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1. Influenza Virus A (H1N1)
Clinicopathologic
Conference
(Medical Unit 2, Sir
Ganga Ram Hospital,
Lahore)
Associate Professor Dr.
Tahir Bashir
Contributed by: Dr. Madah

2. Influenza• Seasonal influenza is an acute respiratory infection caused by influenza
viruses that affect mainly the nose, throat, bronchi & occasionaly the
lungs
Classification: (on the basis of core Ribonucleoprotein & Matrix
protein)
Influenza virus A, B, C & D
The subtypes of influenza A viruses are determined by envelope
glycoproteins possessing either haemagglutinin (HA) or
neuraminidase (NA) activity
• There are 16 (HA) and 9 (NA) Antigens
• Subtypes H1, H2 or H3, and N1 or N2 infect humans
• Currently circulating in humans are subtype A(H1N1) and
A(H3N2) influenza viruses.
• The A(H1N1) caused the pandemic in 2009 and subsequently
replaced the seasonal influenza A(H1N1) virus which had
circulated prior to 2009.

4. Influenza viruses
belong to the family
Orthomyxoviridae (A
family of RNA viruses)
• Minor point mutations
(“antigenic drift”)
enables the virus to
evade immune
recognition, resulting
in repeated influenza
outbreaks during
interpandemic years.

5. • Major changes in the
HA antigen (“antigenic
shift”) are caused by
reassortment of genetic
material from different
A subtypes.
• Result in new pandemic
strains
• Rare events
• Occur through
reassortment between
animal and human
subtypes.

7.  Influenza A (H1N1) virus: emerged in 2009.
It is a new reassortment that has never before
circulated among humans, not closely related to
previous or current human seasonal influenza
viruses
 Influenza B viruses: sporadic cases
 Influenza C virus: detected less frequently and
usually causes mild infections
 Influenza D viruses primarily affect cattle and
are not known to infect or cause illness in people


9. Mode of transmission:
• Droplet/ aerosol/ airborne
infection: via coughing &
sneezing
• Contact:
 Direct (Hand to hand)
 Indirect (Hand to surface to
hand)
Incubation Period:1-7 days
Communicability:
• From 1 day before to 7 days
after the onset of symptoms
• Chances may persist till
complete resolution of
symptoms

10. Epidemiology/ Agent Factors
Reservoir of infection:
• Humans- Primary reservoir for human
infections
• Major reservoir: animals & birds (Swine,
horses, dogs, cats, domestic poultry, water &
wild birds)
Source of infection:
• A case or a subclinical case

11. Pathogenesis
• Infects the respiratory tract
• Even 3 or few viral particles can infect
• Neuraminidase facilitates infection by reducing
the viscosity of mucous
• Ciliated cells are infected in the respiratory
tract
• When superficial layers are damaged, exposes
the basal layers & causes bacterial infections

12. Case Definitions
Suspected Case
• A person with
acute febrile
illness(fever)
with sorethroat,
cough, headache
& myalgias
Probable Case
• In addition to meeting the
criteria of suspected case,
one of the following:
• H/o close contact with a
confirmed case in last 7 days
• H/O travel to a community
having 1 or more confirmed
cases in last 7 days or
residence in it
• Individual who died of an
unexplained acute
respiratory illness despite
having a clinically
compatible illness
Confirmed Case
•A person with an
acute febrile
respiratory illness
with laboratory
confirmed
pandemic influenza
A (H1N1) infection
by 1 or more:
•Real Time- PCR
•Viral Culture
•Four fold rise in
Pandemc influenza
A (H1N1) virus
specific neutralizing
antibodies

13. In 2009, cases of influenza like
illness were first reported in
Mexico on March 18; the
outbreak was subsequently
confirmed as H1N1 influenza A
On June 11, 2009, WHO raised
the pandemic alert level to
phase 6 (indicating a global
pandemic) because of
widespread infection beyond
North America to Australia, the
United Kingdom, Argentina,
Chile, Spain, and Japan.
As of September 1, 2009, the
WHO reported that H1N1
influenza had been confirmed in
over 200,000 people in more
than 100 countries and that they
are aware of at least 2185
confirmed deaths.

