Management of polymicrobial infections including MRSA · 2010-09-13 · broad spectrum antibiotics,...
Transcript of Management of polymicrobial infections including MRSA · 2010-09-13 · broad spectrum antibiotics,...
2010流感與禽流感之最新發展
衛生署 疾病管制局中區傳染病防治醫療網
王任賢 指揮官
Outline Overview 2009 pandemic Role of animal surveillance Bacterial superinfection of influenza Global monitoring of antiviral susceptibility of
pandemic influenza A(H1N1) 2009 virus
Overview of 2009 pandemic H1N1 influenza
As if 15 August 2010, 215 countries and territories have reported cases
18,631 laboratory-confirmed deaths in 125 countries
Official number significantly underestimate actual number
Widespread community transmission in all areas From April 2009 to August 2010
Pandemic Response Tools
1918 1957 1968 1997 2003 2009Spanish flupandemic
Asia flupandemic
HK flupandemic
H5N1 HK18 cases (C)6 deaths (D)
H5N1 Asia504 C299 D
A H1N12009
pandemic
PH measures (ie school closures, mask, mass gathering) Nonpharmaceutical intervention
Inactivated influenza vaccine (IIV)
1944
GISN
1952
Purified IIV, LAIV
1960
Fragmented IIV
Suo unit IIV
1980
AdjuvantedIIV
LAIVUSA
Cell-basedIIV
Vaccine
2007
AmantadaneFor influenza (1966)
Rimantadane(1993)
Neuraminidase inhibitorOseltamivir & Zanamivir (1999)
Antivirals
Infection and disease Broad spectrum of disease
High proportion of pauci or asymptomatic
10-50% of GI symptoms Severe viral pneumonia in health
adult 10-20% of hospitalizations
required ICU Groups at increased risk of
severe disease once infected (hospitalization, ICU, death) Chronic medical conditions Pregnancy women Very young and the elderly Obese Aboriginal/ethnic minorities 40% were previously healthy
Highest rate of clinical infection: Teens and young adult
Highest rate of hospitalization: Children < 5 (mediam age
20s-30s) Highest rate of death:
Adult 50-64 (median 35-51; younger age group compared to seasonal influenza)
How is this pandemic different ? First large scale response under the revised International Health
Regulation (2005) framework Global sharing of information and viruses through expert network
E.g. virus sharing: As of 5 May 2010, 155 countries share 26,066 specimens with WHO Collaborating Centers
Significant, previous pandemic preparedness efforts, including the area of risk communication E.g. 140 countries with pandemic preparedness plans before the
pandemic Access to:
Antibiotics, antiviral, vaccines (developed and available in 6 months), high-quality health cares (ie ICU)
Early detection and response at international level E.g. virus sequence made publicly available on 25 April 2009 RT-PCR kit available on 2 May 2009
Spread of pandemics 1957: Spread throughout China in 6 weeks
and throughout the world in 6 months 2009-2010: Started in North America; spread
to all continents in less than 9 weeks and throughout the world in 10 months Announcement of pandemic phase 6 on 11 June
2009 74 countries reporting cases of (H1N1) 2009 virus
West Africa reported A(H1N1) pandemic outbreak only in early 2010
Early responses to the pandemic
No travel restrictions Attempt to contain the spread with societal
measures (e.g. school closures or antiviral prophylaxis in close communities)
More information is needed to assess the impact and cost effectiveness of the various strategies
Challenges Surveillance and severity assessment Phases in preparedness guidelines Communications Naming of the pandemic Global health challenges
Surveillance and severity assessment Severity assessed and monitored with a basket of indicators
3 dimentions: Severity of the disease (clinical epidemiological and virological) Vulnerability of the population Capacity to spread
During the pandemic, the heterogeneity of systems and indicators has been a major challenge for global monitoring Different age groups No standardized definition of underlying factors No standardized definition of influenza deaths Different laboratory capacity
More than 100 countries have very limited or no influenza surveillance capacity
流感大流行各個時期之分配
1 - 3
Phases 5-6
有效人傳人
時間
以動物疫情為主,偶而傳給人
擴散期
5 - 6
4
後高峰期
後流行期
Phases in preparedness guidelines Since 1999, pandemic phases have been
used as a tool for planning pandemic responses at global and country levels
Pandemic phases were never used during a pandemic
Main challenge: Publication of new guidelines in early 2009 presented a communications challenge, namely helping the media and Member States (MS) understand the meaning of the phases.
