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Rashid A. Chotani, MD, MPH, DTMAdjunct Assistant ProfessorUniformed Services University of the Health Sciences (USUHS)[email protected]

Just-in-Time LectureInfluenza A(H1N1) (Swine Flu): A Global Outbreak (Version 11, first JIT lecture issued April 26)

Tuesday, May 26, 2009 (01:30 AM EST)

Credit: L. Stammard, 1995

• RNA, enveloped

• Viral family: Orthomyxoviridae

• Size: 80-200nm or .08 – 0.12 μm (micron) in diameter

• Three types• A, B, C

• Surface antigens• H (haemaglutinin)• N (neuraminidase)

Virus

H1 N1H2 N2H3 N3H4 N4H5 N5H6 N6H7 N7H8 N8H9 N9

H10H11H12H13H14H15H16

Haemagglutinin subtype Neuraminidase subtype

HA monomer. Sites A-E are immunodominant epitopes (From Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig.40-4)

Structure of the influenza hemagglutinin monomer

HA trimer. (From Fields Virology, 2nd ed, Fields & Knipe, eds, Raven Press, 1990, Fig.39-6)

Structure of the influenza hemagglutinin trimer

Influenza A reservoir

Wild aquatic birds are the main reservoir of influenza A viruses. Virus transmission has been reported from weild waterfowl to poultry, sea mammals, pigs, horses, and humans. Viruses are also transmitted between pigs and humans, and from poultry to humans. Equine influenza viruses have recently been transmitted to dogs. (From Fields Vriology (2007) 5th edition, Knipe, DM & Howley, PM, eds, Wolters Kluwer/Lippincott Williams & Wilkins, Philadelphia, Fig 48.1)

Influenza replication

Replication of influenza A virus. After binding (1) to sialic acid-containing receptors, influenza is endocytosed and fuses (2) with the vesicle membrane. Unlike for most other RNA viruses, transcription (3) and replication (5) of the genome occur in the nucleus. Viral proteins are synthesized (4), helical nucleocapsid segments form and associate (6) with the M1 protein-lined membranes containing M2 and the HA and NA glycoproteins. The virus buds (7) from the plasma membrane with 11 nucleocapsid segments. (-), Negative sense; (+), positive sense; ER, endoplasmic reticulum. (From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Figure 60-2.)

Pathogenesis of influenza A virus. The symptoms of influenza are caused by viral pathologic and immunopathologic effects, but the infection may promote secondary bacterial infection. CNS, Central nervous system. (From Medical Microbiology, 5th ed., Murray, Rosenthal & Pfaller, Mosby Inc., 2005, Figure 60-3.)

Influenza pathogenesis

• Epidemic – a located cluster of cases• Pandemic – worldwide epidemic• Antigenic drift

• Changes in proteins by genetic point mutation & selection • Ongoing and basis for change in vaccine each year

• Antigenic shift • Changes in proteins through genetic reassortment• Produces different viruses not covered by annual vaccine

Definitions General

Survival of Influenza Virus Surfaces and Affect of Humidity & Temperature*

• Hard non-porous surfaces 24-48 hours• Plastic, stainless steel

• Recoverable for > 24 hours• Transferable to hands up to 24 hours

• Cloth, paper & tissue• Recoverable for 8-12 hours• Transferable to hands 15 minutes

• Viable on hands <5 minutes only at high viral titers• Potential for indirect contact transmission

*Humidity 35-40%, Temperature 28C (82F)

Influenza The Normal Burden of Disease

• Seasonal Influenza• Globally: 250,000 to 500,000 deaths per year• In the US (per year)

• ~35,000 deaths• >200,000 Hospitalizations• $37.5 billion in economic cost (influenza &

pneumonia)• >$10 billion in lost productivity

• Pandemic Influenza• An ever present threat

Swine Influenza A(H1N1) Introduction

• Swine Influenza (swine flu) is a respiratory disease of pigs caused by type A influenza that regularly cause outbreaks of influenza among pigs

