF (Makino Y et al. 1994)

Why hasn’t YF broken out in Asia? • Ecuador: serological surveys showed • “. . . previous exposure to dengue infection may have induced an anamnestic immune response that – did not prevent yellow fever infection but – greatly reduced the severity of the disease (Izurieta RO et al. 2009)

Why hasn’t YF broken out in Asia? Vector competence theory • Asian strains of Aedes aegypti mosquitoes not as competent vectors of YF as in Africa & South America? BUT they can still cause urban epidemics, e. g. Nigeria 1987 (Miller BR, Monath TP, Tabachnick WJ, Ezike VI 1989)

What has changed in the last 10 years? • Yellow fever in emerging phase (Sudan & 5 more Yellow fever African outbreaks 2012) • Dengue continues its worldwide spread • Ae. aegypti has spread to Europe

Aedes albopictus & A. aegypti, aegypti Europe, March 2013 RUSSIA GEORGIA MADEIRA (PT) 2012 ECDC 2013

What has changed in the last 10 years? • Yellow fever in emerging phase (Sudan & 5 more Yellow fever African outbreaks 2012) • Dengue continues its worldwide spread • Ae. aegypti spread to Europe • Air travel connections ever faster

Yellow fever, Africa 2013 Airline connections to Europe

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

Travel times: Endemic zones Asia (including connections) AFRICA • Abidjan (Côte d’Ivoire) Dubai Pakistan • Total 23 hrs* SOUTH AMERICA • Asuncion (Paraguay) Dubai Jakarta • Total 35 hrs* *Well within the incubation period of YF

What has changed in the last 10 years? • Yellow fever in emerging phase (Sudan & 5 more Yellow fever African outbreaks 2012) • • Dengue continues its worldwide spread Ae. aegypti spread to Europe Air travel connections ever faster YF vaccine production faltering

Vaccine situation (1) • Stocks: existing world stocks (6 million doses) are insufficient to counter an epidemic in Asia • Supply: production cannot be expanded fast enough to provide protection to all of Asia (viz. current worldwide shortage of single dose vials) • However, see next presentation in this session on dose-sparing solutions • Distribution: vaccine requires a cold chain, but in some Asian countries this is probably only adequate to handle enough vaccine for SNIDs (sub-national immunization days)

Vaccine situation (2) • Application: a crash program of mass training and mobilization of vaccinators takes time • Adverse effects: 1 or 2 deaths agttributed to the vaccine (inevitable during mass campaigns) are sufficient to shut down a vaccination program • Resistance: some Asian countries may resist vaccination (as happened recently with polio vaccination in West Africa & measles vaccination in Pakistan).

Fake vaccination certificates (1) • Nigeria: In March 2012, 125 Nigerians on a plane to Johannesburg were denied entry and deported by the South African port health authority. The authority had concerns about the validity of the yellow fever vaccination cards • Source: Pro. MED • http: //promedmail. org/direct. php? id=20120724. 1213759

Fake vaccination certificates (2) • India • In March 2011, WHO organised a consultation on the yellow fever threat to India and SE Asia in which it was concluded that the threat of introduction of YF [virus] into Asia was very real in the age of faster air travel. BUT • Black market: certificates were issued in India without vaccination during the 2013 vaccine shortage • Source: Pro. MED http: //www. promedmail. org/direct. php? id=20130719. 1833351

Fake vaccination certificates (3) • Tanzania: black market in certificates • Source: Pro. MED • http: //promedmail. org/direct. php? id=1530747 • Risk of spread by a single apparently healthy unvaccinated passenger incubating YF virus arriving in a country with the mosquito vector (e. g. Chikungunya virus: India Italy 2007)

What has changed in the last 10 years? • Yellow fever in emerging phase (Sudan & 5 more Yellow fever African outbreaks 2012) • • • Dengue continues its worldwide spread Ae. aegypti spread to Europe Air travel connections ever faster YF vaccine production faltering Fake YF vaccination certificates Interruption of mass vaccination in endemic zones

Vaccine situation Interruption of mass vaccination in many endemic countries/areas e. g. • Francophone West & Central Africa: no mass vaccination since independence -- except in areas with outbreaks • Nigeria: no mass vaccination since 1987 urban epidemics -- except in areas with outbreaks

What has changed in the last 10 years? • Yellow fever in emerging phase (Sudan & 5 more Yellow fever African outbreaks 2012) • • • Dengue continues its worldwide spread Ae. aegypti spread to Europe Air travel connections ever faster YF vaccine production faltering Fake YF vaccination certificates Interruption of mass vaccination in endemic zones • Failure of vector control

Vector control situation Existing vector control programs in Africa & Asia are failing to control dengue • Reintroduction of DDT could help (India) • BUT a crash program of training & deployment of spray workers will take time • AND ground or aerial spraying: – householders find spray obnoxious – close up their houses when it passes – protecting the mosquitoes inside!

Hospital situation No specific therapy for YF • Stocks of antiviral drugs will soon be exhausted In rural areas: • Stocks of intravenous fluids will soon be exhausted, • followed by delay in re-supply Fortunately, YF is not transmitted by fomites, because • Stocks of disposable syringes/needles, will run out – & be re-used with associated risks

Diagnosis & Surveillance situation • Nobody in Asia is expecting to see a case of YF – 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, even under the new IHR

Containment situation • Populace may flee – when plague broke out in Surat, India in 1994, 400 000 people (one-fifth of population) fled the city (including doctors & nurses!) • Some reached New Delhi & even Pakistan – potentially spreading the infection

Population at risk for YF, Asia 2010 Country Pop. x 1000 Bangladesh 151 125 Nepal 26 846 Bhutan 717 Pakistan 173 149 Cambodia 14 365 Papua N. Guinea* 6 065 China Ϯ 406 477 Philippines 93 444 Hong Kong SAR 7 050 Singapore 5 079 Macau SAR 535 Sri Lanka 20 759 East Timor 1 079 Taiwan* 23 160 India 1 205 625 Thailand 66 402 Indonesia 240 676 Viet Nam 89 407 Laos 6 396 Yemen 22 763 Malaysia 28 276 TOTAL 2 641 326 Myanmar* 51 931 20 countries UNDP Population estimates 2010 Ϯsouthern provinces under 10° isotherm *non-UN sources 2010

Conclusion Why hasn’t YF broken out in Asia yet? • We don´t know -- BUT because of – Fast airline routes – and YF currently being in an expansion phase • the risk is higher than it has ever been, SO • if it does break out, there will be – insufficient vaccine, and – inadequate vector control • With an untreated CFR of at least 20% -- HUGE NUMBERS OF DEATHS COULD OCCUR

YF contingency plan? • We have had 10 years to worry about avian flu • There are now plans in many countries to combat its spread • We have had decades to think about YF invading Asia, Europe & the USA • Is there even ONE contingency plan for that?

THE RISK OF YELLOW FEVER INTRODUCTION INTO USA, EUROPE & ASIA IS GREATER THAN AT ANY TIME IN THE LAST 150 YEARS! What are we going to do about it?

OR MAKE CONTINGENCY PLANS?

Yellow Fever contingency plan • A Regional Workshop was held by WHO/SEARO in Goa in 2011 • It included developing a proposed country contingency plan for Yellow Fever • (JW & DG were facilitators) • Copies of the report are available from SEARO

THANK YOU! JACKWOODALL 13@GMAIL. COM WWW. PROMEDMAIL. COM