Title Serological assessmet of measles-r campaig amog uiversity studets. Author(s) Takeuchi, Jiro; Goto, Masashi; Kawa Atsushi Citatio Pediatrics iteratioal : official Society (2014), 56(3): 395-399 Issue Date 2014-06-03 URL http://hdl.hadle.et/2433/199813 This is the peer reviewed versio o Takeuchi, J., Goto, M., Kawamura, T Serological assessmet of measles r up campaig amog uiversity stude RightIteratioal, 56: 395 399. doi: 10 bee published i fial form at [10 article may be used for o-commerc with Wiley Terms ad Coditios for Japa Pediatric Society Type Joural Article Textversio author Kyoto Uiversity
1 Short title ruig head: Serology of catch-up vacciatio Authors ruig head: J Takeuchi et al. Correspodece: Masashi Goto, MD MPH PhD, Health Service, Kyoto Uiversity, Yoshida-Homachi, Sakyo-ku, Kyoto 606-8501, Japa. Email: goto@msa.biglobe.e.jp Received 20 April 2012; revised 16 November 2013; accepted 20 November 2013. Origial Article Serological assessmet of measles rubella vacciatio catch-up campaig amog uiversity studets Jiro Takeuchi, 1 Masashi Goto, 1 Takashi Kawamura 1 ad Atsushi Hiraide 2 1 Health Service, Kyoto Uiversity, Kyoto ad 2 Departmet of Acute Medicie, Kiki Uiversity Faculty of Medicie, Osaka- Sayama, Japa Abstract Backgroud: I Japa, 5000 300 000 persos succumbed to measles every year util 2001. The measles/rubella-combied (MR) vacciatio at age 17 18 years (phase 4 MR vacciatio: MR-IV) was lauched i 2008 i Japa as a measles rubella catch-up campaig. A serological assessmet of this campaig has ot bee thoroughly performed. Methods: Titers of ati-measles ad ati-rubella immuoglobuli G atibodies, ad past medical history icludig measles ad rubella vacciatio ad ifectio were obtaied from first-year uiversity studets i 2008 ad 2009, ad the immue status agaist measles ad rubella was compared betwee studets at the target MR-IV age (the target age group) ad those 1 year older tha the target age (o-target age group). Results: A total of 186 studets were i the target age group ad 146 were i the o-target age group. The proportio of studets with a history of measles ad rubella ifectio was ot sigificatly differet betwee the two groups (8.8% vs. 6.3%, P = 0.41 ad 11.0% vs. 9.9%, P = 0.75, respectively). A history of two or more measles ad rubella vacciatios was sigificatly more frequet i the target age group (85.2% ad 54.9%, respectively) tha i the o-target age group (20.8% ad 13.2%, respectively; both P < 0.001). Prevalece of seropositivity for measles ad for rubella was also higher i the target age group (98.9% ad 97.8%, respectively) tha i the o-target age group (91.0% ad 87.5%, respectively; both P < 0.001). Coclusios: The MR-IV catch-up campaig helped achieve herd immuity ad will cotribute to the elimiatio of measles ad rubella. Key words atibody, catch-up campaig, materal ad child health hadbook, measles rubella vacciatio, uiversity studets. I the past the govermet of Japa madated people to receive oly a sigle-dose vacciatio for measles ad rubella, ad partially due to this 5000 300 000 persos had succumbed to measles every year before 2001. 1,2 Mathematical models idicated that >95% of people i a commuity should be immuized to prevet a epidemic of measles, ad the correspodig proportio is 85% for rubella. 3 5 The World Health Orgaizatio (WHO), therefore, recommeds 95% immuizatio to elimiate measles, 6 but oly 80.7% of Japaese people of all ages had received immuizatio for measles i 2001. 7 The govermet the lauched a campaig with the theme Give a measles vaccie as a first birthday gift! i 2001. 8 Nevertheless, Japa experieced measles outbreaks maily amog high school ad college studets i both 2006 ad 2007. Especially i 2007, 1657 studets (0.58%) suffered from measles atiowide. 9 Prevetio of vaccie-prevetable ifectious diseases amog youth the became a urget matter. The greatest cocers were ovacciatio ad vaccie failure. Ideed, a survey durig the measles outbreak foud that oly 64.8% of patiets had a history of measles vacciatio. 10 Vaccie failure occurred i 7.4% of first-year studets who had udergoe the first vacciatio at college
