Molecular Epidemiology Of Mycobacterium Tuberculosis In Chongming Island

Tuberculosis(TB) is still a major health threat globally,and China is one of 22 high-burden countries for TB disease with the second highest infected TB patients in the world.Traditional contact investigation is limited for tracking Mycobacterium tuberculosis,due to the long latent period of M.tuberculosis.Since 1990s,molecular biology technologies,which have been used for differentiating distinct M.tuberculosis,combined with traditional contact investigation become useful tools for interpretation the transmission of M.tuberculosis and guide tuberculosis-control strategies.In China,molecular epidemiology research just begin to carry out and few reports about molecular epidemiology of tuberculosis on the base of population exist.The present study established a simple and rapid VNTR typing method for differentiating Beijing genotype strains in China and further investigated molecular epidemiology of M.tuberculosis in Chongming Island during 2003-2005.PartⅠ.Established a simple and rapid VNTR typing method for differentiating M.tuberculosis Beijing genotype strains in China.M.tuberculosis was predominative in many provinces in China.More than 60%M.tuberculosis clinical strains belong to Beijing genotype family in Beijing, Shanghai and Ningxia,and Beijing genotype strains account for 50.75%M. tuberculosis strains obtained from nationwide random survey for the epidemiology of tuberculosis in China in 2000.Furthermore,Beijing genotype strains widespread worldwide.Such strains have attracted a great amount of attention because they were reported association with outbreaks,multiple-drug resistance and their ability to multiply rapidly in human macrophages.W-Beijing genotype strains were associated with outbreak of drug-resistant strain in New York.VNTR typing method is a promising,simple and rapid typing method for differentiating Beijing genotype strains.However,one VNTR locus showed different discriminatory power among Beijing genotype strains from distant geographic area.In this study, we conducted a literature search for all identified VNTR loci and determined the Hunter-Gaston discriminatory index(HGI) values of each of 45 VNTR loci we identified,using Beijing genotype strains from a population with low immigration, Chongming Island,Shanghai,China.We optimized two select sets of VNTR loci, which we named VNTR-7 and VNTR-16,for typing.The HGI value of VNTR-7 was slightly lower than that of IS6110 restriction fragment length polymorphism (RFLP),and the HGI values of VNTR-16 and IS6110 RFLP were comparable. VNTR-7 can be a useful first-line typing method,followed by IS6110 RFLP for secondary typing,and VNTR-16 could be used alone or in addition to IS6110 RFLP typing as a secondary genotyping method,to study the molecular epidemiology of tuberculosis in China.PartⅡ.Molecular epidemiology of M.tuberculosis during 2003-2005 in Chongming IslandChongming Island is located in the estuary of the Yangtze River and isolated by geography.Most residents are farmers and a few of migration people.Although DOTS control strategy has been conducted for more than 10 years in Chongming Island,the tuberculosis incidence rate is decreasing slowly.M.tuberculosis isolates from newly diagnosed culture positive lung tuberculosis patients in Chongming Island were subjected to IS6110 RFLP typing.Patients with identical patterns were grouped in clusters.DNA fingerprinting identified 29 clusters,28 of which consisted of only 2 persons and the largest of which consisted of 6 persons.The estimated rate of recent transmission was 16.2%by the n-1 method.Patients in clusters were more likely to be elders(mean age,63 years vs.57 years for patients not in clusters;p=0.003).The incidence rate of clustered tuberculosis among males and females were both increased from ages＞65 years.The clustering was not associated with gender,drug resistant strains and Beijing genotype strains.Drug resistant strains were associated with Beijing genotype strains.Recent transmission of tuberculosis contributes less to the increase in tuberculosis,but increasing incidence rate of elder clustered tuberculosis(≥65 years of age) should not be ignored.Therefore,measures for effective treatment older tuberculosis patients should be enforced.