A Brief Update of Global Situation and Response to Pandemic Influenza A(H1N1) 2009 Wenqing Zhang MD...
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Transcript of A Brief Update of Global Situation and Response to Pandemic Influenza A(H1N1) 2009 Wenqing Zhang MD...
A Brief Update ofGlobal Situation and
Response to Pandemic Influenza A(H1N1) 2009
Wenqing Zhang MDGlobal Influenza Programme WHO HQTHE 3rd MEETING OF NATIONAL INFLUENZA CENTRES IN THE WESTERN PACIFIC AND
SOUTH EAST ASIA REGIONS18-20 August 2009 • Beijing China
Global Influenza Programme
Pandemic preparedness and response phases
Pandemic preparedness and response phases
Global Influenza Programme
Pandemic requirements Pandemic requirements
Global outbreak of disease
Emergence of a novel influenza virus– With efficient human-to-human transmission– No immunity in human population
! Now we are in a pandemic !
Phase 6 is characterized by community level outbreaks of the same virus in at least 1 other country in a different WHO region.
Designation of this phase would indicate that a global pandemic is under way
Global Influenza Programme
Timeline of pandemic A(H1N1) 2009Timeline of pandemic A(H1N1) 2009
April 12: an outbreak of influenza-like illness in Veracruz, Mexico reported to WHO
April 15-17: two cases of the new A(H1N1) virus infection identified in two southern California counties in U.S.A.
April 23: novel influenza A (H1N1) virus infection confirmed in several patients in Mexico.
April 24: HQ SHOC activated (first TC at 4:00 AM with Mexico)
April 26: IHR Emergency Committee convened and WHO declares a Public Health Emergency of International Concern
April 27: WHO increases pandemic alert phase from 3 to 4 and concludes geographic Containment not feasible
April 29: WHO raises pandemic alert phase from 4 to 5
June 11: WHO declares pandemic phase 6 (spread to 2 WHO regions)
In 9 weeks, all WHO 6 regions reporting cases of pandemic A(H1N1) 2009
Global Influenza Programme
WHO Responses WHO Responses
Emergency response rooms – mobilised – 24/7
Operations– Field teams– GOARN network activated
Situation monitoring and assessment– Development/update/distribution of laboratory diagnostic protocols and reagents– GISN intensive functioning – lab confirmation and virus characterization– Triage of information and follow up of alerts, coordination with Regions and National Focal Points (NFP)
Antiviral Taskforce– Oseltamivir stockpile distribution to regions and 72 priority countries (including Mexico)– Consultation with manufacturers
Technical guidance – Guidelines on surveillance, lab and diagnostic, infection control, health care management, pandemic response plan,
vaccines made available to the public– Analysis of available data, including modelling
Vaccine Taskforce – WHO recommendation on pandemic vaccine viruses and reassortant vaccine virus development– Regulatory response to pandemic– Broad consultation on issues related to the switch from seasonal vaccine to pandemic vaccine production– Broad efforts to improve global supply of pandemic vaccine
Communications
Global Influenza Programme
WHO Region
Cumulative total
Cases * Deaths
WHO Regional Office for Africa (AFRO) 591 1
WHO Regional Office for the Americas (AMRO) 102905 1274
WHO Regional Office for the Eastern Mediterranean (EMRO) 2346 7
WHO Regional Office for Europe (EURO) over 32000 53
WHO Regional Office for South-East Asia (SEARO) 11432 83
WHO Regional Office for the Western Pacific (WPRO) 28120 43
Total 177457 1462
Lab confirmed pandemic influenza A (H1N1) cases as of 6 Aug 2009
