title: Estimating strain-specific and overall efficacy of polyvalent vaccines against recurrent pathogens from a cross-sectional study.
abstract: Evaluating vaccine efficacy for protection against colonization with bacterial pathogens is an area of growing interest. Colonization of the nasopharynx is an asymptomatic carrier state responsible for person-to-person transmission. It differs from most clinical outcomes in that it is common, recurrent, and observed only in its prevalent state. To estimate rates of acquisition and clearance of colonization requires repeated active sampling of the same individuals over time, an expensive and invasive undertaking. Motivated by feasibility constraints in efficacy trials with colonization endpoints, investigators have been estimating vaccine efficacy from cross-sectional studies without principled methods. We present two examples of vaccine studies estimating vaccine efficacy from cross-sectional data on nasopharyngeal colonization by Streptococcus pneumoniae (pneumococcus). This study presents a framework for defining and estimating strain-specific and overall vaccine efficacy for susceptibility to acquisition of colonization (VE(acq)) when there is a large number of strains with mutual interactions and recurrent dynamics of colonization. We develop estimators based on one observation of the current status per study subject, evaluate their robustness, and re-analyze the two vaccine trials. Methodologically, the proposed estimators are closely related to case-control studies with prevalent cases, with appropriate consideration of the at-risk time in choosing the controls.
authors: Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Finland. kari.auranen@thl.fi
authors: Kari
authors: K
authors: Auranen
authors: Hanna
authors: H
authors: Rinta-Kokko
authors: M Elizabeth
authors: ME
authors: Halloran
mesh_terms: D002353:Carrier State / Q000276:immunology* / Q000382:microbiology; D003198:Computer Simulation; D003430:Cross-Sectional Studies / Q000379:methods* / Q000592:standards; D006801:Humans; D007223:Infant; D015233:Models, Statistical; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000276:immunology* / Q000592:standards; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards; D013296:Streptococcus pneumoniae / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology / Q000592:standards
chemical_list: D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
references: Am J Epidemiol. 1992 May 1;135(9):1042-50
references: 1595690
references: J Infect Dis. 1999 Oct;180(4):1171-6
references: 10479145
references: J Microbiol Methods. 2008 Dec;75(3):540-4
references: 18801391
references: Pediatr Infect Dis J. 2007 Apr;26(4):319-24
references: 17414395
references: J Infect Dis. 2002 Apr 1;185(7):927-36
references: 11920317
references: Am J Epidemiol. 2007 Jul 15;166(2):228-35
references: 17517684
references: Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6571-6
references: 9177259
references: J Infect Dis. 2007 Oct 15;196(8):1211-20
references: 17955440
references: Hum Vaccin. 2008 Nov-Dec;4(6):444-8
references: 18728401
references: N Engl J Med. 2010 Apr 22;362(16):1511-20
references: 20410516
references: Am J Epidemiol. 2010 Jan 15;171(2):169-76
references: 19969530
references: Cad Saude Publica. 1994;10 Suppl 2:310-26
references: 15042221
references: Vaccine. 2000 Jun 15;18(25):2895-901
references: 10812233
references: J Chronic Dis. 1986;39(5):379-88
references: 3700579
references: Math Biosci. 1998 Dec 15;154(2):117-35
references: 9949651
references: Vaccine. 2009 Jun 12;27(29):3831-7
references: 19490983
references: Epidemiology. 2012 Jul;23(4):510-9
references: 22441543