摘要
风疹是由风疹病毒(Rubella virus,RV)引起的一种以发热、出疹为主要表现的急性呼吸道传染病,孕早期感染RV可引起先天性风疹综合征(Congenital rubella syndrome,CRS)。风疹是疫苗可预防性传染病,2008年我国将风疹疫苗纳入国家扩大免疫规划,通过连续10年免疫规划的实施,风疹发病率迅速下降,2014~2017年已接近风疹消除的目标(风疹发病率为0.8/10万~0.12/10万)。加强对风疹可疑病例的报告和实验室鉴别诊断,对隔离传染源、指导疫苗使用以及阻断RV传播具有重要的作用。《麻疹和风疹病毒感染实验室诊断手册》要求在风疹暴发流行阶段,只针对每起暴发采集5~10份血标本,检测风疹IgM是风疹病例确诊的金标准;而在消除风疹和CRS阶段要求对每一例散发疑似病例采集血清标本和鼻咽拭子,分别进行IgM抗体和RV核酸的检测。本文对我国在消除风疹和CRS阶段将RV核酸检测应用于风疹病例早期诊断的必要性进行了阐述。
Rubella is an acute respiratory infection caused by rubella virus(RV),which is characterized by fever and rash. Transplacental infection of fetus during the first trimester of pregnancy results in a group of congenital anomalies called as congenital rubella syndrome(CRS). As a vaccine preventable disease,rubella vaccine was incorporated into the national immunization program in China in 2008. Through the implementation of the 10-year immunization program,the incidence rate of rubella decreased rapidly. From 2014 to 2017,the incidence rates of rubella were 0.8/100,000~0.12/100,000,which is close to the goal of rubella elimination. Strengthening the reporting of suspected cases of rubella and laboratory differential diagnosis play important roles in isolating the pathogen of infection,guiding the use of vaccines,and blocking the spread of RV. In the epidemic stage of rubella outbreak,5~10 blood samples should be collected for each outbreak. RV-specific IgM Enzyme-linked immunosorbent assay(ELISA)is the gold standard for the diagnosis of rubella cases. While in the rubella elimination stage,a sensitive surveillance with laboratory confirmation of each sporadic suspected case is required.Serum samples and nasopharyngeal swabs should be collected from each case,then IgM antibodies and RV nucleic acids are detected,respectively. In this article,we review the necessity and importance of nucleic acid detection to supplement the early laboratory diagnosis of rubella cases in the rubella elimination stage in China.
引文
[1] Lambert N,Strebel P,Orenstein W,Icenogle J,Po-land G A. Rubella. Lancet,2015,385(9984):2297-2307
[2] Verma R,Khanna P,Chawla S. Rubella vaccine[J].Hum Vacc Immunother,2012,8(6):831-833.
[3] Centers for Disease Control and Prevention. Three cases of congenital rubella syndrome in the postelimination era-Maryland,Alabama,and Illinois,2012[J]. Mmwr-Morbid Mortal W,2013,62(12):226-229.
[4] Su Q,Ma C,Wen N,Fan C X,Yang H,Wang H Q,Yin Z,Feng Z J,Hao L X,Yang W Z. Epidemiological profile and progress toward rubella elimination in China10 years after nationwide introduction of rubella vaccine.[J]. Vaccine,2018,36(16):2079-2085.
[5]PAHO. Americas region is declared the world′s first to eliminate rubella(press release). Washington,DC:PA-HO;2015 April 25[EB/OL].https://www.paho.org/hq/index.php? option=com_content&view=article&id=10798:2015-americas-free-of-rubella&Itemid=1926&lang=pt
[6] Hübschen,Judith M,Bork S M,Brown K E,Mankertz A,Santibanez S,Ben Mamou M,Mulders M N,Mull-er C P. Challenges of measles and rubella laboratory di-agnostic in the era of elimination[J]. Clin Microbiol In-fec,2017,23(8):511-515.
[7] Martínez-Quintana E,Castillo-Solórzano C,Torner N,Rodrigue-González F. Congenital rubella syndrome:a matter of concern[J]. Rev Panam Salud Publ,2015,37(3):179-186.
