seroprevalence OF ANTIBODIes TO DIPhTheRIA, TeTANUs AND PeRTUssIs AMONg healthy ADOlesCeNTs AND ADUlTs IN IRAN

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1 seroprevalence OF ANTIBODIes TO DIPhTheRIA, TeTANUs AND PeRTUssIs AMONg healthy ADOlesCeNTs AND ADUlTs IN IRAN Babak Pourakbari 1, Behnaz Moradi 2, Farin Mirzaee 2, Shima Mahmoudi 1, Mostafa Teymuri 1, Setareh Mamishi 1,3* 1 Pediatrics infectious diseases Research Center, Tehran University of Medical Sciences, Tehran, iran 2 School of Medicine, Tehran University of Medical Sciences, Tehran, iran 3 department of Pediatric infectious diseases, School of Medicine, Tehran University of Medical Sciences, Tehran, iran ABsTRACT Serologic data on diseases that are preventable by vaccine are useful to evaluate the success of immunization programs. In this study we evaluated the serologic levels of antibodies to diphtheria, tetanus, and pertussis. In a cross sectional study, a total of 360 people aged years were randomly selected and classified by sex and age (10-14, 15-20, years). Overall, 78.8% of people aged years had fully protected levels of diphtheria antibody ( 0.1 IU/ML), and 89.7% had fully protected levels of tetanus antibody ( 0.1 IU/ML), 94.3% of women aged years had anti tetanus antibody sufficient to protect against neonatal tetanus ( 0.1 IU/ML). Antibodies to Pertussis toxin (PT) were found in 44.2% samples but only 1.4% had fully protective levels. Antibodies to PT increased with age, ranging from 33.5% in aged years to 54.6 % in aged years. No differences were found between male and female, except for diphtheria in age group years. Results of this study reveal that diphtheria and tetanus (dt) are efficient between booster doses. About pertussis, most people are susceptible to pertussis and increased PT antibodies with age suggest acquired asymptomatic Bordeella pertussis infection. Also B. pertussis infections in adolescents and adults are of concern, as they are the most important source of transmission of pertussis to young, unprotected infants. So one booster dose in adolescents and adults (as CDC recommended), to reduce mortality and morbidity in infants, is therefore suggested. ReZUMAT Datele serologice privind bolile prevenibile prin vaccinare sunt utile în evaluarea reuşitei programelor de imu - nizare. În studiul de faţă, evaluăm titrul anticorpilor anti difterie, tetenos şi pertussis. Într-un studiu transversal, au fost selectate aleator şi clasificate în funcţie de sex şi vârstă un număr total de 360 de persoane, cu vârste cuprinse între ani (10-14, 15-20, 21-25). 78,8% dintre persoanele cu vârste cuprinse între ani prezentau nivele protectoare de anticorpi anti difterie ( 0,1 UI/ml), 89,7% aveau nivele protectoare de anticorpi antitetanos ( 0,1 UI/ml) şi 94,3% dintre femeile cu vârste cuprinse între ani prezentau nivele de anticorpi antitetanos suficiente să asigure protecţie împotriva tetanosului neonatal ( 0,1 UI/ml). Anticorpi anti pertussis au fost detectaţi în 44,2% dintre probe, dar numai 1,4% prezentau nivele protectoare. Nivelele anticorpilor anti pertussis au crescut la grupele cu vârstă mai mare, fiind cuprinse între 33,5% la persoanele din grupa de vârstă ani și 54,6% la grupa ani. Nu s-au găsit diferenţe între bărbaţi şi femei, cu excepţia titrului de anticorpi anti difterie la grupa de vârstă ani. Rezultatele studiului arată că nivelul anticorpilor anti difterie și anti tetanos rămâne protector între dozele de rapel. În ceea ce priveşte pertussis, majoritatea indivizilor sunt susceptibili la infecţie, iar nivelele crescute de anticorpi anti pertussis la vârste mai mari sugerează infecţie asimptomatică cu B. pertussis. De asemenea, sunt de interes infecţiile cu B. pertussis la adolescenţi şi adulţi, deoarece sunt cea mai importantă sursă de transmitere la copii neprotejaţi. De aceea, se recomandă o doză de rapel la adolescenţi şi adulţi (conform recomandării CDC) pentru a reduce mortalitatea şi morbiditatea în rândul copiilor mici. Keywords: diphtheria, tetanus, pertussis, vaccination, immunization INTRODUCTION Vaccination against diphtheria and tetanus has markedly reduced the number of cases and deaths from these diseases. In the United States, during , seven cases of respiratory diphtheria were reported to CDC [1] but in Iran, during , 159 cases of respiratory diphtheria were reported [2]. Exposure to diphtheria remains possible during travel to coun- *Corresponding author: Setareh Mamishi, Department of Pediatric Infectious Diseases; Children Medical Center Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran, smamishi@sina.tuns.ac.ir 250

