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科學(xué)簡(jiǎn)報(bào):2022年Clade IIb爆發(fā)期間Mpox(前猴痘)病毒的檢測(cè)和傳播

2023-07-18 01:05 作者:絕對(duì)不要點(diǎn)開我的空間  | 我要投稿

原文來(lái)自:https://www.cdc.gov/poxvirus/mpox/about/science-behind-transmission.html

變更摘要

*截至2023年2月2日的更新

??? ? 越來(lái)越多的科學(xué)證據(jù)表明,一些人可以在多囊卵巢綜合征癥狀出現(xiàn)前一到四天將多囊卵巢病毒傳播給其他人。目前沒(méi)有證據(jù)表明從未出現(xiàn)過(guò)癥狀的人會(huì)將mpox病毒傳播給其他人。

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關(guān)于mpox病毒如何傳播的知識(shí)在不斷發(fā)展。在當(dāng)前疫情期間,人們主要是在性活動(dòng)期間因接觸mpox患者的皮膚或粘膜表面(如喉嚨、肛門或直腸)上的mpox損傷而感染的。一些感染是由于在臨床情況下使用鋒利的儀器對(duì)皮膚損傷進(jìn)行采樣而造成的,CDC建議反對(duì)的做法.猴痘還通過(guò)皮膚穿孔和紋身傳播,以及在沒(méi)有尖銳物接觸的情況下通過(guò)職業(yè)傳播給醫(yī)療工作者;這些病例的確切傳播途徑尚不清楚。通過(guò)接觸受污染的表面或物體(即螨蟲或被動(dòng)媒介)而感染的風(fēng)險(xiǎn)被認(rèn)為較低。一些病例報(bào)告稱,在受感染伴侶出現(xiàn)皮疹、皮損或其他疾病跡象或癥狀(即與癥狀前感染的伴侶接觸)之前,曾與該伴侶發(fā)生過(guò)性接觸。沒(méi)有明確的傳播病例與接觸從未出現(xiàn)疾病癥狀或體征(即無(wú)癥狀感染)的感染者有關(guān)。隨著有關(guān)mpox病毒感染的新科學(xué)證據(jù)和其他信息可用,本簡(jiǎn)介將更新。

本文目錄

一、受影響人群和臨床表現(xiàn) ?1

二、皮膚皮疹以外的人體樣本中的猴痘病毒及其傳播意義 ?2

三、檢測(cè)表面、材料和物體上的猴痘病毒 ?4

四、在沒(méi)有疾病癥狀或體征的情況下檢測(cè)和傳播猴痘 ?4

另、參考文獻(xiàn) 6

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一、受影響人群和臨床表現(xiàn)

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在本次疫情期間,大多數(shù)mpox病毒感染是通過(guò)與有癥狀的人密切接觸傳播的,主要是在性接觸期間。大多數(shù)感染是在男性與男性的性接觸期間傳播的[1-7]; 然而,異性性傳播[8-14]通過(guò)與照料者的非性皮膚接觸傳播給兒童[15-17]通過(guò)帶有皮膚損傷的尖銳刺繡進(jìn)行傳播[18-21]通過(guò)身體穿孔和紋身[22-24]此外,還報(bào)告了在缺乏全面或足夠有效的個(gè)人防護(hù)裝備(PPE)的情況下的職業(yè)接觸[25, 26].

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皮疹通常伴有肛門生殖器或口咽/口周粘膜損傷,是診斷時(shí)mpox病毒感染的主要癥狀[1, 4-6, 13, 27-37]患者也經(jīng)常報(bào)告發(fā)燒、寒戰(zhàn)、頭痛和淋巴結(jié)??;然而,與以往的疫情相比,這些癥狀通常先于皮疹發(fā)作(即前驅(qū)癥狀),在目前的疫情中,多達(dá)一半的患者報(bào)告皮疹為他們的第一癥狀[1, 4, 5, 27, 38].從感染到發(fā)病的估計(jì)潛伏期平均為7天,上限約為3周[1, 5, 13, 39-43]目前,證據(jù)表明所有人都會(huì)感染疾?。雌ふ罨蚱渌嚓P(guān)癥狀),但有些人在出現(xiàn)癥狀或體征(即癥狀前)之前的四天內(nèi)也會(huì)將病毒傳播給其他人[41, 42, 44, 45]目前沒(méi)有證據(jù)表明,感染但最終清除了感染而沒(méi)有發(fā)展成疾?。礋o(wú)癥狀感染)的人傳播了mpox病毒。


