INFECTION

1. INFLUENZA H1N1
DR. SUBODH KUMAR MAHTO
PGIMER,DR.RML HOSPITAL
NEW Delhi

2. • Commonly known as flu
• Word INFLUENZA given by Italians in 1743
• Upper and / or lower respiratory tract involvement
accompanied by systemic symptoms
• Occurs in seasonal and pandemic form
• Initially influenza considered to be caused by
Pfeiffer bacillus
• Influenza virus is RNA virus, having 8 genes.
Influenza

3. Influenza virus
• Orthomyxoviridae
• Enveloped RNA virus with segmented genome
• Three types of influenza A, B & C
• Size 80-200 nm in diameter
• Virus contains two surface antigens H
(hemagluttinin) and N (neuraminidase)

4. Influenza A ,B , C
Influenza A Influenza B Influenza C
18 H antigen
subtypes
Less Intratypic
variations
No Intratypic
variation
11 N antigen
subtypes
Major
epidemics
associated
Seasonal
outbreaks
Sporadic
cases

5. • Segmented genome
• Genetic re-assortment
• Antigenic drift
• Antigenic shift
• Propensity of causing pandemics
Special features of Influenza virus

6. Antigenic Shift and Antigenic Drift
Antigenic shift Antigenic drift
Major antigenic variation Minor antigenic variation
Re-assortment Point mutations over period
of time.
Epidemics and Pandemics Seasonal outbreaks(Inter
pandemic)
Influenza A only Influenza A , B

7. Human
virus
Avian
virus
Mechanisms of Antigenic
Shift
Swine
virus
Reassorted
virus

8. Terminology
• Epidemic refers to an increase, often sudden, in the
number of cases of a disease above what is normally
expected in that population in that area
• Outbreak carries the same definition of epidemic,
but is often used for a more limited geographic area
• Pandemic refers to an epidemic that has spread over
several countries or continents, usually affecting a
large number of people
Cdc/gov/epidemiology

9. Seasonal Influenza
– A public health
problem each year
– Usually some
immunity built up from
previous exposures to
the same subtype
– Infants and elderly
most at risk
Influenza Pandemics
– Appear in the human
population rarely and
unpredictably
– Human population
lacks any immunity
– All age groups,
including healthy young
adults
Seasonal Epidemics vs. Pandemics

10. Pre-requisites to start Influenza
Pandemic
Emergence of a novel virus to
which population is susceptible
Able to replicate and cause
disease
Transmitted efficiently from
human-to-human
www.cdc.gov/h1n

11. Circulating Influenza Strains and
Pandemics in The 20th Century
1920 1940 1960 1980 2000
H1N1
H2N2
H3N2
1918: “Spanish Flu” 1957: “Asian Flu” 1968: “Hong Kong Flu”
20-40 million deaths 1-4 million deaths 1-4 million deaths

12. “Swine flu” & “Novel H1N1”
• The first cases of human infection with H1N1
Influenza A is noted on 18th March 2009 from
Mexico.
• In India first case reported on 16th May 2009 from
Hyderabad.
• Originally called "swine flu" because it's a
descendant of viruses that have long infected pigs
• The virus is now called "novel H1N1.“
• Post pandemic phase- part of the circulating
influenza viruses.

13. Pathogenesis
• Enters the respiratory epithelial cell via
hemagglutinin
• 4-6 hours after replication infected virions are
released
• Cells become necrotic and desquamate
• Alter respiratory defense mechanism
• Systemic features due to induction of cytokines
• Antibodies to hemagglutinin – Protective
• Antibodies to neuraminidase – Limit viral spread
Robbins and cotran pathologic basis of dis

14. Clinical features
• Incubation period :1-4 days (upto 7 days)
• Communicability : 1 day before to 7 days after the
onset of symptoms. Prolonged in case of
immunosuppression(Prolonged shedding of virus)
• Transmission : droplet infection , air borne and
fomites

15. • Starts with systemic symptoms like fever with
chills,myalgias,malaise followed by upper respiratory
symptoms such as cough, running nose and sore
throat
• Respiratory symptoms more prominent as systemic
symptoms subside
• Some times with diarrhea(in children) and vomiting
• Associated with features of complications in the later
stage
• Elderly can present directly with complications
Clinical features