2 Seroprevalence of antibodies to diphtheria, tetanus and pertussis tries where diphtheria is endemic or epidemic, follo - wing exposure to toxin producing strains of Coryne - bacterium ulcerans, contact with dairy animals or consumption of unpasteurized dairy products [1]. Tetanus rarely occurs in people who have received a complete vaccination course. During , 81 cases of tetanus and one case of neonatal tetanus were reported in Iran [2]. Neonatal tetanus occurs as the result of Clostridium tetani infection of umbilical stump of an infant born to mother with a maternal tetanus antitoxin level insufficient to protect infants from neonatal tetanus [1, 3-6]. Only three cases of neonatal tetanus were reported to CDC during in the United States. Since 1980 the number of reported pertussis cases has been steadily increasing especially among adolescents and adults, despite high immunization rates in childhood [1, 7]. Protection against pertussis wanes approximately 5-10 years after completion of childhood pertussis vaccination [1, 3]. Neither natural immunity nor vaccine-induced immunity to Bordetella pertussis is long lasting [8]. B. pertussis infection in adolescents and adults is often not typical so real incidence of pertussis is markedly underestimated [8]. Also adolescents and adults are the most important source of transmission of pertussis to infants [7, 9]. In this study we report serosurvey immunity to diphtheria, tetanus and pertussis in Iran to evaluate the efficiency of vaccination against these diseases and finding susceptible persons especially to pertussis. METHODS Study population and design: The survey was conducted during 2007 at Children Medical Center. People with history of immune deficiency (primary or secondary), unvaccinated or with uncertain history of administration of three doses of combined diphtheria, tetanus and pertussis (DTP) vaccine in childhood, and who did not receive booster vaccination at 15 years old, were excluded. Recruitment was done by randomized routes system. Questionnaires about demographic and history of cough more than two weeks were filled for each participant. Serum samples were collected and then frozen and stored at -70ºC until assayed at the same time. This study was designed as cross-sectional study on a population aged years. Cluster sampling by sex and age was performed and distributed in three age groups (10-14, 15-20, 21-25). Sample size: Blood samples were obtained from 360 healthy adolescents and adults aged years in Tehran city, Iran January - June Serum sample size for this study was determined on the basis of expected levels of immunity to diphtheria, tetanus and pertussis in each of the age groups 10-14, and years. Laboratory tests: IgG antibodies against diphtheria and tetanus were detected using enzyme linked immunosorbent assay (ELISA) (IBL, Hamburg, Germany) and IgG antibodies to Pertussis toxin (PT) were determined by ELISA, (Pertusscan, Euro-Diagnostica, Malmö, Sweden). Determination of each antibody was in accordance with the instructions provided in the package insert. For diphtheria and tetanus assay, sera were classified as negative (susceptible) when the antitoxin level was < 0.01 International Unit (IU)/ml and positive (immune) when it was 0.1 IU/ml. Anti toxin levels in the range of IU/ml were classified as low positive (partially immune). Childbearing aged females (15-25 years of age) with anti-tetanus antitoxin level 0.1 IU/ml could protect against neonatal tetanus. About pertussis, according to manufacturer, absorbance