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

描述(申请人提供)：在撒哈拉以南非洲，疟疾和艾滋病毒混合感染的公共卫生危机正在迅速扩大。特别是肯尼亚西部低地，疟疾传播十分普遍，艾滋病毒/艾滋病感染率极高。2006年在该地区传播的数学模型回顾地预测，自1980年以来，混合感染已导致累计超过8500例艾滋病毒-1感染和980,000例疟疾发作。感染艾滋病毒的人经历了更频繁和更严重的临床疟疾发作，并且随着艾滋病毒疾病的进展，风险增加。然而，我们的初步研究和大量已发表的数据也表明，在疟疾全流行区的艾滋病毒感染者中，无症状寄生虫病和配子细胞症的具体增加也可能发生。虽然许多研究在横断面研究中审查了混合感染和有症状疟疾的一个或多个复杂方面，但还没有研究试图确定联合感染对无症状疟疾的纵向流行病学影响，特别是对这两种疾病高传播率和增加抗疟疾耐药性的地区的疟疾传播的影响。抗叶酸被广泛用于预防艾滋病毒相关的机会性感染，但众所周知，它们也可以增加配子细胞的出现。我们假设，与艾滋病毒合并感染和相关治疗，可能直接导致无症状寄生虫携带率和配子细胞症的显著增加，以及抗抗叶酸寄生虫基因型别的增加，因此，直接导致恶性疟疾负担的增加。为此，我们建议在肯尼亚西部高度流行的地区使用高度敏感和特定的分子工具，重点进行补充的临床和昆虫学研究，以评估合并感染的点和纵向流行率，特别是配子细胞症，重点放在流行的艾滋病毒治疗背景下疟疾传播的纵向风险。 与公共卫生相关：艾滋病毒和疟疾合并感染已导致临床疟疾患病率增加，尽管这种增加的原因尚不完全清楚。在我们的研究中，我们将检验一个新的假设，即肯尼亚疟疾负担的增加部分是由于共同感染的患者通过蚊子传播疟疾的增加。

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.