Transcript Global Health Studies

Global Trade and Microbial Traffic
Ann Marie Kimball, MD., MPH
School of Public Health and
Community Medicine
University of Washington
Global Trade and Infections
• Conceptual framework, background
• Summarize four illustrative infections:
HIV/AIDS, enteric infections from sprouts,
cyclospora from rasberries, BSE from beef
products
• Examine surveillance, prevention and
control options extant through the
WHO,WTO
“Trade-Related Infection” an
infectious disease whose
• Emergence is hastened by ecological
pressure of “scaling up” production to meet
international trade markets
• Transmission is broadened through
transportation or trade in goods
• Economic impact is large in terms of trade
disruption
Uneven Access to
Water/Sanitation
Uncontrolled Urbanization
International Agricultural Trade,
1961-2000
Fruit & Vegetable
140,000
120,000
Meat & Meat
Preparations
100,000
80,000
Dairy Products &
Eggs
60,000
40,000
20,000
Live Animals
6
19 1
6
19 4
6
19 7
7
19 0
7
19 3
7
19 6
7
19 9
8
19 2
8
19 5
8
19 8
9
19 1
9
19 4
9
20 7
00
0
19
US Dollars (millions)
160,000
Years
Source: UN Food and Agriculture Organization
***Value of food trade in US alone
in 1994: $266 billion
Global Trade /Globalization
• Major increases in global trade, particularly
in meats and fresh produce over the past
thirty years
• Increased traffic of goods an humans
overlayed on inadequate public health
infrastructure, and increasing population,
urbanization
Human Disease as Travelers on
the Global Express
Examples of Global Epidemics
• HIV/AIDS- factors of
urbanization,
transportation,
technology,trade,
• Enteric Disease
• Bovine Spongiform
Encephalopathy (New
variant Jacob Creutzfeldt
Disease)
Adults and Children Estimated to be
Living with HIV/AIDS as of end 2001
Eastern Europe
Western Europe & Central Asia
560 000 1 millionEast Asia & Pacific
North Africa
1 million
South
& Middle East
& South-East Asia
440 000
6.1 million
North America
940 000
Caribbean
420 000
Latin America
1.4 million
Sub-Saharan
Africa
28.1 million
Total: 40 million
Source: UNAIDS, 12/01
Australia
& New Zealand
15 000
HIV in Factor VIII, IX
• Factor VIII
development, late
1970’s
• 1 unit derived from
20,000 units of plasma
• US hemophiliac HIV
epidemic 1982-85,
(followed hepatitis
epidemic)
• US main exporter of
factor VIII in 1980’s
• Japan epidemic began
with commercial
product introduction
• 1993 64% of HIV/AIDS
cases in Japan in
hemophiliacs
Big Four Pharma
Plasma to Blood Products Fractionation
• Alpha Therapeutic
(owned by Green
Cross, Japan)
• Armour Pharmaceutical
• Hyland of Travenol Labs
(later Baxter)
• Cutter Division, Miles
labs (later Bayer)
• 1981 sales $10 million,
1988 $38m
• 1982 sales $51m,1988
$125m.
• 1982 sales $60 million,
1988 $98 m.
• 1982 sales $69 million,
1988 $123m.
US Export of Blood Fractions & Modified
Immunological Products
1989 – 2000
1,000 US Dollars
1,600,000
1,400,000
1,200,000
1,000,000
Blood Fractions &
Modified
Immunological
Products
800,000
600,000
400,000
1999
1997
1995
1993
1991
0
1989
200,000
Years
United States International Trade Commission, Interactive Tariff and Trade DataWeb
Sprouts and Enteric Disease
• Global trade provides access to
fresh produce year-round
• Consumers seek fresh fruits and
vegetables as part of a healthy
diet
• Unlike bacteria traveling on
meat, those on produce often
escape cooking “kill-step”
• Seed contamination probable,
bacteria multiply in sprouting
Sprout Production Process
• Seeds purchased from a distributor and sprouted locally
• Several opportunities for contamination
• Provides ideal conditions for bacterial growth
Many unexpected cases
• Serotype specific
CDC surveillance
system begun
• Salmonella stanley
isolates were the
cause of numerous
reports of
gastroenteritis in
1995
Three S. stanley outbreaks
• Two states
– Michigan
– Arizona
• SALM-Net
– Finland
– from Mahon, BE et al, JID
1997;175:876
Identifying a common source
• Case control studies conducted in each location
• Confirmed the role of alfalfa sprouts in
transmitting the variant Salmonella
Molecular Epidemiology
• PFGE &
antibiogram
– common source
for the three
outbreaks
– Unique isolate
found at all
locations
outbreak
sporadic
1–5, outbreak isolates (1 and 2, Arizona; 3, Michigan; 4, Finland; 5, Ohio). Lanes 7–10,
sporadic isolates not linked to outbreak (7, Arizona;8, Missouri; 9, Finland; 10, Virginia).
