In 1743, when disease was presumed to be astral in origin, European newspapers reported on a contagious influence (influenza in Italian) that was being visited on the citizens of Rome. Two hundred years later, Wilson Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family. Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family of viruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes of influenza A known as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swine flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases are known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection may be higher, since most cases only cause a very mild disease, and will probably never be reported or diagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” and the data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 to January 2010.

1.
SWINEE INFLUEN
NZA

2. Review Article
THE PRESENT SCENARIO-2009 H1N1
INFLUENZA (“SWINE FLU”)
2009 H1N1influenza, (sometimes called “swine flu”) is
a new influenza virus causing illness in people. This new
virus was first detected in people in the United States in
April 2009. This virus is spreading from person-to-person
worldwide, probably in much the same way that regular
seasonal influenza viruses spread. On June 11, 2009, the
World Health Organization (WHO) signaled that a
pandemic of 2009 H1N1 flu was underway.
This virus was originally referred to as “swine flu”
because laboratory testing showed that many of the genes in
this new virus were very similar to influenza viruses that
normally occur in pigs (swine) in North America [1]. But
further study has shown that this new virus is very different
from what normally circulates in North American pigs [2-
4]. It has two genes from flu viruses that normally circulate
in pigs in Europe and Asia and bird (avian) genes and
human genes [5]. Scientists call this a “quadruple
reassortant” virus [6] (Fig. 1).
Illness with 2009 H1N1 virus has ranged from mild to
severe. While most people who have been sick have
recovered without needing medical treatment,
hospitalizations and deaths from infection with this virus
have occurred.The information analyzed by CDC supports
the conclusion that 2009 H1N1 flu has caused greater
disease burden in people younger than 25 years of age than
older people [7]. At this time, there are relatively fewer
cases and deaths reported in people 65 years and older,
21 Apollo Medicine, Vol. 7, No. 1, March 2010
SWINE INFLUENZA
Suresh Chandra*and Neelam Bisht**
*Senior Consultant,**Associate Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals, Sarita Vihar,
New Delhi 110076, India.
Correspondence to: Dr Suresh Chandra, Senior Consultant, Department of Internal Medicine, Indraprastha Apollo Hospitals,
Sarita Vihar, New Delhi 110 076, India.
In 1743, when disease was presumed to be astral in origin, Europeannewspapers reported on a contagious
influence (influenza inItalian) that was being visited on the citizens of Rome. Twohundred years later, Wilson
Smith and colleagues would isolate an influenza A virus, one of the members of the orthomyxovirus family.
Swine influenza virus (SIV) or S-OIV (swine-origin influenza virus) is any strain of the influenza family of
viruses that is endemic in pigs. As of 2009, the known SIV strains include influenza C and the subtypes of
influenzaAknown as H1N1, H1N2, H3N1, H3N2, and H2N3. Swine influenza (also called Pig influenza, swine
flu, hog flu and pig flu) is an infection by any one of several types of swine influenza virus. In all, 50 cases are
known to have occurred since the first report in medical literature in 1958, which have resulted in a total of six
deaths. Of these six people, one was pregnant, one had leukemia, one had Hodgkin disease and two were
known to be previously healthy. Despite these apparently low numbers of infections, the true rate of infection
may be higher, since most cases only cause a very mild disease, and will probably never be reported or
diagnosed. This article presents the scenario of the 2009 H1N1 influenza, popularly known as “swine flu” and
the data from inpatient admissions in Indraprastha Apollo Hospitals, Delhi, for the duration October 2009 to
January 2010.
Key words: Swine flu, H1N1 influenza, Apollo experience.
Fig.1. Electron microscope image of the reassorted H1N1
influenza virus

3. Apollo Medicine, Vol. 7, No. 1, March 2010 22
Review Article
getting sick to 5 to 7 days after. This can be longer in some
people, especially children and people with weakened
immune systems [10,11].
SIGNS AND SYMPTOMS
Mild or uncomplicated illness is characterized by
typical symptoms like fever (although not everyone with
influenza will have a fever), cough, sore throat, rhinorrhea,
muscle pain, headache, chills, malaise, sometimes diarrhea
and vomiting, but no shortness of breath and little change in
chronic health conditions [12].
Progressive illness is characterized by typical
symptoms plus signs or symptoms suggesting more than
mild illness: chest pain, poor oxygenation (e.g., tachypnea,
hypoxia, labored breathing in children), cardiopulmonary
insufficiency (e.g., low blood pressure), CNS impairment
(e.g., confusion, altered mental status), severe dehydration,
or exacerbations of chronic conditions (e.g., asthma,
chronic obstructive pulmonary disease, chronic renal
failure, diabetes or other cardiovascular conditions) [13].
