Emerging Infectious Diseases: Does Nature strike back?
Transcript of Emerging Infectious Diseases: Does Nature strike back?
Emerging Infectious Diseases: Does Nature strike back?
Malik Peiris Centre of Influenza Research HKU-Pasteur Research Pole The School of Public health
The University of Hong Kong
• “Human destiny is bound to remain a gamble, because at some unpredictable time and some unforeseeable manner, nature will strike back.”
Rene Dubos, 1959
“One can think of the middle of the 20th Century as one of the most important societal changes in history – the conquest and elimination of infectious diseases as a significant factor in society” - McFarlane Burnet, 1962
Genetic and Biological Factors
Physical Environmental Factors
Microbe
Human
Ecological Factors Social, Political and Economic Factors
The Convergence Model
One Health “Collaborative effects of multiple disciplines
working locally, nationally and globally to attain optimal health for people, animals and the environment.” – American Veterinary Association 2008
Animal Human
Environment
Japanese Encephalitis - Sri Lanka: 1985-7
But why now? Cx.tritaeniorhynchus 4/10,959 (0.036%) Cx. Gelidus, other
Sri Lanka
Maintain food production Minimise health risk
Emergence of a obscure nephropathy in areas
covered by the irrigation scheme
H5N1: First detected in Hong Kong 1997
Epidemic Curve of Influenza A (H5N1) Cases in HKSAR, May - Dec 1997
01234567
15-M
ay
06-J
un
11-J
un
06-J
ul
10-J
ul
03-A
ug
17-A
ug
31-A
ug
12-S
ep
16-S
ep
12-O
ct
26-O
ct
01-N
ov
09-N
ov
16-N
ov
23-N
ov
30-N
ov
07-D
ec
12-D
ec
21-D
ec
26-D
ec
29 D
ec
Dates of onset (Beginning of week)
No.
of C
ases
Recovered Deceased
Active surveillance Avian flu H5N1-Post 1997
• 2000 Reassortment in ducks
• 2001 Live poultry markets
• 2002 Farm outbreaks
HK/1997
• 2002 Wild birds
• Progressive implementation of evidence based interventions
• Avian flu task force: Convener Dr PY Leung
Live poultry markets maintain, amplify AND DISSEMINATE avian influenza viruses
Poultry farms Wholesale poultry market Retail poultry
Market
Kung et al Emerg Infect Dis 2007
Kung et al Avian Dis 2003; Lau et al EID 2007; Leung et al - 2012
0%
4%
8%
12%
Bef or e Af ter Bef or e After Bef or e After
July August September
Sims & Peiris Current Top Microbiol Infect 2012
Cultural resistance to close all live poultry markets
Evidence based interventions in live poultry markets Isolation rates of H9N2 viruses in chicken
1 rest day 2 rest days Ban holding live poultry overnight
1999-2011; monthly surveillance; 5-8 FEHD poutlry markets; 53,541 samples
Leung et al EID 2012
Live poultry markets: A “dead-end” for the poultry, not for the virus.
Poultry farms Wholesale poultry market Retail poultry
Market
Kung et al Emerg Infect Dis 2007
Sims & Peiris Current Top Microbiol Infect 2012
Lessons Active surveillance, evidence-based intervention
and applying a “One health” approach protected Hong Kong. Hong Kong: a “sentinel post” for the region. What if - - - - -? 15
2004 2004 – to date
As of Aug 2012, 608 human cases, 359 deaths
Qinghai Lake outbreak: April 2005
Qinghai Lake:April 2005 Bar headed geese, Brown headed gull Great black headed gull, Great cormorant
“There is a danger that it may spread to the south Asian subcontinent …. And Europe” Chen et al Nature July 2005 16
Epi-curve of human H7N9 cases by province: (as of April 22, 2013)
19 http://www.who.int/influenza/human_animal_interface/influenza_h7n9/ChinaH7N9JointMissionReport2013u.pdf
China-WHO Joint Mission on Human Infection with Avian Influenza A(H7N9) virus: April 2013
How long will the live poultry markets stay closed? • Cultural preference • Food security
Surveillance of H5N1 viruses in “HEALTHY” poultry in live poultry markets in China
(2000-2004)
Li et al Nature 2004; 430: 209-213
Influenza H7N9 vs. H5N1 infection in ex vivo cultures of human conjunctiva, bronchus and lung
H5N
1
H
7N9
Immunohistochemistry of infected tissues, 24 hours post infection with comparable viruses dose
Conjunctiva Bronchus Lung
Chan et al - unpublished
Viral load in throat swabs after commencement of antiviral therapy
ECMO
Ventilator
Pneumonia
Emergence of antiviral resistance correlates with rebound of viral load (2/14 patients).