2 admissio. 11 Therefore, a two-dose policy with a measles/rubella-combied (MR) vaccie, requirig immuizatio at age 12 23 moths (phase 1 MR vacciatio: MR-I) ad at age 5 6 years (just before school etry, phase 2 MR vacciatio: MR-II) was eforced i 2006, ot oly to icrease vaccie coverage but also to miimize vaccie failure. 12 16 I additio, a catch-up campaig with MR vacciatios at age 12 13 years (first-year juior high school studets, phase 3 MR vacciatio: MR-III) ad at age 17 18 years (third-year high school studets, phase 4 MR vacciatio: MR-IV), has bee carried out for 5 years sice 2008 uder the Prevetive Vacciatio Law. 6 By these efforts, the aual umber of measles cases decreased from a estimated 286 000 i 2001 to 11 005 i 2008, 741 i 2009, 457 i 2010, ad 434 i 2011. 7,17 20 The umber of measles outbreaks also rapidly decreased after peakig i 2007, ad there has bee o remarkable outbreak from 2009 o. Accordig to the pediatric fixedpoit survey of measles, the proportio of patiets aged 10 years gradually icreased, while that of patiets aged 1 4 years gradually decreased util 2007. 21 The proportio of patiets 10 years old, however, has dramatically decreased sice 2008 whe the catch-up campaig was itroduced. The catch-up campaig seems successful i prevetig measles ad rubella epidemics amog adolescets. The two-dose vacciatio campaig has bee kow to reduce the icidece of measles early i the followig year, as it did i Eglad ad Wales. We, therefore sought to evaluate the efficacy of the catch-up campaig i detail. 22 Methods Study desig This study was carried out as a aalytical epidemiological study at a sigle istitutio. The 2008 ad 2009 first-year studets of Kyoto Uiversity Faculty of Medicie (School of Medicie, medical doctor course, ad School of Huma Health Scieces, co-medical professioal course) ad Faculty of Pharmaceutical Scieces (Divisio of Pharmacy, pharmacist course) were ivited to participate i the study. Because the MR-IV lauched i 2008 for 5 years was targeted at last year (third-year) high school studets, first-year studets i 2009 who etered the uiversity right after graduatig from high school were at the target MR-IV age. Meawhile, all of the first-year studets i 2008 were off the target MR-IV age. We therefore recruited the studets who etered the uiversity right after graduatig from high school, both i 2009 ad 2008, for the study. Idividual writte iformed coset was obtaied from all participats. After mergig data from differet sources, all persoal idetifiers were removed from the database. This ivestigatio was approved by the Ethics Committee of Kyoto Uiversity Graduate School of Medicie (approval umber, E-590). Questioaire survey A iformed coset form ad a self-admiistered questioaire with a reply evelope were haded out to the 2009 first-year studets ad mailed to the 2008 first-year studets. The questioaire icluded items o demographic characteristics ad past medical history, icludig measles ad rubella ifectio. Studets were asked to complete the questioaire ad retur it with the coset form ad a photocopy of the immuizatio record from the Materal ad Child Health (MCH) Hadbook. Ufortuately, however, the welfare committee of the School of Huma Health Scieces did ot allow us to collect photocopies of the MCH Hadbook for the 2008 first-year co-medical studets due to a lack of time for obtaiig their coset. The MCH Hadbook is issued by the local govermet of oe s residetial area, ad etries are completed by medical professioals maily at pre- ad postatal periodic health checkups ad o-demad periatal medical office visits, accordig to the MCH law. Biomarker assay
3 Titers of ati-measles ad ati-rubella immuoglobuli (Ig) G atibodies were measured o ezyme immuoassay (EIA) ad hemagglutiatio ihibitio (HI) test, o 23, 24 ad 27 Jue 2008, or 2 April 2009, respectively. Microbiology tests were examied by a cliical laboratory compay outside Kyoto Uiversity, Kyoto Medical Sciece Laboratory. The cut-off levels of ati-measles ad ati-rubella atibody titers were set at 6.0 IU/mL ad 8 (dilutio ratio of 1:8), respectively. 23 A HI titer 8 10 correspods to a EIA level of 15 IU/mL. 24 Durig the research period, o icidece of measles or rubella was reported o campus. Statistical aalysis Vaccie coverage, atibody titer levels ad the prevaleces of seropositivity for measles ad rubella were compared betwee the two groups: the target age group ad the otarget age group. The ativirus atibody titers were logarithmically trasformed to be ormalized for statistical tests. For compariso, Studet s t-test was used for cotiuous variables after cofirmatio of ormality, ad Pearso s chi-squared test or Fisher s exact test was used for categorical variables. All tests of sigificace were two-tailed, ad P < 0.05 was cosidered statistically sigificat. Statistical aalysis was doe with STATA 10.0 (STATA, College Statio, TX, USA). Results Studet characteristics A total of 379 eligible studets (129 medical, 202 co-medical, ad 48 pharmaceutical), were