Evaluation of anti-diphtheria toxoid antibody persistence in school-age children in Jakarta, Indonesia

Theresia Santi; Ari Prayitno; Zakiudin Munasir; Sri Rezeki S. Hadinegoro; Alida Roswita Harahap; Retno Asti Werdhani; Ivo Novita Sah Bandar; Juandy Jo; Badriul Hegar

Theresia Santi Doctoral Program in Medical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Ari Prayitno Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Zakiudin Munasir Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Sri Rezeki S. Hadinegoro Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Alida Roswita Harahap Doctoral Program in Medical Science, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Retno Asti Werdhani Department of Community Medicine, Cipto Mangunkkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia
Ivo Novita Sah Bandar Iwate Medical University, Morioka, Japan
Juandy Jo Department of Biology, Faculty of Science and Technology, Universitas Pelita Harapan, Tangerang, Indonesia; Mochtar Riady Institute for Nanotechnology, Tangerang, Indonesia;
Badriul Hegar Department of Child Health, Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia; Indonesian Medical Education and Research Institute, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia

Keywords: diphtheria; anti-diphtheria toxoid; children; booster vaccination

Abstract

Background Diphtheria can be effectively prevented by adequate immunization. A combined vaccine against diphtheria toxoid, pertussis, and tetanus toxoid (DPT) is currently used in routine pediatric immunizations. Outbreaks of diphtheria could emerge in Indonesia as a consequence of declining routine vaccination during the COVID-19 pandemic.

Objective To analyze the impact of the first (administered at 18-24 months of age ) and second diphtheria boosters (administered at 5-7 years of age ) in retaining protective levels of anti-diphtheria toxoid antibodies. We also investigated for relevant factors associated with anti-diphtheria toxoid antibody titers.

Methods This cross-sectional study was conducted in the Senen District of Jakarta, Indonesia. The inclusion criteria were healthy children aged 6 to 7 years with documented history of DPT vaccination. Primary vaccination defined as 3 doses of DPT at age less than 1 year , first booster was DPT vaccination at 18-24 years of age, and second booster was diphtheria-tetanus (DT) vaccination received at 5 to 7 years of age. Peripheral blood specimens were obtained from participating children, after informed consent was provided by their parents. Antibodies against diphtheria in sera specimens were assessed by commercial anti-diphtheria toxoid immunoglobulin G (IgG) enzyme-linked immunosorbent assay.

Results There were 154 children included in the study, with a female majority (61%). Overall, specific humoral immunity against diphtheria was observed in 113 children (73.4%). There was no statistical difference in immunity level between genders. Importantly, children who received the first and second diphtheria booster had significantly higher anti-diphtheria antibody level than those who did not receive both diphtheria booster (P<0.001).

Conclusion Booster vaccinations are crucial among school-age children in Indonesia to improve their anti-diphtheria immunity and to minimize a risk of diphtheria outbreaks.