Lab confirmed pandemic influenza A (H1N1) cases as of 6 Aug 2009
Global Influenza Programme
Severity of the diseaseSeverity of the disease
Majority of cases show mild disease - resolves without treatment
Asymptomatic cases reported
So far overall severity falls within seasonal flu boundaries– Hospitalization and case fatality in young adults higher than
seasonal flu
CFR: < 1% of confirmed cases
Global Influenza Programme
Age groups of confirmed casesAge groups of confirmed cases
0%
5%
10%
15%
20%
25%
30%
35%
40%
0-9 10-19 20-29 30-39 40-49 50+
Age groups
Per
cen
t o
f ca
ses
Confirmed cases (Chile, EU and EFTA, Japan, Panama, Mexico)
Global Influenza Programme
Monitoring the viruses globally – Scientific, consistent
19 Apr – 1 Aug– A total of 73 countries– 61,742 positive specimens
• 35,758 - pandemic H1N1 (58%)• 4267 – seasonal H1N1• 7120 - H3N2 (12%)• 11,661 - A (subtype was not reported)• 2804 - B
Last reporting week– 5449 positive specimens
• 3898 - pandemic H1N1(72%)• 102 - seasonal H1N1• 992 - H3N2 (18%)• 428 - A (subtype was not reported) • 29 - B
Lab-based situation monitoring FluNet reporting
Lab-based situation monitoring FluNet reporting
Global Influenza Programme
Lab-based situation monitoring FluNet reporting
Lab-based situation monitoring FluNet reporting
Number of specimens positive for influenza by subtypes (from 19 April to 1 August)
26
1
49
2015
11
43
7784
91 89 89 87
0
200
400
600
800
1000
1200
1400
1600
1800
17 (7, 42%) 18 (9, 43%) 19 (10, 45%) 20 (9, 44%) 21 (10, 45%) 22 (9, 40%) 23 (7, 37%) 24 (7, 37%) 25 (7, 31%) 26 (6, 30%) 27 (6, 30%) 28 (4, 5%) 29 (4, 5%) 30 (4, 5%) 31 (2, 3%)
Week number, 2009
Num
ber of
spe
cim
ens
posit
ive
for in
fluen
za
0
20
40
60
80
100
Seasonal A (H1) Seasonal A (H3)A (Not subtyped) B (Yamagata lineage)B (Victoria lineage) B (Lineage not determined)Pandemic A (H1N1) A (H5)Proportion of all influenza that were pandemic A (H1N1) 2009l
Southern hemisphere
More reporting from GISN in the coming weeks will allow better observation of the trend
Global Influenza Programme
Epidemiological situation (1)Southern hemisphere
Epidemiological situation (1)Southern hemisphere
Temperate areas passing through their winter season now.
This season, pandemic H1N1 has been the predominant influenza virus in nearly all of the temperate regions of southern hemisphere
– South Africa an exception
Rapid increases in cases of pandemic influenza early in their winter season. Now decreases in the numbers of people seeking care and being admitted to hospital.
Overall trends downward– Pandemic virus still circulating in these areas and spreading into areas not
affected earlier
South Africa– an early influenza season with H3N2 predominating. – When reaching its peak in early to mid June and began to decline, pandemic
influenza H1N1 appeared and has now become the dominant subtype
Global Influenza Programme
Epidemiological situation (2)Northern hemisphere and tropical areas
Epidemiological situation (2)Northern hemisphere and tropical areas
In temperate areas including North America and Europe
– Virus continues to spread to new areas – Overall trend downward
Tropical areas– Now increases, for example in tropical areas of Central and
South America and in South and South East Asia
Global Influenza Programme
Virological surveillanceGenetic characterization
Virological surveillanceGenetic characterization
Genetic make‐up not previously detected among viruses infecting either swine or human populations