[8]马姗姗,池益强,章国辉,谢群,林勇.厦门市2004-2011年风疹流行病学特征分析[J].海峡预防医学杂志,2013,19(4):39-41.
[9]中国疾病预防控制中心.全国麻疹监测方案(2014版)[S].中疾控疫发〔2014〕36号,2014-02-21
[10]Cooper L Z,Ziring P R,Ockerse A B,Fedun B A,Kiely B,Krugman S. Rubella. Clinical manifestations and management[J]. Am J Dis of Child,1969,118(1):18-29.
[11]Cooper L Z,Krugman S. Clinical manifestations of post-natal and congenital rubella[J]. Arch Ophthalmol,1967,77(4):434-439.
[12]Tran D N,Vu M P,Ha M T,Giang T P,Komase K,Mizuguchi M,Ushijima H. Viral molecular characteriza-tion of the first congenital rubella syndrome case in Viet-nam[J]. Clin Lab,2011,57(5-6):397-401.
[13]Jivraj I,Rudnisky C J,Tambe E,Tipple G,Tennant M T S. Identification of ocular and auditory manifesta-tions of congenital rubella syndrome in Mbingo[J]. Int J Telemed Appl,2014,2014:1-5.
[14]CSTE. Public health reporting and national notification for congenital rubella syndrome,CSTE position state-ment 09-ID-61. Atlanta,GA:CSTE,2009[EB/OL].http://c. ymcdn. com/sites/www. cste. org/resource/resmgr/PS/09-ID-61.pdf
[15]Givens K T,Lee D A,Jones T,Ilstrup D M. Congeni-tal rubella syndrome:ophthalmic manifestations and as-sociated systemic disorders[J]. Brit J Ophthalmol,1993,77(6):358-363.
[16]Ginsberg-Fellner F,Witt M,Yagihashi S,Dobersen M J,Taub F,Fedun B,McEvoy R C,Roman S H,Da-vies T F,Cooper Z,Rubinstein P,Notkins A L. Con-genital rubella syndrome as a model for type 1(insulin-dependent)diabetes mellitus:increased prevalence of is-let cell surface antibodies[J]. Diabetologia,1984,27(1):87-89.
[17]Freij B J,South M A,Sever J L. Maternal rubella and the congenital rubella syndrome[J]. Clin Perinatol,1988,15(2):247-257.
[18]Viskari H,Paronen J,Keskinen P,Simell S,Zawilins-ka B,Zgorniak-Nowosielska I,Korhonen S,Ilonen J,Simell O,Haapala A M,Knip M. Humoralβ-cell auto-immunity is rare in patients with the congenital rubella syndrome[J]. Clin Exp Immunol,2003,133(3):378-383.
[19]Ohkusa Y,Sugawara T,Arai S,Satoh H,Okuno H,Tanaka-Taya K,Oishi K. Short-term prediction of the incidence of congenital rubella syndrome[J/OL]. PLoS Curr, 2014, 6. pii:ecurrents. outbreaks.8c74272f4348781c5d01c81e6150c2f7.
[20]Ueda K,Nishida Y,Oshima K,Thomas M D. Congen-ital rubella syndrome:correlation of gestational age at time of maternal rubella with type of defect[J]. J Pedi-atr,1979,94(5):763-765.
[21]Miller E,Cradock-Watson J,Pollock T. Consequences of confirmed maternal rubella at successive stages of pregnancy[J]. Lancet,1982,320(8302):781-784.
[22]Cusi M G,Rossolini G M,Valensin P E,Cellesi C,Zanchi A. Serological evidence of reinfection among vac-cinees during rubella outbreak[J]. Lancet,1990,336(8722):1071.
[23]Davidkin I,Jokinen S,Paananen A,Leinikki P,Peitoia H. Etiology of mumps-like illnesses in children and ado-lescents vaccinated for measles,mumps,and rubella[J].J Infect Dis,2005,191(5):719-723.
[24]Sanjaya S. Dengue fever and dengue haemorrhagic fever-A diagnostic challenge[J]. Aust Fam Physician,2006,35(8):609-612.
