The Burden of Malaria Transmission due to Asymptomatic HIV Co-Infection

描述（由申请人提供）：疟疾-艾滋病毒合并感染的公共卫生危机正在撒哈拉以南非洲迅速扩大。特别是肯尼亚西部的低地是疟疾传播的地方病，艾滋病毒/艾滋病感染率高得令人灾难。2006年该地区的一个传播数学模型回顾性地预测，自1980年以来，合并感染已导致累计超过8 500例HIV-1感染和980 000例疟疾发作。感染艾滋病毒的个人经历更频繁和更严重的临床疟疾发作，风险随着艾滋病毒疾病的进展而增加。然而，我们的试点研究和大量已发表的数据也表明，在疟疾全流行地区的艾滋病毒感染者中，无症状寄生虫血症和配子体血症也可能发生特定的增加。虽然许多研究在横断面研究中审查了合并感染和有症状疟疾的一个或多个复杂方面，但没有研究试图确定合并感染对无症状疟疾的纵向流行病学影响，特别是在这两种疾病传播率高和抗疟药物抗药性增加的地区对疟疾传播的影响。抗叶酸剂被广泛用于预防HIV相关的机会性感染，但它们也被认为会增加配子体的出现。我们假设，合并感染HIV和相关治疗可能直接导致无症状寄生虫携带和配子体血症的显著增加以及抗叶酸剂耐药寄生虫基因型的增加，因此，直接导致恶性疟疾负担的增加。为此，我们建议集中互补的临床和昆虫学研究，在肯尼亚西部的一个高度流行的地区，使用高度敏感和特异性的分子工具，以评估点和纵向的共同感染的患病率一般和配子体血症，特别是在流行的艾滋病毒治疗的背景下，疟疾传播的纵向风险的重点。 公共卫生相关性：艾滋病毒和疟疾合并感染导致疟疾临床发病率上升，尽管对发病率上升的原因尚不完全清楚。在我们的研究中，我们将研究一个新的假设，即肯尼亚疟疾负担的增加部分是由于合并感染患者的疟疾蚊媒传播增强。

DESCRIPTION (provided by applicant): The public health crisis of malaria-HIV co-infection is rapidly expanding in sub-Saharan Africa. Lowland western Kenya in particular is holoendemic for malaria transmission and is plagued with catastrophically high rates of HIV/AIDS infection. A 2006 mathematical model of transmission in this region retrospectively predicted that co-infection has resulted in a cumulative excess of 8,500 HIV-1 infections and 980,000 malaria episodes since 1980. Individuals infected with HIV experience more frequent and more severe episodes of clinical malaria and the risk increases with advancing HIV disease. However, our pilot studies and a significant body of published data also suggest that specific increases in asymptomatic parasitemias and gametocytemias also are likely to occur in HIV-infected individuals in malaria-holoendemic areas. While numerous studies have examined one or more of the complicating aspects of co-infection and symptomatic malaria in cross-sectional studies, no studies have attempted to determine the longitudinal epidemiological impact of co-infection on asymptomatic malaria and specifically on malaria transmission in regions characterized by high transmission of both diseases and by increasing antimalarial drug resistance. Antifolates are widely prescribed for prophylaxis of HIV-associated opportunistic infections, yet they are also known to increase the appearance of gametocytes. We hypothesize that co-infection with HIV, and associated therapy, could be directly responsible for significant increases in asymptomatic parasite carriage and gametocytemia as well as increased antifolate- resistant parasite genotypes and, therefore, contribute directly to the increased burden of falciparum malaria. To this end, we propose to focus complementary clinical and entomological studies using highly sensitive and specific molecular tools in a highly endemic area of western Kenya to assess point and longitudinal prevalence's of co-infection in general and gametocytemia in particular with an emphasis on longitudinal risk of malaria transmission in the context of prevailing HIV therapies. PUBLIC HEALTH RELEVANCE: HIV and malaria co-infection has resulted in increased clinical malaria prevalence, although the causes for this increase are incompletely understood. In our studies, we will examine a novel hypothesis that increased malaria burden in Kenya is due in part to enhanced mosquito-borne transmission of malaria from co-infected patients.