16. Symptoms of H1N1 in people

18. High risk groups/complications
• Children younger than 5 years old
• Adults 65 years of age and older
• Chronic medical disorders:
• Heart disease, kidney disease, lung disease
• Immunosuppression
• Pregnant women and 2 weeks post partum
• Morbid Obesity(body mass index is equal to or
greater than 40)
MMWR/cdc/gov 2015

19. Complications
1. Otorhinological :
– Sinusitis
– otitis media
– Croup
2. Respiratory:
– Primary influenza viral pneumonia
– Secondary bacterial pneumonia (with or without
sepsis)
– bronchiolitis
– status asthamaticus
– Respiratory failure

20. Continued…
3. cardiovascular:
– Myocarditis
– Pericarditis
4. Musculoskeletal:
– Myositis
– Rhabdomyolysis
5. CNS:
– Confusion
– Encephalitis
– Seizures
6. Renal insufficiency/toxic shock syndrome/Multi
organ failure.

21. COMPLICATIONS
• PULMONARY:
1. Primary influenza viral pneumonia-
-Least common but more severe
-presents as acute influenza that does not resolves
instead progresses
-sputum production is scanty, but the sputum can
contain blood.
-chest x ray shows diffuse interstitial infiltrate or ARDS
pattern.
-this is most commonly seen in people with underlying
cardiac disease.

22. 2. Secondary bacterial pneumonia
-improvement in patient condition over 2- 3
days is followed by reappearance of fever and
clinical signs and symptoms.
- presents as cough with production of
purulent sputum.
-x ray shows signs of consolidation.
-most common etiology includes streptococcus
pneumonia, staphylococcus auerus and
H.influenza.

23. Categorisation
• All individuals seeking consultation for flu-like
symptoms should be screened at health care
facilities and categorized under three
categories:
• Category-A :
– Patients with mild fever plus cough/sore throat
with or without body ache, headache, diarrhoea
and vomiting
– Do not require Oseltamivir (Tamiflu)
– should be given symptomatic treatment.
– These patients should be monitored for their
progress and reassessed by doctor after 24 to 48
hours.

24. Continued…
• Category B :
• Category B has two subcategories.
• Category BI -
– high grade fever and severe sore throat
• Category BII -
– high risk conditions ( 1 or more ):
• children < 5 yrs age
• pregnant women
• persons aged 65 years or older
• patients with lung/ heart/ liver / kidney disease/ blood
disorders/ neurological disorders
• Diabetes
• cancer / AIDS/ long term cortisone therapy.

25. Continued…
• Category C :
• Category-A/B + one or more of the following
problems:
– Breathlessness
– chest pain
– Drowsiness
– fall in blood pressure
– sputum mixed with blood
– bluish discoloration of nails
– irritability among small children
– refusal to accept food
– worsening of underlying chronic conditions.
• require testing, immediate hospitalization and
treatment.

26. When to test
• All category C patients should be tested
• Category A & B pts need not be tested
• Confirmatory tests for H1N1:
1. Real time RT-PCR(sensitive and specific)
2. Isolation of virus in culture(time consuming)
3. Four fold rise in virus specific antibodies
• Specimen:
– nasopharyngeal swab/ throat swab/ nasal swab,
wash or aspirate/ tracheal aspirate (for
intubated patients)

27. Continued…
• Specimen collection:
– sample should be collected before administration
of the anti-viral drug.
– Keep specimens at 4°C in viral transport media
until transported for testing.
– The samples should be transported to designated
laboratories with in 24 hours.
– If they cannot be transported then it needs to be
stored at -70°C.
– For serological testing, Paired blood samples at an
interval of 14 days should also be collected.

28. When to admit
• All patients of Category- A & B should confine
themselves at home and avoid mixing with
public and high risk members in the family.
• Only category C patients need to be
hospitalized.

29. Suspected case
Acute febrile respiratory illness: fever>38C,
 Within 7 days of close contact with a person who
is a probable or confirmed case of the new
influenza A (H1N1) virus infection
or
 Within 7 days of travel to a community where
there has been one or more confirmed influenza A
(H1N1) cases
or
Resides in a community where there are one or more
confirmed new influenza cases

30. • A probable case:
 a person with an acute febrile respiratory
illness who:
is positive for influenza A by an influenza rapid
test or an influenza immunofluorescence assay
(IFA) plus meets criteria for a suspected case
 individual with a clinically compatible illness who
died of an unexplained acute respiratory –illness
who is considered to be epidemiologically linked
to a probable or confirmed case.

