The effect of mixed Plasmodium infections on morbidity

描述(申请人提供)：拟议的研究旨在通过对巴布亚新几内亚全流行地区的1-4岁儿童进行纵向跟踪研究，加深我们对不同疟疾物种相互作用对疟疾感染发病率和由此产生的发病率的影响的了解。特别是，我们将确定与以前和同时感染不同疟原虫相关的急性单纯性疟疾和贫血的模式，并确定跨物种保护、疟疾发病率和贫血测试假设，即与间日疟原虫和/或间日疟原虫混合感染可降低合并或随后感染恶性疟原虫的临床疾病的发病率和严重程度。我们还将在无症状感染的水平上评估潜在的相互作用。更好地了解潜在的跨物种保护对于了解疟疾发病率的流行病学和主要针对某一物种的疟疾疫苗等干预措施的可能影响至关重要。为了实现这些目标，我们将在当地卫生中心跟踪250名患有双月出血、两周一次的主动发病率监测和被动病例发现的儿童。所有横断面出血和检测到的病程的血液样本都将通过光镜和聚合酶链合酶检测反应(LDR)分析进行疟疾感染评估。同时，还将测定血红蛋白水平。针对发病率的跨物种保护和异源感染之间的关联将使用队列研究的标准方法和包括混合模型和广义估计方程(GEE)在内的创新方法的混合来分析。强大的纵向设计、现有的最佳物种鉴定方法和复杂的统计分析相结合，为深入研究同一个体的跨物种相互作用的所有方面提供了独特的机会，从而有助于解决疟疾流行病学的这一重要方面。

DESCRIPTION (provided by applicant): The proposed study aims at deepening our understanding of the effect of interactions of different malaria species on incidence of malarial infections, and resulting morbidity by conducting a longitudinal follow-up study of children 1 - 4 years of age in a holoendemic are of Papua New Guinea. In particular we will determine patterns of acute simple malaria and anemia associated with prior and concurrent infections of different Plasmodium species and ascertain cross-species protection malarial morbidity and anemia test the hypothesis that co-infections with P. vivax and/or P. malariae reduce the incidence and severity of clinical disease with concurrent or subsequent P. falciparum infections. We will also assess potential interactions at the levels of asymptomatic infections. Better knowledge of potential cross-species protection is crucial to understanding the epidemiology of malarial morbidity and the possible effects of interventions, such as a malaria vaccine, primarily directed at one of the species. In order to achieve those aims we will follow-up 250 children with bi-monthly bleeds, fortnightly active morbidity surveillance and passive case detection at local health centers. All blood samples from cross-sectional bleeds and detected morbid episodes will be evaluated for malarial infections with both light microscopy and PCR-ligase detection reaction (LDR) assay. At the same time hemoglobin levels will be determined. Cross-species protection against morbidity and associations between heterologous infections will be analyzed with a mixture of standard methods for cohort studies and innovative approaches including mixed models and generalized estimating equations (GEE). The combination of a powerful longitudinal design, the best available methods of species identifications and sophisticated statistical analyses offers a unique opportunity for an in-depth examination of all aspects of cross-species interactions in the same individuals and thereby help to resolve this important aspect of malaria epidemiology.