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INFLUENZA
Otavio Oliva
Regional Consultant for Viral diseases
Pan American Health Organization
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Pan American
Health
Human Influenza Virus
• Types of virus “A,” “B,” and “C”
• Type C
– Associated with sporadic cases
– Cases that are not serious
– Stable Antigenitically speaking
• Type B
– Associated with epidemics
• Type A
– text
Associated with epidemics and pandemics
– Unique with subdivisions according to the HA and NA.
• H3N2
• H1N1
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Influenza Virus type A
 Subtype depends on surface glyco
HA
proteins:
• Hemagglutinate (HA) -16
• Neuraminidases (NA) - 9
Human circulating Subtypes:
textH1N1, H3N2, H1N2
NA
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Influenza type A: Ecological Aspects
• Infects several animal species
– Birds
– Mammals
• Horses
• Hogs
• Humans
• Wild birds
– Principal reservations
– Infected by all the 16 subtypes of “A” virus
text– They may transmit the virus to domestics birds and other animals
• Humans
– Normally they get infected only with human strains
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Influenza Type A: Antigenic changes
• Changes in “drift” Type may occur with HA and NA
– They are associated with seasonal epidemics
– Frequent appearance of new strains in response to a selection provoked by
collective immunity
– The Influenza A virus change more frequently than the virus B
• Changes in “shift” Type occur both in the HA as well as NA
– They are associated with pandemics
– Originates the appearance of new influenza A virus
text presenting a new HA or HA & NA.
– Population without any immunity
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Antigenic “Shift” Mechanisms
of the Influenza Type A virus
16 HAs
9 NAs
Animal
Strain
Human
Virus
text
Source: CDC / OMS
Reassociated
Virus
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Genetic Mechanisms associated with
the occurance (surgimiento) of pandemics: Shift
• Genetic Re-associations
• Adaptive Mutations of an avian virus
– Pandemic of 1918
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Terminology
• Seasonal Influenza
• Avian Influenza
– In migratory jungle birds
– Infection among domestic birds
• Enzootic Status (Asia, Africa???)
• Pandemic Influenza
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Seasonal Influenza (Seasonal)
•
•
•
•
•
Circulating Strain A (H1) and A (H3)
Vaccine against influenza would be first line of defense
Propagation by respiratory secretions (micro drops)
Incubation Period 1-4 days (average 2 days)
Infectious period starts the day before the appearance of symptoms
until approximately 5 days after the start of the disease
• disease generally lasts between 3-7 days
(cough and general malaise during >2 weeks)
• For U.S.A.:
text
– Rate of attack is 5-20%
– 200,000 hospitalizations
– 36,000 deaths
http://www.placer.ca.gov/hhs/hhs-sub/com-diseases/flu-fact-sheet.htm
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Prevention and control of Influenza
Vaccination
• Technical consulting Group of PAHO in Prophylactic
immunization of diseases (TAG – 2004) recommended using it
in risk groups
• Annual vaccination with influenza is being
gradually introduced in the Region
• Studies in (disease load)
• Economic impact of annual epidemics
that back the priority policy of vaccination
text
with influenza
• Limited quantities of the pandemic vaccination
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Prevention and Control of Influenza
Antivirals
Two types of antivirals in preventing or treating
influenza infections :
• Inhibitors of the ionic M2 channel (cyclic
amines)
– amantadine and rimantadine:
• Inhibitors of Neuraminidase
–textOseltamivir and Zanamivir.
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Requirements for having a variant of
epidemic influenza
• Total lack of immunity among the world
population
• Capable of causing disease among humans
• Effective
Transmission of
the virus from
person to person
text
http://www.rivm.nl/infectieziektenbulletin/bul1211/scenario.html
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Historic Data on Influenza Pandemics
3 Epidemicity*
H1
2
H2
H1
1
10
20
30 years
10
10
1953
1963
H3 (ducks)
38 years?