[25]Tipples G A,Hamkar R,Mohktari-Azad T,Gray M,Parkyn G,Head C,Ratnam S. Assessment of immuno-globulin M enzyme immunoassays for diagnosis of mea-sles[J]. J Clin Microbiol,2003,41(10):4790-4792.
[26]王慧玲,毛乃颖,高凌玉,朱贞,许松涛,崔爱利,张燕,许文波.中国2016年麻疹风疹实验室网络运转分析[J].中国疫苗和免疫,2017,23(3):241-245.
[27]王慧玲,毛乃颖,张燕,许松涛,崔爱利,蒋小泓,朱贞,姬奕昕,石晶,唐浏英,许文波.中国2010年麻疹/风疹实验室网络运转情况分析[J].中国疫苗和免疫,2013,19(3):217-221.
[28]World Health Organization. Alternative specimens for IgM antibody testing. Manual for the Laboratory-based Surveillance of Measles,Rubella,and Congenital Rubel-la Syndrome. 2018. https://www. who. int/immuniza-tion/monitoring_surveillance/burden/laboratory/manu-al_section3.4/en/
[29]Vijaylakshmi P,Muthukkaruppan V R,Rajasundari A,Korukluoglu G,Nigatu W L A Warrener,Samuel D,Brown D W G. Evaluation of a commercial rubella IgM assay for use on oral fluid samples for diagnosis and surveillance of congenitalrubella syndrome and postna-tal rubella[J]. J Clin Virol,2006,37(4):265-268.
[30]World Health Organization. Rubella. Vaccine-Prevent-able Disease surveillance standards[EB/OL]. 2018.https://www. who. int/immunization/monitoring_sur-veillance/burden/vpd/WHO_SurveillanceVaccinePre-ventable_20_Rubella_R2.pdf?ua=1
[31]Mulders M N,Rota P A,Icenogle J P,Brown K E,Takeda M,Rey G J,Ben Mamou M C,Dosseh A R G A,Byabamazima C R,Ahmed H J,Pattamadilok S,Zhang Y,Gacic-Dobo M,Strebel P M,Goodson J L.Global measles and rubella laboratory network support for elimination goals,2010-2015[J]. MMWR-Morbid Mortal W,2016,65(17):438-442.
[32]Grant G B,Reef S E,Dabbagh A,Gacic-Dobo M,Strebel P M. Global progress toward rubella and congeni-tal rubella syndrome control and elimination-2000-2014[J]. MMWR,2015,64(37):1052-1055.
[33]Shelly B,Gillian L,Vica D,Natasha C,Jonathan G,Tony M,Richard S. The utility of measles and rubella IgM serology in an elimination setting,Ontario,Cana-da,2009-2014[J/OL]. PLoS One,2017,12(8):e0181172.
[34]World Health Organization. Interpretation of IgM results among suspected cases with recent vaccine history. Man-ual for the Laboratory-based Surveillance of Measles,Rubella, and Congenital Rubella Syndrome. 2018.https://www. who. int/immunization/monitoring_sur-veillance/burden/laboratory/manual_section4.3/en/
[35]Vauloup-Fellous C,Grangeot-Keros L. Humoral im-mune response after primary rubella virus infection and after vaccination[J]. Clin and Vaccine Immunol,2007,14(5):644-647.
[36]Marina A,Yermalovich,Galina V,Semeiko,Elena O,Samoilovich,Ekaterina Y,Svirchevskaya,Claude P,Muller,Judith M,Hübschen. Etiology of maculopapular rash in measles and rubella suspected patients from Belar-us[J/OL]. PLoS One,2014,9(10):e111541.
[37]Ratnam S,Tipples G,Head C,Fauvel M,Fearon M,Ward B J. Performance of indirect immunoglobulin M(IgM)serology tests and IgM capture assays for labora-tory diagnosis of measles[J]. J Clin Microbiol,2000,38(1):99-104.
[38]Davis W J,Larson H E,Simsarian J P,Parkman P D,Meyer H M Jr. A study of rubella immunity and resis-tance to infection[J]. JAMA,1971,215(4):600-608.
