Abstract
The present study was performed to determine the seroprevalence of IgG measles antibodies in Dongguan residents (irrespective of vaccination status), to analyze the changes in age-related serological susceptibility patterns. A total of 1960 residents aged 0–60 years and 315 mother–infant pairs were studied. Serum IgG antibodies against measles virus were measured by ELISA. The overall seroprevalence was 93.4% in the general population in Dongguan, China. In subgroups aged 1–29 years who were likely vaccinated, there was a declining trend of seropositivity with age from 98.6% at 1–4 years to 85.7% at 20–29 years (P < 0.0001). Seroprevalence were near or >95% in the older population (30–39 years and ≥40 years) who had not been immunized against measles. Age and sex were independent factors associated with seropositivity. Seroprevalence in pregnant women and their newborns was 87.0% and 84.1%, respectively. Our results suggest that the waning vaccine-induced immunity may be the main cause of increased serological susceptibility in young adults and young infants. An additional vaccination strategy that targets young adults is important for elimination of measles.
Introduction
Resurgence of measles in recent years has disrupted the drive to eliminate the disease in China. As a member of the World Health Organization (WHO) Western Pacific Region, China had targeted measles for elimination by 2012. The national government has made major efforts to eliminate measles by sustaining high two-dose measles vaccination coverage (>95%), implementing supplementary immunization activities (SIAs), and maintaining an effective surveillance system.Citation1
Measles vaccine was introduced in China in 1967, and routine administration (corresponding to WHO Expanded Program on Immunization) in 1981–1984. Two doses of measles vaccine–the first at 9–12 mo and the second at 7 y–were introduced in 1985.Citation2 The age for the second dose was lowered to 4 y in 2000 (measles-containing vaccine (MCV), such as measles–mumps–rubella (MMR) vaccine, or measles–rubella (MR) vaccine, has also been recommend since then), and then lowered to 18–24 mo in 2006.Citation3
In Guangdong province, routine measles vaccination was implemented in 1981 and coverage has been maintained at >85%, which is similar to the historical changes in vaccination strategies at a national level. In 2000 the measles vaccine coverage rate reached 95.9%. The annual incidence was 4.35 per 100 000 population during 1987–2000, and the lowest annual incidence was 1.32 per 100 000 population in 1999.Citation4 The annual incidence was under 5.0 per 100 000 population during 2001–2003.Citation5 However, increased incidence rates have been reported since 2004 (8.66, 12.54, 15.10, 21.20, 16.10 per 100 000 during 2004–2008). The increase in measles incidence has been accompanied by significant changes in epidemiological characteristics such as age distribution. Infants <1 y have become the most vulnerable population. Also, the incidence in people aged 15–35 y has been high, accounting for 23.31% of the total number of cases.Citation6 These results imply that the age-related susceptibility pattern for measles has changed. Age-related susceptibility pattern in the population is an important factor in determining measles vaccination strategy. A serological survey was conducted in Dongguan city, Southern Guangdong province, which has 7.8 million registered inhabitants. The prevalence of seropositivity for measles in the general population and pregnant women and their offspring was analyzed according to age. The findings from this study should provide useful information to identify the subpopulation at risk and address possible additional immunization strategies.
Results
Demographics
A total of 1969 individuals (952 [48.6%] male and 1008 [51.4%] female) in Dongguan city aged 0–60 y were enrolled in the seroprevalence study. The birth cohorts, vaccination doses, and vaccination coverage by age groups are shown in .
Table 1. History of measles immunization in Dongguan, PR China
Adequate specimens (n = 1960) were obtained and anti-measles IgG testing was completed. There were 639 (32.6%) children and students, 599 (30.6%) workers and 202 (10.3%) farmers. Education status was low (primary school or below) in 704 (35.9%) individuals, middle level (high school) in 1033 (52.7%), and high (college or graduate school) in 223 (11.4%). For marital status, 1163 (59.3%) individuals were married, 780 (39.8%) were unmarried, and 17 (0.9%) had other status. Three hundred and seventy-two individuals (19.0%) recalled that they had received two doses of MCV, 82 (4.2%) had received one dose of MCV, and 1506 (76.8%) had not received measles vaccination or were unclear about it. There were 954 (48.7%) local residents and 1006 (51.3%) immigrants ().