0 text
1883
1893
1903
1913
1923
1933
1943
1: epidemics, 2: probable pandemic, 3: pandemic
Potter, C.W: Textbook of Influenza by Nichols, Webster, Hay, Blackwell Science 1998
1973
1983
1993
2006
2003
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Influenza Pandemics in the XX Century
Credit: US National Museum of Health and
Medicine
1918:
text“Spanish Flu”
A(H1N1)
40-100 millions of
deaths
1957: “Asian Flu”
A(H2N2)
1-4 millions of
deaths
1968: “Hong Kong Flu”
A(H3N2)
1-4 millions
deaths
of
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Economic Impact of certain
infectious disease
SARS,
Ch, HK, SGP, Can
$30-50 billion
$50 mm
Estimated Costs
$40 mm
Mad Cow, U.K.
$25-30 billion
$30 mm
$20 mm
$10 mm
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avian flu, Asia
$8-12 billion
EEB, RU
$10-13 billion
Mad Cow, Taiwan
$5-8 billion
Fowl Pest , Nl, $2-3 mm
1990 91 92 93
EEB, Jap
$1,5 mm
avian influenza,
$500 m
Nipah, mayo
HPAI, Italia
$350-400 million $400 million
94 95 96
97 98
EEB, U.S.A.
$3-5 mm
NLEEB, Can
$1,5 mm
99 00 01 02
03
04 05 2006
Source: Bio Economic Research Associates
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Impact on the hospital capacity per week in LAC
outbreak of 8 weeks; attack rate of 25%; scenario 1968
Week
1
2
3
4
Weekly Hospital
Admissions
88,408
147,346
221,020
279,958
% of Hospital
capacity needed
26%
43%
65%
82%
84%
70%
53%
34%
% of capacity in the
ICU needed
98%
209%
321%
423%
458%
446%
354%
245%
344%
730%
1122%
1482%
1604%
1560% 1240% 856%
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% of Respiratory
Use
5
6
7
8
279,958 221,020 147,346 88,408
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Human Infection
with
Influenza A H5N1
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H5N1 Chronology
•
•
•
•
1996 – Highly pathogenic H5N1 isolated in a farm goose in Guangdong, China
1997 – First infection in humans with H5N1 (18 cases, 6 deaths) in Hong Kong.
Mid 2003 – H5N1 starts causing outbreaks in Asia (not detected and not reported)
End of 2003 – beginning of 2004 – Korea, Vietnam, Japan, Thailand, Cambodia, Lao PDR,
Indonesia and China communicate detection of H5N1 in poultry
Feb-Mar 2004 – First human cases in Vietnam and Thailand
Feb 2005 – Cambodia communicates its first case in humans
Jul 2005 – Indonesia communicates its first case in humans
Jul - Ago 2005 – Russia, Kazakhstan and Mongolia communicate H5N1 in poultry
•
•
•
•
• Oct 2005 – Reconstruction of the lethal pandemic of 1918, concludes that it was exclusively
avian and found some similarities with H5N1.
Oct 2005 – H5N1 confirmed in game birds (poultry) in Turkey, Romania and Croatia
text
November 2005 – Flamenco migrant tested positive in Kuwait
•
•
• January 2006 – Confirmed human Cases in Turkey and Iraq
• February 2006 – Outbreaks in poultry in Nigeria and Iraq. Wild poultry tested positive in
Azerbaijan, Bulgaria, Greece, Italy, Slovenia, Iran, Austria and Germany
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Characteristics H5N1
• Avian influenza Virus generally does not infect humans, however
several cases have been reported of H5N1 since 1997
• Domestic ducks may act as reservoirs, excreting large quantities of
the highly pathogenic virus and only show minimum signs of the
disease or non at all.
• H5N1 has become progressively in the most lethal for mammals and
may kill aquatic birds, considered until now as natural reservoir free
from the disease.
• There
text are reports that indicate atypical H5N1 infection in Thailand
(since March 04) and Vietnam (since Feb 04), presenting fever and
diarrhea without any respiratory symptoms .
→ Clinical spectrum of the disease may be greater that previously thought.
