Situation Update Pandemic (H1N1) 2009 31 August 2009
Timeline pandemic (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: WHO declares a public health event of international concern (PHEIC). April 27: WHO declares pandemic phase 4 - sustained community transmission in Mexico April 29:WHO declares pandemic phase 5 (2 countries affected) June 11: WHO declares pandemic phase 6 (spread to more than 2 WHO regions) In 9 weeks, all WHO regions reporting cases of pandemic (H1N1) 2009
WHO Pandemic Phases Based on transmissibility, and geographical spread, not severity
Pandemic (H1N1) geographic distribution of laboratory confirmed cases and deaths as reported to WHO (28 August 2009)
Pandemic and seasonal influenza virus co-circulation Pandemic H1N1 2009 and seasonal viruses have cocirculated at varying levels over time in multiple countries Potential for reassortments (e.g., oseltamivir resistance in N1) Pandemic H1N1 2009 (as % of isolates) in: Chile: ~90%; USA: > 98% (since mid-june) Victoria, Australia: ~67%; South Africa: < 1% Patterns in upcoming Northern Hemisphere season are uncertain- new drift variant H3N2 under analysis
Virus circulation Map: International Co-circulation of Novel and Seasonal Influenza (As of August 4, 2009; posted August 7, 2009, 11:00 AM ET)
Pandemic monitoring New surveillance guidance published in July 4 Indicators: Geographical spread of influenza activity Intensity of acute respiratory diseases in the population Trend of respiratory disease activity Impact on health care services
Pandemic H1N1 2009 Distribution of cases by age group Confirmed cases (Chile, EU and EFTA, Japan, Panama, Mexico) Percent of cases 40% 35% 30% 25% 20% 15% 10% 5% 0% 0-9 10-19 20-29 30-39 40-49 50+ Age groups
Age-Related distribution of deaths from severe pneumonia, Mexico, 24 March- 29 April 09 compared to influenza seasons 2006-8 During 5-weeks period, 2155 cases of severe pneumonia with 821 hospitalizations + 100 deaths: 87% of deaths and 71% of severe pneumonia cases aged 5-59 yrs Chowell G et al, NEJM 2009
Pandemic (H1N1) 2009 transmissibility Secondary attack rate estimates School outbreaks: 22-33% (USA) Households: 19% (USA) to 43% (Chile) Community transmission in multiple countries NYC community-based telephone survey: 6.9% of the population developed an influenza-like illness (ILI) between 1-20 May 09. Explosive outbreaks/amplification in schools Ro estimates Pandemic H1N1: 1.2 1.7 ( 3.5 in special setting) Seasonal influenza: 1.2 1.4 Prodrome (e.g.sore throat, cough) present prior to fever onset
Clinical spectrum of infection Majority of cases have uncomplicated influenza-like illness that resolves without antiviral treatment More GI complaints (e.g., emesis, diarrhea) than seasonal Non-febrile, mild, and asymptomatic (viral RNA+) cases Hospitalization: up to 10% of confirmed cases 1-10% in US, 2-6% in Canada, 3.5% in Chile CFR: < 1% of confirmed cases Higher risk in adults (> 20 yrs old) and those with co-morbidities US < 0.4%; Mexico < 1.5%; Chile- 0.1%; Argentina < 1.5%
Age distributions for outpatients and hospitalised patients Age distribution of severe and fatal cases is older than that of all confirmed cases Laboratory confirmed cases: Median 12-17 yrs old (UK, USA, Japan, Chile, Canada) Hospitalized cases: USA (N= 567): 46% < 18 yrs (median 26 yrs) California, USA (N=30): median 27.5 yrs Fatal cases: USA (N=87): 61% aged 30-64 yrs (median, 37 yrs) Mexico (N=74): 68% aged 20-49 yrs
Age-Related distribution of deaths from severe pneumonia, Mexico, 24 March- 29 April 09 compared to influenza seasons 2006-8 During 5-weeks period, 2155 cases of severe pneumonia with 821 hospitalizations + 100 deaths: 87% of deaths and 71% of severe pneumonia cases aged 5-59 yrs Chowell G et al, NEJM 2009
Burden on the health care system New York City: > 2500 patient visits at peak (50 hospitals) 30-50 hospitalization daily Utah: 4% of total ED visits compared to < 2% at the peak of past winter season Intensive care unit: about 15-30% of hospitalized cases were admitted to ICU (USA, Canada) Mechanical ventilation: about 10% of hospitalized cases had mechanical ventilation (USA, Canada)
Burden on the health care system Thailand Outpatient general ward specialized ward ICU Outpatient First wave: mainly 'worried-well' Information needs Second wave: overwhelming ILI patients Triage needs Intensive care unit: severe ARDS with mechanical ventilatory support staff needs 4X of usual influenza season for 2 months!
