广西耐药结核病流行特征及结核分枝杆菌基因分型的研究
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摘要
目的了解广西耐药结核病的流行状况、耐药谱,探讨广西结核病耐药性产生的影响因素；了解广西结核分枝杆菌基因型及其分布情况,结核分枝杆菌成簇性特征及影响因素；探讨结核分枝杆菌北京基因型与耐药的相关性,初步探索适合广西结核分枝杆菌北京基因型鉴定的方法。从而掌握广西耐药结核病流行的基线资料,为制定广西耐药结核病的预防控制措施提供参考,并为后续的分子生物学研究奠定基础。
方法采用现场流行病学与现代分子生物学技术相结合的方法,开展以人群为基础的结核病分子流行病学研究。采用整群随机抽样方法在全区抽取30个县(区)作为项目点,于2010年7月-2011年6月连续不间断纳入符合条件的涂阳肺结核患者作为研究对象,采用统一设计的调查表和查阅病史记录的方式获取患者基本信息和相关流行病学资料；对研究对象的痰标本进行一线和二线抗结核药物敏感性试验,获取耐药性资料。同时,运用VNTR基因分型技术对收集的结核分枝杆菌菌株进行基因分型,应用RD105和RD207缺失基因检测法鉴定广西结核分枝杆菌北京基因型,探索适合广西结核分枝杆菌北京基因型的鉴定方法。研究全程进行严格质量控制。数据资料采用Epidata3.1软件建立数据库进行双录入及核对,应用SPSS19.0统计分析软件进行数据统计分析。
结果1.广西耐药结核病流行情况
广西结核分枝杆菌对INH、RFP、EMB、SM、KM、OFX6种抗结核药物的总体耐药率为16.45%,单耐药率为7.88%,多耐药率为2.67%,MDR率为5.90%,XDR率为0.19%。获得性耐药率(32.98%)、获得性单耐药率(10.47%)、获得性多耐药率(4.19%)、获得性MDR率(18.32%)分别高于初始耐药率(11.31%)、初始单耐药率(7.08%)、初始多耐药率(2.20%)和初始MDR率(2.03%)(P=0.00,P=0.03,P=0.03,P=0.00)。结核分枝杆菌对6种抗结核药物的耐药率顺位由高到低依次为INH(11.55%)、RFP(7.88%)、 SM(7.26%)、EMB(4.35%)、OFX(2.67%)、KM(0.43%)。复治患者分离株对6种药物的耐药率均高于初治患者分离株(P=0.00)。初治、复治患者分离株均对INH的耐药率最高,分别为7.32%和25.13%。单一耐药的菌株中耐INH所占比例最高,为46.45%,其次是耐SM,为30.71%。共有10种不同形式的多耐药情况,INH+SM这种耐药形式在初治和复治患者中均占最大比例。INH耐药菌株中51%为MDR菌株,RFP耐药菌株中75%为MDR菌株,MDR在RFP耐药菌株所占比例高于在INH耐药菌株中所占比例。
OFX耐药与一线抗结核药物耐药及MDR有关。一线药物耐药菌株中OFX耐药率为13.62%,一线药物敏感菌株中OFX耐药率为0.59%,一线药物耐药菌株中OFX耐药率高于一线药物敏感菌株中OFX耐药率(P=0.00,OR=26.53,95%CI=12.15-57.93)。MDR菌株中OFX耐药率为30.53%,非MDR菌株中OFX耐药率为0.92%,MDR菌株中OFX耐药率高于非MDR菌株中OFX耐药率(P=0.00,OR=47.14,95%CI=23.79-93.41)。85.71%的卡那霉素耐药菌株分离自复治患者；7株卡那霉素耐药的菌株均同时合并对一线药物中的至少一种耐药。
耐药结核病在不同性别(X2=2.40,P=0.12)和年龄组(X2=5.74,P=0.13)患者中分布的差异无统计学意义。41-60岁年龄组MDR率高于≤20岁年龄组(X2=5.52,P=0.02)和>60岁年龄组(X2=5.25,P=0.02)。耐药率在西部、中部高于东部(X2=8.46,P=0.00；X2=4.29,P=0.04)；MDR率在南部和西部高于东部和中部(P<0.05)。
2.结核病耐药性影响因素分析：单因素Logistic回归分析显示,分析的因素与初治患者耐药的产生均未显示有统计学意义。性别、民族、居住地区、治疗次数、首次治疗持续时间、治疗中断次数、最近一次治疗过程中停药累计时间等7个因素与复治患者耐药性的产生有统计学关联(P<0.05)；年龄、民族、文化程度、家庭收入、居住地区、治疗次数、治疗中断次数、最近一次治疗过程中停药累计时间等8个因素与复治患者MDR的产生有统计学关联(P<0.05)。多因素非条件logistic回归分析显示：女性、多次治疗、多次治疗中断与复治患者耐药的产生有统计学关联(P<0.05),家庭经济收入低、多次治疗、多次治疗中断与复治患者MDR的产生有统计学关联(P<0.05)。
