SWINE FLU H1N1 INFLUENZA

H1N1 INFLUENZA SWINE FLU Dr. GurRaunaq Singh

926 Swine Flu Deaths, Over 16,000 Infected

INTRODUCTIONInfluenza is a serious respiratory illness of humans.

Influenza pandemics have been associated with high morbidity and mortality worldwide.

Influenza A(H1N1) virus is a subtype of influenza A virus and the most common cause of influenza(flu) in humans.

In 2009, the WHO declared the new strain of swine origin H1N1 as a pandemic which is often referred as swine flu.

What is Influenza (flu)?It is an acute respiratory illness caused by influenza virus

It infects the nose, throat and lungs

It is highly contagious and spreads rapidly from person to person

http://www.cdc.gov/flu/about/disease/

RNA virus

Type AORTHOMYXOVIRIDAEFamily:Genus:TypesSpecificityManAnimalBirdsManManInfluenza virus

Type BType C

Influenza viruses

Single-strandedhttp://emedicine.medscape.com/article/219557-overview#a0101

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80 to 120 nm

Lipid bilayer

16 types H1-H169 types N1- N9

SurfaceantigensRelevant parts of the virusSubtypes of type A - depend on H & N antigens and are many.Type B & C - not many subtype variationsH & N antigens of Influenza virus A change every year.Neuraminidase (NA)Haemaglutinin (HA)http://emedicine.medscape.com/article/219557-overview#a0101

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Pandemics of influenza

H1N1H2N2

1889RussianinfluenzaH2N2H2N2

1957AsianinfluenzaH2N2

H3N2

1968Hong KonginfluenzaH3N2

H3N8

1900Old Hong Kong influenzaH3N81918SpanishinfluenzaH1N11915192519551965197519851995200518951905

201020152009PandemicinfluenzaH1N1H1N1

PandemicH1N1

What are pandemics? Pandemics are when a new influenza A emerges to which most or many of the population have no immunity. The result usually from an animal influenza combining some of its genes with a human influenza. To be a pandemic strain an influenza A virus needs to have three or four characteristics. They need to be able to infect humans, to cause disease in humans and to spread from human to human quite easily. An additional criteria that is often applied is that many or most of the population should be non-immune to the new virus.

Note this animated slide was first developed by the National Institute of Infectious Disease in Japan and we are grateful to them and especially Masato Tashiro for letting us use it.

The Novel 2009 H1N1 VirusQuadruple reassortment virus from pigs (North American and Eurasian), Avian and human

2009 H1N1 virusReplicates in the lungs more efficiently

How does it spread ?

Flu viruses spread mainly from person to person through coughing, sneezing, or talking to someone with the flu.

Direct contamination The virus is transmitted by respiratory aerosols (droplets) loaded with virus that is expelled during coughing & sneezing.Respiratory aerosols (loaded with virus)Gets infectedPeople with flu can spread it to others up to about 6 feet away.http://www.cdc.gov/flu/about/disease/spread.htm

How does it spread ?

People may also catch flu by touching their mouth or nose after touching something with the virus on it, such as doorknobs, tables, or an infected persons dirty hand.

Indirect contamination Infected person Gets infected

http://www.cdc.gov/flu/about/disease/spread.htm

Source: Bean B, et al. JID 1982;146:47-51Survival of Influenza Virus Surfaces and Affect of Humidity & Temperature*Hard non-porous surfaces 24-48 hoursPlastic, stainless steelRecoverable for > 24 hoursTransferable to hands up to 24 hoursCloth, paper & tissueRecoverable for 8-12 hoursTransferable to hands 15 minutesViable on hands 38C

Any 2SIGNS AND SYMPTOMS: Lab tests not easily available & diagnosis is clinical

If fever is accompanied with any of these 2 signs and symptoms, then diagnosis is confirmed in 70% of cases during the influenza season

Signs and symptomsTwo less common signs of the flu include:Not everyone who is sick with flu will have all the signs of the flu at the same time. Its important to note that not everyone with flu will have a fever.These signs are more common in children than adults.

Case Definitions A suspected case of Pandemic influenza A (H1N1) virus infection is defined as a person with acute febrile respiratory illness (fever 38 0 C) with onset.:

within 7 days of close contact with a person who is a confirmed case of pandemic influenza A (H1N1) virus infection, or

within 7 days of travel to community where there are one or more confirmed pandemic influenza A(H1N1) cases, or

resides in a community where there are one or more confirmed pandemic influenza cases.

Case Definitions A probable case of Pandemic influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness who:

is positive for influenza A, but unsubtypable for H1 and H3 by influenza RT-PCR or reagents used to detect seasonal influenza virus infection, or

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.

Case DefinitionsA confirmed case of pandemic influenza A (H1N1) virus infection is defined as a person with an acute febrile respiratory illness with laboratory confirmed pandemic influenza A (H1N1) virus infection at WHO approved laboratories by one or more of the following tests:

Real Time PCR

viral culture

Four-fold rise in pandemic influenza A (H1N1) virus specific neutralizing antibodies.