Hu et al Lancet on line 2013
First detected April 2009
April 2009
May 2009
June 2009
WHO, 2009. Pandemic (H1N1) 2009, situation update, available at: http://www.who.int/csr/don/2009_07_06/en/index.html (accessed 6 July 2009)
July 6 2009
1–10 11–50 51–500
500–5000
Cumulative cases
>5000
In a few weeks, the 2009 H1N1 pandemic spread around the world affecting all countries * Reports up to July 2009
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Reverse zoonosis of pandemic H1N1 to pigs worldwide global perturbation of swine influenza, leading to emergence of novel reassortants in pigs
Science 2010; 328: 1529
USA: July 2012 – Present: 309 human cases; 10 states, 16 hospitalized, 1 fatal.
http://newshopper.sulekha.com/pig-scramble_photo_1921995.htm
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Different genotypes detected in swine: Hong Kong / China (2010-2012)
PB2 PB1 PA HA NP NA M NS isolates
pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 32 pH1N1 pH1N1 pH1N1 H3-VTN pH1N1 N2-VTN pH1N1 pH1N1 53 pH1N1 pH1N1 pH1N1 H3-VTN TR-VTN N2-VTN pH1N1 pH1N1 3 pH1N1 TR pH1N1 H3-VTN pH1N1 N2-VTN pH1N1 pH1N1 5 pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 N2-early pH1N1 pH1N1 1 pH1N1 pH1N1 pH1N1 H3-VTN pH1N1 TR-N2 pH1N1 pH1N1 1 pH1N1 pH1N1 pH1N1 pH1N1 pH1N1 TR-N2 pH1N1 pH1N1 22 pH1N1 pH1N1 pH1N1 pH1N1 TR TR-N2 pH1N1 pH1N1 5 pH1N1 pH1N1 pH1N1 TR-H1 pH1N1 TR-N2 pH1N1 pH1N1 4
TR TR pH1N1 TR-H1 pH1N1 TR-N2 pH1N1 pH1N1 7 pH1N1 pH1N1 pH1N1 H1 pH1N1 TR-N2 pH1N1 TR 1 pH1N1 pH1N1 pH1N1 EA pH1N1 TR-N2 pH1N1 pH1N1 1 pH1N1 pH1N1 pH1N1 EA TR TR-N2 EA pH1N1 1
TR TR TR EA TR pH1N1 TR TR 1 pH1N1 pH1N1 pH1N1 EA pH1N1 EA pH1N1 pH1N1 29
EA EA EA EA EA EA pH1N1 EA 4 EA EA EA H1 EA N2 EA EA 5 EA EA EA EA EA EA EA EA 37 EA EA EA EA EA EA EA TR 25 TR TR TR EA TR EA EA TR 2 TR TR TR EA TR TR-N2 EA TR 7 TR TR TR EA TR EA TR TR 1 TR TR TR TR TR TR-N2 EA TR 7 TR TR TR TR-H1 TR TR-N2 TR TR 7
261 isolates 64.9% with pH1N1 gene 24 genotypes
Peiris & Guan - Unpublished
SARS
Peiris et al 2003; Drosten et al 2003; Ksiazek et al 2003
Lau et al PNAS 2005; Li et al Science 2004
Guan et al 2003
? ?
Body equilibrium and food
The novel human MERS coronavirus/2012: Closely related to bat coronaviruses
Chan & Poon mBio 2013
55 human cases 31 deaths • Jordan, Qatar, Saudi
Arabia, UAE • Travel associated
cases in France, Germany, Italy, Tunisia, UK
Ex vivo human lung and bronchus experimentally infected with coronaviruses
Chan et al J Virol 2013
HCoV-EMC ≥ SARS CoV
Cellular localization of HCoV-EMC in the ex vivo lung
Type 1 alveolar epithelium: YES
Alveolar macrophage: NO
Bronchiolar epithelium : YES Bronchus: ciliated
cells: NO
Type II alveolar epithelium: YES Pulmonary endotheilal cells: YES
HCoV-EMC (compared with H5N1) fails to induce an interferon response in alveolar
epithelial cells A549
Chan et al - submitted
SARS Legacy: Outbreak reporting is expected and respected
David L Haymann, John S MacKenzie, Malik Peiris. Lancet 2013; 381: March 9th; pp 779-781
“How the global public health and animal health communities respond to the recent emerging coronavirus threat will be a test of what has been achieved and whether the one-health notion can move beyond words to practical action.”