3.广西结核分枝杆菌基因型的分布：广西结核分枝杆菌基因多态性水平较高。对1310株菌株进行基因分型,共有964个基因型,其中779(59.47%)例患者的分离株为单一基因型,其他531(40.53%)例患者的菌株可归入185个基因型。北京基因型菌株746株(57.0%),非北京基因型564株(43.0%)。北京家族菌株中,古老型菌株313株(42.0%),现代型菌株433株(58.0%)。非北京家族菌株中,发现了原北京菌株及3个非北京型菌株亚群,分别占7.4%、45.6%、30.7%和16.3%。
4.广西结核分枝杆菌成簇特征及其影响因素：全敏感结核菌株成簇率高于耐药(24.40%vs.9.55%,P=0.000)和MDR菌株(24.40%vs.8.97%,P=0.004)。北京家族菌株成簇率高于非北京家族(40.88%vs.37.77%,P=0.032)。全敏感菌株的成簇比例高于耐药菌株和MDR菌株,北京家族分离株的成簇比例高于非北京家族分离株。年龄在40-60岁之间的患者成簇率低于年龄在20岁以下的患者(P=0.04)。
5.北京基因型与耐药的关系：北京基因型中链霉素(P=0.03)和乙胺丁醇(P=0.03)耐药率高于非北京基因型;总体耐药、MDR、耐异烟肼、耐利福平、耐卡那霉素及耐氧氟沙星在北京基因型和非北京基因型中的差异均未显示出有统计学意义。
6.RD207缺失基因检测法鉴定广西结核分枝杆菌北京基因型：本研究共对1611株结核分枝杆菌分离株进行RD207缺失基因检测,有866株为北京基因型,占53.76%;553株为非北京基因型,占34.32%；160株为北京基因型和非北京基因型的混合感染,占9.93%,32株无扩增条带,占1.99%。与RD105缺失基因检测法相比较,两种检测法对北京基因型的检测结果的差异没有统计学意义(P=0.23),对混合感染检出能力,RD207缺失基因检测法高于RD105缺失基因检测法(P=0.00,OR=12.58,95%CI=7.25-21.82)。
结论1.广西结核病耐药率较低,但MDR形势不容乐观。75%的利福平耐药菌株为MDR菌株,临床上利福平耐药的同时应警惕MDR的可能。链霉素耐药水平较低,链霉素在广西仍有很大的临床抗结核价值。氧氟沙星耐药率较低,但与一线抗结核药物的耐药及MDR有关,在临床治疗制定用药方案时需予以关注。耐药结核病的分布无性别年龄差异,耐药率中部和西部高于东部,耐多药率在41-60岁年龄组较高,西南部高于中东部。女性、多次治疗和多次中断治疗是耐药结核产生的危险因素,经济收入低、多次治疗和多次中断治疗是耐多药结核产生的危险因素,获得性耐药是广西耐药结核病产生的重要原因。
2.广西结核分枝杆菌基因多态性水平较高,北京基因型与非北京基因型所占比例相当。全敏感结核菌株成簇率和成簇比例均高于耐药和MDR菌株。北京家族菌株成簇率和成簇比例高于非北京家族菌株。年龄与成簇具有相关性。北京基因型与耐药、MDR无相关性。
3.初步认为广西结核分枝杆菌北京基因型的鉴定应联合应用RD105缺失基因检测法及RD207缺失基因检测法,该结论仍需进一步研究验证。
Objectives To understand the epidemic characteristics, spectrum and related factors of drug-resistant TB in guangxi; To know genotype and its distribution of MTB, to discuss the characteristics of MTB'clusters'and its related factors, the relation between Beijing strain and drug-resistant. To provide the reference for TB control and lay the foundation for further molecular biology research.
