Influenza

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Influenza

• SHU Xin MD
• The department of infectious diseases,
• 3rd affiliated hospital of SUN Yet-Sen university
  

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• Definition
• Etiology
• Epidemiology
• Pathology and pathogenesis
• Clinical manifestations
• Complications
• Laboratory findings
• Diagnosis and differential diagnosis
• Treatment
• Prophylaxis

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Definition

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

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Etiologic agent
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Etiologic agent
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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
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Epidemiology

• Source of infection patients and covert
  infection carrier.

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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.

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Epidemiology
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Street car conductor in Seattle not allowing
passengers aboard without a mask in 1918
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• 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.

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The epidemic of influenza in China
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Pathogenesis
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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.

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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.

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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.

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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.

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

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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.

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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.

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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.

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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.

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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.

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Diagnosis

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

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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.

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• Leptospirosis
• calf muscle tenderness,
• lymphadenopathy

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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.

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• 2 antiviral therapy
• M2 inhibitors amantadine and rimantadine
• Side effects
• rimantadine only for adults.
• Dose 200mg/d for 3-4 days.

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• 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.

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Prophylaxis

• Vaccination

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Human avian influenza
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Definition

• Influenza caused by influenza virus A adapted to
  birds.

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Etiology

• Avian influenza virus A
• Highly pathogenic avian influenza( HPAI )
• H5N1
• H7N7
• H9N2

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• 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

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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?

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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.

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wild waterfowl likely plays a role in the avian
influenza cycle and could be the initial source
for AI viruses.
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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)
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• 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.

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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

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• 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.

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• A/H7N7 infections mainly result in conjunctivitis
  and/or an influenza-like illness.

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• 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.

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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.

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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.

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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.

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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

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Laboratory findings
The 1st day after the admission
The 2nd day after the admission
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The 4th day after the admission
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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).
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Extensive pneumonic infiltrations showing
segmental and multifocal distribution in CT.
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CT in a 6 years Chinese boy
The CT at the 2nd week of the illness.
Infiltrations in the left lung.
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Complications

• ARDS
• Lung hemorrhage
• pleural effusions
• Renal failure
• Shock
• sepsis
• Reye syndrome

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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

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• 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

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• 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.

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• 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.

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• 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

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Differential diagnosis

• Influenza
• Cold
• Bacterial pneumonia
• SARS
• Infectious mononucleosis
• chlamydia pneumonia
• mycoplasma pneumonia

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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)

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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