Table 2. Demographic characteristic of the subjects
Prevalence of seropositivity for measles in the general population
The median anti-measles antibody titer was 1350.35 mIU/mL (interquartile range: 734.64–2455.96 mIU/mL). The titer differed among the age groups (χ2 = 91.889, P < 0.001). Older individuals (age ≥30 y) who acquired infection tend naturally to have higher titers than younger individuals (age <30 y) who were likely to have acquired their immunity from vaccination (1441.53 mIU/Ml, interquartile range: 873.58–2449.03 mIU/mL vs. 1234.58 mIU/Ml, interquartile range: 613.59–2408.35 mIU/mL; Z = 3.941, P < 0.001).
A total of 1830 individuals were positive for measles antibodies, giving a seroprevalence of 93.4% (95% confidence interval [CI]: 92.3–94.5%); 76 individuals were equivocal (3.9%, 95% CI: 3.0–4.8%); and 54 were negative (2.8%, 95% CI: 2.0–3.5%) for measles antibodies. Seropositivity differed among the age groups (χ2 = 67.669, P < 0.001): 5 age groups (1–4, 5–9, 10–14, 30–39, and ≥40 y) had seropositivity rates >90%, and 3 groups (<1, 15–19, and 20–29 y[s]) had seropositivity rates <90%. In children <1 y, 85.2% were found to be seropositive. Seroprevalence rates significantly increased in children aged 1–4 y (98.6%). Then, there was a decrease in seroprevalence until age 20–29 y (χ2 linear = 39.68, P < 0.001). Seroprevalence rates significantly increased to 94.7% and 97.6% in the 30–39 and ≥40 y age groups, respectively ().
Table 3. Measles seroprevalence in general population in Donguan, by age group and sex (%)
The proportion of equivocal sera was unevenly distributed by age group, increasing steadily from 1 y to 20–29 y (1.4% to 8.8%) (χ2 linear = 25.06, P < 0.001). In the 20–29 y age group, the proportion of equivocal sera was significantly higher than that observed in all the other age groups (P < 0.001). By contrast, <3% of adults aged ≥30 y had equivocal results ().
Factors associated with measles seroprevalence in the general population
The seropositive rate in females was 95.3% (961/1008), which was higher than that in males (91.3% [869/952]) (odds ratio [OR] = 1.95, 95% CI: 1.35–2.83; χ2 = 13.005, P < 0.001). Seropositivity was higher in people who had a history of measles vaccination than in those without vaccination or who were unclear of their vaccination status (OR = 1.82, 95% CI: 1.11–3.00; χ2 = 5.716, P = 0.017). Education status was associated with seropositivity (χ2 = 17.335, P < 0.001). There was no significant association between occupation, marital status, and residential status and anti-measles antibody positivity (P > 0.05) ().
Table 4. Unadjusted (univariate analysis) and adjusted odds ratio (multivariate analysis) and 95% CI for seroprevalence of measles by demographic characteristics in the general population
Multiple logistic regression models were used to control potential confounders, which showed that there was a significant association between measles seroprevalence and sex and age group. Compared with males, the females were more likely to have higher seropositivity to measles virus (OR = 2.18, P < 0.001). Four age groups had a lower chance of being seropositive (compared with >40 y: <1 y, OR = 0.11, P = 0.011; 10–14 y, OR = 0.22, P = 0.009; 15–19 y, OR = 0.20, P < 0.001; 20–29 y, OR = 0.15, P < 0.001). Variance inflation factor (VIF) was used to check for multi-colinearity. None of the VIF values was up to 5, which meant there was no colinearity in the model ().
Prevalence of antibody against measles in pregnant women and their offspring
Sera from 315 mother–infant pairs were examined for anti-measles antibody titer. The mean age of these pregnant women was 26.55 ± 4.97 y (range: 17–45 y), and most were aged 20–29 y (n = 215, 68.3%).
The median anti-measles antibody titer was 925.10 mIU/mL (interquartile range: 359.93–1979.09 mIU/mL) in the pregnant women, and 995.89 mIU/mL (interquartile range: 371.96–2453.57 mIU/mL) in their newborn infants. Two hundred and 74 (87.0%) pregnant women had protective levels of measles antibodies; 33 (10.5%) were negative; and 8 (2.5%) were equivocal. Antibody seroprevalence in the newborns was 84.1% (n = 265), 36 (11.4%) were negative, and 14 (4.4%) were equivocal. A significant correlation was observed between anti-measles antibody titer in newborn infants and their paired mothers (r = 0.440, P < 0.0001).