Methods A population-based molecular epidemiological studies of tuberculosis was carried out by a method of combination of field epidemiology and the modern molecular biology technology. Sample size was calculated according to the cross-sectional survey statistical requirements, sputum smear-positive TB patients in30counties were selected by random cluster sampling method. Basic information and related epidemiological data of patients was collected from questionnaire and medical records. First-line and second-line anti-tb drugs sensitivity test was performed. The VNTR genotyping technology was used to identify the genotype of mycobacterium tuberculosis. RD105deletion test and RD207deletion test were used to identify the "Beijing family " strains of MTB in order to determine the distribution of "Beijing family" strains and finding the best way to identify "Beijing family " strains of MTB in Guangxi province. Quality control throughout the whole research process. Data were double entered into Epidate3.1and analyaed using SPSS19.0.
Results1. Drug-resistant tuberculosis epidemic in guangxi:The overall rate of resistance to anti-tb drugs(including INH,RFP,EMB,SM,KM,OFX)was16.45%, the single-resistance rate was7.88%, the poly-resistance rate was2.67%, MDR rate was5.90%, XDR rate was0.19%. The overall rate (32.98%), single-resistance rate (10.47%), poly-resistance rate (4.19%)、MDR rate (18.32%) were higher in re-treated patients than those in initial patients (11.31%,7.08%,2.20%,2.03%)(P=0.00, P=0.00, P=0.03, P=0.00). The sequence of resistance rate of6anti-tuberculosis drugs was in turn to INH (11.55%), RFP (7.88%), SM (7.26%), EMB (4.35%), OFX (2.67%)and KM (0.43%). The resistance rates of6anti-tuberculosis drugs in re-treated patients were higher than in initial patient, respectively(P=0.00). The INH resistant rate was the highest both in re-treat patients and initial patient,it was7.32%and25.13%, respectively. The single-resistant rate to INH (46.45%) took the highest proportion among all the drugs, followed by resistance to SM(30.71%). There were10kinds of different forms of poly-resistance, the form'INH+SM' accounted for the largest proportion in both initial and re-treated patients.51%of the INH resistance strains were MDR strains,when75%of the RFP resistance strains were MDR strains, the MDR proportion in RFP strains was higher than in INH strains.
The OFX resistant rate was related to first-line anti-tb drug resistance and MDR. The OFX resistant rate in first-line drug resistant strains was13.62%, which was higher than in first-line drugs sensitive strains (P=0.00, OR=0.00,95%CI=12.15-57.93). The OFX resistant rate in MDR strains was30.53%, which was higher than in nor MDR strains (P=0.00, OR=47.14,95%CI=23.79-93.41).85.71%of the KM resistant strains was isolated from re-treated patients,7KM resistant strains were resistance to at least one first-line drug at the same time.
The distribution of Drug-resistant TB showed no statistical significance difference in different gender (X2=2.40, P=0.12) and age groups (X2=5.74, P=5.74). MDR rate in41-60years group was higher than in≤20years groups (X2=5.52, P=0.02) and>60years groups (X2=5.25, P=5.25). The Drug-resistant rate was higher in the west area and middle aera than in the east area.(X2=8.46, P=0.00; X2=4.29, P=0.04); MDR rate was higher in south and west aeras than in middle and east aeras (P＜0.05).
2. Factors related to drug resistance:female, treatment times and treatment interruption times were related to the drug resistance of the re-treated patients (P＜0.05), family economic income, treatment times and treatment interruption times were associated with re-treated patients with MDR (P＜0.05), according to multi-factor unconditioned logistic regression analysis.
3. Distribution of mycobacterium tuberculosis genotype in guangxi: guangxi had a high level of MTB gene polymorphism.There was a total of964genotypes, of which779(59.47%) were single genotypes, other531(40.53%) were classified as185genotypes. Of1310MTB strains,746(57.0%)were Beijing strains,564(43.0%) were nor-Beijing strains. Of all Beijing strains,313(42.0%) were old type strains,433(58.0%) were modern strains. The original Beijing strains and3subgroup were found in the nor-Beijing strains,accounted for7.4%,45.6%,30.7%and7.4%respectively.
