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

无症状艾滋病毒合并感染导致疟疾传播的负担

• 批准号: 8466428
• 负责人: Shirley Luckhart
• 金额: $ 57.1万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-24 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466428
• 关键词: AIDS/HIV problem; Address; Adult; Africa South of the Sahara; Anti-Retroviral Agents; Anti-malarial drug resistance; Appearance; Area; Awareness; Cessation of life; Child; Clinical; Communities; Cotrimoxazole; Cross-Sectional Studies; Culicidae; Data; Diagnosis; Disease; Disease Reservoirs; Drug Combinations; Drug resistance; Drug usage; Epidemiology; Erythrocytes; Falciparum Malaria; Folic Acid Antagonists; Frequencies; Genotype; Growth; HIV; HIV Infections; HIV Seropositivity; HIV therapy; HIV-1; Immunologic Deficiency Syndromes; Incidence; Individual; Infection; Kenya; Knowledge; Macaca; Malaria; Measures; Microscopic; Molecular; Mothers; Mutation; Opportunistic Infections; Parasite resistance; Parasitemia; Parasites; Patients; Peripheral; Persons; Pilot Projects; Plague; Prevalence; Production; Prophylactic treatment; Public Health; Publishing; Reporting; Resistance; Retroviridae; Risk; Series; Staging; Time; Trimethoprim-Sulfamethoxazole; Work; experience; immunoregulation; mathematical model; next generation; novel; programs; tool; transmission process; vector mosquito

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.

描述（由申请人提供）：疟疾-艾滋病毒双重感染的公共卫生危机正在撒哈拉以南非洲迅速蔓延。肯尼亚西部低地地区尤其是疟疾传播的大流行地区，并且艾滋病毒/艾滋病感染率极高。 2006 年该地区传播数学模型回顾性预测，自 1980 年以来，混合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 HIV 的个体会经历更频繁、更严重的临床疟疾发作，随着艾滋病毒疾病的进展，风险也会增加。然而，我们的试点研究和大量已发表的数据也表明，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出现特定增加。虽然许多研究在横断面研究中检验了混合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混合感染对无症状疟疾的纵向流行病学影响，特别是对有特征的地区的疟疾传播的影响。这两种疾病的高传播率和抗疟药物耐药性的增加。抗叶酸剂被广泛用于预防艾滋病毒相关的机会性感染，但众所周知，它们也会增加配子体的出现。我们假设，HIV 合并感染和相关治疗可能直接导致无症状寄生虫携带和配子体增多以及抗叶酸抗性寄生虫基因型增加，因此直接导致恶性疟疾负担增加。为此，我们建议在肯尼亚西部的高流行地区使用高度敏感和特定的分子工具重点开展补充性临床和昆虫学研究，以评估一般混合感染和配子体血症的点和纵向患病率，特别是纵向风险流行的艾滋病毒治疗背景下的疟疾传播。 公共卫生相关性：艾滋病毒和疟疾双重感染导致临床疟疾患病率增加，但造成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，即肯尼亚疟疾负担增加的部分原因是共同感染患者的蚊媒疟疾传播增强。