H1N1 Influenza A


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Influenza-A(H1N1 virus) Shokit Amin Paswal CENTRAL UNIVERSITY OF PUNJAB .

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INFLUENZA Influenza (“the flu”) is a seasonal respiratory illness that affect mainly nose, throat, bronchi and occasionally lungs. Infection usually lost for about a week and characterised by sudden onset of fever, fatigue, headache and severe malaise, non-productive cough, sore throat and rhinitis (WHO) The viruses can cause mild to severe illness sometimes resulting in death.


SEASONAL VS PENDEMIC Seasonal refers to annually or periodic outbreaks of respiratory illness. Mostly in winter. Caused by influenza A or B subtypes Between 15–20 percent of the population may be infected annually Most people have some immunity against seasonal influenza virus Happens annually and usually peaks in January or February An influenza A pandemic is a global disease outbreak. Occurs when there is little or no immunity to that strain of influenza in the human population. Causes serious illness, and can sweep through populations. Spreads worldwide Can be spread from human to human Symptoms may be more severe Rarely happens (Three times in 20th century)


INFLUNZA PENDEMICS There were three flu pandemics in the last century 1918 – most deadly (H1N1) more than 500,000 deaths in the U.S. and up to 50 million people worldwide Played a role in ending World War I 1957 –H2N2 about two million deaths 1968 – H3N2 “Hong Kong Flu” about one million deaths 2009 -H1N1 swine flu is the first pandemic of the 21 st century Source: CDC

Swine Influenza A(H1N1) March 2009 Timeline:

Swine Influenza A(H1N1) March 2009 Timeline In March and early April 2009, Mexico experienced outbreaks of respiratory illness and increased reports of patients with influenza-like illness (ILI) in several areas of the country Quickly spread through North America The H1N1 virus traveled around the world in six weeks as widely as it normally takes a regular flu virus to spread in six months. Analysis of genetic matches shows it is a novel influenza virus with genetic material from swine, avian, and human influenza strains, April 29 2009 Mexico’s first probable case confirmed on May 2, 2009 CDC determines that this virus is contagious and is spreading from human to human By June, swine flu was spreading in Europe, South America, and Asia June 11, 2009 WHO declares pandemic phase 6.

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Source: WHO

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Virus type Strain number Virus subtype Place virus isolated Year of isolation   A/California/04/2009(H1N1) Influnza nomenclature

Hemagglutinin (HA) and Neuraminidase (NA). :

Hemagglutinin (HA) and Neuraminidase (NA).  H or hemagglutinin – 18 versions and aprox . 13.5 nanometer long, needed by virus for recognition and binding with host cells. Earlier 16 versions, 16 th discovered 1n 2004 in Seagulls but recently in 2012 H17 was discovered in fruit bats and now in 2013 H18 was discovered in peruvian bats. All H16 are found in aves but only H1, H2 and H3 found in human Infuenza viruses. N or neuraminidase has 9 versions now 11 ( oct . 2013) and plays an essential role in release and spread of virus progeny. It removes sialic acid from oligosaccharides on cell-surface proteins and glycolipids , thus destroying receptors for the virus. Also removes sialic acid from HA so that progeny influenza virions cannot aggregate.

Origin of swine flu pandemic:

Origin of swine flu pandemic ( Gavin J. D. Smith et.al, 2009). Origins and evolutionary genomics of the 2009 swine-origin H1N1 influenza A epidemic. Vol 459-25 . 1998

Antigenic Drift:

Antigenic Drift Source: Aina Meducci 2012 Small changes in HA and NA genes Forming new strain of virus Responsible for localised outbreaks Deletion of a single amino acid in H gene (H1N1) Confers antigenic change. Easy to treat (antibody and drugs available) Population may have immunity .

