Investigation of the Seroprevalence of Antimeasles Immunoglobulin G Antibody in Students at Shiraz University of Medical Sciences

Introduction

Measles virus (MV) is a negative single-stranded RNA virus from the Morbillivirus genus of the Paramixoviridae family (Goldani, 2018). This virus is transmitted by direct contact and aerosol (Naim, 2015). The virus causes an acute, highly contagious illness that begins with a prodromal phase, including fever, cough, runny nose, and conjunctivitis. Maculopapular rashes appear 24 days after the onset of fever, spread from the head to the body, and then resolve in order of appearance over the next 34 days (Strebel and Orenstein, 2019). Koplik's spots, small bluish-white plaques, are considered pathognomonic for measles and appear on the buccal mucosa 12 days before the rash begins in up to 70% of cases (Naim, 2015). It has been reported that the all-cause mortality rate in unvaccinated children under 5 years and 9 months was 16.2% and 24%, respectively (Burström et al., 1993). The high morbidity and mortality from measles has placed a heavy burden on the public health system (Holzmann et al., 2016). The live-attenuated measles vaccine was first approved in the United States in 1963, after which the mortality rate was significantly reduced (Strebel and Orenstein, 2019).

Annual measles cases worldwide have decreased from 4,211,431 in 1980 to 292,952 in 2010 (Cottrell and Roberts, 2011). Preventive vaccination remains the most important task in developing countries, where 115,000–160,000 patients die from measles every year (Holzmann et al., 2016). Although mass measles vaccination campaigns and supplementary immunization activities (SIAs) reduced 87% of measles incidence and 84% of measles-related deaths between 2000 and 2016 (Piri et al., 2019), measles outbreaks still occur. The total number of measles cases reported by the World Health Organization (WHO) increased from 12,939 in January to 364,808 at the end of July 2019 (Saffar et al., 2021). Measles outbreaks in Madagascar (October 2018) and New York City (2018–2019) showed that 67.2% and 85.8% of cases were unvaccinated, respectively (Nimpa et al., 2020; Zucker et al., 2020). Establishing stable herd immunity and preventing the spread of MV in a community requires a population immunity rate of >9,395% with >95% vaccination coverage (Holzmann et al., 2016).

Measles vaccination was introduced in Iran's Expanded Immunization Program in 1988 as two routine vaccine doses at 9 and 15 months of age (Yekta et al., 2009). In 2003, one of the largest mass vaccination campaigns was carried out in Iran due to the increasing incidence of measles in older children and the experiences in other countries. Thus, the total population 5–25 includes 33,579,082 subjects who have been vaccinated against measles and rubella (MR) regardless of their vaccination status (Yekta et al., 2009). After the widespread catch-up campaign, overall MR vaccine coverage was estimated at 97% and measles cases dropped to zero (Mohammadbeigi et al., 2019; Yekta et al., 2009).

The mean annual incidence rate of measles in Iran from 2014 to 2016 was 3,442 per 1 million people (Mohammadbeigi et al., 2019). Based on the evidence, measles outbreaks in many Iranian provinces, including Khuzestan, Fars, and Ardabil led to an increase in reported cases from 58 in 2014 to 668 in 2015 (Mohammadbeigi et al., 2019). In 2016, measles cases fell dramatically (90 cases) with an increase in the percentage of vaccine coverage through SIAs, and the incidence rate per million people fell to 1,154 annually (Mohammadbeigi et al., 2019).

Local outbreaks with an average number of 1,020 measles cases are reported each year in rural and urban areas due to declining immunity levels and immigration (Karimi et al., 2004; Namaki et al., 2020). One study found that in Bahar district, west of Hamadan province in northwestern Iran, which was affected by the spring 2018 measles outbreak, 24.26% of individuals had low levels of antibodies (Abs) to the disease (Karami et al., 2020). In addition, a cross-sectional study of healthy individuals 7–33 years of age with a history of measles vaccination found that 12% of participants were serologically susceptible to measles (Saffar et al., 2021). Serosurvey studies are strongly recommended to locate measles immunity gaps in specific age groups and to revaccinate seronegative vaccines. Therefore, in this study, we wanted to examine the frequency of antimeasles immunoglobulin G (IgG) Ab among students at the Shiraz University of Medical Sciences (SUMS).

Materials and Methods

Results

The mean age of the participants was 22.2 (±4.3) years (ranged from 18 to 48 years). Of 450 participants, 225 cases (50%) were male and 225 (50%) female. Overall, 286 (63.6%) cases were positive for antimeasles IgG Ab and 164 (36.4%) were negative. Information on the age and sex of the participants is provided in Table 1. There was no significant difference in the seroprevalence of antimeasles IgG between groups A and B (p = 0.612). Regarding the gender of the participants, 60.9% of men (137/225) and 66.2% of women (149/225) were positive for measles-Ab, which was not statistically significant (p = 0.240). Group B was divided into three groups according to the age of the students (Table 2). Although the frequency of antimeasles IgG Ab differed in the three groups, it was not statistically significant (p = 0.43) (Supplementary Table S1).

Discussion

Measles infection affects multiple organ systems and can lead to a variety of complications, including encephalitis, pneumonia, and miscarriage. These complications are more likely to occur in unvaccinated pregnant women and newborns (Hirschberg et al., 2021). The high morbidity and mortality from measles has placed a heavy burden on the public health system (Holzmann et al., 2016). Although SIAs reduced incidence of measles and measles-related deaths, measles are still being detected even in high-income European countries (Piri et al., 2019). Studies have shown that antimeasles Ab titers decrease over time after vaccination and that people who have received the vaccine have lower geometric mean titers than those who have acquired immunity through natural infection (Dimech and Mulders, 2016). Serosurvey studies are therefore strongly recommended to identify gaps in measles immunity in specific age groups and to revaccinate seronegative individuals.