Anti-measles antibody seropositivity in pregnant women was significantly lower than in women of childbearing age (20–39 y. in China, the conventional childbearing age is 20–39 y of age due to legitimate marriage age [20 for women, the Law of Marriage of People’s Republic of China, amended on April. 28, 2001]) (χ2 = 8.217, P = 0.004). Pregnant women were divided into 3 groups according to age (<20 y, 20–29 y, ≥30 y). Age did not significantly influence the seroprevalence of the antibodies in pregnant women (χ2 = 1.796, P = 0.407) ().
Table 5. Measles seroprevalence in the pregnant women and newborn infants (%)
Discussion
The results of our study showed a total seropositivity of 93.4% in the general population in Dongguan, which demonstrates that the population immunity is insufficient to achieve measles elimination. Similar results have been reported in other recent seroepidemiological studies of measles in China.Citation7,Citation8
Measles elimination is feasible and practical.Citation9 However, the goal of elimination can only be achieved when the population susceptibility is below the level that can sustain transmission. Thus, 95% population immunity is necessary to interrupt transmission and eliminate measles.Citation1
Seroprevalence study results may help to evaluate the age-specific or population-specific serological susceptibility (people with anti-measles antibody titer under positive cut-off value) profile of measles. In our study, when considering age group, seroprevalence in children aged 1–4 and 5–9 y was >95%, which may have been due to both the effect of routine measles vaccination and SIAs. Since 1987 the coverage rate for first-dose MCV has been maintained at a high level, and second-dose MCV has also reached the 95% level since 2000 in Dongguan.Citation5 In 2009, a catch-up SIA that targeted all children aged 9 mo–14 y was conducted in Dongguan, in which the coverage rate was 98.1%.Citation10 Children and young adults may be more likely to benefit from these vaccination activities. Seroprevalence was relatively high in participants aged ≥30 y, who were born before routine vaccination against measles. In the pre-vaccination era, the average annual incidence of measles was 639.10 per 100 000 population in Guangdong provinceCitation4; nearly everyone had acquired measles in childhood and therefore were more likely to have acquired immunity from natural infection.
People born after 1981 (age <30 y) were more likely to have received routine measles vaccination. Three age groups (<1, 15–19, and 20–29 y) had comparatively low rates of anti-measles antibody positivity. The data from pregnant women and their newborns are consistent with these findings. After controlling for potential risk factors, people in these 3 age groups were more likely have lower rates of anti-measles antibody positivity than those aged ≥40 y (people born before 1970 acquired immunity from natural infection). The apparently low positive rate in these age groups may be explained by the ‘equivocal group’Citation11. Similar to previous studies, our data showed that the equivocal rate was high in the vaccinated age groups,Citation12,Citation13 and in participants aged 1–29 y, a decrease in seroprevalence with age, along with an increase in the proportion of individuals with equivocal titers, which is probably explained by lower antibody titer after vaccination (or more rapid antibody loss) than after natural infection.Citation12 Anti-measles antibody titer in newborn infants was significantly correlated with the anti-measles antibody level in their mothers. Nowadays, in China, more mothers who acquired immunity from vaccination in childhood, which resulted in attenuation of protective antibody titer, passed on to their offspring less passive protection against the measles virus in the first year of life. These findings provide seroepidemiological evidence for the shift in age distribution of measles cases in recent years in our area.
We agree with Chen et al., who suggested that the waning vaccine-induced immunity may have some impact on the control of measles.Citation12 This hypothesis may be proved indirectly by measles outbreaks or epidemics still occurring in communities with high measles vaccine coverage.Citation14 In a country or an area with high measles vaccination coverage and low incidence of measles, people have less chance to acquire enhanced immunity from natural infection. The lost opportunity for enhanced immunity from natural infection, combined with waning of immunity from vaccination may have contributed to the increase in measles susceptibility in young adults and infants. An increasing number of mothers acquire immunity against measles by vaccination rather than natural infection. Together with increasing maternal age at delivery, newborns in the future could acquire fewer antibodies from their mothers. This could increase the disease burden of measles in this subpopulation. Some researchers have suggested that the time of administering the first vaccine dose should be advanced.Citation15,Citation16 However, other studies have reported that vaccination in younger infants (6–9 mo) usually results in lower seroconversion rates and neutralizing titers compared with immunization in older infants (12–15 mo).Citation17 In China, the first dose of measles vaccine is offered at 9 mo of age. The number of cases of measles in infants aged <9 mo is high and increases markedly after the infants reach 6 mo of age.Citation14 Therefore, we suggest that in addition to maintenance of optimum routine vaccination coverage, it is necessary to administer additional vaccination to susceptible young adults. This will have the benefits of protecting susceptible young adults as well as infants who are below the measles vaccination age.
