H1N1 2009 1

H1N1 2009: Review Studies and Current Issues

Prepared By
Arafat Siddiqui
Dept. of Pharmacy
East-West University
Dhaka, Bangladesh
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INTRODUCTION
H1N1 influenza virus caused a pandemic worldwide in 2009. Though our mother land
Bangladesh was affected by it in late 2009, it made us worried within very short time. This virus
killed lots of people worldwide including some Bangladeshis. In August 2010 the World Health
Organization declared the swine flu pandemic officially over but still it is one of the most
common influenza in some countries including England and Australia, forcing people to take
vaccines. Newer vaccines are developed by different pharmaceutical companies and further
research is going on.
H1N1 influenza virus is responsible for 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.
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 virus is common throughout pig populations worldwide. Transmission of the
virus from pigs to humans is not common and does not always lead to human influenza, often
resulting only in the production of antibodies in the blood. If transmission does cause human
influenza, it is called zoonotic swine flu. During the mid-20th century, identification of influenza
subtypes became possible, allowing accurate diagnosis of transmission to humans. Since then,
only 50 such transmissions have been confirmed. These strains of swine flu rarely pass from
human to human.
HISTORY
Swine influenza was first proposed to be a disease related to human influenza during the
1918 flu pandemic, when pigs became sick at the same time as humans. The first identification
of an influenza virus as a cause of disease in pigs occurred about ten years later, in 1930. For the
following 60 years, swine influenza strains were almost exclusively H1N1. Then, between 1997
and 2002, new strains of three different subtypes and five different genotypes emerged as causes
of influenza among pigs in North America. In 1997–1998, H3N2 strains emerged.
These strains, which include genes derived by reassortment from human, swine and avian
viruses, have become a major cause of swine influenza in North America. Reassortment between
H1N1 and H3N2 produced H1N2. In 1999 in Canada, a strain of H4N6 crossed the species
barrier from birds to pigs, but was contained on a single farm. The H1N1 form of swine flu is
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one of the descendants of the strain that caused the 1918 flu pandemic. As well as persisting in
pigs, the descendants of the 1918 virus have also circulated in humans through the 20th century,
contributing to the normal seasonal epidemics of influenza. However, direct transmission from
pigs to humans is rare, with only 12 recorded cases in the U.S. since 2005. Nevertheless, the
retention of influenza strains in pigs after these strains have disappeared from the human
population might make pigs a reservoir where influenza viruses could persist, later emerging to
reinfect humans once human immunity to these strains has waned. Swine flu has been reported
numerous times as a zoonosis in humans, usually with limited distribution, rarely with a
widespread distribution. Outbreaks in swine are common and cause significant economic losses
in industry, primarily by causing stunting and extended time to market. For example, this disease
costs the British meat industry about £65 million every year.
CLASSIFICATION
Of the three genera of influenza viruses that cause human flu, two also cause influenza in
pigs, with influenza A being common in pigs and influenza C being rare. Influenza B has not
been reported in pigs. Within influenza A and influenza C, the strains found in pigs and humans
are largely distinct, although because of reassortment there have been transfers of genes among
strains crossing swine, avian, and human species boundaries. Influenza C viruses infect both
humans and pigs, but do not infect birds. Transmission between pigs and humans have occurred
in the past. For example, influenza C caused small outbreaks of a mild form of influenza
amongst children in Japan and California. Because of its limited host range and the lack of
genetic diversity in influenza C, this form of influenza does not cause pandemics in humans.
Swine influenza is known to be caused by influenza A subtypes H1N1, H1N2, H2N3, H3N1, and
H3N2. In pigs, three influenza A virus subtypes (H1N1, H1N2, and H3N2) are the most common
strains worldwide. In the United States, the H1N1 subtype was exclusively prevalent among
swine populations before 1998; however, since late August 1998, H3N2 subtypes have been
isolated from pigs.
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Figure: Electron microscope image of the reassorted H1N1 influenza virus.

As of 2004, H3N2 virus isolates in US swine and turkey stocks were triple reassortants,
containing genes from human (HA, NA, and PB1), swine (NS, NP, and M), and avian (PB2 and
PA) lineages.
