Download Swine Flu

Clinical management of
human infection with
Pandemic (H1N1) 2009 virus
Professor Dr Mukhtiar Zaman
Khyber Teaching Hospital
Peshawar
Virus
• 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)
Credit: L. Stammard, 1995
Haemagglutinin subtype
H1
H2
H3
H4
H5
H6
H7
H8
H9
H10
H11
H12
H13
H14
H15
H16
Neuraminidase subtype
N1
N2
N3
N4
N5
N6
N7
N8
N9
Timeline of Emergence
Influenza A Viruses in Humans
Reassorted Influenza
virus (Swine Flu)
1976 Swine
Flu Outbreak,
Ft. Dix
H1
Avian
Influenza
H9 H7
H5 H5
H1
H3
H2
H1
1918
1957
Spanish
Influenza
H1N1
Asian
Influenza
H2N2
1968
1977
Hong
Russian
Kong
Influenza
Influenza
H3N2
1997
2003
1998/9
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
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 32year-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 Through Species
Human Virus
Avian Virus
Avian/Human
Reassorted Virus
Swine Virus
Reassortment in Pigs
Influenza A(H1N1)
•
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
Pandemic Influenza H1N1
As of 8 November 2009, worldwide
more than 206 countries and
overseas territories or communities
have reported laboratory confirmed
cases of pandemic influenza H1N1
2009, including over 6250 deaths.
Swine Influenza A(H1N1)
Mexico Epidemic Curve Confirmed, by Day
As of June 09, 2009
Total Number of Confirmed Cases = 6,241*
Suspension of Non-essential Activities
School Closure
400
No. of Confirmed Cases
400
School Open
385
350
309
290
300
270
262
250
224
2 17
2 14
19 9 2 0 1
221
200
18 6
17 6
16 8
15 8
14 8
150
12 8
12 7 12 6
12 2
Epidemiological Alert
100
112
92
90
76
50
6 7 7
8 4
1 0 0 0 1 12 1 1 1 12 2 4 3 2 0 2 3 5 3
3 2
8
3 1 3 4
141510 1014
77
85
76
31
22
71
69
65
75
61
5959
52
50
41 37
36
3 12 93 3
25
20
8
16
4
0
Day
*NOTE: 54 confirmed cases not included
Source: Secretaria de Salud, Mexico
Swine Influenza A(H1N1)
Mexico Confirmed Case Distribution, by Age
As of June 09, 2009
No. Confirmed Cases
Total Number of Confirmed Cases = 6,241*
2000
1800
1600
1400
1200
1000
800
600
400
200
0
1776
1720
1191
638
476
273
127
0-9
10-19
20-29
30-39
40-49
50-59
60+
40
NA
Age Group
*NOTE: 54 confirmed cases not included
Source: Secretaria de Salud, Mexico
Swine Influenza A(H1N1)
Mexico Confirmed Cases & Death, by Age Groups
Male:
48.1%
Fem ale:
51.9%
As of June 09, 2009
Total Number of Confirmed Cases = 6,241*
Deaths = 108
Deaths
16
%
100
71.3% Deaths
No. of Deaths
80
12
70
10
60
8
50
40
6
30
4
12
2
2.8
3.7
6.5
12
9.3
20
13.9
7.4
3.7
8.3
8.3
5.6
1.9
0.9
0
0.9
1.9
Case-Fatality (%)
90
14
10
0
>75
70-74
65-69
60-64
55-59
50-54
45-49
40-44
35-39
30-34
25-29
20-24
15-19
10-14
5-9
1-4
<1
Age Group
*NOTE: 43 confirmed cases not included
Source: Secretaria de Salud, Mexico
Swine Influenza A(H1N1)
Mexico Death, by Occupation
House Bound
22
Independent Worker
15
Private Sector Worker
13
Student
8
Tradesmen
5
Minor
5
N=80
Professional
4
Pubic Sector Worker
3
Unemployed
3
Retired
2
0
5
10
15
Deaths
20
25
Key epidemiological features
• Younger (5 to 49 years) rather than older (>65 years)
age groups are most affected by the pandemic (H1N1)
2009 influenza virus.
• Human-to-human transmission appears to be similar to
seasonal influenza viruses occurring primarily through
close unprotected contact with large respiratory droplets.
• The incubation period (time between infection and onset
of symptoms) appears to be approximately 2-3 days, but
could range up to 7 days.