Severe or complicated illness is characterized by signs
of lower respiratory tract disease (e.g., hypoxia requiring
supplemental oxygen, abnormal chest radiograph,
mechanical ventilation) (Fig. 2), CNS findings
(encephalitis, encephalopathy), complications of low blood
pressure (shock, organ failure), myocarditis or
rhabdomyolysis, or invasive secondary bacterial infection
which is unusual when compared with seasonal flu
(Table 1). However, pregnancy and other previously
recognized high risk medical conditions from seasonal
influenza appear to be associated with increased risk of
complications from this 2009 H1N1. These underlying
conditions include asthma, diabetes, suppressed immune
systems, heart disease, kidney disease, neurocognitive and
neuromuscular disorders.
CDC laboratory studies have shown that no children
and very few adults younger than 60 years old have existing
antibody to 2009 H1N1 flu virus; however, about one-third
of adults older than 60 may have antibodies against this
virus. It is unknown how much, if any, protection may be
afforded against 2009 H1N1 flu by any existing antibody.
EPIDEMIOLOGY
Spread of 2009 H1N1 virus is thought to occur in the
same way that seasonal flu spreads. Flu viruses are spread
mainly from person to person through coughing or
sneezing by people with influenza [8]. Sometimes people
may become infected by touching something – such as a
surface or object – with flu viruses on it and then touching
their mouth or nose [9]. The 2009 H1N1 virus is not
zoonotic swine flu, as it is not transmitted from pigs to
humans, but from person to person.
People infected with seasonal and 2009 H1N1 flu shed
virus and may be able to infect others from 1 day before
Table 1. CDC estimates of 2009 H1N1 cases and related hospitalizations and deaths fromApril-November 14,
2009, by age group
2009 H1N1 Mid-level range* Estimated range *
Cases
0-17 years ~16 million ~12 million to ~23 million
18-64 years ~27 million ~19 million to ~38 million
65 years and older ~4 million ~3 million to ~6 million
Cases Total ~47 million ~34 million to ~67 million
Hospitalizations
0-17 years ~71,000 ~51,000 to ~101,000
18-64 years ~121,000 ~87,000 to ~172,000
65 years and older ~21,000 ~15,000 to ~29,000
Hospitalizations Total ~213,000 ~154,000 to ~303,000
Deaths
0-17 years ~1,090 ~790 to ~1,550
18-64 years ~7,450 ~5,360 to ~10,570
65 years and older ~1,280 ~920 to ~1,810
Deaths Total ~9,820 ~7,070 to ~13,930

4. Review Article
23 Apollo Medicine, Vol. 7, No. 1, March 2010
based on laboratory testing or clinical signs (e.g. persistent
high fever and other symptoms beyond three days) [14].
People at high risk for developing flu-related
complications
• Children younger than 5, but especially children
younger than 2 years old
• Adults 65 years of age and older
• Pregnant women
• People who have medical conditions including:
• Asthma
• Neurological and neurodevelopmental conditions
[including disorders of the brain, spinal cord,
peripheral nerve, and muscle such as cerebral
palsy, epilepsy (seizure disorders), stroke,
intellectual disability (mental retardation),
moderatetoseveredevelopmentaldelay,muscular
dystrophy, or spinal cord injury].
• Chronic lung disease (such as chronic obstructive
pulmonary disease [COPD] and cystic fibrosis)
• Heart disease (such as congenital heart disease,
congestive heart failure and coronary artery
disease)
• Blood disorders (such as sickle cell disease)
• Endocrine disorders (such as diabetes mellitus)
• Kidney disorders
• Liverdisorders
• Metabolic disorders (such as inherited metabolic
disorders and mitochondrial disorders)
• Weakened immune system due to disease or
medication (such as people with HIV or AIDS, or
cancer, or those on chronic steroids)
• People younger than 19 years of age who are
receiving long-term aspirin therapy.
DIAGNOSIS
Case definition of H1N1 influenza
Suspected case
A suspected case of swine influenza A (H1N1) virus
infection is defined as: a person with acute febrile
respiratory illness (fever = 38ºC) with onset: within 7 days
of close contact with a person who is a confirmed case of
Swine influenzaA(H1N1) virus infection, or within 7 days
of travel to areas where there is one or more confirmed
Swine influenzaA(H1N1) cases, orresides in a community
where there is one or more confirmed swine influenza
cases.
Probable case
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 RTPCR or
reagents used to detect seasonal influenza virus infection,
or is positive for influenza A by an influenza rapid test or
influenza immunofluorescence assay (IFA) plus meets
criteria for a suspected case, or an 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.
Fig.2. The radiograph (A) shows bilateral alveolar opacities
in the base of both lungs that progressed and became
confluent. The specimen (B, hematoxylin and eosin)
shows necrosis of bronchiolar walls (top arrow), a
neutrophilic infiltrate (middle arrow), and diffuse alveolar
damage with prominent hyaline membranes (bottom
arrow).

5. Apollo Medicine, Vol. 7, No. 1, March 2010 24
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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.
