SWINE FLUSWINE FLUDr Nirmal B TapariaDr Nirmal B Taparia

MD MedicineMD Medicine

Physician & IntensivistPhysician & Intensivist

Ashwini HospAshwini Hosp

What is Swine FluWhat is Swine Flu

Swine influenza virusSwine influenza virus (referred to (referred to as as SIVSIV) refers to influenza cases that ) refers to influenza cases that are caused by Orthomyxovirus are caused by Orthomyxovirus endemic to pig populations. SIV endemic to pig populations. SIV strains isolated to date have been strains isolated to date have been classified either as Influenza(virus C classified either as Influenza(virus C or one of the various subtypes of the or one of the various subtypes of the genus Influenza virus A)genus Influenza virus A)

What is H1N1 Influenza A Virus (Swine Flu)?What is H1N1 Influenza A Virus (Swine Flu)? H1N1 (referred to as “swine flu” early on)

is a new influenza virus causing illness in people.

This new virus was first detected in people in April 2009 in the United States.

H1N1 Influenza A (swine flu) is transmitted by respiratory secretions

This virus was originally referred to as This virus was originally referred to as “swine flu” because laboratory testing “swine flu” because laboratory testing showed that many of the genes in this showed that many of the genes in this new virus were very similar to influenza new virus were very similar to influenza viruses that normally occur in pigs in viruses that normally occur in pigs in North America.North America.

What are the Signs & Symptoms of What are the Signs & Symptoms of H1N1 Influenza A in Humans?in Humans?

The symptoms of this new influenza A H1N1 virus in people are similar to the symptoms of regular human flu and include fever (greater than 100.0º F or 37.8 º C), cough, sore throat, body aches, headache, chills and fatigue.

A significant number of people who have been infected with this virus also have reported diarrhea and vomiting.  

Also, like seasonal flu, severe illnesses and death has occurred as a result of illness associated with this virus.

Different Strains circulate Different Strains circulate PeriodicallyPeriodically

In the United States the H1N1 subtype In the United States the H1N1 subtype was exclusively prevalent among swine was exclusively prevalent among swine populations before 1998; however, populations before 1998; however, since late August 1998, H3N2 subtypes since late August 1998, H3N2 subtypes have been isolated from pigs. As of have been isolated from pigs. As of 2004, H3N2 virus isolates in US swine 2004, H3N2 virus isolates in US swine and turkey stocks were triple and turkey stocks were triple reassortants, containing genes from reassortants, containing genes from human (HA, NA, and PB1), swine (NS, human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and PA) NP, and M), and avian (PB2 and PA) lineages.lineages.

Swine Influenza (Flu)Swine Influenza (Flu)

Swine Influenza (swine flu) is a Swine Influenza (swine flu) is a respiratory disease of pigs caused by respiratory disease of pigs caused by type A influenza that regularly cause type A influenza that regularly cause outbreaks of influenza among pigs. outbreaks of influenza among pigs. Swine flu viruses do not normally infect Swine flu viruses do not normally infect humans, however, human infections humans, however, human infections with swine flu do occur, and cases of with swine flu do occur, and cases of human-to-human spread of swine flu human-to-human spread of swine flu viruses has been documented. viruses has been documented.

Swine Flu in MexicoSwine Flu in Mexico

In the Federal District of Mexico, In the Federal District of Mexico, surveillance began picking up cases of ILI surveillance began picking up cases of ILI starting 18 March. The number of cases starting 18 March. The number of cases has risen steadily through April and as of has risen steadily through April and as of 23 April there are now more than 854 23 April there are now more than 854 cases of pneumonia from the capital. Of cases of pneumonia from the capital. Of those, 59 have died. In San Luis Potosi, in those, 59 have died. In San Luis Potosi, in central Mexico, 24 cases of ILI, with three central Mexico, 24 cases of ILI, with three deaths, have been reported.deaths, have been reported.

(NEJM Aug. 2009) (NEJM Aug. 2009)

Swine Flu and VirusSwine Flu and Virus Swine Influenza (swine flu) is a respiratory Swine Influenza (swine flu) is a respiratory

disease of pigs caused by type A influenza disease of pigs caused by type A influenza virus that regularly causes outbreaks of virus that regularly causes outbreaks of influenza in pigs. Swine flu viruses cause influenza in pigs. Swine flu viruses cause high levels of illness and low death rates in high levels of illness and low death rates in pigs. Swine influenza viruses may circulate pigs. Swine influenza viruses may circulate among swine throughout the year, but most among swine throughout the year, but most outbreaks occur during the late fall and outbreaks occur during the late fall and winter months similar to outbreaks in winter months similar to outbreaks in humans. The classical swine flu virus (an humans. The classical swine flu virus (an influenza type A H1N1 virus) was first influenza type A H1N1 virus) was first isolated from a pig in 1930. isolated from a pig in 1930.

