Dietz Klaus, Raddatz Günter, Molineaux Louis
Department of Medical Biometry, University of Tübingen, Tübingen, Germany.
Am J Trop Med Hyg. 2006 Aug;75(2 Suppl):46-55. doi: 10.4269/ajtmh.2006.75.46.
We present a dynamic model of the highly pathogenic first wave of Plasmodium falciparum asexual parasitemia in non-immune persons. The model was successfully fitted to malaria therapy data. This required four case-specific parameters: the basic two-day multiplication factor, the time of onset of adaptive immunity, and the effective dose 50 densities for the innate and adaptive immune responses, respectively. All four parameters show large case-dependent variation that is mainly attributable to host factors. According to the model, the maximum value of the first wave is controlled mainly by the innate immune response. We used the model to explore the expected effects of vaccines targeting the parasite's asexual blood stages on the basis of what we consider to be the biologically most plausible assumptions concerning the parameter modifications induced by vaccination. According to our simulations, the benefit of antiparasitic vaccination is strongly host dependent and vaccine efficacy at low immunogenicity is much larger against severe disease than against fever. This has implications for the early testing of the protective efficacy of a vaccine in humans.
我们提出了一个针对非免疫人群中恶性疟原虫无性疟原血症高致病性第一波的动态模型。该模型成功拟合了疟疾治疗数据。这需要四个病例特异性参数：基本的两天增殖因子、适应性免疫开始时间以及先天免疫和适应性免疫反应的有效剂量50密度。所有这四个参数都显示出很大的病例依赖性变化，这主要归因于宿主因素。根据该模型，第一波的最大值主要由先天免疫反应控制。我们基于我们认为关于疫苗接种引起的参数改变在生物学上最合理的假设，使用该模型来探索针对寄生虫无性血液阶段的疫苗的预期效果。根据我们的模拟，抗寄生虫疫苗接种的益处强烈依赖于宿主，并且在低免疫原性下疫苗对严重疾病的效力比对发烧的效力要大得多。这对疫苗在人体中的保护效力的早期测试具有启示意义。