• Most commonly, human cases of swine flu happen in people who are around pigs

• Swine flu viruses do not normally infect humans, however, human infections with swine flu do occur, and cases of human-to-human spread of swine flu viruses have been documented

Swine Influenza A(H1N1) History in US

• A swine flu outbreak in Fort Dix, New Jersey, USA occurred in 1976 that caused more than 200 cases with serious illness in several people and one death• More than 40 million people were vaccinated• However, the program was stopped short after

over 500 cases of Guillain-Barre syndrome, a severe paralyzing nerve disease, were reported

• 30 people died as a direct result of the vaccination

• In September 1988, a previously healthy 32-year-old pregnant woman in Wisconsin was hospitalized for pneumonia after being infected with swine flu and died 8 days later.

• From December 2005 through February 2009, a total of 12 human infections with swine influenza were reported from 10 states in the United States

Swine Influenza A(H1N1) Transmission to Humans

• Through contact with infected pigs or environments contaminated with swine flu viruses

• Through contact with a person with swine flu

• Human-to-human spread of swine flu has been documented also and is thought to occur in the same way as seasonal flu, through coughing or sneezing of infected people

Swine Influenza A(H1N1) Transmission Through Species

Avian Virus

Human Virus

Swine Virus

Avian/HumanReassorted Virus

Reassortment in Pigs

Swine Influenza A(H1N1) March 2009Timeline

• In March and early April 2009, Mexico experienced outbreaks of respiratory illness and increased reports of patients with influenza-like illness (ILI) in several areas of the country

• April 12, the General Directorate of Epidemiology (DGE) reported an outbreak of ILI in a small community in the state of Veracruz to the Pan American Health Organization (PAHO) in accordance with International Health Regulations

• April 17, a case of atypical pneumonia in Oaxaca State prompted enhanced surveillance throughout Mexico

• April 23, several cases of severe respiratory illness laboratory confirmed as influenza A(H1N1) virus infection were communicated to the PAHO

• Sequence analysis revealed that the patients were infected with the same strain detected in 2 children residing in California• Samples from the Mexico outbreak match swine

influenza isolates from patients in the United States

Source: CDC

Swine Influenza A(H1N1) March 2009Facts

• Virus described as a new subtype of A/H1N1 not previously detected in swine or humans

• CDC determines that this virus is contagious and is spreading from human to human

• The virus contains gene segments from 4 different influenza types: • North American swine• North American avian• North American human and • Eurasian swine

Swine Influenza A(H1N1) US Response

• The Strategic National Stockpile (SNS) is releasing one-quarter of its • Anti-viral drugs• Personal protective equipment and• Reparatory protection devices

• President Obama today asked Congress for an additional $1.5 billion to fight the swine flu

• On April 27, 2009, the CDC issued a travel advisory that recommends against all non-essential travel to Mexico

Source: CDC

Swine Influenza A(H1N1) Global Response

• The WHO raised the alert level to Phase 5• WHO’s alert system was revised after Avian influenza began to spread in 2004, and April 27 was the first time it

was raised above Phase 3 and on April 29 to Phase 5.

• European Union (EU) issued a travel advisory to the 27 EU member countries recommending that “non-essential” travel to affected parts of the U.S. and Mexico be suspended

Source: WHO

Swine Influenza A(H1N1) May 25, 2009Status Update

• MEXICO: March 01-May 22, a total of • 4,174 Laboratory confirmed cases, with 80

deaths and 1311 hospitalizations (for pneumonia) reported in 32 of 32 States

• UNITED STATES: March 28-May 25, a total of • 6,764 Laboratory confirmed cases, with 10

deaths (Arizona 3; Missouri 1; New York 1; Texas 3; Utah 1 and; Washington 1) from 48 States (including District of Columbia)

• Over 100 Hospitalizations• Most cases mild

• CANADA: As of May 25, a total of• 921 Laboratory confirmed cases, with one

deaths (1 Alberta) from 10 of 13 States• 116 new Laboratory confirmed cases May

25• Most cases mild

Source: Secretaria de Salud, Mexico, CDC, Public Health Agency of Canada, European CDC, WHO