Our results showed that women had higher seropositivity rates than men. Similarly, Kelley et al. conducted a national serological survey of US Army recruits and found lower susceptibility to measles in women.Citation18 Hutchins et al. reported that among persons born in the vaccine era, male sex was an independent predictor of measles susceptibility.Citation19 The higher seropositivity in women might be partly due to sex differences in the humoral antibody response to measles vaccine.Citation20 However, inconsistent results have been reported in previous studies. Castro et al. conducted serological surveillance of measles in blood donors in Rio de Janeiro, Brazil. The results showed that women had a higher proportion of seronegative results than men had.Citation21 In a seroepidemiological study in Southern China in 2008, Fu et al. also found that men had higher levels of measles IgG than women had.Citation22 In a seroprevalence survey of measles in a multinational healthcare workforce in Saudi Arabia, Almuneef et al. demonstrated that there was no significant different between men and women with regard to immunity to measles.Citation23 This inconsistency may be partly explained by difference in measles infection and vaccination histories in different study populations.
There were some limitations to the present study. First, the proportion who reported a history of measles vaccination was small, which could have led to bias in the analysis of the effect of the vaccine. Second, our study was conducted just after an epidemic of measles and SIAs in the area, and the natural infection and immunity acquired from SIAs could have affected the seroprevalence in the population. Our results cannot show the age-specific serological susceptibility profile before the epidemic. However, the measles antibodies prevalence was low in young adults and young infants even in this situation, and the results confirm the high burden of disease in these populations during measles outbreaks.
In conclusion, our study revealed that young adults and infants aged <1 y had low rates of measles seropositivity, which may have resulted from waning vaccine-induced immunity. Therefore, in communities with high measles vaccine coverage and low incidence, adult susceptibility to measles could increase with time. Consequently, infants born to mothers vaccinated in childhood may acquire a relatively small amount of maternal anti-measles antibody and may lose immunity to measles before the age of vaccination. Immunization before 9 mo of age is not systematically recommended because of immature humoral immune responses in infants.Citation24 Thus, we suggest that in addition to maintenance of optimum routine vaccination coverage, additional vaccination of susceptible young adults should be considered, especially in women before pregnancy.
Materials and Methods
Study design
A multistage cluster sampling design was used. The 33 towns in Dongguan were stratified into 5 regions (east, south, central, west, and north) to account for variations in geographic status. One town in each region was sampled at random. Two villages in each town were selected randomly. Our study frame consisted of 10 randomly chosen villages with a total of 42 325 households previously enumerated by Dongguan Center for Disease Control and Prevention (CDC). One hundred and 50 households were randomly chosen within each village, with a total of 3663 individuals in 1461 households from which eligible subjects (age ≤60 y) were invited to participate, 1969 (53.8%) eventually participated by filling out a questionnaire and by donating a single blood sample. The main reason for refusal to participate was unwillingness to donate a blood sample. There was not significant difference in demographic data (such as sex, occupation, education status, marital status, residential status, MCV history, and age distribution) in the two groups (participants vs. those who refused). These 1969 serum samples from individuals aged 0–60 y were collected. Sera were stratified into 8 age groups: <1 y, 1–4 y, 5–9 y, 10–14 y, 15–19 y, 20–29 y, 30–39 y, and ≥40 y. Participants were asked to fill out a questionnaire anonymously about personal information such as sex, date of birth, occupation, education status, marital status, residential status, vaccination status, and date of sampling. The serological survey was conducted from July to October, 2011.
Another study was designed to investigate the seroprevalence of measles in pregnant women and their offspring in Houjie Hospital, which is the most frequently attended by pregnant women in Dongguan. During July 7 to October 31, 2011, 315 consecutive pregnant women who gave birth in Houjie Hospital were interviewed. Maternal and cord blood samples were collected.