Cause by Reassortment of Cause by Reassortment of different strainsdifferent strains

Like all influenza viruses, Like all influenza viruses, swine flu viruses change swine flu viruses change constantly. Pigs can be constantly. Pigs can be infected by avian infected by avian influenza and human influenza and human influenza viruses as well influenza viruses as well as swine influenza viruses. as swine influenza viruses. When influenza viruses When influenza viruses from different species from different species infect pigs, the viruses can infect pigs, the viruses can reassort (i.e. swap genes) reassort (i.e. swap genes) and new viruses that are a and new viruses that are a mix of swine, human mix of swine, human and/or avian influenza and/or avian influenza viruses can emerge viruses can emerge

Swine Flu differs from Swine Flu differs from Human FluHuman Flu

The H1N1 swine flu The H1N1 swine flu viruses are viruses are antigenically very antigenically very different from human different from human H1N1 viruses and, H1N1 viruses and, therefore, vaccines therefore, vaccines for human seasonal for human seasonal flu would not provide flu would not provide protection from H1N1 protection from H1N1 swine flu viruses swine flu viruses

Present Swine Flu Present Swine Flu strainsstrains

At this time, there are At this time, there are four main influenza four main influenza type A virus subtypes type A virus subtypes that have been that have been isolated in pigs: H1N1, isolated in pigs: H1N1, H1N2, H3N2, and H1N2, H3N2, and H3N1. However, most H3N1. However, most of the recently of the recently isolated influenza isolated influenza viruses from pigs have viruses from pigs have been H1N1 viruses. been H1N1 viruses.

Swine flu…Swine flu…

Influenza A is most virulent.Influenza A is most virulent. It is known to cause pandemics.These It is known to cause pandemics.These

strains evolve and mutate thru several strains evolve and mutate thru several stages while infecting the humans.stages while infecting the humans.

Interpandemic influenza A is less virulent Interpandemic influenza A is less virulent as compared to pandemic strains.as compared to pandemic strains.

B is less virulent more localised.B is less virulent more localised. C is least with good serum antibody C is least with good serum antibody

response in humans. response in humans.

Presentation…Presentation…

Our Our Experience…Experience…

Our experience…Our experience…

Background :Background : From mid January 2015 to March 8 2015, From mid January 2015 to March 8 2015,

patients with similar pattern of illness were patients with similar pattern of illness were admitted to our hospital later proved to be admitted to our hospital later proved to be caused by Swine Flu.caused by Swine Flu.

Methods :Methods : we used retrospective medical chart we used retrospective medical chart

reviews to collect data on the hospitalised reviews to collect data on the hospitalised patients.patients.

Our experience… Our experience…

Swine flu was confirmed with Swine flu was confirmed with samples sent to NIV Pune by use of a samples sent to NIV Pune by use of a real time reverse transcriptase PCR.real time reverse transcriptase PCR.

Conclusions :Conclusions : acute swine flu can cause severe acute swine flu can cause severe

illness, ARDS, and death in illness, ARDS, and death in previously healthy persons who are previously healthy persons who are young to middle age.young to middle age.

Analysis…Analysis…

A total of 28 pts were positive for A total of 28 pts were positive for swine flu during this period.swine flu during this period.

18 male & 10 female.18 male & 10 female. Pts.admitted were from all over the Pts.admitted were from all over the

district and were suspected for swine district and were suspected for swine flu. flu.

Data was gathered and analysed Data was gathered and analysed retrospectively to study the disease. retrospectively to study the disease.

Tables…Tables…

Statistics…Statistics…

Analysis…Analysis…

variable value percentage

Male sex 18/28 64

median 44.4

All patients 15 to 50 yrs

19/28 68

>50 yrs 9/28 32

Patients who died value percentage

15 to 50 yrs 7/19 37

> 50 yrs 2/9 22

Analysis…Analysis…

Symptoms or outcome

No. Of total percentage

cough 26/28 93

rhinorrhea 17/28 61

wheezing 10/28 36

headache 6/28 21

myalgia 7/28 25

fever 25/28 89

Resp. distress 23/28 82

diarrhoea 3/28 10

hypotension 7/28 25

Mechanical ventilation

10/28 36

deaths 9/28 32

Analysis…Analysis…

sex Total cases survived death

male 18 13 5

female 10 6 4

Analysis… Analysis…

variable median range SD

Leukocyte count

6550 3200-16000 3239.28

Lymphocyte count

Creatine kinase Mean– 95.5 34-186 53.52

LDH Mean– 740.2 322-1206 740.2

Apache score 9 1--30 7.1

Hypotension requiring inotrope

80 (6 of 9 pts who died)

