Influenza Epidemic In Jiangsu Province And Anti-influenza Drug Research

Background and Objective: Influenza is an acute respiratory infectious disease caused by influenza virus. According to the different antigenicity of virus nucleoproteins and matrix proteins, influenza is classified as A, B or C type and each type can be further divided into various subtypes. Influenza has repeatedly caused worldwide pandemics due to the antigen shift of the virus. Influenza puts a heavy threat to human health, affecting economic development and social stability. China is a country with a high incidence of influenza. The Ministry of Health of China and the World Health Organization(WHO) have launched an influenza surveillance project since 2000. The surveillance network of influenza in China gives a priority to collect data of influenza-like cases and virus isolation in 31 provinces. It aims to continuously monitor the epidemic dynamics of influenza, early detect the outbreak, take effective measures and reduce excess mortality caused by the disease. The main strategies to prevent and control influenza include vaccination and antiviral treatment. Due to frequent shrifts of influenza virus, one type of vaccine can’t be always effective for another type of influenza virus. Thus, to successfully control the epidemic of influenza, developing new antiviral drugs is necessary. At present, the majority of clinical anti-influenza drugs are the M2 ion channel inhibitors and neuraminidase inhibitors. Oseltamivir(Tamiflu) is one representative drug ofneuraminidase inhibitors. It can selectively inhibit the neuraminidase of influenza virus, prevent the spread of virus and alleviate the symptoms of the influenza. It has been observed that antiviral drugs were prone to develop resistance and increase the occurrence of adverse drug reactions, which further affect the treatment outcomes. Previous studies found that bone marrow mesenchymal stem cells(MSCs) had a function in repairing the injury of lungs. We hypothesize that it may also play a role in treating influenza-related damages. However, data with experimental evidences are lacking. In the present study, we collected surveillance data of influenza in Jiangsu province, described the epidemiological distribution of influenza and influenza-like diseases and evaluated the network laboratory and sentinel hospitals. We also performed a system review to analyze the efficacy and safety of oseltamivir in treating influenza. We further explored the effect of MSCs in the treatment of severe influenza using a experimental design. This study will provide evidences for the prevention and control of influenza.Methods:(1) We collected the surveillance data of influenza-like cases(ILI), virological genotyping, outbreak reports and human infections with avian influenza virus during 2011-2014 in Jiangsu province. Epidemiological characteristics of influenza-like cases and the trend of the disease were analyzed. We also described the surveillance quality of sentinel hospitals and the virus nucleic acid detection and virus isolation.(2) We searched literatures in Pubmed, wan fang database and CNKI database using the terms of(“oseltamivir” AND “influenza” AND “effect”). The last search was updated in March 2015. The data were extracted from the literatures, including general information(title, authors, publication year, sample capacity and study site); characteristics of the study subjects(age, sex, therapies and time of follow-up); elements for quality assessment(randomization methods, allocation concealment, blinded methods and follow-up); and outcomes(duration of fever, duration of symptoms, complications, adverse events, hospitalization and antibiotic usage). We used the weighted mean difference(WMD) and relative risk(RR), together with the 95% confidence interval(95% CI), to compare differences in continuous or discrete variables between the experimental and control groups.(3) Weselected 80 SPF C57BL/6 female mice and randomly divided them into four groups. MSCs were transplanted into the mice who were infected with influenza virus. The respiratory function and structural changes in the lungs were observed. We used different combinations of transforming growth factor-beta(TGF-β) and inhibitory factor Dickkopf 1 to treat different groups of mice. The function of the Wnt/beta-catenin signal pathway was detected by using the flow cytometry, cellular immunofluorescence experiments, western blot and real-time PCR.Results:(1) There were 845798 ILI cases being reported by the sentinel hospitals in Jiangsu Provence during 2011-2014, accounting for 3.86% of all outpatients at the same time period. This proportion(4.01%) reached to the peak during 2013-2014. Among 57954 samples collected from the sentinel hospitals, 4912 were proved to be influenza virus nucleic acid positive. The main types of influenza virus were A-H3(39.60%), B(34.08%) and A-H1(25.86%). A total of 13 influenza/influenza-like outbreaks were reported during 2011-2014.(2) The meta-analysis indicated that the application of oseltamivir can effectively shorten the duration of fever and other influenza-related symptoms. It could also reduce the incidence of hospitalization, otitis media, non-specific complications and antibiotic usage. The use of oseltamivir didn’t significantly increase the risk of adverse drug reactions.(3) Mice with MSCs transplantation had a significantly lower damage in lungs than untreated mice. After adding the Dickkopf-1, the expression of β-Catenin, TCF, GSK-3β, Axin1 and JNK in the Wnt signal pathway was decreased. The expression of fibroblast surface-related proteins including vimentin,α-SMA,β-Catenin, TCF and GSK-3β were reduced or tendered to normal.Conclusions: In recent years, the major types of influenza virus circulating in Jiangsu province were type A and B. The outbreaks of influenza were often reported in local areas. The prescription of oseltamivir can effectively shorten the duration of fever and symptoms; but will not increase the risk of adverse drug reactions. MSCs have potential values in treating influenza at an early stage, by suppressing the immune response, reducing lung injury and improving the lung function. Findings from this study provide valuable references for exploring new treating methods of influenza.