Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Evaluation of Antibodies Against Haemophilus influenzae Type b in Korean Adults

우리나라 성인에서 Haemophilus influenzae type b에 대한 항체 평가

  • Lee, Ji Hyen (Department of Pediatrics, Ewha Womans University School of Medicine) ;
  • Kim, Han Wool (Center for Vaccine Evaluation and Study, Medical Research Institute, Ewha Womans University School of Medicine) ;
  • Lee, Soyoung (Center for Vaccine Evaluation and Study, Medical Research Institute, Ewha Womans University School of Medicine) ;
  • Kim, Kyung-Hyo (Department of Pediatrics, Ewha Womans University School of Medicine)
  • 이지현 (이화여자대학교 의과대학 소아과학교실) ;
  • 김한울 (이화여자대학교 의과대학 의과학연구소 백신효능연구센터) ;
  • 이소영 (이화여자대학교 의과대학 의과학연구소 백신효능연구센터) ;
  • 김경효 (이화여자대학교 의과대학 소아과학교실)
  • Received : 2017.03.03
  • Accepted : 2017.06.10
  • Published : 2017.12.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: After the introduction of Haemophilus influenzae type b (Hib) vaccine in 1995 in Korea, it was included in the national immunization program in 2013. In the post-Hib vaccine era, some studies in other countries reported that invasive Hib disease affects adults, especially the elderly and immunocompromised persons, more often than it affects children. To evaluate disease susceptibility, quantitative and qualitative analysis of anti-polyribosylribitol phosphate (PRP) antibodies were carried out in Korean adults aged 20 to 85 years. Methods: Sera were collected from 39 healthy adults (20 to 50 years of age) and from 30 elderly adults (75 to 85 years of age) who did not have immune-compromising conditions. The concentration of anti-PRP immunoglobulin G (IgG) and serum bactericidal indices (SBIs) were measured by enzyme-linked immunosorbent assay and serum bactericidal assay. Results: Geometric mean concentrations of anti-PRP IgG and geometric mean SBIs were $0.88{\mu}g/mL$ (95% confidence interval [CI], 0.17 to 3.85) and 354 (95% CI, 50 to 2,499) in young adults and $1.67{\mu}g/mL$ (95% CI, 0.53 to 5.24) and 449 (95% CI, 146 to 1,376) in elderly adults, respectively. When the threshold of seropositivity for anti-PRP IgG was applied as 0.15 or $1.0{\mu}g/mL$, which is the protective antibody level in children, seropositive rates were 87.2% or 53.8% in young adults and 100% or 60% in elderly adults. The seropositivity rates of the SBI ($SBI{\geq}4$) were 82.1% and 100% in the groups, respectively. Conclusions: Most subjects in the adult and elderly adult groups display immunity to Hib based on quantitative and qualitative antibody levels, but not all. Because high immunization and low Hib circulation rates may reduce the natural Hib immunity in the population, monitoring Hib immunity as well as disease are needed continuously.

목적: 1995년 한국에서 b형 헤모필루스 인플루엔자(Haemophilus influenzae type b [Hib]) 백신이 도입된 이후, 2013년 국가예방접종에 포함되었다. Hib 백신 도입 시기 이후 다른 나라의 일부 연구에 따르면, 침습적 Hib 질환은 소아보다 성인, 특히 노인 및 면역 저하 환자에서 더 자주 발생한다고 보고하였다. 따라서, 본 연구는 20-85세의 한국 성인에서 항-polyribosylribitol phosphate (PRP) 항체의 양적 및 질적 측정을 통하여 질병 감수성을 평가하고자 하였다. 방법: 혈청은 39명의 건강한 성인(20-50세)과 면역 저하 상태가 아닌 30명의 노인(75-85세)에서 수집하였다. 모든 피험자는 7일 이내에 항생제를 복용하지 않았다. 항-PRP 면역글로불린 G (immunoglobulin G [IgG]) 항체가 및 혈청 살상능 역가(serum bactericidal index [SBI])는 효소결합면역흡착측정법과 혈청 살상능 평가분석을 통해 측정하였다. 결과: 항-PRP IgG 항체가의 기하평균 및 SBI의 기하평균은 성인군에서 각각 $0.88{\mu}g/mL$ (95% 신뢰 구간, 0.17-3.85) 및 354 (95% 신뢰구간, 50-2,499)이었고, 노인군에서는 각각 $1.67{\mu}g/mL$ (95% 신뢰구간, 0.53-5.24) 및 449 (95% 신뢰구간, 146-1,376)이었다. 소아에서 Hib 감염에 대한 방어 농도로 인정하고 있는 0.15 및 $1.0{\mu}g/mL$을 적용하였을 때, 항체 양성률은 성인군에서 87.2%, 노인군에서 100%였다. SBI의 양성률($SBI{\geq}4$)은 성인군에서 82.1%, 노인군에서 100%였다. 결론: 대부분의 성인군과 노인군에서 양적으로나 기능적으로 Hib 질환에 대한 방어 면역력을 가지고 있었으나 모두는 아니었다. 높은 면역력과 낮은 Hib 순환율은 인구에서 Hib에 대한 자연면역을 감소시킬 수 있으므로, Hib 면역과 질병에 대한 지속적인 감시가 필요하다.

