SWINE FLU

Dr. Meely PandaMBBS, MDCommunity MedicineSWINE FLU

CONTENTS

Burden of the diseaseNatural history of diseaseLifecyclePathogenesisManagement (Diagnosis & treatment)Future prospectsSummary

BURDENSoon after the outbreak of H1N1 virus in the United States and Mexico in March 2009, the Government of India started screening people coming from the affected countries at airports for swine flu symptoms. The first case of the flu in India was found on the Hyderabad airport on 13 May, when a man traveling from US to India was found H1N1 positive.Subsequently, more confirmed cases were reported and as the rate of transmission of the flu increased in the beginning of August, with the first death due to swine flu in India in Pune panic began to spread.As of 24 Aug 2010, 10193 cases of swine flu have been confirmed with 1835 deaths

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Influenza Laboratory Surveillance - Information generated on 29/03/2013 06:27:13 by the Global Influenza Surveillance and Response System (GISRS)

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Influenza Laboratory Surveillance - Information generated on 29/03/2013 06:27:13 by the Global Influenza Surveillance and Response System (GISRS)

BURDEN

States of India per confirmed deaths

0 deaths1+ deaths10+ deaths100+ deaths200+ deaths

States of India per confirmed cases4000+ cases2000+ cases1000+ cases500+ cases100+ cases1+ cases

From Wikipedia, the free encyclopedia

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BURDEN At least 30 people have died from swine flu inHaryanathis year with 49 people diagnosed positive withH1N1 virus being quarantined at their homes across the state. Since January 1, a total of 455 suspected cases have been tested, out...

http://www.who.int/influenza/gisrs_laboratory/flunet/charts/en/

MAJOR PANDEMICS

observed that pigs could also catch the flu..1918

1930 - The virus was isolated in pigs by Dr. Shoppe - H1N1 - close to the humanH1N1.North America1976 - Also circulated in pigs from Europe and Asia through a contamination in Italy1997 - the swine virus gained genes from an avian influenza and another from humans. This triple rearrangement circulates until today and it was one of the two viruses in pigs that gave origin to the Influenza A (H1N1) in 2009.The Greek physician Hippocrates, the "Father of Medicine", first described influenza in 412 BC. First influenza pandemic - 1580 and since then influenza pandemics occurred every 10 to 30 years.

An epidemic is a outbreak of a disease, where the number of people who have the disease is increasing rapidly.

A Pandemic is a outbreak that is literally everywhere. (From the Greek pan- meaning all.)

Endemic refers to a disease which is based in a population without outside vectors of transmission. It is also used to mean a disease which isn't increasing nor decreasing in numbers.8

ANTIGENIC VARIATION

Types of Antigenic shift

Antigenic shift - two or more different strains of a virus combine to form a new subtype having a mixture of the surface antigens of the two strains. Antigenic drift is the natural mutation over time of known strains of influenza which may lead to a loss of immunity, or in vaccine mismatch.

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MORPHOLOGY

16 versions of HA & 9 versions of NA.. . The most effective ones are the ones against hemagglutinin, which block infection of new cells. Antibodies against neuraminidase, like the ones shown here from PDB entry 1nca, can reduce the severity of the flu, playing a supporting role in the fight against the virus.

. At the center (PDB entry 3b7e) is zanamivir bound to neuraminidase from the "Spanish flu" virus that caused a pandemic in 1918. At the bottom (PDB entry 2hu4) is oseltamivir bound to an avian flu virus. 10

MORPHOLOGY

COMPARISON

TYPE ATYPE B TYPE C

Severity of illness++++++ +

Animal reservoiryes nono

Human pandemicsyes no no

Human epidemicsyesyesno (sporadic)

Antigenic changesshift, drift drift drift

Segmented genomeyes yesyes

Amantadine, rimantidine sensitiveno effectno effect

Zanamivir (Relenza)sensitivesensitiveNo effect

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Type A influenza - classified into subtypes depending on which versions of two different proteins are present on the surface of the virus. For example: A virus with version 1 of the HA protein and version 2 of the NA protein would be called influenza A subtype H1N2 = A H1N2The influenza A - further classified into strainsTherefore, an H1N1 strain isolated in California in 2009 is referred to as = A/California/07/2009 (H1N1).