4. Clusters characteristics and its related factors of MTB:The clusters rate of drug-sensitive strains was higher than drug-resistance strains (24.40%vs.9.55%, P=0.000) and MDR strains (24.40%vs.8.97%, P=0.004).The clusters rate of Beijing strain was higher than nor-Beijing strains (40.88%vs.37.77%, P=0.032). The clusters ratio of drug-ensitive strains was higher than that of drug-resistant strains and MDR strains, the clusters ratio of Beijing strain was higher than that of nor-Beijing family strains. Patients aged between40and60had a greater probability to be clusters vs.aged less than20(P=0.04).
5. Relationship between Beijing genotype and drug resistance:Beijing strains did not show statistical significance relation with drug-resistant.
6. RD207deletion test for Beijing strains identifying in Guangxi:A total of1611MTB strains was included in RD207deletion test for Beijing strains identified,of which866(53.76%) were Beijing strains,553(34.32%) were nor-Beijing strains,160(9.93%) were mixed infection with Beijing strains and nor-Beijing strains.(160/1611),32(1.99%) could not amplify target fragment. For the detection power on mixed infection, RD207deletion test was better than RD105deletion test.
Conclusions1. The overall drug-resistance rate in guangxi was low,but MDR situation was serious.75%RFP resistant strains were MDR, so RFP resistance should be wary of MDR in clinical. SM has a great value on anti-tuberculosis. OFX resistance was linked to the first line anti-tuberculosis drug resistance and MDR,it shoud be paid more attention on clinical treatment regimen. The distribution of Drug-resistant TB showed no statistical significance difference in different gender and age groups,but he Drug-resistant rate was higher in the west area and middle aera than in the east area. MDR rate was higher in41-60years group than in age groups,and was higher in south and west aeras than in middle and east aeras. Women, treated many times and treatment interrupted many times were the risk factors of drug-resistant;low income, treated many times and treatment interrupted many times were the risk factors of MDR. Acquired drug resistance was one of the most important reasons for drug-resistant TB.
2. MTB gene polymorphism showed a high level in guangxi. Beijing genotype and nor-Beijing genotype took a same proportion. The clusters rate and ratio of drug-sensitive strains were higher than that of drug-resistant and MDR strains. The clusters rate and ratio of Beijing strains were higher than that of nor-Beijing strain. Clusters were associated with age. Beijing genotype had no link to drug-resistanceand and MDR.
3. Combination of RD105and RD207deletion test should be used for Beijing strain identifying in Guangxi.
