Yellow fever: Global threat

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Yellow feverGlobal threat

• Jack Woodall, PhD
• Institute of Medical Biochemistry
• Federal University of
• Rio de Janeiro, Brazil (retired)
• (Formerly CDC WHO Geneva)

Not me!
ASTMH Annual Meeting, 16 Nov.2013
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YF endemic zones
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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).

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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)

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Last Yellow fever epidemicsUSA Sailing-ship era

• 1905 New Orleans, Louisiana, 8,399 cases)
  Pensacola, Florida
• 1911 last indigenous case http//www.gideononline.
  com

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Last Yellow fever epidemicsEUROPESailing-ship
era
1861 France (St Nazaire) 44 cases, 24 deaths
1828 Gibraltar (UK) 1500 deaths
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Yellow fever, imported cases,
1999-present Airline era
Netherlands 2000
Surinam
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What has changed in the last 10 years?

• Yellow fever in emerging phase

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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

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WEST AFRICA URBANIZATIONWHO ALERT

• Date 2005
• Source WHO Global Alert and Response (GAR)
• http//www.who.int/csr/disease/yellowfev/urbanoutb
  reaks/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
  non-immune population in settings where, high
  vector and population density, the main factors
  contributing to increased virus transmission are
  present.

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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
• ProMED-mail ltpromed_at_promedmail.orggt

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Yellow fever in emerging phase 2013

• SOUTH AMERICA
• Peru 2013
• Bolivia 2013
• Brazil 2012 (monkey deaths)
• Source ProMED lthttp//www.promedmail.org/gt

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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 lthttp//wwwnc.cdc.gov/travel/noticest
  ravel-notice-definitionsgt

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Yellow fever in South Americaincreasing since
2008
Brazil

• ARGENTINA
• 2008 Ministry of Health confirmed 5 cases of
  jungle yellow fever in Misiones Province
• Source ProMED 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
• lthttp//promedmail.org/direct.php?id171703gt

Paraguay
Misiones
Corrientes
Uruguay
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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 ProMED lthttp//promedmail.org/direct.php?
  id204930gt
• in English

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What has changed in the last 10 years?

• Yellow fever in emerging phase
• Dengue continues its worldwide spread

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Map 2.
Madeira (PT) 2005
range of Aedes aegypti
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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 (ProMED 3 June
  2013
• Dengue/DHF update (46) Asia, Africa)

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Dengue, imported into Europe, 2012
Madeira 2012
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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)

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any- where the mosquito vectors are found!
Where dengue goes, YELLOW FEVER can follow
Beavis to Butthead
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But if USA Europe, why not Asia?

• All of tropical Asia is infested with the yellow
  fever vector mosquito,
• Aedes aegypti

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Why hasnt 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

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Why hasnt YF broken out in Asia?

• Cross-immunity theory
• Asian population protected by broad
  cross-immunity, because of dengue, Japanese
  encephalitis other flavivirus infections

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Why hasnt YF broken out in Asia?

• BUT neither dengue nor Japanese encephalitis
  patients produce neutralising antibodies to YF
• (Makino Y et al. 1994)

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Why hasnt 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)

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Why hasnt 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)

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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  African outbreaks 2012)
• Dengue continues its worldwide spread
• Ae. aegypti has spread to Europe

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Aedes albopictus A. aegypti, Europe, March 2013
RUSSIA
GEORGIA
MADEIRA (PT)
2012
ECDC 2013
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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  African outbreaks 2012)
• Dengue continues its worldwide spread
• Ae. aegypti spread to Europe
• Air travel connections ever faster

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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  African outbreaks 2012)
• Dengue continues its worldwide spread
• Ae. aegypti spread to Europe
• Air travel connections ever faster

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Yellow fever, Africa 2013
Airline connections to Europe
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Yellow fever in capital citieswith
international airports

• SOUTH AMERICA, 2008
• Asuncion, Paraguay
• AFRICA, 2010
• Abidjan, Côte dIvoire

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Travel times Endemic zones ? Asia (including
connections)

• AFRICA
• Abidjan (Côte dIvoire) ?Dubai ? Pakistan
• Total 23hrs
• SOUTH AMERICA
• Asuncion (Paraguay) ? Dubai ? Jakarta
• Total 35hrs
• Well within the incubation period of YF

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(No Transcript)
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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  African outbreaks 2012)
• Dengue continues its worldwide spread
• Ae. aegypti spread to Europe
• Air travel connections ever faster
• YF vaccine production faltering

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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)

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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 has happened recently with polio
  vaccination in West Africa measles vaccination
  in Pakistan).

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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 ProMED
• http//promedmail.org/direct.php?id20120724.12137
  59

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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 ProMED http//www.promedmail.org/direct.ph
  p?id20130719.1833351

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Fake vaccination certificates (3)

• Tanzania black market in certificates
• Source ProMED
• http//promedmail.org/direct.php?id1530747
• 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)

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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  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

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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

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What has changed in the last 10 years?

• Yellow fever in emerging phase (Sudan 5 more
  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

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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!

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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

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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

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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

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Population at risk for YF, Asia 2010
Country Pop. x1000 Country Pop. x1000
Bangladesh 151 125 Nepal 26 846
Bhutan 717 Pakistan 173 149
Cambodia 14 365 Papua N. Guinea 6 065
China ? 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
?southern provinces under 10 isotherm
non-UN sources 2010
UNDP Population estimates 2010
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Conclusion

• Why hasnt YF broken out in Asia yet?
• We dont 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

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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?

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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?

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?
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(No Transcript)
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MAKE CONTINGENCY PLANS?
OR
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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

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Thank You!jackwoodall13_at_gmail.comwww.promedma
il.com