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Yellow Fever: Risk Mapping
Wellington, August 2013
David R Hill MD DTM&H FRCP FFTM FASTMH
Professor of Medical Sciences
Director, Global Public Health
Frank H Netter MD School of Medicine
Quinnipiac University
Assessing Geographic Risk of Yellow Fever
• Defining disease risk in travellers
• Goals, rationale and process
• Outcomes: new categories of risk
• Specific country examples
• Implications: travel medicine & IHR (2005)
• Implementation
• For relatively high incidence disease we combine:
 global epidemiology of disease
 imported cases / # travellers / destination / time
Defining Disease Risk for Travel
Defining Disease Risk: Malaria
US Civilian Travellers, 2008
Mali S, et al. MMWR
59(SS-7):1, 2010
Travellers Visiting Friends and Relatives:
3.7 x  risk to West Africa Smith AD, et al. BMJ 337:a120, 2008
• Enteric fever imported to UK:
 93% of cases from South Asia
Defining Disease Risk: Enteric fever
UK Travellers
Country
Rate*
VFR
Rate Non-
VFR
India 28.8 3.3
Pakistan 26.4 8.2
Bangladesh 36.9 10.5
* Rate of S. Typhi and S. Paratyphi A/100,000 visits
Lawrence J, Jones J. Enhanced enteric fever surveillance.
UK Public Health England, 2008.
• For low volume disease we take into account:
 global epidemiology (geography of risk)
 severity of disease
 case reporting becomes anecdotal
• Polio, Japanese encephalitis, yellow fever
• Define risk based on geography and exposure
Defining Disease Risk for Travel
Base prevention on sensible,
‘evidence-based’ measures
Imported Yellow Fever Cases: 1970-2013
Country Year Case Outcome Vaccinated?
Senegal 1979 42, M Death No
Senegal 1979 25, M Death No
Guinea-Bissau 1985 27, F Survived No
West Africa 1988 37, F Survived Yes
Brazil 1996 53, M Death No
Brazil 1996 42, M Death No
Cote d’Ivoire 1999 40, M Death No
Venezuela 1999 48, M Death No
The Gambia 2001 47, F Death No
Brazil 2002 47, M Death No
2011 WHO Yellow Fever
Vaccination Maps
Vaccination recommended
Vaccination usually not recommended
Not recommended
Historical Determination of YF Risk
• Clinical case reports
– severe illness, foreigners,
coastal ports, rivers and railways
– non-specific: e.g. confused with
malaria, hepatitis, leptospirosis
• Serosurveys: mouse protection
assay (1931)
• Viscerotomies in persons dying
with a febrile illness; mostly in
S. America
Yellow Fever Epidemiology: Africa
Sawyer WA. Harvey Lectures. 66-92, 1936.
Human Cases: 1920-1934 Human Serology: 1930-1934
Yellow Fever Endemic Regions, 1945
UN Relief and Rehabilitation Administration. Epidemiol Inf Bull. 1:687, 1945.
South America Africa
• Response to:
– recognition of serious adverse events
– changing epidemiology of yellow fever
• Goals:
– more accurate definition of risk areas
– unify risk maps between CDC & WHO
– transparency of recommendations
– inform country policy around IHR (2005)
WHO Consultation on Yellow Fever Risk, 2008
Jentes E, et al. Lancet Infect Dis. 11:622, 2011
Curr Infect Dis Rep 14:246, 2012
Evidence Used for Risk Mapping
• Human and non-human primates: cases,
clusters and outbreaks
• Human serology prior to YF vaccination;
most data generated in 1950s and earlier
• Vegetation and altitude
• Vector distribution
Kenya: Yellow Fever Serology and Cases
Courtesy Tom Monath
PAHO: July 2010
South America: Altitude limit of 2,300 m
Regional land cover:
Horn of Africa
• Endemic
• Transitional
• Low potential (risk)
for exposure
• No risk
Yellow Fever Consultation
Creation of New Categories of Risk
Yellow Fever Risk Classification
Risk
Classification
Examples
Criteria for Risk
YF vectors
and NHP
present?
Human or
NHP YF
cases?
Serosurvey
evidence?
