Serological prevalence of viral hemorrhagic fevers in Equatorial Africa

赤道非洲病毒性出血热的血清学流行情况

• 批准号: 8698969
• 负责人: GRAHAM SIMMONS
• 金额: $ 24.65万
• 依托单位: VITALANT
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8698969
• 关键词: Acute; Adolescent; Africa; African; Antibodies; Antigens; Area; Arenavirus; Biological Assay; Blood donor; Cameroon; Caregivers; Cells; Clinical; Country; Crimean Hemorrhagic Fever; Crimean-Congo Hemorrhagic Fever Virus; Democratic Republic of the Congo; Disease; Disease Outbreaks; Ebola virus; Enzyme-Linked Immunosorbent Assay; Event; Exposure to; Family; Filovirus; Flavivirus; Frankfurt-Marburg Syndrome Virus; General Population; Glycoproteins; Health Personnel; Hemorrhage; Human; Individual; Infection; Lassa virus; Learning; Link; Lipids; Nucleic Acids; Orthobunyavirus; Patients; Penetrance; Plasma; Population; Prevalence; Process; Rattus; Recombinants; Reverse Transcriptase Polymerase Chain Reaction; Rhabdoviridae; Sampling; Serological; Seroprevalences; Serum; South American; Surveys; Symptoms; System; Technology; Testing; Time; Togo; Uganda; Vesicular stomatitis Indiana virus; Viral; Viral Hemorrhagic Fevers; Viral Proteins; Virus; Weather; Western Blotting; Work; base; deep sequencing; exposed human population; falls; glycoprotein G; hemorrhagic fever virus; high throughput screening; indexing; internal control; neutralizing antibody; nonhuman primate; novel; public health relevance; repository; research study; screening; transmission process; vector; viral RNA

DESCRIPTION (provided by applicant): Viral hemorrhagic fevers (VHF) describe a diverse group of often-fatal illnesses accompanied by severe bleeding. All known VHF are caused by viruses from four distinct families of lipid- enveloped viruses, including the filoviruses (ebolavius and marburgvirus), arenaviruses (e.g. Lassa virus), bunyaviruses, and flaviviruses. The rhabdovirus Bas-Congo virus (BASV) was first identified by deep sequencing of nucleic acids extracted from a serum sample obtained from a patient with hemorrhagic fever in the Democratic Republic of Congo (DRC). Prior to falling ill, the mentioned patient was a caregiver for two adolescents from the same village who succumbed to a severe disease with similar symptoms, including hemorrhage. A vesicular stomatitis virus (VSV)-based pseudotype system enables us to test serum samples for the presence of antibodies that neutralize pseudoviruses bearing the BASV glycoprotein (BASV-G). A serum sample obtained from the initial patient almost 3 years after recovering from the disease revealed strong neutralization activity specific for BASV-G pseudotypes. Surprisingly, an asymptomatic close contact of the patient tested positive for BASV-G neutralizing antibodies with even higher titers, whereas other health care workers from the village did not show signs of exposure to BASV. Testing of 50 sera from blood donors identified one individual with moderate neutralizing activity specific to BASV-G. A key step in estimating the level of human exposure to BASV will be the screening of large numbers of serum samples from the area and surrounding countries for the presence of antibodies to BASV. The pseudotype neutralization assay is suitable for high-throughput processing of large sample numbers. However, it will exclusively detect antibodies targeting the viral glycoprotein, thereby interfering with infection of target cells. Consequentially, we confirm positivity with additional assays for other viral proteins, such as M and N. We plan to screen over 8000 sera from a total of seven countries for serological evidence of BASV infection, as well as looking at the basal seroprevalence of three additional VHFs - ebolavirus, marburgvirus and Lassa virus, as well as an additional African rhabdovirus, Kotonkan that is believed to infect humans, but is not thought to be a VHF.

描述（由申请人提供）：病毒性出血热（VHF）描述了一组经常伴随严重出血的致命疾病。所有已知的甚高频都是由来自四个不同脂膜病毒家族的病毒引起的，包括丝状病毒（埃博拉病毒和马尔堡病毒）、沙粒病毒（例如拉沙病毒）、布尼亚病毒和黄病毒。弹状病毒Bas-Congo病毒（BASV）首先通过对从刚果民主共和国（DRC）出血热患者获得的血清样品中提取的核酸进行深度测序来鉴定。在患病之前，该患者是来自同一村庄的两名青少年的照顾者，这两名青少年死于具有类似症状的严重疾病，包括出血。基于水泡性口炎病毒（VSV）的假型系统使我们能够检测血清样品中是否存在中和携带BASV糖蛋白的假病毒（BASV-G）的抗体。在从疾病中恢复后近3年从初始患者获得的血清样品显示对BASV-G假型特异的强中和活性。令人惊讶的是，患者的一名无症状密切接触者检测出BASV-G中和抗体阳性，滴度甚至更高，而该村的其他医护人员没有显示出接触BASV的迹象。对来自献血者的50份血清进行检测，发现1名个体对BASV-G具有中度特异性中和活性。估计人类接触BASV水平的关键步骤是筛查来自该地区和周边国家的大量血清样本，以确定是否存在BASV抗体。假型中和试验适用于大量样品的高通量处理。然而，它将专门检测靶向病毒糖蛋白的抗体，从而干扰靶细胞的感染。因此，我们通过其他病毒蛋白（如M和N）的额外检测确认阳性。我们计划对来自7个国家的8000多份血清进行筛查，以获得BASV感染的血清学证据，并观察另外3种VHF的基础血清阳性率-埃博拉病毒、马尔堡病毒和拉沙病毒，以及另外一种非洲弹状病毒，Kotonkan，据信它会感染人类，但不认为是VHF。