LIFECYCLE

Incubation period - 1-7 days.Communicability - From 1 day before to 7 days after the onset of symptoms.

WHY PIGS???

Pigs have both types of receptors for Influenza in the respiratory system, the sialic acid 2,3 and 2,6. While the virus circulating in birds have difficulties to infect us because it uses mostly 2,3 and we only have this receptor in the lower respiratory tract (lung region), which makes the spread by cough or sneeze difficult if this virus enters pigs it will find the 2,3 in the entire respiratory system, including the upper respiratory system. It will also find the 2,6 that, if it is able to use it, it will guarantee a higher chance of transmission among humans.There is also the issue of temperature. Birds have a more active metabolism than ours, chickens for instance have an average temperature of 42C, in such a way that a virus adapted to replicate in birds generally has its enzyme functioning with less efficiency in humans. Pigs, however, have an average temperature of 39C, very close to ours, a convenient intermediary between birds and humans.

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PATHOGENESIS

The influenza virus infects by binding its haemagglutinin protein to sialic acid-containing molecules on the surfaces of host cells, thereby facilitating entry. The species specificity of influenza viruses is attributable in part to the type of sialic acid and the type of linkage to galactose on host cells. For this reason, avian influenza, which binds with high affinity to alpha-2,3-Gal-terminated sialosaccharides, only infrequently infects human respiratory epithelium, which contains sialic acid (SA)-alpha-2,6-Gal-terminated saccharides. However, pig respiratory epithelium contains both types of sialic acid and linkages, which may explain the ability of swine to serve as a common host for human and avian influenza viruses.The swine influenza virus is spread by aerosolised droplets or direct contact. It may also be spread by contact with bodily fluids, including diarrhoeal stools. Transmission can occur by person-to-person contact or pig-to-person contact. Eating pork or handling meat does not cause infection. Infection by one H1N1 influenza virus does not confer protection against infection by other H1N1 influenza A viruses, hence the need for annual immunisation against circulating strains.

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Symptoms Cold Flu

FeverRare or mildCharacteristic, high(100-102 F); lasts 3-4 daysHeadacheRare Prominent General Aches, PainsSlightUsual; often severeFatigue, WeaknessQuite mildCan last up to2-3weeksExtreme ExhaustionNeverEarly and prominentStuffy NoseCommonSometimesSneezingUsualSometimesSore ThroatCommonSometimesChest Discomfort,CoughMild to moderate;hacking coughCommon; can become severeComplications Sinus congestionor earacheBronchitis, pneumonia;can be life-threatening

PHASES OF PANDEMICPhase 1 No influenza viruses circulating in animals reported to cause infections in humansPhase 2 Influenza virus circulating in animals reported to cause infection in humansPhase 3 Small clusters of infections in humans, but no human-to-human transmissionPhase 4 Human-to-human transmission resulting in community-wide outbreaksPhase 5 Human-to-human transmission in at least two countries within one WHO regionPhase 6 Community level outbreaks in at least one other country in a different WHO region in addition to the criteria defined in Phase 5

Swine influenza, or swine flu, is a very contagious respiratory disease of pigs. Swine flu viruses produce high levels of illness in pigs, but do not generally cause them to die. Pigs become infected year round, although the highest incidence of infection occurs in late fall and winter, similar to outbreaks in humans. In addition to infection with swine influenza viruses, pigs are also susceptible to infection by avian influenza or human seasonal influenza viruses. This can lead to a dangerous mixing or reassortment of different influenza types, resulting in the creation of new virus subtypes.Courtesy:CDCC. S. Goldsmith and A. BalishSwine influenza viruses do not usually infect humans, except for occasional cases where a person has had close contact with an infected pig. In 1976, a highly publicized outbreak of swine flu occurred among soldiers in Fort Dix, New Jersey. The cause of this outbreak was a swine influenza virus that mutated in such a way to allow it to spread among humans. This virus caused disease and one death among otherwise healthy individuals. Fearing that a flu pandemic was imminent, officials rushed to produce a vaccine, but the vaccination drive was quickly halted after hundreds of people reported developing a paralyzing disorder called Guillain-Barre syndrome after getting immunized. There was limited transmission outside of the group of soldiers, and the virus disappeared after a short time.

