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Swine flu “influenza A” (H1N1) epidemic – 2009

Mahendra Maharjan
Central Department of Zoology
Tribhuvan University, Kirtipur

A new strain of swine flu - influenza A (H1N1) - is spreading throughout the world. The first
detection of swine flu case started from Mexico on 18 March of this year. It soon stroke United
States after 10 days. Within a period of one month, seven countries (United States, Mexico,
Canada, New Zealand, the United Kingdom, Israel and Spain) started reporting confirmed cases
of the swine flu. List of cases and affected countries are increasing day by day. 331 cases from
11 countries on 1st May, 985 cases in 20 countries on 4th May with 25 deaths in Mexico, all
together 2500 cases from 25 countries with 44 deaths on 8 th May had been reported. Similarly on
13th May, 33 countries have reported 5728 cases of H1N1 to World Health Organization (WHO).
62 countries had reported 17,410 cases till 1st June 2009. As of 1st July 2009, 120 countries
reported 77,201 laboratory confirmed cases of swine flu infection including 332 deaths globally-
mostly from Mexico and the United States. Most cases outside Mexico and the United States
have caused by travelers. Our neighboring country India has confirmed 116 cases and numbers
of cases are increasing in Tibet as well. Avian Influenza Control Project (AICP), Nepal had
confirmed first case of Swine flu on 29th June and till 5th July it reached at the total number of 5.
Nepal shares open borders with India, through which around 10,000 people commute. In
airports, infected people can be easily identified and quarantined however it is difficult in open
land borders. It increases the risk for both countries. Therefore, it is urgent to fully functionalize
Avian Influenza Control Project (AICA) and immediately set up the health checkup desk in all
land crossing borders. Although the swine flu infection caused by influenza A (H1N1) virus
seems to be mild, careful monitoring is necessary and we need to be prepared for the potential
emergence of more virulent variants in the days to come.

Influenza viruses cause annual epidemics and occasional pandemics that have claimed the lives
of millions. The emergence of new strains will continue to pose challenges to public health and
the scientific communities. A prime example is the recent emergence of swine-origin H1N1
viruses that have transmitted to and spread among humans, resulting in outbreaks globally.

Due to the genome plasticity of influenza virus, point mutation and reassortment events are
frequent phenomenon, which contribute to emergence of new strains of the virus. “Influenza A”
viruses belong to the family Orthomyxoviridae. The viruses are classified on the basis of the
antigenicity of their haemagglutinin (HA) molecules and neuraminidase (NA) molecules. There
are 16 HA (H1-H16) and 9 NA (N1-N9) identified antigens. “Influenza A” viruses contain a
genome composed of eight segments of single-stranded, negative-sense RNA that each encodes
one or two proteins. HA protein facilitates fusion of viral and endomosal membrane while NA
protein facilitates virus release from infected cells by removing sialic acids from cellular and
viral HA and NA proteins. Replication and transcription of viral RNAs are carried out by the
three polymerase subunits PB2, PB1 and PA and the nucleoprotein NP. PB2 protein is associated
with the viral replication. Recently it has been shown that the PB2 and HA proteins of the
Spanish influenza virus were critical for droplet transmission. PB1 protein is associated with the
virulence of the influenza virus. NS1 protein is believed to be associated with inactivation of
hosts’ RNase. Direct contribution of NS1 is still not known.

Influenza outbreaks

Spanish influenza (H1N1)

Spanish influenza was pandemic during 1918-1919 which killed around 50 million people
worldwide. By that time mortality rate due to influenza was unusual.

Asian influenza (H2N2)

In 1957, the Asian influenza originated from china and spread throughout the globe killing more
than 70,000 people worldwide. The pandemic was caused by a human/avian reassortant that
introduced avian virus H2HA and N2 NA genes into human populations which also contains
PB1 gene of avian virus origin.

Hong Kong influenza (H3N2)

In 1968, H2N2 subtype viruses were replaced by another human/avian reassortant that possessed
an H3 HA gene of avian virus origin H3N2 “seasonal flu” which again contains PB1 gene of the
pandemic virus. The virus was first isolated in Hong Kong.

Russian influenza (H1N1)

The outbreak of Russian influenza caused by influenza viruses of the H1N1 was occurred during
1977 to 1978. The re-emergence of this virus did not replace the H3N2 viruses. Both viruses
remain co-circulating in humans as a result in 2001, H1N2 new virus emerged out, but this virus
soon disappeared.

Highly pathogenic H5N1 influenza viruses

The avian influenza caused by H5N1 viruses is highly pathogenic disease, which was first
reported in Hong Kong. Remarkable features of these viruses are (I) they are lethal even to the
natural reservoir host - waterfouls, (II) they are able to infect fatally to several mammalian
species. (III) pathogenecity increases over the time passed (IV) their continued transmission to
humans, resulting in severe respiratory infection with high mortality rates. Till May 2009, WHO
has reported 424 human infections with 261 deaths. In this case human to human infection has
not been reported. Hence H5N1 viruses are characterized by a high mortality rate but inefficient
spread among humans.

Outbreak of swine origin H1N1 virus

Epidemiological data indicate that an outbreak of influenza-like illness started in the Mexican
town of La Gloria, Veracruz, in mid-February of 2009. By the end of April, the disease was
spread internationally and clusters of human to human transmission prompted the WHO to
increase the pandemic alert from phase-3 to phase-4, and shortly after, to phase-5 (human-to –
human spread in at least two countries, and signs of an imminent pandemic). Soon WHO has
declared the pandemic status of the disease with phase-6 designation. The simple meaning of
pandemic is that all the population of the world is at the risk of infection and phase 6 designation
defines sustained community level outbreak in at least one country in different WHO regions.
Nepal and its neighbors are WHO member countries, hence WHO guideline is equally applicable
to all countries to remain in high alert in order to prevent and control of the cases. In this case,
substantial social-distancing measures needs to be implemented. Moreover, massive campaigns
need to be undertaken to educate the public about precautionary hygiene measures.

Emergence of H1N1 virus

It is believed that H3N2 and H1N2 swine viruses, which are circulating in North American swine
at present, were emerged through triple reassortment of avian-human-swine viruses. Now
emergence of H1N1 is believed probably due to quadruple reassortants of those viruses with
Eurasian avian-like swine viruses. Because, present swine flu (H1N1) virus possess PB2 and PA
genes of North American avian virus origin, A PB1 gene of human H3N2 virus origin, HA (H1),
NP, and NS genes of classical swine virus origin, and NA(N1) and M genes of Eurasian avian-
like swine virus origin.

Prevention and Control

For the prevention and control of influenza virus infections, both vaccines and antiviral drugs are
available. At present two classes of antiviral drugs are licensed for use against influenza A
viruses – ion channel inhibitors and neuraminidase inhibitors.

Drug “Adamantanes” – ion channel inhibitor block the ion channel formed by the M2 protein
which is critical in the release of vRNPs into the cytoplasm.

Two drugs “Oseltamivir and Zanamivir” - neuraminidase inhibitors interfere with the enzymatic
activity of the NA protein, which is critical for the efficient release of newly synthesized viruses
from infected cells.

Since viruses have ability to mutate frequently and can develop resistance to these drugs,
although not observed yet, careful monitoring during treatment is necessary.