1) YELLOW FEVERGroup Group IV ((+) ssRNA)Order Unassigned.pdf
Our Experience with SWINE FLU
1. SWINE FLUSWINE FLU
Dr Nirmal B TapariaDr Nirmal B Taparia
MD MedicineMD Medicine
Physician & IntensivistPhysician & Intensivist
Ashwini HospAshwini Hosp
2. What is Swine FluWhat is Swine Flu
Swine influenza virusSwine influenza virus (referred to as(referred to as
SIVSIV) refers to influenza cases that are) refers to influenza cases that are
caused by Orthomyxovirus endemic to pigcaused by Orthomyxovirus endemic to pig
populations. SIV strains isolated to datepopulations. SIV strains isolated to date
have been classified either ashave been classified either as
Influenza(virus C or one of the variousInfluenza(virus C or one of the various
subtypes of the genus Influenza virus A)subtypes of the genus Influenza virus A)
3. 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 asThis virus was originally referred to as
“swine flu” because laboratory testing“swine flu” because laboratory testing
showed that many of the genes in thisshowed that many of the genes in this
4. What are the Signs & Symptoms ofWhat 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
5. Different Strains circulateDifferent Strains circulate
PeriodicallyPeriodically
In the United States the H1N1 subtypeIn the United States the H1N1 subtype
was exclusively prevalent among swinewas exclusively prevalent among swine
populations before 1998; however, sincepopulations before 1998; however, since
late August 1998, H3N2 subtypes havelate August 1998, H3N2 subtypes have
been isolated from pigs. As of 2004, H3N2been isolated from pigs. As of 2004, H3N2
virus isolates in US swine and turkeyvirus isolates in US swine and turkey
stocks were triple reassortants, containingstocks were triple reassortants, containing
genes from human (HA, NA, and PB1),genes from human (HA, NA, and PB1),
swine (NS, NP, and M), and avian (PB2swine (NS, NP, and M), and avian (PB2
and PA) lineages.and PA) lineages.
6. Swine Influenza (Flu)Swine Influenza (Flu)
Swine Influenza (swine flu) is a respiratorySwine Influenza (swine flu) is a respiratory
disease of pigs caused by type Adisease of pigs caused by type A
influenza that regularly cause outbreaks ofinfluenza that regularly cause outbreaks of
influenza among pigs. Swine flu viruses doinfluenza among pigs. Swine flu viruses do
not normally infect humans, however,not normally infect humans, however,
human infections with swine flu do occur,human infections with swine flu do occur,
and cases of human-to-human spread ofand cases of human-to-human spread of
swine flu viruses has been documented.swine flu viruses has been documented.
7. 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 ILIsurveillance began picking up cases of ILI
starting 18 March. The number of casesstarting 18 March. The number of cases
has risen steadily through April and as ofhas risen steadily through April and as of
23 April there are now more than 85423 April there are now more than 854
cases of pneumonia from the capital. Ofcases of pneumonia from the capital. Of
those, 59 have died. In San Luis Potosi, inthose, 59 have died. In San Luis Potosi, in
central Mexico, 24 cases of ILI, with threecentral Mexico, 24 cases of ILI, with three
deaths, have been reported.deaths, have been reported.
(NEJM Aug. 2009)(NEJM Aug. 2009)
8. Swine Flu and VirusSwine Flu and Virus
Swine Influenza (swine flu) is a respiratorySwine Influenza (swine flu) is a respiratory
disease of pigs caused by type A influenza virusdisease of pigs caused by type A influenza virus
that regularly causes outbreaks of influenza inthat regularly causes outbreaks of influenza in
pigs. Swine flu viruses cause high levels ofpigs. Swine flu viruses cause high levels of
illness and low death rates in pigs. Swineillness and low death rates in pigs. Swine
influenza viruses may circulate among swineinfluenza viruses may circulate among swine
throughout the year, but most outbreaks occurthroughout the year, but most outbreaks occur
during the late fall and winter months similar toduring the late fall and winter months similar to
outbreaks in humans. The classical swine fluoutbreaks in humans. The classical swine flu
virus (an influenza type A H1N1 virus) was firstvirus (an influenza type A H1N1 virus) was first
isolated from a pig in 1930.isolated from a pig in 1930.
