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Just-in-Time Lecture

Influenza A(H1N1) (Swine Flu): A Global Outbreak


(Version 11, first JIT lecture issued April 26)
Tuesday, May 26, 2009 (01:30 AM EST)

Rashid A. Chotani, MD, MPH, DTM


Adjunct Assistant Professor
Uniformed Services University of the Health Sciences
(USUHS)
240-367-5370
chotani@gmail.com

CHOTANI © 2009.
Virus
• RNA, enveloped

• Viral family: Orthomyxoviridae

• Size:
80-200nm or .08 – 0.12 μm
(micron) in diameter
Credit: L. Stammard, 1995
• Three types
• A, B, C

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

CHOTANI © 2009.
Haemagglutinin subtype Neuraminidase subtype

H1 N1
H2 N2
H3 N3
H4 N4
H5 N5
H6 N6
H7 N7
H8 N8
H9 N9
H10
H11
H12
H13
H14
H15
H16© 2009.
CHOTANI
Structure of the influenza hemagglutinin monomer

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

CHOTANI © 2009.
Structure of the influenza hemagglutinin trimer

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

CHOTANI © 2009.
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)

CHOTANI © 2009.
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.,
CHOTANI2005, Figure 60-2.)
© 2009.
Influenza pathogenesis

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.)
CHOTANI © 2009.
Definitions
General

• 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

CHOTANI © 2009.
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)

CHOTANI © 2009. Source: Bean B, et al. JID 1982;146:47-51


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

CHOTANI © 2009.
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

CHOTANI © 2009.
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

CHOTANI © 2009.
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

CHOTANI © 2009.
Swine Influenza A(H1N1)
Transmission Through Species

Human Virus

Avian Virus

Avian/Human
Reassorted Virus

Swine Virus

Reassortment in Pigs
CHOTANI © 2009.
Swine Influenza A(H1N1) March 2009
Timeline

• 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

CHOTANI © 2009. Source: CDC


Swine Influenza A(H1N1) March 2009
Facts

• 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

CHOTANI © 2009.
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

CHOTANI © 2009. 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

CHOTANI © 2009. Source: WHO


Swine Influenza A(H1N1) May 25, 2009
Status 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
CHOTANI © 2009. Source: Secretaria de Salud, Mexico, CDC, Public Health Agency of Canada, European CDC, WHO
Swine Influenza A(H1N1) May 25, 2009
Status 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

CHOTANI © 2009. 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

CHOTANI © 2009. 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


• 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

CHOTANI © 2009. 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 Symptoms Number %


(n=44)
• Illness onset dates ranged from April 20 to
April 24
Cough 43 98%
• 10 (23%) of the patients had illness onset on
April 22, and 28 (64%) had illness onset on April Fever 42 96%
23 (Figure).
• Among 35 patients who reported a maximum Fatigue 39 89%
temperature, the mean was 102.2°F (39.0°C)
(range: 99.0-104.0°F [37.2--40.0°C]) Headache 36 82%
• In total, 42 (95%) patients reported subjective
fever plus cough and/or sore throat, meeting the Sore throat 36 82%
CDC definition for influenza-like illness (ILI)
• At the time of interview on April 27, 37 patients Runny nose 36 82%
(84%) reported that their symptoms were stable
or improving, three (7%) reported worsening Chills 35 80%
symptoms (two of whom later reported
improvement), and four (9%) reported complete Muscle aches 35 80%
resolution of symptoms
• Only one reported having been hospitalized for Nausea 24 55%
syncope and released after overnight
observation Stomach ache 22 50%

Diarrhea 21 48%

Shortness of breath 21 48%

Joint pain 20 46%

CHOTANI © 2009. Source: CDC. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm58d0428a2.htm