So far, genetically all viruses analyzed in GISN are homologues to A/California/7/2009
PB2
PB1
PA
HA
NP
NA
MP
NS
Human infections with H1N1 triple
reassortants
PB2
PB1
PA
HA
NP
NA
MP
NS
Outbreak of the recent novel H1N1
Influenza
Classical Swine – North American Lineage
Eurasian Swine Lineage
Avian – North American Lineage
Seasonal H3N2
A/swine/Iowa/00239/2004 H1N1 A/Iowa/CEID23/2005 H1N1
A/Texas/14/2008 H1N1 A/Iowa/01/2006 H1N1
A/swine/Korea/CAS08/2005 H1N1 A/SW/MO/1877/01 H1N2 A/Swine/Korea/CY02/02 H1N2
A/SW/CO/17871/01 H1N2 A/duck/NC/91347/01 H1N2
A/Swine/North Carolina/98225/01 H1N2 A/Swine/North Carolina/93523/01 H1N2
A/swine/OH/511445/2007 H1N1 A/Ohio/01/2007 H1N1
A/Wisconsin/87/2005 H1N1 A/swine/Minnesota/00194/2003 H1N2
A/swine/Kansas/00246/2004 H1N2 A/swine/Korea/PZ14/2006 H1N2 A/swine/Korea/Asan04/2006 H1N2
A/Swine/Ohio/891/01 H1N2 A/Swine/Illinois/100084/01 H1N2
A/Swine/Indiana/9K035/99 H1N2 A/Wisconsin/10/1998 H1N1 A/Turkey/MO/24093/99 H1N2 A/Swine/Indiana/P12439/00 H1N2
A/swine/Guangxi/17/2005 H1N2 A/swine/Guangxi/13/2006 H1N2
A/California/05/2009 H1N1 A/California/06/2009 H1N1 A/Mexico/4482/2009 H1N1
A/California/09/2009 H1N1 A/California/04/2009 H1N1
A/California/07/2009 H1N1 A/Texas/04/2009 H1N1 A/Texas/05/2009 H1N1 A/Mexico/4486/2009 H1N1 A/Mexico/4108/2009 H1N1
A/swine/Iowa/24297/1991 H1N1 A/Swine/Wisconsin/125/97 H1N1
A/Ohio/3559/1988 H1N1 A/swine/Ratchaburi/NIAH1481/2000 H1N1 A/Philippines/344/2004 H1N2
A/swine/Ratchaburi/NIAH550/2003 H1N1 A/New Jersey/1976 H1N1
A/Wisconsin/301/1976 H1N1 A/swine/Chachoengsao/NIAH587/2005 H1N1
A/swine/Chonburi/05CB1/2005 H1N1 A/Thailand/271/2005 H1N1
A/swine/Iowa/15/1930 H1N1 A/PuertoRico/8/34 H1N1
A/Washington/10/2008 H1N1 A/Brisbane/59/2007 H1N1
A/Solomon Islands/03/2006 H1N1 A/Florida/3/2006 H1N1 A/New Caledonia/20/1999 H1N1
A/mallard/MD/161/2002 H1N1 A/swine/Saskatchewan/18789/02 H1N1
A/mallard/Minnesota/Sg-00121/2007 H1N1 A/duck/NY/13152-13/1994 H1N1 A/duck/Italy/69238/2007 H1N1 A/swine/Belgium/1/83 H1N1
A/swine/England/WVL14/1996 H1N1 A/swine/England/WVL7/1992 H1N1
A/swine/Denmark/WVL9/1993 H1N1 A/swine/Zhejiang/1/2007 H1N1
A/Swine/Spain/50047/2003 H1N1 A/swine/Spain/53207/2004 H1N10.05
HA gene
Recent novel H1N1 OutbreakHighest NT Blast
Human cases of H1 SwineSeasonal H1
North American Swine
Eurasian Swine
Seasonal
North American
Avian
Global Influenza Programme
HI tests using post-infection ferret antisera, antigenically: – homogeneous – most closely related to A/California/7/2009(H1N1)v viruses– distinct from currently circulating seasonal influenza A (H1N1) viruses – similar to North American lineage triple-reassortant A (H1N1) swine
influenza viruses• represented by A/Illinois/09/2007• circulated in pigs over the last 10 years in the USA, and occasionally infected humans
Viruses from severe cases do not show differences – genetically and antigenically
Virological surveillanceAntigenic characterization
Virological surveillanceAntigenic characterization
Global Influenza Programme
GISN continuous monitoring antiviral susceptibility – > 500 isolates and 180 clinical specimens tested
Neuraminidase Inhibitors– Resistant to Oseltamivir: 8 cases (4 from Japan, 1 each from Hong Kong,
Denmark, Canada and Singapore)• Cases in Denmark, Japan and Canada had received prophylactic treatment, while the
Hong Kong traveller returning USA had not been treated with oseltamivir. • All 8 cases did not have severe disease and all subsequently recovered. • Resistant viruses have not been detected in close contacts of these individuals. • Sensitive to Zanamivir
