Mali International Center for Excellence in Research

2010年，我们发表了对从马里捕获的纳塔尔蚊虫中分离出的一种基因独特的拉萨病毒株的第一次描述，马里以前被认为没有拉萨病毒。在过去九年中，我们继续进行实地研究，绘制拉萨病毒在整个撒哈拉以南马里地区的地理分布情况。随着对这种病毒在马里的流行地区有了更好的了解，LASSA计划已经过渡到旨在确定LASSA在自然啮齿动物宿主中的感染动态和传播性的研究。为此，我们在落基山实验室建立了一群纳塔尔沼虾。几项研究表明，动物可以持续感染不同的拉萨病毒株，没有明显的临床症状，但病毒通过不同的途径传播(研究仍在进行中)。我们还调查了马斯提斯家作为罗氏疏螺旋体宿主的可能性，这种螺旋体是复发发热的原因之一。我们发现，这些动物支持长期感染，实际上可能是这种致病细菌的未报告宿主物种。因此，该菌落为未来研究拉萨病毒在自然宿主中的感染提供了独特的工具。最近，我们建立了方法和技术来研究纳塔尔沼虾的先天和获得性免疫反应。 几年前，我们启动了一些项目，以确定马里南部人类感染拉萨病毒的发病率。在三个地点进行了两项人类血清调查研究；在所有地点都发现了从16%到44%的免疫球蛋白血清阳性。有趣的是，在后续研究中，我们发现年感染率为6.3%。由于马里没有拉沙热的临床报告，这表明可能经常发生无症状和轻度感染。使用来自马里的一种名为Soromba的Lassa分离物进行的实验研究支持这一假设，因为Soromba在动物模型中的毒力较低，并在食蟹猴中表现出一种非典型的呼吸道疾病(Safronetz等人，J Infect Dis 2013)。一项涵盖更大地理区域的新的两部分人体研究原计划在本财政年度进行，但由于新冠肺炎大流行而不得不推迟。在这项研究中，我们将检查整个人群的横断面，寻找拉萨病毒的流行情况，并从医院收集临床样本，以确定拉沙热的流行情况。这项研究将确认和扩大我们以前的结果，并确定人类感染情况，以确定马里拉萨病毒感染对公共卫生的重要性。 马里实地方案已扩大到包括其他人畜共患病病毒，包括监测其他人畜共患病病毒(拉萨、卢乔)、布尼亚病毒(汉坦病毒、克里米亚-刚果出血热病毒(CCHFV)、裂谷热病毒)、丝状病毒(埃博拉和马尔堡)、黄病毒(登革热、寨卡病毒)和冠状病毒(MERS-CoV、SARS-CoV-2)。我们还开始检测人、牲畜和野生动物物种的血清/血液，以确定人畜共患病病原体对马里动物和公共卫生的流行率和重要性。到目前为止，我们可以证明MERS冠状病毒在马里骆驼中的感染，以及在马里牛中的高CCHFV感染率。对于人类，我们可以建立黄病毒(登革热、寨卡病毒)、布尼亚病毒(汉坦病毒)、托加病毒(基孔肯雅)感染以及钩端螺旋体感染的血清学证据；所有这些都导致马里的人类疾病。最近，我们可以在马里南部展示埃博拉的血清阳性反应。这些结果表明，其中几种人畜共患病病原体在马里各地广泛分布，但未得到充分报告。 我们继续在动物模型中测试法韦拉韦对克里米亚-刚果出血热病毒(CCHFV)和拉萨病毒的临床前疗效。此外，我们正在使用水泡性口炎病毒载体等载体疫苗扩大CCHFV和Lassa病毒的疫苗研究。 在2月份的一次定期访问中，我们开发并建立了针对新出现的SARS-CoV-2的诊断测试。当时马里没有任何新冠肺炎病例，这种情况已经发生了巨大变化。ICER站点(G点)现在是马里4个国家COVID检测诊断中心之一。 该方案还包括对马里年轻科学家的教育和培训。目前，Sidy Bane正在巴马科大学攻读博士学位的第二年。

In 2010, we published the first description of a genetically unique strain of Lassa virus isolated from Mastomys natalensis captured in Mali, an area previously thought to be free of Lassa virus. Over the last nine years we have continued to conduct field studies mapping the geographic distribution of Lassa virus in peridomestic settings across sub-Saharan Mali. With a better understanding of the endemic regions for this virus in Mali, the Lassa program has transitioned into studies aimed at defining the infection dynamics and transmissibility of Lassa in the natural rodent hosts. For this we have established a colony of Mastomys natalensis at the Rocky Mountain Laboratories. Several studies have shown that the animals can be persistently infected with different Lassa strains without showing obvious clinical signs but virus shedding through different routes (studies still ongoing). We have also investigated the possibility of the Mastomys as a host for a spirochete Borrelia Crocidurae, a cause of relapsing fever. We found that these animals support a long-term infection and may in fact be an unreported host species for this disease-causing bacterium. Thus, this colony provides a unique tool for future Lassa virus infection studies in the natural host. More recently, we have established methodology and technology to study innate and adaptive immune responses in Mastomys natalensis. A few years back, we have started projects to define the incidence rates of Lassa virus infection in