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A new swine flu emergesIn April, a new influenza virus that originated in swine was detected that is capable of infecting humans and spreading from person to person. This virus is called influenza A (H1N1), although it is commonly referred to as swine flu. It is distinct from the swine flu virus of 1976 and also from human seasonal H1N1 influenza viruses. Although it is called swine flu, the new H1N1 virus is transmitted from person to person, and not through contact with pigs or pork products.The new H1N1 virus appears to be made up of a novel combination of segments from four different influenza virus strains - a Eurasian swine virus, a North American swine virus, and avian and human influenza virus segments (probably as a result of the mixing of a swine/avian/human triple assortment virus with the Eurasian swine virus, with H1 derived from a classical swine virus and N1 from the Eurasian virus).Reassortment of segments from these different viruses has produced a unique virus that has not been seen before by the human population, although some of the pieces of the new virus may have been circulating in pigs as early as 1998. Whenever a new virus passes directly from animals to people, limited or no natural immunity is likely to exist in humans, and so therefore nearly everyone may be susceptible.The 2009 H1N1 pandemic

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CASE DEFINITION

A suspected case of swine 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 swine influenza A (H1N1) virus infection, or within 7 days of travel to community where there are one or more confirmed swine influenza A(H1N1) cases, or resides in a community where there are one or more confirmed swine influenza cases.

A probable case of swine 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.

A confirmed case of swine influenza A (H1N1) virus infection is defined as: A person with an acute febrile respiratory illness with laboratory confirmed swine 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 swine influenza A (H1N1) virus specific neutralizing antibodies.

DIAGNOSIS

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

Keep specimens at 4C in viral transport media until transported for testing. Transported to designated laboratories with in 24 hours. If no - stored at -70C. Repeat blood samples after 14 days.

Routine investigations - haematological, biochemical, radiological and microbiological tests as necessary.Confirmation of influenza A(H1N1) swine origin infection is through: Real time RT PCR or Isolation of the virus in culture or Four-fold rise in virus specific neutralizing antibodies.

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MethodRapid influenza diagnostic tests (RIDT)Direct and indirect immunofluorescence assays (DFA and IFA)Viral isolation in tissue cell cultureNucleic acid amplification tests (including rRT-PCR)

AvailabilityAntigen detectionWideAntigen detectionWideVirus isolationLimitedRNA detectionLimited

TypicalProcessing Time20.5 hour2 4 hours2 -10 days48 96 hours

Sensitivity3 for 2009 H1N1 influenza10 70%4793%-86 100%

Distinguishes 2009 H1N1 influenza from other influenza A viruses?NoNoYes Yes

1 - Serologic testing on paired acute- (within 1 week of illness onset) and convalescent-phase (collected 2-3 weeks later) sera is limited to epidemiological and research studies, is not routinely available through clinical laboratories, and should not inform clinical decisions.2 - The amount of time needed from specimen collection until results are available. 3 - Compared with rRT-PCR tests; rRT-PCR tests are compared to other testing modalities including other rRT-PCR assays.4 - Rapid Influenza Diagnostic Tests include tests that are CLIA waived (can be performed in an outpatient setting) and tests that are moderately complex (can be performed only in a laboratory). Clinical specimens approved for RIDTs vary by test, and may not include all respiratory specimens. 5 - Performance of these assays relies heavily on laboratory expertise and requires a fluorescent microscope6 - Requires additional testing on the viral isolate7 - The performance of rRT-PCR assays specific for 2009 H1N1 influenza have not been established for bronchoalveolar lavage and tracheal aspirates. If testing these specimens for 2009 H1N1 influenza consider testing in parallel with a nasopharyngeal, nasal, or oropharyngeal swabs or a nasal aspirate.

