الفهرس 
Chapter I: IntroductionOnly 14 pages are availabe for public view
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Abstract
Summary
Influenza viruses cause viral respiratory infections among humans, mammals, and avian species. Historically Influenza A viruses causes serious epidemics and pandemics among humans, four pandemics were occurred hence the early 20th century to date, described as the 1918 H1N1 ‘Spanish flu’, the 1957 H2N2 ‘Asian flu’, the 1968 H3N2 ‘Hong Kong flu’ and the 2009 H1N1 ‘pdm09’ pandemics. Influenza infections are usually self-limited. However, it may be associated with increased morbidity and mortality in certain high-risk populations (children, elderly aged persons, immunocompromised individuals, and those have comorbidities).
In addition to seasonal H1N1, H3N2, and influenza B, avian influenza (AI) viruses of subtypes H5, H6, H7, H9 and H10, have crossed the species barrier and caused human infections during last 2 decades. There is a little information on the evolution of seasonal influenza A/H1N1 and H3N2 viruses in Egypt. Although AI H5N1 and H9N2 viruses are known to be circulating among poultry in Egypt, recent studies indicated that; number of human infections with AI viruses in Egypt are much larger than the number of reported confirmed cases. Up to 2% of poultry-exposed humans had neutralizing antibodies against H5N1 virus and around 7% had neutralizing antibodies against.
Interventions to influenza infections are accomplished either by vaccination and antiviral agents, many events of vaccine induced immunity and or antiviral agents escaped mutants had been reported.
Influenza vaccination is recommended by the world health authorities for those group at high risk. Two universal seasonal influenza vaccines (i) trivalent inactivated vaccine for immunizing populations against H1N1, H3N2, and influenza B for all people aged more than 6 months, and (ii) live attenuated influenza vaccines for healthy non pregnant people aged 2-49 years. Vaccine efficacy in randomized trials was ranged 42-66% in all population groups. Reduction in mortality after vaccination ranged from 27% to 75%. Current influenza vaccines are less effective to control influenza infections and encounter several problems including
(a) inducing narrow strain specific immunity.
(b) continuous mutation in viruses (antigenic drift) make vaccines un-effective to use from one season to the next.
(c) developing updated influenza vaccines is a complex, costly and time-consuming process.
Egypt included in the northern hemisphere of the WHO influenza vaccination strategies, with little information on the prevalence and evolution of seasonal influenza A(H1N1) pdm09 and H3N2 viruses, little available sequences of Egyptian human influenza viruses in influenza data bases.
The study results can be summarized in some points as follow:
1- Design: We designed a cohort study to understanding the evolution of A(H1N1) pdm09 and H3N2 viruses, diversification, determining genetic and antigenic relations, and choosing vaccine strains to be included in the annual influenza vaccine as well as vaccine evolution in comparison with those recommended to be used in vaccination global vaccination programs.
2- Timeline: The study was accomplished during 2017-20, three active influenza seasons, at which enrollment of 2405 participants at 5 sites, health status, demographic, and economical status were observed to assessing risks to influenza infections, weekly or biweekly visits were arranged by field team to determine influenza like illness in all participants with sampling for those became ill. Annual follow up for assessing dynamics in health status, and demographics of study participants.
3- Many laboratory assays were accomplished to determine seroprevalence rate, incidence, diversity, viral characteristics, antigenic diversity of influenza viruses with comparison with vaccine recommended strains. The study findings reinforced our concept about the situation of inequity in influenza surveillance and control.
4- Seroprevalence rates wase ranged 46-68% for H3N2, and 24-52% for H1N1 for all study populations, this seroprevalence rates differ within the sub demographic groups to reach around 80% in some seasons for H3N2 viruses. On the other hand low levels of seroprevalence for avian influenza were reported, 0.2, 0.4% for H5N1 and 11.1, 0.1 % for H9N2 virus at 2017 and 2018 respectively
5- Influenza like illness was ranged from season to another as 2017-18 was 16% in all cohort while in 2018-19 reached to 33% then increased to be 47% in 2019-20 season. Influenza infection incidence was in dynamic status as an infection with specific subtype of influenza virus be dominant at specific season and less dominant in others, not only human influenza H1N1 and H3N2 were detected in the study populations, some avian H5N1 and H9N2 viruses were detected.
6- Genetic characteristic of the cohort viruses was significantly different from those recommended for vaccine production; hence antigenic characteristics of cohort influenza viruses isolates were differed.
7- Many risk factors were detected for infection with influenza viruses, as younger aged, students, and those with kidney or blood disorders were likely to be seropositive for influenza infections.