ivited to participate, ad 332 who coseted (87.6% i total; 91.6% i the target age group ad 83.0% i the o-target age group, P = 0.011) were erolled i the study. Their characteristics are listed i Table 1. Amog the erollees, 186 studets (56.0%) were i the target age group, 168 of whom (90.3%) had already received the MR-IV vacciatio. The umber of studets i the o-target age group was 146 (44.0%). Iformatio o vacciatio history is summarized i Table 2. A history of at least oe measles vacciatio was slightly more frequet amog studets i the target age group tha i the o-target age group (98.9% vs. 95.4%, P = 0.07). A history of two or more measles vacciatios was sigificatly more frequet amog studets i the target age group tha i the o-target age group (85.2% vs. 20.8%, P < 0.001). A history of at least oe rubella vacciatio i the target age group was sigificatly more frequet tha i the o-target age group (98.9% vs. 77.5%, P < 0.001). A history of two or more rubella vacciatios i the target age group was sigificatly more frequet tha i the o-target age group (54.9% vs. 13.2%, P < 0.001). Ati-measles immue status Ati-measles immue status is summarized i Table 2. The proportio of studets with a history of measles ifectio was ot sigificatly differet betwee the target ad otarget age groups (8.8% vs. 6.3%, P = 0.41). Measles atibody titers were sigificatly higher amog the target age group tha the o-target age group (geometric mea titer, 28.3 [ 1 SD, 13.2; +1 SD, 60.6] vs. 16.8 [ 1 SD, 6.9; +1 SD, 40.8]; P < 0.001). The prevalece of seropositivity agaist measles was also sigificatly higher amog the target age group tha the o-target age group (98.9% vs. 91.0%, P = 0.001). Ati-rubella immue status Ati-rubella immue status is summarized i Table 2. The proportio of studets with a history of rubella ifectio was ot sigificatly differet betwee the two groups (11.0% vs. 9.9%, P = 0.75). Rubella atibody titers were sigificatly higher amog the target age group tha the o-target age group (geometric mea titer, 44.5 [ 1 SD, 17.2; +1 SD, 115.0] vs. 30.8 [ 1 SD, 9.7; +1 SD, 97.8]; P = 0.002). The prevalece of seropositivity agaist rubella was therefore sigificatly higher amog the studets i the target age group tha i the o-target age group (97.8% vs. 87.5%, P < 0.001).
4 Discussio The studets at the target MR-IV age had higher vaccie coverage ad were more frequetly seropositive agaist measles ad rubella tha those 1 year older tha them. Eve though a history of two or more vacciatios for measles ad rubella remaied 85.2% ad 54.9%, respectively, i the target age group, seropositivity agaist measles ad rubella was 98.9% ad 97.8%, respectively, achievig the WHO-recommeded level for disease elimiatio at 95% ad 85%. 3 5 The prevalece of seropositivity agaist measles icreased by 7.9% after this catch-up campaig. This is similar to the icrease i measles immuity i the target age groups observed i previous catch-up campaigs i Eglad ad Wales, the Americas, Australia, ad Korea. 22,25 27 The Miistry of Health, Labor ad Welfare of Japa also set a desired vacciatio coverage of 95% for the two doses to elimiate measles by 2012. The MR-IV coverage of 90.3% i the preset study ad that of 77.3% i the atiowide survey, however, idicate that this level has ot yet bee reached. 28 Further efforts to icrease vaccie coverage should be made by local govermets, by, for istace, periodic moitorig of vaccie coverage ad repeated ivitatios to vacciate those who are uvacciated, alog with close cooperatio with schools ad the board of educatio of local govermets. The proportio of studets with a history of at least oe measles or rubella vacciatio before the MR-IV period was higher i the o-target age group compared to the target age group. A cosiderable umber of the 2008 first-year studets might have received a MR vaccie i 2007 o their ow, followig the iitiative accordig to the social requiremets do so after the measles outbreak i 2006 ad 2007, or i order to stay healthy for their etrace examiatios. I the o-target age group, the seroprevalece for measles did ot reach the WHOrecommeded level, ad the two-dose measles ad rubella vaccie coverage was far from the level demaded by the Japaese govermet. Thus, we still have a problem with isufficiet immuizatio of youth who are ot covered by the MR catch-up campaig. I particular, with regard to the future of health-care professioals, we eed to provide a opportuity for further vacciatio before cliical traiig. I light of the fact that more tha half of the Japaese populatio receives higher educatio, uiversity health services are expected to play a key role i prevetig outbreaks of adolescet ifectious diseases. 