Approval for the study was obtained each year from the Medical Ethics Committee of the Guangdong Medical College. Written informed consent was signed by individuals or by parents of children.
Laboratory assay
Anti-measles antibody (IgG) was estimated using commercially available ELISA kits (Virion Serion). The laboratory results were interpreted according to the manufacturer’s instructions. The positive cut-off value was 300 mIU/mL, and weakly positive samples (170–300 mIU/mL) were considered equivocal. A value of <170 mIU/mL was considered negative.
Statistical analysis
Statistical analysis was performed using SPSS for Windows version 15.0. The associations between anti-measles antibody positivity and sex, occupation, education status, marital status, residential status, MCV history, and age was analyzed using the Pearson χ2 test or χ2 test with continuity correction. The Kruskal–Wallis H and Mann–Whitney U tests were used for comparisons of measles antibody titers between groups. The trend in seropositivity and the proportion of equivocal changes among the different age groups (1–29 y) were compared using the Mantel–Haenszel method (linear-by-linear association). Multivariate logistic regression was applied to determine the factors that influenced anti-measles antibody positivity. VIF was used to check for multi-colinearity. Correlation between anti-measles antibody titer in pregnant women and their newborn infants was analyzed with Spearman rank correlation coefficients. A P value < 0.05 was taken as the level of significance.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This work was partly supported by grants from Science Foundation of Dongguan (2011105102003, 201010815214).
References
- WHO. Field guidelines for measles elimination; 2004, http://www.wpro.who.int/publications/docs/FieldGuidelines_for_MeaslesElimination_0F24.pdf.
- Zhiwei Y, Xinglu Z, Jian Z, Gonghuan Y, Guang Z, Kean W. An Analysis of Current Measles Epidemiological Situation in China. Chin J Vaccin Immuni 1998; 4:14 - 8
- Li L, Wenzhou Y, Tiejun S, Chao M, Ning W, Xiaofeng L. Analysis on Epidemiological Characteristics of Age Distribution of Measles in China During 2003-2006. Chin J Vaccin Immuni 2007; 13:101 - 5
- Weisheng L, Ruiheng X, Xiaoping S, Xinge Y. Epidemiological Analysis and Control Strategies of Measles in Guangdong Province. S China J Prev Med 2002; 28:17 - 21
- Guowen P, Xiongcai L, Chenggang W. Epidemiology of measles and control strategy of Guangdong province in 2001-2005. S China J Prev Med 2006; 32:15 - 7
- Qiu T, Chenggang W, Zhiqiang P. Jun, Shu. Analysis on Epidemiological Characteristics of Measles in Guangdong province During 2004-2008. S China J Prev Med 2010; 36:42 - 4
- Fu C, Xu J, Liu W, Zhang W, Wang M, Nie J, Rüdiger K. Low measles seropositivity rate among children and young adults: a sero-epidemiological study in southern China in 2008. Vaccine 2010; 28:8219 - 23; http://dx.doi.org/10.1016/j.vaccine.2010.07.071; PMID: 20688039
- Liu Y, Lu P, Hu Y, Wang Z, Deng X, Ma F, Tao H, Jia C, Ding X, Yang H, et al. Cross-sectional surveys of measles antibodies in the Jiangsu Province of China from 2008 to 2010: the effect of high coverage with two doses of measles vaccine among children. PLoS One 2013; 8:e66771; http://dx.doi.org/10.1371/journal.pone.0066771; PMID: 23825562
- de Quadros CA, Andrus JK, Danovaro-Holliday MC, Castillo-Solórzano C. Feasibility of global measles eradication after interruption of transmission in the Americas. Expert Rev Vaccines 2008; 7:355 - 62; http://dx.doi.org/10.1586/14760584.7.3.355; PMID: 18393605
