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。在过去的十三年里，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（Safronetz, Rosenke 2022）。我们还调查了Mastomys作为螺旋体Borrelia Crocidurae（一种导致回归热的病原体）宿主的可能性，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（Boardman等人，Am J Trop Med Hyg 2019）。在马里收集的组织样本用于分离和鉴定该物种中的新型巨细胞病毒（CMV） （Hansen等）。J Gen Virol，已接受)。这些新的巨细胞病毒被用来产生含有拉沙病毒抗原的疫苗，作为传播疫苗使用。我们还利用Mastomys菌落开始测试这种疫苗，并证明了疫苗在动物之间的传播。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。（Nuismer等人，PLoS Negl Trop Dis 2020； Safronetz等人，Viruses 2021； Smith等人，Lab anim2021； Tang-Huau等人，Viruses 2021）

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 thirteen 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 (Safronetz, Rosenke 2022). We have also investigated the possibility of the Mastomys as a host for a spirochete Borrelia Crocidurae, a cause of relapsing fever and found that these animals support a long-term infection and may in fact be an unreported host species for this disease-causing bacterium (Boardman et al., Am J Trop Med Hyg 2019). Tissue samples collected in Mali were used to isolate and characterize new Cytomegaloviruses (CMV) in the species (Hansen et al. J Gen Virol, accepted). These new CMVs were used to generate a vaccine containing Lassa virus antigen for use as a disseminating vaccine. We have also used the Mastomys colony to begin testing this vaccine and have demonstrated transmission of the vaccine between animals. 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. (Nuismer et al., PLoS Negl Trop Dis 2020; Safronetz et al., Viruses 2021; Smith et al., Lab Anim 2021; Tang-Huau et al., Viruses 2021) 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. A two-part human study covering a larger geographic area is currently in its final year. In this study we are examining a cross-section of the population as a whole looking for Lassa virus prevalence and collecting 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 (Falzarano et al., One Health 2017) and high CCHFV infection rates in Malian cattle (Maiga et al., Am J Trop Med Hyg 2017). 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 (Safronetz et al., Emerg Infect Dis 2016). Most recently, we demonstrated seroprevalence for Ebola in southern Mali (Bale et al., Emerg Infect Dis 2021). 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. In February 2020, 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 changed dramatically. We are currently establishing a similar diagnostic testing program for monkeypox virus. The ICER site (Point G) continues to be one of 4 national diagnostic centers for COVID testing in Mali. We have continued to support the diagnostic effort and are maintaining our field program through the clinical study. This program continues to educate and train young Malian scientists. Currently, Sidy Bane is in his fourth year of graduate studies for a PhD degree from the University of Bamako. He has recently published a manuscript on Ebola prevalence in Southern Mali. A new lab member was recently hired, Hamady Sissoko, who was a medical student of ours associated with the human study. Hamady will continue his molecular biology training and will be working as a lab technician. He supports all the field activities and subsequent lab activities in support of the field work. The human study has now provided eight Malian students the necessary work and experience to earn their medical degrees from the University in June of 2022. We currently have four new students on the project and expect them to successfully defend their dissertations in June of 2024.