29 Their easy access, durig their routie activities, to the immue status of studets from their history of ifectio ad vacciatio, would be the first step. Oe study showed that a questioaire aloe merely provides ureliable iformatio regardig studet immue status. 30 I cotrast, the MCH Hadbook ca provide more objective ad precise iformatio o ifectio ad immue history ad, therefore, should be utilized more. Some potetial limitatios of the curret aalysis must be ackowledged. First, oly the specific ati-viral IgG atibody was measured for immue status. Immuoprophylaxis from ifectious diseases ivolves the humoral, cellular ad mucosal immue systems, ad the ati-viral IgG atibody plays oly a small role i humoral immuity. Atimeasles- ad ati-rubella-specific atibodies, however, have correspoded well with cliical respose to ifectio. 22,27,31 35 Furthermore, because measuremet of the specific ati-viral IgG atibody is a relatively simple ad ecoomical method for ascertaiig immue status compared to other laboratory examiatios, the preset results are easily applicable to cliical ad public health settigs. Secod, there are some ucertaities about the exteral validity of the study results due to potetial selectio bias. Further studies are warrated to ivestigate whether the preset fidigs are applicable to other Japaese uiversities. Third, the participatio rate of the 2008 first-year studets was sigificatly lower tha that of the 2009 first-year studets, which might distort the results. Because the icluded studets were more selective ad might have bee more health-coscious i 2008 tha i 2009, the better immue status of the target age studets may have bee uderestimated. Fourth, we could ot collect photocopies of the MCH Hadbook for co-medical course
5 studets who etered i 2008, which could have caused misclassificatio of immuizatio status. Cosequetly, the vaccie coverage of co-medical studets i the o-target age group could be uderestimated. From aalyzig the data o the specific ati-viral IgG atibody titers ad the vacciatio ad ifectio history amog the 2008 ad 2009 first-year uiversity studets, we coclude that the MR catch-up campaig helped achieve herd immuity ad will cotribute to the elimiatio of measles. Ackowledgmets The authors sicerely thak Professor N. Tsuboyama, Professor S. Kioshita, Professor M. Suzuki, Dr Y. Maeda, Mr N. Matsui, Dr M. Sakuma, Ms Y. Kubota, Mr J. Itoh, Professor A. Akaike, Dr Y. Yao, Ms N. Yoezawa, ad Mr H. Terakawa for settig up the research fields, ad Dr T. Kitamura, Dr T. Ihara, Professor C. Misago, Professor Y. Nakamura ad Dr Y. Takeuchi for geerously providig helpful advice. This study was ot supported by ay exteral fuds. Refereces 1 Terada K. Rubella ad cogeital rubella sydrome i Japa: Epidemiological problems. Jp J. Ifect. Dis. 2003; 56: 81 7. 2 Ifectious Agets Surveillace Ceter. Measles, Japa, 2001 2003. IASR 2004; 25: 62 3 (i Japaese). 3 Aderso RM, May RM. Vacciatio ad herd immuity to ifectious diseases. Nature 1985; 318: 323 9. 4 Scherer A, McLea A. Mathematical models of vacciatio. Br. Med. Bull. 2002; 62: 187 92. 5 Aderso RM. The cocept of herd immuity ad the desig of commuity-based immuizatio programmes. Vaccie 1992; 10: 928 35. 6 WHO Regioal Office for the Wester Pacific. 2004. Field Guidelies for Measles Elimiatio. [Cited November 2013.] Available from URL: http://whqlibdoc.who.it/wpro/2004/929061126x_part2.pdf. 7 Ifectious Agets Surveillace Ceter. Measles, Japa, 2001 2003. IASR 2004; 25: 71 3. 8 Ifectious Agets Surveillace Ceter. Measles atibody prevalece ad vaccie coverage i Japa, 2002: Natioal epidemiological surveillace of vaccie-prevetable diseases. IASR 2004; 25: 71 3 (i Japaese). 9 The Japaese Miistry of Health, Labour ad Welfare. The icidece of measles ad adult measles surveillace accordig to istitutios (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/pdf/meas070727.pdf. 10 Koshida R, Kawashima H, Nakamura H et al. Adult measles outbreak i a college (i Japaese). J. Jp. Pediatr. Soc. 2005; 109: 351 8. 11 Terada K, Kosaka Y, Niizuma T, Ogita S, Kataoka N. Compariso of atibodies ad past history of ifectio ad vacciatio for measles ad rubella of studets eterig colleges or uiversities (i Japaese). J. Jp. Pediatr. Soc. 2006; 110: 767 72. 12 Coh ML, Robiso ED, Faerber M et al. Measles vaccie failures: Lack of sustaied measles-specific immuoglobuli G resposes i revacciated adolescets ad youg adults. Pediatr. Ifect. Dis. J. 1994; 13: 34 8.
