Abstract
Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host’s immune system. Seasonal influenza causes 4–50 million symptomatic cases in the EU/EEA each year, with a global death toll reaching 650,000 deaths. That being the case, in 2014 North Macedonia introduced the sentinel surveillance in addition to the existing influenza surveillance in order to obtain more precise data on the burden of disease, circulating viruses and to implement timely preventive measures. The aims of this study were to give a comprehensive virological and epidemiological overview of four influenza seasons (2016–2020), assess the frequency and distribution of influenza circulating in North Macedonia and to carry out molecular and phylogenetic analyses of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09, A(H3N2) from ILI and SARI patients. Our results showed that out of 1,632 tested samples, 46.4% were influenza positive, with influenza A(H1N1)pdm09 accounting for the majority of cases (44%), followed by influenza B (32%) and A(H3N2) (17%). By comparing the sentinel surveillance system to the routine surveillance system, we showed that the newly applied system works efficiently and gives great results in the selection of cases. Statistically significant differences (p = < 0.0000001) were observed when comparing the number of reported ILI cases among patients aged 0–4, 5–14, 15–29, and 30–64 years to the reference age group. The phylogenetic analysis of the HA sequences unveiled the resemblance of mutations circulating seasonally worldwide, with a vast majority of circulating viruses belonging to subclade 6B.1A. The PROVEAN analysis showed that the D187A substitution in the receptor binding site (RBS) of the A(H1N1)pdm09 HA has a deleterious effect on the its function. The A(H3N2) viruses fell into the 3C.2a and 3C.3a throughout the analyzed seasons. Molecular characterization revealed that various substitutions in the A(H3N2) viruses gradually replaced the parental variant in subsequent seasons before becoming the dominant variant. With the introduction of sentinel surveillance, accompanied by the advances made in whole-genome sequencing and vaccine therapeutics, public health officials can now modify their approach in disease management and intervene effectively and in a timely manner to prevent major morbidity and mortality from influenza.
Highlights
Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host’s immune system, enabling them to circulate between species and occasionally cross the interspecies barriers
During this season within the group of influenza B viruses, B/Yamagata and B/Victoria co-circulated in North Macedonia with frequency of 90 and 10%, respectively
The percentage of positive samples from the Influenza like Illnesses (ILI) and Severe Acute Respiratory Infections (SARI) surveillance was similar for all subtypes throughout the analyzed seasons
Summary
Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host’s immune system, enabling them to circulate between species and occasionally cross the interspecies barriers. Owing to the negative-stranded segmented RNA genome, influenza viruses constantly undergo spontaneous mutations resulting in small changes in their antigenic properties year to year (Guldemir et al, 2019). These high mutation rates allow for the evasion of immunity. Two surface glycoproteins of the influenza virus, hemagglutinin (HA) and neuraminidase (NA), are of major importance in both clinical and biological terms Changes in these two proteins may sometimes lead to the acquisition of glycosylation sites, which is believed to efficiently generate antigenic variants and play a critical role in virus evolution (Gallagher et al, 1988; Igarashi et al, 2010). The aims of this study were to give a comprehensive virological and epidemiological overview of the past four influenza seasons (2016–2020), to assess the frequency and distribution of the influenza virus types and subtypes circulating in North Macedonia as well as to carry out molecular and phylogenetic analyses of the HA and NA gene sequences of influenza A(H1N1)pdm, A(H3N2), B/Victoria and B/Yamagata from patients from the sentinel surveillance
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
