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Epidemiological Analysis Of Measles And Etiology Study Of Wild-type Measles Viruses In Jilin Province Of China

Posted on:2008-06-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:J BianFull Text:PDF
GTID:1104360212997749Subject:Pathogen Biology
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The measles virus (Measles Virus, MV) is pathogen of the measles. Before measles vaccine is applied, it is one of extremely serious infectious diseases to harms child life and health in the world. According to the World Health Organization (WHO), it is estimated there are 45 million examples measles every year in the world. One million of babies and the children died of the measles in the developing countries, especially in the African. The measles still is the most cases of death virulent diseases that may be prevented by vaccine. Before the implementation measles vaccine, every child is difficult to avoid measles.Since 70's of the 20th century, the whole world has started to implement the expanded immunity plan (EPI), the measles vaccine vaccination rate is enhanced year by year. Incidence rate and mortality rate of the measles are dropped in large scale. There are 1.3 millions children died of the measles at present every year. After extinct smallpox and polio, the measles will possibly become the third disease which will eliminate in the world.Our country has got the very great progress in the control measles. Our country started the application measles vaccine in 1965 and especially in 1984 the strengthening planned immunization program was done, the incidence rate and fatality rate of measles were obviously reduced. The measles prevalence in the large scale basically is under the controlled. Incidence rate of disease is about10/10 ten thousands. In our country all provinces, cases of the measles obviously dropped, but the popular intensity still had great difference. Incidence rate of measles was still relative higher in the remote province and outbreak in some regions. The new problem was observed. These caused measles to sometimes occur popularly in small scale. The national measles morbidity rise is obvious. The new problem is proposed about measles control.This article carries on the description epidemiology analysis and the data processing on the Jilin Province from 2004 to 2006 year measles epidemic disease material and the measles epidemic situation monitor material. Fifty-three examples were reported in the whole Jilin Province in 2004 and measles incidence rate reported was 0.2 per hundred thousands. Measles incidence rate compared with 2003 dropped 78.33%. In 2005, the whole province measles arose 1 978 examples. Measles incidence rate was 7.27 per hundred thousands and compared with 2004 rose 3553.65%. The first overtopping was 3 per hundred thousands of disease incidence rates from 1985. Measles outbreak was in 8 districts of Jilin Province different degree. In 2006, 4 278 examples were reported in the whole Jilin Province. Measles incidence rate was 17.41 per hundred thousands, compared with 2005 rose 138.42%.There were no death cases of illness. Analysis of age distributes had two peaks of age of onset every year in all age group. Two peaks were 0~2 years old group and 10~40 years old group respectively, but 1 year old of group was the measles rises peak age section. From sex, sick probability of the male was higher than the female. The measles arose has the obvious seasonal characteristic and was high stage from March to June every year. Case of illness number these two months reported accounts for the whole year to report case of illness number 69.81%(2004),69.41%(2005) and 80.36%(2006) separately. Reported case of illness number both in April and May was the most and lowest in September. Distributes from the region looked that, there was only 8 districts (according to administrative division Jilin Province to be divided 9 areas) to report the measles case of illness in 2004, but in 2005 all 9 districts have the measles case reporting. Measles outbreak was in some districts. In 2006, the measles epidemic situation nearly affects all counties and city, the popular intensity surpassed in 2005 the same time 3~5 times. Tendency to assume partial exploded the situation to spread the entire province was. Measles arises about the occupation distribution situation was in following four kinds of occupations that the measles arises the number were more. They were lives scattered the child, the student, the day care children and the farmer in turn. Occupies always arose the number were 70% above proportion. Looked from the immunity vaccination and the immunity history, not the immunity and the immunity history is unclear case of illness number occupies always sends case of illness number 83.32%, the crowd only has about 91% to the measles immunity, cannot prevent the measles virus circulation dissemination.The epidemiology analysis result indicated that, (1) the crowd has not carried on the vaccination measles vaccine according to the stipulation related, has not specially carried on the second strengthened