Severe outcomes Majority of deaths caused by severe viral pneumonia ARDS Renal failure/multiple organ failure, hypotension and shock Bacterial co-infection in minority at presentation + nosocomial Other : myocardial infarction, paediatric encephalopathy, pulmonary embolism 50-80% of severe cases have underlying conditions Pregnancy (especially 3rd trimester), asthma or other lung disorders, cardiovascular, diabetes, immunosuppression, neurologic Obesity appears to be newly recognized risk factor Severe cases and deaths have occurred in young and previously healthy adults and less often children Delay in hospitalization, delay in antiviral therapy
Pregnancy and Influenza: Outcomes in Pregnant Women Seasonal influenza assoc. with cardiopulmonary hospitalizations Risk with duration of pregnancy; highest in 3 rd trimester 3-5 fold rates than non-pregnant during season Risk further if co-morbidities 2-5 fold rates than healthy pregnant and 3-8 fold rates than non-pregnant with co-morbidities Prior pandemics (USA) 1918: 27 to 45% mortality; 52% pregnancy loss 1957: up to 1/2 of deaths in women of reproductive years Pandemic H1N1 infections (USA) Among 20 pregnant women, 3 hospitalizations + 1 death Reports of spontaneous abortion, premature labor Neuzil et al. Amer J Epidmiol 148:1094, 1998; Dodds et al. Can Med Assoc J 176:463, 2007; Rasmussen et al. Emerg Infect Dis 14:95, 2008; CDC. MMWR 12 May 2009
Antivirals The new H1N1 virus is currently susceptible to NAIs (oseltamivir and zanamivir) Resistant to M2-inhibitors (amantadine and rimantadine) The virus is new - clinical efficacy data not yet available May be beneficial especially in: Pregnant women Patients with progressing disease or pneumonia Patients with underlying conditions Can be used: ideally early, and at any stage of active disease when ongoing viral replication is observed Important pharmacological differences of oseltamivir and zanamivir (e.g. oral vs inhalation)
Antiviral resistance WHO has been notified of 12 cases of oseltamivir resistant virus. Japan 4, USA 2, China, Hong Kong SAR China 2, and 1 in Denmark, Canada, Singapore and China No epidemiological links. No evidence of onward transmission from these cases. These viruses have a mutation in the neuraminidase (H275Y) that confers high-level resistance to oseltamivir, Viruses remain sensitive to zanamivir. 8 associated with oseltamivir post exposure prophylaxis, one with treatment of uncomplicated illness, and two have been from immunocompromised patients receiving oseltamivir treatment.
Antiviral policy and recommendations WHO on 21 Aug 09 issued guidelines on use of antivirals in patients infected with pandemic H1N1 virus Healthy patients with uncomplicated illness need not be treated with antivirals. Initial treatment decisions should be based on clinical assessment and knowledge about the virus in the community: Patients in risk groups - even with mild or uncomplicated influenza, should be treated with either oseltamivir or zanamivir WHO recommends prompt antiviral treatment for children with severe or deteriorating illness
Vaccine policy and recommendations Immunization of health care workers is a priority (1-2% of population) Stepwise approach vaccinate particular groups: based on country epidemiology and objectives Pregnant women (2% of the population) Those with chronic medical conditions Healthy young adults >15-49 years; Healthy children Healthy adults >49-65 years Healthy adults >65 years H1N1 influenza vaccine will be not be available in sufficient quantities - a stepwise approach to vaccinate will be necessary
Survey of WHO Europe countries To estimate population covered through advanced purchase agreements (APA) or other means (eg. selfproducing) Total population WHO European Region ~890 million Population of countries with APA is 561 million Population of countries Early Detection without APA but are selfproducers is 144 million Population not covered 185 million Countries without APA but expecting to purchase: 82 million GAVI countries depending upon donation:105 million
WHO support: global pandemic vaccine stockpile WHO stockpile (global): 150M doses assured WHO access at reduced price: under negotiation Timeframe for both: October 2009-April 2010 Early Detection WHO decision on country eligibility will depend on global equity, epidemiology, hemisphere sequence and whether countries have already secured access
Lessons learned Influenza viruses are unpredictable didn't allow containment operation New WHO pandemic phases did not have enough time to be adopted and sometimes caused confusion Virus spread quickly causing mainly mild illness countries had difficult times in deciding public health measures (school closing, cancelling mass gathering) Many countries had difficult time to shift from containment to mitigation Investments in pandemic planning and stockpiling antiviral medications paid off Response plans must be adaptable and science-driven Providing clear, straightforward information to the public is essential for allaying fears and building trust Even with a moderate pandemic, the health care delivery system was overwhelmed in some countries Negotiations on access to vaccines with major manufacturers for countries most in need