Journal of Medical Virology 84:548–550 (2012)

Rubella Immune Status Among Immigrant andNonimmigrant Women in Spain

J.M. Ramos,1* A. Milla,2 J.C. Rodrıguez,3 and F. Gutierrez1,4

1Infectious Diseases Unit, Hospital General Universitario de Elche, Alicante, Spain2Service of Obstetrics and Gynecology, Hospital General Universitario de Elche, Alicante, Spain3Section of Microbiology, Hospital General Universitario de Elche, Alicante, Spain4Department of Clinical Medicine, Universidad Miguel Hernandez, Elche, Alicante, Spain

A cross-sectional study of seroprevalence ofrubella antibodies was carried out in allimmigrant pregnant women (1,627) fromFebruary 2006 to June 2010. For each immi-grant woman one Spanish pregnant womanwas recruited. The seroprevalence of IgG anti-bodies against rubella in immigrant womenwas 92% (95% confidence interval [CI]: 90.4–93.3), and in native women was 97.7% (95%CI:96.7–98.4) (P < 0.001). Immunity against waslowest among women from Latin America(odds ratio [OR]: 0.17), followed by womenfrom Asia (OR: 0.20), Sub-Saharan Africa(OR: 0.27) and Northern Africa (OR: 0.37).Female immigrants from developing countriesshould be targeted for immunization to reducethe risk of congenital rubella. J. Med. Virol.84:548–550, 2012. � 2012 Wiley Periodicals, Inc.

KEY WORDS: rubella; pregnant women;immigrants; vaccination;prevention

INTRODUCTION

Rubella causes damage in the developing fetus andproduces a congenital rubella syndrome, if the infec-tion is acquired in the first 16 weeks of pregnancy[Robinson et al., 2006]. Rubella immunization is effec-tive in preventing congenital rubella syndrome, andsince 1974 it has been increasingly used in developedcountries [Sheridan et al., 2002]. Most cases of rubellareported over the last few years in developed coun-tries have been in immigrants from African or Asiancountries with no rubella immunization programs[Anonymous, 2006].

The large wave of immigration in Spain has oc-curred within the last 10 years. Between 1998 and2009, the number of foreigners registered in Spainhas grown more than 10 times, from 637,058 to6,466,278, which in 2009 accounted for 13.8% of the

total Spanish population. Of the immigrant popula-tion, 2.35 million were born in the European Union,1.73 million came from Latin America, 1.04 millionfrom Africa, and 323,000 from Asia [Instituto Nacio-nal de Estadıstica, 2010]. Information on seropreva-lence of rubella IgG antibodies among immigrantpregnant women is important to design targetedstrategies aimed to prevent congenital rubella. Threesurveys have shown that overall rubella susceptibilityin pregnant women from low-income countries ishigher than in native women [Dominguez et al., 2007;McElroy et al., 2009; Vargas-Leguas et al., 2009].However, data analyzing the susceptibility to rubellain immigrant pregnant women from different geo-graphical regions are lacking. The objective of thisstudy was to investigate the prevalence of immunestatus in immigrant pregnant women in EasternSpain according to countries of origin.

METHODS

From January 2006 to May 2010, a cross-sectionalstudy was conducted in all pregnant women attendedat Hospital General Universitario de Elche, Alicante,a general medical center located in the MediterraneanCoast of Spain. During the study period, the hospitalprovided medical care to 290,481 inhabitants, fromthree municipalities, distributed in 11 Primary CareCenters. A total of 44,341 women were foreign: 12,955from Latin America and The Caribbean (29.9%),11,271 from Western Europe (25.4%), 9,330 fromEastern Europe (2%), 7,508 from Northern Africa(16.9%), 1,666 from Sub-Saharan Africa (3.7%), and

Declaration of interest: None.

*Correspondence to: J.M. Ramos, MD, Infectious DiseasesUnit, Hospital General Universitario de Elche, Camino de laAlmazara 11, 03203 Elche, Alicante, Spain.E-mail: jramosrincon@yahoo.es

Accepted 17 October 2011

DOI 10.1002/jmv.23195Published online in Wiley Online Library(wileyonlinelibrary.com).

� 2012 WILEY PERIODICALS, INC.

1,611 from Asia (3.6%). All immigrant women attend-ing the antenatal clinic during the weeks previous todelivery were invited to participate and wererecruited in a consecutive manner (migrant group).For each immigrant enrolled, one Spanish pregnantwoman with the same age attending in the same daywas recruited (Spanish control group). Blood samplesfor rubella virus IgG antibody testing were taken inthe trimester term of gestation for antenatal routineexamination in Primary Care Centers. The study wasapproved by the local Ethics Committee, and all thepatients gave their informed consent.