14. Clinical Features
• Asymptomatic infection
• Uncomplicated upper respiratory tract disease
Influenza‐like illness (ILI) symptoms include:
 Fever ≥ 38°C
 cough, sore throat, nasal congestion or rhinorrhea
 headache
 muscle pain and malaise
 NO DYSPNEA/ SOB
 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.
 Some patients with uncomplicated illness may experience atypical
symptoms and may not have fever (e.g. elderly or
immunosuppressed patients)

16. Complicated or severe influenza
o Presenting features (dyspnoea, tachypnoea, hypoxia) and/or
radiological signs of lower respiratory tract disease (e.g. pneumonia)
o CNS involvement
(e.g. encephalopathy, encephalitis)
o Severe dehydration
o Presenting secondary complications, such as
renal failure, multi-organ failure and septic shock
o Other complications
can include rhabdomyolysis and myocarditis.
o Exacerbation of underlying chronic disease, including asthma,
chronic obstructive pulmonary disease (COPD), chronic hepatic or
renal insufficiency, diabetes, or other cardiovascular conditions (e.g.
congestive cardiac failure).
Signs and symptoms of progressive disease
Patients who present initially with uncomplicated influenza may
progress to more severe disease: rapid (i.e. within 24
hours).

17. Indicators of progression
Symptoms and signs suggesting oxygen impairment or
cardiopulmonary insufficiency:
 Shortness of breath (with activity or at rest)
 Tachypnoea
 Cyanosis
 Bloody or coloured sputum, chest pain, and low blood pressure
 Hypoxia as indicated by pulse oximetry or arterial blood gases
Symptoms and signs suggesting CNS complications:
 Altered mental status
 Recurring or persistent convulsions (seizures)
 Confusion, unconsciousness
 Weakness or paralysis
Severe dehydration:
 decreased activity, dizziness, decreased urine output and lethargy
Evidence of sustained virus replication or invasive secondary
bacterial infection:
 based on laboratory testing or clinical signs persistent or recurrent
high fever and other symptoms beyond 3 days

18. Workup/ Diagnostic Modalities
• Hematological:
CBC counts nonspecific but leukopenia & relative lymphopenia are
nonspecific.
Thrombocytopenia maybe present
• Microbiological: Isolation of the viral culture (Confirmatory:
may take more than 7 days)
• Biochemical: Raised hepatic enzymes
• Radiological: Chest Xrays
• Confirmation of pandemic Influenza A H1N1 is through
 Nasal, Nasopharyngeal & throat swabs, wash/ aspirate
 Tracheal aspirate
 RT-PCR, RIDTs
 Paired serum for serological testing at an interval of 14
days: four fold rise in influenza specific antibodies

19. Rapid influenza diagnostic tests (RIDTs)
are antigen detection tests that detect influenza viral
nucleoprotein antigen
 Can provide results within 30 minutes or less
 Cannot distinguish between influenza A virus subtypes
cannot provide any information about antiviral drug
susceptibility
 low sensitivity than viral culture or RT-PCR
Real-time reverse transcriptase-polymerase chain
reaction (rRT-PCR):
 Detection of influenza-specific RNA
 Can provide results within 4 hours

21. Sample Collection
• The sample should be collected by a trained
physician/ microbiologist preferably before
administration of the antiviral drug
• Swab with synthetic tip made of calcium
alginate is ideal within 5 days of the onset of
symptoms
• Keep at 4°C
• in viral transport media upto 24 hours
• If more than that, store at -70°C

22. Treatment guidelines
• Infection control precautions: Early implementation
• Prompt treatment
• Early identification & follow up of persons at risk
• Infrastructure/ Manpower/ Material Support:
 Isolation facilities: Wards with beds kept 1 metre apart
 Manpower: Dedicated doctors & paramedics
 Equipment: Portable Xray machines, ventilators & pulse
oximeters
 Supplies: Adequate quantities of personal protection
equipment, disinfectants, medication

