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Global Infectious Diseases
Objectives
Problem
 Determinants
 Diseases


Control and eradication
Triumphs
 Tribulations

Away All Disease! DEFINITIONS
CONTROL:
Reduction of disease incidence,
prevalence, morbidity, mortality, and
disability to a locally acceptable level
ELIMINATION: Reduction of infection and disease to
zero in a defined area.
Continued efforts required.
ERADICATION: Permanent reduction of worldwide
incidence to zero as a result of
deliberate interventions.
Continued efforts not required.
DESTRUCTION: Destruction of all isolates of microbial
agent.
Problems in Defining Burden
Poor case definition
 Poor recognition
 Poor diagnosis
 Poor reporting
 Poor statistical use
 Poor understanding of problem
 Poor control actions
 Poor resource allocation

Human
Eradication Programs
Hookworm, 1909
Animal
Yellow fever, 1915
Bovine contagious
pleuropneumonia (cows), 1884
Aedes aegypti, 1934-42
Anopheles gambiae, 1939-68
Glanders (horses, mules)
Malaria, 1955-1973
Piroplasmosis (cattle, “Texas
fever”
Yaws, 1950
Dourine (STD of horses)
Smallpox, 1958, 1966-80
Rinderpest
Poliomyelitis, 1985
Sheep pox
Dracunculiasis, 1987
Fogarty Internationa
Center
Eradication and Elimination Programs
Eradication
Elimination
Yellow fever (failed)
Onchocerciasis
Aedes aegypti (failed)
(Onchocera volvulus)•
Anopheles gambiae (failed)
Filariasis
Yaws (failed)
(Wuchereria bancrafti) •
Malaria (failed)
Measles •
Smallpox (success)
Chagas disease
Guinea worm
(Tryanasomia cruzi) •
(dracunculiasis)*
Tuberculosis
Poliomyelitis
*
* eradication underway
• elimination underway
Candidates for Elimination
Haemophilus influenzae type B
Neonatal tetanus
Rabies
Yellow fever
Japanese B encephalitis
Hepatitis A
Hepatitis B
Rubella
Global Infectious Diseases
Objectives
Problem
 Determinants
 Diseases
 Control and eradication


Triumphs

Tribulations
Control vs. Eradication
Control
Eradication
Cost
Continual
Limited/high initial
Time
Continual
Limited
Cases
Acceptable
Zero
Political will
Useful
Essential
Epidemiology
Known/unknown
Completely known
Research
Essential
Essential
Edward Jenner’s Clairvoyance
“…It now becomes too manifest to admit of
controversy, that the annihilation of the Small
Pox, the most dreadful scourge of the human
species, must be the final result of this
practice.”
— Edward Jenner, The Origin of the Vaccine
Inoculation, 1801
Fogarty International
Center
Biologic and Epidemiolgic Basis for
Smallpox Eradication
• Humans were the only reservoirs and vectors
• No intermediate host
• All cases symptomatic with typical rash
• Lifelong immunity after disease
• Laboratory diagnosis effective
• Incubation period 7-17 days, conducive to control
• Effective heat-stable vaccine
• Mode of acquisition and transmission known
• Pathogenesis and pathology known
• Research important
Social, Political and Economic Factors
Favoring Smallpox Eradication
•
•
•
•
•
•
Disfiguring disease
Periodic epidemics
Endemic countries started activities at same time
All non-endemic countries at peril
Prestige to countries, bilateral and international
organizations
Economic benefits to all
* stop vaccination
* stop vaccination card and border controls
* stop medical costs due to vaccine complications
Rahima Banu, age 3, Last Case of variola
major, Bangladesh, 1975
Poliovirus Importations in 2000 and 2001
Label, 2002
Savings from International Disease Eradication Programs
U.S. Eradication
Disease
Smallpox
World
1949 – 1977
Cost/Contribution
$30 million/30 1998
million
Savings
$30 million every 26 days
in U.S.
$421 million per year
$11 billion since 172 when
vaccination stopped in U.S.
Poliomyelitis 1979 – 2000
Ongoing
2000
2015
Measles
Americas
2000 Ongoing
Europe
2007
Middle East 2010
$500 million yearly
worldwide
$3 billion yearly
Huge
Fogarty International Center
Vaccination and Savings to Society
Vaccine
Diphtheria – titanus – pertussis
Savings per Dollar Spent
$29
(DPT)
Measles – mumps – rubella
$13
Oral polio vaccine
$ 6
(MMR)
(OPV)
Varicella (chickenpox)
$5
Hemopulus influenza, type b
$2
Hepatitis B (infant)
$
2
____
Savings per $6 dollars invested =
$57
Ratio of savings to investment
~ 10: 1
Global Infectious Diseases
Objectives
Problem
 Determinants
 Diseases
 Control and eradication
 Triumphs


Tribulations
Ebola Virus, Zaire, 1976
Unfixed diagnostic specimen from Vero cell
passage: sodium phosphotungstate x90,000
(Fred Murphy)
Number of Cases of Ebola Hemorrhagic Fever in the
Equator
Region,
by
Day
of
Onset
and
Probable
Type
of
50
Transmission, 1976
Probable Type of
Transmission
Person to Person
Both
Syringe
45
40
35
30
25
20
15
10
5
1-3
4-6
7-9
10-12 13-15 16-18
19-21 22-24 25-27 28-30
September
1-3
4-6
7-9
10-12 13-15 16-18 19-21 22-24
October
25-27 28-30
Patient with Ebola Hemorrhagic Fever, Bumba Zone,
Equateur Province, DR Congo (Zaire), October 1976
Ebola Virus
Marburg Virus
Both
Syndromes Potentially Resulting
from Bioterrorism

Encephalitis

Hemorrhagic mediastinitis

Pneumonia with abnormal liver function tests
(LFTs)