Swine Influenza A(H1N1) May 25, 2009Status Update

• EUROPEAN UNION & EFTA COUNTRIES: April 27- May 25, a total of• 360 Laboratory confirmed cases, with no

deaths from 19 countries• 11 confirmed cases reported on May 24• 130 in-country transmissions• Vast majority of cases reported between

20-49 years of age• Most cases (except 1) report mild disease

• GLOBALLY: March 1-May 25, a total of • 12,727 Laboratory confirmed cases, from

46 countries• 92 Deaths among laboratory confirmed

cases from 4 countries• Mexico: 80 deaths• US: 10 deaths• Canada: 01 death• Costa Rica: 01 death

Source: Secretaria de Salud, Mexico, CDC, Public Health Agency of Canada, European CDC, WHO

Swine Influenza A(H1N1)MMRW Report, April 28

• MMWR, April 28, 2009 / 58(Dispatch);1-3 • 47 patients reported to CDC with known ages (out of 64)

the median age was 16 years (range: 3-81 years)• 38 (81%) were aged <18 years• 51% of cases were in males• Of the 25 cases with known dates of illness onset, onset

ranged from March 28 to April 25 • Five patients hospitalized• Of 14 patients with known travel histories

• 3 had traveled to Mexico• 40 of 47 patients (85%) had not been linked to travel or to

another confirmed case

Source: CDC. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0428a2.htm

MMWR, April 30, 2009 / 58(Dispatch);1-3 • NYC school (high school A)

• 2,686 students and 228 staff members • April 23-24, 222 students visited the school nursing office and left school because of

illness • DOHMH collect nasopharyngeal swabs from any symptomatic students• April 24 (Friday), DOHMH collected nasopharyngeal swabs from five newly symptomatic

students identified by the school nurse and four newly symptomatic students identified at a nearby physician's office

• April 27, School closed • DOHMH also provided nasopharyngeal test kits to selected physicians' offices in the

vicinity of high school A • April 26, 7 of 9 specimens collected on April 24 were positive for the new strain of

influenza• April 26-28, 37 (88%) of 42 specimens collected tested positive, bringing the total

number of confirmed cases to 44• April 27 DOHMH conducted telephone interviews with the 44 patients

• Median age was 15 years (range: 14-21 years)• All were students, with the exception of one student teacher aged 21 years• Thirty-one (70%) of the 44 were female• Thirty (68%) were non-Hispanic white; seven (16%) were Hispanic; two (5%) were non-

Hispanic black; and five (11%) were other races• Four patients reported travel outside NYC within the United States in the week before symptom

onset, and an additional patient traveled to Aruba in the 7 days before symptom onset. None of the 44 patients reported recent travel to California, Texas, or Mexico

Swine Influenza A(H1N1)MMRW Report, April 30

Source: CDC. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0428a2.htm

Swine Influenza A(H1N1) MMRW Report, April 30

MMWR, April 30, 2009 / 58(Dispatch);1-3

• Illness onset dates ranged from April 20 to April 24• 10 (23%) of the patients had illness onset on

April 22, and 28 (64%) had illness onset on April 23 (Figure).

• Among 35 patients who reported a maximum temperature, the mean was 102.2°F (39.0°C) (range: 99.0-104.0°F [37.2--40.0°C])

• In total, 42 (95%) patients reported subjective fever plus cough and/or sore throat, meeting the CDC definition for influenza-like illness (ILI)

• At the time of interview on April 27, 37 patients (84%) reported that their symptoms were stable or improving, three (7%) reported worsening symptoms (two of whom later reported improvement), and four (9%) reported complete resolution of symptoms

• Only one reported having been hospitalized for syncope and released after overnight observation

Symptoms Number (n=44)