60--180 ---Pts survived

Pts died Odds ratio P value

Opacity in ¾ 2/17 5/9 9.37 0.026

Quadrant in initial xray

1.29—67.65

Analysis…Median valuesAnalysis…Median values

pH Paco2 Pao2 Fio2 Pao2:Fio2

APACHE

survived 7.4 30 62 o.32 193.7 8.5

Median

death 7.35 37.1 59 o.6 165.1 17

RESULTS (Observations)RESULTS (Observations)

Admissions for respiratory symptoms Admissions for respiratory symptoms and pneumonia increased during this and pneumonia increased during this period.period.

Median age of pts was 44.4Median age of pts was 44.4 More than half were between 15 and 50 More than half were between 15 and 50

yrs.yrs. More than half (64%) were male.More than half (64%) were male. None of the pts had a h/o None of the pts had a h/o

pneumococcal vaccination.pneumococcal vaccination.

Results…Results…

Time between onset of symptoms Time between onset of symptoms and presentation to casualty was and presentation to casualty was between 1 to 8 days.(Median of 4.81)between 1 to 8 days.(Median of 4.81)

Symptoms of cough(93%), Symptoms of cough(93%), fever(89)% and respiratory distress fever(89)% and respiratory distress (82%) were predominant.(82%) were predominant.

14 pts had associated comorbid 14 pts had associated comorbid conditions like DM, HTN, IHD, COPD,conditions like DM, HTN, IHD, COPD,

Results…Results…

1 pt was pregnant and 2 were RVD +ve.1 pt was pregnant and 2 were RVD +ve. 14 pts needed ventilation in total 14 pts needed ventilation in total

(bipap+invasive)(bipap+invasive) 10 pts eventually went on mechanical 10 pts eventually went on mechanical

ventilation of which 1 survived.ventilation of which 1 survived. In investigations Lymphopenia, raised In investigations Lymphopenia, raised

CK and LDH and ¾ quadrant opacities CK and LDH and ¾ quadrant opacities on xray, hypotension, low Ph were on xray, hypotension, low Ph were important features diagnostically. important features diagnostically.

Higher risk of complications in… Higher risk of complications in…

Age <4 yrsAge <4 yrs PregnancyPregnancy Elderly >65 yrs oldElderly >65 yrs old Pts. With chronic disorders of the Pts. With chronic disorders of the

CVS and RS.CVS and RS. Pts. Who have chronic metabolic Pts. Who have chronic metabolic

diseases.diseases. Health care workers.Health care workers.

Adults Need attention if Adults Need attention if Present withPresent with

Difficulty breathing or shortness of Difficulty breathing or shortness of breath breath

Pain or pressure in the chest or Pain or pressure in the chest or abdomen abdomen

Sudden dizziness Sudden dizziness Confusion Confusion Severe or persistent vomiting Severe or persistent vomiting

Summing up…Summing up…

Discussion…Discussion…

Discussion…Discussion…

We presented retrospective analysis We presented retrospective analysis o 28 pts. Detected to have H1N1 in o 28 pts. Detected to have H1N1 in our hospital.our hospital.

28 patients of which 18 were male 28 patients of which 18 were male and 10 female, were admitted from and 10 female, were admitted from Jan to 8 Mar 2015.Jan to 8 Mar 2015.

9 pts died during treatment i.e 9 pts died during treatment i.e mortality of 32.14%.mortality of 32.14%.

Pathogenesis & Immunity…Pathogenesis & Immunity…

Infection by a small particle Infection by a small particle aerosol<10um is more efficient.aerosol<10um is more efficient.

Initially virus infects the ciliated columnar Initially virus infects the ciliated columnar epithelial cells.epithelial cells.

Virus replicates by 4-6 hrs and released to Virus replicates by 4-6 hrs and released to infect nearby cells foll. By cytokine storm.infect nearby cells foll. By cytokine storm.

Infected cells desquamate and replaced Infected cells desquamate and replaced by flat metaplastic cells.by flat metaplastic cells.

Rare in extra-pul sites including blood. Rare in extra-pul sites including blood.