DIAGNOSTIC TESTS
This season CDC recommends that influenza
diagnostic testing be prioritized for (i) hospitalized patients
with suspected influenza, (ii) patients for whom a diagnosis
of influenza will inform decisions regarding clinical care,
infection control, or management of close contacts; and (iii)
patients who died of an acute illness in which influenza was
suspected.
Most patients with a clinical illness consistent with
uncomplicated influenza who reside in an area where
influenza viruses are circulating do not require diagnostic
influenza testing for clinical management [15,16].
Rapid influenza diagnostic tests (RIDTs)
Rapid influenza diagnostic tests (RIDTs) are widely
available, commercial diagnostic tests that can detect
influenza viruses in 30 minutes or less. Depending on
which commercially available RIDT is used, the test can
either (i) detect and distinguish between influenza Aand B
viruses; or (ii) detect both influenza A and B but not
distinguish between influenza A and B viruses. Rapid
influenza diagnostic tests (RIDTs) are widely available but
have variable sensitivity (range 10-70%) for detecting 2009
H1N1 influenza when compared with real-time reverse
transcriptase polymerase chain reaction (rRT-PCR), and a
negative RIDT result does not rule out influenza virus
infection. RIDTs have a high specificity (>95%).
Viral culture
Viral culture is available in certain laboratories but
often does not provide results in time to help with clinical
decisions. However, viral culture is an important source of
public health virologic data on influenza antigenic
characteristics and antiviral susceptibilities. Viral culture is
highly sensitive and specific.
Direct immunofluorescence assays (DFAs) and
Indirect immunofluorescence assays (IFAs)
Immunofluorescence (fluorescent antibody staining) is
available at many hospital laboratories and can generally
yield test results in 2 to 4 hours, and sensitivities are
generally higher than rapid tests, but lower than viral
culture or real-time reverse transcriptase polymerase chain
reaction (rRT-PCR). Like RIDTs, direct immunofluore-
scence assays (DFAs) are widely available and have
variable sensitivity for detecting 2009 H1N1 virus (range
47-93%). DFAs detect and distinguish between influenzaA
and B viruses but do not distinguish among different
influenzaAsubtypes.
Real-time reverse transcriptase polymerase chain
reaction (rRT-PCR)
Nucleic acid amplification tests, including rRT-PCR,
are the most sensitive and specific influenza diagnostic
tests, but they may not be readily available, obtaining test
results may take one to several days, and test performance
depends on the individual rRT-PCR assay. As with any
assay, false negatives can occur. Table 2 summarises the
diagnostic tests for influenza.
Hospitalized patients with suspected influenza should
be considered for testing with an available influenza
diagnostic test. 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 rRT-PCR, if influenza
infection is clinically suspected.
Specimens
The following specimens are generally appropriate for
influenza virus diagnostic testing: nasopharyngeal swab;
nasal aspirate, wash or swab; endotracheal aspirate;
bronchoalveolar lavage (BAL); and combined
nasopharyngeal or nasal swab with oropharyngeal swab.
The performance of rRT-PCR assays specific for 2009
H1N1 influenza has 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.
TREATMENT
Antiviral drugs for treatment of influenza
The neuraminidase inhibitors are the drugs of choice for
treatment of 2009 H1N1 influenza and influenza-like
illness in both children and adults [17].
Oseltamivir: The neuraminidase inhibitor oseltamivir
formulated as capsules or oral suspension (Tamiflu®) is
FDA-approved for the treatment of uncomplicated acute
influenza in patients 1 year and older who have been
symptomatic for no more than 2 days.

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25 Apollo Medicine, Vol. 7, No. 1, March 2010
Definitive testing for 2009 H1N1 requires real-time
reverse transcriptase-polymerase chain reaction (rRT-PCR)
or viral culture. These tests should be prioritized for
persons with suspected or confirmed influenza requiring
hospitalization and based on guidelines from local and state
health departments.
Rapid influenza diagnostic tests (RIDTs) should not be
used to rule out influenza because false negative results are
common. The sensitivity of rapid tests in detecting 2009
H1N1 has ranged from 10% to 70%. Clinicians should not
withhold treatment based on a negative rapid test result.
Zanamivir: The neuraminidase inhibitor zanamivir
formulated for oral inhalation (Relenza®) is FDA-
approved for the treatment of influenza in patients 7 years
of age and older who, similar to approved uses for
oseltamivir, have uncomplicated illness and have been
symptomatic for no more than 2 days.
Peramivir: A third neuraminidase inhibitor peramivir
formulated for intravenous (IV) administration is an
investigational product currently being evaluated in clinical
trials.As of October, 2009, safety and/or efficacy data from
1,891 patients with acute uncomplicated seasonal
influenza A has been submitted to the FDA. Efficacy and
safety have not been evaluated in hospitalized patients [18].
