Seroepidemiology of Bordetella pertussis Infection in Fresh College Students in Iran: A Multicenter Study

Pertussis is caused by Bordetellapertussis, and is a highly communicable, acute bacterial infection of the respiratory tract (1, 2). This organism is a gram-negative, fastidious, pleomorphic bacillus that continues to cause a global public health problem and can lead to a fatal illness in young infants (3-7). Neither its infection nor its vaccination provides permanent immunity (8-10). Therefore, In spite of high vaccination coverage in childhood, this disease remains a cause of substantial morbidity in the world (8-15). It is the only disease with universal childhood vaccination but with an escalating trend in the US (16, 17).

Adults and adolescents with mild or subclinical infections are important sources of Pertussis for Infants and young children (6, 7, 17-19). Most related reports are from high-income communities, and limited experience exists from low- and middle-income countries. The current study aimed to report the prevalence of Pertussis in a sample of Iranian young adults.

Overall, 1617 freshman students of four universities of medical sciences in Iran were studied. The mean age was 19.64 ± 2.1 years with a range of 17 to 38 years. Distribution of age subgroups was as follows: 1079 (66.9%) cases were aged under 20 years, 470 (29.1%) cases were 20-24 years, 61 (3.8%) cases were 25-29 years and 4 (0.2%) cases were more than 30 years. Overall, 980 (60.7%) students were female and 635 (39.3%) were male. The mean number of family members was 5.5 ± 1.8 (median = 5) with the minimum of 2 and the maximum of 14. Distribution of family member subgroups was: 498 (31%) cases ≤ 4 members, 434 (27%) cases 4-5 members and 676 (42%) cases > 6 members. The mean serum IgG titer was 66.19 ± 51.8 U/mL with the minimum 2 U/mL and maximum 250 U/mL. The mean of serum IgG titer was 61.97 ± 52 U/mL in females and 72.71 ± 50 U/mL in males. Table 1 presents the frequency of sero-positivity of Pertussis according to gender, and Table 2 presents it according to age groups. The prevalence of Pertussis was 37.7% (609 cases) by considering cut-off point of anti-PT IgG of 80U/mL, i.e. IgG titer ≥ 80 U/mL, 31.6% (511 Cases) by cut-off point of 94 U/mL (14), and 28.4% (460 Cases) by cut-off point of 100 U/mL (Table 3).

We found a considerably high prevalence of university students with positive anti-PT IgG. Given that vaccination against Pertussis leads to short-term increase in antibody level (7, 10, 11, 20), the possibility of false positive titers due to previous vaccination seems to be unlikely. As the age of our cases ranged between 17 to 38 years and according to the national immunization schedule of Iran, they had taken the last booster dose of DTP at the age of 4 to 6 years, the elevated anti PT IgG levels were attributed to recent infection with Bordetellapertussis. Similar to many previous studies (14, 18, 21-23), we used different cut-off points of anti-PT IgG levels for estimating the prevalence of Pertussis infection. A study in Poland (23) reported the prevalence of Bordetellapertussis infection according to three cut-off points of 40, 80 and 100 U/mL, reflecting contact with this bacteria in the previous two, three, and 12 months. In this study, the prevalence was reported 7.2%, 6.6% and 5.2%, respectively; whereas in our study, the corresponding figures were 55.4%, 37.7% and 28.4%, respectively. The higher prevalence of infection in our study than that of Poland is suggested to be because our study was conducted in October, the beginning of the academic year in Iran, with its previous 5 months being in spring and summer time, which have the highest prevalence of Bordetellapertussis. In a survey in Singapore (24) by using the cut-off point of 5 U/mL, the prevalence of Pertussis infection was 97% among 18-45 years old persons. It is similar to the prevalence of 98.7% documented in our study. In a study in Turkey, seropositivity in cut-off point of 9 U/mL is reported as 30%, but interestingly at the same cut-off point, 93.2% of our study population were seropositive. This difference probably comes from the routine use of a cellular Pertussis vaccine in the national immunization program in Turkey instead of the cellular vaccine, which has more efficacy and latency (25). While the specificity of cut-off point of 94 U/mL for acute infection was estimated 99% in a study in United States (14), The incidence of acute infection in same cut-off point was 31.6% in our study. However, by using all cut-off points - except than 5 U/mL - the prevalence of Pertussis infection was significantly different in terms of gender. In a study among Turkish children (26), IgG titer had no significant correlation with the number of family members, but in another study in Cameroon, (27) significant differences are reported in IgG titer of children according to the number of family members. In our study, we found significant differences in anti-PT IgG levels in cut-points of 40, 50, and 80 U/mL. We found clear differences in the prevalence of Bordetellapertussis infection in our study with other reports. A previous study in Iranian young adults was conducted among 424 randomly selected military garrisons, aged 18 to 21 years, in Tehran. By considering a cut point of 20 U/mL, the seropositivity is reported to be 60.6% (28). The corresponding figure in our study was 74%. Furthermore, a study in Iranian university students was conducted in Hamedan. A number of 163 students were studied, and by considering a cut point of 24 U/mL, the sero-prevalence rate of IgG-PT was 47.67% (29). It is noteworthy to mention that to have an ideal group for studying the sero-prevalence of IGG-PT, we recruited our study participants at the first day of their entry to university, and before their stay in the crowded environment of dormitories, whereas this point has not been considered in previous studies in Iran. Different cut-off points have been used to determine the seropositivity for Bordeellapertussis; one of the recent recommendations states that a single serum sample showing anti-PT IgG above 100 U/mL may indicate a recent infection (30). Regardless to the cut-off point used, studies of various countries revealed a substantially high prevalence of infection with Bordetellapertussis among adolescents and young adults.

Although the incidence of Pertussis is reduced in infants and young children - because of the introduction of universal childhood immunization - in countries with high vaccination rates it has been increasing in adolescents and young adults in recent years especially in ages ranging between 35-39 years. An accumulating body of evidence proposes that the current childhood immunization schedule is not efficient and long lasting for eradication of Pertussis, thus a booster dose of a cellular vaccine is recommended in later life. Several scientific consensus statements, as the American Academy of Pediatrics (31, 32) have recommended to consider a booster dose in adolescence. The recent recommendations in immunization schedule suggest that adolescents should receive a single dose of Tdap vaccine instead of Td for booster immunization against tetanus, diphtheria, and Pertussis and the preferred age for Tdap immunizations is 11 through 12 years of age (31-38).

Pertussis continues to challenge medical and public health professionals; recent increases in the prevalence and incidence may be because of the limited efficacy and latency of childhood vaccination. Moreover, age-cohort effects, vaccine effectiveness, or changes in testing patterns should be considered. Our study can serve as one of the scarce population-based reports from developing countries. A universal cut-off point should be determined for diagnosis of seropositivity, and a booster of a cellular vaccine is recommended in adolescence.