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二、皮膚皮疹以外的人體樣本中的痘病毒及其傳播意義

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建議使用皮膚損傷(如水皰、潰瘍)的拭子(而非尖銳物)通過(guò)聚合酶鏈反應(yīng)(PCR)檢測(cè)mpox病毒,以確認(rèn)有癥狀的人是否感染,因?yàn)槠つw損傷含有最高濃度的病毒(圖)最有可能產(chǎn)生積極的結(jié)果[31, 34, 46-52]臨床拭子樣本中病毒DNA的濃度與存在的具有復(fù)制能力的病毒數(shù)量相關(guān),表明PCR評(píng)估的病毒負(fù)荷越大,感染的可能性越大[53].PCR已在多種樣本中檢測(cè)到病毒DNA(表); 然而,僅從皮膚病變拭子、口咽拭子,肛門直腸拭子以及尿道拭子和結(jié)膜拭子及精液中分離出具有復(fù)制能力(即潛在傳染性)的病毒(表). 病毒DNA通常在發(fā)病后3周內(nèi)仍能檢測(cè)到[47, 54-60]盡管上呼吸道拭子中周期閾值(Ct)值>35(即低病毒載量)的標(biāo)本在此時(shí)間之后被報(bào)告(長(zhǎng)達(dá)41天,可能73天)[54],唾液(最多76天)[58]和精液(最多54天)[58]在一項(xiàng)單一研究中,僅在發(fā)病后的前3周內(nèi),在皮膚病變拭子、肛門直腸拭子,口咽拭子或精液中檢測(cè)到具有復(fù)制能力的病毒[34]。接觸皮膚和粘膜損傷完全愈合的多功能性腸病患者未報(bào)告感染。

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口咽和唾液:

當(dāng)前疫情中多發(fā)性肺炎的臨床表現(xiàn)值得注意的是,在診斷時(shí)口咽和口周病變的發(fā)病率很高[1, 4-6, 27].口咽粘膜可出現(xiàn)典型的mpox病毒感染病變[1]多項(xiàng)研究通過(guò)PCR在鼻咽和口咽拭子中檢測(cè)到mpox病毒DNA[9, 29, 34, 38, 51, 55, 61-67]口咽拭子可以包括來(lái)自拭子粘膜病變和唾液的病毒。至少有兩份報(bào)告描述了從這些標(biāo)本中回收具有復(fù)制能力的病毒[34, 55]也有記錄表明,感染源是與口腔結(jié)痂患者的口腔接觸(接吻)[68]對(duì)口咽病變和非口咽病變患者的唾液進(jìn)行PCR也檢測(cè)到了痘病毒DNA[38, 52, 61, 66, 69, 70]; 然而,在沒(méi)有口咽損傷的情況下,還沒(méi)有明確的報(bào)道描述僅從唾液中分離出復(fù)制活性病毒。在某些情況下,唾液中的病毒DNA濃度與皮膚損傷(即同時(shí)采集的唾液和皮膚損傷)配對(duì)樣本中觀察到的病毒DNA的濃度相當(dāng)[38, 69]總的來(lái)說(shuō),這一證據(jù)表明接觸口咽和唾液可以傳播感染;然而,數(shù)據(jù)不足以確定暴露時(shí)是否需要口腔病變。

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肛門:

當(dāng)前疫情中多發(fā)性腸病的臨床表現(xiàn)也值得注意,因?yàn)樵\斷時(shí)肛門和肛周病變的發(fā)病率很高[1, 4-6, 27].肛門粘膜也可出現(xiàn)典型的多囊卵巢綜合征病毒感染病變[1, 71, 72]多項(xiàng)研究已通過(guò)PCR在肛門直腸拭子中檢測(cè)到mpox病毒DNA,包括從沒(méi)有可見(jiàn)肛門周圍病變或沒(méi)有直腸炎的人身上采集的肛門直腸簽[34, 45, 55, 61, 62, 67, 69, 73]在兩份報(bào)告中,拭子產(chǎn)生了具有復(fù)制能力的病毒[34, 73]通過(guò)肛門粘膜接觸傳播,例如通過(guò)插入性肛門接觸(例如陰莖或手指)或通過(guò)肛門肛門肛管傳播,尤其難以評(píng)估,因?yàn)檫@種接觸通常發(fā)生在性交期間的其他親密身體接觸中,包括皮膚接觸。目前還沒(méi)有報(bào)告能夠確定接觸肛門直腸粘膜是唯一的感染源。然而,肛門直腸粘膜損傷的存在是mpox的特征,并且能夠在肛門直腸拭子中恢復(fù)具有復(fù)制能力的病毒,這種拭子的病毒DNA濃度與皮膚損傷相當(dāng)[48](圖)至少有一份報(bào)告中的結(jié)果與同時(shí)采集的皮膚和肛門直腸拭子(即配對(duì)樣本)的結(jié)果具有可比性[31]支持肛門直腸接觸可傳播感染。

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精液:

用PCR在感染者精液中檢測(cè)到了痘病毒DNA[34, 38, 59, 66, 67, 69, 74-76]在三份報(bào)告中,精液中產(chǎn)生了具有復(fù)制能力的病毒[34, 59, 76],但到目前為止,還沒(méi)有報(bào)道過(guò)接觸精液是mpox病毒傳播的唯一可能方式(例如,使用精液在體外施肥)。通過(guò)接觸精液傳播,如通過(guò)肛門、陰道或口腔的接受性性接觸,尤其難以評(píng)估,因?yàn)檫@種接觸通常發(fā)生在包括皮膚接觸的性交環(huán)境中。精液中病毒DNA的濃度低于皮膚損傷中觀察到的濃度[38, 69, 74](圖). 流行病學(xué)數(shù)據(jù)目前表明,接觸精液可能會(huì)傳播感染,但目前的數(shù)據(jù)不足以明確支持這種接觸是感染源。

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尿液和尿道粘膜:

幾項(xiàng)研究已經(jīng)通過(guò)PCR在尿液或尿道拭子中檢測(cè)到了mpox病毒DNA[9, 62, 63, 65, 67, 69, 75]在一例病例中,尿道拭子也產(chǎn)生了具有復(fù)制能力的病毒;沒(méi)有尿道損傷[62]未發(fā)現(xiàn)與尿液接觸有關(guān)的流行病學(xué)傳播病例,經(jīng)評(píng)估,病毒DNA的濃度低于皮膚損傷的濃度(圖)包括成對(duì)皮膚病變的樣本[9, 65]流行病學(xué)數(shù)據(jù)目前表明,接觸尿液或尿道粘膜可能會(huì)傳播感染,但目前的數(shù)據(jù)不足以明確支持這種接觸是感染源。

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結(jié)膜或眼液:

PCR已在眼瞼病變的結(jié)膜拭子或拭子中以及有證據(jù)表明眼部多痘病毒感染的人的角膜上皮中檢測(cè)到多痘毒DNA[61, 65, 77-80]在一例病例中,結(jié)膜拭子產(chǎn)生了具有復(fù)制能力的病毒[65]; 然而,迄今為止,沒(méi)有任何傳播與接觸結(jié)膜液或眼組織有關(guān)。在一個(gè)病例中,結(jié)膜炎患者的結(jié)膜拭子中的病毒DNA濃度與成對(duì)皮膚病變相當(dāng),但眼瞼或結(jié)膜上沒(méi)有病變[77]因此,接觸結(jié)膜或眼液可能會(huì)傳播感染,尤其是在有結(jié)膜炎的情況下,但目前的數(shù)據(jù)不足以肯定這種接觸是感染源。

