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09 / 01

2021

阴道毛滴虫病诊治指南(2021修订版)

本指南为提高临床医师对阴道毛滴虫病的认识,规范道毛滴虫病的相关诊治工作。

【摘要】阴道毛滴虫病系由阴道毛滴虫所致的性传播感染,可同时累及生殖道及泌尿道,引起阴道炎、尿道炎、膀胱炎或无症状,常与细菌性阴道病、沙眼衣原体感染和淋病并存。阴道毛滴虫病可导致不良生殖健康结局。持续性阴道毛滴虫病已经在我国出现,并成为临床治疗的难点。根据临床表现和实验室检查如阴道分泌物悬液显微镜检查或核酸扩增等诊断。治疗方案包括甲硝唑2g顿服或替硝唑2g顿服,需要对患者的性伴同时治疗,对持续性阴道毛滴虫病需要应用高剂量或超高剂量替硝唑治疗。


阴道毛滴虫病(trichomoniasis)系由阴道毛滴虫(trichomonas vaginalis)感染所致。传统上阴道毛滴虫病被诊断为“滴虫阴道炎”。由于阴道毛滴虫可同时感染生殖道及泌尿道,可引起尿道炎或膀胱炎[1],而大部分患者无症状,本病现在更多被称为“阴道毛滴虫病”。阴道毛滴虫病属于性传播感染(sexually transmitted infection,STI),常与细菌性阴道病、沙眼衣原体感染和淋病并存[1‑3]

阴道毛滴虫病可导致不良生殖健康结局,包括子宫颈病变、子宫切除术后残端蜂窝织炎或脓肿、盆腔炎症性疾病、不孕症、增加HIV感染易感性[1,4‑6]、增加子宫颈癌风险,尤其是阴道毛滴虫与HPV共同感染时增加子宫颈癌风险更明显[7]。阴道毛滴虫病还可能增加精神疾病风险,特别是治疗困难的阴道毛滴虫病患者精神疾病风险更高[8]。妊娠合并阴道毛滴虫病患者早产、胎膜早破、低出生体重儿、新生儿滴虫感染和新生儿死亡发生率增高[1,9‑11]

阴道毛滴虫病对人体危害较大,持续性阴道毛滴虫病(persistent trichomoniasis)是临床治疗的难点[12‑14]。中华医学会妇产科学分会感染性疾病协作组结合近年来阴道毛滴虫病的诊治进展,对2011年《滴虫阴道炎诊治指南(草案)》[2]进行修订,以期提高临床医师对阴道毛滴虫病的认识,规范道毛滴虫病的相关诊治工作。本指南适用于女性阴道毛滴虫病的诊断和治疗。

一、流行病学

阴道毛滴虫病是最常见的STI,在不同国家和地区阴道毛滴虫病的发病率存在较大差异,范围为0.3%~20%[15]。非妊娠期妇科门诊患者阴道毛滴虫病的发病率为1.7%~4.5%,孕妇的阴道毛滴虫病发病率为1.7%~3.2%[16‑17]。高危性行为、HIV感染、性伴数增加、低社会经济地位及阴道灌洗是阴道毛滴虫病的高发因素[1],我国阴道毛滴虫病的发病率较低。

二、临床特点

1.感染途径:阴道毛滴虫病的感染途径主要为性接触(异性或同性间)或垂直传播(阴道分娩)[1]。潜伏期为4~28d[18]。目前已从阴道、子宫颈、尿道、尿道旁腺、巴氏腺、膀胱和输卵管分离到阴道毛滴虫。

2.临床表现:阴道毛滴虫病有症状者,可表现为阴道分泌物增多伴异味,分泌物黄绿色,伴有外阴瘙痒、灼热感等刺激症状,并可出现性交困难、排尿困难、尿频、下腹痛等;查体可见外阴阴道红斑、水肿、有泡沫的黄灰或绿色的阴道分泌物、pH值增高(pH>6),约2%的患者出现草莓样子宫颈[19]。阴道毛滴虫病患者也可无明显症状,在经培养证实的阴道毛滴虫病妇女中,只有11%~17%出现分泌物异常、瘙痒、排尿困难或阴道灼烧等[19]。85%的感染者无症状,1/3的感染者在感染6个月内出现症状[18],90%的患者存在泌尿道感染[20]

三、诊断方法

阴道毛滴虫病根据临床特征和实验室检查诊断。常用的实验室检查方法包括:

(1)显微镜检查阴道分泌物悬液:可见活动的阴道毛滴虫,特异性高,但敏感性仅有50%~60%[4]。采集阴道分泌物立即进行显微镜检查可获得最佳效果;寒冷环境需要保温,否则不活动的阴道毛滴虫与白细胞很难区分。

(2)核酸扩增试验(nucleic acid amplification test,NAAT):诊断敏感性和特异性均超过95%[4,21‑23]

(3)阴道毛滴虫培养:诊断敏感性为75%~96%,特异性高达100%,但临床应用较少[1,24]

(4)其他诊断方法:还包括阴道毛滴虫抗原检测[4],其敏感性为82%~95%,特异性为97%~100%[25‑26]

阴道毛滴虫病属STI,强调实验室检查在诊断中的作用。推荐对阴道毛滴虫病患者及其性伴同时检查其他STI[1,27]

四、治疗

1.治疗方案:治疗阴道毛滴虫病主要选用口服硝基咪唑类药物,包括甲硝唑和替硝唑[1,19,28]