Even though the data are insufficient to allow FDA
approval,under the EUA, treatment of adult patients with
IV peramivir is approved only if: (i) the patient has not
responded to either oral or inhaled antiviral therapy; (ii)
drug delivery by a route other than IV is not expected to be
dependable or is not feasible; or (iii) the clinician judges IV
therapy is appropriate due to other circumstances.
Initiation of treatment
Uncomplicated influenza illness
The algorithm for treating uncomplicated influenza
illness is as follows (Fig.3). Treatment should be started
empirically based on clinical judgment as early as possible
even before definitive diagnostic test results become
available, i.e., treatment should not wait for laboratory
confirmation of influenza. Treatment is most effective
when started in the first 48 hours of illness.As noted above,
however, evidence suggests treatment may benefit patients
with prolonged or severe illness even when started more
than 48 hours after the onset of illness (Table 3). Fig.3. Algorithm for treating uncomplicated influenza illness
Table 2. Diagnostic tests for influenza
Influenza diagnostic Method Availability Typical Sensitivity for Distinguishes 2009
tests processing 2009 H1N1 H1N1 influenza
time influenza from other
influenzaA
viruses?
Rapid influenza diagnostic Antigen detection Wide 0.5 hour 10-70% No
tests (RIDT)
Direct and indirect immuno- Antigen detection Wide 2-4 hours 47-93% No
fluorescence assays (DFA
and IFA)
Viral isolation in tissue cell Virus isolation Limited 2-10 days – Yes
culture
Nucleic acid amplification tests RNA detection Limited 48-96 hours 86-100% Yes
(including rRT-PCR) (6-8 hours to
perform test)

7. Apollo Medicine, Vol. 7, No. 1, March 2010 26
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Treatment of influenza when oseltamivir-resistant
viruses are circulating
Oseltamivir resistance is common among seasonal
influenzaA(H1N1) viruses.These viruses typically remain
susceptible to zanamivir, rimantadine, and amantadine.
However, since April 2009, very few seasonal H1N1
viruses have circulated in the United States. Therefore,
treatment, when indicated, with either oseltamivir or
zanamivir is appropriate. However, if viral surveillance
data indicate that oseltamivir-resistant seasonal H1N1
viruses have become more common or are associated with
identified community outbreaks, zanamivir or a
combination of oseltamivir and rimantadine or amantadine
should be considered for use as empiric treatment for
patients who might have oseltamivir-resistant seasonal
human influenzaA(H1N1) virus infection (Table 4) [19].
Oseltamivir-resistant infection with the 2009 pandemic
influenzaA(H1N1) virus has so far been described only in
a cluster in Vietnam and is conferred by the H275Y
substitution in the neuraminidase enzyme. The resistant
2009 H1N1 are transmissible and can replicate and cause
illness in healthy people in the absence of selective drug
pressure. Although data are limited, it is likely that the
detected levels of oseltamivir resistance are clinically
relevant [20]. The risk of resistance is considered higher in
patients with severely compromised or suppressed immune
systems who have prolonged illness, have received
oseltamivir treatment (especially for an extended duration),
but still have evidence of persistent viral replication.
The risk of resistance is also considered higher in
people who receive oseltamivir for so-called “post-
exposure prophylaxis” following exposure to another
person with influenza, and who then develop illness despite
taking oseltamivir [21].
The loss of oseltamivir as a treatment option for severe
2009 H1N1 infection could have profound consequences.
To minimize this risk, the use of oseltamivir should be
restricted to prophylaxis and treatment in high-risk
persons or the treatment of people with severe or
deteriorating illness, antiviral stockpiles should be
diversified, and optimal dosages and combination
therapies should be urgently studied. Close monitoring and
reporting of resistance to neuraminidase inhibitors are
essential [22].
Table 3. Antiviral medication dosing recommendations for treatment or chemoprophylaxis of 2009 H1N1 infection
Medication Treatment(5 days) Chemoprophylaxis(10 days)
Oseltamivir
Adults
75 mg twice daily 75 mg once daily
Children 12 months
Body weight (kg) Body weight (lbs)
15 kg 33lbs 30 mg twice daily 30 mg once daily
> 15 kg to 23 kg >33 lbs to 51 lbs 45 mg twice daily 45 mg once daily
>23 kg to 40 kg >51 lbs to 88 lbs 60 mg twice daily 60 mg once daily
>40 kg >88 lbs 75 mg twice daily 75 mg once daily
Children 3 months to < 12 months
3 mg/kg/dose twice daily 3 mg/kg/dose once per day
Children 0 to < 3 months
3 mg/kg/dose twice daily Not recommended unless
situation judged critical due to
limited data on use in this age
group
Zanamivir
Adults
10 mg (two 5 mg 10 mg (two 5 mg inhalations) once daily
inhalations) twice daily
Children ( 7 years or older for treatment, 5 years for chemoprophylaxis)
10 mg (two 5 mg inhalations) 10 mg (two 5 mg inhalations) once daily twice daily

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27 Apollo Medicine, Vol. 7, No. 1, March 2010
Antiviral chemoprophylaxis of exposed
individuals
Infectious period
One day before fever begins until 24 hours after fever
ends.