SIGNS AND SYMPTOMS IN HUMAN
According to the Centers for Disease Control and Prevention (CDC), in humans the
symptoms of the 2009 "swine flu" H1N1 virus are similar to those of influenza and of influenza-
like illness in general. Symptoms include fever, cough, sore throat, body aches, headache, chills
and fatigue. The 2009 outbreak has shown an increased percentage of patients reporting diarrhea
and vomiting. The 2009 H1N1 virus is not zoonotic swine flu, as it is not transmitted from pigs
to humans, but from person to person. Because these symptoms are not specific to swine flu, a
differential diagnosis of probable swine flu requires not only symptoms but also a high
likelihood of swine flu due to the person's recent history. For example, during the 2009 swine flu
outbreak in the United States, CDC advised physicians to "consider swine influenza infection in
the differential diagnosis of patients with acute febrile respiratory illness who have either been in
contact with persons with confirmed swine flu, or who were in one of the five U.S. states that
have reported swine flu cases or in Mexico during the 7 days preceding their illness onset." A
diagnosis of confirmed swine flu requires laboratory testing of a respiratory sample (a simple
nose and throat swab). The most common cause of death is respiratory failure. Other causes of
death are pneumonia (leading to sepsis), high fever (leading to neurological problems),
dehydration (from excessive vomiting and diarrhea), electrolyte imbalance and kidney failure.
Fatalities are more likely in young children and the elderly.The CDC recommends real time RT-
PCR as the method of choice for diagnosing H1N1. This method allows a specific diagnosis of
novel influenza (H1N1) as opposed to seasonal influenza. Near-patient point of care tests are in
development.
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PREVENTION OF HUMAN TO HUMAN TRANSMISSION

Influenza spreads between humans when infected people cough or sneeze, then other
people breathe in the virus or touch something with the virus on it and then touch their own face.
Swine flu cannot be spread by pork products, since the virus is not transmitted through food. The
swine flu in humans is most contagious during the first five days of the illness although some
people, most commonly children, can remain contagious for up to ten days. Recommendations to
prevent spread of the virus among humans include using standard infection control against
influenza. This includes frequent washing of hands with soap and water or with alcohol-based
hand sanitizers. Chance of transmission is also reduced by disinfecting household surfaces,
which can be done effectively with a diluted chlorine bleach solution. Anyone with flu-like
symptoms such as a sudden fever, cough or muscle aches should stay away from work or public
transportation and should contact a doctor for advice. Social distancing is another tactic.
TREATMENT
If a person becomes sick with swine flu, antiviral drugs can make the illness milder and
make the patient feel better faster. They may also prevent serious flu complications. For
treatment, antiviral drugs work best if started soon after getting sick (within 2 days of
symptoms). Beside antivirals, supportive care at home or in hospital, focuses on controlling
fevers, relieving pain and maintaining fluid balance, as well as identifying and treating any
secondary infections or other medical problems. The U.S. Centers for Disease Control and
Prevention recommends the use of Tamiflu (oseltamivir), made by Roche Holding, a
pharmaceutical company or Relenza (zanamivir) for the treatment and/or prevention of infection
with swine influenza viruses; however, the majority of people infected with the virus make a full
recovery without requiring medical attention or antiviral drugs. The virus isolates in the 2009
outbreak have been found resistant to amantadine and rimantadine. The Japanese health
authorities warned that Tamiflu should not be given to teenagers, after reports that some children
who took the drug exhibited bizarre behavior.
VACCINES FOR SWINE FLU
Vaccines given to children during last year's pandemic have mostly minor side-effects
and should provide "good protection" against infection, researchers revealed today. Some 98% of
children under three responded well to two doses of an "adjuvanted" vaccine, which contains an
emulsion to boost immunity. This vaccine – also known as a "split-virus" vaccine – was the most
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common type given to children last year. Two doses of a second "whole-virus" version of the
vaccine, without the booster, produced a weaker result, with 80% of under-threes responding.
While the adjuvanted vaccine was the most likely to produce side-effects such as fever, most
children experienced only minor reactions.