Communications The first phase went well: Early announcement,
transparent communication Then things started to unravel: Conspiracy theories
started to spread in media and through networks on the internet
The consequence were: Misunderstanding of the public health response from the
general public and low uptake of vaccine in some countries A number of parliamentary enquiries and external reviews
of technical agencies’ response to the pandemic New sources of information dissemination have to
be taken into account in future pandemic preparedness plans: internet, blogs, virtual social networks
Naming of the pandemic Do pork products cause swine flu? Yes, just as the Rocky Mountains cause rocky
mountain fever….. Legionnaires’ cause Legionnaires disease Limes cause Lyme disease!
Global health challenges International mass gatherings Global solidarity Access to antivirals Deployment to 72 countries
Access to pandemic vaccines Deployment started in November 2009 As of 30 August 2010, reached 72 countries 73 million doses
Concluding observations Certain events were correctly anticipated Eventual emergence of a pandemic Spread was more rapid than in the past
Certain events theoretically acknowledged, but still a surprise Started in North America Origin of pandemic virus came from swine H1 viruses
Certain events were simply surprising Effectiveness of one vaccine dose
Preparedness was crucial but remains incomplete Impact of control measures on the spread and
severity of the disease are being assessed.
Characteristics of 2009 H1N1 influenzaApril 15 2009 to April 10 2010, USA
Deaths 12,470 (8.9K-19.3K) Hospitalizations 274,000 (195K-403K) Cases 61,000,000 (43M-89M)
www.cdc.gov/flu
Asssessing severity assessments
Mortality alone does not reflect the full pandemic impact 90% of deaths generally among > 65 yos For H1N1, 90% among < 65 yos Lab-confirmed cases underreported Estimates of years of potential life lost range
334K to 1.2M Many difficult decisions need to be made
early when limited data may be availablewww.cdc.gov/flu
Next steps for severity assessment Efforts underway at WHO to identify new approach
to severity assessment CDC gathering input on a new framework drafted by
Reed and Biggerstaff which allows for: Data collection from early virologic and field investigations,
as well as established systems Assessment based on categories of transmission and
clinical severity Translation of the findings into context-appropriate
recommendations
www.cdc.gov/flu
Role of animal surveillance
Influenza-Ecology in the Aquatic Bird Reservoir Migratory bird reservoirs of all influenza A (16
HA and 9 NA subtypes) viruses Divided globally into two major clades:
Eurasian and American Influenza viruses cause no apparent disease
in natural reservoir species Replicate predominantly in the intestinal tract Most interspecies transmissions are
transitory
Spread of H5N1: to Sep 2010 Poultry: +500 millions Human cases: 504 Human deaths: 299
Changes required for successful avian to mammalian spread of influenza A viruses
Avian Mammalian
Temperature 42℃ 37℃
Site of replication Intestinal Respiratory
Mode of spread Fecal/waterborne Respiratory
Receptor specificity SAα,2-3 SAα,2-6
Duck influenza Ducks are mostly resistant to disease signs
after influenza infection Ducks possess an influenza sensor (RIG-I),
chicken lack RIG-I RIG-I initiates production of interferon-β Leads to activation of antiviral innate immunity
gene Transfer of duck RIG-I to chicken cells permit
induction of antiviral response
Barber et al PNAS 2010
Animal surveillance: looking to the future Improve biosecurity- eliminate live poultry markets The burden of influenza in swine- locally and
globally Virological and serological surveillance in apparently
healthy pigs- The Hong Kong model Genomics of influenza viruses from reservoir
species Predict which viruses have pandemic potential
Bacterial super-infection of influenza
Secondary bacterial infections R.T.H Laennec was the first to describe
secondary bacterial infections following influenza
He noted that the prevalence of pneumonia increase during an epidemic of “la grippe” in 1803 in Paris
Today it is well-appreciated that many influenza-related deaths are due to secondary invaders such as S. pneumoniaeand S. aureus
Bacterial pneumonia and pandemics It is estimated that 95% of all deaths during the
1918 pandemic were complicated by secondary bacterial pneumonia (primarily S. pneumoniae)
Estimated at 50-70% in 1957 and 1968 This has been a key concern for pandemic planning The emergence of the novel pandemic H1N1 strain
has led to increased opportunities to study the epidemiology and pathogenesis of secondary bacterial infection following influenza
Influenza and S. aureus S. aureus was the primary secondary invader in 1957 In recent decades, however, it had not been a