[39]Donadio,Flávia F,Siqueira,Marilda M,Vyse,An-drew,Jin Li,Oliveira,Solange A. The genomic analy-sis of rubella virus detected from outbreak and sporadic cases in Rio de Janeiro state,Brazil[J]. J Clin Virol,2003,27(2):205-209.
[40]Vyse A J,Jin L. A RT-PCR assay using oral fluid sam-ples to detect rubella virus genome for epidemiological surveillance[J]. Molecular and Cellular Probes,2002,16(2):93-97.
[41]Zhu,Z,Xu W B,Abernathy E S,Chen M H,Zheng Q,Wang T Z,Zhang Z Y,Li C Y,Wang CY,He W K,Zhou S J,Icenogle J. Comparison of four methods using throat swabs to confirm rubella virus infection[J].J Clin Microbiol,2007,45(9):2847-2852.
[42]Hübschen,Judith M,Kremer,Jacques R,De Landt-sheer,Sébastien,Muller,Claude P. A multiplex Taq-Man PCR assay for the detection of measles and rubella virus[J]. J Virol Methods,2008,149(2):246-250.
[43]Mosquera Mdel M,de Ory F,Moreno M,Echevarria J E. Simultaneous detection of measles virus,rubella vi-rus,and parvovirus B19 by using multiplex PCR[J]. J Clin Microbiol,2002,40(1):111-116.
[44]朱贞,蔡茹,崔爱利,张燕,毛乃颖,许松涛,姬奕昕,王慧玲,张盛,许文波,吴宏伟.中国大陆流行的风疹病毒的变异变迁规律研究[J],病毒学报,2017,33(1):67-76. DOI:10.13242/j.cnki.bingduxuebao.003096
[45]World Health Organization. Utility and limitations for molecular testing in elimination settings. Manual for the Laboratory-based Surveillance of Measles,Rubella,and Congenital Rubella Syndrome. 2018. https://www.who.int/immunization/monitoring_surveillance/burden/labo-ratory/manual_section8.2/en/
[46]薄芳,马玉杰,黄鹤,彦子博,宋婧,张世婷.实时荧光定量RT-PCR和血清学方法联合应用检测风疹病毒[J].中国公共卫生管理,2014,30(3):450-451.
[47]Abernathy E,Cabezas C,Sun H,Zheng Q,Chen M H,Castillo-Solorzano C,Ortiz A C,Osores F,Olivei-ra L,Whittembury A,Andrus J K,Helfand R F,Iceno-gle J. Confirmation of rubella within 4 days of rash on-set:comparison of rubella virus RNA detection in oral fluid with immunoglobulin M detection in serum or oral fluid[J]. J Clin Microbio,.2009,47(1):182-188.
[48]Bouthry E,Picone O,Hamdi G,Grangeot-Keros L,Ayoubi J M,Vauloup-Fellous C. Rubella and pregnan-cy:diagnosis,management and outcomes[J]. Prenatal Diag,2014,34(13):1246-1253.
[49]MacéM,Cointe D,Six C,Levy-Bruhl D,Parent du Chatelet I,Ingrand D,Grangeot-Keros L. Assessment of the diagnostic value of RT-PCR on amniotic fluid for prenatal diagnosis of congenital rubella infection[J].Pathol Biol,2004,52(9):540-543.
[50]Tanemura M,Suzumori K,Yagami Y,Katow S. Diag-nosis of fetal rubella infection with reverse transcription and nested polymerase chain reaction:a study of 34 cas-es diagnosed in fetuses[J]. Am Jobstet Gynecol,1996,174(2):578-582.
[51]Robyn M,Dufort E,Rosen J B,Southwick K,Bryant P W,Greenko J,Adams E,Kurpiel P,Alvarez K J,Burstein G,Sen K,Vasquez D,Rausch-Phung E,Schulte C,Lutterloh E,Blog D. Two imported cases of congenital rubella syndrome and infection-control chal-lenges in New York State,2013-2015[J]. J Pediat Inf Dis Soc,2018,7(2):172-174.