Seasonal flu comes back in slightly different forms each year. But the H1N1 2009 is an
entirely new combination of four genetic elements: a bird flu, some human flu genes and two
types of swine flu. Right now, about 90 percent of the circulating flu is H1N1, although seasonal
flu, which typically peaks in winter, has also been detected. The H1N1 2009 vaccine contains
only the novel H1N1 virus. This year’s seasonal vaccine contains three influenza viruses — one
A (H3N2) virus, one regular seasonal A (H1N1) virus unrelated to the swine flu strain and one B
virus. The C.D.C. identifies and tests a viral strain, then distributes a version of it to vaccine
manufacturers, who inject it into millions of eggs, where it multiplies. Then the virus is
harvested, purified and developed into a vaccine. The injectable vaccine or flu shot is made from
a killed influenza virus that is highly purified and broken into tiny pieces. It is not harmful but
stimulate the immune system to produce antibody. The nasal vaccine, called FluMist, is made of
an attenuated live virus. This is a weakened version of the virus that has been tamed in the
laboratory so it cannot cause illness. The attenuated virus cannot survive in the higher
temperatures of the respiratory tract. When the vaccine is sprayed into the nose, it multiplies on
the mucous membranes in the nose and throat, triggering the body’s immune response without
causing any illness. Some studies suggest the nasal mist is more effective than the traditional flu
shot. Flu vaccine packaged in a multidose vial contains thimerosal, a preservative that prevents
contamination of the vial during repeated use. One dose from a multiuse vial contains about 25
micrograms of mercury. However, people who want to minimize mercury exposure can ask for a
vaccine in a single-dose package, which has only trace amounts. Thimerosal is not used in the
production of FluMist.
CURRENT ISSUES
The Swedish Medical Products Agency has received reports from health care
professionals regarding narcolepsy as suspected adverse drug reaction following Pandemrix flu
vaccination. The reports concern teenaged children who developed narcolepsy symptoms one to
two months after vaccination against the H1N1 pandemic. Finland is also looking into the
possible link following an increase in the sleeping disorder among children this spring.
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The Pandemrix package insert shows that “somnolence”, although not narcolepsy, is a
known potential side effect of the drug. Six cases of narcolepsy with cataplexy – a rare disorder
characterized by chronic sleepiness, together with a loss of muscle tone – have been detected in
France in persons vaccinated against influenza A/H1N1. Australia also banned the swine flu
vaccine for children under the age of 5, back in April, 2010, due to excessively high rates of
febrile convulsions. Currently approximately 80% of the Australian population is not vaccinated
against swine flu. Now Australian government has launched free vaccination to everyone over 6
months. Vaccination is particularly recommended for: Pregnant, children over 6 months,
indigenous, obese with a Body Mass Index (BMI) of more than 35, a parent or guardian of a
child aged 0 - 6 months, a healthcare worker, suffer from a chronic or respiratory disease
including heart, renal, kidney, liver and lung disease, asthma, cancer, diabetes, neurological
disease. In December 2009, the Therapeutic Goods Administration approved the Australian-
made Panvax H1N1 Vaccine Junior, which now enables children from 6 months to 9 years of
age to be protected against the swine flu. These children need to receive two doses of the vaccine
given at least 28 days apart to be fully vaccinated.
SWINE FLU IN BANGLADESH
The first case of swine flu in Bangladesh was detected in an incoming traveller at the Zia
International Airport on 18 June 2009. A three-month-old infant died pushing the official death
count from the H1N1 virus to two. Thirty-six more cases were detected in early September,
taking the total tally to 311. According to IEDCR in Bangladesh, the number of cases in the
country rose to 604 in late September 2009. Gulf Times reported that a Bangladeshi child in
Doha was detected with swine flu some days back. The two-year old boy was on his way to
Bangladesh from the US. The child is undergoing treatment in Doha. ICDDR, B, in collaboration
with the Government of Bangladesh, was monitoring the virus through its already-existing
influenza surveillance system. The Centre had also started to provide testing and clinical services
to the victims since the first week of September. ICDDR, B was providing its services free of
charge to the swine flu patients as well. Bangladesh launched its H1N1 pandemic vaccination
campaign, targeting 15.6 million people who fall within the priority groups for vaccination to
combat swine flu. The U.S. government, through the United States Agency for International
Development, has provided 2.6 million syringes and 30,200 safety boxes to Bangladesh to ensure
that these vaccines are appropriately positioned in targeted areas.
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Reference
http://www.guardian.co.uk/world/2010/may/28/children-swine-flu-vaccine-trial
http://www.guardian.co.uk/world/2010/nov/03/pupil-dies-swine-flu
http://www.nytimes.com/info/swine-flu-h1n1-vaccine/
http://centre.icddrb.org/pub/publication.jsp?classificationID=3&pubID=10517
http://bdnews24.com/details.php?id=142177&cid=2
http://www.thefinancialexpress-bd.com/2009/06/20/70394.html
http://www.allheadlinenews.com/articles/7018592931
http://www.flu.gov/individualfamily/vaccination/index.html
http://www.health.qld.gov.au/swineflu/html/vacc.asp
http://www.kidspot.com.au/familyhealth/Infections-&-Diseases-Colds-&-Flu-Swine-flu-
vaccination-advice-2010+2745+195+article.htm
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