方法采用现场流行病学与现代分子生物学技术相结合的方法,开展以人群为基础的结核病分子流行病学研究。采用整群随机抽样方法在全区抽取30个县(区)作为项目点,于2010年7月-2011年6月连续不间断纳入符合条件的涂阳肺结核患者作为研究对象,采用统一设计的调查表和查阅病史记录的方式获取患者基本信息和相关流行病学资料；对研究对象的痰标本进行一线和二线抗结核药物敏感性试验,获取耐药性资料。同时,运用VNTR基因分型技术对收集的结核分枝杆菌菌株进行基因分型,应用RD105和RD207缺失基因检测法鉴定广西结核分枝杆菌北京基因型,探索适合广西结核分枝杆菌北京基因型的鉴定方法。研究全程进行严格质量控制。数据资料采用Epidata3.1软件建立数据库进行双录入及核对,应用SPSS19.0统计分析软件进行数据统计分析。
结果1.广西耐药结核病流行情况
广西结核分枝杆菌对INH、RFP、EMB、SM、KM、OFX6种抗结核药物的总体耐药率为16.45%,单耐药率为7.88%,多耐药率为2.67%,MDR率为5.90%,XDR率为0.19%。获得性耐药率(32.98%)、获得性单耐药率(10.47%)、获得性多耐药率(4.19%)、获得性MDR率(18.32%)分别高于初始耐药率(11.31%)、初始单耐药率(7.08%)、初始多耐药率(2.20%)和初始MDR率(2.03%)(P=0.00,P=0.03,P=0.03,P=0.00)。结核分枝杆菌对6种抗结核药物的耐药率顺位由高到低依次为INH(11.55%)、RFP(7.88%)、 SM(7.26%)、EMB(4.35%)、OFX(2.67%)、KM(0.43%)。复治患者分离株对6种药物的耐药率均高于初治患者分离株(P=0.00)。初治、复治患者分离株均对INH的耐药率最高,分别为7.32%和25.13%。单一耐药的菌株中耐INH所占比例最高,为46.45%,其次是耐SM,为30.71%。共有10种不同形式的多耐药情况,INH+SM这种耐药形式在初治和复治患者中均占最大比例。INH耐药菌株中51%为MDR菌株,RFP耐药菌株中75%为MDR菌株,MDR在RFP耐药菌株所占比例高于在INH耐药菌株中所占比例。
OFX耐药与一线抗结核药物耐药及MDR有关。一线药物耐药菌株中OFX耐药率为13.62%,一线药物敏感菌株中OFX耐药率为0.59%,一线药物耐药菌株中OFX耐药率高于一线药物敏感菌株中OFX耐药率(P=0.00,OR=26.53,95%CI=12.15-57.93)。MDR菌株中OFX耐药率为30.53%,非MDR菌株中OFX耐药率为0.92%,MDR菌株中OFX耐药率高于非MDR菌株中OFX耐药率(P=0.00,OR=47.14,95%CI=23.79-93.41)。85.71%的卡那霉素耐药菌株分离自复治患者；7株卡那霉素耐药的菌株均同时合并对一线药物中的至少一种耐药。
耐药结核病在不同性别(X2=2.40,P=0.12)和年龄组(X2=5.74,P=0.13)患者中分布的差异无统计学意义。41-60岁年龄组MDR率高于≤20岁年龄组(X2=5.52,P=0.02)和>60岁年龄组(X2=5.25,P=0.02)。耐药率在西部、中部高于东部(X2=8.46,P=0.00；X2=4.29,P=0.04)；MDR率在南部和西部高于东部和中部(P<0.05)。
2.结核病耐药性影响因素分析：单因素Logistic回归分析显示,分析的因素与初治患者耐药的产生均未显示有统计学意义。性别、民族、居住地区、治疗次数、首次治疗持续时间、治疗中断次数、最近一次治疗过程中停药累计时间等7个因素与复治患者耐药性的产生有统计学关联(P<0.05)；年龄、民族、文化程度、家庭收入、居住地区、治疗次数、治疗中断次数、最近一次治疗过程中停药累计时间等8个因素与复治患者MDR的产生有统计学关联(P<0.05)。多因素非条件logistic回归分析显示：女性、多次治疗、多次治疗中断与复治患者耐药的产生有统计学关联(P<0.05),家庭经济收入低、多次治疗、多次治疗中断与复治患者MDR的产生有统计学关联(P<0.05)。
3.广西结核分枝杆菌基因型的分布：广西结核分枝杆菌基因多态性水平较高。对1310株菌株进行基因分型,共有964个基因型,其中779(59.47%)例患者的分离株为单一基因型,其他531(40.53%)例患者的菌株可归入185个基因型。北京基因型菌株746株(57.0%),非北京基因型564株(43.0%)。北京家族菌株中,古老型菌株313株(42.0%),现代型菌株433株(58.0%)。非北京家族菌株中,发现了原北京菌株及3个非北京型菌株亚群,分别占7.4%、45.6%、30.7%和16.3%。
4.广西结核分枝杆菌成簇特征及其影响因素：全敏感结核菌株成簇率高于耐药(24.40%vs.9.55%,P=0.000)和MDR菌株(24.40%vs.8.97%,P=0.004)。北京家族菌株成簇率高于非北京家族(40.88%vs.37.77%,P=0.032)。全敏感菌株的成簇比例高于耐药菌株和MDR菌株,北京家族分离株的成簇比例高于非北京家族分离株。年龄在40-60岁之间的患者成簇率低于年龄在20岁以下的患者(P=0.04)。
5.北京基因型与耐药的关系：北京基因型中链霉素(P=0.03)和乙胺丁醇(P=0.03)耐药率高于非北京基因型;总体耐药、MDR、耐异烟肼、耐利福平、耐卡那霉素及耐氧氟沙星在北京基因型和非北京基因型中的差异均未显示出有统计学意义。
6.RD207缺失基因检测法鉴定广西结核分枝杆菌北京基因型：本研究共对1611株结核分枝杆菌分离株进行RD207缺失基因检测,有866株为北京基因型,占53.76%;553株为非北京基因型,占34.32%；160株为北京基因型和非北京基因型的混合感染,占9.93%,32株无扩增条带,占1.99%。与RD105缺失基因检测法相比较,两种检测法对北京基因型的检测结果的差异没有统计学意义(P=0.23),对混合感染检出能力,RD207缺失基因检测法高于RD105缺失基因检测法(P=0.00,OR=12.58,95%CI=7.25-21.82)。
结论1.广西结核病耐药率较低,但MDR形势不容乐观。75%的利福平耐药菌株为MDR菌株,临床上利福平耐药的同时应警惕MDR的可能。链霉素耐药水平较低,链霉素在广西仍有很大的临床抗结核价值。氧氟沙星耐药率较低,但与一线抗结核药物的耐药及MDR有关,在临床治疗制定用药方案时需予以关注。耐药结核病的分布无性别年龄差异,耐药率中部和西部高于东部,耐多药率在41-60岁年龄组较高,西南部高于中东部。女性、多次治疗和多次中断治疗是耐药结核产生的危险因素,经济收入低、多次治疗和多次中断治疗是耐多药结核产生的危险因素,获得性耐药是广西耐药结核病产生的重要原因。
2.广西结核分枝杆菌基因多态性水平较高,北京基因型与非北京基因型所占比例相当。全敏感结核菌株成簇率和成簇比例均高于耐药和MDR菌株。北京家族菌株成簇率和成簇比例高于非北京家族菌株。年龄与成簇具有相关性。北京基因型与耐药、MDR无相关性。