Lane 6, l ladder molecular weight marker.
Tracebacks
• Case interviews
– Trace contaminated sprouts to their source
– identify retail outlets and dates of purchase
– determine shippers and growers who provided sprouts
– Invoices and delivery records identify seed suppliers, lot
numbers, and dates of sprouting
• 50 successful tracebacks
– 9 growers used single U.S. supplier
– seeds from Netherlands distributor
– combination of lots from Hungary, Pakistan, & Italy
Sprouts: an international threat
Year Pathogen
No. of
Cases
Location of
Outbreak
Type of
Sprout
Likely Source of
Contamination
Reference
1988 S. Saint -Paul
143
United
Kingdom
Mung
Bean
Seed
O'Mahony et al., 1990
1989 S. Gold -Coast
31
United
Kingdom
Cress
Unkown
Joce et al., 1990
1994 S.
Bovismorbificans
492
Sweden,
Finland
Alfalfa
Seed
Ponca et al., 1995
Puohiniemi et al., 1997
1995 S. Stanley
114
Finland
Alfalfa
Seed
Kontiainen et al., 1996
Mahon et al., 1997
1995 S. Newpor t
????
Denmark,
Canada
Alfalfa
Seed
Oregon Health Division, 1995
Aabo and Baggesen, 1997
Japan
Radish
Unknown
Nat'l Inst. Infect. Dis. and
Infect. Dis. Ctrl Div., Ministry
of Health and Welfare of Japan,
1997
1996 . E coli O157:H7
>6,000
1997 S. Meleagrid is
78
Canada
Alfalfa
Seed
Buck et al., 1998
1997 E. coli O157:H7
126
Japan
Radish
Unkown
Gutierrez, 1997
Cylcospora cayetanesis
•
•
•
•
•
Emerging infection
First documented case in 1977
Confirmed coccidian parasite in 1993
Received its name in 1994
Outbreaks starting in 1995
Lifecycle
• Not completely understood
• Humans are only known host
• Infectious spores are ingested
• Prolonged GI illness
• Oocysts excreted in feces
“Sentinel” Outbreaks in 1995
• First North American outbreaks
• New York and Florida
• Three small clusters
• Inconclusive investigation
• Suggested raspberries and
strawberries
Difficult Detective Work
• Trace-back and case-control studies
• Delayed GI illness
– Delayed diagnosis
– Difficult to remember food intake
– Fresh fruit no longer available
• No brand name recognition
Outbreak in 1996
•
•
•
•
1465 cases in US and Canada
55 event clusters
Guatemalan Raspberries were implicated
Widespread contamination prior to export
– Multiple farms
– Varied ports of entry
– Many distribution patterns within North
America
– Herwaldt B et al NEJM 1997
• Canada and US both
experienced clusters
of disease
• 737 lab confirmed
cases clustered
seasonally
Cultivation Related
Contamination
• Infected humans contaminate water
sources
• Water used in crop treatments
– Insecticides
– Fertilizers
• Contaminated raspberries exported
Virulence Factors
•
•
•
•
Single raspberry can cause infection
Simple water wash ineffective
Resistant to Chlorine treatment of water
Oocyst is very strong and can survive
difficult environments
• Food-borne and water-borne transmission
Outbreak in 1997
• Guatemalan Berry Commission implemented
voluntary control measures
– Hygiene
– Sanitation
– Water sources
• Another multi-state, multi-cluster outbreak in the
U.S, Canada
• Suspension of export by Guatemala to N.
American markets ended the outbreak
Despite measures,
41 new clusters occurred
Shipments were stopped
from Guatemala end of
May, 1997 (voluntary)
Outbreak in 1998
• FDA prohibited importation of Guatemalan
raspberries
• “Interventional study” where Canada was
exposed and the US was the control
• No outbreak in the US
• Multi-cluster outbreak in Canada
Guatemalan Raspberries
• The epidemiologic evidence was strong
• Tighter controls within Guatemala
decreased number of outbreaks in following
years
• Definitive control with trade import
restriction by U.S.