Cough 43 98%

Fever 42 96%

Fatigue 39 89%

Headache 36 82%

Sore throat 36 82%

Runny nose 36 82%

Chills 35 80%

Muscle aches 35 80%

Nausea 24 55%

Stomach ache 22 50%

Diarrhea 21 48%

Shortness of breath 21 48%

Joint pain 20 46%

Source: CDC. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0428a2.htm

Laboratory-Confirmed Cases of New Influenza A(H1N1) by Countries, May 25, 2009

2 16 1 7 9

805

44 15 13 28 4 1 10 6 2 16 17 1 4 1 1 1 1 8 19345

3 18 2

4174

3 9 4 76 25 1 3 1 1 133 3 3 2 2 122

6764

1000

2000

3000

4000

5000

6000

7000

Arg

entin

stralia

stria

Belg

ium

Brazil

Can

ada

ile

ina

lom

bia

sta Rica

Den

mark

Ecu

ado

El S

alvado

Fin

land

Fran

Germ

any

Greece

atemala

uras

Iceland

Ind

Ireland

Israel

Italy

Japan

rea, Rep

lic of

wait

Malaysia

Mexico

Neth

erland

New

Zealan

rway

Pan

ama

Peru

ilipp

ines

land

rtug

ssia

ain

eden

itzerland

ailand

rkey

ited K

ing

ited S

tates of A

merica

Countries

. Co

nfi

rme

d C

Chinese Taipei has reported 1 confirmed case of influenza A (H1N1) with 0 deaths. Cases from Chinese Taipei are included in the cumulative totals provided in the table above.

12,727 Cases & 92 Deaths

Global Distribution of Reported Cumulative & Probable Cases of Swine Influenza A(H1N1) by Countries, May 25,

2009 (08:00 GMT)

Source: WHO12,727 Cases & 92 Deaths

Total

12,727 Cases

92 deaths

US6,767 cases10 deaths

Swine Influenza A(H1N1) US Case Definitions

• A confirmed case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed swine influenza A (H1N1) virus infection at CDC by one or more of the following tests: • real-time RT-PCR • viral culture

• A probable case of swine influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who is:• positive for influenza A, but negative for H1 and H3 by influenza RT-PCR, or • positive for influenza A by an influenza rapid test or an influenza

immunofluorescence assay (IFA) plus meets criteria for a suspected case

• A suspected case of swine influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness with onset • within 7 days of close contact with a person who is a confirmed

case of swine influenza A (H1N1) virus infection, or • within 7 days of travel to community either within the United

States or internationally where there are one or more confirmed swine influenza A(H1N1) cases, or

• resides in a community where there are one or more confirmed swine influenza cases.

Source: CDC

Swine Influenza A(H1N1) US Case Definitions

• Infectious period for a confirmed case of swine influenza A(H1N1) virus infection is defined as 1 day prior to the case’s illness onset to 7 days after onset

• Close contact is defined as: within about 6 feet of an ill person who is a confirmed or suspected case of swine influenza A(H1N1) virus infection during the case’s infectious period

• Acute respiratory illness is defined as recent onset of at least two of the following: rhinorrhea or nasal congestion, sore throat, cough (with or without fever or feverishness)

• High-risk groups: A person who is at high-risk for complications of swine influenza A(H1N1) virus infection is defined as the same for seasonal influenza (see Reference)

Source: CDC

Swine Influenza A(H1N1) Guidelines for Clinicians

• Clinicians should consider the possibility of swine influenza virus infections in patients presenting with febrile respiratory illness who • live in areas where human cases of swine influenza A(H1N1)

have been identified or • have traveled to an area where human cases of swine influenza

A(H1N1) has been identified or • have been in contact with ill persons from these areas in the 7

days prior to their illness onset

• If swine flu is suspected, clinicians should obtain a respiratory swab for swine influenza testing and place it in a refrigerator (not a freezer)• once collected, the clinician should contact their state or

local health department to facilitate transport and timely diagnosis at a state public health laboratory

Source: CDC

Swine Influenza A(H1N1) Guidelines for Clinicians

• Signs and Symptoms• Influenza-like-illness (ILI)

• Fever, cough, sore throat, runny nose, headache, muscle aches. In some cases vomiting and diarrhea. (These cases had illness onset during late March to mid-April 2009)

• Cases of severe respiratory disease, requiring hospitalization including fatal outcomes, have been reported in Mexico

