Introduction to Epidemiology of Influenza A (HINI) Infection Dr. Tong Ka Io Center for Disease Control & Prevention 4 th May, 2009

Outline Situation update Characteristics of the disease Risk assessment Preventive measures

Situation update

Characteristics of the disease

Risk assessment

Preventive measures

Situation Update

Influenza A (H1N1) human cases (2009.05.04) 26 … 1 25 Deaths 20 other countries …… Canada US Mexico 985 … 85 226 590 Confirmed

Situation in Mexico Jan to Mar 11: all samples reconfirmed to be negative Mar 15/17: 1 st probable/confirmed case Apr 12: reported to WHO an ILI outbreak in a small community (Veracruz) Apr 17: Issued alert due to a case of “atypical pneumonia” (Oaxaca) and enhanced surveillance Apr 23: Canada HPA helped to confirm swine flu infection and reported to WHO Apr 27: School suspension in the whole country May 3: Epidemic easing

Jan to Mar 11: all samples reconfirmed to be negative

Mar 15/17: 1 st probable/confirmed case

Apr 12: reported to WHO an ILI outbreak in a small community (Veracruz)

Apr 17: Issued alert due to a case of “atypical pneumonia” (Oaxaca) and enhanced surveillance

Apr 23: Canada HPA helped to confirm swine flu infection and reported to WHO

Apr 27: School suspension in the whole country

May 3: Epidemic easing

Asia Pacific region Confirmed New Zealand...6 Hong Kong……1 Korea……1 Suspected Australia Thailand Japan

Confirmed

New Zealand...6

Hong Kong……1

Korea……1

Suspected

Australia

Thailand

Japan

Characteristics of Disease

Virology H1N1 Same virus found in Mexico and US A new subtype not previously detected. A large part of the gene sequence is similar to that of the swine flu virus in US while a small part similar to that in Eurasia Resistant to amantadine and rimantidine but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza)

H1N1

Same virus found in Mexico and US

A new subtype not previously detected. A large part of the gene sequence is similar to that of the swine flu virus in US while a small part similar to that in Eurasia

Resistant to amantadine and rimantidine but sensitive to oseltamivir (Tamiflu) and zanamivir (Relenza)

Epidemiology 03.28 ~ 03.15 ~ Temporal distribution US Mexico

Number of confirmed (N = 97) and probable (N = 260) cases of swine-origin influenza A (H1N1) virus (S-OIV) infection by date of illness onset Mexico, March 15--April 26, 2009

Confirmed human cases of swine-origin influenza A (H1N1) infection with known dates of illness onset United States, March 28--April 27, 2009

Epidemiology Cases first found in California and Texas that are adjacent to Mexico Cases are currently found in 30 states; 63 in NY , 40 in Texas, 26 in California…… A double in the number of ILI cases over the country starting from the end of March All 32 states report suspected or probable cases Clusters of severe pneumonia cases and deaths in several administrative regions Temporal distribution US Mexico

Epidemiology Confirmed cases are aged between 3-81, the median being 16. Non-healthcare workers, no contact history with pigs. The minority have travelled to Mexico but 85% are without travel history or contact history with confirmed cases . Confirmed cases are aged between 1-59. Fatal cases are mostly healthy people aged between 20 to 45 Fatal cases include healthcare workers and their families Human distribution US Mexico

Number of patients and deaths from laboratory-confirmed infection with swine-origin influenza A (H1N1) virus (S-OIV) by age group Mexico, April 1--27, 2009

Places of transmission Families Medical establishments Schools

Families

Medical establishments

Schools

Clinical manifestation Incubation: undefined at present, estimated to be 2-7 days by US. WHO adopts the longest incubation period of 14 days Manifestation: US: relatively mild self-limiting ILI. Vomiting and diarrhea are commonly seen Mexico: Mild cases are common, mostly with symptoms of fever, cough, shortness of breath, vomiting, diarrhea. Severe cases have rapidly developed severe pneumonia and severe acute respiratory disease with high fatality Diagnosis: RT-PCR on respiratory samples yields positive results for influenza A virus but unable to differentiate subtype

Incubation: undefined at present, estimated to be 2-7 days by US. WHO adopts the longest incubation period of 14 days

Manifestation:

US: relatively mild self-limiting ILI. Vomiting and diarrhea are commonly seen

Mexico: Mild cases are common, mostly with symptoms of fever, cough, shortness of breath, vomiting, diarrhea. Severe cases have rapidly developed severe pneumonia and severe acute respiratory disease with high fatality

Diagnosis: RT-PCR on respiratory samples yields positive results for influenza A virus but unable to differentiate subtype