Endemic Nigeria Yes Repeatedly High levels
Transitional Paraguay Yes
Reported at
long intervals
Present
Low potential
for exposure
Tanzania Yes None Low levels
No New Zealand Yes / No None No
Use of Elevation Data: Bolivia
Areas below 2,300 m, determined from
global digital elevation model (GTOPO30 )
Areas below 2,300 m classified endemic
Altitude limit of 2,300 m
Use of Vegetation Data: Niger
Barren or sparsely vegetated areas
as determined from normalized
difference vegetation index (NDVI)
Areas classified as endemic
Peru:
 no risk: coastal, south of La
Libertad, Andes above 2,300 m
 low potential: Tumbes,
Lambayeque, and parts of
Piura and Cajamarca
 transitional: eastern Piura state
 endemic: remainder of country
New Yellow Fever Risk Maps
Kenya:
 low potential: North
Eastern zone, Coastal
zone and Nairobi
 endemic: remainder of
country
New Yellow Fever Risk Maps
Tanzania
 low potential
for exposure
New Yellow Fever Risk Maps
Zambia
 low potential: North
West and Western
provinces
 no risk: remainder
of country
New Yellow Fever Risk Maps
Special Considerations
• Examined high volume destinations, in attempt to
avoid vaccinating many travelers unnecessarily
• Low potential for exposure:
 port cities in South America
 Cartagena, Baranquilla, Port of Spain
 Nairobi
• No risk:
 transit of 12 h or less in international airports
 Inca Trail (Peru)
Yellow Fever Risk Mapping:
Shift from risk maps to vaccination maps
• Vaccination recommended
– endemic
– transitional
• Vaccination generally not recommended
– low potential for exposure (low risk)
– exceptions: prolonged, often rural,
extensive mosquito exposure
• Vaccination not recommended
– no risk
Risk
Vaccination recommended
Vaccination usually not recommended
Not recommended
Vaccination
Implications for IHR (2005)
Low risk countries

Low potential for exposure
Thus, low risk countries will never appear in Annex 1

IHR (2005): Annex 1B, 2f
Afghanistan, Australia, & India require YF vaccine
from travellers arriving from countries with a (low) risk
of YF transmission; e.g. historically from Tanzania,
Eritrea, Zambia.
South Africa considers ‘low potential’ as risk and
requires vaccine of travelers from Tanzania &
Zambia, including those in transit.
2011 WHO Yellow Fever
Vaccination Maps
Vaccination recommended
Vaccination usually not recommended
Not recommended
http://www.who.int/ith/en/
Conclusions
• Robust process using best available evidence
• Transparency in decision making
• Attempts at ‘shrinking’ risk map
• Achieved globally agreed risk categorization
• Implications for travel medicine practitioners
• Implications for Annex 1 (ITH) under IHR (2005)
• Continuous review of model and epidemiology

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Yellow Fever: Risk Mapping

  • 1. Yellow Fever: Risk Mapping Wellington, August 2013 David R Hill MD DTM&H FRCP FFTM FASTMH Professor of Medical Sciences Director, Global Public Health Frank H Netter MD School of Medicine Quinnipiac University
  • 2. Assessing Geographic Risk of Yellow Fever • Defining disease risk in travellers • Goals, rationale and process • Outcomes: new categories of risk • Specific country examples • Implications: travel medicine & IHR (2005) • Implementation
  • 3. • For relatively high incidence disease we combine:  global epidemiology of disease  imported cases / # travellers / destination / time Defining Disease Risk for Travel
  • 4. Defining Disease Risk: Malaria US Civilian Travellers, 2008 Mali S, et al. MMWR 59(SS-7):1, 2010 Travellers Visiting Friends and Relatives: 3.7 x  risk to West Africa Smith AD, et al. BMJ 337:a120, 2008
  • 5. • Enteric fever imported to UK:  93% of cases from South Asia Defining Disease Risk: Enteric fever UK Travellers Country Rate* VFR Rate Non- VFR India 28.8 3.3 Pakistan 26.4 8.2 Bangladesh 36.9 10.5 * Rate of S. Typhi and S. Paratyphi A/100,000 visits Lawrence J, Jones J. Enhanced enteric fever surveillance. UK Public Health England, 2008.