• The potential for exacerbation of underlying chronic medical conditions or invasive bacterial infection with swine influenza virus infection should be considered

• Non-hospitalized ill persons who are a confirmed or suspected case of swine influenza A (H1N1) virus infection are recommended to stay at home (voluntary isolation) for at least the first 7 days after illness onset except to seek medical care

Source: CDC

FDA Issues Authorizations for Emergency Use (EUAs) of Antivirals• On April 27, 2009, the U.S. Food and Drug Administration (FDA) issued

EUAs in response to requests by the Centers for Disease Control and Prevention (CDC) for the swine flu outbreak

• One of the reasons the EUAs could be issued was because the U.S. Department of Health and Human Services (HHS) declared a public health emergency on April 26, 2009

• The swine influenza EUAs aid in the current response:• Tamiflu: Allow for Tamiflu to be used to treat and prevent influenza in children

under 1 year of age, and to provide alternate dosing recommendations for children older than 1 year. Tamiflu is currently approved by the FDA for the treatment and prevention of influenza in patients 1 year and older.

• Tamiflu and Relenza: Allow for both antivirals to be distributed to large segments of the population without complying with federal label requirements that would otherwise apply to dispensed drugs and to be accompanied by written information about the emergency use of the medicines.

Swine Influenza A(H1N1) Guidelines for Clinicians

Source: FDA

Swine Influenza A(H1N1) Biosafety Guidelines for Laboratory Workers

• Diagnostic work on clinical samples from patients who are suspected cases of swine influenza A (H1N1) virus infection should be conducted in a BSL-2 laboratory• All sample manipulations should be done inside a biosafety cabinet (BSC)

• Viral isolation on clinical specimens from patients who are suspected cases of swine influenza A (H1N1) virus infection should be performed in a BSL-2 laboratory with BSL-3 practices (enhanced BSL-2 conditions)

• Additional precautions include:• recommended personal protective equipment (based on site specific risk

assessment)• respiratory protection - fit-tested N95 respirator or higher level of protection• shoe covers• closed-front gown• double gloves• eye protection (goggles or face shields)

• Waste• all waste disposal procedures should be followed as outlined

in your facility standard laboratory operating procedures

Source: CDC

Swine Influenza A(H1N1) Biosafety Guidelines for Laboratory Workers

• Appropriate disinfectants• 70 per cent ethanol• 5 per cent Lysol• 10 per cent bleach

• All personnel should self monitor for fever and any symptoms. Symptoms of swine influenza infection include diarrhea, headache, runny nose, and muscle aches

• Any illness should be reported to your supervisor immediately

• For personnel who had unprotected exposure or a known breach in personal protective equipment to clinical material or live virus from a confirmed case of swine influenza A (H1N1), antiviral chemoprophylaxis with zanamivir or oseltamivir for 7 days after exposure can be considered

Source: CDC

FDA Issues Authorizations for Emergency Use (EUAs) of Diagnostic Tests

• On April 27, 2009, the U.S. Food and Drug Administration (FDA) issued EUAs in response to requests by the Centers for Disease Control and Prevention (CDC) for the swine flu outbreak

• One of the reasons the EUAs could be issued was because the U.S. Department of Health and Human Services (HHS) declared a public health emergency on April 26, 2009

• The swine influenza EUAs aid in the current response:• Diagnostic Test: Allow CDC to distribute the rRT-PCR Swine

Flu Panel diagnostic test to public health and other qualified laboratories that have the equipment and personnel to perform and interpret the results.

