The document discusses H1N1 influenza A virus. It describes the virus's pathogenesis, including that it is an RNA virus belonging to the Orthomyxoviridae family. Major changes in surface proteins HA and NA can lead to antigenic shifts and pandemics, while minor changes cause antigenic drift and localized outbreaks. The 2009 H1N1 strain was a novel quadruple reassortant virus. Clinical presentation is usually similar to seasonal flu but gastrointestinal symptoms may be more common. Treatment involves oseltamivir, zanamivir or peramivir. Vaccination is recommended for at-risk groups.

1. H1N1
By Dr.Sunil Thomas George
Dr.C.Ramakrishnana’s Unit (M4)

2. Introduction
 Influenza is an acute respiratory illness caused by inz A or inz B virus that occurs in
outbreaks and epidemics worldwide, mainly in the winter season

3. Pathogenesis
 Human influenza viruses are single-strand RNA viruses that belong to the Orthomyxoviridae
family, consisting of the genera influenza A, B, and C viruses.
 Only influenza A and B viruses cause epidemics in humans.
 Based on their main antigenic determinants, the haemagglutinin (H or HA) and
neuraminidase (N or NA) transmembrane glycoproteins, influenza A viruses are further
subdivided into 18 H (H1–H18) and 11 N (N1–N11) subtypes

4. Pathogenesis
 Among influenza A viruses that infect humans, three major subtypes of hemagglutinins (H1,
H2, and H3) and two subtypes of neuraminidases (N1 and N2) have circulated stably in the
human population and are responsible for annual epidemics
 HA and NA are critical for virulence

5. Pathogenesis
 Influenza A viruses, in particular, have a remarkable ability to undergo periodic changes in
their antigenic envelope glycoproteins, the hemagglutinin and the neuraminidase.

6. Pathogenesis
 Major changes in the hemagglutinin and neuraminidase glycoproteins are referred to as
antigenic shifts,
 Minor changes are called antigenic drifts.
 Antigenic shifts are associated with epidemics and pandemics of influenza A
 Antigenic drifts are associated with more localized outbreaks of varying extent

7. Microbiology
 Influenza viruses have a segmented genome that can result in high rates of reassortment
among viruses coinfecting the same cell. Reassortment between animal and human viruses
may result in the emergence of pandemic strains.
 It was found that this new (novel) virus has gene segments from the swine, avain and
human flu virus genes, and hence named “Swine Flu”
 Scientists call this a ‘Quadruple reassortant’ virus and hence this new virus is christened
“influenza-A (H1N1) virus”

8. Incubation Period
 The estimated median incubation period was approximately 1.5 to 3 days.

9. Virus Shedding
 Influenza shedding begins the day prior to symptom onset and often persists for five to
seven days or longer in immunocompetent individuals
 Even longer periods of shedding may occur in children, elderly adults, patients with chronic
illnesses, and immunocompromised hosts.

10. Mortality
 High rates of morbidity and mortality were noted among children and young adults
worldwide
 Although the majority of reported deaths occurred in individuals with underlying health
problems, up to one-third of hospitalized patients had no underlying chronic illness.

11. Mortality
 The mortality rate from the H1N1 influenza A pandemic among pregnant women was higher
than among the general population.
 Obesity was found to be an independent risk factor for severe infection.
REFERENCE:
Louie JK, Acosta M, Samuel MC, et al. A novel risk factor for a novel virus: obesity and 2009
pandemic influenza A (H1N1). Clin Infect Dis 2011; 52:301.

12. Pandemic vs Seasonal
 Pandemic H1N1 influenza A infections were uncommon in persons older than 65 years,
possibly as a result of preexisting immunity against antigenically similar influenza viruses
that circulated prior to 1957

13. Pandemic vs Seasonal
 The signs & symptoms of influenza caused by pandemic H1N1 A virus was similar to that of
seasonal influenza, although gastrointestinal manifestation appear to be more common with
pandemic H1N1 Influenza A.
 In a study that compares patients with pandemic H1N1 with patients having seasonal
influenza infection , those with pandemic H1N1 influenza A had higher rate of
extrapulmonary complications, ICU admission and death despite being younger and having
fewer comorbidities.

14. Clinical Diagnosis
A. During outbreaks – During an inz outbreak, acute febrile respiratory illnesses can be
diagnosed as influenza with a high likelihood by clinical criteria- Fever and cough within
48hrs of development of symptoms malaise, chills.
A Study suggests that presence of sneezing made influenza (pandemic) less likely
B. Sporadic cases- of influenza cannot be differentiated from infection caused by other
respiratory viruses like rhinovirus or coronavirus on clinical grounds alone

15. Risk Groups
 Patients with comorbidities
 Immunocompromised hosts
 Pregnant women
 Healthcare workers
 Indigenous populations
 Older populations
 Obesity
 Smoking
REFERENCE:
October 21, 1982NEJM 1982; 307:1042-1046
DOI: 10.1056/NEJM198210213071702

16. Imaging
 Infiltrates suggestive of pneumonia or acute respiratory distress syndrome (ARDS) on chest
radiography
 Common CT findings included patchy consolidation or ground glass opacities, with or
without consolidation; there was a lower lung zone predominance, and the most commonly
affected regions were the peripheral and central perihilar areas

17. Laboratory findings
 Elevated alanine aminotransferase
 Elevated aspartate aminotransferase
 Anemia
 Leukopenia
 Leukocytosis
 Thrombocytopenia
 Thrombocytosis
 Elevated total bilirubin

18. Laboratory tests
1) Molecular assays –
a) Conventional RT-PCR : It is the most sensitive and specific test – it is a rapid test and takes 1-8
hours
-it can differentiate between influenza types and subtypes including pandemic H1N1, H5N1 avian
infection and H7N9 avian influenza
b) Rapid molecular assay : Have been developed which provide results in less than 20 min. They
either use
Isothermic
nuclear acid
amplicication
Modified RT-
PCR

