Urbanization of Yellow Fever
Thomas P. Monath M.D.
Risk of Urban Yellow fever
• Vector
– Ae. aegypti distribution, density
– Vector competence
• Virus
– Proximity of and intensity of jungle cycle
transmission
• Human factors
– Movements, migrations
– Sanitation, crowding
– Susceptibility
• Immunization policy and vaccine coverage
th
th
18 -19
Centuries
• Urban epidemics in US, Europe, West
indies linked to colonial development
and the slave trade
• Most dreaded disease in North America
– 500,000 cases, 100,000 deaths total
– Texas to New England affected
Historical YF Epidemics
Massachusetts,
1801
Boston,
Albany,
1734
1691, 1693, 1694, 1803, 1821
New Haven,
1747
New York,
1668, 1694, 1702, 1734,
1743, 1745, 1751, 1791, 1801,
1819, 1821, 1822, 1870
Alabama,
1821, 1854, 1873
PhiladelphiA
1668, 1693, 1694, 1699, 1751,
1778, 1791, 1793, 1802, 1803,
1805, 1819, 1820, 1821, 1867
Baltimore
1783, 1817, 1819, 1821
New Jersey,
Washington,
1811
1825
Norfolk,
VirginiA,
1801
1741, 1743
Mississippi,
1821, 1843, 1855,
1873, 1878
Memphis,
1828, 1873, 1879
Galveston,
1839, 1843, 1853, 1867, 1870
Vera Cruz,
1699, 1725
Mexico
New orleans
1811, 1817, 1819, 1820, 1821,
822, 1824, 1827, 1828, 1829,
1837, 1841, 1847, 1854, 1856,
1867, 1873, 1878, 1905
Charleston,
1690, 1693, 1699, 1703, 1728,
1732, 1745, 1748, 1792, 1807,
1817, 1819, 1821, 1824, 1839,
1843, 1852, 1854, 1856, 1858, 1876
Mobile,
1825, 1827, 1829,
1837,
1839, 1843,
1847,1854, 1867
Florida,
1811, 1823, 1829,
1841, 1867
South carolina,
1877
© WHO 2005. All rights reserved.
Source: WHO
Epidemic of 1878
• One of the worst disasters in US history
• Mississippi Valley from New Orleans to
Ohio
• 20,000 deaths
• Financial loss $200 million ($4.25 billion)
• Disrupted commerce and society
• Huge controversies over causality,
transmission, value of quarantine
Spanish American War, 1898
• Casualties
– 260 die in battleship Maine explosion
– 968 die in combat
– 5000+ die of disease, mostly yellow fever
Reed Commission- 1900
• Mosquito (Ae. aegypti) transmission (volunteer
studies)
• Incubation period 3-6 days
• Extrinsic incubation period in mosquito required
(12 days)
• Filterable virus
• Not transmissible by air, contact, fomites
Conquest of Urban Yellow Fever
William Crawford Gorgas
1854-1920
Control of Yellow Fever
• Infected port cities (key centers)
– Shipboard transmission
•
•
•
•
•
Low sanitation
No piped water
Water storage in and around homes
High Ae. aegypti density and exposure
Source reduction (larval breeding sites)
eliminated risk of urban yellow fever
Last Outbreak in United States
500
450
400
350
300
250
200
150
100
50
0
Water cisterns
Ambulance
22 29 5 12 19 27 3 10 17 26 3 10 17 26 2 9 16 23
Jul
Aug
Sep
Oct
Nov
New Orleans 1905
House screening gang
(YF patients’ houses)
Fumigation crew
Jungle YF- 1937-1941
Alexander Haddow
(1907-1976)
Jorge
Boshell
Fred L Soper
(1893-1977)
Aedes aegypti eradication campaign in
the Americas, initiated 1947
1940
1954
Trinidad, 1954
• 1907 Urban outbreak
• 1914 Epizootic, few jungle cases
• 1954 Epizootic-epidemic
– Multiple isolations from Haemagogus
– Island wide monkey deaths; 30% seropositive monkeys
– 15 human cases, at least 3 Ae. aegypti-borne (1 from Port-ofSpain)
– Human population not vaccinated
– Ae. aegypti house indices >70% island-wide
• First case diagnosed in April, next cases August
– Ae. aegypti campaign initiated in June
– Island wide immunization initiated July
– Larger outbreak averted
Distribution of Ae. aegypti in the Americas
