REVIEW H1N1Maj SK Mishra

Dr Rajeev Gupta

Dr Prashant Malviya

Chair Person

Surg Cdr Anuj Singhal

Introduction Epidemiology Sign and symptom Diagnosis Treatment Prevention

WHAT IS SWINE FLU

Swine influenza Refers to influenza cases that are caused by

Orthomyxovirus endemic to pig populations. Is a respiratory disease of pigs caused by

type A influenza Regularly cause outbreaks among pigs. Swine flu viruses do not normally infect

humans

VIRAL INFLUENZA A - HUMAN HISTORY

1889-901900-031918-19

H2N8H3N8H1N1(HswN1)

Severe epidemicMod epidemicSevere epidemic

1933-351946-471957-58

H1N1(HON1)H1N1H2N2

Mild epidemicMild epidemicSevere epidemic

1968-691977-78

H3N2H1N1

Mod epidemicMild epidemic

HISTORY

The H1N1 form of swine flu is one of the descendants of the Spanish flu that caused a devastating pandemic in humans in 1918–1919

In 1957, an Asian flu pandemic infected some 45 million Americans and killed 70,000. It caused about 2 million deaths globally

Eleven years later, lasting from 1968 to 1969, the Hong Kong flu pandemic afflicted 50 million Americans and caused 33,000 deaths

In 1976, about 500 soldiers became infected with swine flu over a period of a few weeks.

COUNTRIES AFFECTED TILL NOW

PANDEMICS OF INFLUENZA

7

H1N1

H2N2

1889RussianinfluenzaH2N2

H2N2

1957AsianinfluenzaH2N2

H3N2

1968Hong KonginfluenzaH3N2

H3N8

1900Old Hong Kong influenzaH3N8

1918SpanishinfluenzaH1N1

1915 1925 1955 1965 1975 1985 1995 20051895 1905 2010 2015

2009PandemicinfluenzaH1N1

Reproduced and adapted (2009) with permission of Dr Masato Tashiro, Director, Center for Influenza Virus Research, National Institute of Infectious Diseases (NIID), Japan. Animated slide: Press space bar

H1N1Pandemic

H1N1

SEASONAL INFLUENZA COMPARED TO PANDEMIC — PROPORTIONS OF TYPES OF CASES

8

Asymptomatic

Clinicalsymptoms

Deaths

Requiring hospitalisation

Seasonal influenza Pandemic

Asymptomatic

ClinicalsymptomsDeaths

Requiring hospitalisation

SOME OF THE 'KNOWN UNKNOWNS' INTHE 20TH CENTURY PANDEMICS

Three pandemics (1918, 1957, 1968). Each quite different in shape and waves. Some differences in effective reproductive

number. Different groups affected. Different levels of severity including case

fatality ratio. Imply different approaches to mitigation.

9

INDIAN SCENARIO- 2009

NO OF CASES 10 MAIN AFFECTED CITIES-2009

CITIES NO OF CASES

PUNE 574

MUMBAI 324

DELHI 316

BANGALORE 131

HYDERABAD 67

CHENNAI 82

GURGAON 39

AHEMDBAD 34

KOLKATA 25

CALICUT 23

COMPARATIVE MORTALITY

Avian flu(H7N7) HK 07Hantavirus PS China

06SARS-CoV China 07Swine flu(H1N1)Dengue

60 % 30-40 %9.5 %<1 %(177457 and

1462)< 1>1 %

INFLUENZA VIRUS Three types of influenza viruses:

A, B and C. A and B seasonal epidemics of disease C infections mild respiratory illness and are

not thought to cause epidemics.

ORTHOMYXOVIRUSES 80-200nm

M1 protein

helical nucleocapsid (RNA plus NP protein)

HA - hemagglutinin –attaches to sialicAcid receptor

polymerase complex

lipid bilayer membrane

NA – neuraminidase-helps inBudding out of infected cell

type A, B, C : NP, M1 protein sub-types: HA or NA protein

INFLUENZA -A

Two proteins on the surface of the virus Hemagglutinin (H)

16 subtypes Neuraminidase (N)

09 subtypes

CLASSIFICATION=

The antigenic type (e.g., A, B, C) The host of origin (e.g., swine, equine,

chicken, etc. For human-origin viruses, no host of origin designation is given.)

Geographical origin (e.g., Mexico, Taiwan, etc.)

Strain number (e.g., 15, 7, etc.) Year of isolation (e.g., 57, 2009, etc.)