Who may be considered for antiviral
chemoprophylaxis
The following persons who are a close contact of a
person with suspected or confirmed 2009 H1N1 influenza
during the infectious period: Persons at high risk for
complications of influenza, health care workers and
emergency medical personnel, pregnant women.
Whom not to treat chemoprophylactically
Groups of healthy children or adults based on potential
exposures in the community, workplace, school, camp or
other settings, if >48 hours have elapsed since the last close
contact, the close contact did not occur during the
infectious period .
PREVENTION
Everyday steps to protect your health
• Cover your nose and mouth with a tissue when you
cough or sneeze. Throw the tissue in the trash after
you use it.
• Wash your hands often with soap and water. If soap
and water are not available, use an alcohol-based hand
rub.Avoid touching your eyes, nose or mouth. Germs
spread this way.
• Avoid close contact (i.e., being within about 6 feet)
with persons with influenza like illness.
• If you are sick with flu-like illness, CDC recommends
that you stay home for at least 24 hours after your
fever is gone except to get medical care or for other
necessities. (Your fever should be gone without the
use of a fever-reducing medicine.) Keep away from
others as much as possible to keep from making others
sick
• Chance of transmission is also reduced by
disinfecting household surfaces, which can be done
effectively with a diluted chlorine bleach solution.
Studies have shown that influenza virus can survive
on environmental surfaces and can infect a person for
2 to 8 hours after being deposited on the surface.
Interim recommendations for facemask and
respirator use to reduce 2009 influenza A (H1N1)
virus transmission
Use of N95 respirators or facemasks generally is not
recommended for workers in non-healthcare occupational
settings for general work activities. For specific work
activities that involve contact with people who have
ILI(influenza like illness), such as escorting a person with
ILI, interviewing a person with ILI, providing assistance to
Table 4.When to consider the use of antibiotics in the treatment of 2009 H1N1 influenza–associated pneumonia
Indication Primary influenzal Secondary bacterial pneumonia
lower respiratory disease following influenza
Identification of influenza +++ ++; lower rate of recovery because later in illness
Fever +++ +++; secondary fever after a period of
defervescence
Diagnostic specimen from lower Normal flora Gram's stain or culture shows pre-
respiratory tract (sputum speci- dominant organism (Streptococcus
men, tracheal aspirate, specimen pneumoniae, Staphylococcus aureus,
obtained on bronchoscopy of Streptococcus pyogenes, Hemophilus
intubation) influenzae, Moraxella catarrhalis)
X-ray Diffuse process Lobar consolidation
White-cell count Normal to low Increased
Onset of respiratory compromise 1-2 days after initial symptoms 4-7 days after initial symptoms
ill contacts in family +++ +++
Underlying risk factors (particularly ++ ++
neuromuscular, immunologic
++ denotes often found, and +++ usually found.

9. Apollo Medicine, Vol. 7, No. 1, March 2010 28
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an individual with ILI, the following are recommended:
• workers should try to maintain a distance of 6 feet or
more from the person with ILI;
• workers should keep their interactions with ill persons
as brief as possible;
• the ill person should be asked to follow good cough
etiquette and hand hygiene and to wear a facemask, if
able, and one is available;
• workers at increased risk of severe illness from
influenza infection should avoid people with ILI
(possibly by temporary reassignment); and,
• where workers cannot avoid close contact with
persons with ILI, some workers may choose to wear a
facemask or N95 respirator on a voluntary basis.
• In the occupational healthcare setting, respiratory
protection is recommended.
VACCINES
Vaccination is the best way to prevent influenza
infection and its complications. Seasonal influenza
vaccines are highly effective in preventing influenza
disease [23]. The vaccines against 2009 H1N1 influenza
are expected to work in a similar fashion to the seasonal
influenza vaccines. CDC and FDA believe that the benefits
of vaccination with the 2009 H1N1 influenza vaccine far
outweigh the risks.
• Killed, inactivated vaccines – Manufacturers are
using WHO recommended recombinant/re-assortant
vaccine seed strains. This is most accepted type of
strategy and is being followed by three Indian
manufacturers (Serum Institute of India, Bharat
Biotech and Panacea Biotech).
• Live attenuated nasal vaccines (LAIV)– These
vaccines are based on the principle of production of
seasonal influenza vaccine originally manufactured
by Russians but now marketed in USA also.
(Proposed by Serum Institute of India Ltd).
• Vaccines using virus like particles (VLP)– These
are genetically engineered vaccines in which only the
proteins are expressed which form non-infectious
virus-like-particles. So far only one vaccine
developed this technology has been approved by the
FDA (USA) – a vaccine for prevention of cervical
cancer. Cadila Pharmaceutical India Ltd. has
proposed production of an H1N1 vaccine using this
technology in technical collaboration with a US based
company Novavax , in which Cadila has a majority
share. The technology has been licensed to Cadila in
India and it will set up a plant to manufacture the
vaccine in India. This has already been assessed and
approved by Review Committee for genetically and
Engineered Modified Organisms (RCGEM) of DBT.