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Accumulated Confirmed Human Cases of Influenza
H5N1 Notified to the WHO*
12 April, 2006
Countries
Cases
Deaths
Mortality
Azerbaijan
8
5
63%
Cambodia
6
6
100%
China
16
11
69%
Egypt
4
2
50%
Indonesia
31
23
74%
Iraq
2
2
100%
Thailand
24
14
58%
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Turkey
12
4
33%
Vietnam
93
42
45%
Total
194
109
56%
*Referred to confirmed cases by labs
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text
Source: FAO
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WHO phases of a pandemia
• Interpandemic Period
– Phase 1. No new subtype of
flu in persons. Low risk of
infection due to the circulating
virus of animal flu
– Phase 2. No new subtype of
flu in persons. New animal flu
virus circulating represents a
risk for people
text
•Alert Period of the pandemia
– Phase 3. Human Infection with
the new subtype but without
transmission among persons
– Phase 4. Small accumulations
with limited transmissions
between persons.
– Phase 5. Major Accumulations
but transmission among
persons are still localized
• Pandemic Period
- Phase 6. Pandemic: transmission increases
and sustained in the general population
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Possible Scenarios
• Humans – traveling
– People exposed to game animals who are ill in affected areas
during the pre-pandemic period
– Pandemic
• Birds
– From abroad
• Migratory birds
text
Backyard farm
(cock)
Personas
• Illegal Imports
– Local
• Avian Influenza Strain of high patogenicity circulating in the region
• Avian Influenza Strain of low patogenicity circulating in the region
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What we do
not know about the next
pandemic
• The probability that a pandemic may occur
• When is it going to occur
• Where is it going to start
• Which will be the pandemic strain
– H5N1 is probable
• What will be the patogenecity degree of the new
pandemic strain
text
– The same as the Spanish flu
– More severe than the Spanish flu
– The same as the Asian and Hong Kong
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What we know ………
• That in human history we never had so many
opportunities to generate a pandemic strain
• That the virus has already turned enzootic in Asia and that
there is a possibility that the same may occur in Africa
and Europe increasing the opportunity of human infection
and the risk of generating a pandemic strain
• That the probability that a pandemic may occur is not zero
text
• That we have to be prepared as if the pandemic would be
within the next few days
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Risk Evaluation
• The risk of a pandemic is large and it will continue
• The evolution of the the threat can not be predicted
• A pandemic would produce considerable diseases, deaths and it would
impact the health, social and economic system
• Presentation of unprecedented levels of diseases and deaths.
• Air travel may increment the dissemination of the virus and reducing the
time available needed to prepare the interventions.
• The health systems may get over saturated quickly, the economy may
be compromised and the social order altered.
• Window
of opportunity for intervening
text
– Strengthening the public health system at the national
and international level in order to assume the
management of epidemiological issues
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Purpose of the Workshop
text
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Preparing for a Pandemic
• It is urgent to have National Preparation Plans for the Influenza
Pandemic.
– Compulsory dispositions mandated via resolutions of the Managing Council in
the 56 World Health Assembly and the 44th Pan American Health Organization
• Guidelines
– Global Influenza Prep Plan of the WHO (in Spanish)
– Check List for the Prep Plan for the Influenza Pandemic of the WHO (in
Spanish)
text
• Considering the worse scenario possible
– No vaccines, nor anti viral medicine
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Components of the National Preparation
Plans for an influenza Pandemic
1. Preparation for an
emergency
2. Vigilance (supervision)
3. Investigating cases and
treatment
text
4. Preventing the
dissemination of the
disease in the
community
5. Management of the
essential services
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Task Force on Epidemic
Alert & Response
• Inter-programmatic and multidisciplinary Task Force on
Epidemic Alert and Response
• Advise, Enable, Coordinate, and Monitor:
– PAHO activities for to influenza pandemic preparedness and response
– Implementation of the International Health Regulations in the Region
• Responsible for drafting the PAHO Strategic and
Operational Plan for responding to pandemic influenza
text
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Strategic & Operational Plan in
Responding to Pandemic Influenza
Objectives:
• To direct PAHO Technical Cooperation activities to prepare
the Region for an influenza pandemic
• To assist countries in their Development of National
influenza pandemic preparedness plans
• To assist countries in the supporting actions that need to be
carried out in parallel to drafting plans to have capacity to
text
detect and respond
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Governance,
policy &
partnerships
Disease
Prevention &
Control
Sustainable
Dev’t
&
Environmental
Health
Family &
Community
Health
Emergency
Preparedness &
Disaster Relief
Tech &
Health Services
Delivery
PAHO
Strategic &
Operational Plan
Procurement
Info.