31. Confirmed case
With laboratory confirmed influenza A (H1N1) virus
by one or more of the following:
• Real-time RT-PCR
• Viral culture
• Four-fold rise in new influenza A(H1N1) virus-specific
neutralizing antibodies

32. Treatment
• The guiding principles are:
– Early implementation of infection control
precautions to minimize nosocomial / household
spread of disease
– Prompt treatment to prevent severe illness &
death.
– Early identification and follow up of persons at
risk.

34. Continued…
• Oseltamavir medication:
– Category B & C
• Dose for treatment:
– By Weight:
• <15kg - 30 mg BD for 5 days
• 15-23kg - 45 mg BD for 5 days
• 24-40kg- 60 mg BD for 5 days
• >40kg - 75 mg BD for 5 days
– For infants:
• < 3 months - 12 mg BD for 5 days
• 3-5 months- 20 mg BD for 5 days
• 6-11 months- 25 mg BD for 5 days

35. Continued…
• Supportive therapy:
– IV fluids
– Parenteral nutrition
– Antibiotic prophylaxis for secondary infection
– Vasopressors for shock
– Paracetamol/ ibuprofen for fever/ myalgia/ headache
– Salicylate/ aspirin strictly C/I in influenza patient
(Reye’s syndrome)
– Patients with signs of tachypnea/ dyspnoea/
respiratory distress and oxygen saturation< 90%
should be supplemented with oxygen therapy
– Patients with severe pneumonia and acute respiratory
failure (SpO2 < 90% and PaO2 <60 mmHg with oxygen
therapy) must be supported with mechanical
ventilation

36. Ventilatory settings
• Ventilator Settings:- Low tidal volume ventilator
support ,Tidal volume - 6 ml/Kg ideal body weight
(Respiratory rate to a maximum of 30-35 per minute.)
• PEEP titration to keep the lung recruited to achieve an
FIo2 of < 0.5 and a saturation of >90%.
• Plateau (Pause) pressure not to exceed of >30-35
mmHg.
• Alternative modes of ventilation: IRV: Inverse Ratio
ventilation- in patients with persistent Hypoxemia
(Spo2 of < 90% with high pEEp &FIO> 0.8).
• Sedation,Neuromuscular Blockage & Prone ventilations
can be considered if above oxygen goals not met.

37. When to discharge
• Pt responding within 2-3 days of treatment –
– Discharge on 5th day
– No need for repeat test
• Pt still symptomatic on 5th day –
– t/t for 5 more days
– No need to test further if becomes asymptomatic
• Pt continues to be symptomatic after 10 days of
treatment or cases with respiratory distress –
– Test for resistance to antiviral therapy
– Dose to be adjusted on case to case basis

38. Why to Treat?
• Early treatment of hospitalized patients can reduce
death
• In hospitalized children, early antiviral treatment has
been shown to shorten the duration of
hospitalization
• Clinical benefit is greatest when antiviral treatment is
administered early, especially within 48 hours of
influenza illness onset
• Shorten the duration of fever and illness symptoms
(1- 1.5 day)
• Reduce the risk of complications from influenza (e.g.,
otitis media in young children, pneumonia, and
respiratory failure)

39. • Reviewers found evidence of publication and reporting biases
• Studies did not show that Tamiflu reduced the risk of
hospitalization
• Studies were inadequate to determine the effect of Tamiflu on
complications and reduce risk of transmission
• However, did reduce the duration of symptoms by about a
day
• Sponsored trails
• In prophylaxis trials, oseltamivir and zanamivir reduced the
risk of symptomatic influenza in individuals
Jefferson et al The Cochrane Libra

40. Dobson et al, Lancet 2015; 385:
• Data from nine trials including 4328 patients
• Oseltamivir in adults with influenza accelerates time to
clinical symptom alleviation
• Reduces risk of lower respiratory tract complications,
and admittance to hospital
• Increases the occurrence of nausea and vomiting
Lancet 2015; 385:
1729–37