References

1. Sharma N, Efstratiou A, Mokrousov I, Mutreja A, Das B, Ramamurthy T. Diphtheria. Nat Rev Dis Primers. 2019;5:81. DOI: https://doi.org/10.1038/s41572-019-0131-y
2. Hadfield TL, McEvoy P, Polotsky Y, Tzinserling VA, Yakovlev AA. The pathology of diphtheria. J Infect Dis. 2000;181:S116–20. DOI: https://doi.org/10.1086/315551
3. World Health Organization. Diphtheria vaccine: WHO position paper - August 2017. Wkly Epidemiol Rec. 2017;31:425-34. [cited 2023 Nov 1]. Available from: https://iris.who.int/bitstream/handle/10665/258681/WER9231.pdf?sequence=1
4. Indonesian Pediatric Society. Childhood immunization update 2023. Proceeding on childhood immunization update 2023 May 28- 29; Jakarta: 2023. [internet]. [cited 2023 Nov 1]. Available from: https://www.idai.or.id/publications/buku-idai/proceeding-book-childhood-immunization-update-2023.
5. Kementerian Kesehatan Republik Indonesia. Profil Kesehatan Indonesia 2017. [cited 2023 Nov 1]. Available from: https://www.kemkes.go.id/app_asset/file_content_download/Profil-Kesehatan-Indonesia-2017.pdf.
6. Tosepu R, Gunawan J, Effendy DS, Ahmad OAI, Farzan A. The outbreak of diphtheria in Indonesia. Pan Afr Med J. 2018;31:249. DOI: https://doi.org/ 10.11604/pamj.2018.31.249.16629
7. Harapan H, Anwar S, Dimiati H, Hayati Z, Mudatsir M. Diphtheria outbreak in Indonesia, 2017: an outbreak of an ancient and vaccine-preventable in the third millennium. Clin Epidemiol Glob Health. 2018;7:261–2. DOI: https://doi.org/10.1016/j.cegh.2018.03.007
8. Arguni E, Karyanti MR, Satari HI, Hadinegoro SR. Diphtheria outbreak in Jakarta and Tangerang, Indonesia: epidemiological and clinical predictor factors for death. PLoS One. 2021;16:e0246301. DOI: 10.1371/journal.pone.0246301. eCollection 2021
9. The Ministry of Health, Indonesia & UNICEF Indonesia. Routine immunization for children during the COVID-19 pandemic in Indonesia: perception of parents and caregivers. August 2020. [cited 2023 Sep 20]. Available from: https://www.unicef.org/indonesia/reports/routine-immunization-children-during-covid-19-pandemic-indonesia.
10. Nina A. Loasana. West Java regency declares diphtheria outbreak after 7 deaths. The Jakarta post. 2023 Feb 25. [cited 2023 Nov 5]. Available at : https://www.thejakartapost.com/indonesia/2023/02/24/west-java-regency-declares-diphtheria-outbreak-after-7-deaths.html.
11. Gunardi H, Rusmil K, Fadlyana E, Dhamayanti M, Sekartini R, Tarigan R, et al. DTwP-HB-Hib: antibody persistence after a primary series, immune response and safety after a booster dose in children 18-24 months old. BMC Pediatr. 2018;18:1–8. DOI: https://doi.org/10.1186/s12887-018-1143-6
12. Le TV, Nguyen VT, Nguyen QH, Nguyen TT, Duong TT, Ly TT, et al. The evaluation of anti-diphtheria toxoid antibodies in healthy population in Kon Tum, Vietnam: a population-based study. IJID Reg. 2022;3:171-6. DOI: https://doi.org/10.1016/j.ijregi.2022.03.019
13. Lassi ZS, Naseem R, Salam RA, Siddiqui F, Das JK. The impact of the COVID-19 Pandemic on immunization campaigns and programs: a systematic review. Int J Environ Res Public Health. 2021;18:988. DOI: https://doi.org/10.3390/ijerph18030988. PMID: 33499422.
14. World Health Organization. At least 80 million children under one at risk of diseases such as diphtheria, measles and polio as COVID-19 disrupts routine vaccination efforts, warn Gavi, WHO and UNICEF. WHO News release. 2020. Sep 2020 [cited 2023 Sep 20]. Available from: https://www.who.int/news/item/22-05-2020-at-least-80-million-children-under-one-at-risk-of-diseases-such-as-diphtheria-measles-and-polio-as-covid-19-disrupts-routine-vaccination-efforts-warn-gavi-who-and-unicef
15. UNICEF. Indonesia targets low vaccination areas to tackle decline in childhood immunization. 2023. [cited 2023 Nov 1]. Available from: https://www.unicef.org/indonesia/press-releases/indonesia-targets-low-vaccination-areas-tackle-decline-childhood-immunization.
16. Metcalf CJ, Farrar J, Cutts FT, Basta NE, Graham AL, Lessler J, et al. Use of serological surveys to generate key insights into the changing global landscape of infectious disease. Lancet. 2016;388:728-30. DOI: https://doi.org/10.1016/S0140-6736(16)30164-7
17. Yusoff AF, Sharani ZZM, Cheong KC, Iderus NH, Zamri AS, Nagalingam T, et al. Seroprevalence of diphtheria toxoid IgG antibodies in the Malaysian population. BMC Infect Dis. 2021;21:581.DOI: https://doi.org/10.1186/s12879-021-06285-3
18. Murhekar MV, Kamaraj P, Kumar MS, Siraj Ahmed Khan SA, Allam RR, Barde PV, et al. Immunity against diphtheria among children aged 5–17 years in India, 2017–18: a cross-sectional, population-based serosurvey. The Lancet Infect Dis. 2021;21:868–75. DOI: https://doi.org/10.1016/S1473-3099(20)30595-8
19. Josephine P. Vaccine preventable diseases, current status, outbreak and mitigation. In: Hadinegoro SRH, Gunardi H, Handryastuti S, Kaswandhani N, Raihan, eds. Proceeding Book Childhood Immunization Update 2023. Jakarta: Badan Penerbit Ikatan Dokter Anak Indonesia; 2023. p.1-16.