| BackgroundNoroviruses (NoVs) belonging to Caliciviruses,Norovirus, have long been recognized as one of the important causes of the world’s human acute gastroenteritis outbreak, which can infect all age groups. NoVs have the characteristicsof strong infectiousness, rapid mutation and being stable in the environment. And the outbreaks oftenoccurredin relatively enclosed spaces such as schools, homes, hospitalsand military. In addition, NoVs are also common pathogen which caused diarrhea in infants and children less than 5 years old, ranking only second to rotavirus.After developed countries include rotavirus vaccine into their immunization programs, NoVs quickly replaced rotavirus and became the most important pathogen causing infantile diarrhea.A new NoVsmutant strain appears every few years and causes a global outbreak. It is reported that 21 million peoplein the United States caused by norovirus infection each year, including 1.9 million outpatients,0.4 million emergency cases,71,000 hospitalizations and 800 deaths.medical expenses and productivity lossin the United States causing byfoodborne outbreaks of NoVs reached $200 million. In developing countries, NoVsled to 218,000 deaths for children under age 5.With the development of economics andpathogen detection capability in China, outbreaks ofNoVshave caused great concern in the whole society and people. DuringJanuary to March in 2013, NoVs outbreaks occurred in 6 schools in the Guangzhou University City, with652 incidence cases.On December 2014, NoVs outbreak in 10 schools and 3 nursery schoolsin Jiaxing, Zhejiang Province, with 511 incidence cases. Long-term monitoring study showed that NoVs-positive children under age 5 were as high as 10%-20%, while in adults were 20%-40%. Thus, NoVs gastroenteritis is a global public health problem, including in China. Therefore, study on the molecular epidemiology of NoVs, understanding on the epidemic regularity and pandemic strain characteristic of NoVs in China is of vital importance for the prevention and control of viral diarrhea.ObjectivesAnalysis of the disease burden, epidemiological characteristics and molecular variation law of NoVs in hospitalized infants for diarrhea under age 5 in some areas of China from 2011 to 2014, could provide basic data and scientific evidence for the prevention and control of NoVs gastroenteritis.Methods1. Collect and organize 19798 demographic data, clinical information and test results of hospitalized infants for diarrhea under age 5 in 19 monitoring areas from January 2011 to December 2014. Statistical methods were used to analyze the epidemic characteristics of NoVs in China.2. Collect 1068 samples of faecesof NoVs-positive hospitalized infants for diarrhea under age 5in some areas of China from 2011 to 2014. RT-PCR was used to amplify the gene fragment inthe polymerase region of NoVs.Gene sequencing, sequence processing, alignment and phylogenetic analysis method was used to determine NoVsgenotypes in the polymerase region and analyze genetic characteristics and variation of epidemic NoVsstrains.3. For 494 NoVs-positive strains obtained in 2013-2014, RT-PCR was used to amplify the gene fragment in the capsid protein area of No Vs. Gene sequencing, sequence processing, alignment and phylogenetic analysis method was used to determine NoVsgenotypes in thecapsid protein area. Polymerase region and capsid protein was used together to analyze genetic characteristics of NoVs,and to determine different NoVsstrainswith genotypesin the polymerase region and capsid region.Results1.19798 demographic data, clinical information and test results of hospitalized infants for diarrhea under age 5 in 19 monitoring areas from January 2011 to December 2014 were collected, with 3454 NoVs-positive. The average detection rate was 17.5%, with the highest 20.25% in 2012 and the Iowest14.48% in 2013. The age groups with highest NoVs-positive rate in hospitalized infants for diarrhea under age 5 in 2011-2014 were 9-11 months (24.01%),12-17 months (24.27%),12-17 months (17.75%) and 6-8 months (20.28%), respectively. The average detection rates of NoVs from the first quarter to the fourth quarter in 2011-2014 were 20.04%,16.62%, 19.87% and 15.48%, respectively. Monitoring data showed thatNoVs infections in hospitalized infants for diarrhea in China have occurred throughout the whole year from 2011 to 2014, and the peak season showed in February-March and September, while the peak in September (detection rate of 23.3%) is slightly higher than February-March (22.5% and 21.6%).NoVs detection rate showed differences (chi-square=542.963, P<0.05) in the 19 monitoring areas in 2011-2014. The top three areas are Fujian, Jiangsu and Sichuan, and the detection