1930's
1970
2007
Risk of urban YF
Ae. aegypti
Jungle YF 1998-2008
1998
Urban YF
2008
1
2
5
≥10
Increase of Ae. aegypti Infestation by
municipality, Brazil 1991-2000*
4000
3500
3000
2500
2000
1500
1000
500
0
1991
1992
Fonte:CR’s/SES’s
FUNASA/CENEPI/GT-FAD
1993
1994
1995
1996
1997
1998
1999
2000
Yellow fever Vaccination
• Population in endemic areas vaccinated
– Mass campaigns
– Routine EPI
– High coverage in South America
• Barrier to urbanization in Ae. aegypti
infested towns in endemic region
19
30
19
34
19
38
19
42
19
46
19
50
19
54
19
58
19
62
19
66
19
70
19
74
19
78
19
82
19
86
19
90
19
94
19
98
Cases/deaths
200
120
100
80
40
Vaccinations
300
Cases, deaths, vaccinations
BRAZIL 1930 - 2000
200
160
Risk of Urban Yellow Fever
• Expansion of epizootic and jungle
yellow fever to areas where vaccination
coverage is low
– Recent examples (Bolivia, Paraguay)
• Movement of unvaccinated people from
endemic to non-endemic zone
Yellow fever Vaccination
• Non-endemic areas
–
–
–
–
Coastal zones, Altiplano, not vaccinated
Large populations
Receptive to YF introduction (Ae. aegypti present)
High rate of migration, movement to/from endemic
areas
• Some countries extending vaccination to
adjacent, within-border non-endemic areas
– Bolivia, Peru
• Vaccine shortages and YF vaccine related
adverse events have limited policy
implementation
Brazil yellow fever endemic
zone and population
Urban Yellow Fever
Santa Cruz, Bolivia
1998
• 6 cases (5 deaths) in
city (pop 891,000)
• 3 with no possible
exposure to sylvatic
transmission
• Low immunization
coverage ~41%
• Other IgM + urban
residents
• High Ae aegypti
Van der Stuyft et al., Lancet, 353:1558, 1999
Expansion of Epizootic YF 2008
To areas with low vaccination coverage
First well documented urban
outbreak in South America since
1942 (Asuncion)
Paraguay, 2008
San Pedro Department
First YF activity since 1974
SanEstanislao
Estanislao
San
Firstcases
casesdetected
detected
First
Dec2007-Jan
2007-Jan2008
2008
Dec
cases–likely
likelyjungle
jungleYF
YF
88cases–
Ringvaccination
vaccination
Ring
Targetedvector
vectorcontrol
control
Targeted
SantaDomingo
Domingo
Santa
February2008
2008
February
cases(3
(3Female)
Female)
77cases
Ae.aegypti
aegyptiand
andSabethes
Sabethes
Ae.
Sourceunclear
unclear
Source
Ringvaccination
vaccination
Ring
Vectorcontrol
control
Vector
Caazaga
Caazaga
March2008
2008
March
cases
44cases
Junglevectors
vectorsand
andAe.
Ae.
Jungle
aegyptipresent
present
aegypti
SanLorenzo
Lorenzo
San
February2008
2008
February
cases(5
(5Female)
Female)
99cases
Ae.aegypti
aegyptihouse
houseindex
index26%
26%
Ae.
Nojungle
junglevectors
vectors
No
Suburbanenvironment
environment
Suburban
Massvaccination
vaccination
Mass
Intensivevector
vectorcontrol
control
Intensive
Increasing risk of urban yellow
fever in the American region
VECTOR
• Re-infestation of the South American
continent by Ae. aegypti
• Juxtaposition of urban and jungle cycles
within endemic areas
• Presence of vector in non-endemic
(receptive) areas
• High vector density in crowded, low
socioeconomic areas of many cities
• Insecticide resistance
Increasing risk of urban yellow
HUMAN
HOST
fever
in the American region
• Increased risk of introduction to receptive
areas (unvaccinated, densely populated
coastal zone)
– Increased movement of migrant workers from nonendemic to endemic zones and back
– Human urbanization, crowding, low
socioeconomic and sanitary standards
Major Urban Epidemic of Yellow
Fever in South America
• Not if
• When?