23. • Standard Operating Procedures
(SOPS):
 Reinforce standard infection control
precautions: high efficacy gowns, masks,
goggles, gloves, cap, shoe cover
 Restrict no. of visitors
 Antiviral prophylaxis to healthcare
personnel managing the cases
 Proper waste disposal

24. Supportive Treatment
IV fluids, plenty of oral fluids: Hydration & maintenance of
electrolyte balance
Supplemental O2 therapy: tachypnea, dyspnea, respiratory
distress, O2 saturation <90%
Mechanical ventilatory support: Severe pneumonia/ Acute
respiratory failure (SpO2 < 90% & PaO2 <60% with O2 therapy
Antibiotics for secondary infection, Vasopressors for shock
Paracetamol/ ibuprofen for fever, myalgia & headache
Avoidance of smoking
For sorethroat: short course of topical decongestants, saline
nasal drops, throat lozenges & steam inhalation
Salicylate/ aspirin- contraindicated in children (potential to
cause Reye’s syndrome)
Constant monitoring of suspected cases for clinical/ radiologic
evidence of LRTI & for hypoxia (Respiratory rate, O2
saturation, level of consciousness)

25. Antiviral Treatment
 Prompt initiation within 48 hours of the onset of symptoms
 Recommended duration of treatment: 5 days
 Effective against Influenza A virus: Amantadine & Rimantadine
 Effective against Influenza A & B viruses: Oseltamivir (Tamiflu) &
Zenamivir (Relenza): Neuraminidase inhibitors

26. Pharmacological Management
(WHO guideline August 20th, 2009)
• Healthy people who catch mild to moderate
cases of swine flu don’t need the drug at all
• CDC has warned that the indiscriminate use of
antiviral medications to prevent & treat
influenza could ease the way for drug resistance
to emerge

27. Antiviral susceptibilities
of Circulating viruses:

28. Severe or Progressive symptoms
• Confirmed or Strongly suspected
• Severe or progressive
• Antivirals are available
• Treatment should be initiated as soon as possible
• Treat with oseltamivir
• Treat with Zanamivir if oseltamivir is not
available

29. Uncomplicated
• Confirmed or strongly suspected
• Uncomplicated
• Antivirals are available
• Need not be treated with antivirals (patient not in “at
risk” groups)
• Treated with oseltamivir or zanamivir (patients in “at
risk” groups)

30. Uncomplicated
• At Risk means
• Infants & children aged less than 5
• Elderly (more than 65)
• Nursing home residents
• Pregnant women
• Patients with chronic comorbid
conditions
• Immunosuppression

31. Oseltamivir is the recommended drug of choice both for prophylaxis &
treatment. However in view of increasing resistance Relenza
(Zenamivir) in the dosage of 5mg BD may be preferred.
Dosage of Oseltamivir: (By weight)
For weight <15 kg : 30 mg BD for 5 days
For weight 15-23 kg : 45 mg BD for 5 days
For weight 24- <40 kg : 60 mg BD for 5 days
For weight>40kg : 75 mg BD for 5 days

32. Inhaled Zanamivir (Relenza) Dosage
Influenza A & B, treatment
• Start within 2 days of symptom onset: administer 2 doses
on day 1, at least 2 hours apart
• 10 mg inhaled 12 hourly for 5 days. May consider longer
treatment for patients severely ill after 5 days
Influenza A & B (Prophylaxis)
House hold settings: 10mg inhaled qDay for 10 days
Initiate within 36 hours of exposure
Community Outbreaks: Begin within 5 days of outbreak;
May administer for upto 28 days

33. Oseltamivir/ Prophylaxis dosage
• H1N1 influenza (swine flu) prophylaxis:
75mg PO qDay
• Post exposure prophylaxis:
Start within 7 days and continue for at least 10
days
Incase of community outbreak: may be
administered for upto 6 weeks

34. Chemoprophylaxis
Indications
• Risk of human to human transmission is high or low
but the likelihood of complications is high
• Oseltamivir or zanamivir might be used
• For health care personnel at high risk only if not
previously vaccinated
• For contacts only if clinically indicated
• Zanamivir can also be given for chemoprophylaxis
(10mg, 2 inhalations OD)