PATHOPHYSIOLOGY

Antigenic drift Mutations within the virus antibody-binding sites

accumulate over time Circumvent the body's immune system A and B

Antigenic shift Sudden change in antigenicity Recombination of the influenza genome Cell becomes simultaneously infected by two

different strains of type A influenza. Humans live in close proximity swine, that human

strains and bird strains, may readily infect a pig at the same time, resulting in a unique virus.

ANTIGENIC SHIFT

H1N1

NOVEL H1N1 INFLUENZA

The first cases of human infection with novel H1N1 influenza virus were detected in April 2009 in San Diego and Imperial County, California and in Guadalupe County, Texas.

The virus has spread rapidly.

The virus is widespread in the United States

Has been detected internationally as well.

WHO CAN CATCH THE “FLU” ?

WHO CAN CATCH THE FLU ?

As in all epidemics ChildrenElderlyPregnant womenImmuno-suppressed or Immuno-compromisedChronic medical conditions Occupational exposure-paramedics, medics

HOW DOES NOVEL H1N1 INFLUENZA SPREAD?

spread the same way seasonal flu spreads

Primarily through respiratory droplets CoughingSneezingTouching respiratory

droplets on yourself, another person, or an object, then touching mucus membranes (e.g., mouth, nose, eyes) without washing hands

CAN YOU GET NOVEL H1N1 INFLUENZA FROM EATING PORK?

No You cannot get novel H1N1 flu from eating pork or pork products.

Eating properly handled and cooked pork products is safe.

DEFINITIONS- CDC

CDC INTERIM GUIDANCE REPORT

CONFIRMED CASE is defined as a person with an acute

febrile respiratory infection and a confirmed positive test for S-OIV by RT-

PCR and/or viral culture.

PROBABLE CASE is defined as a person with an acute febrile respiratory infection who tests positive for influenza A but negative

for H1 and H3 by viral RT-PCR.

SUSPECTED CASE is defined as a person with an acute febrile respiratory infection with onset Within 7 days of close contact with a person who is a confirmed case of S-

OIV infection.Within 7 days of travel to a community

where there are one or more confirmed cases.

Resides in a community where there are one or more confirmed cases of SIV

infection.

INFECTIOUS PERIOD for a confirmed case of H1N1 is defined as 1 day prior to the cases illness onset to 7 days after onset.

CLOSE CONTACT is defined as being within 6 feet of a confirmed or suspected case of H1N1 during the case’s infectious period.

ACUTE ONSET OF A RESPIRATORY ILLNESS is defined as having at least 2 of the following: rhinorrhea, sore throat and cough with or without fever

INFECTIVITY PERIOD Should be considered potentially contagious

as long as they are symptomatic and possible for up to 7 days following illness

onset.

Children - might potentially be contagious for longer periods.

INDIVIDUALS AT INCREASED RISK Elderly > 65 years Children less than two years Certain chronic diseases

Heart (except HTN) or lung disease (including asthma)

Metabolic disease, including diabetes HIV/AIDS, other immuno-suppression (drugs

induced) Chronic renal disease chronic hepatic disease

http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm,Influenza Antiviral Medications: Summary for Clinicians (Current for the 2012-2013 Influenza Season)

Pregnant/postpartum (2 weeks after delivery) Hemoglobinopathies Aged younger than 19 years, receiving long

term Asprin therapy Person who are morbidly obese (BMI >40) Residents of nursing homes and other

chronic care facilities

SIGNS AND SYMPTOMS

SYMPTOMS

Mild or uncomplicated illness

Progressive illness  typical symptoms chest pain poor oxygenation

(eg, tachypnea) cardiopulmonary insufficiency central nervous system (CNS) impairment (eg,

confusion, altered mental status) severe dehydration

Severe illness  mechanical ventilation CNS findings (encephalitis, encephalopathy) complications of hypotension (shock, organ

failure) myocarditis or rhabdomyolysis invasive secondary bacterial infection persistent high fever and other symptoms

beyond three days.

