https://orcid.org/0000-0002-1940-2216
ABSTRACT
Few studies have addressed the seroepidemiological profile of rubella among a representative population of young adult women. This study aims to determine the immunity and susceptibility rate against rubella in a representative population of women in reproductive age in Iran through serological evaluation. This cross-sectional study was conducted in 2012 on 804 pre-marriage women in Iran. Multi-stage random sampling was used for choosing study sample. Serologic test were used to assess subjects’ immunity to rubella and their titers of IgG antibody against rubella with ELISA method was measured. In total, 98.4% (95% CI: 97.5% −99.2%) of study participants were immune against rubella. Five women (0.6%) were in borderline category and 1% (8 women) was susceptible to rubella. The proportion of immune people in low and high incidence regions was 99.3% (95% CI: 97.8–99.9%), and 97.5% (95% CI: 96.4–98.5%), respectively (P = 0.05). Our data indicated that level of immunity to rubella in women of reproductive age in Iran is satisfactory. This finding indicates the achievement of Iran to the goal of high level of serum immunity against rubella among young women.
1. Introduction
Rubella is an acute viral disease with generally mild manifestations in children and other susceptible groups. However clinical importance of rubella is due to its potential complications during pregnancy. Infection during pregnancy, especially during the first trimester, can cause miscarriage, stillbirth or infants with congenital malformations known as congenital rubella syndrome (CRS).Citation1 CRS is more specific to the countries with a high percentage of women in reproductive age which are susceptible to rubella. Before development and introduction the rubella vaccine, the incidence of CRS was ranged from 0.1 to 0.2 per 1,000 live births and in epidemic conditions it reached to 0.4–0.8 per 1,000 live births.Citation2
Annually, about 100,000 people are born with congenital rubella syndrome worldwide. Fortunately, there is an effective vaccine for the prevention of rubella and CRS.Citation3 At the end of 2016, 152 out of 194 countries have introduced rubella vaccine into their national immunization programs; however vaccine coverage in these countries varies from 13% to 99%.Citation4 Since 2012, rubella has also been included in the measles elimination program, and according to the goal of the World Health Organization (WHO), measles and rubella should be eliminate in at least 5 WHO regions by the end of 2020.Citation4,Citation5 Serum immune testing studies are useful to determine the status of both immunity and susceptibility rate against rubella and address the status of rubella elimination.Citation6
Before the start of rubella immunization program in Iran, the incidence of CRS is estimated to be about 0.2 per 1000 people. In December 2003, a national immunization campaign against measles and rubella was conducted in all 5 to 25 year old Iranian people. One month after the completion of the program, in a population-based study, 2000 people were evaluated for rubella serology in five geographical regions of the center, north, south, west and east of Iran. The findings of this study showed that 61.9% of the subjects were immune against rubella before immunization and 38.1% were susceptible to rubella. Of susceptible individuals, 98% were immunized against rubella following immunization.Citation5,Citation7
The principal objective of the rubella immunization program among communities is to reduce the incidence of CRS. Majority of countries are struggling to achieve the goal of CRS elimination. To support the goal of measles and rubella elimination under the light of WHO’s global measles and rubella strategic plan, countries need to address and monitor the high level of serum immunity against rubella among young women.Citation8 Published literature indicate that published studies in Iran have conducted in different subgroups of population include students.Citation9–Citation11 However, no study aims to address the seroepidemiological profile of a representative population of Iranian young adult women. This work aims to determine the immune status and rubella susceptibility in pre-marriage women as a representative of women in reproductive age in Iran through serological evaluation.
2. Material & methods
This cross-sectional study was conducted in 2012. In Iran all pre marriage couples referred to premarital education class for strengthening marriage. From this sampling frame we recruited 804 pre-marriage women. We recruited eligible participants throughout Iran from both low and high incidence areas of rubella. According to data from national notifiable rubella surveillance system, Iranian provinces were divided into two regions include high incidence and low incidence based on the median incidence of rubella (0.5 per100, 000 population), We devoted 402 people to each region, continuously 3 provinces randomly selected from each region (Sistan and Balouchestan, Kurdistan and Lorestan from low incidence and Isfahan, Semnan and North Khorasan from high incidence provinces, respectively). After that two marriage consulting center were randomly choose from each province and 67 pre-marriage women were selected randomly from referring women per marriage consulting enter consecutively. Women with viral infectious diseases, immunodeficiency or autoimmune diseases and those receiving immunosuppressive drugs were excluded. Demographic data including age and place of residence as well as women’s rubella immunization history and disease history were gathered from participations by our trained interviewers.
After obtaining informed consents from participation, a sample of 5 ml of venous blood was taken from each subject. After that, serum was separated using centrifuge and kept frozen at −20°C until test and transferred to Department of Virology, School of Public Health, Tehran University of Medical Sciences. ELISA method and ELISA reader were used to assess subjects’ immunity to rubella. Anti-rubella IgG level was measured using a kit from Siemens Company, ELISA; Enzygnost, Siemens, Marburg, Germany, according to the manufacturer’s instructions. The IgG measurement unit was Optic Density (OD). According to the manufacturer’s standards, subjects were divided into three groups; OD more than 0.2 as positive or immune, 0.1–0.2 borderline and less than 0.1 negative.
Data were analyzed using descriptive statistics including frequency tables, percentage, mean and standard deviation, as well as analytical statistics including T-test and Chi-square. All the analyses were done using SPSS-18 software (Chicago, IL, USA). Significance level was considered less than 0.05.
