The Israeli Winter of 2018-19: Unique Circulation and Substantial Genetic Changes of Influenza Viruses

Influenza is a contagious viral infection, leading to an acute respiratory disease, causing substantial morbidity and mortality. While vaccination is considered the most effective mean to prevent influenza morbidity, influenza vaccine effectiveness varies yearly, depending on the circulating influenza strains.

Seasonal surveillances in outpatient clinics allow the identification of the circulating influenza virus strains in Israel. In winter of 2018-19, the dominate influenza strain was influenza A/H3N2 virus, detected in 76% of influenza-positive samples obtained in outpatient sentinel clinics and in 63% of hospitalized influenza-positive patients in Sheba medical center; some of the positive cases were vaccinated.

Interestingly, while the dominant strain circulating this season in most parts of the northern hemisphere was influenza A/H1N1pdm09, in Israel it was detected only in 22% of the outpatient influenza-positive cases and in 30% of the hospitalized influenza-positive patients. Influenza B morbidity was negligible in Israel, as in the rest of the northern hemisphere.

Molecular analysis revealed substantial differences between the circulating influenza A/H3N2 strain and the vaccine strain, with approximately 18 amino acid mutations; a total of 8 amino acid mutations occurred in antigenic sites. Phylogenetic analysis indicated that the circulating strain belongs to clade 3C.3a, while the vaccine strain belongs to a different clade-3C.2a1. Unlike influenza A/H3N2, molecular analysis of influenza A/H1N1pdm09 revealed fewer mutations in the circulating strains compared with the vaccine strain. However, phylogenetic analysis revealed that the circulating strain belong to a new sub-clade, different from the vaccine strain clade-6B.1.

Additional molecular analysis of the Israeli influenza strains and the influenza strains worldwide are necessary to further understand the unique widespread and most importantly, the significance of the influenza A/H3N2 mutations in Israel. The ongoing genetic changes that occur among influenza viruses, in general, and influenza A/H3N2 in particular highlight the potential advantage of a universal influenza vaccine.