knowledge &
management
PWRs &
CAREC
text
Legal
Affairs
Public
Info
Strategic
Health
Dev’t
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Technical Cooperation
Development of NIPPPs
• Assessments of National plans with WHO checklist (CA)
• PWR-level Task Forces to promote and accelerate the
development of national plans
• Introduction of modeling tools (FluAid, FluSurge, Flu
Workloss) for planning purposes to assessment surge
capacity / health services requirements to respond to a
pandemic (CDC)
• Sub-regional exercise to train multi-disciplinary national
teams (USAID):
text
–
Develop self-assessments of their national plans
– Develop action plans to fill identified gaps
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Technical Cooperation
Early Warning Systems
• Shift in influenza surveillance paradigm to comply with the newly adopted
International Health Regulations
• Hands-on training on viral isolation and immune fluorescence
• Assessments of national laboratories by Regional experts
• Expansion Global Influenza Network:
– Designation of additional NICs (PAR, ELS)
– Re-activation of non-reporting centers (ECU, HON)
• Pilot interventions to support PAR and COR for the development &
operationalization of National Plans down to local level
• Development of tool to assess countries’ capacity to detect and
text
respond
to an influenza pandemic or any epidemiologic emergency
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Technical Cooperation
Vaccines and Antivirals
• Estimate of Regional demand in progress
• Meeting with international vaccine producers and potential regional
producers to promote technology transfer in November, 2005
• Contact with Roche over possible mechanisms to supply Tamiflu to
the Region (October-November, 2005)
–
–
Assessment of Regional production capacity
Brazil negotiating with Roche – PAHO’s cooperation
• Immunizations unit promoting seasonal influenza vaccine.
–
Seasonal vaccination is taking place in 15 countries targeting high risk
populations
text
– Low global production capacity is a major stumbling block in the
introduction of vaccine
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Since PAHO’s 46th Directing Council
• “International Partnership on Avian and Pandemic Influenza” in US
Department of State, October, 2005
•
•
•
•
“Global Pandemic Influenza Readiness” in Ottawa, Canada
Meeting of Andean Ministers of Health
Videoconference of Central American Ministers of Health, October, 2005
Meeting in Geneva to work towards a global consensus to control the virus in
domestic animals and prepare for a potential human influenza pandemic.
November 2005
• Presidential Summit (Summit of the Americas) yielded a plan of action which
tasks PAHO with supporting countries in finalizing their plans by June 2006
text
(November, 2005)
• Launching of Brazil’s NIPPP, Rio de Janeiro, November, 2005
• “Hemispheric Conference on Surveillance and Prevention of Avian Influenza”
Brasilia, November, 2005
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Challenges
• Public Health Infrastructure: Strengthening of core
capabilities within the framework of the recently adopted
International Health Regulations (IHR-2005)
• Financial mechanisms and instruments (incentives,
compensation, contingency plans and emergency response)
• Interagency coordination (Shared Agenda)
• Political commitment in view of competing priorities
• text
Guidelines and emergency plans for UN/IO staff.
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Final Remarks
• Develop a specific scenario for the Americas,
based on:
– Preparedness for pandemic influenza beyond H5N1
– Strengthen response and containment in animal
health sector
– Strengthen public health response in the framework
text
of the INH requirements.
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Thank you !
text
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