Keywords

References

  1. Chandran A, Watt JP, Santosham M. Haemophilus influenzae vaccine. In: Plotkin SA, Orenstein WA, Offit PA, editors. Vaccines. 6th ed. Philadelphia: Elsevier Health Sciences, 2013:167-82.
  2. Pittman M. Variation and type specificity in the bacterial species Hemophilus influenzae. J Exp Med 1931;53:471-92. https://doi.org/10.1084/jem.53.4.471
  3. Kim KH, Lee H, Chung EH, Kang JH, Kim JH, Kim JS, et al. Immunogenicity and safety of two different Haemophilus influenzae type b conjugate vaccines in Korean infants. J Korean Med Sci 2008;23:929-36. https://doi.org/10.3346/jkms.2008.23.6.929
  4. Kim HW, Kim KH, Kim J, Nahm MH. A high throughput serum bactericidal assay for antibodies to Haemophilus influenzae type b. BMC Infect Dis 2016;16:473. https://doi.org/10.1186/s12879-016-1808-4
  5. Mackenzie GA, Ikumapayi UN, Scott S, Idoko O, Odutola A, Ndiaye M, et al. Increased disease due to Haemophilus influenzae type b: population-based surveillance in eastern Gambia, 2008-2013. Pediatr Infect Dis J 2015;34:e107-12. https://doi.org/10.1097/INF.0000000000000645
  6. Idoko OT, Roberts E, Cox M, Jafali J, Njie-Jobe J, Mackenzie G, et al. Antibodies against Haemophilus influenzae type b in The Gambia: investigating the extent of protection across age groups. Vaccine 2014;32:4620-4. https://doi.org/10.1016/j.vaccine.2014.06.078
  7. McVernon J, Trotter CL, Slack MP, Ramsay ME. Trends in Haemophilus influenzae type b infections in adults in England and Wales: surveillance study. BMJ 2004;329: 655-8. https://doi.org/10.1136/bmj.329.7467.655
  8. Dworkin MS, Park L, Borchardt SM. The changing epidemiology of invasive Haemophilus influenzae disease, especially in persons > or = 65 years old. Clin Infect Dis 2007;44:810-6. https://doi.org/10.1086/511861
  9. Rubach MP, Bender JM, Mottice S, Hanson K, Weng HY, Korgenski K, et al. Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah, USA. Emerg Infect Dis 2011;17:1645-50. https://doi.org/10.3201/eid1709.101991
  10. Shuel M, Hoang L, Law DK, Tsang R. Invasive Haemophilus influenzae in British Columbia: non-Hib and nontypeable strains causing disease in children and adults. Int J Infect Dis 2011;15:e167-73. https://doi.org/10.1016/j.ijid.2010.10.005
  11. Kim KH, Lim SY. Validation of enzyme immunoassay for the quantitative measurement of human IgG antibodies specific for Haemophilus influenzae type b capsular poly saccharide. Korean J Pediatr 2007;50:143-50. https://doi.org/10.3345/kjp.2007.50.2.143
  12. Peltola H, Kayhty H, Sivonen A, Makela H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 1977;60: 730-7.
  13. Oh SY, Griffiths D, John T, Lee YC, Yu LM, McCarthy N, et al. School-aged children: a reservoir for continued circulation of Haemophilus influenzae type b in the United Kingdom. J Infect Dis 2008;197:1275-81. https://doi.org/10.1086/586716
  14. Kayhty H, Peltola H, Karanko V, Makela PH. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis 1983;147:1100. https://doi.org/10.1093/infdis/147.6.1100
  15. Nix EB, Hawdon N, Gravelle S, Biman B, Brigden M, Malik S, et al. Risk of invasive Haemophilus influenzae type b (Hib) disease in adults with secondary immunodeficiency in the post-Hib vaccine era. Clin Vaccine Immunol 2012;19:766-71. https://doi.org/10.1128/CVI.05675-11
  16. Chalmers C. Necrotising fasciitis complicating Haemophilus influenzae type b epiglottitis in an adult. J Laryngol Otol 2010;124:807-9. https://doi.org/10.1017/S0022215109992076