41. Chemoprophylaxis
• Drug approved
– Oseltamivir is approved for prophylaxis of
influenza in individual > 1 year of age
– Zanamivir for > 5 years of age
• 84-89% efficacious against influenza A and B

42. Chemoprophylaxis
• Should be provided to –
– All close contacts (household /social contacts, family
members, workplace etc.) and contacts at high risk.
– All health care personnel coming in contact
• Oseltamivir is the drug of choice.
• Prophylaxis should be provided till 10 days after
last exposure (maximum period of 6 weeks)
• Dose by Weight:
– <15kg- 30 mg OD
– 15-23kg - 45 mg OD
– 24-40kg - 60 mg OD
– >40kg - 75 mg OD

43. Oseltamivir Zanamivir Peramivir
Route Oral Inhalational Intravenous
Treatment (>40
Kgs)
75 mg Twice
daily for 5 days
10 mg Twice
daily for 5 days
One 600 mg IV
infusion for 15-
30 minutes
Chemoprophyla
xis
(>40 Kgs)
75 mg Once
daily for 7 days
10 mg Once
Daily for 7 days
Not applicable
Side effects GI discomfort,
vertigo, delirium
Exacerbates
Asthma,COPD,
GI discomfort,
ent infections
Skin Rash, SJS
,nausea
,vomiting
Age group
recommended
Treatment: > 2
weeks
Prophylaxis: > 1
Treatment :>7
years
Prophylaxis:> 5
> 18 years

44. Vaccination
• Current strain
• A/California/7/2009 (H1N1)
• A/Switzerland/9715293/2013 (H3N2)-like virus
• B/Phuket/3073/2013-like (Yamagata lineage)
• B/Brisbane/60/2008-like (Victoria lineage) virus(For
quadrivalent vaccine)
• Antibodies develop in 2 weeks after vaccination.
• Vaccines are effective 70-80% in yrs when there is a
good match between vaccines and strains in
circulation.
• Vaccines changes every year.

45. Types of Vaccines
Factor Live attenuated Inactivated Influenza
vaccine
Route Intranasal spray Intramuscular
injection
Strains Four Three or Four
Approved age 2 – 49 years > 6 months
High risk individuals No Yes
Persons with asthma No Yes
Interaction with anti
virals
Yes No

46. Contra-indications for Vaccine
Inactivated vaccine
• Persons with
history of egg
allergy
• Previous severe
allergic reactions
to influenza
vaccine
Live attenuated vaccine
•<2 years of age
•>49 years of age
•Immunocompromised
persons
•Pregnant women
•Asthma
•History of egg allergy

47. • Antiviral chemoprophylaxis can be administered
simultaneously with inactivated vaccine
• Concurrent administration of chemoprophylaxis
and live attenuated vaccine may interfere
• Antiviral drugs should not be administered until
at least 2 weeks after administration of live
vaccine, and administration of live vaccine should
not begin until at least 48 h after antiviral drug
administration has been stopped
Vaccination

48. CDC Recommendations(7/7/2015)
Important recommendations
• Routine annual influenza vaccination for all persons aged >
6 months
• Vaccination offered by October
• Children aged 6 months to 8 years be given 2 doses
separated by 4 weeks interval
• Preference of live attenuated over inactivated influenza
vaccine is not recommended as there is no evidence
regarding superiority.

49. Indian Government policy
• MOHFW-Vaccination for health care
workers
• Routine vaccination to public not
advocated at present juncture
MOHFW:Ministry of Health and Family Welfare,In

50. Key Messages For Infection
Prevention And Control
• Vaccination
• Isolate suspected or confirmed cases in single
isolation rooms or specific isolation wards or
confinement to home
• Appropriate use of personal protective
equipment (PPEs) and hand washing, cough
etiquette
• Information education and communication

51. Recommendations for public gatherings
1. Hand hygiene –
– single most important
measure to reduce the risk
of transmission
– Avoid hand shaking
– Hands should be washed
frequently with soap and
water / alcohol based hand
rubs
2. Respiratory Hygiene/Cough
Etiquette
3. Stay arms length away
from those showing
symptoms of influenza like
illness
4. Use of mask

52. Guidelines for home care
• Large no. of cases are mild- cat A , B home
isolation.
• Patient should; stay home 7 days, isolate in
well ventilated room, wear mask, avoid
smoking, maintain arm’s length, avoid visitors,
wash hands frequently.
• Warning signs: Shortness of breadth, chest
pain, coughing blood, altered sensorium.
• All contacts need to monitor their health.