• Secondary attack rates of influenza-like illness (ILI) in
households and other closed settings typically range
between 7% and 13%; however, lower and higher
rates have been reported.
• Most persons experience an uncomplicated ILI, with full
recovery within a week, even without medical treatment.
• The most commonly reported symptoms include cough,
fever, sore throat,
muscle aches, malaise and
headache. Some patients experience gastrointestinal
symptoms (nausea, vomiting and/or diarrhoea). In some
instances, sore throat
and cough can precede fever.
• A small minority of patients develop severe illness,
principally severe progressive pneumonia. Risk factors for
severe disease are similar to those identified for
complications from seasonal influenza. (children <2 years,
persons >65 years, pregnant women, persons of any age
with chronic pulmonary, cardiac, renal, and/or liver disease;
persons with certain neurological conditions,
hemoglobinopathies, primary or secondary
immunosuppression, and children receiving chronic aspirin
therapy.)
• Women who are pregnant may be four to five
times more likely to develop severe disease
compared to non-pregnant persons.
• Minority groups and indigenous populations
appear to be disproportionately affected by
severe disease but the reasons are not fully
understood.
• Approximately 1% to 10% of persons with
clinical illness require hospitalization.
• Children <5 years have rates of hospitalization
at least two to three times higher than other age
groups
Swine Influenza A(H1N1)
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)
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
Pandemic H1N1
A wide clinical spectrum of disease ranging from
• Non-febrile, mild upper respiratory tract illness,
• Febrile influenza like illness (ILI)
• Severe or even fatal complications, including
rapidly progressive pneumonia has been
described.
Case description
Uncomplicated influenza
• ILI symptoms include: fever, cough, sore
throat, rhinorrhea, headache, muscle pain,
and malaise, but no shortness of breath
and no dyspnoea. Patients may present
with some or all of these symptoms.
• Gastrointestinal illness may also be
present, such as diarrhoea and/or
vomiting, especially in children, but without
evidence of dehydration.
Complicated or severe influenza
• Presenting clinical (e.g. shortness of breath/dyspnoea,
tachypnea, hypoxia) and/or radiological signs of lower
respiratory tract disease (e.g. pneumonia), central
nervous system (CNS) involvement (e.g.
encephalopathy, encephalitis), severe dehydration, or
presenting secondary complications, such as renal
failure, multiorgan failure, and septic shock. Other
complications can include rhabdomyolysis and
myocarditis.
• Exacerbation of underlying chronic disease, including
asthma, COPD, chronic hepatic or renal failure,
diabetes, or other cardiovascular conditions.
• Any other condition or clinical presentation requiring
hospital admission for clinical anagement.
Cont:
• Any of the signs of disease progression listed below.
– Symptoms and signs suggesting oxygen impairment or cardiopulmonary
insufficiency:
• Shortness of breath (with activity or at rest), difficulty in breathing
• turning blue, bloody or coloured sputum, chest pain, and low blood pressure;
– In children, fast or laboured breathing; and
– Hypoxia, as indicated by pulse oximetry.
• Symptoms and signs suggesting CNS complications:
– Altered mental status, unconsciousness, drowsiness, or difficult to
awaken and recurring or persistent convulsions (seizures), confusion,
severe weakness, or paralysis.
• Evidence of sustained virus replication or invasive secondary
bacterial infection based on laboratory testing or clinical signs (e.g.
persistent high fever and other symptoms beyond 3 days).
• Severe dehydration, manifested as decreased activity, dizziness,
decreased urine output, and lethargy.
H1N1 Virus in the Tissue
Infection control
•
•
•
•
Evidence to date suggests that pandemic (H1N1) 2009 virus is transmitted
similarly to seasonal influenza A and B viruses. Appropriate infection control
measures (Standard plus Droplet Precautions) should be adhered to at all
times.
Whenever performing high risk aerosol-generating procedures (for example,
bronchoscopy or any procedure involving aspiration of the respiratory tract)
use a particulate respirator (N95, FFP2 or equivalent), eye protection,
gowns, and gloves and carry out the procedure in an adequately ventilated
room, either naturally or mechanically.
The duration of isolation precautions for hospitalized patients with influenza
symptoms should be continued for 7 days after onset of illness or 24 hours
after the resolution of fever and respiratory symptoms, whichever is longer,
while a patient is in a health-care facility. For prolonged illness with
complications (i.e. pneumonia), control measures should be used during the
duration of acute illness (i.e. until the patient has improved clinically).
Special attention is needed in caring for immunosuppressed patients who
may shed virus for a longer time period and are also at increased risk for
development of antiviral-resistant virus.
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)
Source: Bean B, et al. JID 1982;146:47-51
Types of Protective Masks
•
Surgical masks
–
•
High-filtration respiratory mask
–
–
–
•
Easily available and commonly used for routine surgical and examination procedures
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-technology which are capable of blocking
particles as small as 0.027 micron.
Infection control
Diagnosis
Molecular diagnostics
• Molecular diagnostics( real time-PCR) are currently the method of
choice for pandemic (H1N1) 2009 virus.
• Results obtained using the WHO (HAI) kit H1 monoclonal antibodies
should not be taken as conclusive and further verification is
recommended.
Rapid tests or immunofluorescence
• Point‐of‐care antigen detection tests evaluated so far, their analytical
sensitivity for the novel H1N1 virus is comparable with their
sensitivity for detecting seasonal influenza.
– It should be noted that these tests have appreciably lower sensitivity
than RT‐PCR for both novel H1N1 and seasonal H1N1 or H3N2 viruses.
– It should be emphasized that these tests will not differentiate seasonal
influenza from pandemic (H1N1) 2009 virus.
Serology
• HAI and microneutralization tests using
pandemic (H1N1) 2009 virus are expected
to be able to detect antibody responses
following infection.
Interpretation of laboratory results
• PCR — A sample is considered positive if
results from tests using two different PCR
targets (e.g. primers specific for universal
M gene and swine H1 haemagglutinin
gene) are positive but the PCR for human
H1 + H3 is negative. (A negative PCR
result does not rule out that a person may
be infected with pandemic (H1N1) 2009
virus. )
Cont:
• Serology — A four‐fold or greater rise in specific
pandemic (H1N1) 2009 antibody titres indicates recent
infection with the virus.
• Sequencing — Sequence analyses of the type A
influenza matrix gene PCR product using the primers in
the WHO protocols (see Annex 1) will differentiate
between M genes of pandemic and seasonal H1N1
viruses, however, additional analysis should be
performed to confirm the origin of the virus.
• Virus isolation — Identification and typing of a cultured
influenza virus can be carried out by PCR, indirect
fluorescent antibody (IFA) testing using specific NP
monoclonal antibodies, or HA and antigenic analysis
(subtyping) by HAI using selected reference antisera.
Treatment
• Approximately 10% to 30% of hospitalized patients require intensive
care.
• Prompt treatment with antiviral drugs, namely oseltamivir, zanamivir
or peramivir, reduces the severity of illness and improves the rate of
survival. Resistance is not a significant clinical problem
– Through systematic surveillance to date, 28 resistant viruses have been
detected and characterized worldwide.
– All of these viruses show the same H275Y mutation that confers
resistance to the antiviral oseltamivir, but not to the antiviral zanamivir.
Zanamivir remains a treatment option in symptomatic patients with
severe or deteriorating illness due to oseltamivir-resistant virus.
– Twelve of these drug-resistant viruses were associated with the use of
oseltamivir for post-exposure prophylaxis.
– Six were associated with the use of oseltamivir treatment in patients
with severe immunosuppression.
– Four were isolated from samples from patients receiving oseltamivir
treatment.
• The availability and coverage of pandemic (H1N1) 2009 influenza
vaccines will vary greatly and many countries will have little or no
access to this primary prevention measure.
Oseltamivir (Tamiflu)
Treatment
Zanamivir (Relenza)
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
15–23 kg: 90 mg
per day divided
into 2 doses
45 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)
24–40 kg: 120 mg 60 mg once per
per day divided
day
into 2 doses
>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
Source: CDC
Summary of clinical management of the
Pandemic (H1N1) 2009 virus infection
Modalities
Antibiotics
Strategies
In case of pneumonia, empiric treatment for
community acquired pneumonia (CAP)
Antiviral therapy
oseltamivir or zanamivir
Corticosteroids
Moderate to high dose steroids are NOT
recommended.
Infection control
Standard plus Droplet Precautions. For
aerosol generating procedure, use particulate
respirator, eye protection, gown, gloves, and
an airborne precaution room.
NSAIDS,
antipyretics
Paracetamol or acetaminophen given orally or
by suppository. Avoid aspirin.
Oxygen therapy
Monitor oxygen saturation and maintain SaO2
over 90%