Symptoms in an outbreak in a New York high school Cough…...…98% Subjective fever...96% Fatigue……..89% Headache…..82% Sore throat…82% Runny nose…82% Chills………..80% Myalgia…..…80% Nausea……………55% Abdominal pain…50% Diarrhea……48% Shortness of breath…48% Joint pain……46%

Cough…...…98%

Subjective fever...96%

Fatigue……..89%

Headache…..82%

Sore throat…82%

Runny nose…82%

Chills………..80%

Myalgia…..…80%

Nausea……………55%

Abdominal pain…50%

Diarrhea……48%

Shortness of breath…48%

Joint pain……46%

Mexico official sources 25% among patients of ILI are suspected cases Among which, 10% are hospitalized for observation Among which, 1/3 are severe cases requiring an operation Fatality rate approximately 1.2%

25% among patients of ILI are suspected cases

Among which, 10% are hospitalized for observation

Among which, 1/3 are severe cases requiring an operation

Fatality rate approximately 1.2%

Risk Assessment

WHO assessment Event fulfils all 4 criteria for public health emergencies of international concern as defined in IHR (2005) Serious public health impact; unusual or unexpected; international spread; significant risk of international travel or trade restrictions On April 25, on the advice of the Emergency Committee, WHO's Director-General announced that the situation constituted a public health emergency of international concern Recommending all countries to heighten surveillance for unusual outbreaks of ILI and pneumonia

Event fulfils all 4 criteria for public health emergencies of international concern as defined in IHR (2005)

Serious public health impact; unusual or unexpected; international spread; significant risk of international travel or trade restrictions

On April 25, on the advice of the Emergency Committee, WHO's Director-General announced that the situation constituted a public health emergency of international concern

Recommending all countries to heighten surveillance for unusual outbreaks of ILI and pneumonia

WHO assessment On April 27, WHO's Director-General raised the level of influenza pandemic alert from phase 3 to phase 4, stating Likelihood of a pandemic has increased but not inevitable Virus is capable of human-to-human transmission and community-level outbreaks. Given the widespread presence of the virus, containment of the outbreak is not feasible . The current focus should be on mitigation measures.

On April 27, WHO's Director-General raised the level of influenza pandemic alert from phase 3 to phase 4, stating

Likelihood of a pandemic has increased but not inevitable

Virus is capable of human-to-human transmission and community-level outbreaks.

Given the widespread presence of the virus, containment of the outbreak is not feasible . The current focus should be on mitigation measures.

WHO assessment On April 29, WHO's Director-General raised the level of influenza pandemic alert from phase 4 to 5 , stating The pandemic is imminent All countries should immediately activate their pandemic preparedness plans At this stage, effective and essential measures include heightened surveillance, early detection and treatment of cases, and infection control in all health facilities

On April 29, WHO's Director-General raised the level of influenza pandemic alert from phase 4 to 5 , stating

The pandemic is imminent

All countries should immediately activate their pandemic preparedness plans

At this stage, effective and essential measures include heightened surveillance, early detection and treatment of cases, and infection control in all health facilities

WHO phases of pandemic alert - Phase 4 Verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.” The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic. Indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.

Verified human-to-human transmission of an animal or human-animal influenza reassortant virus able to cause “community-level outbreaks.”

The ability to cause sustained disease outbreaks in a community marks a significant upwards shift in the risk for a pandemic.

Indicates a significant increase in risk of a pandemic but does not necessarily mean that a pandemic is a forgone conclusion.

Phase 5 Human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage Is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.

Human-to-human spread of the virus into at least two countries in one WHO region. While most countries will not be affected at this stage

Is a strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.

Phase 6 (pandemic phase) Community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5. Indicate that a global pandemic is under way.

Community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5.

Indicate that a global pandemic is under way.

Local assessment More serious than SARS outbreak in Feb 2003 With both the characteristics of flu and SARS Conforming to initial characteristics of a pandemic

More serious than SARS outbreak in Feb 2003

With both the characteristics of flu and SARS

Conforming to initial characteristics of a pandemic

Influenza A (H1N1) vs. SARS Spread to 3 continents and at least 8 countries Limited to Guangdong Scope of transmission >2000 infected >100 died 305 infected 5 died No. of suspected cases and deaths 1 mth 3 mths Development Influenza A (H1N1) 2009.04 SARS 2003.02

With characteristics of flu Adapted for human transmission Rapid transmission Invisible transmission Enlarged through outbreaks in schools