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

12,727 Cases & 92 Deaths


10

7000 6764

6000
No. Confirmed Cases

5000 80
4174
4000

3000

2000
1
805
1000 1
345
2 16 1 7 9 44 15 13 28 4 1 10 6 2 16 17 1 4 1 1 1 1 8 19 3 18 2 3 9 4 76 25 1 3 1 1 133 3 3 2 2 122
0
 
Argentina
Australia
Austria
Belgium
Brazil
Canada
Chile
China
Colombia
Costa Rica
Cuba
Denmark
Ecuador
El Salvador
Finland
France
Germany
Greece
Guatemala
Honduras
Iceland
India
Ireland
Israel
Italy
Japan
Korea, Republic of
Kuwait
Malaysia
Mexico
Netherlands
New Zealand
Norway
Panama
Peru
Philippines
Poland
Portugal
Russia
Spain
Sweden
Switzerland
Thailand
Turkey
United Kingdom
United States of America
Countries

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.
CHOTANI © 2009.
Global Distribution of Reported Cumulative & Probable Cases of Swine
Influenza A(H1N1) by Countries, May 25, 2009 (08:00 GMT)

US
6,767
cases
10 deaths

Total
12,727 Cases
92 deaths

12,727 Cases & 92 Deaths


CHOTANI © 2009. Source: WHO
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.

CHOTANI © 2009. 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)

CHOTANI © 2009. 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

CHOTANI © 2009. 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

CHOTANI © 2009. Source: CDC


Swine Influenza A(H1N1)
Guidelines for Clinicians

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.

CHOTANI © 2009. 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

CHOTANI © 2009. 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

CHOTANI © 2009. Source: CDC


Swine Influenza A(H1N1)
Biosafety Guidelines for Laboratory Workers

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.

CHOTANI © 2009. 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

CHOTANI © 2009.
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.

CHOTANI © 2009. Source: CDC


Swine Influenza A(H1N1)
Treatment

Oseltamivir (Tamiflu) Zanamivir (Relenza)


Treatment Prophylaxis Treatment Prophylaxis

Adults 75 mg capsule twice 75 mg capsule once Two 5 mg inhalations Two 5 mg inhalations


per day for 5 days per day (10 mg total) twice per (10 mg total) once per
day day

Children 15 kg or less: 60 mg 30 mg once per day Two 5 mg inhalations Two 5 mg inhalations


per day divided into 2 (10 mg total) twice per (10 mg total) once per
doses day (age, 7 years or day (age, 5 years or
older) older)
15–23 kg: 90 mg per 45 mg once per day
day divided into 2
doses

24–40 kg: 120 mg per 60 mg once per day


day divided into 2
doses

>40 kg: 150 mg per 75 mg once per day


day divided into 2
doses

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
CHOTANI © 2009. Source: CDC
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

CHOTANI © 2009. 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.
CHOTANI © 2009. Source: CDC
Swine Influenza A(H1N1)
Other Protective Measures

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.

CHOTANI © 2009. Source: CDC


Swine Influenza A(H1N1)
Other Protective Measures

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.

CHOTANI © 2009. Source: CDC


Types of Protective Masks
• 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.

CHOTANI © 2009.
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
CHOTANI © 2009.
Timeline of Emergence
Influenza A Viruses in Humans

Reassorted Influenza virus


(Swine Flu)
H1
1976 Swine
Flu Outbreak,
Ft. Dix Avian
Influenza

H9 H7
H5 H5
H1
H3
H2
H1

1918 1957 1968 1977 1997 2003 2009


Spanish Asian Hong Russian
Influenza Influenza Kong Influenza 1998/9
H1N1 H2N2 Influenza
H3N2

CHOTANI © 2009.
CHOTANI © 2009.
Lessons Learned form
Past 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

CHOTANI © 2009.
Lessons Learned form
Past Pandemics

• 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

CHOTANI © 2009.
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

CHOTANI © 2009.
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

CHOTANI © 2009.
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
CHOTANI © 2009.
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

CHOTANI © 2009.

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