3. Results
In this study, a total of 804 pre-married women referred to marriage counseling centers in six provinces were underwent serologic evaluation of rubella. The mean age of women under study was 22.2 ± 5.5 years. The mean age of women in both low and high incidence regions was not significantly different (p > 0.05). In terms of the place of residence of the subjects under study, a total of 67.9% of women lived in urban areas and 32.1% lived in rural areas. There was no statistically significant difference between the place of residence of these people in two regions with low and high incidence (p = 0.07).
In total, more than half of the studied population (56.3%) had a history of rubella immunization, 19.9% (160) had no history of immunization in national immunization campaign, and 23.8% (191) did not remember the participation in this national program. In the low incidence region, the proportion of women with a history of mass immunization was 51.7% and in the high incidence region was 60.9%. The difference between the two indices was statistically significant (p = 0.002). The lowest numerical value of this index was observed in Bojnourd (23.9%) and its highest value was in Isfahan (88.1%).
Findings related to the immunity status against rubella in the study population by regions, provinces and counties are presented in . In total, 98.4% (95% CI: 97.5% −99.2%) of them were safe, 0.6% (5 persons) were in borderline category and 1% (8 patients) were susceptible. The proportion of immune people in low and high incidence regions was 99.3% (95% CI: 97.8–99.9%), and 97.5% (95% CI: 96.4–98.5%), respectively (P = 0.05). In the low incidence region, all of women with a history of immunization and without prior immunization were safe. However, in the high incidence region, 98.4% and 95.2% of women with a history of immunization and without previous history of immunization were immune, respectively (P = 0.12). In regard of residency, 98.9% and 100% of women in low incidence and 98.6% and 94.9% in high incidence region were immune in urban and rural areas, respectively.
Table 1. Distribution of immunity status against rubella in the study population by different geographical regions.
shows the distribution of immune subjects’ proportion in three age groups (less than 20 years, 20–24, 25 years old and above). The proportion of immune subjects in these three age groups was 97.9%, 98.6% and 98.7%, respectively. However, the increasing trend of immunity with age, was not significant (Chi square for trend = 0.55, P = 0.46). assessment of indicators of women safe at age three, by two areas of low and high showed that the area of low share of women safe in three groups of almost equal and the difference is statistically not (p = 0.83). But in the area of the high proportion of women safety in this three age groups respectively 96.5%, 97.8% and 98.4%, which is the process spite of increasing women’s share securely with age, it was not statistically significant in both low and high incidence region (P > 0.05).
Table 2. Distribution of immune women against rubella by age groups.
4. Discussion
In this population-based cross-sectional study, with an acceptable sample size in 6 provinces of Iran (about 20 percent of the total provinces of Iran) and in each province in two counties (12 counties in total), women aged 15–59 years old as the target group the CRS elimination program, were evaluated for rubella serological status. According to the findings of this study, 98.4% of the investigated women had sufficient antibodies to the rubella virus and were considered immune. Fortunately, differences in this index were not significant by different age groups, subject’s residency, and the history of rubella immunization.
In agreement with our finding, results of other studies in different parts of Iran showed that mass vaccination of rubella caused noticeable rubella seropositivity among women at marriage, so that this index in Mashhad,Citation12 Shahre-kord,Citation13 HamadanCitation14 Sari,Citation13 TehranCitation14 and KermanshahCitation15 reached to 89.5%, 96.9%, 98.4%, 93%, 97.4% and 99.3% respectively which indicating efficacy of vaccination in providing appropriate immunity in target groups. Also effectiveness of rubella mass vaccination it has also proven in other countries.Citation16–Citation18
The increased trend of anti-rubella antibody with aging was shown in this study, which is maybe due to higher risk of disease or contact with virus with increase in age. Although this trend was not significant which could be due to the fact that the sample size of present study did not have enough power to show changes in trend. This increasing trend with aging has been confirmed in other studies.Citation12,Citation19 While results of the Barari Sawadkohi et al. study showed a contradict trend.Citation20
The rate of rubella immunity in migrants is relatively lower. Greenaway et al. showed that immigrant women were more susceptible to rubella (Odds ratio = 1.7).Citation21 Iran has the most Afghan refugees and many Iraqi refugees due to the neighboring with these countries; therefore, assessing the immunity level of women in this vulnerable group and targeted for immunization should be taken account to reduce the risk of congenital rubella.
It is emphasizes that immunization is the best way for eliminating CRS. In this regard two immunization master plans can be implemented: (1) selective immunization allowing rubella to continue circulating and (2) Public immunization of children which has the goal of preventing both rubella and CRS as the more effective tactics.Citation22
In should kept in mind, the acceptable level for each of the three above indicators should be provided over a relatively long period of time, that is, the sustainability or stability of these indicators for a multi-year period is also important. Just pursuing an acceptable level of an indicator for a short period of time (for example one year) cannot lead to the goal of eliminating congenital rubella syndrome in a community.Citation23
Some limitations of this study should be acknowledged. The limited examined areas and provinces can be considered as one of the limitations of the present study which can affect the generalizability of the findings to the whole country. The generalizability of the age group studied in the present study to the whole women of reproductive age is another challenge. Since the age of marriage has increased in Iran, it is evident that the mean pregnancy age has also increased, although this may have different patterns in different regions of the country. Therefore, it is necessary to repeat similar studies in different parts of the country with the acceptable sample size of women aged 35–49 years.
5. Conclusion
Findings indicated that level of immunity to rubella among pre- marriage women in Iran is high. Moreover, this finding supports the goal of high level of serum immunity against rubella among young women and CRS elimination in Iran.
Disclosure of potential conflicts of interest
No potential conflict of interest was reported by the authors.
Acknowledgments
We gratefully acknowledge all contributors to this project. Special thanks for collaborators of the project at district and provincial levels who make this project possible.
Additional information
Funding
References
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