The merits of this technology are to be debated by a
high-powered committee.
• Recombinant fusion protein subunit vaccine using
toll like receptors (TLR) in E coli expression
vector– Biological E Ltd. Hyderabad, has proposed
production of an H1N1 vaccine using this technology
platform in technical collaboration with Vaccinate (a
US based biotech company). The technology is being
transferred to Biological E and the vaccine would be
manufactured at Hyderabad. Approval of the
RCGEM is being sought. Further details of the time-
lines of preclinical and human studies are awaited.
2009 H1N1 ACIP vaccination recommendations
CDC’sAdvisory Committee on Immunization Practices
(ACIP), a panel made up of medical and public health
experts, met July 29, 2009, to make recommendations on
who should receive the 2009 H1N1 vaccine [24]. The
groups recommended to receive the 2009 H1N1 influenza
vaccine include:
• Pregnant women because they are at higher risk of
complications and can potentially provide protection
to infants who cannot be vaccinated;
• Household contacts and caregivers for children
younger than 6 months of age because younger infants
are at higher risk of influenza-related complications
and cannot be vaccinated. Vaccination of those in
close contact with infants younger than 6 months old
might help protect infants by “cocooning” them from
the virus;
• Healthcare and emergency medical services
personnel because infections among healthcare
workers have been reported and this can be a potential
source of infection for vulnerable patients. Also,
increased absenteeism in this population could reduce
healthcare system capacity;
• All people from 6 months through 24 years of age;
• Children from 6 months through 18 years of age
because cases of 2009 H1N1 influenza have been
seen in children who are in close contact with each
other in school and day care settings, which increases
the likelihood of disease spread;

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29 Apollo Medicine, Vol. 7, No. 1, March 2010
• Young adults 19 through 24 years of age because
many cases of 2009 H1N1 influenza have been seen
in these healthy young adults and they often live,
work, and study in close proximity, and they are a
frequently mobile population; and,
• Persons aged 25 through 64 years who have health
conditions associated with higher risk of medical
complications from influenza.
The 2009 H1N1 vaccine is not intended to replace the
seasonal flu vaccine. It is an additional influenza vaccine
for this influenza season. Many people will be
recommended to get both vaccines. So the best advice is,
get the seasonal flu vaccine as soon as it is available in your
community, and if you are in one of the recommended
groups, get the 2009 H1N1 vaccine when it becomes
available .
The 2009 H1N1 influenza vaccine is showing a similar
safety profile to seasonal flu vaccines, which have a very
good safety track record [24]. The most common side
effects following flu vaccinations are mild, such as
soreness, redness, tenderness or swelling where the shot
was given.
In 1976, there was a small risk of GBS following
influenza (swine flu) vaccination (approximately 1
additional case per 100,000 people who received the swine
flu vaccine).That number of GBS cases was slightly higher
than what is normally seen in the population, whether or not
people were vaccinated. Since then, numerous studies have
been done to evaluate if other flu vaccines were associated
with GBS. In most studies, no association was found, but
two studies suggested that approximately 1 additional
person out of 1 million vaccinated people may be at risk for
GBS associated with the seasonal influenza vaccine [25-
26]. FDA and CDC are closely monitoring reports of
serious problems following the 2009 H1N1 influenza
vaccines, including GBS. Flu antiviral drugs taken from 48
hours before through 2 weeks after getting LAIV can lower
or prevent the vaccinated person from responding to the
vaccine and the person may not get immune protection
from the vaccine.
Contraindication for vaccination
People who have a severe (life-threatening) allergy to
chicken eggs or to any other substance in the vaccine
should not be vaccinated.
APOLLO EXPERIENCE OF 2009 H1N1 DISEASE
Starting from October 2009 till January 2010,there
were 94 admissions for suspected H1N1 disease. Of
these,72 were confirmed to be H1N1 influenza by throat
swab RTPCR test. The mean age of presentation was 32
yrs, and 21% of patients were less than 18 years of age. The
male and female ratio was 1:1, and the median time of
presentation to our hospital was 6 days.
Symptomatology
Fever was present in all the patients, while the
occurrence of other symptoms were as follows-cough 88%,
sore throat 55.6%, shortness of breath 58.3%, diarrhea
22.2% and vomiting 13.9% (Fig. 4).
Coexisting illnesses
Coexisting illness were present in 75% patients-
hypertension (9), diabetes mellitus (11), allergic bronchitis
(3), COPD (2), bronchial asthma (6), dyslipidemia (2),
pulmonary tuberculosis (1), coronaryartery disease(4),
hypothyroidism (2), pregnancy (2), obesity (1), psoriasis
(1), post op meningioma (1), old splenic infarct (1), post
AVR (1), Wegener’s disease (1), polycystic ovarian disease
(1), post renal transplant (2), CLL (1), CVA(1) (Fig.5).