In this study, an examination of the immunity status to measles among SUMS students showed that 63.6% of cases were positive for antimeasles IgG Ab and 36.4% were negative. In this regard, Zahraei et al. (2020) reported that the seroprevalence of measles-specific IgG was 80.7% among 1,569 women who attended health centers for routine premarital counseling. In addition, Honarvar et al. (2013) showed that the seroprevalence of protective level of antimeasles IgG-Abs in 175 pregnant women 16–42 years of age in Shiraz, southern Iran was 81.7%. A cross-sectional study evaluating immunity to measles in the under 25-year-old population of Ahvaz, southwestern Iran, showed that 821 (91.2%) of the population examined were seropositive (Shakurnia et al., 2014). Another study by Saffar et al. in 2021 among 635 people also showed that nearly 87.7% of fully vaccinated people 7–33 years of age were seropositive for measles (Saffar et al., 2021).

In the other countries, the seroprevalence of antimeasles Ab in Mexico was 99.5% (1,254/1,260) and 98.3% (798/811) among adolescents 15–19 and 30–39 years of age, respectively (Díaz-Ortega et al., 2020). In Italy, Anichini et al. (2020) reported that 77.2% of 1,092 healthy adults, either vaccinated or naturally infected, were seropositive for MV. Although in most studies cited 10–30% of the subjects were negative for specific IgG-Abs against measles, they could be protected if exposed to MV through long-standing cellular immunity. In this regard, Jamehdar et al. suggest that measles-specific protective cell-mediated immunity is measurable longer than humoral immunity. Therefore, in some children, lymphocyte proliferation responses may be better maintained than Ab titers. They measured the measles-specific cellular and humoral immune responses of 100 high school students in Tehran. Results showed that 89% had protective cellular immune responses, while only 77% had protective neutralizing measles Ab titers (Jamehdar et al., 2007).

The results of our study showed that the frequency of antimeasles IgG Ab in groups A and B was not statistically significant. Consistent with our results, Maryam et al. (2016) showed that 79.2% of 53 medical students at Tehran University of Medical Sciences between 20 and 30 years of age who had been vaccinated during the nationwide MR vaccination in 2003 had a protective IgG level (>11 IU/mL) against measles exhibited.

On the other hand, Shakurnia et al. (2014) found that high immunity in older age groups is attributed to mass national vaccination against measles and rubella. Saffar et al. (2021) reported that the highest susceptibility rates for measles were observed in 15–19-year-olds born before the national MR immunization program. In addition, Zahraei et al. (2020) reported a significant difference between participants older than 18 years and participants younger than this age in their seroprevalence of antimeasles Abs, which could be due to an effect of mass vaccination. All studies showing high levels of antimeasles IgG in those receiving the national MR immunization program were conducted immediately after the program, while our study was performed over 25 years later. Therefore, our results are rational and predictable.

We have shown that there is no significant correlation in antimeasles IgG seroprevalence by age. Maryam et al. (2016) reported no significant correlation between antimeasles IgG seroprevalence and age. Honarvar et al. (2013) also reported no association between immunity to measles and age.

On the other hand, in Ahvaz, Iran, it was shown that antimeasles Ab titers increased with age and there were significant statistical differences between age groups. The reason for such a high immunity in the older age groups has been attributed to nationwide mass vaccination against measles and rubella (Shakurnia et al., 2014). A cross-sectional study by Saffar et al (2021) among 635 people showed that the highest measles susceptibility rates were observed in 15–19-year-olds born before the national MR immunization program. A seroprevalence study assessing the level of immunity to measles in Thais of all ages showed that the age group >30 years who were naturally infected and received a second measles vaccination at age 6 (compared with others who received a second measles vaccination at age 2.5) had the highest seroprotection rate against measles (Wanlapakorn et al., 2019).

Another study describing the seroprevalence of measles Abs in Mexico in 2012 found that susceptibility was correlated with young age (Díaz-Ortega et al., 2020). In Italy, the neutralizing Abs titer of vaccinated subjects tended to decrease over time and there was a significant fall in Abs titer when the interval between the two doses was 11 years (Anichini et al., 2020).

Furthermore, our results showed that there was no significant correlation in the seroprevalence of antimeasles IgG by sex. Consistent with this, a study among Thai subjects showed no significant differences in immunity levels between male and female populations (Wanlapakorn et al., 2019). Maryam et al. (2016) reported no significant correlation between antimeasles IgG seroprevalence and gender. Also, Shakurnia et al. (2014) found that immunity to measles was not statistically significant between the two sexes. A meta-analysis study that included 68 measles surveys conducted in 37 different countries between January 1998 and June 2014 found that gender was not conclusive evidence that the level of immunity was influenced by gender (Dimech and Mulders, 2016). Taken together, gender may not affect the level of immunity in vaccinated subjects. The limitation of this study was that we assessed humoral immunity to measles using an ELISA test, which showed lower protective immunity compared with the neutralization/hemagglutination inhibition.

In conclusion, the results of the study indicated that the frequency of antimeasles IgG Ab is lower than required to predict the spread of the MV in the population impede. Therefore, a booster dose of measles vaccine may be required to induce and maintain a level of protective immunity against measles. Further studies are recommended to clarify the results.