Global Infectious Diseases Objectives

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Global Infectious Diseases Objectives

• Problem
• Determinants
• Diseases
• Control and eradication
• Triumphs
• Tribulations

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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.
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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

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Eradication Programs
Human Hookworm, 1909 Yellow fever, 1915 Aedes
aegypti, 1934-42 Anopheles gambiae,
1939-68 Malaria, 1955-1973 Yaws, 1950 Smallpox,
1958, 1966-80 Poliomyelitis, 1985 Dracunculiasis,
1987
Animal Bovine contagious pleuropneumonia (cows),
1884 Glanders (horses, mules) Piroplasmosis
(cattle, Texas fever Dourine (STD of
horses) Rinderpest Sheep pox
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Eradication and Elimination Programs

• Eradication
• Yellow fever (failed)
• Aedes aegypti (failed)
• Anopheles gambiae (failed)
• Yaws (failed)
• Malaria (failed)
• Smallpox (success)
• Guinea worm (dracunculiasis)
• Poliomyelitis

• Elimination
• Onchocerciasis (Onchocera
  volvulus)
• Filariasis
  (Wuchereria bancrafti)
• Measles
• Chagas disease
  (Tryanasomia cruzi)
• Tuberculosis

• eradication underway
• elimination underway

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Candidates for Elimination

• Haemophilus influenzae type B
• Neonatal tetanus
• Rabies
• Yellow fever
• Japanese B encephalitis
• Hepatitis A
• Hepatitis B
• Rubella

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Global Infectious Diseases Objectives

• Problem
• Determinants
• Diseases
• Control and eradication
• Triumphs
• Tribulations

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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
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Edward Jenners 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

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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

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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

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Rahima Banu, age 3, Last Case of variola major,
Bangladesh, 1975
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Poliovirus Importations in 2000 and 2001
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Label, 2002
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Savings from International Disease Eradication
Programs
U.S. Eradication
Savings
Disease
Cost/Contribution
World
Smallpox
1949 1977
30 million/30
1998
30 million every 26 days in U.S.
million
421 million per year
11 billion since 172 when
vaccination stopped in U.S.
Poliomyelitis
1979 2000
Ongoing
2000
500 million yearly worldwide
2015
3 billion yearly
Measles
Americas 2000
Ongoing
Huge
Europe 2007
Middle East 2010
Fogarty International Center
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Vaccination and Savings to Society
Savings per Dollar Spent
Vaccine
Diphtheria
titanus
pertussis
29
(DPT)
Measles mumps rubella
13
(MMR)
Oral polio vaccine
6
(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
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Global Infectious Diseases Objectives

• Problem
• Determinants
• Diseases
• Control and eradication
• Triumphs
• Tribulations

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Ebola Virus, Zaire, 1976
Unfixed diagnostic specimen from Vero cell
passage sodium phosphotungstate x90,000 (Fred
Murphy)
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Number of Cases of Ebola Hemorrhagic Fever in the
Equator Region, by Day of Onset and Probable Type
of Transmission, 1976
50 45 40 35 30 25 20 15 10 5
Probable Type of Transmission
Person to Person Both Syringe
Cases
1-3 4-6 7-9 10-12 13-15 16-18
19-21 22-24 25-27 28-30
1-3 4-6 7-9 10-12 13-15
16-18 19-21 22-24 25-27 28-30
September
October
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Patient with Ebola Hemorrhagic Fever, Bumba Zone,
Equateur Province, DR Congo (Zaire), October 1976
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Ebola Virus Marburg Virus Both
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Syndromes Potentially Resulting from Bioterrorism

• Encephalitis
• Hemorrhagic mediastinitis
• Pneumonia with abnormal liver function tests
  (LFTs)
• Papulopustular rash
• Hemorrhagic fever
• Descending paralysis
• Nausea, vomiting diarrhea

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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
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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
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The TribulationsSmallpox and Biologic Terrorism

• Does smallpox virus exist outside of two WHO
  collaborating centers? Ken Alibeks story in
  Biohazard other countries, groups Verification
  Preparedness Diagnosis Primary care
  Antiviral therapy Vaccination
• Prevention of hysteria and disorder

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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

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Research, Training, and Support Needs According
to Understanding of Diseases and Efficacy of
Control Methods
High
High
Training
Efficacy of Control Methods
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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Research, Training, and Support Needs According
to Understanding of Diseases and Efficacy of
Control Methods
High
High
Training
Efficacy of Control Methods
DengueMalaria HIV/AIDSTuberculosisEbola/Marburg
InfluenzaCancersAlzheimers
SmallpoxGuinea wormPoliomyelitisH. influenzae
type BMeaslesTetanus
Research Needs
Low
Low
Some
High
Moderate
Research Support Needs
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Infectious Causes of Common Chronic Diseases

• Helicobacter pylori (peptic ulcers)
• Hepatitis B and C (cirrhosis and liver cancer)
• Human herpesvirus 8 (Kaposis sarcoma)
• Human papillomavirus (cervical cancer, recurrent
  respiratory infections, and papillomatosis)
• Epstein-Barr virus (posttransplant
  lymphoproliferative disease, B-cell lymphoma)

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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 (stroke) 4
Ischaemic heart disease 5 Chronic obstructive pulmonary disease 5
Cerebrovascular disease 6 Lower respiratory infections 6
Tuberculosis 7 Tuberculosis 7
Measles 8 War 8
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Rank Order of Disease Burden for 15 Leading
Causes (2)
Disease or Injury 1990 Rank Disease or Injury 2020 Rank
Road traffic accidents 9 Diarrhoeal diseases 9
Congenital anomalies 10 HIV 10
Chronic obstructive pulmonary disease 11 Perinatal conditions 11
Malaria 12 Violence 12
Falls 13 Congenital anomalies 13
Iron deficiency anemai 14 Self-inflicted injuries 14
Protein-energy malnutrition 15 Trachea, bronchus and lung cancer 15
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For More Information
E-mail jbreman_at_nih.gov
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Ebola, Zaire, 1976 Spectrum of Emotion and
Activity
Highest
Anxiety
Less high
Confidence (false)
Uncertainty
Anger
Emotion
Celebration
Terror
Sorrow
Understanding
Comfort (false)
Fear
People fleeing
Active case detection
Activity
Patient management
Rapid Surveillance
Chaos
Plasmapheresis
Com-mission formed
Isolation and quarantine
Field Investigations
Investigations/ quick
Information Sharing
Low
High
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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

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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

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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

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Lessons Applicable to Other Programs (4)

• Confirmation of eradication Independent
  commissions Certification format Credibility
  and confidence

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Lessons Applicable to Other Programs (5)

• Exchange of experiences Routine disease
  surveillance Special communications (research,
  outbreaks) Cross-notification of importations
  TransparencyPolitical, 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 Achieve altruistic goal