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血液:

在血漿和血清標(biāo)本中用PCR很容易檢測(cè)出痘病毒DNA[9, 29, 34, 38, 44, 55, 59, 60, 63, 65, 67, 75]然而,迄今為止還沒(méi)有研究發(fā)現(xiàn)血液或血液制品中存在復(fù)制能力強(qiáng)的病毒,盡管很少有研究人員嘗試培養(yǎng)病毒,因?yàn)橥ǔz測(cè)到的DNA濃度很低(圖). 迄今為止,沒(méi)有因接觸血液或血液制品而傳播的病例。評(píng)估時(shí),病毒DNA的濃度低于皮膚損傷和其他接觸源樣品中觀察到的濃度(圖)包括成對(duì)的皮膚損傷[9, 55, 63, 65]或成對(duì)結(jié)痂/結(jié)痂[38]流行病學(xué)數(shù)據(jù)目前不足以證明血液接觸是感染源。

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糞便:

有兩項(xiàng)研究報(bào)告了用PCR檢測(cè)糞便中的mpox病毒DNA[38, 69]; 然而,尚未從糞便中分離出具有復(fù)制能力的病毒,傳播也未在流行病學(xué)上與接觸糞便有關(guān)。流行病學(xué)數(shù)據(jù)目前不足以支持接觸糞便作為感染源。

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陰道:

在最有可能通過(guò)性接觸獲得mpox病毒的順性別女性中,當(dāng)前疫情的臨床表現(xiàn)是診斷時(shí)生殖器損傷的高流行率[8, 13, 34, 81-84]三項(xiàng)研究報(bào)告了通過(guò)PCR在陰道拭子中檢測(cè)mpox病毒DNA[13, 34]以及外陰和宮頸病變[85]尚未從陰道粘膜或陰道液中分離出復(fù)制抑制病毒。通過(guò)陰道或口腔性交接觸陰道液體傳播尤其難以評(píng)估,因?yàn)檫@種接觸通常發(fā)生在包括皮膚接觸的性交環(huán)境中。然而,盡管缺乏明確的流行病學(xué)證據(jù)將陰道接觸與傳播聯(lián)系起來(lái),但來(lái)自兩例病例的間接證據(jù)[8]這與一個(gè)似是而非的假設(shè)是一致的,即mpox可通過(guò)接觸外陰陰道組織和體液進(jìn)行性傳播。

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母乳:

目前,現(xiàn)有數(shù)據(jù)不足以估計(jì)母乳中可能存在的多聚體病毒DNA或具有復(fù)制能力的病毒的程度。目前沒(méi)有流行病學(xué)數(shù)據(jù)支持母乳接觸是感染源。由于母乳接觸通常包括皮膚接觸,因此確定通過(guò)母乳傳播對(duì)評(píng)估尤其具有挑戰(zhàn)性。

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受污染的銳器傷以及刺穿和紋身:

在目前的疫情中,至少有四例記錄在案的醫(yī)護(hù)人員通過(guò)皮膚穿透?jìng)腥玖薽pox病毒,這種皮膚穿透?jìng)怯捎糜谄つw損傷取樣的非血性銳器造成的;在所有病例中,醫(yī)護(hù)人員感染后的第一個(gè)或唯一的病灶都出現(xiàn)在接種點(diǎn)[18-21].CDC建議不要使用銳器對(duì)病變進(jìn)行采樣涉及的尖銳物被水泡或膿皰物質(zhì)污染;然而,沒(méi)有對(duì)鋒利物進(jìn)行病毒DNA或復(fù)制能力強(qiáng)的病毒的檢測(cè)。