Conclusions • Proactive surveillance short term pain / long term gain stay “ahead-of-the-curve” • Risk-assessment
– Animal health – Human health
• Evidence-based interventions “One Health” pays!!
軒轅黃帝 The superior physician
• The superior physician helps before the early budding of the disease 上工救其萌牙
• The inferior physician begins to help when the disease has already developed; he helps when the destruction has already set in. And since his help comes when the disease has already developed, it is said of him that he is ignorant.
下工救其已成,救其已敗, 救其已成者,言不知三部,九之相失。
黃帝內經素問 Wong Dae Noi Ging Sou Men
(2697-2597 BCE) The Yellow Emperor's Classic of
Internal Medicine
Slide courtesy of Gabriel Leung
School of Public Health; The University of Hong Kong Centre of Influenza Research / HKU Pasteur Research Pole Yi Guan, Leo Poon, Michael Chan, Renee Chan, H Yen, Huachen Zhu, Ken Shortridge Department of Pathology: John Nicholls Depts of Agriculture & Food / Environmental Hygiene, Health: Les Sims, Trevor Ellis, Geraldine Luk, Miranda Lee (PY Leung) St Jude Children’s Research Hospital, Memphis: RG Webster, R Webby
Michael Chan
John Nicholls
H Yen Renee Chan Yi Guan
Ben Cowling Joe Wu
Gabriel Leung
Leo Poon
Ex vivo human lung and bronchus experimentally infected with coronaviruses
Chan et al J Virol 2013
HCoV-EMC ≥ SARS CoV
Cellular localization of HCoV-EMC in the ex vivo lung
Type 1 alveolar epithelium: YES
Alveolar macrophage: NO
Bronchiolar epithelium : YES Bronchus: ciliated
cells: NO
Type II alveolar epithelium: YES Pulmonary endotheilal cells: YES
HCoV-EMC (compared with H5N1) fails to induce an interferon response in alveolar
epithelial cells A549
Chan et al - submitted
Interventions • Changes in wholesale and retail poultry
marketing system – Modifications to wholesale poultry market. – No live ducks and geese in live poultry markets
since 1998. – Ducks and geese slaughtered separately and sold
as freshly killed poultry carcasses. – Surveillance tests on all imported poultry for
evidence of H5N1 infection.
41
Transient
Reconstructing the emergence of the pandemic
Seven gene segments “pandemic-like”. But phylogeny suggests NOT pandemic precursor
• What are the viral genetic determinants of transmission in humans?
Vijaykrishna et al Nature 2011
2009 Pandemic
a Nasopharyngeal
Transmission in ferrets Yen et al PNAS 2011 Chan et al J Virol 2011
Transmission in ferrets Transmission risk to humans
Pandemic 2009 H1N1
Nasopharynx Bronchial Alveoli
915/04 (H1N2); Differs in NA
201/10 (H1N1); Differs in HA
TRIG (H1N2); Differs in NA/M
✔ ✔ ✔
✔ ✔
✔ RG-sw915 x HK415742NA
Yen et al PNAS 2011 Chan et al J Virol 2011
Tropism in ex vivo cultures of human respiratory tract
Classical swine (H1N1) Differs in PB2/PB1/PA/NA/M
Pandemic H1N1 Classical swine H1N1
Triple reassortant
A/Sw/HK/4167/99 (H1N1)
A/Sw/Arkansas/2976/02 (H1N2) Seasonal influenza
A/Sw/HK/915/04 (H1N2) A/Sw/HK/201/10 (H1N1)
A/HK/415742/09 A/CA/04/09
Differed by NA Differed by HA, M
Differed by NA, M
Differed by PB2, PB1, PA, NA, M
Eurasian swine H1N1 A/Sw/NS29/2009 (H1N1)
Differed by PB2,PB1,PA, HA,NP,NS
Yes
Yes/Weak
Yes
No/No
No/No
No/No No/No
Correlation between upper respiratory tract virus tropism in ex-vivo cultures and ferret transmission studies
AGREE !
Chan et al J Virol 2011; Yen et al PNAS 2011