immunity; (2) the individual place appears the immunity blind spot, the easy feeling crowd to increase related; (3) the immunity defeat, after adds the primary immunity to grow but the immunity along with the age gradually to reduce, the partial measles patient arises in the age to move concerns. These are main reasons of measles erupts the popular in our province from 2005 to 2006.This research collects measles specimen from case of illness 89 from November, 2004 to April, 2006, and succeeds separate 19 viruses with the VERO/SLAM cell line. The monoclonal antibody was carried on neutralization test with viruses to be isolated in the measles wild virus appraisal, and took the measles vaccine, measles standard Edmonston as the parallel sample. The results show: 1: 10 dilutions can neutralize all 19 measles viruses, but 1: 20 steps majority of samples hole can be neutralized. On 1: 40 steps there were only half sample holes to be neutralized. The result confirmed, completely19 virus for measles virus.To separates 19 strains wild-type measles virus had conducted the molecular epidemiology signature analysis. Gene characteristic and the molecular difference of wild-type measles virus in different year separation had further analyzed. Viral RNA prepared from 19 strains wild-type measles viruses was used as a template for RT-PCR (reverse transcript polymerase chain reaction). 450 nucleotide pieces of the C- terminal region of the nucleoprotein gene were amplified and sequenced. Phylogenetic analysis and diversity analysis were done with Bioedit7.0 and the MEGA3.1. These analyses were done: phylogenetic trees, the nucleotide variation, the amino acid variation and the heredity distance of among 19 strains wild-type measles viruses and measles WHO reference strains. To use measles international Edmonston strain, measles vaccine Changchun47 strain and three strains wild-type measles virus separated from 2004 to 2006 prepares the immune serum separately, and then carried on the cross neutralization experiment with all measles strains. IgM antibody in the measles patient acute stage blood serum was determined. Neutralizing antibody titer from the different origin crowd blood serum had separately carried on the determination.N gene carboxyl group terminal 450 nucleotides sequences of nineteen strains wild-type measles viruses were amplified by using RT-PCR and compared with the gene WHO reference with 23 genotype as well as the Chinese vaccine Changchun47 sequence to make phylogenetic analysis. It is obvious that nineteen strains wild-type measles viruses separated from Jilin province belong to the clade H and were one of big branch with H1 reference Hunan.China93-7. The bootstrap value respectively was 99% and 97%. The average genetic distance of these nineteen strains to H1 genotype Hunan.China93-7,H2 genotype Beijing.China94-1 and other WHO reference strains respectively were 0.004~0.023, 0.068~0.071and 0.069~0. 073. The average genetic distance of these nineteen strains to H1 genotype was 0.019 and it could infer that the average genetic distance of these strains was the nearest to H1 genotype. Two kind of analysis methods demonstrated basic consistent result that wild-type measles viruses separated are H1 gene. Further wild-type measles viruses separated from Jilin province in the 2004-2006 compared with genotype H1 and H2 separated from China in 1993-1994 and build phylogenetic tree. H1 genotype wild-type measles viruses compared with represented wild-type measles viruses separated from China from 1993 to 1994. It was discovered H1 genotype wild-type measles viruses belonged to H1a subgenotype that represented strains were China93-2 and China93-4 of WHO reference strains. The bootstrap value achieved 85% and 96% respectively. H1b and the H1c subgenotype had not discovered yet. Major subgenotypes of wild-type measles viruses circulated in Jilin Province from 2004to 2006 were H1a subgenotypes, but it could not completely deny other subgenotypes existence.Compared with the heredity distance of among 19 strains wild-type measles viruses separated from different year and measles WHO reference strains, and themselves, N terminal 450 nucleotides homology and the amino acid homology of nineteen strains wild-type measles viruses measles viruses separated from Jilin province are 98.8%~100%(nucleotide difference were 0~6bp) and 99.2%~100% respectively. Compared with the Edmonston, nucleotide homology and amino acid homology were 92.8%-93.5% (nucleotide difference is 30-32bp) and 92.8%-93.5% respectively. Compared with Chinese vaccine Changchun47, nucleotides homology and amino acid homology were 92.8%~93.3% (nucleotide difference is 30~32bp) and 90.0%~90.6% respectively. Compared variation separated wild-type measles viruses with Edmonston was 0%~7.11%, namely nucleotide difference was in 0~32 bp.Meanwhile from the homology analysis, it was not difficult to know that the nucleotide sequence the homology and the amino acid sequence homology always were not consistent, the nucleotide mutation possibly certainly did not cause the amino acid the variation, and could not affect the protein