COMPLICATIONS 

Refractory respiratory failure Not improving on mechanical ventilator Inhaled nitric oxide high-frequency oscillatory ventilation extracorporeal membrane oxygenation (ECMO)

COMPLICATIONS

Bacterial superinfection  Streptococcus pneumoniae Streptococcus pyogenes Staphylococcus aureus, Streptococcus mitis Haemophilus influenzae Moraxella catarrhalis

BACTERIAL SUPERINFECTION

Clinical findings: Secondary fever after a period of defervescence. Sputum Gm stain or culture Lobar consolidation on chest imaging (diffuse

pattern in normal viral pneumonia) Leukocytosis (normal or low white blood cell

count) Onset of respiratory compromise occurring four

to seven days after initial symptoms

COMPLICATIONS

Neurologic  Seizure Confusion acute or postinfectious encephalopathy quadriparesis encephalitis severe acute disseminated encephalomyelitis stroke, and transient ischemic attack

COMPLICATIONS

Other  Myocarditis Renal insufficiency Rhabdomyolysis Multisystem organ failure. Hypercoagulability

LABORATORY FINDINGS 

Elevated SGOT/SGPT Anemia Leukopenia Thrombocytopenia /Thrombocytosis Elevated total bilirubin Elevations of CPK ,LDH

 

DIAGNOSTIC ASSAYS

Real-time reverse transcriptase (rRT)-PCR

most sensitive and specific test culture

too slow A negative viral culture does not exclude pandemic H1N1 influenza A infection.

LIMITATIONS

Analysts should be trained and familiar with testing procedures and interpretation of results prior to performing the assay.

A false negative result may occur if inadequate numbers of organisms are present in the specimen due to improper collection, transport or handling.

DIAGNOSTIC ASSAYS

Combined nasopharyngeal and throat swabs (CNTS) Nasopharyngeal aspirates (NPA)

DIAGNOSTIC ASSAYS

Rapid antigen tests Distinguish between influenza A and B viruses Cannot distinguish among different subtypes of

influenza A sensitivity -10 to 70 percent specificity of rapid antigen testing was generally

>95 percent

DIAGNOSTIC ASSAYS

Immunofluorescent antibody testing  Direct or indirect immunofluorescent antibody

testing (DFA or IFA) Distinguish between influenza A and B does not distinguish among different influenza A

subtypes Low sensitivity and specificity

METHOD Acceptable Specimens Test Time

Viral cell culture NP swab, throat swab, NP ,bronchial wash, nasal endotracheal aspirate, sputum

3-10 days

Direct (DFA) or Indirect (IFA) Antibody

NP swab or wash, bronchial wash, nasal or endotracheal aspirate

1-4 hours

RT-PCR NP swab, throat swab, NP or bronchial wash, nasal or endotracheal aspirate, sputum

1- 6 hours

Rapid Influenza Diagnostic Tests

NP swab, (throat swab), nasal wash, nasal aspirate

<30 min.

Treatment of H1N1

Treatment

• Adamantane agents – Amantadine – Rimantadine

• Neuraminidase inhibitor – Oseltamivir (oral)– Zanamivir (aerosolized) – Peramivir (intravenous)

CDC recommends

• Treatment and prevention of H1N1/seasonal flu

• Neuraminidase inhibitor – Oseltamivir (oral)– Zanamivir (aerosolized)

GUIDELINES ON CATEGORIZATION OF INFLUENZA A H1N1 CASES DURING SCREENING FOR HOME ISOLATION, TESTING TREATMENT AND HOSPITALIZATION

Ministry of Health & Family Welfare Pandemic Influenza A (H1N1) Govt of India

Category- A• Patients with mild fever plus cough / sore throat with

or without body ache, headache, diarrhoea and vomiting

• Do not require Oseltamivir • Symptomatic treatment • Monitored for their symptom progress and reassessed

at 24 to 48 hours by the doctor• No testing of the patient for H1N1 • Confine themselves at home • Avoid mixing up

– Public and high risk members in the family

Category-B

i. Category-A + high grade fever & severe sore throat

– Require home isolation and Oseltamivirii. Category-A + one or more of high risk conditions

i. Shell be treated with Oseltamivir• No tests required for Category-B (i) and (ii)• All patients of Category-B (i) and (ii)

i. should confine themselves at home ii.Avoid mixing with public and high risk members in

the family

Category-C• Category-A and B

– Breathlessness, chest pain, drowsiness, fall in blood pressure, sputum mixed with blood, bluish discoloration of nails

– Children with 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

• Require testing, immediate hospitalization and treatment

• Treatment should be started as soon as possible after illness onset– Ideally within 48 hrs

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

Guidelines on chemoprophylaxis

• Healthy persons after community exposure – No chemoprophylaxis

• If states qualify the criteria for community spread – Family contacts that are at high risk – Co-morbid condition

• Irrespective of laboratory testing

Guidelines on chemoprophylaxis, Ministry of Health & Family Welfare Pandemic Influenza A (H1N1) Govt of India

