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Influenza

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Acute respiratory illness caused by influenza viruses. ... changes, including granulation, vacuolization, swelling, and pyknotic nuclei. ... – PowerPoint PPT presentation

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Title: Influenza


1
Influenza
  • 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

3
Definition
  • Acute respiratory illness caused by influenza
    viruses.
  • Typical symptoms-fever, chills, myalgia,
    headache, sore throat, cough.
  • Serious cases in young children and elderly.

4
Etiologic agent
5
Etiologic agent
6
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

Virus subtype
Geographic origin
Strain number
Year of Isolation
7
Epidemiology
  • Source of infection patients and covert
    infection carrier.

8
Epidemiology
  • 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.

9
Epidemiology
10
Street 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.

12
The epidemic of influenza in China
13
Pathogenesis
14
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.

15
Manifestations
  • 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.

16
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.

17
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.

18
  • Mild form influenza
  • Other forms
  • stomach flu
  • encephalitis, transverse myelitis,
  • myocarditis and pericarditis,
  • myositis

19
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.

20
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.

21
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.

22
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.

23
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.

24
Diagnosis
  • Influenza season winter and spring
  • Clinic manifestations
  • Laboratory findings

25
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.

26
  • Leptospirosis
  • calf muscle tenderness,
  • lymphadenopathy

27
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 (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.

30
Prophylaxis
  • Vaccination

31
Human avian influenza
32
Definition
  • Influenza caused by influenza virus A adapted to
    birds.

33
Etiology
  • 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

35
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?

36
Epidemiology
  • 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.

37
wild waterfowl likely plays a role in the avian
influenza cycle and could be the initial source
for AI viruses.
38
virus may be passed on through contact with
resident waterfowl or domestic poultry
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Cumulative 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.

43
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

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.

47
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.

48
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.

49
Laboratory 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.

50
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

51
Laboratory findings
The 1st day after the admission
The 2nd day after the admission
52
The 4th day after the admission
53
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).
54
Extensive pneumonic infiltrations showing
segmental and multifocal distribution in CT.
55
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56
CT in a 6 years Chinese boy
The CT at the 2nd week of the illness.
Infiltrations in the left lung.
57
Complications
  • ARDS
  • Lung hemorrhage
  • pleural effusions
  • Renal failure
  • Shock
  • sepsis
  • Reye syndrome

58
Diagnosis
  • 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

63
Differential diagnosis
  • Influenza
  • Cold
  • Bacterial pneumonia
  • SARS
  • Infectious mononucleosis
  • chlamydia pneumonia
  • mycoplasma pneumonia

64
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)

65
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

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prophylaxis
  • Control the infection sources
  • Cut off the transmission
  • Protect the susceptible people
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