  17. Saito T, Matsunaga H, Matsumura Y, Segawa H, Takakura S, Nagao M, et al. Necrotizing fasciitis caused by Haemophilus influenzae type b in an elderly patient. J Clin Microbiol 2009;47:852-4. https://doi.org/10.1128/JCM.01196-08
  18. Chew CG, Clarkson AR, Faull RJ. Relapsing CAPD peritonitis with rapid peritoneal sclerosis due to Haemophilus influenzae. Nephrol Dial Transplant 1997;12:821-2. https://doi.org/10.1093/ndt/12.4.821
  19. Neuhaus TJ, Iselin H, Nadal D. Haemophilus influenzae: a cause of peritonitis in peritoneal dialysis. Nephrol Dial Transplant 1996;11:199-200. https://doi.org/10.1093/ndt/11.1.199
  20. Public Health Agency of Canada. Canadian immunization guide 2006. 7th ed. Ottawa: Public Health Agency of Canada, 2006.
  21. Collins S, Ramsay M, Campbell H, Slack MP, Ladhani SN. Invasive Haemophilus influenzae type b disease in England and Wales: who is at risk after 2 decades of routine childhood vaccination? Clin Infect Dis 2013;57:1715-21. https://doi.org/10.1093/cid/cit579
  22. Skoff TH, Farley MM, Petit S, Craig AS, Schaffner W, Gershman K, et al. Increasing burden of invasive group B streptococcal disease in nonpregnant adults, 1990-2007. Clin Infect Dis 2009;49:85-92. https://doi.org/10.1086/599369
  23. Edwards MS, Baker CJ. Group B streptococcal infections in elderly adults. Clin Infect Dis 2005;41:839-47. https://doi.org/10.1086/432804
  24. Jelonek MT, Chang SJ, Chiu CY, Park MK, Nahm MH, Ward JI. Comparison of naturally acquired and vaccineinduced antibodies to Haemophilus influenzae type b capsular polysaccharide. Infect Immun 1993;61:5345-50.
  25. Kim YJ, Hwang JY, Choi SH, Kong E, Kim Y, Park KS, et al. Antibody responses in hematopoietic cell transplantation recipients after vaccination against Haemophilus influenzae type b and Streptococcus pneumoniae. Korean J Pediatr Infect Dis 2014;21:81-95. https://doi.org/10.14776/kjpid.2014.21.2.81
  26. Lee H, Nahm MH, Burton R, Kim KH. Immune response in infants to the heptavalent pneumococcal conjugate vaccine against vaccine-related serotypes 6A and 19A. Clin Vaccine Immunol 2009;16:376-81. https://doi.org/10.1128/CVI.00344-08
  27. Song JY, Moseley MA, Burton RL, Nahm MH. Pneumococcal vaccine and opsonic pneumococcal antibody. J Infect Chemother 2013;19:412-25. https://doi.org/10.1007/s10156-013-0601-1
  28. World Health Organization. Guidelines on clinical evaluation of vaccines: regulatory expectations. Proposed revision of WHO TRS 924, Annex 1 [Internet]. Geneva: World Health Organization; 2004 [cited 2017 Nov 7]. Available from: http://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf.
  29. Cho HK, Park IH, Burton RL, Kim KH. Impact of IgM antibodies on cross-protection against pneumococcal serogroups 6 and 19 after immunization with 7-valent pneumococcal conjugate vaccine in children. J Korean Med Sci 2016;31:950-6. https://doi.org/10.3346/jkms.2016.31.6.950
  30. Kim KH. Present status and prospects of Haemophilus influenzae type b (Hib) immunization. Korean J Pediatr 2006;49:242-50. https://doi.org/10.3345/kjp.2006.49.3.242
  31. Shinefield HR, Black S. Postlicensure surveillance for Haemophilus influenzae type b invasive disease after use of Haemophilus influenzae type b oligosaccharide CRM197 conjugate vaccine in a large defined United States population: a four-year eight-month follow-up. Pediatr Infect Dis J 1995;14:978-81. https://doi.org/10.1097/00006454-199511000-00011
  32. Watt JP, Levine OS, Santosham M. Global reduction of Hib disease: what are the next steps? Proceedings of the meeting Scottsdale, Arizona, September 22-25, 2002. J Pediatr 2003;143(6 Suppl):S163-87.