above 0.3 indicates antibodies. Absorbance values of IgG to PT above 1 indicate previous, current/recent pertussis infection or immunization. The 0.1 limit represents approximately 100 EU/ml. Statistical analysis: Differences in antibody prevalence were determined by disease, sex and age group, and compared using the Chi-square test and P-values less than 0.05 were considered statistically significant. Statistical calculations were performed with SPSS statistical software (version 13.0; SPSS Inc., Chicago, IL, USA). RESULTS Tetanus: The proportion of subjects susceptible to tetanus and partially immune was higher in aged years than in other age groups (Table 1) but did not differ significantly between age groups. No differences between males and females were detected when comparing the overall prevalence and the prevalence by age groups (Fig. 1) % of women aged years had anti tetanus antibody sufficient to protect against neonatal tetanus. Diphtheria: As for tetanus, the proportions of subjects susceptible to diphtheria and partially immune were higher in aged years than in other age groups (Table 1) and were statistically significant (P = 0.001). Anti diphtheria antibodies were lower than anti tetanus antibody in all age groups especially in years of age (Table 1). Proportions 251

3 POURAKBARI et al. Table 1 - Immunity to diphtheria, tetanus and pertussis by age group Age group (years) Total Diphtheria Number tested Susceptible¹ 18 (5%) 13 (10%) 2 (1.9%) 3 (2.5%) Partially immune² 58 (16.1%) 33 (25.4%) 13 (11.9%) 12 (9.9%) Immune³ 284 (78.9%) 84 (64.6%) 94 (86.2%) 106 (87.6%) Tetanus Number tested Susceptible¹ 4 (1.1%) 3 (2.3%) 1 (0.9%) 0 (0%) Partially immune² 33 (9.2%) 22 (16.9%) 6 (5.5%) 5 (4.1%) Immune³ 323 (89.7%) 105 (80.8%) 102 (93.6%) 116 (95.9%) Pertussis Number tested Susceptible* 195 (55.7%) 85 (66.4%) 56 (54.4%) 54 (45.4%) Partially immune 50 (42.9%) 42 (32.8%) 45 (43.7%) 63 (52.9%) Immune 5 (1.4%) 1 (0.8%) 2 (1.9%) 2 (1.7%) ¹Susceptible : < 0.01 IU/ml, ²Partially immune: 0.01 to < 0.1 IU/ml, ³Immune 0.1 IU/ml *Susceptible: Absorbance value < 0.3, Partially immune: Absorbance value 0.3 to < 1, Immune: Absorbance value 1 of males and females with immunity did not differ significantly in each age group except in years of age (83.3% of female v 95.3% of males, P= 0.03, had levels 0.1 IU/ml) Pertussis: Of the 360 serum samples tested, 44.3% had antibodies to PT but only 1.4% were immune against pertussis. Prevalence of subjects seropositive for anti PT increased with age, ranging from 33.6 % in the years of age to 54.6% in the years of age (Table 1). Chi-square test for linear trend was highly significant (p = ) with rates peaked at aged years. A total of 195 (55.7%) subjects were seronegative. Percentage of anti PT increasing with age in women is higher than in men (Fig. 1), but these differences were not significant statistically (p > 0.05). The prevalence of cough for more than two weeks was found to be 5%. Sixty six percent of them had antibody to PT. DISCUSSION In Iran, little is known about seroprevalence of antidiphtheria, tetanus and pertussis antibodies Fig. 1. Percentage of sera with antitoxin levels 0.01 IU/ml for diphtheria and tetanus and percentage of seropositive sera for anti PT by sex and age group 252

4 Seroprevalence of antibodies to diphtheria, tetanus and pertussis among healthy adolescents and adults. The Iranian Advisory Committee on the immunization practices has implemented a primary course of combined DTP vaccine in childhood (at age 2, 4 and 6 months, with two additional doses at the age of months and 4-6 years), plus booster doses containing only diphtheria and tetanus (dt) every 10 years thereafter. Also to prevent neonatal tetanus pregnant women whose vaccination state is unknown or who have not received three primary doses of tetanus vaccination series during their lives should receive two doses of dt vaccine at 4th and 6-7th month of pregnancy and those who complete their childhood vaccination courses, but receive last tetanus toxoid containing vaccines 10 