Complications…Complications…

Pulmonary:Pulmonary: Primary influenza pneumonia:Primary influenza pneumonia: Least common. Xray findings of diffuse Least common. Xray findings of diffuse

interstitial infiltrates and/or ARDS.interstitial infiltrates and/or ARDS. ABG shows marked HypoxemiaABG shows marked Hypoxemia Predilection in diseased pts and pregnancyPredilection in diseased pts and pregnancy

Secondary bacterial pneumoniaSecondary bacterial pneumonia Improvement over 2-3 days is followed by Improvement over 2-3 days is followed by

Comp…Comp…

Reappearance of fever and s/s of Reappearance of fever and s/s of bacterial pneumonia.bacterial pneumonia.

Commonly caused by streptococcus Commonly caused by streptococcus pneu. Staph. Aureus, H influenzae.pneu. Staph. Aureus, H influenzae.

Common in high risk individuals.Common in high risk individuals.

Mixed pneumonia :Mixed pneumonia : Most common pneumonic complication Most common pneumonic complication

during outbreaks.during outbreaks.

Comp…Comp…

Xrays show less widespread involvement Xrays show less widespread involvement of the lung compared to primary of the lung compared to primary pneumonia.pneumonia.

Extra pulmonary complications:Extra pulmonary complications: Myositis, rhabdomyolysis, myoglobinuria.Myositis, rhabdomyolysis, myoglobinuria. Myocarditis, pericarditis.Myocarditis, pericarditis. CNS: encephalitis, GBS, transverse- CNS: encephalitis, GBS, transverse-

myelitis myelitis

DiagnosisDiagnosis To diagnose swine To diagnose swine

influenza A infection, a influenza A infection, a respiratory specimen respiratory specimen would generally need would generally need to be to be collected within collected within the first 4 to 5 days the first 4 to 5 days of illnessof illness (when an (when an infected person is most infected person is most likely to be shedding likely to be shedding virus). However, some virus). However, some persons, especially persons, especially children, may shed children, may shed virus for 10 days or virus for 10 days or longer. Identification as longer. Identification as a swine flu influenza A a swine flu influenza A virus virus

Drugs which are effective in Drugs which are effective in Swine FluSwine Flu

There are four different There are four different antiviral drugs that are antiviral drugs that are licensed for use in the licensed for use in the US for the treatment of US for the treatment of influenza: influenza: Amantidine, Amantidine, rimantadine, rimantadine, oseltamivir and oseltamivir and zanamivirzanamivir. While most . While most swine influenza viruses swine influenza viruses have been susceptible have been susceptible to all four drugsto all four drugs

DRUG TREATMENTDRUG TREATMENT

Oseltamivir: Oseltamivir: Treatment :75 mg bd for 5 daysTreatment :75 mg bd for 5 days Prophylaxis :75 mg qday for10 days.Prophylaxis :75 mg qday for10 days. (S/E: nausea, dizziness, headache, (S/E: nausea, dizziness, headache,

insomnia)insomnia) Zanamivir :Zanamivir : Treatment :10 mg inhalation bd for 5 daysTreatment :10 mg inhalation bd for 5 days Prophylaxis :10 mg inh. Qday for 10 days.Prophylaxis :10 mg inh. Qday for 10 days.

Drugs…Drugs…

Amantadine & Rimantadine also can Amantadine & Rimantadine also can be used for t/t though less effective.be used for t/t though less effective.

Doses :200mg/day for 3-7 days.Doses :200mg/day for 3-7 days. Their use for prophylaxis is being Their use for prophylaxis is being

evaluated but amantadine has evaluated but amantadine has considerable CNS toxicity.considerable CNS toxicity.

Drugs decrease s/s of uncomplicated Drugs decrease s/s of uncomplicated flu by 1.5 to 2 days if started within 48 flu by 1.5 to 2 days if started within 48 hrs of onset.hrs of onset.

Newer Drugs…Newer Drugs…

Iv zanamivir is been developedIv zanamivir is been developed Peramivir :iv & im preparations are Peramivir :iv & im preparations are

under development. Its a under development. Its a neuraminidase inhibitor.neuraminidase inhibitor.

Fludase 181DAS :cleaves the influenza Fludase 181DAS :cleaves the influenza receptors and removes them from receptors and removes them from epithelial cells.epithelial cells.

Cyanovirin N :a hemagluttinin receptor Cyanovirin N :a hemagluttinin receptor inhibitor that blocks viral entry.inhibitor that blocks viral entry.

Newer drugs…Newer drugs…

T 705 :active against N-inhibitor T 705 :active against N-inhibitor resistant, amantadine resistant virus.resistant, amantadine resistant virus.

(nejm:aug 13 2009)(nejm:aug 13 2009) Also global transmission of Also global transmission of

oseltamivir resistant influenza is also oseltamivir resistant influenza is also on the rise. on the rise.