humans in southern Mali. Two human serosurvey studies were conducted at three sites; IgG seroprevalence was found at all sites ranging from 16-44%. Interestingly, in the follow-up study we identified an annual infection rate of 6.3%. As there are no clinical reports of Lassa fever in Mali, this indicates that asymptomatic and mild infections may frequently occur. Experimental studies using a Lassa isolate from Mali, designated Soromba, support this hypothesis as Soromba is less virulent in animal models and presents with an atypical respiratory disease in cynomolgus macaques (Safronetz et al., J Infect Dis 2013). A new two-part human study covering a larger geographic area was planned for this fiscal year but had to be postponed due to the COVID pandemic. In this study we will examine a cross-section of the population as a whole looking for Lassa virus prevalence and collect clinical samples from hospitals to determine the prevalence of Lassa Fever. This study will confirm and expand upon our previous results and identify human infections to determine the public health importance of Lassa virus infections in Mali. The Mali field program has expanded to include other zoonotic viruses including surveillance for additional arenaviruses (Lassa, Lujo), bunyaviruses (hantaviruses, Crimean-Congo hemorrhagic fever virus (CCHFV), Rift Valley fever virus), filoviruses (Ebola and Marburg), flaviviruses (Dengue, Zika), and coronavirus (MERS-CoV, SARS-CoV-2). We have started to also test serum/blood from humans and livestock and wildlife species to determine the prevalence and importance of zoonotic pathogens for animal and public health in Mali. As of today, we could demonstrate MERS-CoV infections in Malian camels and high CCHFV infection rates in Malian cattle. For humans, we could establish serologic evidence for flavivirus (Dengue, Zika), bunyaviruses (hantavirus), and togaviruses (Chikungunya) infections as well as infections with Leptospira spp.; all contributing to human illness in Mali. Most recently, we could demonstrate seroprevalence for Ebola in southern Mali. These results implying that several of these zoonotic pathogens are widely distributed yet underreported throughout Mali. We have continued to test the preclinical efficacy of favipiravir for Crimean-Congo hemorrhagic fever virus (CCHFV) and Lassa virus in animal models. In addition, we are expanding vaccine research for CCHFV and Lassa virus using vectored vaccines such as vesicular stomatitis virus vectors. During a regular visit in February, we developed and established diagnostic testing for the emerging SARS-CoV-2. At that time Mali did not have any COVID cases, a situation that has changed dramatically. The ICER site (Point G) is now one of 4 national diagnostic centers for COVID testing in Mali. This program also includes education and training of young Malian scientists. Currently, Sidy Bane is in his second year of graduate studies for a PhD degree from the University of Bamako.