9. Cause by Reassortment ofCause by Reassortment of
different strainsdifferent strains
Like all influenza viruses,Like all influenza viruses,
swine flu viruses changeswine flu viruses change
constantly. Pigs can beconstantly. Pigs can be
infected by avianinfected by avian
influenza and humaninfluenza and human
influenza viruses as wellinfluenza viruses as well
as swine influenzaas swine influenza
viruses. When influenzaviruses. When influenza
viruses from differentviruses from different
species infect pigs, thespecies infect pigs, the
viruses can reassort (i.e.viruses can reassort (i.e.
swap genes) and newswap genes) and new
viruses that are a mix ofviruses that are a mix of
swine, human and/orswine, human and/or
avian influenza virusesavian influenza viruses
can emerge
10. Swine Flu differs from HumanSwine Flu differs from Human
FluFlu
The H1N1 swine fluThe H1N1 swine flu
viruses areviruses are
antigenically veryantigenically very
different from humandifferent from human
H1N1 viruses and,H1N1 viruses and,
therefore, vaccinestherefore, vaccines
for human seasonalfor human seasonal
flu would not provideflu would not provide
protection from H1N1protection from H1N1
swine flu virusesswine flu viruses
11. Present Swine Flu strainsPresent Swine Flu strains
At this time, there are fourAt this time, there are four
main influenza type Amain influenza type A
virus subtypes that havevirus subtypes that have
been isolated in pigs:been isolated in pigs:
H1N1, H1N2, H3N2, andH1N1, H1N2, H3N2, and
H3N1. However, most ofH3N1. However, most of
the recently isolatedthe recently isolated
influenza viruses frominfluenza viruses from
pigs have been H1N1pigs have been H1N1
viruses.viruses.
12. Swine flu…Swine flu…
Influenza A is most virulent.Influenza A is most virulent.
It is known to cause pandemics.TheseIt is known to cause pandemics.These
strains evolve and mutate thru severalstrains evolve and mutate thru several
stages while infecting the humans.stages while infecting the humans.
Interpandemic influenza A is less virulentInterpandemic 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 antibodyC is least with good serum antibody
response in humans.response in humans.
14. 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 werepatients with similar pattern of illness were
admitted to our hospital later proved to beadmitted to our hospital later proved to be
caused by Swine Flu.caused by Swine Flu.
Methods :Methods :
we used retrospective medical chartwe used retrospective medical chart
reviews to collect data on the hospitalisedreviews to collect data on the hospitalised
patients.patients.
15. Our experience…Our experience…
Swine flu was confirmed with samplesSwine flu was confirmed with samples
sent to NIV Pune by use of a real timesent to NIV Pune by use of a real time
reverse transcriptase PCR.reverse transcriptase PCR.
Conclusions :Conclusions :
acute swine flu can cause severe illness,acute swine flu can cause severe illness,
ARDS, and death in previously healthyARDS, and death in previously healthy
persons who are young to middle age.persons who are young to middle age.
16. Analysis…Analysis…
A total of 28 pts were positive for swine fluA total of 28 pts were positive for swine flu
during this period.during this period.
18 male & 10 female.18 male & 10 female.
Pts.admitted were from all over the districtPts.admitted were from all over the district
and were suspected for swine flu.and were suspected for swine flu.
Data was gathered and analysedData was gathered and analysed
retrospectively to study the disease.retrospectively to study the disease.
18. 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
23. RESULTS (Observations)RESULTS (Observations)
Admissions for respiratory symptoms andAdmissions for respiratory symptoms and
pneumonia increased during this period.pneumonia increased during this period.
Median age of pts was 44.4Median age of pts was 44.4
More than half were between 15 and 50More 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 pneumococcalNone of the pts had a h/o pneumococcal
vaccination.vaccination.
24. Results…Results…
Time between onset of symptoms andTime between onset of symptoms and
presentation to casualty was between 1 topresentation to casualty was between 1 to
8 days.(Median of 4.81)8 days.(Median of 4.81)
Symptoms of cough(93%), fever(89)% andSymptoms of cough(93%), fever(89)% and
respiratory distress (82%) wererespiratory distress (82%) were
predominant.predominant.
14 pts had associated comorbid14 pts had associated comorbid
conditions like DM, HTN, IHD, COPD,conditions like DM, HTN, IHD, COPD,
25. 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 total14 pts needed ventilation in total
(bipap+invasive)(bipap+invasive)
10 pts eventually went on mechanical10 pts eventually went on mechanical
ventilation of which 1 survived.ventilation of which 1 survived.
In investigations Lymphopenia, raised CKIn investigations Lymphopenia, raised CK
and LDH and ¾ quadrant opacities onand LDH and ¾ quadrant opacities on
xray, hypotension, low Ph were importantxray, hypotension, low Ph were important
features diagnostically.features diagnostically.
26. 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 CVSPts. With chronic disorders of the CVS
and RS.and RS.