Swine Influenza A(H1N1) Biosafety Guidelines for Laboratory Workers

Source: CDC

Swine Influenza A(H1N1) Guidelines for General Population

• Covering nose and mouth with a tissue when coughing or sneezing• Dispose the tissue in the trash after

use. • Handwashing with soap and water

• Especially after coughing or sneezing. • Cleaning hands with alcohol-based

hand cleaners • Avoiding close contact with sick

people• Avoiding touching eyes, nose or

mouth with unwashed hands• If sick with influenza, staying home

from work or school and limit contact with others to keep from infecting them

Swine Influenza A(H1N1) Treatment

• No vaccine available

• Antivirals for the treatment and/or prevention of infection: • Oseltamivir (Tamiflu) or • Zanamivir (Relenza)

• Use of anti-virals can make illness milder and recovery faster

• They may also prevent serious flu complications

• For treatment, antiviral drugs work best if started soon after getting sick (within 2 days of symptoms)

• Warning! Do NOT give aspirin (acetylsalicylic acid) or aspirin-containing products (e.g. bismuth subsalicylate – Pepto Bismol) to children or teenagers (up to 18 years old) who are confirmed or suspected ill case of swine influenza A (H1N1) virus infection; this can cause a rare but serious illness called Reye’s syndrome. For relief of fever, other anti-pyretic medications are recommended such as acetaminophen or non steroidal anti-inflammatory drugs.

Source: CDC

Swine Influenza A(H1N1) Treatment

Source: CDC

Oseltamivir (Tamiflu) Zanamivir (Relenza)

Treatment Prophylaxis Treatment Prophylaxis

Adults 75 mg capsule twice per day for 5 days

75 mg capsule once per day

Two 5 mg inhalations (10 mg total) twice per day

Two 5 mg inhalations (10 mg total) once per day

Children 15 kg or less: 60 mg per day divided into 2 doses

30 mg once per day Two 5 mg inhalations (10 mg total) twice per day (age, 7 years or older)

Two 5 mg inhalations (10 mg total) once per day (age, 5 years or older)

15–23 kg: 90 mg per day divided into 2 doses

45 mg once per day

24–40 kg: 120 mg per day divided into 2 doses

60 mg once per day

>40 kg: 150 mg per day divided into 2 doses

75 mg once per day

Dosing recommendations for antiviral treatment of children younger than 1 year using oseltamivir. Recommended treatment dose for 5 days. <3 months: 12 mg twice daily; 3-5 months: 20 mg twice daily; 6-11 months: 25 mg twice daily

Dosing recommendations for antiviral chemoprophylaxis of children younger than 1 year using oseltamivir. Recommended prophylaxis dose for 10 days. <3 months: Not recommended unless situation judged critical due to limited data on use in this age group; 3-5 months: 20 mg once daily; 6-11 months: 25 mg once daily

Swine Influenza A(H1N1) Other Protective Measures

Defining Quarantine vs. Isolation vs. Social-Distancing • Isolation: Refers only to the sequestration of symptomatic

patents either in the home or hospital so that they will not infect others

• Quarantine: Defined as the separation from circulation in the community of asymptomatic persons that may have been exposed to infection

• Social-Distancing: Has been used to refer to a range of non-quarantine measures that might serve to reduce contact between persons, such as, closing of schools or prohibiting large gatherings

Source: CDC

Swine Influenza A(H1N1) Other Protective Measures

Personnel Engaged in Aerosol Generating Activities • CDC Interim recommendations:

• Personnel engaged in aerosol generating activities (e.g., collection of clinical specimens, endotracheal intubation, nebulizer treatment, bronchoscopy, and resuscitation involving emergency intubation or cardiac pulmonary resuscitation) for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator

• Pending clarification of transmission patterns for this virus, personnel providing direct patient care for suspected or confirmed swine influenza A (H1N1) cases should wear a fit-tested disposable N95 respirator when entering the patient room

• Respirator use should be in the context of a complete respiratory protection program in accordance with Occupational Safety and Health Administration (OSHA) regulations.

Source: CDC

Infection Control of Ill Persons in a Healthcare Setting • Patients with suspected or confirmed case-status should be placed

in a single-patient room with the door kept closed. If available, an airborne infection isolation room (AIIR) with negative pressure air handling with 6 to 12 air changes per hour can be used. Air can be exhausted directly outside or be recirculated after filtration by a high efficiency particulate air (HEPA) filter. For suctioning, bronchoscopy, or intubation, use a procedure room with negative pressure air handling.