3.初步认为广西结核分枝杆菌北京基因型的鉴定应联合应用RD105缺失基因检测法及RD207缺失基因检测法,该结论仍需进一步研究验证。
Objectives To understand the epidemic characteristics, spectrum and related factors of drug-resistant TB in guangxi; To know genotype and its distribution of MTB, to discuss the characteristics of MTB'clusters'and its related factors, the relation between Beijing strain and drug-resistant. To provide the reference for TB control and lay the foundation for further molecular biology research.
Methods A population-based molecular epidemiological studies of tuberculosis was carried out by a method of combination of field epidemiology and the modern molecular biology technology. Sample size was calculated according to the cross-sectional survey statistical requirements, sputum smear-positive TB patients in30counties were selected by random cluster sampling method. Basic information and related epidemiological data of patients was collected from questionnaire and medical records. First-line and second-line anti-tb drugs sensitivity test was performed. The VNTR genotyping technology was used to identify the genotype of mycobacterium tuberculosis. RD105deletion test and RD207deletion test were used to identify the "Beijing family " strains of MTB in order to determine the distribution of "Beijing family" strains and finding the best way to identify "Beijing family " strains of MTB in Guangxi province. Quality control throughout the whole research process. Data were double entered into Epidate3.1and analyaed using SPSS19.0.
Results1. Drug-resistant tuberculosis epidemic in guangxi:The overall rate of resistance to anti-tb drugs(including INH,RFP,EMB,SM,KM,OFX)was16.45%, the single-resistance rate was7.88%, the poly-resistance rate was2.67%, MDR rate was5.90%, XDR rate was0.19%. The overall rate (32.98%), single-resistance rate (10.47%), poly-resistance rate (4.19%)、MDR rate (18.32%) were higher in re-treated patients than those in initial patients (11.31%,7.08%,2.20%,2.03%)(P=0.00, P=0.00, P=0.03, P=0.00). The sequence of resistance rate of6anti-tuberculosis drugs was in turn to INH (11.55%), RFP (7.88%), SM (7.26%), EMB (4.35%), OFX (2.67%)and KM (0.43%). The resistance rates of6anti-tuberculosis drugs in re-treated patients were higher than in initial patient, respectively(P=0.00). The INH resistant rate was the highest both in re-treat patients and initial patient,it was7.32%and25.13%, respectively. The single-resistant rate to INH (46.45%) took the highest proportion among all the drugs, followed by resistance to SM(30.71%). There were10kinds of different forms of poly-resistance, the form'INH+SM' accounted for the largest proportion in both initial and re-treated patients.51%of the INH resistance strains were MDR strains,when75%of the RFP resistance strains were MDR strains, the MDR proportion in RFP strains was higher than in INH strains.