– Otherwise, mutations previously identified to confer resistance to oseltamivir or zanamivir not observed in the NA gene of the viruses characterized to date
• Sensitive to both these antiviral drugs
M2 Inhibitors– All viruses tested so far in GISN resistant to Admantine (Amantadine and
Rimantadine)
Virological surveillanceAntiviral susceptibility
Virological surveillanceAntiviral susceptibility
Global Influenza Programme
Pandemic vaccinesWHO recommendation on vaccine viruses
Pandemic vaccinesWHO recommendation on vaccine viruses
An A/California/7/2009-like virus – 26 May
The recommendation based on comprehensive analysis of available data from the WHO Global Influenza Surveillance Network and other sources
WHO, with its Network and other partners, continuously monitoring the evolution of the virus, reviewing the recommendation. Will update whenever needed
Global Influenza Programme
Pandemic vaccinesAvailability of vaccine virusesPandemic vaccinesAvailability of vaccine viruses
Reassortant viruses: 10– Classical
• NYMC-X179A and IVR-153 (from A/California/7/2009) – Reverse Genetics
• NIBRG-121 and NIBRG-121xp (from A/California/7/2009)• CBER-RG2 (from A/California/4/2009)• IDCDC-RG15 and IDCDC-RG20 (from A/Texas7/2009)• NIBRG-122 (from A/Engliand/195/2009)• IDCDC-RG18 (from A/Texas/5/2009 and A/New York/18/2009)• IDCDC-RG22 (from A/New York/18/2009)
Wild type viruses– A/California/7/2009– A/California/4/2009– A/Texas/5 /2009– A/England/195/2009– A/New York/18/2009
All above vaccine viruses are available from WHO CCs and ERLs – by 6 Aug a total of 418 shipments made– http://www.who.int/csr/disease/swineflu/guidance/vaccines/candidates/en/index.html
Global Influenza Programme
Pandemic vaccinesGrowth property of vaccine viruses
Pandemic vaccinesGrowth property of vaccine viruses
NIBRG-121xp – recently available – By NIBSC through extended passages in eggs – A 2-3 fold increase in yield in preliminary evaluation
• Similar to normal seasonal H1N1 component– Further evaluation ongoing by manufacturers, ERLs and CCs
Other reassortant vaccine viruses– X-179A better than others– 30- 50% compared to normal seasonal H1N1 component– Comparable to poor growing B component
Wild type vaccine viruses– A/California/7/2009 – similar to normal seasonal H1N1 component in Vero-
cell
Global Influenza Programme
General preparation process– Prepared independently by 4 ERLs (CBER/FDA, NIBSC, NIID and
TGA)– Reference antigen – large amount of bulk antigen from
manufacturers• Egg-based for testing of egg-based vaccines• Cell-based for testing of cell-based vaccines
– Reference antiserum – from sheep by ERLs or for ERLs by local manufacturers
• Small amount of purified HA – Distribution
• Exchange among ERLs immediately for calibration• Once available, antigen and antisera distributed to requesting manufactures
in parallel to the calibration among ERLs• Requests directly to originating ERLs
Pandemic vaccinesVaccine potency reagents (1)Pandemic vaccinesVaccine potency reagents (1)
Global Influenza Programme
First available pandemic vaccine reagents:– First available reference antigen
• Egg-based (NYMC X-179A)• Prepared by CSL and labelled by TGA• 9000 vials filled and capped from Jul 8• Distribution started Jul 10-15 to requesting manufactures
– First available reference antiserum• A/california/7/2009• First lot prepared by NIBSC on Jun 24 – 2000 vials• Limited ongoing distribution: 50 vials per ERL; 30 vials per manufacturers upon request• Larger distribution from subsequent larger lots
Subsequent development– Reference antigen