• The ill person should wear a surgical mask when outside of the patient room, and should be encouraged to wash hands frequently and follow respiratory hygiene practices. Cups and other utensils used by the ill person should be washed with soap and water before use by other persons. Routine cleaning and disinfection strategies used during influenza seasons can be applied to the environmental management of swine influenza.

Swine Influenza A(H1N1) Other Protective Measures

Source: CDC

Infection Control of Ill Persons in a Healthcare Setting • Standard, Droplet and Contact precautions should be used for all

patient care activities, and maintained for 7 days after illness onset or until symptoms have resolved. Maintain adherence to hand hygiene by washing with soap and water or using hand sanitizer immediately after removing gloves and other equipment and after any contact with respiratory secretions.

• Personnel providing care to or collecting clinical specimens from suspected or confirmed cases should wear disposable non-sterile gloves, gowns, and eye protection (e.g., goggles) to prevent conjunctival exposure.

Swine Influenza A(H1N1) Other Protective Measures

Source: CDC

• Surgical masks • Easily available and commonly used for routine surgical and examination

procedures • High-filtration respiratory mask

• Special microstructure filter disc to flush out particles bigger than 0.3 micron. These masks are further classified:• oil proof• oil resistant• not resistant to oil

• The more a mask is resistant to oil, the better it is• The masks have numbers beside them that indicate their filtration efficiency. For

example, a N95 mask has 95% efficiency in filtering out particles greater than 0.3 micron under normal rate of respiration.

• The next generation of masks use Nano-technologywhich are capable of blocking particles as small as 0.027 micron.

Types of Protective Masks

Summary

• WHO raised the alert level to Phase 5 on April 29, 2009• There is a disparity between the % case-fatality-rate between Mexico (1.91%), Canada

(0.11%) and USA (0.15%)• The overall global case-fatality (12,727 cases and 92 deaths) is 0.72%• ~ 1,500 cases worldwide (reported) needed hospitalization

• Majority in Mexico

• Epidemiological Data• US • Median Age 16 years (range: 1-81 years)• Over 80% of the cases in <18 years • 60% female; 40% Male

• Mexico • Majority of the cases reported in health young adults• 77.5% of the deaths were reported in healthy young adults, 20-54 years • Individuals 60+ seem to be protected as the number of cases and have a lower case-fatality

compared to the rest of the population• 56% female; 44% Male

• EU• Majority of the cases reported in health young adults (20-29 years). • In-country transmission (36%) has been documented

• No vaccine is available• Anti-virals available

Timeline of EmergenceInfluenza A Viruses in Humans

1918 1957 1968 1977 1997

1998/9

2003

H3H2

H5H5H9

SpanishInfluenza

H1N1

AsianInfluenza

H2N2

RussianInfluenza

AvianInfluenza

Hong Kong

InfluenzaH3N2

2009

Reassorted Influenza virus (Swine Flu)

1976 Swine Flu Outbreak,

Ft. Dix

Lessons Learned formPast Pandemics

• First outbreaks March 1918 in Europe, USA• Highly contagious, but not deadly• Virus traveled between Europe/USA on troop

ships• Land, sea travel to Africa, Asia• Warning signal was missed

• August, 1918 simultaneous explosive outbreaks in in France, Sierra Leone, USA• 10-fold increase in death rate• Highest death rate ages 15-35 years

• Cytokine Storm?• Deaths from primary viral pneumonia, secondary

bacterial pneumonia• Deaths within 48 hours of illness• Coincident severe disease in pigs

• 20-40 million killed in less than 1 year• World War I –8.3 million military deaths over 4

years• 25-35% of the world infected

• Pandemics are unpredictable• Mortality, severity of illness, pattern of spread

• A sudden, sharp increase in the need for medical care will always occur

• Capacity to cause severe disease in nontraditional groups is a major determinant of pandemic impact