Papulopustular rash

Hemorrhagic fever

Descending paralysis

Nausea, vomiting ± diarrhea
Biologic Warfare with Smallpox
… at the time of the Pontiac rebellion, 1763:
QUESTION:
“Could it not be contrived to send smallpox
among those disaffected tribes of Indians? We
must on this occasion use every strategem in our
power to reduce them.”
— Sir Jeffrey Amherst, Commander-in-Chief, British
Forces, North America
Heagerty, 1928, cited in Fenner et al, 1988
Biologic Warfare with Smallpox
… at the time of the Pontiac rebellion, 1763:
ANSWER:
“I will try to inoculate them with some blankets
that may fall in their hands, and take care not to
get the disease myself.”
— Colonel Henry Bousquet
Heagerty, 1928, cited in Fenner et al, 1988
The Tribulations
Smallpox and Biologic Terrorism
• Does smallpox virus exist outside of two WHO
collaborating centers?
* Ken Alibek’s story in Biohazard; other countries, groups
* Verification
Preparedness
* Diagnosis
* Primary care
* Antiviral therapy
* Vaccination
• Prevention of hysteria and disorder
Fogarty International
Center
Scientific Needs for Live Variola Virus
Institute of Medicine, 1999

Development of antiviral agents

Development of improved and new vaccines

Detection and diagnosis

Bioinformatics, genetic variability

Understanding the biology of the variola virus

Research on expressed protein products of
variola
Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High
High
Training
Efficacy
of Control
Methods
Low
Research
Needs
Some
Moderate
Research Support Needs
High
Low
Research, Training, and Support Needs
According to Understanding of Diseases and
Efficacy of Control Methods
High
Efficacy
of Control
Methods
Low
High
Training
Dengue
Malaria HIV/AIDS
Tuberculosis
Ebola/Marburg
Influenza
Cancers
Alzheimer’s
Smallpox
Guinea worm
Poliomyelitis
H. influenzae type B
Measles
Tetanus
Some
Moderate
Research Support Needs
High
Research
Needs
Low
Infectious Causes of Common
Chronic Diseases

Helicobacter pylori (peptic ulcers)

Hepatitis B and C (cirrhosis and liver cancer)

Human herpesvirus 8 (Kaposi’s sarcoma)

Human papillomavirus (cervical cancer, recurrent
respiratory infections, and papillomatosis)

Epstein-Barr virus (posttransplant
lymphoproliferative disease, B-cell lymphoma)
Rank Order of Disease Burden for 15 Leading Causes
Disease or Injury 1990
Rank
Disease or Injury 2020
Rank
Lower respiratory infections
(pneumonia)
1
Ischaemic heart disease
1
Diarrhoeal diseases
2
Unipolar major depression
2
Perinatal (newborn) conditions
3
Road traffic accidents
3
Unipolar major depression
4
Cerebrovascular disease
4
(stroke)
Ischaemic heart disease
5
Cerebrovascular disease
6
Tuberculosis
7
Measles
8
Chronic obstructive
pulmonary disease
Lower respiratory
infections
5
Tuberculosis
War
7
6
8
Rank Order of Disease Burden for 15 Leading Causes (2)
Disease or Injury 1990
Road traffic accidents
Congenital anomalies
Rank
9
10
Chronic obstructive pulmonary disease
11
Malaria
Falls
Iron deficiency anemai
Protein-energy malnutrition
12
13
14
15
Disease or Injury 2020
Diarrhoeal diseases
HIV
Perinatal conditions
Violence
Congenital anomalies
Self-inflicted injuries
Trachea, bronchus and
lung cancer
Rank
9
10
11
12
13
14
15
For More Information
E-mail: [email protected]
Fogarty
International
Center
www.nih.gov/fic
www.nih.gov
Ebola, Zaire, 1976
Spectrum of Emotion and Activity
Highest
Anxiety
Less high
Activity
Confidence
Uncertainty
Anger
(false)
Celebration
Terror
Sorrow Understanding
Comfort
Fear
(false)
People
fleeing
Active case
Patient
Rapid
detection
Chaos Surveillance management
Plasmapheresis
ComIsolation Investigations/ Field
mission and
Investigations
quick
formed quarantine
Information Sharing
Low
High
Lessons Applicable to
Other Programs
• Clear objectives known to all
• Scientifically justifiable
* No animal reservoir
* Clinically manifest
* Two-week incubation period
* Virus did not survive in environment
Fogarty Internationa
Center
Lessons Applicable to
Other Programs (2)
• Operationally feasible but difficult
* Effective, heat-stable vaccine
* Vaccine protection of long duration
* Vertical programs supported nationally and
internationally
* All programs started together
* field staff needs are top priority
Fogarty Internationa
Center
Lessons Applicable to
Other Programs (3)
• Research and evaluation is crucial
* Diagnosis
* Active surveillance for cases
* Coverage surveys for vaccination
* Epidemiology to define groups at risk
* Vaccine delivery systems
* Adverse events from vaccination
* Monkeypox and other orthopoxviruses
* Poxviruses as vaccine vectors
* Therapeutics
Fogarty Internationa
Center
Lessons Applicable to
Other Programs (4)
• Confirmation of eradication
* Independent commissions
* Certification format
* Credibility and confidence
Fogarty Internationa
Center
Lessons Applicable to Other Programs (5)
• Exchange of experiences
* Routine disease surveillance
* Special communications (research, outbreaks)
* Cross-notification of importations
* Transparency
Political, administrative, and economic
* Commitment of high-level leadership
* Use political/administrative infrastructure
* Sustaining interest is difficult at the end
* Show medical and economic improvements
* Use staff who have been successful in one program
in others
Fogarty
International
* Achieve altruistic goal
Center