Once influenza activity has been documented in a community or geographic area, most patients with an uncomplicated illness consistent with influenza can be diagnosed clinically and do not require influenza testing for clinical management, including antiviral treatment decisions. In certain situations, influenza diagnostic testing of patients who are not severely ill may help inform decisions regarding clinical care, infection control, or management of close contacts. Clinicians should use their clinical judgment in these situations to decide when to test for influenza in patients who are not severely ill. When interpreting the test results, clinicians should consider the following factors: sensitivity of the influenza diagnostic test used (Table 1) the patients stage of illness (influenza diagnostic tests are more likely to be positive when performed in the first three days of illness when viral levels are highest)local surveillance information on circulating influenza viruses and other respiratory viruses that can cause influenza-like illness Given the lower sensitivity of RIDT and DFA relative to rRT-PCR, a negative test result does not rule out influenza virus infection. A positive RIDT or DFA result, however, is informative because the specificity of these tests is high. These tests do not provide information on the influenza A subtype (e.g., 2009 H1N1 vs. seasonal H3N2) but if most circulating influenza A viruses have similar antiviral susceptibilities, influenza A subtype information may not be needed to inform clinical care. Under conditions where the majority of circulating influenza viruses are 2009 H1N1, a positive RIDT or DFA test result for influenza A virus can be assumed to be 2009 H1N1 influenza.If identification of 2009 H1N1 influenza is required, testing with an rRT-PCR assay specific for 2009 H1N1 influenza or viral culture should be performed. For example, specific influenza diagnostic testing for 2009 H1N1 influenza with rRT-PCR may be important for patients with certain conditions, such as pregnancy or severe immunosuppression.Hospitalized PatientsHospitalized patients with suspected influenza should receive immediate empiric antiviral treatment and be tested with an available influenza diagnostic test (Table 1). Identification of influenza infection can improve clinical care and infection control in hospitalized patients. Appropriate antiviral treatment and infection control measures should not be delayed pending diagnostic testing results. Since a negative RIDT or DFA test result does not exclude influenza virus infection, hospitalized patients with a negative RIDT or DFA result should have priority for further testing with a nucleic acid amplification test, such as rRT-PCR, if influenza infection is clinically suspected. For patients with severe lower respiratory

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DIAGNOSIS The samples are to be tested & at present the following laboratories are the identified laboratories for this purpose:

(i) National Institute of Communicable Diseases, 22, Sham Nath Marg, Delhi [Tel. Nos. Influenza Monitoring Cell: 011-23921401; Director: 011-23913148](ii) National Institute of Virology, 20-A, Dr. Ambedkar Road, Pune-411001 [Tel.No. 020-2612

NATIONAL INFLUENZA CENTREIndia - Kasauli Usha Soren Singh National Influenza Center Central Research Institute Kasauli (H.P.) India Fax: +91 (1792) 72016

India Mumbai Ranjana Deshmukh Department of Virology Acharya Donde Marg Parel, Mumbai India Fax: +91 (22) 416 1787

India Pune A.C. Mishra National Institute of Virology 20-A Dr Ambedkar Road P.O. Box 11411001 Pune India Fax: +91 (20) 26122669

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

Infrastructure / manpower / material supportIsolation facilities: if dedicated isolation room is not available then patients can be cohorted in a well ventilated isolation ward with beds kept one metre apart.Manpower: Dedicated doctors, nurses and paramedical workers.Equipment: Portable X Ray machine, ventilators, large oxygen cylinders, pulse oxymeterSupplies: Adequate PPE, disinfectants and medications (Oseltamivir, antibiotics and other medicine)

Standard Operating ProceduresReinforce standard infection control precautions i.e. all those entering the room must use high efficiency masks, gowns, goggles, gloves, cap and shoe cover.Restrict number of visitors and provide them with PPE.Provide antiviral prophylaxis to health care personnel managing the case and ask them to monitor their own health twice a day.Dispose waste properly by placing it in sealed impermeable bags labeled as Bio- Hazard.

Oseltamivir is the recommended drug both for prophylaxis and treatment.

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