The detection of IgG antibodies against rubella wasperformed by enzyme immunoassay (Enzygnost Anti-Rubella-Virus/IgG, Siemens, Marburg, Germany)according to the manufacturer’s instructions. Rubellavirus IgG concentrations of �5 IU/ml were considerednegative, those between 5 and 10 IU/ml were consid-ered indeterminate or equivocal, and those of �10 IU/mlwere considered positive. The indeterminate resultswere excluded of the analysis. Estimates of the preva-lence were obtained with confidence intervals (CI) of95% by the method of Newcombe (1998). The oddsratio (OR) with 95% of CI of each group of migrantswith respect to the Spanish group (reference group)was calculated.

RESULTS

A total of 1,627 migrant pregnant women partici-pated in this study. The pregnant were from LatinAmerican and The Caribbean (564; 34.6%), NorthernAfrica and Middle East (550; 33.8%), Eastern Europe(288; 15.7%), Sub-Saharan Africa (99; 6.1%), Asia (77;4.7%), and Western Europe (49; 3.0%). The mean agewas 28.4 years (range: 15–45 years). The mean timeelapsed from arrival to Spain to consultation at the

antenatal clinic was 48 months (range: 1 week to 170months).

From 1,627 immigrant women, the serology of ru-bella virus infection was performed in 1,431 (88%).The percentage was similar than in the control group(87.8%: 1,429 from 1,627 native pregnant women). Atotal of 1,313 samples were positive for rubella anti-bodies in immigrant women, a prevalence of 91.8%(CI 95%: 90.2–93.1) and 4 (0.2%) samples were consid-ered indeterminate results. The prevalence of antibod-ies was 96.8% (CI 95%: 95.8–97.7) (1,384 from 1,429)in the native women (P < 0.001). Twelve (0.8%) sam-ples of native women were considered indeterminateor equivocal. Seroprevalence in pregnant women fromLatin American (87.6%), Asia (89.6%), Sub-SaharanAfrica (92.3%), and Northern Africa (93.9%) was sig-nificantly lower than in Spaniards (OR: 0.17; 0.20;0.27, and 0.37, respectively), while in Eastern andWestern Europe pregnant women it was similar tothe native women (Table I). Among Latin Americanpregnant women, those from Ecuador, Paraguay, andColombia had a seroprevalence lower than 86%, while93.5% of the Argentinean women were immune, a pro-portion not significantly different from Spaniards(Table I).

DISCUSSION

This study found that the rates of rubella immunityare lower among immigrant women than amongSpanish native population. Other studies performedin Spain and other Western countries have alsorecorded a lower rate of rubella antibodies among mi-grant pregnant women than among native popula-tions [Dominguez et al., 2007; McElroy et al., 2009;Vargas-Leguas et al., 2009]. This study found that therates of rubella immunity were lower in women from

TABLE I. Seroprevalence of IgG Anti-Rubella Virus Antibodies in Immigrant and Native Pregnant Women

No positive/nototal screened Prevalence (95% CI) ORa (95% CI)

All migrants 1,313/1,427 92.0 (90.4–93.3) 0.27 (0.19–0.41)Spaniards 1,384/1,417 97.7 (96.7–98.4) 1Geographical regionNorthern Africa and Middle East (þ) 465/495 93.9 (91.4–95.8) 0.37 (0.22–0.61)Latin America and the Caribbean 424/484 87.6 (84.3–90.3) 0.17 (0.11–0.26)Eastern Europe (f) 244/253 96.4 (93.1–98.3) 0.59 (0.28–1.2)Sub-Saharan Africa (z) 84/91 92.3 (84.3–96.6) 0.27 (0.13–0.65)Asia (f) 60/67 89.6 (79.1–95.3) 0.20 (0.09–0.47)Western Europe (d) 36/37 97.3 (84.2–99.9) 1.4 (0.86–5.0)Latin American countriesColombia 123/143 86.0 (78.9–91.0) 0.41 (0.14–1.2)Ecuador 101/120 84.2 (76.1–90.0) 0.35 (0.12–1.05)Argentina 60/64 93.8 (84.0–98.0) 1Paraguay 35/41 85.4 (70.1–93.9) 0.38 (0.11–1.3)Bolivia 27/30 90.0 (72.3–97.4) 0.60 (0.13–2.6)

OR: Odds ratio; CI confidence interval.aThe reference group of OR was Spaniards, and in Latin American countries the reference group was Argentina. (þ) Main country of birth ofscreened women was Morocco (n ¼ 446); (f) main country of screened women was Romania (n ¼ 189); (z) main country of birth of screenedwomen was Nigeria (n ¼ 40); (f) main country of birth of screened women was China (n ¼ 65); (d) and main country of birth of screenedwomen was United Kingdom (n ¼ 9).

Rubella Immune Status Among Immigrant Pregnant in Spain 549

J. Med. Virol. DOI 10.1002/jmv

Latin America, Northern Africa, Asia, and Sub-Saharan Africa. These results are in line with thosefound in another survey conducted in Catalonia,Spain, in 2003, where the prevalence of antibodieswas inferior in women from America, Africa and Asiathan in Spaniards. However, in a more recent studyperformed in Barcelona city, Vargas-Leguas et al.(2009) found a higher susceptibility in women fromAfrica than in those coming from Latin America. Var-iations in the profile of the immigration populationmay probably account for these differences.