- Xianghuan M. Jianmeng, Zhou. Wenwei, Chen. Survey on measles vaccine coverage in the measles supplemental immunization activities in 2010, in Dongguan. Srait J Prev Med 2011; 17:33 - 4
- Tharmaphornpilas P, Yoocharean P, Rasdjarmrearnsook AO, Theamboonlers A, Poovorawan Y. Seroprevalence of antibodies to measles, mumps, and rubella among Thai population: evaluation of measles/MMR immunization programme. J Health Popul Nutr 2009; 27:80 - 6; http://dx.doi.org/10.3329/jhpn.v27i1.3320; PMID: 19248651
- Chen CJ, Lee PI, Hsieh YC, Chen PY, Ho YH, Chang CJ, Liu DP, Chang FY, Chiu CH, Huang YC, et al. Waning population immunity to measles in Taiwan. Vaccine 2012; 30:6721 - 7; http://dx.doi.org/10.1016/j.vaccine.2012.05.019; PMID: 22634294
- de Melker H, Pebody RG, Edmunds WJ, Lévy-Bruhl D, Valle M, Rota MC, Salmaso S, van den Hof S, Berbers G, Saliou P, et al, Spaendonck MCV. The seroepidemiology of measles in Western Europe. Epidemiol Infect 2001; 126:249 - 59; http://dx.doi.org/10.1017/S0950268801005234; PMID: 11349976
- Ni JD, Xiong YZ, Li T, Yu XN, Qian BQ. Recent Resurgence of Measles in a Community With High Vaccination Coverage. Asia Pac J Public Health 2012; Forthcoming http://dx.doi.org/10.1177/1010539512451852; PMID: 22815303
- Janaszek W, Slusarczyk J. Immunity against measles in populations of women and infants in Poland. Vaccine 2003; 21:2948 - 53; http://dx.doi.org/10.1016/S0264-410X(03)00113-0; PMID: 12798638
- Gagneur A, Pinquier D. Early waning of maternal measles antibodies: why immunization programs should be adapted over time. Expert Rev Anti Infect Ther 2010; 8:1339 - 43; http://dx.doi.org/10.1586/eri.10.126; PMID: 21133659
- Gans HA, Arvin AM, Galinus J, Logan L, DeHovitz R, Maldonado Y. Deficiency of the humoral immune response to measles vaccine in infants immunized at age 6 months. JAMA 1998; 280:527 - 32; http://dx.doi.org/10.1001/jama.280.6.527; PMID: 9707142
- Kelley PW, Petruccelli BP, Stehr-Green P, Erickson RL, Mason CJ. The susceptibility of young adult Americans to vaccine-preventable infections. A national serosurvey of US Army recruits. JAMA 1991; 266:2724 - 9; http://dx.doi.org/10.1001/jama.1991.03470190072032; PMID: 1942425
- Hutchins SS, Redd SC, Schrag S, Kruszon-Moran D, Wooten K, McQuillan GM, Bellini W, Meyer PA, Hadler S. National serologic survey of measles immunity among persons 6 years of age or older, 1988-1994. MedGenMed 2001; 24:E5; PMID: 11320344
- Green MS, Shohat T, Lerman Y, Cohen D, Slepon R, Duvdevani P, Varsano N, Dagan R, Mendelson E. Sex differences in the humoral antibody response to live measles vaccine in young adults. Int J Epidemiol 1994; 23:1078 - 81; http://dx.doi.org/10.1093/ije/23.5.1078; PMID: 7860159
- Castro-Silva R, Camacho LA, Amorim L, Medeiros AD, Ferreira DA, Oliveira SA, Siqueira MM. Serological surveillance of measles in blood donors in Rio de Janeiro, Brazil. Rev Panam Salud Publica 2003; 14:334 - 40; http://dx.doi.org/10.1590/S1020-49892003001000008; PMID: 14766033
- Fu C, Xu J, Liu W, Zhang W, Wang M, Nie J, Rüdiger K. Low measles seropositivity rate among children and young adults: a sero-epidemiological study in southern China in 2008. Vaccine 2010; 28:8219 - 23; http://dx.doi.org/10.1016/j.vaccine.2010.07.071; PMID: 20688039
- Almuneef MA, Memish ZA, Balkhy HH, Otaibi B, Helmi M. Seroprevalence survey of varicella, measles, rubella, and hepatitis A and B viruses in a multinational healthcare workforce in Saudi Arabia. Infect Control Hosp Epidemiol 2006; 27:1178 - 83; http://dx.doi.org/10.1086/508826; PMID: 17080374
- Leuridan E, Sabbe M, Van Damme P. Measles outbreak in Europe: susceptibility of infants too young to be immunized. Vaccine 2012; 30:5905 - 13; http://dx.doi.org/10.1016/j.vaccine.2012.07.035; PMID: 22841972