Primate pilot study: coincident AIDS/relapsing malaria

描述(由申请人提供)： 人类免疫缺陷病毒和各种疟原虫在世界同一地区出现高流行率，造成严重的发病率和死亡率。我们提出了一项实验，将试验发展慢病毒和疟疾寄生虫共同感染的灵长类动物模型。我们将模拟的混合感染模式是生活在东南亚等世界地区的成年人，这些地区是间日疟原虫的地方性流行区，并且正在经历新的HIV-1感染的爆炸性增长。我们的研究将结合恒河猴艾滋病和疟疾的成熟模型：1)SIV，一种慢病毒，建立一种严重的免疫缺陷疾病(猴艾滋病，SAID)；2)食蟹猴疟原虫，导致类似于由间日疟原虫引起的复发疾病，间日疟原虫是人类传播最广泛的疟原虫物种。提出的研究假设是食蟹猴疟原虫引起的疟疾复发将改变SAID的进程和对SIV的免疫反应，而SIV的免疫抑制将改变P、食蟹猴生长、复发和对疟疾寄生虫的免疫反应。在具体目标I中，我们建议在恒河猴中进行一项关于SIV和食蟹猴混合感染的初步研究。在特定目标2中提出的研究将检查免疫参数，包括淋巴细胞亚群、趋化因子和细胞因子的表达，以及对选定的SIV和食蟹猴疟原虫蛋白的体液和细胞免疫反应，以确定这些参数中的哪些(如果有的话)与混合感染或单一感染动物中SAID或食蟹猴疟原虫复发的进展相关。拟议的试点试验的结果将指导进一步的研究，这些研究可能导致在世界上艾滋病和疟疾双重流行的地区改善个人保健的战略。

DESCRIPTION (provided by applicant): Human immunodeficiency viruses and various Plasmodium species have emerged to high prevalence in the same regions of the world Causing intense morbidity and mortality. We propose an experiment that will pilot development of a primate model of lentivirus and malaria parasite co-infection. The pattern of co- infection we will model is adults living in regions of the world, such as Southeast Asia, that are endemic for P. vivax malaria and are experiencing the most explosive increase in new HIV-1 infections. Our studies will combine well-established models of AIDS and malaria in rhesus macaques: 1) SIV, a lentivirus that establishes a severe immunodeficiency disease (simian AIDS, SAIDS) and 2) Plasmodium cynomolgi, which causes relapsing disease resembling malaria induced by P. vivax, the most wide-spread human Plasmodium species. The hypotheses underlying the proposed studies are that relapsing malaria induced by P. cynomolgi will alter the course of SAIDS and immune responses to SIV, and that immunosuppression by SIV will alter P, cynomolgi growth, relapse and immune responses to the malaria parasite. In Specific Aim I we propose to conduct a pilot study of co-infection with SIV and P. cynomolgi in rhesus macaques. The studies proposed in Specific Aim 2 will examine immunological parameters including lymphocyte subsets, chemokine and cytokine expression, and humoral and cellular immune responses to selected SIV and P. cynomolgi proteins to determine which, if any, of these parameters correlate with progression of SAIDS or P. cynomolgi relapsing malaria in co-infected or singly infected animals. Results of the proposed pilot experiment will direct further studies that may lead to strategies for improving health care of individuals in regions of the world where there are dual epidemics of AIDS and malaria.