The Guatemalan Incident
• Unsafe cultivation in resource poor setting
of a newly introduced cash crop
• Role of surveillance
• Is trade restriction the only remedy?
BSE/nCJD Disease
• Change in rendering,
husbandry practice
implicated in emergence
• silent global circulation
in product
• Novel agent (prion),
long latency,
Cases of vCJD, worldwide,
as of end of August 2001
30 number of cases
25
20
15
10
5
0
1995
1996
1997
1998
1999
2000
2001
Source: UK, France
Bovine Spongiform Encephalopathy,
United Kingdom
BSE and vCJD: potential exposure
through international trade, early 1990s
Live cattle
Meat and
bone meal
Human and
bovine
tissue used
in biologicals
Food containing beef
Blood
and blood
products
Pharmaceuticals
UK Beef Exports
1970 - 1999
1,000 US Dollars
900,000
800,000
700,000
600,000
500,000
UK Bovine
UK Beef an
400,000
300,000
200,000
1997
1994
1991
1988
1985
1982
1979
1976
1973
0
1970
100,000
Years
Food and Agriculture Organization of the United Nations, FAOSTAT
Contaminated Meat
• Numerous examples of enteritis outbreaks from
contaminated meat worldwide and in U.S. (Ecoli
O157, Salmonella typhimurium DT104)
Coincides with marked increase in meat and meat
product trading worldwide
US Meat Exports
1989 – 2000
1,000 US Dollars
7,000,000
6,000,000
5,000,000
4,000,000
US Bovine Meat
3,000,000
Total US Meat and
Edible Offal
2,000,000
1999
1997
1995
1993
1991
0
1989
1,000,000
Years
United States Department of Agriculture, Foreign Agriculture Service
E. Coli in Meat, BSE analogies
Changes in production
to dramatically increase
yield, and economize in
expense predated outbreak
emergent infections linked
to meat products for human
consumption.
Was Global Trade a
driver?
Addressing Direct Trade Related
Infections
• “Primary prevention”
prevention of
emergence of new
infections
• “Secondary
Prevention” through
prevention of
dissemination through
trade
• “Surveillance and
timely control”
through enhanced
surveillance systems
• What is new in Trade related surveillance for
trade related
infections?
Public Health and Trade
WHO
•Improve health
WTO
•Establish trade rules
•Solve trade problems
•Prevent/control disease
•Provides health input to
Codex Alimentarius
standards
•Develops and manages
health regulations (IHR)
IHR
•WHO establishes IHR
under Constitution
Codex
Alimentarius
•Sets food
standards
SPS Agreement
•Recognizes Codex
Alimentarius standards as the
reference for food safety
requirements when they affect
health and international trade
Evolution of the WTO
• Bretton Woods 1944
• General Agreement on
Tariffs and Trade 1947
• Codex Alimentarius
Commission 1963
(FAO/WHO)
• Technical Barriers to
Trade (TBT)1979
• WTO created from
1994 GATT, SPS
supersedes TBT
Application of the International
Health Regulations, 1969
Strengthen the global framework
Formal Country Disease notification
(cholera, plague or yellow fever)
National
containment of
disease
Notification of cases in Weekly
Epidemiologial Record &
recommendation by WHO of
pre-set public health measures
Application of International Health
Regulations, proposed revision
Strengthen the global framework
Public health risk reporting from
WHO alert and response network
Public health risk
reporting by countries
Decision-tree analysis to determine if of urgent
international public health importance
YES
NO
National
containment of
public health risk
National
containmen
t of public
health risk
Collaborative risk-based
public health measures
identified and
recommended by WHO
Global surveillance of infectious
diseases:
Network
of
networks
Detect and respond to the unexpected
WHO Regional
& Country Offices
WHO Collaborating
Centres/Laboratories
MOH/National
Disease Control
Centres
Epidemiology and
Surveillance Networks
Military
Laboratory
Networks
UN
Sister Agencies
GPHIN
NGOs
Media
Electronic
Discussion
sites
FORMAL
INFORMAL
Global Public Health Intelligence
Network, Canada
Detect and respond to the unexpected
WTO Committee on Sanitary and
Phytosanitary Measures,
“Notifications of Emergency Measures”
• Format for emergency notifications adopted in 1995
with revisions in 1996, 1999, and 2002.