53. GUIDELINES ON INFECTION CONTROL
MEASURES-health facility.
• During Pre Hospital Care
– Three layer surgical mask(health care plus patient)
– Full complement of PPE(Personal Protection
Equipments )- person with patient in cabin
– No Aerosol generating procedures
– Three layered surgical mask for driver
– Ambulance equipment sanitized using sodium
hypochlorite / quaternary ammonium compounds

54. During Hospital care:
– Patient directed to Isolation facility and continue to
wear a three layer surgical mask
– Visual alerts in appropriate languages
– Hand wash
• Before and after patient contact
– Identified medical, nursing and paramedical personnel
attending the pt should wear full complement of PPE
(Personal Protection Equipments)
• Contaminated surfaces and equipments
• Disinfectants
– 70% ethanol, 5% benzalkonium chloride (Lysol) and
10% sodium hypochlorite

55. STEPS : Handwashing
Hand hygeine is single most
important measure to educe risk of
transmitting infection.
1. wash palms and fingers
2. back of hands
3. fingers and knuckles.
4. wash thumbs.
5. Finger tips.
6. wash wrist.

56. Isolation Rooms
Single isolation room with attached washroom Overview of Isolation
ward

57. Unidirectional Flow Of
Healthcare Personnel
Through Isolation WardTriage
Centre
Healthcare
Personnel
Flow of Heathcare personnel
Flow of Patient
Donning
Putting on PPEs
Doffing

58. Guidelines for mask
Surgical mask used for : health
care workers in community
settings, for patients at home
care, general public, for security
personnel at hospital, ambulance
drivers, mortuary workers.
N95 mask for health care
workers at isolation facilities
and critical care areas, sample
collection centres.

59. N-95 Filtering Masks

60. Wearing triple layer surgical mask
• Unfold the pleats, make sure that they are facing down.
• Fit flexible nose piece over nose bridge.
• Secure with tie strings.
• Ensure there are no gaps on either side of the mask, adjust to
fit.
• Change the mask after six hours.
• Disposable masks are never to be reused
• While removing the mask great care must be taken not to
touch the potentially infected outer surface of the mask
• To remove mask first untie the tie-string below and then the
tie string above and handle the mask using the upper strings.

61. Continued…
• Personal protection
equipments: (PPE)
– Gloves (nonsterile),
– Mask (high-efficiency mask) /
Three layered surgical mask
– Long-sleeved cuffed gown
– Protective eyewear
(goggles/face shields)
– Cap (may be used in high risk
situations where there may be
increased aerosols)
– Plastic apron if splashing of
blood, body fluids, excretions
and secretions is anticipated.
– Shoe covers

62. Special Precautions while using PPEs
Donning(Wearing PPEs):
• PPEs must be donned correctly in proper order
before entry into patient room
• Donning and doffing must be directly observed by
a trained observer
• Frequent use of Hand Hygiene

63. Hand
Disinfectio
n
Inner
Gloves
Googles,
shoe cover
Wear
coverall
Mask
change 6
hrly
Head cover
N95
Respirator
Outer
Gloves
Sequence of Wearing PPEs

64. Special Precautions while using PPEs
• Doffing(Removing PPEs):
• Designated area separate from donning area
• PPEs must be removed slowly and in correct
sequence
• Use hand disinfection after each step

65. Hand
Disinfectio
n
Remove
gown
Wash
hands
Gloves
Wash
hands.
Face shield
Cap
Remove
mask
Sequence of Removing PPEs

66. Take home message
• H1N1 now in post pandemic phase.
• Early detection of cases
• Categorization of cases-treat accordingly.
• Hospitalize only category C patients.
• Vaccination for high risk group.
• Implement infection control precautions.
• Prevention of nosocomial spread.
• Protect yourself, using PPE.
• Not to create panic.

67. Thank you