years previously, should receive one dose dt during their pregnancy. Diphtheria and tetanus: In this study over 90% of children had tetanus and diphtheria antitoxin levels 0.01 IU/ml. For both diphtheria and tetanus the lowest antitoxin levels were seen in persons aged years whereas subjects aged years had the highest levels. Diphtheria antitoxin levels were lower than tetanus antitoxin in all age groups and compatible with other studies [10, 11]. In one study in Razi Institute in Iran, the immunity level against tetanus and diphtheria 2-4 weeks after DTP vaccination was evaluated; thus, 99.4% of children were immune against both tetanus and diphtheria, so lower diphtheria antitoxin level than tetanus in this study shows that people lose their immunity against diphtheria sooner than tetanus. Also 94.3 % of women aged years had sufficient tetanus antitoxin to protect against neonatal tetanus compatible with CDC recommendation [3]. Our results are comparable with those of serosurvey in other countries with similar vaccination histories, such as Australia, Thailand and the United States [11-13], and reflect the efficiency of the vaccination program in Iran. To reduce the risk of reintroducing diphtheria to Iran, travelers to endemic or epidemic regions like Afghanistan need to be fully immunized; also, maintaining high childhood vaccination rates is necessary to achieve herd immunity to diphtheria and to protect individuals against tetanus. Insufficient maternal anti tetanus concentration is the most important reason for neonatal tetanus, so screening and vaccination of eligible women during pregnancy is essential. In addition to vaccination, promotion of clean deliveries and improvement of surveillance are important to reduce neonatal tetanus cases. Pertussis: Over half of the subjects did not have any antibody to PT and the percentage of immune subjects was very low, compatible with the fact that immunity to pertussis wanes approximately 5-10 years after completion of childhood pertussis vaccination [1, 13, 14] and may be because of lower efficiency of pertussis vaccines produced in Iran [15]. These results were similar to other studies, estimate the antibody to PT in Spain and Australia [8,16] but antibody to PT was lower than in two studies reported in Turkey [17, 18]. In our study the percentage of people who had antibody to PT increased with age and the highest was in years of age, which was not compatible with routine vaccination against pertussis in Iran. This increase reflects the acquisition of natural immunity from asymptomatic B. pertussis infection [8, 14, 17, 19]. These adolescents and adults can then become a source of infection for neonatal and young infants who have not yet completed their vaccination schedules. Also the proportion of persons with cough more than two weeks was 5% which may be the result of subclinical infections. In the United States, two Tdap products (Adacel and Boostrix) were licensed for use in adolescents and adults (11-64 years of age) [1, 20], and in many studies efficiency and safety of these vaccines were evaluated [1, 10, 21-23]. Because of the high proportion of persons without antibody to PT, increasing subclinical B. pertussis infection, and high prevalence of mortality and hospitalization of infants due to pertussis in Iran, the best way to reach higher immunity in adults and adolescents and potentially reduce the incidence of pertussis in infants, is addition of pertussis vaccine in Iranian vaccination schedule for one dose as CDC recommended. However, before these decisions, evaluation of the health benefits, risks, costs and cost effectiveness of pertussis vaccination is necessary. REFERENCES 1. Broder KR, Cortese MM, Iskander JK, Kretsinger K, Slade BA, Brown KH, Mijalski CM, Tiwari T, Weston EJ, Cohn AC, Srivastava PU, Moran JS, Schwartz B, Murphy TV. Advisory Committee on Immunization Practices (ACIP). Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2006: 24;55(RR-3): Saffar MJ, Khalilian AR, Ajami A, Saffar H, Qaheri A. Seroimmunity to diphtheria and tetanus among mother-infant pairs; the role of maternal immunity in 253