Pts. Who have chronic metabolicPts. Who have chronic metabolic
diseases.diseases.
Health care workers.Health care workers.
27. Adults Need attention ifAdults Need attention if
Present withPresent with
Difficulty breathing or shortness of breathDifficulty breathing or shortness of breath
Pain or pressure in the chest or abdomenPain or pressure in the chest or abdomen
Sudden dizzinessSudden dizziness
ConfusionConfusion
Severe or persistent vomitingSevere or persistent vomiting
29. Discussion…Discussion…
We presented retrospective analysis o 28We presented retrospective analysis o 28
pts. Detected to have H1N1 in ourpts. Detected to have H1N1 in our
hospital.hospital.
28 patients of which 18 were male and 1028 patients of which 18 were male and 10
female, were admitted from Jan to 8 Marfemale, were admitted from Jan to 8 Mar
2015.2015.
9 pts died during treatment i.e mortality of9 pts died during treatment i.e mortality of
32.14%.32.14%.
30. Pathogenesis & Immunity…Pathogenesis & Immunity…
Infection by a small particle aerosol<10umInfection by a small particle aerosol<10um
is more efficient.is more efficient.
Initially virus infects the ciliated columnarInitially virus infects the ciliated columnar
epithelial cells.epithelial cells.
Virus replicates by 4-6 hrs and released toVirus 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 replacedInfected 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.
31. Complications…Complications…
Pulmonary:Pulmonary:
Primary influenza pneumonia:Primary influenza pneumonia:
Least common. Xray findings of diffuseLeast 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 andPredilection in diseased pts and
pregnancypregnancy
Secondary bacterial pneumoniaSecondary bacterial pneumonia
32. Comp…Comp…
Reappearance of fever and s/s of bacterialReappearance of fever and s/s of bacterial
pneumonia.pneumonia.
Commonly caused by streptococcus pneu.Commonly caused by streptococcus pneu.
Staph. Aureus, H influenzae.Staph. Aureus, H influenzae.
Common in high risk individuals.Common in high risk individuals.
Mixed pneumonia :Mixed pneumonia :
Most common pneumonic complicationMost common pneumonic complication
during outbreaks.during outbreaks.
33. Comp…Comp…
Xrays show less widespread involvementXrays show less widespread involvement
of the lung compared to primaryof 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-
myelitismyelitis
34. DiagnosisDiagnosis
To diagnose swineTo diagnose swine
influenza A infection, ainfluenza A infection, a
respiratory specimenrespiratory specimen
would generally need towould generally need to
bebe collected withincollected within
the first 4 to 5 daysthe first 4 to 5 days
of illnessof illness (when an(when an
infected person is mostinfected person is most
likely to be sheddinglikely to be shedding
virus). However, somevirus). However, some
persons, especiallypersons, especially
children, may shed viruschildren, may shed virus
for 10 days or longer.for 10 days or longer.
Identification as a swineIdentification as a swine
flu influenza A virusflu influenza A virus
35. Drugs which are effective inDrugs which are effective in
Swine FluSwine Flu
There are four differentThere are four different
antiviral drugs that areantiviral drugs that are
licensed for use in the USlicensed for use in the US
for the treatment offor the treatment of
influenza:influenza: Amantidine,Amantidine,
rimantadine,rimantadine,
oseltamivir andoseltamivir and
zanamivirzanamivir. While most. While most
swine influenza virusesswine influenza viruses
have been susceptible tohave been susceptible to
all four drugsall four drugs
36. 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.
37. Drugs…Drugs…
Amantadine & Rimantadine also can beAmantadine & Rimantadine also can be
used for t/t though less effective.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 beingTheir use for prophylaxis is being
evaluated but amantadine hasevaluated but amantadine has
considerable CNS toxicity.considerable CNS toxicity.
Drugs decrease s/s of uncomplicated fluDrugs decrease s/s of uncomplicated flu
by 1.5 to 2 days if started within 48 hrs ofby 1.5 to 2 days if started within 48 hrs of
onset.onset.
38. Newer Drugs…Newer Drugs…
Iv zanamivir is been developedIv zanamivir is been developed
Peramivir :iv & im preparations are underPeramivir :iv & im preparations are under
development. Its a neuraminidasedevelopment. Its a neuraminidase
inhibitor.inhibitor.
Fludase 181DAS :cleaves the influenzaFludase 181DAS :cleaves the influenza
receptors and removes them fromreceptors and removes them from
epithelial cells.epithelial cells.