The OFX resistant rate was related to first-line anti-tb drug resistance and MDR. The OFX resistant rate in first-line drug resistant strains was13.62%, which was higher than in first-line drugs sensitive strains (P=0.00, OR=0.00,95%CI=12.15-57.93). The OFX resistant rate in MDR strains was30.53%, which was higher than in nor MDR strains (P=0.00, OR=47.14,95%CI=23.79-93.41).85.71%of the KM resistant strains was isolated from re-treated patients,7KM resistant strains were resistance to at least one first-line drug at the same time.
The distribution of Drug-resistant TB showed no statistical significance difference in different gender (X2=2.40, P=0.12) and age groups (X2=5.74, P=5.74). MDR rate in41-60years group was higher than in≤20years groups (X2=5.52, P=0.02) and>60years groups (X2=5.25, P=5.25). The Drug-resistant rate was higher in the west area and middle aera than in the east area.(X2=8.46, P=0.00; X2=4.29, P=0.04); MDR rate was higher in south and west aeras than in middle and east aeras (P＜0.05).
2. Factors related to drug resistance:female, treatment times and treatment interruption times were related to the drug resistance of the re-treated patients (P＜0.05), family economic income, treatment times and treatment interruption times were associated with re-treated patients with MDR (P＜0.05), according to multi-factor unconditioned logistic regression analysis.
3. Distribution of mycobacterium tuberculosis genotype in guangxi: guangxi had a high level of MTB gene polymorphism.There was a total of964genotypes, of which779(59.47%) were single genotypes, other531(40.53%) were classified as185genotypes. Of1310MTB strains,746(57.0%)were Beijing strains,564(43.0%) were nor-Beijing strains. Of all Beijing strains,313(42.0%) were old type strains,433(58.0%) were modern strains. The original Beijing strains and3subgroup were found in the nor-Beijing strains,accounted for7.4%,45.6%,30.7%and7.4%respectively.
4. Clusters characteristics and its related factors of MTB:The clusters rate of drug-sensitive strains was higher than drug-resistance strains (24.40%vs.9.55%, P=0.000) and MDR strains (24.40%vs.8.97%, P=0.004).The clusters rate of Beijing strain was higher than nor-Beijing strains (40.88%vs.37.77%, P=0.032). The clusters ratio of drug-ensitive strains was higher than that of drug-resistant strains and MDR strains, the clusters ratio of Beijing strain was higher than that of nor-Beijing family strains. Patients aged between40and60had a greater probability to be clusters vs.aged less than20(P=0.04).
5. Relationship between Beijing genotype and drug resistance:Beijing strains did not show statistical significance relation with drug-resistant.
6. RD207deletion test for Beijing strains identifying in Guangxi:A total of1611MTB strains was included in RD207deletion test for Beijing strains identified,of which866(53.76%) were Beijing strains,553(34.32%) were nor-Beijing strains,160(9.93%) were mixed infection with Beijing strains and nor-Beijing strains.(160/1611),32(1.99%) could not amplify target fragment. For the detection power on mixed infection, RD207deletion test was better than RD105deletion test.
Conclusions1. The overall drug-resistance rate in guangxi was low,but MDR situation was serious.75%RFP resistant strains were MDR, so RFP resistance should be wary of MDR in clinical. SM has a great value on anti-tuberculosis. OFX resistance was linked to the first line anti-tuberculosis drug resistance and MDR,it shoud be paid more attention on clinical treatment regimen. The distribution of Drug-resistant TB showed no statistical significance difference in different gender and age groups,but he Drug-resistant rate was higher in the west area and middle aera than in the east area. MDR rate was higher in41-60years group than in age groups,and was higher in south and west aeras than in middle and east aeras. Women, treated many times and treatment interrupted many times were the risk factors of drug-resistant;low income, treated many times and treatment interrupted many times were the risk factors of MDR. Acquired drug resistance was one of the most important reasons for drug-resistant TB.
2. MTB gene polymorphism showed a high level in guangxi. Beijing genotype and nor-Beijing genotype took a same proportion. The clusters rate and ratio of drug-sensitive strains were higher than that of drug-resistant and MDR strains. The clusters rate and ratio of Beijing strains were higher than that of nor-Beijing strain. Clusters were associated with age. Beijing genotype had no link to drug-resistanceand and MDR.
3. Combination of RD105and RD207deletion test should be used for Beijing strain identifying in Guangxi.
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