rates were29.71%,26.48% and 23.96%, respectively. The detection rates of Xinjiang, Hunan, Henan were lower, with 11.18%, 10.17%,4.03%, respectively.5809 samples were detected in the coastal areas, with 1189NoVs-positive samples, and the positive rate was 20.47%.13989 samples were detectedin the inland areas, with2265 NoVs-positive samples, and the positive rate was 16.19%. The NoVs detection ratesin coastal and inland were statistically significant (chi-square=52.31,P<0.05). The NoVsdetection rates between northern and southern regions were statistically significant (chi-square=30.678, P<0.05). The NoVs detection rates in the south region were higher than that in the northern region. And the NoVs detection rates in coastal southern region and inland southern regionwere also statistically significant (chi-square=22.600, P<0.017, a correction= 0.017).The NoVsdetection rates incoastal southern region were higher than that ininland southern region.2.2011--2014 1068 polymerase region sequences of NoVsstrains were obtained, of which GII accounted for 99.3%(1060/1068), GI for 0.7%(8/1068). GII.4 type was as the main detection type, accounting for 58.9%(629/1068); then followed by GII.P12 type, accounting for 33.3% (356/1068); detection rates ofother types accounting for 0.1-3.4%, including GII.P1、GII.P2、 GII.F5、GII.P6、GII.P7、GII.P13、GII.P1、GII.P17、GII.P21、GII.P22、GII.Pe、GII.Pg、 GI.P2、GI.3、GI.4 and GI.6. The GII.4 type in 2011-2014was further divided into three subgroups, GII.P4/DenHaag、GII.P4/New orleansand GII.P4/Sydney 2012. The percentage of GII.P4/ DenHaag mutants accounting for GII.4 type in 2011-2014 was 91.5%,80.4%,16.3% and 1.0%, respectively. The percentage of GII.P4/New Orleans mutants was 8.5%,6.3%,5% and 1%, respectively, while for the GII.P4/Sydney 2012, the percentage was 0,13.3%,78.7%and98%, respectively. The two main detected genotypes GII.P4 and GII.P12 differed in different distribution parts, the proportion of GII.P4 in Xinjiang, Sichuan, Fujian, Shanxi, Beijing, Jiangsu, Guangdong and Guangxi was higher than that of GII.P12.The proportion ofGII.P12 in Inner Mongolia, Hebei, Shanghai and Yunnan was higher than GII.P4.The GII.P12 and GII.P4 accounted similar proportion inJilin and Anhui. Among the hospitalizedchildren for diarrhea under 5 years, the proportion of GII.P4 in children under 4-year-old was about 53% and didn’t have much difference in each age group.Buti the gene type GII.P4 was not found in the 48-59 months group. GII3 accounted for 30% in the children under5 years of age group, but accounted a high proportion in the children under 5-month-old and accounted lower in the children 6 months older.3.494 gene sequencesin the capsid protein area of NoVs in some areas of China in 2013-2014 were obtained, of which the main type was GⅡ.4, accounting for 52.6%.GⅡ.4/Sydney 2012 variants, GⅡ.4/New orleans variants and GⅡ.4/DenHaag variants accounted93.5%,5.4% and 1.1%,respectively. The second was GⅡ.3, accounting for 38.5%, of which GⅡ.3-D and GⅡ.3-E variants accounted 8.9% and 91.1%, respectively; and other types included GⅡ.2, GⅡ.5, GⅡ.6, GⅡ.7, GⅡ.9, GⅡ.13, GⅡ.17, GⅡ.20, GⅡ.21 and GⅡ.22, accounting for 0.2%-3.7%.4.486 strains with both polymerase region and capsid protein region in 2013-2014 were obtained, in which 265 had the same strain type, accounting for 54.5%t, including GⅡ.17 (3 stains), GⅡ.21 (3 stains), GⅡ.6 (1 stains), GⅡ.22 (1 stains), GⅡ.7 (5 stains), GⅡ.4/Sydney 2012 mutant (218 stains), GⅡ.4/New Orleans mutant (17 stains) and GⅡ.4/DenHaag mutant (17 stains).221 strains hadinconsistenttypes, accounting for 45.4%, mainly GⅡ.P12/GⅡ.3 (polymerase/capsid region) (177 strains).Conclusions1. NoVs are important pathogen which caused diarrhea in hospitalized infants and children for diarrhea less than 5 years old. The average detection rate of hospitalized infants for diarrhea under age 5 in China from 2011 to 2014 was 17.5%.2. NoVs primarily infected children less than 2 years and the peak season showed in February-March and September. NoVs detection rate in the South was higher than that in the North and the rate in coastal was higher than that in inland, which had statistically significance.3. Novs of hospitalized children under 5 years in China had genetic diversity, including four GⅠ genotypes and 14GⅡ genotypes, of which the GⅡ.P4 genotype was predominant.In 2012 Sydney 2012 mutant had replaced GⅡ.4/DenHaag variation strain and became the new epidemic strains.In polymerase type, GⅡ.P12 was the predominant strains ranked only after GⅡ.P4.4. Phylogenetic analysisin polymerase region and the capsid protein region showed that the ratio of reorganization or mixed infection ofNoVswas high. |
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