Cyanovirin N :a hemagluttinin receptorCyanovirin N :a hemagluttinin receptor
inhibitor that blocks viral entry.inhibitor that blocks viral entry.
39. Newer drugs…Newer drugs…
T 705 :active against N-inhibitor resistant,T 705 :active against N-inhibitor resistant,
amantadine resistant virus.amantadine resistant virus.
(nejm:aug 13 2009)(nejm:aug 13 2009)
Also global transmission of oseltamivirAlso global transmission of oseltamivir
resistant influenza is also on the rise.resistant influenza is also on the rise.
40. Drugs proved resistant atDrugs proved resistant at
PresentPresent
Most recent swineMost recent swine
influenza virusesinfluenza viruses
isolated from humansisolated from humans
areare resistant toresistant to
Amantidine andAmantidine and
RimantadineRimantadine
41. VaccinationVaccination
The efficacy of influenza vaccine mayThe efficacy of influenza vaccine may
differ from year to year.differ from year to year.
It differs in LIVE and INACTIVATEDIt differs in LIVE and INACTIVATED
vaccines too.vaccines too.
The absolute efficacy against influenza AThe absolute efficacy against influenza A
virus was 72% for INACTIVATED vaccinevirus was 72% for INACTIVATED vaccine
and 29% for LIVE vaccine.and 29% for LIVE vaccine.
(nejm sep 2009)(nejm sep 2009)
42. Vaccination…Vaccination…
In elderly people study showed that HighIn elderly people study showed that High
dose (60ug hemagluttinin per strain)dose (60ug hemagluttinin per strain)
trivalent Inactivated influenza vaccinetrivalent Inactivated influenza vaccine
improves antibody response to influenzaimproves antibody response to influenza
as compared to standard dose (15ug ofas compared to standard dose (15ug of
hemagluttinin)hemagluttinin)
(nejm aug 2014)(nejm aug 2014)
43. Vaccination…Vaccination…
Effective vaccination depends uponEffective vaccination depends upon
development of HAI titers of >1:40 indevelopment 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 vaccinationThe 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 inRecent study in Feb 2015 in
Eurosurveillance shows decreasedEurosurveillance shows decreased
vaccine effectiveness (VE) because ofvaccine effectiveness (VE) because of
genetic andgenetic and
45. Pregnancy and vaccination…Pregnancy and vaccination…
Pregnancy induces immune tolerance.Pregnancy induces immune tolerance.
Tri valent influenza vaccines producesTri valent influenza vaccines produces
immunogenicity and HAI>1:40 andimmunogenicity and HAI>1:40 and
protection to mothers.protection to mothers.
Studies in USA and Bangladesh haveStudies in USA and Bangladesh have
confirmed this.confirmed this.
Antibodies from mothers crossing placentsAntibodies from mothers crossing placents
and protecting fetus is not known but,and protecting fetus is not known but,
(nejm sep.2014)(nejm sep.2014)
46. Pregnancy and vaccination…Pregnancy and vaccination…
Decreased risk of infection in vaccinatedDecreased risk of infection in vaccinated
mother decreases risk to fetus.mother decreases risk to fetus.
WHO safely recommends immunisation inWHO safely recommends immunisation in
pregnancy,pregnancy,
Adaptive changes occur during pregnancyAdaptive changes occur during pregnancy
such as inc. HR & SV and dec.pulmonarysuch as inc. HR & SV and dec.pulmonary
residual capacity,and inc. the risk ofresidual capacity,and inc. the risk of
hypoxia & disease severity.hypoxia & disease severity.
(NEJM Jan 2013)(NEJM Jan 2013)
47. How long can an infected personHow long can an infected person
spread swine flu to othersspread swine flu to others??
People with swine influenza virus infectionPeople with swine influenza virus infection
should be considered potentiallyshould be considered potentially
contagious as long as they arecontagious as long as they are
symptomatic and possible for up to 7 dayssymptomatic and possible for up to 7 days
following illness onset. Children, especiallyfollowing illness onset. Children, especially
younger children, might potentially beyounger children, might potentially be
contagious for longer periods.contagious for longer periods.
48. How long can viruses liveHow long can viruses live
outside the body?outside the body?
We know that some viruses and bacteriaWe know that some viruses and bacteria
can live 2 hours or longer on surfaces likecan live 2 hours or longer on surfaces like
cafeteria tables, doorknobs, and desks.cafeteria tables, doorknobs, and desks.
Frequent hand washing will help youFrequent hand washing will help you
reduce the chance of gettingreduce the chance of getting
contamination from these commoncontamination from these common
surfaces.surfaces.
49. 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.