Mali International Center for Excellence in Research

2010年，我们首次发表了对从马里捕获的Mastomys natalensis中分离出的一种遗传上独特的拉沙病毒株的描述，马里以前被认为没有拉沙病毒。在过去九年中，我们继续进行实地研究，绘制出整个撒哈拉以南马里家庭环境中拉沙病毒的地理分布。随着对该病毒在马里流行地区的更好了解，拉沙项目已转变为旨在确定拉沙病毒在天然啮齿动物宿主中的感染动态和传播能力的研究。为此，我们在落基山实验室建立了一个Mastomys natalensis群落。几项研究表明，动物可以持续感染不同的拉沙病毒株，而不表现出明显的临床症状，但病毒通过不同的途径脱落（研究仍在进行中）。我们还调查了Mastomys作为一种螺旋体Borrelia Crocidurae宿主的可能性，这种螺旋体是导致回归热的原因。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，该菌落为今后拉沙病毒在自然宿主中的感染研究提供了独特的工具。最近，我们已经建立了研究Mastomys natalensis先天和适应性免疫反应的方法和技术。

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.