• States which does not qualify the criteria of community spread – Family contacts, school contacts and social

contacts

• Irrespective of community spread or not – Medical personnel attending to influenza A H1N1

cases

Guidelines on chemoprophylaxis, Ministry of Health & Family Welfare Pandemic Influenza A (H1N1) Govt of India

It is also available as syrup (12mg per ml )

OSELTAMIVIR (Cap.Tamiflu)

ADULTSTREATMENT (5 DAYS) Chemoprophylaxis

(10 days)

75 mg BD 75 mg OD

Children≥ 12 months

Body Weight (kg) TREATMENT (5 DAYS) Chemoprophylaxis(10 days)

≤15 kg 30 mg twice daily 30 mg once daily

> 15 kg to 23 kg 45 mg twice daily 45 mg once daily

>23 kg to 40 kg 60 mg twice daily 60 mg once daily

>40 kg 75 mg twice daily 75 mg once daily

Children 3 months to < 12 months2

TREATMENT (5 DAYS) Chemoprophylaxis(10 days)

3 mg/kg/dose twice daily

3 mg/kg/dose once per day

WHO and The U.S. Centers for Disease Control and Prevention http://www.cdc.gov/H1N1flu/recommendations.htmhttp://www.cdc.gov/H1N1flu/recommendations.htm

ZANAMIVIR (Relenza Diskhaler)

ADULTS and

Children > 5 years

TREATMENT (5 DAYS)

Chemoprophylaxis(10 days)

10 mg (two inhalations)

BD

10 mg (two inhalations) once

daily

WHO and The U.S. Centers for Disease Control and Prevention http://www.cdc.gov/H1N1flu/recommendations.htmhttp://www.cdc.gov/H1N1flu/recommendations.htm

Adverse effect

• Oseltamivir – Nausea– GI discomfort– Vomiting– Vertigo– Insomnia – Neuropsychiatric events

• Delirium• Self-injury

• Zanamivir– Worsen asthma– Diarrhea– Nausea– Sinusitis– Nasal signs and

symptoms– Bronchitis– Headache & dizziness– Ear, nose, and throat

infections

http://www.cdc.gov/flu/professionals/antivirals/antiviral-adverse-events.htm Harrison’s 18th edition, page no.1442

INFLUENZA SEASONAL VACCINE

CDC - Seasonal Influenza (Flu) - Key Facts About Seasonal Flu Vaccine

Vaccination

• Annually • Trivalent

– 2 strain of influenza A & 1 strain of influenza B

• Above the age of 6 months • Quadrivalent vaccine

CDC - Seasonal Influenza (Flu) - Key Facts About Seasonal Flu Vaccine

“Flu shot”

• The "flu shot" – Killed vaccine– Intramuscular – Usually in the arm – approved for use in

people older than 6 months, including healthy people and people with chronic medical conditions.

76

Nasal vaccination

• LAIV (Flumist)– a vaccine made with

live, weakened flu viruses that do not cause the flu

– LAIV (FluMist) is approved for use in healthy people 2-49 years of age who are not pregnant

77

Seasonal influenza vaccine 2012-13

• Influenza vaccines for 2012–13 season – A/California/7/2009 (H1N1)– A/Victoria/361/2011 (H3N2)– B/Wisconsin/1/2010 (Yamagata lineage) antigens

• All individual above the age of 6 mths • 6 months to 8 years– 2 doses – Month apart (4 weeks to 1 years)

CDC- Prevention and Control of Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP) —United States, 2012–13 Influenza Season, August 17, 2012 / 61(32);613-618

Available

Pandemic flu vaccine

• Monovalent vaccine – CELVAPAN – PANDEMRIX

Side effects

• Flu shot– Soreness, redness, or

swelling where the shot was given

– Fever (low grade)– Aches

• LAIV (Flumist)– Children

• runny nose• wheezing• headache• muscle aches• Fever

– Adults • runny nose• headache• sore throat• cough

CDC - Seasonal Influenza (Flu) - Key Facts About Seasonal Flu Vaccine

Who should get the swine flu shot?

• Pregnant women • People who live with or care for children younger

than 6 months of age • Children and young people between the ages of 6

months and 24 years • Health care workers and emergency medical

service providers • 25 and 64 years of age who have chronic medical

disorders or compromised immune systems.

CDC - Seasonal Influenza (Flu) - Key Facts About Seasonal Flu Vaccine

Who Should Not Be Vaccinated?