(1)推荐方案:甲硝唑,2g,单次顿服;或替硝唑,2g,单次顿服。

(2)替代方案:甲硝唑,400mg,口服,2次/d,共7d。

硝基咪唑类药物的主要不良反应包括:恶心、头痛、头晕、皮肤瘙痒、不适、疲乏感、口渴、尿频、水样阴道分泌物、阴道流血及阴道瘙痒[1]。患者服用甲硝唑48h内或服用替硝唑72h内应禁酒。

由于阴道毛滴虫对甲硝唑的耐药率为4.3%~13.3%,且耐药率在不断上升,替硝唑在临床的使用越来越广泛。与甲硝唑比较,替硝唑有以下优势:

(1)替硝唑有较强的抗滴虫效力,甲硝唑的24h最小致死浓度(minimal lethal concentrations,MLC)为1.6~3.2mg/L,72h MLC为1.60~3.83mg/L[29‑30],体外实验数据表明,60%的阴道毛滴虫分离株对替硝唑的MLC较甲硝唑低[31

(2)替硝唑有更长的有效作用时间,替硝唑的血浆消除半衰期为12~14h[12‑13]

(3)患者的耐受性更好。甲硝唑方案对阴道毛滴虫病的治愈率为84%~98%,替硝唑方案的治愈率为92%~100%[1]

2.性伴的治疗:对阴道毛滴虫病患者的性伴应常规进行治疗,并告知患者及其性伴治愈前避免无保护性性接触。性伴的治疗选择替硝唑或甲硝唑单剂量2g顿服[1,32]

3.对硝基咪唑类药物过敏或不耐受者:可以选择硝基咪唑类以外的药物治疗,但疗效较差,基层医院建议转给有经验的专家处理[1]

4.随访和疗效评价:根据随访时阴道毛滴虫阳性或阴性,评价为治愈或失败。需要在治疗后2~4周重复检测评价疗效[1,33‑34]。需要注意区别阴道毛滴虫再次感染和治疗失败。使用NAAT检测治疗后阴道毛滴虫的DNA,阴道毛滴虫首次转阴的中位时间为7d(0~84d),至完成治疗后21d有85%的病例转阴[34]。尚无证据支持需要对患者的性伴重复检查[1]

五、持续性阴道毛滴虫病

持续性阴道毛滴虫病是指由于硝基咪唑类药物耐药、药物吸收不足或药物运输不充分而导致的治疗失败[13‑14]。持续性阴道毛滴虫病在国内已有报道[12]。阴道毛滴虫对替硝唑的耐药率低于甲硝唑,为1%[1,31,35]。

诊断持续性阴道毛滴虫病时需要排除再次感染,评估患者的性生活情况和治疗依从性,排除患者是否有其他合并症[1,19,28]。

如果考虑再次感染,予再次单剂量甲硝唑2g或替硝唑2g顿服治疗[1]

如果推荐方案治疗失败,除外再次感染后,可选择替硝唑2g口服,1次/d,共7d[1,19,28]。如果上述治疗失败,除外再次感染或治疗依从性差者,有条件者进行甲硝唑和替硝唑药敏试验,考虑应用高剂量或超高剂量替硝唑方案[1,19,28]

(1)高剂量替硝唑方案:替硝唑1g,口服,每8小时1次,共14d,替硝唑总剂量42g。

(2)超高剂量替硝唑方案:替硝唑2g,口服,每12小时1次,共14d,替硝唑总剂量56g。

(3)应用高剂量或超高剂量替硝唑方案时均同时配合阴道应用甲硝唑等辅助药物。

(4)高剂量或超高剂量替硝唑方案应请相关专家处理,由于药物剂量超越说明书规定范围,需要签署知情同意书,有条件者进行超说明书用药备案。

(5)需要对患者的性伴常规治疗和检查治疗效果。

(6)绝大多数患者对大剂量替硝唑治疗耐受良好,治疗成功率高。

六、妊娠期和哺乳期阴道毛滴虫病

1.妊娠期阴道毛滴虫病的筛查:并无证据证明对孕妇常规筛查阴道毛滴虫病有益处,对孕妇筛查阴道毛滴虫病并不能降低早产发生率[1]

2.妊娠期阴道毛滴虫病的治疗:对妊娠合并阴道毛滴虫病进行治疗可缓解患者症状,避免新生儿阴道毛滴虫病,避免阴道毛滴虫传播。为降低新生儿感染的风险,妊娠期应对阴道毛滴虫病患者积极治疗。

妊娠期用药应遵循药物说明书[36]。妊娠期应用硝基咪唑类药物需权衡利弊,知情选择,尽量避免在妊娠早期应用硝基咪唑类药物,在妊娠中晚期应用甲硝唑通常是安全的[1,19,28,37]。口服甲硝唑2g单剂量和口服甲硝唑7d方案均可在妊娠期应用[1]

妊娠期推荐方案:甲硝唑,400mg,口服,2次/d,共7d;或甲硝唑,2g,单次口服。

3.哺乳期阴道毛滴虫病的治疗:治疗方案同妊娠期。由于哺乳期应用甲硝唑治疗时,在乳汁中可检出少量甲硝唑,故选择甲硝唑2g单次口服者,服药后12~24h内避免哺乳,以减少甲硝唑对婴儿的影响[19,28,38];口服替硝唑2g单剂量者,服药后3d内避免哺乳[1,19,28,38]


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