structure and the function. It is different with it, the minority position spot nucleotide mutation possibly could cause an amino acid bigger variation, whether the measles virus some criticality position spot nucleotides mutation could cause the measles virus biology character change still to need to be discussed. This caused the measles vaccine the protection effect for the crowd to be further studied.The average genetic distance of wild-type measles viruses strains separated from the Jilin Province 2004~2006 was between 0%~1.2%. It was reported that the average genetic distance of Chinese wild-type measles viruses strains separated from 2002 to 2004 was smaller than 1.8%. By analyzing the N gene terminal 450 basic group of wild-type measles virus's strains and Chinese native popular wild-type measles viruses'strains separated in 1999-2004. Major reasons of the measles outbreak was related with planned immunization program fraction of coverage and the immunity achievement ratio, and in the crowd 95% person had the immunity to be able effectively to block the measles virus the dissemination. Along with immunity blank accumulation, each the 4~5 years possibly could appear the measles outbreak and measles was popular. Therefore it needed further to strengthen and implement the planned immunization program.The findings showed that cross neutralization test through measles virus strains with the corresponding immune serum was done. Antigen ratios between every each measles virus strains were calculated. Three wild-type measles virus antigen ratios only were 1.14, 1.04 and 1.01 respectively. It hinted these three wild poisonous had no non-antigenicity difference. But Antigen ratios between measles vaccine Changchun47 and three wild-type measles virus were 3.07, 5.68 and 6.20 respectively. It cued that current wild-type measles virus had more obvious difference with present measles vaccine strain in the antigenicity. Antigen ratios between Edmonston and three wild-type measles virus were 4.16, 6.03 and 4.50 respectively. It simultaneously prompts early measles virus have a bigger antigenicity difference with wild-type measles virus circulated. The primary immunity child blood serum can completely neutralize wild-type measles virus strain, but ability of neutralization wild-type measles virus was obviously lower than vaccine strain. Result of statistics analysis between ability of neutralization wild-type measles virus (GMT is 1:12.13) and vaccine strain (GMT is 1:66.25) with primary immunity child blood serum indicated that they were significance difference. The significance difference meant that immunity protection ability of measles vaccine had already greatly reduced. The healthy blood serum could neutralize wild-type measles virus strain (GMT is 1:16.25) and vaccine strain (GMT is 1:25.99). Both of neutralization ability was not difference and statistical analysis did not have significance difference. It was extrapolated possibility that there was measles silent infection in crowd. The silent infection had become the main infection type of the current measles. On objective it consolidated and enhanced strength of the measles vaccine immunity protection in the crowd. When neutralizing antibody titer of the healthy crowd drop to the certain degree, the healthy become susceptible population to measles. If susceptible population was accumulated to the certain degree, it may cause the measles outbreak or to be epidemic. It was confirmed the possibility of determination result of neutralizing antibody in the measles acute time patient blood serum.This finding indicated that it was a key that gathering and the preservation of sample were whether the measles virus was isolated in succeeds. The experiment using measles virus isolation specimen is to suspect of the measles patient's urine and swallows swabs. From the measles virus isolation result, the urine specimen separation rate slightly is higher than swallows swabs, but statistics analysis result indicated that both two did not have significance difference. According to measles virus isolation result after the measles patient the different number of days gathering specimen, the measles patient specimen whom the measles happened in 6d to gather were allowed to separate the measles virus, but the specimen that isolated measles virus was best in 3 days to gather. It was significance difference both isolation rate of measles 1~3 day and the 4~6 day measles virus statistics analysis.This research from the epidemiology, the serology and the molecular biology level, compared with comprehensively analyzed our province measles to erupt the popular reason, has discussed the measles wild virus gene and the antigen variation the influence which produced to the measles vaccine immunity protection effect, confirmed our province measles erupted, popular measles wild poisonous is the Hla subgroup, this and eliminated the work for the new measles development and our province measles anticipatory control to provide had the scientific value the reference.
Keywords/Search Tags:Epidemiological
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