Laboratory abnormalities
Laboratory abnormalities observed in the patients were-
leucopenia 19.4%, leucocytosis 16.7%, deranged liver
function tests 38.9%, deranged renal profile 27.8% and
thrombocytopenia 8.3%. Two patients had positive dengue
serology, and the coinfection of H1N1 influenza and
dengue fever has not been reported elsewhere till now.
Fig. 4. Symptomatology of patients (A-fever, B-cough,
C-shortness of breath, D-sore throat, E-diarrhea,
F-vomiting).

11. Apollo Medicine, Vol. 7, No. 1, March 2010 30
Review Article
Chest X ray revealed varied findings like few infiltrates,
bronchopneumonia and ARDS in 56.9% patients and
44.4% patients required non invasive ventilation.33.3%
patients required invasive ventilation and mortality was
high in this group 23.6% (Fig. 6).
During the period October 2009 to January 2010,there
were 94 admissions with suspected swine flu,however,72
of them were confirmed with RTPCR assay.Majority of the
patients presented within 6 days of illness and fever,cough
and shortness of breath were the most common
complaints.An overwhelming 75% of these patients had
varied preexisting medical or surgical illnesses. Patients
with an abnormal Chest X Ray were more likely to receive
ventilatory support.Multiorgan dysfunction was common
in patients with ARDS and this group carried a high
mortality as expected.There were two patients with a
coinfection with Dengue virus,a phenomenon which has
not been reported yet.
Swine flu’s lesson for the medical professionals
Other than humility and a familiar lesson about the
dangers of hubris, what can we learn from the sobering
realities presented by these latest developments? First,
preparation is an important and necessary activity, but in no
way is it protective. One might even argue that it can have
the negative consequence of lulling us into thinking we
have a problem covered, when clearly we never do. In
defense of this panic-driven approach, the product may not
be entirely useless: preparation, albeit for the wrong
invader, sharpens reflexes and can have at least some
minimal practical yield, such as stockpiles of protective
gear for health care workers.
Second, we should marvel at the raw, restless power of
microbes. They have the numbers – trillions and
quadrillions and more that replicate wildly, inaccurately,
and disinterestedly. Nothing microbes do, whether under
the duress imposed by antimicrobials or from some less
evident pressure, should surprise us. It’s their world; we
only live in it. In this regard, it is perhaps fitting that our
most successful incursion against them – Fleming’s
discovery of penicillin on a nearly discarded culture plate –
is immortalized as a fluke, an accident, the product of
sloppy laboratory hygiene, anything but a headlong
Manhattan Project–like assault against the enemy.
Finally, and perhaps most important, doctors should be
reminded against profligate use of antimicrobial agents.
Once again, it seems that our message against profligate use
of antimicrobial agents has crept over into the realm of
morality, that comic-book world of good guys and bad
guys. Yes, over prescribing of antibiotics is an enormous
problem that must be curtailed. It causes predictable
problems, and its interruption results in predictable relief of
drug resistance. Just as we must watch our waistlines and
our bottom lines and not drink to excess and never exceed
the speed limit, in the same spirit we must control runaway
antibiotic use because it will help people’s health and save
money–but not because such restraint is holy or somehow
separates good people from bad. In the future, we must
resolve to keep fire and brimstone out of public health
decisions. Otherwise, good judgment, necessary alertness,
and scientific doubt also may go up in smoke.
Fig. 5. Coexisting illnesses in the patients (A-hypertension,
B-diabetes mellitus, C- allergic bronchitis, D-COPD, E-
bronchial asthma, F-dyslipidemia, G-pulmonary
tuberculosis, H-coronary artery disease, I-
hypothyroidism, J-pregnancy, K-obesity, L-psoriasis, M-
post op meningioma, N-old splenic infarct, O-post AVR,
P-Wegener’s disease, Q-polycystic ovarian disease, R-
post renal transplant, S-CLL, T-CVA ).
Fig. 6. Laboratory abnormalities in the patients (A-leucopenia
B-leucocytosis, C-deranged liver function tests,
D-deranged renal profile, E-thrombocytopenia,
F-abnormal Chest X-ray).

12. Review Article
31 Apollo Medicine, Vol. 7, No. 1, March 2010
REFERENCES
1. Kimura H, Abiko C, Peng G, et al. Interspecies
transmission of influenza C virus between humans and
pigs. Virus Res 1997; 48(1): 71-79.
2. Lynch JP, Walsh EE. Influenza: evolving strategies in
treatment and prevention. Semin Respir Crit Care Med
2007; 28(2): 144-158.
3. Ma W, Vincent AL, Gramer MR, et.al. Identification of
H2N3 influenza A viruses from swine in the United States.