5 POURAKBARI et al. infant immune response to diphtheriatetanus vaccination. Swiss Med Wkly 2008;138: Murphy TV, Slade BA, Broder KR, Kretsinger K, Tiwari T, Joyce PM, Iskander JK, Brown K, Moran JS. Prevention of Pertussis, Tetanus, and Diphtheria Among Pregnant And Postpartum Women And Their Infants. CDC MMWR 2008; 57: Dikici B, Uzun H, Yilmaz-Keskin E, Tas T, Gunes A, Kocamaz H, Konca C, Tas MA. Neonatal tetanus in Turkey; What has changed in the last decade? BMC Infectious disease 2008;8. 5. Poudel P, Singh R, Raja S, Budhathoki S. Pediatric and neonatal tetanus: a hospital based study at eastern Nepal. Med Coll J 2008;10: Roper MH, Vandelaer JH, Gasse OL. Maternal and neonatal tetanus. Lancet 2007; 370: Heininger U, Cherry JD. Pertusiss immunization in adolescents and adults- Bordetella Pertussis epidemiology should guide vaccination recommendations. Expert Opin Biol Ther 2006; 6: García-Corbeira P, Dal-Ré R, Aguilar L, García-de- Lomas J. Seroepidemiology of Bordetella pertussis infections in the Spanish population: a cross-sectional study. Vaccine 2000; Poland GA. The Growing Paradigm of Preventing Disease: Vaccines To Prevent Herpes Zoster and Pertussis in Adults. Ann Intern Med 2005;143: Nakajima H, Kariya H, Ohata R, Ogura H. Investigation of Immunity Level against Diphtheria and Reinforcement of Immunity by Booster Vaccination for Infection Control Staff in Okayama Prefecture. Jpn J Infect Dis 2008; 61: Gidding HF, Backhouse JL, Burgess MA, Gilbert GL. Immunity to diphtheria and tetanus in Australia: a national serosurvey. MJA 2005;183: Chatchatee P, Chatproedprai S, Warinsathien P, Tharmaphornpilas P, Yoocharoen P, Warintrawat S, Theamboonlers A, Chongsrisawat V, Poovorawan Y. Seroprevalence of tetanus antibody in the Thai population: a national survey. Asian Pac J Allergy Immunol 2007; 25: McQuillan GM, Kruszon-Moran D, Deforest A, Chu SY, Wharton M. Serologic immunity to diphtheria and tetanus in United States. Ann Intern Med 2002; 136: Baughman AL, Bisgard KM, Edwards KM, Guris D, Decker MD, Holland K, Meade BD, Lynn F. Establishment of Diagnostic Cutoff Points for Levels of Serum Antibodies to Pertusiss Toxin, Filamentous Hemagglutinin, and Fimberiae in Adolescents and Adults in the United States. Clin Diagn Lab Immunol 2004; 11: Zarei S, Jeddi-Tehrani M, Akhondi MM, Zeraati H, Kheirkhah T, Ghazanfari M, Shokri F. Immunogenicity of a triple diphtheria tetanus - whole cell pertussis vaccine in Iranian preschool children. Iran J Immunol 2007; 4: Cagney M, McIntyre PB, Heron L, Giammanco A, MacIntyre CR. The relationship between Pertussis symptomatology, incidence and serology in adolescents. Vaccine 2008; 26: Cevik M, Beyazova U, Aral AL, Duyan Camurdan A, Ozkan S, Sahin F, Aybay C. Seroprevalence IgG antibodies against Bordetella pertussis in healthy individuals aged 4-24 years in Turkey. Clin Micribiol Infect 2008; 14: Aksakal FN, Cöplü N, Ceyhan MN, Sönmez C, Ozkan S, Esen B, Ilhan MN, Aygün R. High incidence of pertussis among school children with prolonged cough in Turkey. Tohoko J Exp Med 2007; 211: Konda T, Kamachi K, Iwaki M, Matsunaga Y. Distribution of Pertusiss antibodies among different age groups in Japan. Vaccine 2005; 20: Broder KR, Cortese MM, Iskander JK. FDA Approval of Expanded Age Indication for a Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine. CDC MMWR Pichichero ME, Rennels MB, Edwards KM, Blatter MM, Marshall GS, Bologa M, Wang E, Mills E. Combined Tetanus, Diphtheria, and 5-Component Pertussis Vaccine for Use in Adolescents and Adults. JAMA 2005; 293: Huang LM, Chang LY, Tang H, Bock HL, Lu CY, Huang FY, Lin TY, Lee CY. Progetto Petosse Working Group. Immunogenecity and reactogenecity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine in healthy Taiwanese children and adolescents. J Adoesc Health 2005; 37: Pichichero MF, Blatter MM, Kennedy WA, Hedrick J, Descamps D, Friedland L. Acellular pertussis vaccine booster combined with diphtheria and tetanus toxoids for adolescents. Pediatrics 2006;117: