Transcript influenza - Sun Yat

Influenza
SHU Xin MD
The department of infectious diseases,
3rd affiliated hospital of SUN Yet-Sen university










Definition
Etiology
Epidemiology
Pathology and pathogenesis
Clinical manifestations
Complications
Laboratory findings
Diagnosis and differential diagnosis
Treatment
Prophylaxis
Definition



Acute respiratory illness caused by influenza
viruses.
Typical symptoms-fever, chills, myalgia,
headache, sore throat, cough.
Serious cases in young children and elderly.
Etiologic agent
Etiologic agent
Etiologic agent


Influenza A viruses are subdivided on the
basis of the HA and NA antigens.
Designation:
Species/ A/Beijing/32/92(H3N2)
virus type
Geographic Strain Year of
origin
number Isolation
Virus
subtype
Epidemiology


Source of infection: patients and covert
infection carrier.
Epidemiology
Transmission: primarily via respiratory droplets.
person to person( hand-to-hand, hand-to-mouth)
direct contact
aerosols—sneezing, coughing.
 susceptible :the immunity in the population at
risk is the major determinant of the extent and
severity of an outbreak.

Epidemiology
Date
Deaths
1918-20 40-100 million
Subtype
H1N1
1957-58 1-1.5 million
H2N2
Hong
Kong flu
1968-69 0.75-1 million
H3N2
Russian
flu
1977
H1N1
Spanish
flu
Asian flu
Street car
conductor in
Seattle not
allowing
passengers
aboard
without a
mask in 1918


From April 2007 to April 2008 , there are 13553
cases and 191 outbreaks of influenza reported
to CDC in China.
The outbreaks are mainly in primary school and
secondary school.
The epidemic of influenza in China
Pathogenesis
Pathogenesis




Histopathologic study reveals degenerative
changes, including granulation, vacuolization,
swelling, and pyknotic nuclei.
The severity of illness is correlated with the
quantity of virus shed in secretions;
Only rarely been detected in extra pulmonary sites.
Primary influenza viral pneumonia( particularly
the elderly, children, and immuno-suppressed
patients) interstitial infiltration.
Manifestations
Incubation period:1-3 days
 Typical influenza
An illness characterized by the abrupt onset of
systemic symptoms.
Headache, fever, chills, myalgia, or malaise.
respiratory tract signs, particularly cough and
sore throat.
Ocular signs and symptoms include pain on
motion of the eyes, photophobia, and burning
of the eye.

Manifestations
Physical findings:
examination of the pharynx: severe sore throat.
injection of the mucous membranes and
postnasal discharge.
mild cervical lymphadenopathy.
Chest examination: largely negative.
rhonchi, wheezes, and scattered rales.
last for 4-7days.

Manifestations
Primary influenza virus pneumonia:
presents as acute influenza that does not resolve
but instead progresses relentlessly.
persistent fever, dyspnea, and eventual cyanosis.
sputum production is generally scanty.
cardiac failure, liver failure and renal failure.
Physical findings: no consolidation signs.

Mild form influenza:
 Other forms:
stomach flu
encephalitis, transverse myelitis,
myocarditis and pericarditis,
myositis

Complications

Secondary bacterial infection:
pneumonia: cough, purulent sputum, physical
and x-ray signs of consolidation.
Most common bacterial pathogens are
streptococcus pneumoniae, staphylococcus
aureus, and haemophilus influenzae.
Complications
Reye's syndrome:
The disease causes fatty liver with minimal
inflammation, and severe encephalopathy (with
swelling of the brain). The liver may become
slightly enlarged and firm, and jaundice is not
usually present.
 Early diagnosis is vital, otherwise death or severe
brain damage may follow.

Laboratory findings

Blood routine test
WBC counts are variable, frequently being low
early in illness and normal or slightly elevated
later.
while leukocytosis with more than 15,000
cells/ml raises the suspicion to secondary
bacterial infection.
Laboratory findings
Virus isolation
Isolation the virus from throat swabs,
nasopharyngeal wash, or sputum.
virus usually is detected in tissue culture or the
amniotic cavity of chick embryos within 48-72 h
after inoculation.