Drugs proved resistant at Drugs proved resistant at PresentPresent

Most recent swine Most recent swine influenza viruses influenza viruses isolated from isolated from humans are humans are resistant to resistant to Amantidine and Amantidine and Rimantadine Rimantadine

VaccinationVaccination

The efficacy of influenza vaccine may The efficacy of influenza vaccine may differ from year to year.differ from year to year.

It differs in LIVE and INACTIVATED It differs in LIVE and INACTIVATED vaccines too.vaccines too.

The absolute efficacy against influenza The absolute efficacy against influenza A virus was 72% for INACTIVATED A virus was 72% for INACTIVATED vaccine and 29% for LIVE vaccine.vaccine and 29% for LIVE vaccine.

(nejm sep 2009)(nejm sep 2009)

Vaccination…Vaccination…

In elderly people study showed that In elderly people study showed that High dose (60ug hemagluttinin per High dose (60ug hemagluttinin per strain) trivalent Inactivated influenza strain) trivalent Inactivated influenza vaccine improves antibody response vaccine improves antibody response to influenza as compared to standard to influenza as compared to standard dose (15ug of hemagluttinin)dose (15ug of hemagluttinin)

(nejm aug 2014) (nejm aug 2014)

Vaccination… Vaccination…

Effective vaccination depends upon Effective vaccination depends upon development of HAI titers of >1:40 in development of HAI titers of >1:40 in vaccinated individuals. This confers 50% vaccinated individuals. This confers 50% protection.protection.

The incidence of GBS in IM vaccination The incidence of GBS in IM vaccination was less than 0.1%(nejm feb 2011)was less than 0.1%(nejm feb 2011)

Recent study in Feb 2015 in Recent study in Feb 2015 in Eurosurveillance shows decreased Eurosurveillance shows decreased vaccine effectiveness (VE) because of vaccine effectiveness (VE) because of genetic and genetic and

Vaccination…Vaccination…

Antigenic mismatch between Antigenic mismatch between infecting and vaccine strains.infecting and vaccine strains.

Pregnancy and vaccination…Pregnancy and vaccination…

Pregnancy induces immune tolerance.Pregnancy induces immune tolerance. Tri valent influenza vaccines produces Tri valent influenza vaccines produces

immunogenicity and HAI>1:40 and immunogenicity and HAI>1:40 and protection to mothers.protection to mothers.

Studies in USA and Bangladesh have Studies in USA and Bangladesh have confirmed this.confirmed this.

Antibodies from mothers crossing placents Antibodies from mothers crossing placents and protecting fetus is not known but,and protecting fetus is not known but,

(nejm sep.2014) (nejm sep.2014)

Pregnancy and vaccination…Pregnancy and vaccination…

Decreased risk of infection in vaccinated Decreased risk of infection in vaccinated mother decreases risk to fetus.mother decreases risk to fetus.

WHO safely recommends immunisation WHO safely recommends immunisation in pregnancy,in pregnancy,

Adaptive changes occur during Adaptive changes occur during pregnancy such as inc. HR & SV and pregnancy such as inc. HR & SV and dec.pulmonary residual capacity,and inc. dec.pulmonary residual capacity,and inc. the risk of hypoxia & disease severity.the risk of hypoxia & disease severity.

(NEJM Jan 2013)(NEJM Jan 2013)

How long can an infected How long can an infected person spread swine flu to person spread swine flu to

othersothers?? People with swine influenza virus People with swine influenza virus

infection should be considered infection should be considered potentially contagious as long as potentially contagious as long as they are symptomatic and possible they are symptomatic and possible for up to 7 days following illness for up to 7 days following illness onset. Children, especially younger onset. Children, especially younger children, might potentially be children, might potentially be contagious for longer periods. contagious for longer periods.

How long can viruses live How long can viruses live outside the body?outside the body?

We know that some viruses and We know that some viruses and bacteria can live 2 hours or longer on bacteria can live 2 hours or longer on surfaces like cafeteria tables, surfaces like cafeteria tables, doorknobs, and desks. Frequent hand doorknobs, and desks. Frequent hand washing will help you reduce the washing will help you reduce the chance of getting contamination chance of getting contamination from these common surfaces. from these common surfaces.

Clean Hands saves youClean Hands saves you

Clean your hands often. Clean your hands every time you cough or sneeze. Hand washing stops germs. Alcohol-based gels and wipes also work well.

Cartoonists Imagination on Cartoonists Imagination on Swine FluSwine Flu

Thank youThank you