Adapted for human transmission

Rapid transmission

Invisible transmission

Enlarged through outbreaks in schools

Outbreak in a New York high school Apr 23-24: 222 sick students visited the school nursing office Apr 26: 7 out of 9 samples tested positive for influenza A (H1N1) 44 preliminary confirmed cases: Onset date Apr 20-24 Aged between 14-21 68% non-Hispanic white, 16% Hispanic, 5% non-Hispanic black, 11% of other races No travel history ILI symptoms. Only 1 has to be hospitalized for a short period Small number of students in the same school reported having travelled to Mexico

Apr 23-24: 222 sick students visited the school nursing office

Apr 26: 7 out of 9 samples tested positive for influenza A (H1N1)

44 preliminary confirmed cases:

Onset date Apr 20-24

Aged between 14-21

68% non-Hispanic white, 16% Hispanic, 5% non-Hispanic black, 11% of other races

No travel history

ILI symptoms. Only 1 has to be hospitalized for a short period

Small number of students in the same school reported having travelled to Mexico

Number of confirmed cases ( N = 44) of swine-origin influenza A (H1N1) virus infection in a school, by date of illness onset New York City, April 2009

With characteristic of SARS Causes severe acute respiratory tract infection “Super spreaders” may exist Enlarged through outbreaks in medical establishments

Causes severe acute respiratory tract infection

“Super spreaders” may exist

Enlarged through outbreaks in medical establishments

Clusters of severe pneumonia cases Cluster in San Luis Potosi involved 9 cases and 2 persons died Cluster in Mexicali involved 3 cases and 2 persons died Cluster in National Institute of Respiratory Diseases (INER) involved 6 cases and 2 persons died Dead cases were a doctor and his daughter. The other daughter of the doctor was hospitalized for pneumonia Rumour: 2 interns died 6 days after being infected

Cluster in San Luis Potosi involved 9 cases and 2 persons died

Cluster in Mexicali involved 3 cases and 2 persons died

Cluster in National Institute of Respiratory Diseases (INER) involved 6 cases and 2 persons died

Dead cases were a doctor and his daughter. The other daughter of the doctor was hospitalized for pneumonia

Rumour: 2 interns died 6 days after being infected

Conforming to initial characteristics of a pandemic Current situation in Mexico does not conform to expectations for a pandemic Rapid international and inter-continental transmission Initial stage (1 st wave) is usually less severe Severe cases and fatal cases are usually the young and prime aged

Current situation in Mexico does not conform to expectations for a pandemic

Rapid international and inter-continental transmission

Initial stage (1 st wave) is usually less severe

Severe cases and fatal cases are usually the young and prime aged

Questions to be answered What is the real scope and transmission extent in Mexico? How many reported pneumonia cases are caused by Influenza A (H1N1)? Are these cases concentrated or widely dispersed?

What is the real scope and transmission extent in Mexico?

How many reported pneumonia cases are caused by Influenza A (H1N1)?

Are these cases concentrated or widely dispersed?

Questions to be answered Why cases in Mexico and US differ so much in the severity? Weakened virus? “ Super spreaders” and outbreaks in medical settings? Lifestyles/hygiene practices? Level of medical services/vaccination? Genetic difference?

Why cases in Mexico and US differ so much in the severity?

Weakened virus?

“ Super spreaders” and outbreaks in medical settings?

Lifestyles/hygiene practices?

Level of medical services/vaccination?

Genetic difference?

Questions to be answered Can the seasonal influenza vaccine offer partial protection? According to US CDC, the seasonal influenza vaccine is unlikely to provide protection for Influenza A (H1N1) Obviously, cases in Mexico are more severe than those in US. Fatal cases are mostly the young and prime aged.

Can the seasonal influenza vaccine offer partial protection?

According to US CDC, the seasonal influenza vaccine is unlikely to provide protection for Influenza A (H1N1)

Obviously, cases in Mexico are more severe than those in US. Fatal cases are mostly the young and prime aged.

Prognosis – impossible outcomes A false alarm. Situation was being exaggerated Outbreaks controlled or eliminated via public health measures

A false alarm. Situation was being exaggerated

Outbreaks controlled or eliminated via public health measures

Prognosis – possible outcomes Outbreaks stop by itself Transmission continued without touching off a pandemic, eventually becoming part of the seasonal influenza Resulting in a pandemic Serious impact during the first wave Serious impact only in the second wave

Outbreaks stop by itself

Transmission continued without touching off a pandemic, eventually becoming part of the seasonal influenza

Resulting in a pandemic

Serious impact during the first wave

Serious impact only in the second wave

1 st wave 2 nd wave

Estimation for local region Although the origin of outbreak is distant from Macao and there are no direct flights between the two places, early cases may be imported at any time Once a pandemic has started, it will probably enter Macao within several weeks Since 2005, the Influenza Pandemic Preparedness Plan and preparation in Macao is maintained at a satisfactory level. It is believed that when Macao is attacked by the pandemic, the impact on health, society and economics can be reduced to a minimum

