Detection of neuraminidase inhibitor-resistant influenza A (H1N1)pdm09 viruses obtained from influenza surveillance in Indonesia

Abstract

Background: Influenza antiviral resistance has been shown to occur in many countries and is commonly found in influenza A(H1N1)pdm09 and A(H3N2). In this study, we monitored and investigated the neuraminidase inhibitor resistance of influenza A(H1N1)pdm09 viruses through the influenza surveillance system in Indonesia.

Methods: A total of 4752 clinical specimens were collected from patients with influenza-like illness and severe acute respiratory infection during the year 2016. An allelic discrimination assay was conducted by a single base substitution or a single-nucleotide polymorphism that is specific to the H275 wild-type and Y275 mutant. Sequencing was performed to confirm the H275Y mutations, and we analysed the phylogenetic relationship.

Results: The first occurrence of oseltamivir-resistant influenza A(H1N1)pdm09 was observed in the samples from the influenza-like illness surveillance. Two H275Y oseltamivir-resistant viruses (0.74%) out of 272 influenza A(H1N1)pdm09 positives were found. Both of them were collected from untreated patients.

Conclusion: The number of oseltamivir-resistant influenza A(H1N1)pdm09 viruses in Indonesia is very low. However, it is necessary to continue with active surveillance for oseltamivir resistance in severe and mild cases.

Keywords: Neuraminidase inhibitor resistant; influenza A(H1N1)pdm09; surveillance.

Figure 1.

Phylogenetic tree for the HA (a) and NA (b) sequences. The evolutionary history was inferred using the neighbour-joining method, and the evolutionary distances were computed using the Kimura 2-parameter method. Evolutionary analyses were conducted in MEGA7. Red circle and sequences indicate the Indonesian oseltamivir H275Y-resistant influenza A(H1N1)pdm09 virus. Viruses carrying the mutation H275Y found in resistant influenza A(H1N1)pdm09 viruses from other country are marked with coloured circles (magenta circles from Japan, blue circle from United States, green circles from China, and yellow circles from the rest of the country). The blue sequences indicate the vaccine virus 2016/2017 and 2018/2019. All of the sequences are rooted to the vaccine virus 2016/2017 as a reference.