Lin Ximin, Koopman James S, Chick Stephen E
Department of Epidemiology, University of Michigan, 109 Observatory Street, Ann Arbor, MI 48109, USA.
J Theor Biol. 2007 Mar 7;245(1):66-76. doi: 10.1016/j.jtbi.2006.09.034. Epub 2006 Oct 6.
Vaccines to prevent acute otitis media (AOM) caused by non-typeable Haemophilus influenzae (NTHi) are under development. Because NTHi is highly variable and colonization rates are high, special vaccine characteristics and trial designs might be needed. We examined in mathematical models the equilibrium NTHi-caused AOM rate given hypothetical vaccines that generated immunity identical to corresponding maximal naturally acquired immunity. Vaccines were examined with single effects and combinations of immunity affecting (1) AOM rates given colonization (pathogenicity), (2) susceptibility to colonization, and (3) contagiousness given colonization. Percent reductions in AOM across all preschool children were (1) 34%, (2) 31%, (3) 9%, (1 and 2) 57%, (2 and 3) 50%, and (1, 2, and 3) 75%. Effects on children in daycare vs. not in daycare were (1) 18 vs. 48%, (2) -1 vs. 57%, (3) 13 vs. 5%, (1 and 2) 30 vs. 79%, (2 and 3) 33 vs. 60%, and (1, 2, and 3) 64 vs. 85%. Pure pathogenicity effects (1 alone) will need to be supplemented by transmission effects. The effects of susceptibility (2 alone) are diminished or negative because children protected against colonization have lower levels of immunity to (1) and (3) than unvaccinated children. For trials to predict population effects, both colonization and AOM outcomes must be studied and all three effects must be evaluated. This need arises because, unlike H. influenzae type B, high NTHi exposure diminishes cumulative vaccine effects and high colonization rates generate rapid accumulation of natural immunity that alters the indirect effects of vaccine immunity on transmission differently by age and daycare status.
预防由不可分型流感嗜血杆菌（NTHi）引起的急性中耳炎（AOM）的疫苗正在研发中。由于NTHi高度可变且定植率高，可能需要特殊的疫苗特性和试验设计。我们在数学模型中研究了假设疫苗产生与相应最大自然获得性免疫相同的免疫力时，由NTHi引起的AOM的平衡发病率。对疫苗的单一效应以及影响免疫力的组合效应进行了研究，这些效应包括：（1）定植时的AOM发病率（致病性），（2）对定植的易感性，以及（3）定植时的传染性。所有学龄前儿童AOM发病率的降低百分比分别为：（1）34%，（2）31%，（3）9%，（1和2）57%，（2和3）50%，以及（1、2和3）75%。对参加日托的儿童与未参加日托的儿童的影响分别为：（1）18%对48%，（2）-1%对57%，（3）13%对5%，（1和2）30%对79%，（2和3）33%对60%，以及（1、2和3）64%对85%。单纯的致病性效应（仅1）需要通过传播效应来补充。易感性效应（仅2）减弱或为负，因为预防定植的儿童对（1）和（3）的免疫力水平低于未接种疫苗的儿童。为了预测疫苗对人群的影响，必须研究定植和AOM结局，并且必须评估所有三种效应。之所以有这种需求，是因为与B型流感嗜血杆菌不同，高NTHi暴露会降低疫苗的累积效应，高定植率会导致自然免疫力迅速积累，这会因年龄和日托状态不同而改变疫苗免疫对传播的间接效应。