Although the origin of outbreak is distant from Macao and there are no direct flights between the two places, early cases may be imported at any time

Once a pandemic has started, it will probably enter Macao within several weeks

Since 2005, the Influenza Pandemic Preparedness Plan and preparation in Macao is maintained at a satisfactory level. It is believed that when Macao is attacked by the pandemic, the impact on health, society and economics can be reduced to a minimum

Preventive Measures

Vaccines Vaccination is the best method of prevention US CDC has begun to produce specific vaccines. However, mass production generally requires a period of 6 months

Vaccination is the best method of prevention

US CDC has begun to produce specific vaccines. However, mass production generally requires a period of 6 months

1. Basic measures Keep contact with WHO, China MOH, health departments of neighboring regions so as to obtain the latest information Enhance risk communication and release timely information so as to inform all residents of the current situation and development, and adopt appropriate self-protection and personal hygiene measures Meet with the media regularly to report and explain the outbreak development CDC staff on duty and a 24-hr hotline in service Health education and promotion via the community network Health education and promotion by other government departments within their scope

Keep contact with WHO, China MOH, health departments of neighboring regions so as to obtain the latest information

Enhance risk communication and release timely information so as to inform all residents of the current situation and development, and adopt appropriate self-protection and personal hygiene measures

Meet with the media regularly to report and explain the outbreak development

CDC staff on duty and a 24-hr hotline in service

Health education and promotion via the community network

Health education and promotion by other government departments within their scope

2. Deferment measures Issue travel alert and travel warning according to situation so that residents can take appropriate measures before, during and after their trip Strengthen temperature screening at all ports of entry, paying special attention to travellers from affected areas

Issue travel alert and travel warning according to situation so that residents can take appropriate measures before, during and after their trip

Strengthen temperature screening at all ports of entry, paying special attention to travellers from affected areas

3. Early detection and isolation Heighten surveillance for ILI and outbreaks, virology of influenza, pneumonia of unknown causes Maintain close relationship and collaboration with WHO influenza laboratory network to increase the ability of virus testing Issue guidelines to public, private medical settings and healthcare workers so as to promptly detect and refer suspected cases Examine and repair isolation facilities and equipment so as to isolate suspected and confirmed cases when necessary

Heighten surveillance for ILI and outbreaks, virology of influenza, pneumonia of unknown causes

Maintain close relationship and collaboration with WHO influenza laboratory network to increase the ability of virus testing

Issue guidelines to public, private medical settings and healthcare workers so as to promptly detect and refer suspected cases

Examine and repair isolation facilities and equipment so as to isolate suspected and confirmed cases when necessary

4. Measures to prevent outbreaks in high-risk institutions The Health Bureau coordinates all medical institutions to maintain good infection control With the help of DSEJ, coordinates all schools to perform preventive measures such as morning inspection, temperature measurement, school suspension for the sick, outbreak notification; better and revise contingency plans so as to suspend school when necessary With the help of IAS, coordinates all nurseries to perform measures such as morning inspection, temperature measurement, school suspension for the sick; coordinates all social facilities for outbreak notification, better and revise contingency plans so as to suspend social services when necessary

The Health Bureau coordinates all medical institutions to maintain good infection control

With the help of DSEJ, coordinates all schools to perform preventive measures such as morning inspection, temperature measurement, school suspension for the sick, outbreak notification; better and revise contingency plans so as to suspend school when necessary

With the help of IAS, coordinates all nurseries to perform measures such as morning inspection, temperature measurement, school suspension for the sick; coordinates all social facilities for outbreak notification, better and revise contingency plans so as to suspend social services when necessary

5. Measures to respond to pandemic Health Bureau perfects and revises the Influenza Pandemic Preparedness Plan and substantial preparation so as to rapidly adjust functions, allocate resources, raise capacity and rescue patients in times of a pandemic All relevant departments perfect and revise preparedness plans and substantial preparation so as to maintain basic social functions and services in times of a pandemic

Health Bureau perfects and revises the Influenza Pandemic Preparedness Plan and substantial preparation so as to rapidly adjust functions, allocate resources, raise capacity and rescue patients in times of a pandemic

All relevant departments perfect and revise preparedness plans and substantial preparation so as to maintain basic social functions and services in times of a pandemic

6. Restorative measures All relevant departments perfect and revise post-pandemic restorative plans and preparation for social, economic, psychological aspects so as to achieve fast recovery of the community after the pandemic.

All relevant departments perfect and revise post-pandemic restorative plans and preparation for social, economic, psychological aspects so as to achieve fast recovery of the community after the pandemic.