  • 6. • For low volume disease we take into account:  global epidemiology (geography of risk)  severity of disease  case reporting becomes anecdotal • Polio, Japanese encephalitis, yellow fever • Define risk based on geography and exposure Defining Disease Risk for Travel Base prevention on sensible, ‘evidence-based’ measures
  • 7. Imported Yellow Fever Cases: 1970-2013 Country Year Case Outcome Vaccinated? Senegal 1979 42, M Death No Senegal 1979 25, M Death No Guinea-Bissau 1985 27, F Survived No West Africa 1988 37, F Survived Yes Brazil 1996 53, M Death No Brazil 1996 42, M Death No Cote d’Ivoire 1999 40, M Death No Venezuela 1999 48, M Death No The Gambia 2001 47, F Death No Brazil 2002 47, M Death No
  • 8. 2011 WHO Yellow Fever Vaccination Maps Vaccination recommended Vaccination usually not recommended Not recommended
  • 9. Historical Determination of YF Risk • Clinical case reports – severe illness, foreigners, coastal ports, rivers and railways – non-specific: e.g. confused with malaria, hepatitis, leptospirosis • Serosurveys: mouse protection assay (1931) • Viscerotomies in persons dying with a febrile illness; mostly in S. America
  • 10. Yellow Fever Epidemiology: Africa Sawyer WA. Harvey Lectures. 66-92, 1936. Human Cases: 1920-1934 Human Serology: 1930-1934
  • 11. Yellow Fever Endemic Regions, 1945 UN Relief and Rehabilitation Administration. Epidemiol Inf Bull. 1:687, 1945. South America Africa
  • 12. • Response to: – recognition of serious adverse events – changing epidemiology of yellow fever • Goals: – more accurate definition of risk areas – unify risk maps between CDC & WHO – transparency of recommendations – inform country policy around IHR (2005) WHO Consultation on Yellow Fever Risk, 2008 Jentes E, et al. Lancet Infect Dis. 11:622, 2011 Curr Infect Dis Rep 14:246, 2012
  • 13. Evidence Used for Risk Mapping • Human and non-human primates: cases, clusters and outbreaks • Human serology prior to YF vaccination; most data generated in 1950s and earlier • Vegetation and altitude • Vector distribution
  • 14. Kenya: Yellow Fever Serology and Cases Courtesy Tom Monath
  • 15. PAHO: July 2010 South America: Altitude limit of 2,300 m
  • 17. • Endemic • Transitional • Low potential (risk) for exposure • No risk Yellow Fever Consultation Creation of New Categories of Risk
  • 18. Yellow Fever Risk Classification Risk Classification Examples Criteria for Risk YF vectors and NHP present? Human or NHP YF cases? Serosurvey evidence? Endemic Nigeria Yes Repeatedly High levels Transitional Paraguay Yes Reported at long intervals Present Low potential for exposure Tanzania Yes None Low levels No New Zealand Yes / No None No
  • 19. Use of Elevation Data: Bolivia Areas below 2,300 m, determined from global digital elevation model (GTOPO30 ) Areas below 2,300 m classified endemic Altitude limit of 2,300 m
  • 20. Use of Vegetation Data: Niger Barren or sparsely vegetated areas as determined from normalized difference vegetation index (NDVI) Areas classified as endemic
  • 21. Peru:  no risk: coastal, south of La Libertad, Andes above 2,300 m  low potential: Tumbes, Lambayeque, and parts of Piura and Cajamarca  transitional: eastern Piura state  endemic: remainder of country New Yellow Fever Risk Maps
  • 22. Kenya:  low potential: North Eastern zone, Coastal zone and Nairobi  endemic: remainder of country New Yellow Fever Risk Maps
  • 23. Tanzania  low potential for exposure New Yellow Fever Risk Maps
  • 24. Zambia  low potential: North West and Western provinces  no risk: remainder of country New Yellow Fever Risk Maps
  • 25. Special Considerations • Examined high volume destinations, in attempt to avoid vaccinating many travelers unnecessarily • Low potential for exposure:  port cities in South America  Cartagena, Baranquilla, Port of Spain  Nairobi • No risk:  transit of 12 h or less in international airports  Inca Trail (Peru)
  • 26. Yellow Fever Risk Mapping: Shift from risk maps to vaccination maps • Vaccination recommended – endemic – transitional • Vaccination generally not recommended – low potential for exposure (low risk) – exceptions: prolonged, often rural, extensive mosquito exposure • Vaccination not recommended – no risk
  • 27. Risk Vaccination recommended Vaccination usually not recommended Not recommended Vaccination
  • 28. Implications for IHR (2005) Low risk countries  Low potential for exposure Thus, low risk countries will never appear in Annex 1 
  • 29. IHR (2005): Annex 1B, 2f Afghanistan, Australia, & India require YF vaccine from travellers arriving from countries with a (low) risk of YF transmission; e.g. historically from Tanzania, Eritrea, Zambia. South Africa considers ‘low potential’ as risk and requires vaccine of travelers from Tanzania & Zambia, including those in transit.
  • 30. 2011 WHO Yellow Fever Vaccination Maps Vaccination recommended Vaccination usually not recommended Not recommended
  • 32. Conclusions • Robust process using best available evidence • Transparency in decision making • Attempts at ‘shrinking’ risk map • Achieved globally agreed risk categorization • Implications for travel medicine practitioners • Implications for Annex 1 (ITH) under IHR (2005) • Continuous review of model and epidemiology