The effect of mixed Plasmodium infections on morbidity

描述（由申请人提供）：拟议的研究旨在通过对巴布亚新几内亚全流行地区1 - 4岁儿童进行纵向随访研究，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导致的发病率的影响的理解。特别是，我们将确定急性单纯性疟疾和贫血与先前和同时感染不同疟原虫有关的模式，并确定疟疾发病率和贫血的跨物种保护，检验间日疟原虫和/或疟疾疟原虫的共同感染降低了同时感染或随后感染恶性疟原虫的临床疾病的发病率和严重程度的假设。我们还将评估在无症状感染水平上的潜在相互作用。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干预措施（例如主要针对某一物种的疟疾疫苗）可能产生的影响至关重要。为了实现这些目标，我们将在当地卫生中心对250名每两个月出血、每两周进行主动发病率监测和被动病例检测的儿童进行随访。将使用光学显微镜和pcr -连接酶检测反应（LDR）法对所有横断面出血和检测到的发病期的血液样本进行疟疾感染评估。同时测定血红蛋白水平。跨物种预防发病率和异源感染之间的关联将通过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分析。强大的纵向设计、现有的最佳物种识别方法和复杂的统计分析相结合，为深入研究同一个体中跨物种相互作用的各个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.