19. Laboratory tests
2) Rapid antigen test: Immunoassay that can identify inz A & B viral nucleoprotien antigens in
respiratory specimens
NOTE: Results are qualitative. Takes less than 15 min . Much lower sensitivity that RT PCR,RMA and
viral culture

20. Laboratory tests
3) Immunofluorescence – (Direct/Indirect): IMF antibody staining for INZ
4) Digital Immunoassay : Instrument based digital scan of the test strip
5) Viral Culture: Inz virus can be cultured from
a) Nasal washing
b) Throat swab
c) BAL
6) Serology: not useful in acute illness

21. Whom to test?
 During influenza season:
1. Immunocompetent outpatients who are at high risk for infection, AFRI and present within 5 days
on illness onset
2. Immunocompromised outpatient with AFRI regardless of time since onset
3. Inpatients with an AFRI including those with signs of CAP, regardless of time since illness onset
 At anytime of the year:
1. Inz testing should be done in healthcare workers if they present within 5 days of illness onset

22. Choice of diagnostic test?
 RT-PCR or Rapid molecular assay over antigen detection test

23. When to test?
 Testing should be done as soon as possible since viral shedding peaks at 24-48hrs of
illness

24. When to treat ?
 Treatment should not be delayed while awaiting test results
 Work up & treatment should not be stopped based on negative rapid test results due to its
limited sensitivity

25. Treatment

26. Indications
 Based on the CDC guidelines, prompt initiation of antiviral therapy was recommended for
children, adolescents, or adults with suspected or confirmed influenza infection
 It was also recommended that early treatment be considered in patients with suspected or
confirmed influenza infection who were at high risk for complications
 It was recommended that for severely immunosuppressed patients (eg, those receiving
treatment for malignancies, hematopoietic or solid organ transplant recipients) presenting
with an acute respiratory illness, antiviral therapy be started as soon as possible.

27. Antiviral agents
 Oseltamivir
 Zanamivir
 Peramivir
Zanamivir was the preferred agent for patients with oseltamivir-resistant pandemic H1N1
influenza A infection 10 mg (2 x 5-mg inhalations) twice daily for 5 days
. In those who were unable to use inhaled zanamivir (eg, critically ill patients, patients with a
history of bronchospasm), the intravenous formulation was considered appropriate.

28. Oseltamivir Medication
Oseltamivir is the recommended drug for treatment.
Dose for treatment is as follows -
By Weight:
For 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

29. Antibacterial therapy
 It was recommended that patients with H1N1 influenza A who developed pneumonia be
treated empirically for community-acquired pneumonia (CAP) given the risk of secondary
bacterial pneumonia with organisms such as Streptococcus
pneumoniae and Staphylococcus aureus

30. Protocol for the ventilator management of patient with ALI/ARDS following
Seasonal Influenza:
Indications for Mechanical Ventilation:
Severe Respiratory Failure
Failure to achieve oxygen saturation of > or equal to 90% (or pO2 of > or equal to 60 mm
Hg) on an FIO2 < 0.6.
Ventilator Settings:
1. Pressure pre-set (controlled)
2. Low tidal volume ventilator support
3. Tidal volume — 6 ml/kg ideal body weight (Respiratory rate to a maximum of 30-
35 per minute).
4. Open lung strategy of ventilation with PEEP titration to keep the lung recruited to
achieve an FIO2 of < 0.5 and a saturation of > 90% or a PaO2 of > 60 mmHg
5. Plateau (Pause) pressure not to exceed of > 30-35 mmHg.
6. Alternative modes of ventilation APRV (Airway Pressure Release Ventilation), IRV
(Inverse Ratio Ventilation) in patients with persistent Hypoxemia (SpO2 of < 88-
90% with high PEEP & FIO2 > 0.8).
7. Rescue therapy — recruitment manoeuvres, Sedation, Neuromuscular Blockage
& Prone Ventilations can be considered if above oxygen goals are not met.

31. Other treatment modalities
 Extracorporeal membrane oxygenation
 N-acetyl cysteine
 Further study is necessary to determine whether glucocorticoids are harmful or beneficial in
patients with influenza infections.

32. Discharge policy
 Adult patients should be discharged 7 days after symptoms have subsided.
 Children should be discharged 14 days after symptoms have subsided.

33. Antiviral prophylaxis
 Considered for adults and children who had close contact with a confirmed or suspected
case AND also fell into one of the following categories
 Adults who are at high risk for complications of influenza (eg, individuals with certain chronic medical
conditions or who are greater than 65 years of age)
 Pregnant women and women who are up to two weeks postpartum (including following pregnancy loss)
 Children who are <5 years of age or who are at high risk of complications of influenza
 Healthcare workers and emergency medical personnel

34. Vaccination
 Groups recommended to receive influenza vaccine –
 Individuals (≥ 6 months old) in risk groups for severe influenza
 Healthcare workers
 Anyone wishing to protect themselves against influenza

35. Thank you

36. Vaccination
 Recommended inactivated influenza vaccine (IIV) formulation for 2018
 an A/Michigan/45/2015 (H1N1)pdm09-like virus
 an A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus;
 a B/Phuket/3073/2013-like virus.

37. Vaccination
 Dosage of influenza vaccine –
 Adults 0.5ml IMI single dose
 3 years - 8 years – 0.5ml IMI 1 or 2 doses*
 6 months-2 years-0.25ml IMI 1 or 2 doses*
 *2 doses should be administered ≥ 1 month apart during 1st year of vaccination, thereafter one
dose.