• Epidemiology reveals waves of infection• Ages/areas not initially infected likely vulnerable in future

waves• Subsequent waves may be more severe

• 1918- virus mutated into more virulent form• 1957 schoolchildren spread initial wave, elderly died in

second wave• Public health interventions delay, but do not stop

pandemic spread• Quarantine, travel restriction show little effect

• Does not change population susceptibility• Delay spread in Australia— later milder strain causes

infection there• Temporary banning of public gatherings, closing schools

potentially effective in case of severe disease and high mortality

• Delaying spread is desirable• Fewer people ill at one time improve capacity to cope with

sharp increase in need for medical care

Lessons Learned formPast Pandemics

http://www.history.navy.mil/photos/images/h41000/h41730.jpg

Conclusion/Recommendations

1. Past experience with pandemics have taught us that the second wave is worse than the first causing more deaths due to:• Primary viral pneumonia, Acute Respiratory Distress Syndrome (ARDS), &

Secondary bacterial infections, particularly pneumonia• Fortunately compared to the past now we have anti-virals and antibiotics

(to treat secondary bacterial infections)• Though difficult, there is likelihood that there will be a vaccine for this

strain by the emergence of the second wave• In the US each year ~35,000 deaths are attributed to influenza resulting in

>200,000 hospitalizations, costing $37.5 billion in economic cost (influenza & pneumonia) and >$10 billion in lost productivity

• Based upon past experience and the way the current H1N1 outbreak is acting (current wave is contagious, spreading rapidly and in Mexico and Canada based upon preliminary data affecting the healthy), there is a likelihood that come fall there might be a second wave which could be more virulent

Conclusion/Recommendations

2. At present four death due to H1N1 strain has been reported outside Mexico. • The disease, though spreading rapidly across the globe, is of a mild form

(exception Mexico) • Most people do not have immunity to this virus and, as it continues to

spread. More cases, more hospitalizations and some more deaths are expected in the coming days and weeks

• Disease seems to be affecting the healthy strata of the population based upon epidemiological data from Mexico and EU

• 60 years and above age group seems to show some protection against this strain suggesting past exposure and some immunity

3. Each locality/jurisdiction needs to • Have enhanced disease and virological surveillance capabilities• Develop a plan to house large number of severely sick and provide care

if needed to deal with mildly sick at home (voluntary quarantine) • Healthcare facilities/hospitals need to focus on increasing surge capacity

and stringent infection prevention/control• General population needs to follow basic precautions

Conclusion/Recommendations

4. In the Northern Hemisphere influenza viral transmission traditionally stops by the beginning of May but in pandemic years (1957) sporadic outbreaks occurred during summer among young adults• Likelihood that

• This wave will fade in North America within the next 1-3 weeks (influenza virus cannot survive high humidity or temperature)

• Will reappear in autumn in North America with the likelihood of being a highly pathogenic second wave

• Will continue to circulate and cause disease in the Southern Hemisphere

5. Border Closure and Travel Restrictions:• The disease has already crossed borders and continents, thus, border

closure or travel restrictions will not change the course of the spread of disease• Most recently, the 2003 experience with SARS demonstrated the

ineffectiveness of such measures • In China, 14 million people were screened for fever at the airport, train

stations, and roadside checkpoints, but only 12 were found to have probable SARS

• Singapore reported that after screening nearly 500,000 air passengers, none were found to have SARS

• Passive surveillance methods (in which symptomatic individuals report illness) can be important tools

Conclusion/Recommendations

6. School Closures:• Preemptive school closures will merely delay the spread of disease • Once schools reopen (as they cannot be closed indefinitely), the disease

will be transmitted and spread • Furthermore, this would put unbearable pressure on single-working

parents and would be devastating to the economy (as children cannot be left alone)

• Closure after identification of a large cluster would be appropriate as absenteeism rate among students and teachers would be high enough to justify this action

7. High priority should be given to develop and include the present “North American” (swine) influenza A(H1N1) virus in next years vaccine. A critical look at manufacturing capacity is called for

8. It is imperative to appreciate that “times-have-changed” • Though this strain has spread very quickly across the globe and seems to

be highly infectious, today we are much better prepared than 1918. There is better surveillance, communication, understanding of infection control, anti-virals, antibiotics and advancement in science and resources to produce an affective vaccine

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