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多份報(bào)告表明,成人和兒童在接受穿刺和紋身的情況下都可以傳播mpox病毒[16, 22-24]調(diào)查了20起涉及不良無(wú)菌措施的案件,導(dǎo)致暴露在受源患者污染的紋身和穿孔材料中。在設(shè)備(如鋒利物、鑷子和剪刀等其他工作工具)和表面(如椅子、車間表面)上檢測(cè)到病毒DNA[23]然而,在這些報(bào)告中,沒(méi)有一份報(bào)告能夠充分說(shuō)明復(fù)制能力強(qiáng)的病毒的存在,也沒(méi)有明確的流行病學(xué)證據(jù)能夠準(zhǔn)確地解釋傳播是如何發(fā)生的,盡管最初的皮疹損傷往往首先出現(xiàn)在穿孔或紋身的部位[22-24]。


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三、檢測(cè)表面、材料和物體上的猴痘病毒

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在本次疫情期間,在有癥狀的多功能性腸病患者的家庭和病房中發(fā)現(xiàn)了廣泛的表面多功能性肺病病毒污染[86-89],在表面上評(píng)估時(shí),病毒濃度通常較低(即報(bào)告的研究中Ct值>30)[89]和空氣樣品[90]。盡管多次嘗試分離具有復(fù)制能力的病毒,但產(chǎn)生可培養(yǎng)病毒的唯一目標(biāo)是那些被預(yù)計(jì)污染最嚴(yán)重的病毒。例如,在一項(xiàng)基于醫(yī)院的對(duì)患者隔離室的研究中,這些物品包括醫(yī)療服務(wù)提供者檢查患者后使用的手套、患者浴室中的肥皂分配器操作桿和患者床上的毛巾[88]在另一項(xiàng)基于醫(yī)院的研究中,產(chǎn)生可復(fù)制病毒的樣本包括在患者房間更換床單時(shí)采集的空氣樣本,以及在護(hù)理患者的提供者穿戴和脫下PPE的區(qū)域采集的地板拭子[86]。在當(dāng)前疫情期間,沒(méi)有記錄到因接觸表面、材料或其他物體而導(dǎo)致傳播的病例,這些人在護(hù)理多發(fā)性肺炎患者時(shí)采取了建議的預(yù)防措施家或在醫(yī)療環(huán)境2018年發(fā)生一起多功能性卵巢綜合征病例,原因是接觸了患者骯臟的床上用品;然而,在這種情況下,工人沒(méi)有穿戴完整的個(gè)人防護(hù)裝備(即只穿戴一次性圍裙和手套)[91]。其他可能的職業(yè)獲得性多功能性有機(jī)污染物案例(排除了尖銳物暴露)歸因于在缺乏充分或有效的個(gè)人防護(hù)裝備的情況下多功能性無(wú)機(jī)污染物暴露[25, 26].

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四、在沒(méi)有疾病癥狀或體征的情況下檢測(cè)和傳播猴痘

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新出現(xiàn)的證據(jù)表明,一些患者可以在出現(xiàn)可識(shí)別的癥狀或體征之前傳播mpox病毒(即癥狀前傳播)。雖然在一些從未出現(xiàn)癥狀的人的樣本中檢測(cè)到低水平的mpox病毒DNA,但目前沒(méi)有證據(jù)表明這些人對(duì)其他人具有傳染性。需要進(jìn)行更大規(guī)模的研究和建模,以了解有多少病例是由在癥狀出現(xiàn)之前傳播病毒的人引起的,并確定在何種程度上(如果有的話),一些被評(píng)估為癥狀前向他人傳播了mpox病毒的人可能沒(méi)有癥狀感染。