• Egg-based by NIBSC – calibration value this week• Egg-based by CBER – calibration value sent last week• Cell-based by NIBSC – to be filled next week
– Antisera• Both CBER and TGA recommend to source from NIBSC
Pandemic vaccinesVaccine potency reagents (2)Pandemic vaccinesVaccine potency reagents (2)
Global Influenza Programme
Total annual capacity
(106 doses)
2008 Northern hemisphere production
(106 doses)
2009 Southern hemisphere production
(106 doses)
2009 planned Northern
hemisphere production
(106 doses)
Companies A 560.1 (64%) 299.6 103.0 322.8
Companies B 316.4 (36%) 170.4 9.5 170.0
All companies 876.4 470.0 112.5 492.8
Companies A (n=7): with capacity to produce at least 2.106 doses of new H1N1 vaccine / weekCompanies B (n=18): other smaller companies
Source: WHO survey
Seasonal vaccine production capacity
Pandemic vaccinesVaccine production capacity (1)Pandemic vaccines
Vaccine production capacity (1)
Global Influenza Programme
All potential influenza A(H1N1) Vaccine Manufacturers
All potential influenza A(H1N1) Vaccine Manufacturers
Global Influenza Programme
95 M410 M
2,459 M
4,918 M
.0 B
1.0 B
2.0 B
3.0 B
4.0 B
5.0 B
6.0 B
Weekly Monthly 6-month Annual
Assumptions / Methodology
Survey sent to 36 potential influenza vaccine manufacturers
– 100% response rate– All 21 current influenza vaccine
producers responded– 26 manufacturers that intend to
produce pandemic vaccines– Includes LAIV and one recombinant
vaccine capacity
Survey assumes– 1:1 H1N1 to seasonal yields– Most dose sparing formulation for
each manufacturer– Use of full production capacity
H1N
1 d
ose
s
Estimated H1N1 Vaccine CapacityAt 1:1 yields, most dose-sparing formulation, full capacity
TimeframeSource: WHO survey
Pandemic vaccine production capacity
Pandemic vaccinesVaccine production capacity (2)Pandemic vaccines
Vaccine production capacity (2)
Global Influenza Programme
SAGE recommend in July:– Three different objectives to develop vaccination strategy:
• Protect the integrity of the health-care system and the country's critical infrastructure; • Reduce morbidity and mortality; and • Reduce transmission of the pandemic virus within communities.
SAGE suggested the following groups for consideration (countries need to determine their order of priority based on country-specific conditions):
– Pregnant women – Above 6 months with one of several chronic medical conditions – Healthy young adults of 15 to 49 years of age – Healthy children – Healthy adults of 50 to 64 years of age and – Healthy adults of 65 years or above.
Important of post-marketing surveillance of the highest possible quality and rapid sharing of the results of immunogenicity and post-marketing safety and effectiveness studies
Pandemic vaccinesVaccination strategy
Pandemic vaccinesVaccination strategy
Global Influenza Programme
SummarySummary
The pandemic situation is evolving
Efficient response: global, multisectoral, collaborative, timely sharing …– Well-coordinated global efforts is key
Pandemic influenza – at its core a virus problem– Concerns of co-circulating seasonal and pandemic viruses– Concerns of continuous H5N1 infections in human, and its implication– Concerns of unpredictable mutation of the pandemic virus
Challenges on timely available effective vaccines and improvement of vaccine supply
More information is needed to fully understand the virus, the disease and efficacy of various measures
– Human knowledge on influenza limited– Respect science
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Global Influenza Programme