prominent cause of pneumonia With the emergence of USA300 strains of MRSA,
necrotizing pneumonia, particularly in association with influenza, has become much more common
In the 2008-2009 season, 44% of pediatric deaths from influenza (of those tested) had bacterial super-infection, 75% of the etiologic agents were S. aureus
Bacterial pneumonia and pH1N1 Few reports of bacterial superinfections in initial
descriptions of severe pandemic related disease However, most critically ill patients were treated with
broad spectrum antibiotics, and invasive assays (e.g. pleural taps) were not commonly done
Recent evaluations of severe and fatal cases show 25-50% have evidence of bacterial super-infection (S. pneumoniae, S. aureus, S. pyogenes), with 14-46% mortality
4 deaths in healthy children in Memphis from S. aureus super-infection during the H1N1 pandemic
Mechanism of viral-bacterial synergisum Factors enhancing bacterial adherence
Epithelial damage Alteration of epithelium through sialidase activity Upregulation of receptors for bacterial adherence
Factors facilitating bacterial access to normally sterile sites Mechanical alterations to airway or E tube function Changes in tropism of virus (ability to access the lower lung)
Factors altering innate immune response Increase inflammation through expression of cytotoxins Anergy of responses to bacteria during resolution of inflammation Dysregulation of protective immune pathways Alteration of bacterial clearance through effects on immune cells
Complementation of the virus by bacteria Clearance of influenza virus HA by bacterial proteases Complementation of PB1-F2 by bacterial cytotoxins
Timing of secondary infections 0-7 days after influenza infection
Virus replication in lung Innate immunity Pro-inflammatory state Onset of acute lung injury Influx of macrophages, neutrophils
7-14 days after influenza infection Regeneration of airway cells Transition to adaptive immunity Acute lung injury peaks then begins to resolve Influx of T-cells
7-14 days after influenza infection Antibody production Wound healing Anti-inflammatory state transition to memory anergy of innate
responses
PB1-F2: newly identified protein 87 aa peptide with predicted highly cationic,
amphipathic helix at C-terminal end Sequence spanning aa 63-75 targets peptide to
mitochondria Resembles some anti-microbial peptides What is the role of PB1-F2 in pathogenesis ? PB1-F2 from pandemic strains promote inflammation and
responds to morbidity PB1-F2 is important in secondary staphylococcal
pneumonia (yes for H5N1, pH1N1, not for H3N2)
Conclusion: inflammation PB1-F2 has immunostimulatory activity – C-terminal
portion of PB1-F2 from pandemic strains and H5N1 cause inflammation, recent H3N2 does not
Inflammatory lung damage appears to play a role in both induction and severity of bacterial pneumonia following influenza
PB1-F2 from 1918 and H5N1 viruses contribute to virulence in mice and to secondary bacterial pneumonia, 1995 H3N2 PB1-F2 does not
Global monitoring of antiviral susceptibility of pandemic
influenza A(H1N1) 2009 virus
Background Pre-pandemic (seasonal) H1N1 Sporadic oseltamivir resistance up to 2007 Global spread of oseltamivir resistance H275Y virus from
2007 Apparently independent of drug use Change in fitness of H275Y virus prior to spread
Growing public health interest in antiviral drug susceptibility NISN→GISN
Antiviral susceptibility of pandemic H1N1 2009 NAI only (Gubareva et al May 2009)
Why monitor ? Integral part of pandemic monitoring and
assessment Monitor changes to virus, clinical presentation or
epidemiology Risk assessment (including under IHR) Responsibility to inform global community
Implications for clinical management Treatment guidance Reduction in risk for selection of resistant virus
Role of prophylaxis Treatment regimens Infection control
Results I
Western pacific
Euro Americas Africa South-East Asia
Estimated Med
No. of oseltamivir resistance isolate
120 99 82 1 0 1
Test in WHO
1350 1505 8456 140 47 59
Test in other lab.
++ ++ ++ ? ? ?
303/304 had H275Y substitution
Results II Associated with postexposure prophylaxis:
19.6% Immunosuppressed patients: 86.28% Associated with treatment: 98.33% No association with drug use: 28.9% Preliminary notification: 73.24%
Conclusions No evidence of widespread community circulation of
NAI resistance virus Sporadic, geographic dispersed cases Few examples of limited case to case transmission 3 case cluster
Focal, local transmission only Vietnam cluster highest potential public health risk
Severely immunocompromised a vulnerable patient population Presumptive treatment Infection control
Zanamivir remains treatment option where oseltamivir resistance likely or known
懇請賜教