• Collection time period for dataset: 04/96 to 08/01.
• Creation of 24 variables, including: date of report,
country reporting, countries affected, nature of
urgency, objective of reporting, and products covered.
• Frequency analysis conducted using Stata
Notification Format - example
1. Member to Agreement notifying:
If applicable, name of local government involved:
2.
Agency responsible:
3.
Products covered (provide tariff item number(s) as specified in national schedules deposited with
the WTO; ICS numbers may be provided in addition, where applicable). Regions or countries
likely to be affected, to the extent relevant or practicable:
4.
Title and number of pages of the notified document:
5.
Description of content:
6.
Objective and rationale: [ ] food safety, [ ] animal health, [ ] plant protection, [ ] protect
humans from animal/plant pest or disease, [ ] protect territory from other damage from pests
7.
Nature of the urgent problem(s):
8. An international standard, guideline or recommendation does not exist [ ].
If an international standard, guideline or recommendation exists, give its appropriate reference and
briefly identify deviations:
9.
Relevant documents and language(s) in which these are available:
10. Date of entry into force/period of application (as applicable):
11. Texts available from/and agency or authority designated to handle comments:
[ ]
National notification authority, [ ] National enquiry point, or address, fax number and E-mail
address (if available) of other body:
350
319
300
250
200
150
100
50
0
6
8
10
25
28
19
96
19
97
19
98
19
99
20
00
20
01
Number of Reports
Number of Reports by Year
Year
Nature of Urgency by Year
Human &
Animal
Diseases
Plant
Diseases
4%
18%
78%
Human &
Plant
Diseases
Plant
Diseases
Contaminants
65%
GMOs
22%
2%
7%
1%
3%
2000
Contaminants
2001
Regulation of
Pesticide
Residues
Other
Objective for Notifying by Year
Food Safety
200
180
160
Animal Health
140
120
Plant
Protection
100
80
60
40
20
0
1996 1997 1998 1999 2000 2001
Protect
Humans from
Pest/Disease
Protect
Territory from
Pests
Other
Results for 2000 & 2001
• Animal products were reported as products covered in 153
(28.6%) of the notifications.
• The most reported objective or rationale for notifying was
animal health 203 (42.2%), followed by food safety 177
(37.8%).
• 192 (59.8%) of the notifications reported the existence of a
recommendation, standard, or guideline.
• Foot and mouth was most often the nature of urgency 113
(36.2%), followed by bovine spongiform encephalopathy
(BSE) 65 (20.8%).
• New Zealand and the United States reported most frequently
with 66 (19.2%) and 54 (15.7%) notifications, respectively.
Characteristics of WTO Countries
by Reporting Status
All countries within the
WTO notifying
All countries within the
WTO not notifying
2000
2001
2000
2001
(N=16)
(N=39)
(N=124)
(N=104)
Mean GDP (Billions, US$)
459.1
―*
188.9
―*
Mean Agriculture Imports
(Millions, US$)
8301.5
―*
2448.0
―*
93.5
41.7†
21.2
25.3
Year
Mean Population (Millions)
* Complete data not available
† Population estimates of the European Community and Brunei Darussalam not included
WTO Urgent Measures
Preliminary Analysis of an Event
• All BSE related
norifications selected
for 2000
• Product codes imputed
to six digits
• Linked to Trade COM
data for
1998,1999,2000
• 157 forms included
• Net trade value for
products rose from
1998 to 1999
• Fell with restrictions
imposed in 2000
• Further validation
ongoing
Trade data contribution to
Knowledge of Infectious events
• With unknown infections, urgent
notifications may expand insight into scope
of the problem
• With known infections, can study patterns
of restrictions to inform the IHR
implementation process
• May eventually aid in source identification,
determining least disruptive effective
measures
Why is this important
• Trade related
infectious disease is
important to human
population welfare
• Trade related
infections can be very
costly
• Enhancing cooperation
among international
assistance
organizations for
epidemic control
• Assuring “Safe Trade”
In Summary
• Trade related
infections in food,
biological products
have been described
• We are seeing the tip
of the iceberg
• Trade is increasing
and diversifying
• We will see more trade
related infections
• Global Surveillance,
detection is being
enhanced
• Linking trade
information with
disease occurrence is
key