Antigenic Shift:

Antigenic Shift Two or more strains combine and form a new virus Large change result in new H or N May affect globally. Difficult to treat (need new vaccine) May jump from one species to another (animal-human) Examples Spanish flu (1918) Asian flu (1957) Hong Kong flu (1968) Swine flu (2009) Source: Aina Meducci, 2012


STRUCTURE OF H1N1 INFLUNZA A VIRUS Source:- Swiss institute of Bioinformatics Source:   National Institute of Allergy and Infectious Diseases

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INVASION TO HOST CELL Source:- Adrienne Sozansky . etal .( LIQUID BIO.)

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Pol II transcription cycle in uninfected cells Source: A. Y. Chan et al 2006

The role of the influenza virus RNA polymerase in host shut-off:

The role of the influenza virus RNA polymerase in host shut-off Frank T. Vreede and Ervin Fodor, 2010. Sir William Dunn School of Pathology; University of Oxford; Oxford, UK.

Replication cycle of an influenza A virus:

Replication cycle of an influenza A virus Source: C.M. Mair et al (2013)

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H1N1 IN INDIA India ranks first in Asian nations in number of deaths on 15 th of Aug. 2009 The first fatality was a 14 year old girl (Rida Sheikh) from Pune. She had come in contact with 40 students who Travelled from US to Pune. All peoples entering India via the main airport hub of Mumbai, New Delhi, Kolkata, Goa, Kochi, Chennai and Bangalore are being screened. Main focus on passengers from USA, UK Canada, Mexico and New Zeeland. Maximum cases have been reported from Pune (Maharashtra), Gujarat & Tamil Nadu. The general public must be educated about the signs symptoms and spread of Swine flu. This can be done by television, radio, newspaper etc. .

Current status in India:

Current status in India Post pandemic phase. Pandemic phase ended in august 2010. (2898 cases, and 373) Latest outbreak in India is less worrisome with 708 cases and 132 deaths. Maximum number of cases (236) and deaths (65) reported from Rajasthan . Ministry of health and family welfare feb.13, 2013.

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Rapid influenza diagnostic tests Proper sample collection in first few days. Antigen detection test. Provide result within 30 minutes. Blood Test Increased or decreased WBC count Elevated Aminotransferase and Creatinine kinase level. Viral culture “Gold standard” Results take 2-7 days Specific Helpful for vaccine development RT-PCR The FDA issued EUAs for RT-PCR at request of CDC as the method for diagnosing H1N1 in response to current outbreak. Most sensitive and commercial. Public Health Laboratories in US DIAGNOSIS


Catherine Klapperich et al Boston University (2012) Microfluidic chip Catherine Klapperich

Medical Complications And Symptoms:

Medical Complications And Symptoms Pneumonia Sinusitis, croup, bronchitis Myocarditis, myositis, Fatigue (persists for weeks) Sinus and ear infections

High-Risk Groups:

High-Risk Groups People with the following conditions: Chronic pulmonary conditions (asthma, cystic fibrosis) Chronic cardiac conditions. Renal, hepatic disease. (kidney/liver) Sickle cell disease. Neurologic or neuromuscular disorders Diabetes mellitus and other metabolic disorders Obesity Immunosuppression (caused by medications or HIV).


VACCINE PRODUCTION Influenza virus vaccine first developed in 1940 Embryonated egg-grown, formaldehyde inactivated preparation, disrupted with non ionic detergent (Triton X-100) 1 Dose for adult = 45mg = purified viruses obtained from allaontic fluid of 1 infected embryonated egg. Lacking in efficiency and highly pryogenic.