WHO IS AT RISK?????EVERYONE IS AT RISKChildren, Pregnant women, The elderly (over 65)

Those with chronic disease and underlying health conditions

Healthcare professionals

Asthma Neurological and neurodevelopmental conditions (cerebral palsy, epilepsy stroke, mental retardation, moderate to severe developmental delay, muscular dystrophy, or spinal cord injury) Chronic lung disease (chronic obstructive pulmonary disease [COPD] and cystic fibrosis) Heart disease (congenital heart disease, congestive heart failure and coronary artery disease) Blood disorders (sickle cell disease) Endocrine disorders (diabetes mellitus) Kidney disorders Liver disorders Metabolic disorders (inherited metabolic and mitochondrial disorders) Weakened immune system due to disease or medication (people with HIV or AIDS/cancer/those on chronic steroids) People younger than 19 years of age who are receiving long-term aspirin therapy People who are morbidly obese (Body Mass Index (BMI) of 40 or greater)

Emergency warning signs in adults

Emergency warning signs in childrenIn infantsAlso look for these warning signs: being unable to eat, having no tears when crying, and having far fewer wet diapers than normal.

What are its complications? Most people who get influenza will recover in a few days to less than two weeks, but some people may develop complications like: Some people are more likely to get flu complications that result in being hospitalized & occasionally result in death.The flu can make chronic health problems worse.Bacterial pneumonia For example, people with asthma may experience asthma attacks while they have the flu, and people with chronic congestive heart failure may have worsening of this condition that is triggered by the flu.BronchitisSinus/ear infectionsDehydrationhttp://www.cdc.gov/flu/about/disease/symptoms.htm

DIAGNOSIS Confirmation of Pandemic influenza A(H1N1) infection is through:

Real time RT PCR or Isolation of the virus in culture or Four-fold rise in virus specific neutralizing antibodies.

For confirmation of diagnosis, clinical specimens such as nasopharyngeal swab, throat swab, nasal swab, wash or aspirate, and tracheal aspirate (for intubated patients) are to be obtained.

The sample should be collected by a trained physician / microbiologist preferably before administration of the anti-viral drug.

Keep specimens at 4C 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 b stored at -70C.

Paired blood samples at an interval of 14 days for serological testing should also be collected.

RT- PCRThe Human Influenza Virus Real-Time RT-PCR is an in vitro laboratory diagnostic test for direct molecular identification of influenza isolates is a rapid and powerful technique.

Can provide results within 4 hours.

It is the only in vitro diagnostic test for influenza that is cleared by the FDA for use with lower respiratory tract.

The RT-PCR allows template viral RNA to be reverse transcribed producing complementary DNA(cDNA) which can then be amplified and detected.

The kit utilizes a 3-module design and can:Identify and distinguish between influenza A and B viruses,Classify influenza A viruses by subtype, andDetect Pandemic influenza A (H1N1) 2009 strain

TREATMENTThe guiding principles are:

Early implementation of infection control precautions to minimize nosocomical / household spread of disease

Prompt treatment to prevent severe illness & death.

Early identification and follow up of persons at risk.

Guidelines on categorization of Seasonal Influenza A H1N1 cases during screening for home isolation, testing, treatment and hospitalization (Revised on 11.02.2015)

In order to prevent and contain outbreak of Influenza-A H1N1 virus for screening, testing and isolation following guidelines are to be followed:

At first all individuals seeking consultations for flu like symptoms should be screened at healthcare facilities both Government and private or examined by a doctor and these will be categorized as

Category- A

Patients with mild fever plus cough / sore throat with or without bodyache, headache, diarrhoea and vomiting will be categorized as Category-A. They do not require Oseltamivir and should be treated for the symptoms mentioned above. The patients should be monitored for their progress and reassessed at 24 to 48 hours by the doctor.

No testing of the patient for H1N1 is required.

Patients should confine themselves at home and avoid mixing up with public and high risk members in the family.

Category-B (i) In addition to all the signs and symptoms mentioned under Category-A, if the patient has high grade fever and severe sore throat, may require home isolation and Oseltamivir;

(ii) In addition to all the signs and symptoms mentioned under Category-A, individuals having one or more of the following high risk conditions shall be treated with Oseltamivir:

Children with mild illness but with predisposing risk factors. Pregnant women; Persons aged 65 years or older; Patients with lung diseases, heart disease, liver disease kidney disease, blood disorders, diabetes, neurological disorders, cancer and HIV/AIDS; Patients on long term cortisone therapy.

No tests for H1N1 is required for Category-B (i) and (ii).

All patients of Category-B (i) and (ii) should confine themselves at home and avoid mixing with public and high risk members in the family.

Broad Spectrum antibiotics as per the Guideline for Community-acquired pneumonia (CAP) may be prescribed.

Category-C

In addition to the above signs and symptoms of Category-A and B, if the patient has one or more of the following:

Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discolouration of nails;

Children with influenza like illness who had a severe disease as manifested by the red flag signs (Somnolence, high and persistent fever, inability to feed well, convulsions, shortness of breath, difficulty in breathing, etc).

