Abstract
A community outbreak of human influenza A(H1N1)pdm09 virus strains was observed in Myanmar in 2017. We investigated the circulation patterns, antigenicity, and drug resistance of 2017 influenza A(H1N1)pdm09 viruses from Myanmar and characterized the full genome of influenza virus strains in Myanmar from in-patients and out-patients to assess the pathogenicity of the viruses. Nasopharyngeal swabs were collected from out-patients and in-patients with acute respiratory tract infections in Yangon and Pyinmana City in Myanmar during January-December 2017. A total of 215 out-patients and 18 in-patients infected with A(H1N1)pdm09 were detected by virus isolation and real-time RT-PCR. Among the positive patients, 90.6% were less than 14 years old. Hemagglutination inhibition (HI) antibody titers against A(H1N1)pdm09 viruses in Myanmar were similar to the recommended Japanese influenza vaccine strain for 2017-2018 seasons (A/Singapore/GP1908/2015) and WHO recommended 2017 southern hemisphere vaccine component (A/Michigan/45/2015). Phylogenetic analysis of the hemagglutinin sequence showed that the Myanmar strains belonged to the genetic subclade 6B.1, possessing mutations of S162N and S164T at potential antigenic sites. However, the amino acid mutation at position 222, which may enhance the severity of disease and mortality, was not found. One case with no prior history of oseltamivir treatment possessed H275Y mutated virus in neuraminidase (NA), which confers resistance to oseltamivir and peramivir with elevated IC50 values. The full genome sequence of Myanmar strains showed no difference between samples from in-patients and out-patients, suggesting no additional viral mutations associated with patient severity. Several amino acid changes were observed in PB2, PB1, and M2 of Myanmar strains when compared to the vaccine strain and other Asian strains. However, no mutations associated with pathogenicity were found in the Myanmar strains, suggesting that viral factors cannot explain the underlying reasons of the massive outbreak in Myanmar. This study reported the first detection of an oseltamivir-resistant influenza virus in Myanmar, highlighting the importance of continuous antiviral monitoring and genetic characterization of the influenza virus in Myanmar.
Highlights
Influenza outbreaks occur mainly during winter in temperate areas of the northern and southern hemispheres; influenza outbreaks in tropical areas around the equator may occur at any time of the year [1]
Number of samples and detection of influenza virus types and subtypes From January to December of 2017, we collected a total of 328 nasopharyngeal swab samples (267 samples from Yangon study site and 61 samples from Pyinmana study site of Myanmar) from out-patients presenting influenza-like illness symptoms and 288 nasopharyngeal swab samples from in-patients presenting acute respiratory tract infections, and tested the samples for the presence of influenza virus
The differences detected between the median age of out-patients in Yangon and Pyinmana study sites was because the patients who were included in the Pyinmana study site were widely distributed in various age groups, from infants to adults (3 months to 56 years), and majority of the patients who visited the clinic were children less than 5 years old in Yangon for both in out-patients and in-patients groups (Table 2)
Summary
Influenza outbreaks occur mainly during winter in temperate areas of the northern and southern hemispheres; influenza outbreaks in tropical areas around the equator may occur at any time of the year [1]. Influenza is responsible for local epidemics annually and global pandemics. Since the 20th century, there have been four flu pandemics: 1918 H1N1 Spanish flu [2], 1957 H2N2 Asian flu, 1968 H3N2 Hong Kong flu, and 2009 H1N1 swine flu. The 1918 H1N1 Spanish flu, which killed more than 50 million people worldwide, was the most severe pandemic [3]. Influenza virus is a highly infectious respiratory pathogen manifesting a significant threat to global public health [1]. Influenza A(H1N1)pdm virus, which emerged in 2009 and caused a global influenza pandemic, is a seasonal influenza virus that co-circulates with another seasonal influenza (H3N2) and influenza B viruses. Worldwide circulation of A (H1N1)pdm virus has raised concerns about genotypic diversity that enhances virus transmissibility and pathogenicity and affects vaccine efficacy [4]
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