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癥狀前感染

將mpox的潛伏期(即感染后發(fā)病的時(shí)間)與其系列間隔(即指數(shù)病例發(fā)病與繼發(fā)病例發(fā)病之間的時(shí)間)進(jìn)行比較,這與感染mpox病毒的人能夠在疾病癥狀和體征出現(xiàn)之前傳播病毒的可能性是一致的出現(xiàn)。[41, 42]在肛門直腸拭子中檢測(cè)到痘病毒DNA[44, 62, 74, 92]、尿道拭子[62],生殖器拭子[44],口咽拭子[44]和唾液[44]樣本采集時(shí)既沒(méi)有明顯癥狀也沒(méi)有報(bào)告疾病癥狀的人群。其中一些樣本還從肛門直腸拭子中產(chǎn)生了具有復(fù)制能力的病毒[44, 74]和尿道拭子[62],其中一些患者在初次樣本采集后的幾周內(nèi)進(jìn)行檢測(cè)時(shí),發(fā)現(xiàn)了新的血清學(xué)證據(jù),證明接觸了正痘病毒[44, 74]流行病學(xué)調(diào)查提供了足夠的數(shù)據(jù)來(lái)明確評(píng)估傳播時(shí)間和發(fā)病時(shí)間,已證實(shí)mpox病毒的性傳播發(fā)生在發(fā)病前1-4天[45]。

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無(wú)癥狀感染

有記錄在案的病例表明,接觸過(guò)多殺性大腸桿菌病毒的人從未出現(xiàn)疾病癥狀或體征,但其樣本(即肛門直腸拭子、口咽拭子,生殖器拭子和唾液)的病毒DNA檢測(cè)濃度很低,接近檢測(cè)限值。然而,由于Ct值高(即病毒DNA濃度低),沒(méi)有對(duì)樣本進(jìn)行復(fù)制能力病毒評(píng)估[44]這些人中的大多數(shù)在兒童時(shí)期接受過(guò)天花疫苗接種或作為接觸后預(yù)防措施。在其余未接種疫苗的人中,沒(méi)有人顯示出明顯的血清轉(zhuǎn)化證據(jù)。迄今為止,沒(méi)有任何傳播病例與接觸從未出現(xiàn)癥狀或體征(即無(wú)癥狀感染)的感染者有明確聯(lián)系。


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圖.根據(jù)采樣暴露源得出的猴痘病毒濃度(摘自Palich等人。[47])

*在本研究中,PCR檢測(cè)為弱陽(yáng)性(35≤Ct<40)或陰性(Ct≥40)的臨床樣本被排除在本分析之外。所有樣本均為診斷后采集的第一批樣本,發(fā)病后平均5天(IQR 3-6)。未對(duì)樣本進(jìn)行培養(yǎng)測(cè)試,以確認(rèn)是否存在感染性病毒。值得注意的是,在初步診斷后14天,大多數(shù)樣本的多聚酶鏈反應(yīng)病毒呈陰性。為了更全面地了解疾病不同階段的潛在感染性,需要前瞻性收集數(shù)據(jù)來(lái)評(píng)估樣本隨時(shí)間的陽(yáng)性率。結(jié)果以方框圖形式給出,其中紅線表示中值Ct.Ct=周期閾值。MPXV=mpox病毒。

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表.人類樣本中的痘病毒及其傳播意義

*在發(fā)病30天以上的康復(fù)患者中,在上呼吸道拭子、唾液和精液中檢測(cè)到Ct值<35的DNA。

現(xiàn)有數(shù)據(jù)的優(yōu)勢(shì)支持暴露于肛門直腸和外陰陰道組織和液體能夠傳播感染;然而,根據(jù)目前的證據(jù),很難將這些暴露與其他伴隨暴露明確區(qū)分開來(lái)(見(jiàn)正文)。

包括身體修飾、穿孔和紋身。

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上次審核時(shí)間:2023年2月2日

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資料來(lái)源:Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of High-Consequence Pathogens and Pathology (DHCPP)

科學(xué)簡(jiǎn)報(bào):2022年Clade IIb爆發(fā)期間Mpox(前猴痘)病毒的檢測(cè)和傳播的評(píng)論 (共 條)

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