Worsening of underlying chronic conditions.

All these patients mentioned above in Category-C require testing, immediate hospitalization and treatment.

How does one manage influenza?

Treatment1 Prevention1 Drugs (antivirals)

Antivirals (chemoprophylaxis)Good health habits Vaccines

AdamantanesAmantadineRimantadine

Neuraminidase Inhibitors (NAIs)ZanamivirOseltamivirPeramivir LaninamivirVaccination is the most effective measure at preventing influenza and its severe outcomes.22. http://www.apaci.asia/influenza/burden-of-influenza-a-benefit-of-vaccinationEveryone 6 months of age and older should get a flu vaccine every season (CDC)3 3. http://www.cdc.gov/flu/protect/keyfacts.htm1.http://www.who.int/mediacentre/factsheets/fs211/en/ last accessed on 19th January 2014

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Mechanism of action of Antivirals

ADAMANTANESNEURAMINIDASE INHIBITORs

Adverse reactions:

Oseltamivir is generally well tolerated

Gastrointestinal side effects (transient nausea, vomiting) may increase with increasing doses, particularly above 300 mg/day.

Occasionally it may cause bronchitis, insomnia and vertigo.

Less commonly angina, pseudo membranous colitis and peritonsillar abscess have also been reported.

There have been rare reports of anaphylaxis and skin rashes

Commencement within 12 h of symptom onset reduced illness duration by 3.1 days (compared to 48 hrs treatment)

Early treatment with oseltamivir is better!Journal of Antimicrobial Chemotherapy 2003; 51: 123-129

Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults

Chest 2011; 140(4):10251032Time from onset of symptoms to oseltamivir administration (+ 1-day increase) was independently associated with a prolonged duration of the fever, prolonged LOS, more-often need for mechanical ventilation, and higher mortality

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Oseltamivir reduces complications and antibiotic use in influenza infected patients in healthy and high-risk patients

Risk for pneumonia approximately 50% lower than among those persons receiving a placebo and 34% lower among patients at risk for complicationsArch Int Med 2003;163:1667-72

Benefits of oseltamivir in high-risk population with chronic respiratory diseases* or cardiac disease*chronic bronchitis, obstructive emphysema, bronchial asthma or bronchiectasisOseltamivir given within 48 hours of symptom onset significantly reduced:

Duration of influenza symptoms by 36.8% Severity by 43.1% Duration of fever by 45.2% Time to return to baseline health status by 5 daysA decrease in the incidence of secondary complications and antibiotic use, without increasing the total medical cost noted. Curr Med Res Opin. 2006 Jan;22(1):75-82.

Reduction in hospitalizations by 59% with early oseltamivir treatment 1. Arch Int Med 2003;163:1667-72

0.7% vs 1.7%1

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2. The Lancet Infectious Diseases 2014; 14 (2): 1091181. http://www.cdc.gov/flu/news/flu-antiviral-benefits.htmOverall flu symptoms reduced by one day compared with placebo (3 days versus 4 days)

Reduced amount of live virus that was isolated from respiratory specimens by 12% to 50% compared with placebo regardless of whether treatment started before or after 2 days since illness onset.Oseltamivir treatment within 5 days of symptom onset; Crowded, low-income, urban community in Bangladesh, (mostly children< 5 years)2

Treatment not to be delayed while awaiting diagnostic test results, nor should it be withheld in patients with indications for therapy who present >48 after the onset of symptoms3 3. Int. J. Pharm. Sci. Rev. Res., 2014: 25(2), Article No. 48: 252-258

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Dose of Zanamivir - Treatment Adults and children > 5 years5 mg capsules to be inhaled2 inhalations twice a day with DPI2 doses on first day at least 2 hours apartSubsequently 12 hours apart

WarningGenerally not recommended for patients with asthma/COPDOccasionally bronchospasm has been reported. Keep bronchodilator ready

Significant benefits with administration of zanamivir within 48 hours Rapid reduction of the viral load observed. The mean area under the curve for viral load during the first 48 h of treatment was 8.48 log10 vRNA copies/ml x h lower in the zanamivir group compared with placebo2Meta-analysis of 7 trials showed:1 31% reduction of antibiotic prescription in zanamivir Lower incidence of complications (13% vs 18%)Fewer nights of sleep disturbance (median 2 nights vs 3 nights) in asthma or COPD patients Reduced the incidence of complications (requiring antibiotics and a change in respiratory medication) compared with placebo by 58%Clin Drug Invest 2000 Nov; 20 (5): 337-349Scand J Infect Dis. 2003;35(1):52-8.

Patients with signs of tachypnea, dyspnea, respiratory distress and oxygen saturation less than 90 per cent should be supplemented with oxygen therapy.

Types of oxygen devices depend on the severity of hypoxic conditions which can be started from oxygen cannula, simple mask, partial re-breathing mask (mask with reservoir bag) and non re-breathing mask. In children, oxygen hood or head boxes can be used.

Patients with severe pneumonia and acute respiratory failure (SpO2 < 90% and PaO2