35. Chemoprophylaxis
Contraindications
If the likelihood of complications of
infection is low even if
• “At risk” group
• Healthcare workers
• This recommendation applies independent
of human to human transmission

36. Adverse Effects of Oseltamivir:
 Gastrointestinal Side Effects ( Transient Nausea,
Vomiting)
 Occasionally, insomnia & vertigo
 Rare reports of anaphylaxis & rash
 Infrequently, abdominal pain, epistaxis, otitis media,
dermatitis, conjunctivitis
 Should be given cautiously in patients with advanced
renal disease
Discharge Policy:
Response to treatment after 2-3 days of initiation &
patient becomes asymptomatic should be discharged after
5 days of treatment

37. Influenza Vaccines

40. Guidelines on Infection Control Measures
During Pre-hospital care:
• PATIENT SHOULD WEAR A SURGICAL MASK
• Aerosol generating procedures should be avoided during
transportation
• The personnel in the patient’s cabin of ambulance should wear full
complement of PPE. Driver should wear 3 layered surgical mask
• The interior & exterior of the ambulance plus reusable patient care
equipment needs to be sanitized using sodium hypochlorite /
quaternary ammonium compounds
During Hospital Care:
• Admitted directly to isolation facility, MUST WEAR A MASK
• Medic/ paramedic personnel attending the suspected, propbable or
confirmed case should wear full complement of PPE

41. • Aerosol generating procedures such as Endotracheal intubation,
suctioning, nebulization, chest physiotherapyshould be performed
with the health personnel wearing the full complement of PPE with
N95 mask on
• Hand hygiene, Hand washing: Alcohol based sanitizers
• Infection control precautions should continue for 7 days in adults and
14 days in children<12 years after the resolution of symptoms
• Disinfection of contaminated surfaces and equipments should be done
after discharge (Disinfectants used: 70% ethanol, 10% Sodium
hypochlorite)
• All waste generated from influenza patients in isolation wards/ rooms
should be considered as infections waste & treated & disposed off.

42. Personal Protection Equipments (SOPS)
• Gloves (Nonsterile)
• Mask (High
efficiency/surgical
masks)
• Long-sleeved, cuffed
gown
• Protective eyewear
(goggles, face shields)
• Cap (Maybe used in
high-risk situations/
increased aerosols)
• Plastic apron if splashing
of blood, body fluids,
excretions & secretions
is anticipated
• Shoe covers

43. Correct procedure for
applying PPE
1. Hand wash
2. Wear coverall
3. Wear goggles
4. Shoe-cover
5. Head-cover
6. Face mask
7. Gloves
Correct procedure for
removing PPE
1. Remove gown
2. Gloves
3. Hand wash
4. Cap & face shield
5. Remove mask
6. Hand wash
7. Leave the room
8. Hand wash

44. • Guidelines for infection control practices:
• 1. At individual level
1.1: Hand Hygiene: Frequent hand washing with soap & water/
alcohol based hand rubs/ antispetic hand wash & dry thoroughly

46. Or do you wanna end up like them?

47. 1.2 Respiratory Hygiene/
Cough etiquette:
Cover the nose or mouth with a
handkerchief/ tissue paper when
coughing/ sneezing
Use tissues to dispose
respiratory secretions & dispose
of them in the nearest waste
receptacle after use
Perform hand hygiene
1.3: Staying away:
Stay arms length away from
individuals showing influenza
like illness
1.4. Use of mask:
N95 mask for health personnel
working in screening areas&
isolation facilities

48. • 2. At Health Facility:
• 2.1 Droplet precaution:
• Wearing a surgical/
procedure mask
• 2.2: Waste Disposal:
• All waste from isolation
wards, been treated as
infectious waste, to be
decontaminated.
• Articles like swabs and
gauzes discarded in
yellow bag & gloves,
face masks & disposable
syringes discarded in
blue/ white autoclavable
biosafety bags.

50. Putting on PPE

51. Taking off PPE