云南HIV相关NTM病的病原调查及其生物学特性研究

Nontuberculous mycobacteria (NTM) disease is one of AIDS-Related common Opportunistic Infections and seriously affects people's health, and the infection rate of NTM in human has risen with the increase of HIV-infected people and improvement of diagnoses techniques. Currently, reported cases of NTM disease are not mandatory in most of country, and it is unfavorable to find out the epidemic of NTM exactly. Gene polymorphism analysis of NTM is the basic of modern molecular epidemiological research and monitoring, and we could study evolution and variation trend of NTM at molecular level from gene polymorphism analysis. This study propose to isolate and identify causative agent of HIV related NTM disease by staining, culture, biophysical and biochemical tests and genotyping. Then study the phenotype and drug resistance of isolated strain of HIV related NTM, and analyze gene genotyping and polymorphisms of isolated strain by MIRU-VNTR. By studying, we aim to understand the species, distribution, source of infection, epidemiology, drug resistance, correlation of phenotypic variation and gene mutation, and gene polymorphism of HIV related NTM disease, and provide basis for the establishment of diagnosis, prevention and treatment measures of HIV related NTM disease.

非结核分枝杆菌(Nontuberculous mycobacteria，NTM)病是AIDS的常见机会性感染疾病之一，随着HIV感染人群的扩大及实验诊断技术的不断提高，人类NTM的感染率呈现不断上升的趋势，严重影响人们的健康。目前大多数国家对NTM病的报告是非强制性的，不利于准确了解NTM的流行情况。而基因多态性分析是现代分子流行病学研究和监测的基础，并能从分子水平研究病原菌的进化程度和变异趋势。本研究拟对云南地区HIV相关NTM病的病原体通过形态染色、培养、生理生化试验、核型分析等进行菌种分离和鉴定。研究分离株的表型特点、耐药性状况，并利用MIRU-VNTR分子指纹法对分离菌株进行基因分型和多态性分析。以了解云南HIV相关NTM病的病原体种类、分布特点、传染来源、流行现状、耐药情况、表型变异与基因型变异的相关性以及基因多态性特征，为该病的诊断、预防和治疗措施的制定提供基础。

非结核分枝杆菌(Nontuberculous mycobacteria，NTM)病是AIDS的常见机会性感染疾病之随着HIV感染人群的扩大及实验诊断技术的不断提高，人类NTM的感染率呈现不断上升的趋势，严重影响人们的健康。目前大多数国家对NTM病的报告是非强制性的，不利于准确了解NTM的流行情况。对云南 HIV相关NTM病的病原体进行病原学、基因多态性，基因型与耐药性相关性研究，弄清楚病原学特征，感染的优势基因型，基因型与耐药性之间的相关性，这样可以针对优势基因型的特殊基因靶位进行药物研究，从而有利于制定防治NTM的措施，而且对于AIDS的预防和治疗具有重要意义。.随着分子生物学理论和技术的飞速发展，诸多高度特异的基因分型方法得到研究建立。目前使用最为广泛的是IS6110-RFLP、Spoligotyping和VNTR技术。本研究对云南HIV相关NTM病的病原体进行菌株分离培养与鉴定。选择优势菌群MAV用VNTR法进行基因分型和多态性分析，结果显示云南MAV有着较高的基因多态性，VNTR法至少将其分为四个基因群，主要流行菌型为Ⅱ型。并找到了12个分辨力较高适合云南MAV分型的位点。然后用比例法检测菌株对异烟肼、利福布丁、乙胺丁醇、链霉素、卡那霉素、左氧氟沙星和卷曲霉素七种药物的敏感性。通过药敏结果和基因分型结果分析得出细菌耐药与基因多态性之间没有相关性的结论。