6 13 Böttiger M, Christeso B, Romaus V, Tarager J, Stradell A. Swedish experiece of two dose vacciatio programme aimig at elimiatig measles, mumps, ad rubella. Br. Med. J. (Cli. Res. Ed.) 1987; 295: 1264 7. 14 Peltola H, Heioe OP, Valle M et al. The elimiatio of idigeous measles, mumps, ad rubella from Filad by a 12-year, two-dose vacciatio program. N. Egl. J. Med. 1994; 331: 1397 402. 15 Ly TV, Beller M, Fuk EA et al. Icremetal effectiveess of 2 doses of measlescotaiig vaccie compared with 1 dose amog high school studets durig a outbreak. J. Ifect. Dis. 2004; 189: S86 90. 16 Yeug LF, Lurie P, Daya G et al. A limited measles outbreak i a highly vacciated US boardig school. Pediatrics 2005; 116: 1287 91. 17 Natioal Istitute of Ifectious Disease. Weekly measles cases from week 1 to week 52 i 2008 (based o diagosed week as of Jauary 7) (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/2008pdf/meas08-52- 01.pdf. 18 Natioal Istitute of Ifectious Disease. Weekly measles cases from week 1 to week 53 i 2009 (based o diagosed week as of Jauary 6) (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/2009pdf/meas09-53.pdf. 19 Natioal Istitute of Ifectious Disease. Weekly measles cases from week 1 to week 52 i 2010 (based o diagosed week as of Jauary 7) (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/2010pdf/meas10-52.pdf. 20 Natioal Istitute of Ifectious Disease. Weekly measles cases from week 1 to week 52 i 2011 (based o diagosed week as of Jauary 5, 2012) (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/2011pdf/meas11-52.pdf. 21 Okabe N. Measles virus preset epidemiological situatio o measles, ad measures for elimiatio i Japa. Virus 2007; 57: 171 80 (i Japaese). 22 Gay N, Ramsay M, Cohe B et al. The epidemiology of measles i Eglad ad Wales sice the 1994 vacciatio campaig. Commu. Dis. Rep. CDR Rev. 1997; 7: 17 21. 23 Iida K, Wakabayashi K, Mochida Y, Toriumi K. A compariso of measurig methods of measles, mumps, rubella ad varicella atibodies accordig to the results of ivestigatios i 1993 ad 2005. I: XXXX (eds) Refereces About Vaccie, 36th ed. Foudatio of Vacciatio Research Ceter, XXX, 2006; 67 71. 24 Skedzel LP. Rubella immuity. Am. J. Cli. Pathol. 1996; 106: 170 74. 25 de Quadros CA, Olive JM, Hersh BS, Mark A. Measles elimiatio i the Americas. Evolvig strategies. JAMA 1996; 275: 224 9. 26 Turbull FM, Burgess MA, McItyre PB et al. The Australia measles cotrol campaig, 1998. Bull. World Health Orga. 2001; 79: 882 8.