Laboratory findings
 Serum
tests
Fourfold or greater titer rises as
detected by HAI or CF or significant
rises as measured by ELISA are
diagnostic of acute infection.
 viral antigens:
indirect immunofluorescence,
enzyme immunoassays.
Diagnosis



Influenza season– winter and spring
Clinic manifestations:
Laboratory findings:
Differential diagnosis

On clinical grounds alone, an individual case of
influenza may be difficult to differentiate from
an acute respiratory illness caused by any of a
variety of respiratory viruses or by mycoplasma
pneumoniae.----virus isolation and serum test or
antigens detect are very important.

Leptospirosis;
calf muscle tenderness,
lymphadenopathy
Treatment
1 General treatment
Rest, maintain hydration.
symptomatic treatment:
acetaminophen or salicylates
The use of salicylates should be avoided in
children below 18 years of age (reye’s syndrome).
codeine-containing compounds :
Antibiotics for the secondary bacterial infection.

2 antiviral therapy:
M2 inhibitors: amantadine and rimantadine
Side effects:
rimantadine only for adults.
Dose: 200mg/d for 3-4 days.

Neuraminidase inhibitors
oseltamivir: designed to halt the spread of the
virus in the body. These drugs are often
effective against both influenza A and B. they
reduce symptoms and complications. Different
strains of influenza viruses have differing
degrees of resistance against these antivirals.
Prophylaxis

Vaccination
Human avian influenza
Definition

Influenza caused by influenza virus A adapted to
birds.
Etiology
Avian influenza virus A
 Highly pathogenic avian influenza( HPAI )
H5N1
H7N7
H9N2

Distinguish the avian flu and the human flu
HA:
avian flu
α2-3 sialic acid receptors
human flu
α2-6 sialic acid receptors
 The presence of both -2,3 and -2,6 linkages in
the pig tracheal epithelium
 In the human respiratory epithelium, it has been
shown that -2,3 and -2,6 linkages are found on
ciliated and nonciliated cells

Epidemiology
Source of infection:
birds with the avian influenza virus.
others: pig, cat
human?
 Transmission:
direct contact with infectious secretions and
excreta from infected birds or contaminated
poultry products.
direct animal to human transmission
Human to human?

Epidemiology

Susceptible:
people are all susceptible, especially in children
< 12 years.
People who direct contact with infectious
secretions and excreta from infected birds or
contaminated poultry products are at high risk.
wild waterfowl likely plays a role in the avian
influenza cycle and could be the initial
source for AI viruses.
virus may be passed on through
contact with resident waterfowl or
domestic poultry
Cumulative Number of Confirmed Human Cases of Avian
Influenza A/(H5N1) Reported to WHO( Cases/Deaths)
Azerbaijan
2003
2004
2005
2006
2007
2008
total
0
0
0
8/5
0
0
8/5
1/0
1/0
Bangladesh
Cambodia
China
1/1
4/4
2/2
1/1
8/5
13/8
5/3
7/7
3/3
30/20
Djibouti
1/0
Egypt
18/10
25/9
7/3
50/22
55/45
42/37
20/17
137/112
5/5
106/52
Indonesia
20/13
Iraq
3/2
Lao
Viet Nam
1/0
2/2
3/3
Thailand
29/20
61/19
17/12
5/2
Turkey
8/5
3/3
25/17
12/4
12/4
Nigeria
1/1
Pakistan
3/1
total
4/4
46/32
98/43
115/79
88/59
36/28
387/245



1997 in Hong Kong, resulting in 18 documented
cases and six fatalities.
The outbreak was controlled after depopulating
1.5 million chickens in Hong Kong farms and
markets.
Human infections due to A/H5N1 resurfaced in
Hong Kong in 2003.
Pathogenesis and pathology
The pathogenesis and pathology is similar to
that in influenza.
Alveolar hemorrhage and hyaline membranes
were seen in some patients.
H5N1 vs. previous pandemics of human influenza



The human incubation period of avian influenza
A (H5N1) is 1to 3 days (usually less than 7 days)
The main clinical manifestations of avian
influenza infections depend on the viral subtype
causing the disease.

A/H7N7 infections mainly result in
conjunctivitis and/or an influenza-like illness.
A/H5N1 outbreak, an influenza-like illness
typically appeared early in the course of
the disease, and conjunctivitis was seen in
some patients.
 Pneumonia.
 Some patients had prominent GI
symptoms with abdominal pain, diarrhea,
and vomiting.
 Severe cases progressed to respiratory
distress in a week, physical examination
would find the consolidation signs.