The seroprevalence of rubella antibodies among mi-grant women in Spain reflects the prevalence of rubel-la antibodies in their countries of birth, because theimmigration in Spain is a recent fact. In survey stud-ies carried out in Latin America, the seroprevalencevaries from 85 to 93%, it is higher in Argentina thanin other countries [Dayan et al., 2005]. The higher ru-bella susceptibility found in people from low-incomecountries explains rubella outbreaks in developedcountries [Robinson et al., 2006; Vargas-Leguas et al.,2009]. In Spain, Carnicer-Pont et al. (2008) presentedseveral congenital rubella cases, most of them involv-ing in immigrant. In the outbreak of Madrid, in 2005,about half of the patients were female at childbearingage and there were four cases of congenital rubella[Garcia, 2005]. A total of 13 congenital rubella birthshave been reported in Spain from 1997 to 2005. Theplace of births of the mothers was retrieved in eightcases; six cases occurred in newborns from immigrantmothers (three from Latin America, two from Africaand one from the Philippines) [Carnicer-Pont et al.,2008]. Therefore, the risk of congenital rubella syn-drome is real in Spain, especially in the case ofmothers from Latin America, and Africa. The mainstrategies to prevent congenital rubella were highlightedin a review by Sheridan et al. (2002). Measures shouldinclude postpartum vaccination of seronegativeswomen, vaccination of women at childbearing age oradolescents when they consult the health care cen-ters, and the vaccination of immigrants in case of out-breaks concentrated in immigrant population.

In summary, rubella should be considered animported infection in the developed world. Fertilefemale immigrants coming from Latin America,Northern Africa, Asia, and Sub-Saharan Africa are at

higher risk of developing rubella than native Spanish.Implementation of strategies to prevent rubella infec-tion in these populations is critical to reduce the riskof congenital rubella.

ACKNOWLEDGMENTS

We thank midwives of the Health Department ofHospital General Universitario de Elche for theirassistance in collecting the data and samples ofpatients, especially to Ms. Paqui Rodrigo.

REFERENCES

Anonymous. 2006. Global distribution of measles and rubella geno-types—Update. Wkly Epidemiol Rec 81:474–479.

Carnicer-Pont D, Pena-Rey I, de Aragon VM, de Ory F, DominguezA, Torner N, Cayla JA. Regional Surveillance Network. 2008.Eliminating congenital rubella syndrome in Spain: Does massiveimmigration have any influence? Eur J Public Health 18:688–690.

Dayan GH, Panero MS, Urquiza A, Molina M, Prieto S, Del CarmenPerego M, Scagliotti G, Galimberti D, Carroli G, Wolff C, Bi D,Bellini W, Icenogle J, Reef S. 2005. Rubella and measles sero-prevalence among women of childbearing age, Argentina, 2002.Epidemiol Infect 133:861–869.

Dominguez A, Plans P, Espunes J, Costa J, Torner N, Cardenosa N,Plasencia A, Salleras L. 2007. Rubella immune status of indige-nous and immigrant pregnant women in Catalonia, Spain. Eur JPublic Health 17:560–564.

Garcia L, Red de Vigilancia Epidemiologica de la Comunidad deMadrid (Epidemiological Surveillance Network of the AutonomousRegion of Madrid). 2005. Outbreak of rubella in Madrid region ofSpain 2005. Eurosurveillance 10:E050707.2. Available online:http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId¼2742.

Instituto, Nacional de Estadıstica. Avance del Padron Municipala 1 de enero 2010. 2010. http://www.ine.es/prensa/np595.pdf.Accessed 1 May 2010.

McElroy R, Laskin M, Jiang D, Shah R, Ray JG. 2009. Rates of ru-bella immunity among immigrant and non-immigrant pregnantwomen. J Obstet Gynaecol 31:409–413.

Newcombe RG. 1998. Two-sided confidence intervals for the singleproportion: Comparison of seven methods. Statist Med 17:857–872.

Robinson JL, Lee BE, Preiksaitis JK, Plitt S, Tipples GA. 2006.Prevention of congenital rubella syndrome—What makes sensein 2006? Epidemiol Rev 28:81–87.

Sheridan E, Aitken C, Jeffries D, Hird M, Thayalasekaran P. 2002.Congenital rubella syndrome: A risk in immigrant population.Lancet 359:674–675.

Vargas-Leguas H, Campins Martı M, Juste C, Sanchez C, MartınezGomez X, Hermosilla Perez E, Cabero Roura L. 2009. [Rubellasusceptibility of immigrant pregnant women in Catalonia] Sus-ceptibilidad a la rubeola en gestantes inmigrantes con residenciaen Cataluna. Med Clin (Barc) 132:344–347.

550 Ramos et al.

J. Med. Virol. DOI 10.1002/jmv