Discussion
In this study, the time and path of transmission of H1N1 serotype
influenza A viruses in Iran and neighboring countries have been
investigated by using Bayesian phylogeography analysis on the sequences
extracted from the gene bank. As of now several studies on geographical
phylodynamic of different influenza virus serotypes with different goals
and details have been developed and published around the
world.14,15Based on our knowledge, this study is the first study for Influenza in
the field of Bayesian phylogeographical analysis in Iran and the region.
The results of our study showed that based on the extracted sequences,
the age of emergence of H1N1 influenza virus serotype was older in Iran
compared to neighboring countries, and among the cities within the
country, Tehran had a key role and epicenter of transmission to other
cities. In the meanwhile, it should be noted that there were not enough
evidence diverse sequences from Iran and other possible countries of
virus transmission in our genome set.
The global transmission of virus during the pandemic can be explained by
the fact that and based on the existence agreements on previous reports,
started in April 2009 in Mexico, followed by North America. Expanding
transmission of the virus to Europe and its spread in the population of
European countries, in connection with the travel of people living in
European countries to Mexico or the United States one week before the
onset of clinical
symptoms.4,16-18Based on the results of our study, the virus has been circulating in
Tehran with low frequency for some time and gradually it has spread
throughout the region and neighboring countries as sporadic event in the
recent years. Our results showed that after rapid inhibition, the virus
was still present in small numbers in some countries, such as Turkey.
The results of our phylodynamic reconstruction were in accordance with
other evidences that stated disease was initiated by the arrival of air
travelers from non-neighboring European countries, first by an Iranian
teenager living abroad in June and then by other travelers, gradually
coinciding with other foreign trips and return of pilgrims from Hajj
Umrah, the disease spread and was observed almost all over the country,
although the prevalence of the disease in some provinces, especially the
northwestern provinces and Tehran due to more population density was
higher than other centers in the
country.19
In general, the influenza epidemic caused by type A virus usually
occurred in a certain state, for example, the pandemic of influenza,
starts almost suddenly and reaches its maximum within 2-3 weeks, and
lasted for 5-6 weeks.4The small genetic distance between the different branches of these
clusters in this period indicated the high rate of spread of the virus,
which reflected the sudden onset and rapid inhibition of the epidemic in
this period (2007-2009) both in Iran and in other neighbor countries.
The 2009 pandemic influenza virus is like seasonal influenza viruses in
many epidemiological features and when the pandemic is fully subsided
and at least after one year has passed, it is expected to follow the
same trend as other seasonal influenza viruses.
Therefore, due to the significant threat to public health caused by such
viruses, regular monitoring of H1N1 viruses in the country, especially
in entering point to the country, strengthening the social measures and
screening of newcomers and tourists from neighboring countries, should
be considered as impactful tools to fight against future
infections.20 It is
also necessary for countries to have a regional monitoring program in
addition to internal monitoring programs, because control of this
disease would not be possible without such a program. In addition, given
the potential threat to the public health of the H1N1 virus, it is also
important to develop effective measures like establishing a molecular
surveillance program to prevent epidemics and pandemics.
Our study showed that the estimated evolutionary rate for HA and NA
genomes for H1N1 serotype in our genome set from Iran and neighboring
countries is similar to that previously found in different countries in
Scotland, Argentina, Italy, China, India, Japan, South Korea, and
Israel.14,21,22This finding validates the estimates of the recent common ancestor in
our study, and supports the validity of our tree estimates and topology.
Also presence of similar mutation rates for HA and NA genes seems they
were coevolving, and leads to minimizing the possibility of emergence of
new reassortments.23
Based on our results we did not find any positive selection sites, but
other studies identified different number of positive selection sites
and these differences can be attributed to the differences in
significance levels and data sets used in the other
studies.24
This study had some limitations such as, we could not study the
epidemiological parameters of the H1N1 virus in neighboring countries
such as Iraq, Armenia, Afghanistan, and the Persian Gulf countries in
depth due to the existence of limited sequences of these countries in
the gene bank. In addition, we could not directly estimate the full
extent of the evolution of the genome set because the time frame of this
data set was not large enough. Our models and time estimates need to be
further explored in future studies as new sequences from other countries
and wider time periods become available, allowing for a more
comprehensive assessment of the virus’s evolutionary history.
In summary, our results suggested that the H1N1 serotype influenza virus
epidemic in Iran may have started much earlier than in other countries
surveyed in the region, and it was estimated that the date is earlier
than the identified years by molecular detection. Therefore, along with
such measures like resource management, diagnostic approaches, and
preparedness to fight against viruses that already were in place, we
need to initiate continuous monitoring, and screening of H1N1 serotype
influenza virus in the country, especially by implementation of
feasible, effective, and innovative measures at borderline for virus
control. It is also important for countries to have a regional
monitoring program in addition to internal monitoring programs, as well
as to start a virus molecular care program. In the future, with the
availability of new sequences from other countries and more open time
intervals, our model and timeline estimates need to be further explored.