Proc Nat Acad Sci USA 2007; 104 (52): 20949-20954.
4. Shin JY, Song MS, Lee EH, Lee YM, et al. Isolation and
characterization of novel H3N1 swine influenza viruses
from pigs with respiratory diseases in Korea. Virol J 2006;
25(4):123.
5. Kothalawala H, Toussaint MJ, Gruys E. An overview of
swine influenza. Vet Q 2006; 28 (2): 46-53.
6. Yassine HM, Al-Natour MQ, Lee CW, Saif YM.
Interspecies and intraspecies transmission of triple
reassortant H3N2 influenzaAviruses. Virol J, 2007; 28(4):
129.
7. Swine influenza A (H1N1) infection in two children —
Southern California, March-April 2009. Morbidity and
Mortality Weekly Report. Centers for Disease Control. 22
April 2009.
8. Olsen CW. The emergence of novel swine influenza
viruses in North America. Virus Research 2002; 85(2):
199-210.
9. Gaydos JC, Top FH, Hodder RA, Russell PK. Swine
influenza a outbreak, Fort Dix, New Jersey, 1976.
Emerging Infectious Diseases 2006; 12 (1): 23-28.
10. McKinney WP, Volkert P, Kaufman J. Fatal swine influenza
pneumonia during late pregnancy. Archives of Internal
Medicine 1990; 150(1): 213-215.
11. Kimura K, Adlakha A, Simon PM. Fatal case of swine
influenza virus in an immunocompetent host. Mayo Clinic
Proceedings. Mayo Clinic 1998; 73(3): 243-245.
12. Key Facts About Swine Flu (CDC). Cdc.gov. http://
www.cdc.gov/swineflu/key_facts.htm. Retrieved 2009-05-
07.
13. World Health Organization (28 October 2005). H5N1
avian influenza: timeline (PDF). http://www.who.int/csr/
disease/avian_influenza/Timeline_28_10a.pdf.
14. Centers for disease control and prevention > Key Facts
about Swine Influenza (Swine Flu). http://www.cdc.gov/
swineflu/key_facts.htm. Retrieved April 27, 2009.
15. Myers KP, Olsen CW, Gray GC. Cases of swine influenza
in humans: a review of the literature. Clin. Infect. Dis.
2007; 44 (8): 1084-1088.
16. Centers for disease control and prevention. CDC Health
Update: Swine Influenza A (H1N1) Update: New Interim
Recommendations and Guidance for Health Directors
about Strategic National Stockpile Materiel. Health Alert
Network. http://www.cdc.gov/swineflu/HAN/042609.htm.
Retrieved April 27, 2009.
17. McGerA, et al. Antiviral therapy and outcomes of influenza
requiring hospitalization in Ontario, Canada. Clinical
Infectious Diseases 2007: 45(12):1568-1575.
18. Lee N, et al. Factors associated with early hospital
discharge of adult influenza patients. Antiviral Therapy
2007;12(4):501-508.
19. Oseltamivir-resistant pandemic (H1N1) 2009 influenza
virus, October 2009. Wkly Epidemiol Rec 2009;84:453-
459.
20. Moscona A. Global transmission of oseltamivir-resistant
influenza. N Engl J Med 2009; 360: 953-956.
21. Cianco B, Meerhoff T, Kramarz P, et al. Oseltamivir-
resistant influenza A(H1N1) viruses detected in Europe
during season 2007-8 had epidemiological and clinical
characteristics similar to co-circulating susceptible
A(H1N1) viruses. Euro Surveill 2009;14: pii =19412.
22. Wetherall NT, Trivedi T, Zeller J, et al. Evaluation of
neuraminidase enzyme assays using different substrates
to measure susceptibility of influenza virus clinical isolates
to neuraminidase inhibitors: report of the Neuraminidase
Inhibitor Susceptibility Network. J Clin Microbiol
2003;41:742-750.
23. Retailliau, Henry F, Curtis, Arthur C, et al. Illness after
influenza vaccination reported through a nationwide
surveillance system, 1976-1977. American Journal of
Epidemiology (The Johns Hopkins University School of
Hygiene and Public Health) 1980; 111 (3): 270-278.
24. Vellozzi C, Burwen DR, Dobardzic A, Ball R, Walton K,
Haber P. Safety of trivalent inactivated influenza vaccines
in adults: Background for pandemic influenza vaccine
safety monitoring. Vaccine 2009; 27(15): 2114-2120.
25. Haber P, Sejvar J, Mikaeloff Y, Destefano F. Vaccines
and Guillain-Barré syndrome. Drug Saf 2009; 32(4):
309-323.
26. Kaplan JE, Katona P, Hurwitz ES, Schonberger LB.
Guillain-Barré syndrome in the United States, 1979-1980
and 1980-1981. Lack of an association with influenza
vaccination. JAMA 1982; 248 (6): 698-700.

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