7 27 Kim SS, Ha HW, Go U, Chug HW. Sero-epidemiology of measles ad mumps i Korea: Impact of the catch-up campaig o measles immuity. Vaccie 2004; 23: 290 97. 28 Natioal Istitute of Ifectious Disease. Periodic measles ad rubella vaccie coverage rate fial results i 2008 (i Japaese). [Cited November 2013.] Available from URL: http://idsc.ih.go.jp/disease/measles/pdf02/20090812-05.pdf. 29 The Japaese Miistry of Educatio, Culture, Sports, Sciece, ad Techology. Aual report of the Japaese Miistry of Educatio, Culture, Sports, Sciece, ad Techology (i Japaese). [Cited November 2013.] Available from URL: http://www.mext.go.jp/b_meu/toukei/001/04073001/001.htm. 30 Maago K, Yoshiaga M, Nishi J, Miyaohara H, Maeo N, Oda H. The positive rate of atibodies agaist measles, chickepox, rubella, ad mumps i medical studets, ad a study about the availability of questioaires as measures agaist hospital ifectio (i Japaese). Kakyoukase 2004; 19: 471 4. 31 Gustafso TL, Lieves AW, Bruell PA, Moelleberg RG, Buttery CM, Sehulster LM. Measles outbreak i a fully-immuized secodary school populatio. N. Egl. J. Med. 1987; 316: 771 4. 32 Whittle HC, Aaby P, Samb B, Jese H, Beett J, Simodo F. Effects of subcliical ifectio o maitaiig immuity agaist measles i vacciated childre i West Africa. Lacet 1999; 353: 98 101. 33 Samb B, Aaby P, Whittle HC et al. Serologic status ad measles attack rates amog vacciated ad uvacciated childre i rural Seegal. Pediatr. Ifect. Dis. J. 1995; 14: 203 9. 34 Lee MS, Nokes DJ, Hsu HM, Lu CF. Protective titers of measles eutralizig atibody. J. Med. Virol. 2000; 62: 511 17. 35 Orestei WA, Strebel PM, Hima AR. Buildig a immuity fece agaist measles. J. Ifect. Dis. 2007; 196: 1433 5.
8 Table 1 Subject characteristics Total Target MR-IV age No-target age group Male 137 (41.3) 332 82 (44.1) 186 55 (37.7) 146 0.24 Age (years), media (IQR) 18.6 18.5 18.8 331 185 (18.4 18.9) (18.5 18.6) (18.7 18.8) 146 <0.001 Available iformatio Ativiral atibody titers 327 (98.5) 332 183 (98.4) 186 144 (98.6) 146 1.00 Questioaire 319 (96.1) 332 181 (97.3) 186 138 (94.5) 146 0.26 Photocopy of MCH Hadbook 242 (72.9) 332 179 (96.2) 186 63 (43.2) 146 <0.001 Actual vacciatio i the MR-IV period 168 (90.3) 186 MCH, materal ad child health; MR-IV, phase 4 measles/rubella-combied vacciatio at age 17 18 years. P Table 2 Immue status Target MR-IV age No-target age group History of measles ifectio 16 (8.8) 182 8 (6.3) 127 0.41 History of at least oe measles vacciatio before MR-IV period 160 (87.9) 182 124 (95.4) 130 0.02 History of two or more measles vacciatios before MR-IV period 10 (5.5) 182 27 (20.8) 130 <0.001 History of at least oe measles vacciatio icludig MR-IV period 180 (98.9) 182 124 (95.4) 130 0.07 History of two or more measles vacciatios icludig MR-IV period 155 (85.2) 182 27 (20.8) 130 <0.001 Atibody titer for measles (IU/mL) 28.3 (13.2, 60.6) 183 16.8 (6.9, 40.8) 144 <0.001 Immuopositivity agaist measles 181 (98.9) 183 131 (91.0) 144 0.001 History of rubella ifectio 20 (11.0) 181 12 (9.9) 121 0.75 History of at least oe rubella vacciatio before MR-IV period 107 (58.8) 182 100 (77.5) 129 0.001 History of two or more rubella vacciatios before MR-IV period 9 (4.9) 182 17 (13.2) 129 0.01 History of at least oe rubella vacciatio icludig MR-IV period 180 (98.9) 182 100 (77.5) 129 <0.001 History of two or more rubella vacciatios icludig MR-IV period 100 (54.9) 182 17 (13.2) 129 <0.001 Atibody titer for rubella (IU/mL) 44.5 (17.2, 115.0) 183 30.8 (9.7, 97.8) 144 0.002 Immuopositivity agaist rubella 179 (97.8) 183 120 (87.5) 144 <0.001 Geometric mea titer ( 1 SD, +1 SD); tested after logarithmic trasformatio. MR-IV, phase 4 measles/rubella-combied vacciatio at age 17 18 years. P