Laboratory findings
Blood routine test
WBC counts are variable, frequently being low early
in illness.
 The leukopenia, Lymphopenia and
thrombocytopenia are risk factors associated with
severe disease and prognostic indicators for ARDS
and death.

Laboratory findings

Viral antibody:
fourfold rise in serum neutralizing antibody titer
toward the presently circulating genotype of
avian viruses.
The convalescent serum should be taken at least
14 days after the onset of illness.
Laboratory findings



Rapid antigen detection. Results can be
obtained in 15–30 minutes.
Immunofluorescence assay.
Enzyme immunoassay for NP
Virus culture: Provides results in 2–10 days
Polymerase chain reaction and Real-time
PCR assays.
Laboratory findings
Chest X rays
interstitial infiltration, lobar infiltration,
collapse/
consolidation, and air bronchograms, pleural
effusions
 CT
extensive pneumonic infiltration showing
segmental distribution, and air bronchograms

Laboratory findings
The 1st day after the admission
The 2nd day after the admission
The 4th day after the admission
Interstitial infiltrates were seen in the right lower lung fields on admission (A) .after the
treatment, there was prominent improvement observed in involved lung fields (B).
Extensive pneumonic infiltrations showing segmental and
multifocal distribution in CT.
CT in a 6 years Chinese boy
The CT at the 2nd week of the illness. Infiltrations in the
left lung.
Complications







ARDS
Lung hemorrhage
pleural effusions
Renal failure
Shock
sepsis
Reye syndrome
Diagnosis

Person under investigation
A person whom public health authorities have
decided to investigate for possible H5N1
1 exposure to the infectious sources
2 influenza-like symptoms


Suspected H5N1 case
A person presenting with unexplained acute lower respiratory
illness with fever (>38 ºC ) and cough, shortness of breath or
difficulty breathing
one or more of the following exposures in the 7 days prior to
symptom onset:
a. Close contact (within 1 metre) with a person who is a
suspected, probable, or confirmed H5N1 case
b. Exposure to poultry or wild birds or their remains or
to environments contaminated by their faeces in an area
where H5N1 infections in animals or humans have
been suspected or confirmed in the last month;
c. Consumption of raw or undercooked poultry
products in an area where H5N1 infections in
animals or humans have been suspected or
confirmed in the last month
d. Close contact with a confirmed H5N1 infected
animal other than poultry or wild birds
e. Handling samples suspected of containing
H5N1 virus in a laboratory or other setting.
Probable H5N1 case
A person meeting the criteria for a suspected case
a. infiltrates or evidence of an acute pneumonia on chest
radiograph plus evidence of respiratory failure
(hypoxemia, severe tachypnea )
b. positive laboratory confirmation of an influenza A
infection but insufficient laboratory evidence for H5N1
infection.
Probable definition 2:
A person dying of an unexplained acute respiratory
illness who is considered to be epidemiologically linked
by time, place, and exposure to a probable or
confirmed H5N1 case.

Confirmed H5N1 case
 A person meeting the criteria for a suspected or
probable case
a. Isolation of an H5N1 virus;
b. Positive H5 PCR results from tests using two
different PCR targets,
c. A fourfold or greater rise in neutralization
antibody titer for H5N1
. d. A microneutralization antibody titer for H5N1
of 1:80 or greater at day 14 and a positive result
using a different serological assay

Differential diagnosis







Influenza
Cold
Bacterial pneumonia
SARS
Infectious mononucleosis
chlamydia pneumonia
mycoplasma pneumonia
Treatment



Isolation
Symptomatic treatment:
Antiviral treatment
neuraminidase inhibitors (oseltamivir and
zanamivir)
Patients who had survived after oseltamivir treatment
appeared to have received the agent earlier than those
who subsequently died (4.5 days vs 9 days after disease
onset).
adamantanes (amantadine and rimantadine)
Summary of clinical management
advice






Oseltamivir remains the primary recommended
antiviral treatment.
Modified regimens of oseltamivir treatment
Corticosteroids should not be used routinely
Antibiotic chemoprophylaxis should not be used.
Monitoring of oxygen saturation should be
performed
Therapy for A(H5N1) virus-associated ARDS
prophylaxis



Control the infection sources
Cut off the transmission
Protect the susceptible people