Antivirals Adapted from Supplemental Table 5, Writing Committee of the WHO Consultation on Clinical Aspects of Pandemic (H1N1) 2009 Influenza. N Engl J Med 362:1708, 2010 Trade name Mode of action Dose Route Drug NEURAMINIDASE INHIBITOR - do- 150 mg/ 12 hr O Oseltamivir ( Tamiflu) 600 mg /12 hr IV Zanamivir ( Relenza) 600 mg / 24 hr IV Peramivir

Neuraminidase Inhibitor:

Neuraminidase Inhibitor Source: Anne Moscona . Neuraminidase Inhibitors for Influenza 2005;353:1363-73

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Lauren’s protein Sialidase activity of neuraminidase found active even under acidic condition. Severe virulence. Deletion of threonine residue at position 435. And glycine residue at position 455. Researcher concluded that it eliminate this activity to remain stable in acidic condition. Source: Lauren Bylsma (2011 )


ROLE OF VIPERIN AS ANTIVIRAL AND PROVIRAL .Source: Helbig Karla J., Beard Michael R., J Mol Biol (2013), Viperin bind with farnesyl Diphosphate synthase involved In cholesterol and sterol biosynthesis

Infection Control Recommendations:

Infection Control Recommendations Hand hygiene Cough etiquette Vaccination for both seasonal and H1N1 influenza once vaccine becomes available Surgical masks for coughing patients Examinations in separate rooms if available Consider private rooms or cohorting of patients depending on situation Persons with influenza-like illness should stay home until 24 hours after fever resolved Surgical masks should be used by health care workers when providing direct patient care to H1N1 patients.


WHO INFLUENZA A (H1N1) 2009 GLOBAL PANDEMIC RESPONSE PLAN Monitoring and tracking global and regional progression, transmission and impact of the pandemic. Generating and sharing authoritative information and knowledge which minimise impact of pandemic. Providing direct technical guidance and support to countries in need. Accelerating development of vaccines and access to vaccines. (Serum Institute of India, Pune. Accelerating access to antivirals and other essential medicines Providing global health leadership and mobilizing regional and global partnerships across sectors to combat H1N1. Coordinating operational activities related to the deployment of pandemic antivirals and vaccines.


CONCLUSION The world experiences a pandemic of influenza periodically and not at regular or predictable intervals. Swine flu is caused by a new flu virus the 2009 H1N1 virus that never existed before, it spread around the world faster than any other virus. We need to have plans in advance to respond in the event of such pandemics to minimize the death rate keeping in view the virus capability to mutate, developing resistance and escaping immunity . If a pandemic arises preventive measures such as Social distancing Personal protective measures (e.g., masks) and travel screening and restriction are adopted and Public health communication campaigns are carried out for awareness purposes it may help to reduce the risk of transmission of a influenza to individuals and communities.

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References L iu, Y., et al .(2010). Characterization of antibodies specific for hemagglutinin and neuraminidase proteins of the 1918 and 2009 pandemic H1N1 viruses . Vaccine . 29 (2): 183-190. Robertson, J.S., et a. (2011.) The development of vaccine viruses against pandemic A (H1N1) influenza . Vaccine . 29 (9) :1836-1843. Sim , F. and P. Mackie.(2009). Pandemic or no pandemic: Emergence of swine influenza A (H1N1) in 2009 . Public health . 123 (6):405-406. Geerts-Dimitriadou , C., R. Goldbach , and R. Kormelink , (2011). Preferential use of RNA leader sequences during influenza A transcription initiation,in vivo . Virology . 409 (1): 27-32. Ginocchio , C.C., et al .(2009). Evaluation of multiple test methods for the detection of the novel 2009 influenza A (H1N1) during the New York City outbreak . Journal of Clinical Virology . 45 (3): 191-195 .

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Mehle , A. and J.A. Doudna .(2009). Adaptive strategies of the influenza virus polymerase for replication in humans . Proceedings of the National Academy of Sciences . 106 (50): 21312-21316. McKimm‐Breschkin , J.L.(2013). Influenza neuraminidase inhibitors: antiviral action and mechanisms of resistance . Influenza and other respiratory viruses . 7( 1): 25-36. Morimoto, R., et al .(2010). A case of fulminant myocarditis associated with novel N1H1 influenza successfully treated by percutaneous cardiopulmonary support system. Journal of Cardiology Cases . 2 (2): 106-110.

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