YF Epidemics, 1990-2008
2003, 2005
1986-94
1995, 2002
2000-01
1995, 1998
2001
1993, 1996
1992
1996
1990
1994
Aedes africanus
Ae. luteocephalus
Ae. furcifer
Ae. vittatus
Ae. opok
Ae. metallicus
Epidemic Vector
1986-94
1969
1965
1990
1978-79
1987
1940
1962-66
2001
1982-83
Ae. aegypti
Ae. africanus
Ae. luteocephalus
Ae. simpsoni
Ae. vittatus
Ae. furcifer-taylori
1987-91
1970
1977 1970 1986
1983
1994
1993
1972
1992
AR=50.0/100,000
AR=2.7/100,000
AR=43.2/100,000
Breteau index (No. pos. containers/100 houses)
and YF attack rate, the Gambia, 1978-79
Location
Breteau
(dry)
Sambuldu
0
Attack rate Attack rate
(rainy)
(dry)
54.8
0
Serengaba
0
108.5
0
Sere N’Gai
1.5
34.3
0
Belai
9.5
19.7
6.6
Sare Bojo
9.6
8.5
12.8
Modi
Jabbu
14.0
13.6
40.8
Germain et al Am J Trop Med Hyg 29:929, 1980
6000
5000
4000
3000
2000
1000
19
90
19
80
0
Ae. africanus
Ae. aegypti
• Ae. aegypti formosus
–
–
–
–
Dark color
Africa, sylvatic –tree-hold breeding
Exophilic
Zoophilic
• Ae. aegypti aegypti
–
–
–
–
Pale color
Domestic breeding
Endophilic
Anthropophilic
Trop Med Parasitol 1989;40:396
• Urban epidemic 1987, Nigeria
–
–
–
–
Disease incidence high (2.9%)
Breteau index very high (up to 676)
Human biting rate high ( up to 3 mosq/man/hr)
Ae. aegypti formusus
Africa
• Urban cycle has been a common event
– Proximity of sylvatic and urban cycle
– Depends on high vector density
• Low vector competence
– Urbanization of human population, increased
communication, travel
– Severe outbreaks in countries without immunization
policy
• Overall risk of urban yellow fever will be
mitigated by
– Mass immunization campaigns and routine
immunization
YF Vaccination in Africa
2000-2008
1990-99
No vaccination
program
Vaccination program
1980-89
1970-79
1960-69
0
20
40
60
80
100
Percent of endemic countries
Source: WHO, 2008
Map showing countries with
yellow fever vaccine in EPI
with coverage attained by December 2007
YFV coverage >80%
YFV coverage 50-79%
YFV coverage <50%
Endemic, no EPI
Yellow fever distribution (reported cases 1987-2006)
260
73
1
94
1892
21
450
409
2* 1
678 19,226
1178
389
130
628 870 17* 60*
714 176
529
638
Distribution of Ae. aegypti
827
169
37
10 64
Introduction and Spread of Ae.
aegypti-borne Diseases
• Dengue
• Chikungunya
• Ross River
Other potential urban vectors
• Ae. albopictus
– Low vector competence for YF
Imported Cases of Yellow Fever
Date
Age/sex
Vaccination
Residence
Exposure
Outcome
Oct 1979
42M
No
France
Senegal
Died
Oct 1979
25M
No
France
Senegal
Died
Aug 1985 27F
No
Netherlands
W. Africa
Survived
Oct 1988
37F
Yes
Spain
W.Africa
Survived
Apr 1996
53M
No
Switzerland
Brazil
Died
Aug 1996 42M
No
USA
Brazil
Died
Aug 1999 40M
No
Germany
Ivory Coast Died
Sep 1999 48M
No
USA
Venezuela
Died
Nov 2001 47F
No
Belgium
Gambia
Died
Mar 2002 47M
No
USA
Brazil
Died
Distant Introduction Scenario
• Dramatic disease, cases will likely come to light
early
• Outbreak will likely be contained rapidly
• Incidence: few to tens of cases
• High level public concern, panic, high demand
for vaccine
• Ring vaccination, mass vaccination
• Serious vaccine related adverse events
• Impact on trade, travel, tourism
• Likely vaccine shortage
Yellow fever 17D vaccine manufacturers
1970
2008
USA (Connaught)
USA (sanofi pasteur)
England (Wellcome)
France (sanofi pasteur)
France (Aventis-Pasteur)
China (NVSI)
USSR (Inst Polio VE)
Russia (Inst Polio VE)
Senegal (Pasteur)
Senegal (Pasteur)
Brazil (BioManguinhos)
Brazil (BioManguinhos)
Germany (R. Koch)
Switzerland (Berna/Crucell)
Netherlands (Inst Trop Med)
India (CRI)
Australia (CSL)
Nigeria (Yaba)
South Africa (NIV)
Colombia (INS)
60m doses (90m needed)
China (NVSI)
15m dose shortage 2008 (PAHO)