• People who have a severe allergy to chicken eggs

• Severe reaction to an influenza vaccination• Children younger than 6 months of age • People who have a moderate-to-severe illness

with a fever (they should wait until they recover to get vaccinated)

• History of Guillain–Barré Syndrome

CDC - Seasonal Influenza (Flu) - Key Facts About Seasonal Flu Vaccine

GUIDELINES ON INFECTION CONTROL MEASURES

Clinical management Protocol and Infection Control Guidelines; Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

Health facility managing the human cases of Influenza A H1N1

• During Pre Hospital Care – Three layer surgical mask– Full complement of PPE(Personal Protection Equipments )– No Aerosol generating procedures – Three layered surgical mask for driver – Ambulance equipment sanitized using sodium

hypochlorite / quaternary ammonium compounds

Contd

• During hospital care – Isolation ward and continue to wear a three layer

surgical mask– Identified medical, nursing and paramedical personnel

attending the pt should wear full complement of PPE (Personal Protection Equipments)

– Aerosol-generating procedures – Sample collection and packing– Hand wash

• Before and after patient contact• Following contact with contaminated items

Contd

• Infection control precautions – 7 days after resolution of symptoms for adult – 14 days after resolution of symptoms for children

• Contaminated surfaces and equipments• Disinfectants

– 70% ethanol, 5% benzalkonium chloride (Lysol) and 10% sodium hypochlorite

STANDARD OPERATING PROCEDURES ON USE OF PERSONAL PROTECTION

EQUIPMENTS (PPE)

Clinical management Protocol and Infection Control Guidelines; Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

Personal Protection Equipments (PPE)

• Reduces the risk of infection. It includes: – Gloves (nonsterile)– Mask (high-efficiency mask N95) / 3 layered

surgical mask– Long-sleeved cuffed gown– Protective eyewear (goggles/visors/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

Contd

• Correct procedure for applying PPE : – Follow thorough hand wash – Wear the coverall– Wear the goggles/ shoe cover/and head cover – Wear face mask – Wear gloves

The masks should be changed after every six to eight hours

Remove PPE in the following order

• Remove gown (place in rubbish bin)• Remove gloves (peel from hand and discard into

rubbish bin)– Alcohol -based hand-rub or wash hands with soap & water

• Remove cap and face shield (place cap in bin and if reusable place face shield in container for decontamination)

• Remove mask - by grasping elastic behind ears – do not touch front of mask – Use alcohol-based hand-rub or wash hands with soap & water

INFECTION CONTROL MEASURES AT INDIVIDUAL LEVEL

Clinical management Protocol and Infection Control Guidelines; Directorate General of Health Services, Ministry of Health and Family Welfare, Government of India

Hand washing a Top priority

• Single most important measure to reduce the risk of transmitting infectious organism from one person to other

Respiratory Hygiene/Cough Etiquette

• Covering your nose and mouth with a tissue when you cough or sneeze. Throw the tissue in the trash after you use

• Wash hand

Touching face regions can faster the Spread

• Avoiding touching your eyes, nose or mouth. Virus can spread this way in a faster way

Staying home if you are sick

Avoid crowded places more so with young children

Mild cold like symptoms - Take rest

Using N95 mask reduces the Risk

• You can cut your risk of contracting the flu or other respiratory viruses by as much as 80 percent by wearing a mask over your nose and mouth

Emerging Infectious Diseases, the journal of the Centres for Disease Control and Prevention (CDC) .

Infection control measures at health facility

• Droplet Precautions• Visual alerts• Use of PPE• Decontaminating contaminated surfaces,

fomites and equipments• Guidelines for waste disposal

Discharge policy

• Asymptomatic pt after two to three days of treatment – Should be discharged after 5 days of treatment– Repeat test not required

• Continuation of symptoms of fever, sore throat etc. even on the 5th day – should continue treatment for 5 more days – Asymptomatic discharge– No need to test further

Discharge policy

• Symptomatic – Even after 10 days of treatment or – cases with respiratory distress – Suspected secondary infection – if patient continue to shed virus

• Resistance of the patients to anti viral drug would be tested

• Family should be educated on – Personal hygiene – Infection control measures at home

Check list

• S – Stay home (if ill) and sleep well • W –Wash hands, wear masks. Wine not to be

consumed • I – Imbibe fluids• N – No smoking• E – Eat well• F – Fear not ( deaths < 1 %) ,Fully treatable• L – Lessen travel and visits to crowded places• U – Uphold cleanliness and proper disposal of

used masks

Panic and Fear are much dangerous than Swine Flu