Approximately 5 to 15% of the global population is infected with Influenza virus annually. There are estimated 3 to 5 million cases annually of severe influenza illness and about 2,90,000 to 6,50,000 respiratory deaths. Influenza virus is classified into four types: Influenza A, B, C, and D. Both Influenza A and B are known to infect humans, whereas Influenza A causes epidemics and pandemics. Since the first pandemic was reported as early as 876 A.D., the Influenza virus has settled into a pattern of avian and swine / human strain reassortment.

Depending on the presence of hemagglutinin (H) and neuraminidase (N) surface antigens, Influenza A is further classified into different subtypes. As per CDC reports, 18 different subtypes of hemagglutinin (H) and 11 different neuraminidase (N) have been reported; approximately 198 combinations are possible of which only 131 are in circulation. Due to ongoing reassortment and major antigenic changes, around 11 major Influenza pandemics have been reported since 1700.

Two types: H1N1 and H3N2 are responsible for the majority of pandemics during the 20th and 21st centuries. The most virulent pandemic strain of H1N1 emerged during 1918 resulting in almost 50–100 million deaths worldwide. H3N2 is responsible for one of the three major influenza pandemics that occurred in the last century. In 1968, a novel strain of the H3N2 influenza virus emerged in Hong Kong (A/Hong Kong/1/1968 [HK/68]) leading to a global epidemic with more than one million deaths. H3N2 influenza viruses have evolved substantially over the past 51 years due to their rapid antigenic and genetic changes leading to severe infection. According to the latest report by WHO, cases of H3N2 are reported from all over the world affecting more than 30% of the world population.

Most humans are infected with influenza viruses by three to four years of age, and these initial childhood infections are known to elicit strong, long-lasting memory immune responses. Throughout life, humans are repeatedly infected by influenza viruses, primarily due to mutations or antigenic drift. Certain mutations with HA, NA, and non-structural (NS) genes may result in more or less virulent viruses. The first reported flu pandemic H1N1 virus had a high case fatality report (CFR) of 2%, however during the 2009 pandemic reasserted strain (H1N1/09pdm) re-emerged it had attenuated and CFR was just 0.03%. Despite lower morbidity and mortality, influenza A(H3N2) virus infections have become the leading cause of seasonal influenza illness and death over the last 50+ years, with more than twice the number of hospitalizations from A(H3N2) as from A(H1N1) during the past six seasons globally.

Factors that have contributed to the higher impact of H3N2 globally include a higher rate of genetic and antigenic change as compared to H1N1 viruses, a disproportionate impact on older adults mainly due to waning immunity, and a decline in vaccine-related immune protection with generally higher viral loads. Even 50 years later, H3N2 continues to adapt to evade host immunity and cause higher numbers of hospitalizations and deaths than H1N1 and Influenza B viruses. In the last ten years, WHO has recommended six H3N2 influenza vaccine strain changes, primarily due to the emergence of novel clades and sub-clades of H3N2.

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The majority of the H3N2 infected cases experience enhanced symptomology, though the symptoms resemble other respiratory viruses, which include headache, sore throat, fever, nasal discharge, coughing, nasal discharge, and myalgia. In severe cases, pneumonia and bronchitis may occur leading to a high mortality rate. H3N2 is more severe than H1N1 in the case of C-reactive protein, fever, and leukopenia-type diseases. Timely diagnosis of H3N2 is essential for early treatment and management. Among available detection methods, Real-Time PCR is a standard test as recommended by the WHO. Due to the emergence of H3N2

Variant forms mainly due to mutations in the WHO-recommended target region RT-PCR tests may have reduced sensitivity for detecting circulating novel/variant forms. Considering the routine seasonal outbreaks, RT-PCR for Influenza viruses is usually not required particularly in suspected outpatients. However, testing may influence clinical management and treatment decision, particularly in cases with severe symptoms or underlying co-morbidities such as diabetes, hypertension, etc. Influenza virus testing is recommended for all patients with suspected influenza who are being admitted to the hospital. In view of the genetic and antigenic drifts during seasonal outbreaks, the limitations of influenza virus tests and their results, particularly negative results should be interpreted in conjunction with the clinical status of the patient.

Views expressed by Dr Rashmi Khadapkar, Sr. Research Scientist & Sr. DGM R&D Operations at SRL

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