Title: Influenza
1Influenza
- SHU Xin MD
- The department of infectious diseases,
- 3rd affiliated hospital of SUN Yet-Sen university
-
2- Definition
- Etiology
- Epidemiology
- Pathology and pathogenesis
- Clinical manifestations
- Complications
- Laboratory findings
- Diagnosis and differential diagnosis
- Treatment
- Prophylaxis
3Definition
- Acute respiratory illness caused by influenza
viruses. - Typical symptoms-fever, chills, myalgia,
headache, sore throat, cough. - Serious cases in young children and elderly.
4Etiologic agent
5Etiologic agent
6Etiologic agent
- Influenza A viruses are subdivided on the basis
of the HA and NA antigens. - Designation
- Species/ A/Beijing/32/92(H3N2)
- virus type
Virus subtype
Geographic origin
Strain number
Year of Isolation
7Epidemiology
- Source of infection patients and covert
infection carrier. -
8Epidemiology
- Transmission primarily via respiratory droplets.
- person to person( hand-to-hand, hand-to-mouth)
- direct contact
- aerosolssneezing, coughing.
- susceptible the immunity in the population at
risk is the major determinant of the extent and
severity of an outbreak. -
9Epidemiology
10Street car conductor in Seattle not allowing
passengers aboard without a mask in 1918
11- 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.
12The epidemic of influenza in China
13Pathogenesis
14Pathogenesis
- 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.
15Manifestations
- Incubation period1-3 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.
16Manifestations
- 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.
17Manifestations
- 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.
18- Mild form influenza
- Other forms
- stomach flu
- encephalitis, transverse myelitis,
- myocarditis and pericarditis,
- myositis
-
19Complications
- 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. -
20Complications
- 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.
21Laboratory 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.
22Laboratory 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.
23Laboratory 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.
-
24Diagnosis
- Influenza season winter and spring
- Clinic manifestations
- Laboratory findings
25Differential 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.
26- Leptospirosis
- calf muscle tenderness,
- lymphadenopathy
27Treatment
- 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 (reyes syndrome). - codeine-containing compounds
- Antibiotics for the secondary bacterial
infection. -
28- 2 antiviral therapy
- M2 inhibitors amantadine and rimantadine
- Side effects
- rimantadine only for adults.
- Dose 200mg/d for 3-4 days.
29- 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.
30Prophylaxis
31Human avian influenza
32Definition
- Influenza caused by influenza virus A adapted to
birds.
33Etiology
- Avian influenza virus A
- Highly pathogenic avian influenza( HPAI )
- H5N1
- H7N7
- H9N2
34- Distinguish the avian flu and the human flu
- HA
- avian flu a2-3 sialic acid receptors
- human flu a2-6 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
35Epidemiology
- 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?
36Epidemiology
- Susceptible
- people are all susceptible, especially in
children lt 12 years. - People who direct contact with infectious
secretions and excreta from infected birds or
contaminated poultry products are at high risk. -
-
37wild waterfowl likely plays a role in the avian
influenza cycle and could be the initial source
for AI viruses.
38virus may be passed on through contact with
resident waterfowl or domestic poultry
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41Cumulative Number of Confirmed Human Cases of
Avian Influenza A/(H5N1) Reported to WHO(
Cases/Deaths)
42- 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.
43Pathogenesis 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
-
44- 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.
45- A/H7N7 infections mainly result in conjunctivitis
and/or an influenza-like illness.
46- 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. -
47Laboratory 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.
48Laboratory 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.
49Laboratory findings
- Rapid antigen detection. Results can be obtained
in 1530 minutes. - Immunofluorescence assay.
- Enzyme immunoassay for NP
- Virus culture Provides results in 210 days
- Polymerase chain reaction and Real-time PCR
assays. -
50Laboratory 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
51Laboratory findings
The 1st day after the admission
The 2nd day after the admission
52The 4th day after the admission
53Interstitial 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).
54Extensive pneumonic infiltrations showing
segmental and multifocal distribution in CT.
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56CT in a 6 years Chinese boy
The CT at the 2nd week of the illness.
Infiltrations in the left lung.
57Complications
- ARDS
- Lung hemorrhage
- pleural effusions
- Renal failure
- Shock
- sepsis
- Reye syndrome
58Diagnosis
- Person under investigationA person whom public
health authorities have decided to investigate
for possible H5N1 - 1 exposure to the infectious sources
- 2 influenza-like symptoms
59- Suspected H5N1 caseA person presenting with
unexplained acute lower respiratory illness with
fever (gt38 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
60- 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.
61- 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 2A 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.
62- 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 180 or greater at day 14 and a positive
result using a different serological assay
63Differential diagnosis
- Influenza
- Cold
- Bacterial pneumonia
- SARS
- Infectious mononucleosis
- chlamydia pneumonia
- mycoplasma pneumonia
64Treatment
- 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)
65Summary 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
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70prophylaxis
- Control the infection sources
- Cut off the transmission
- Protect the susceptible people