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.