Mali International Center for Excellence in Research

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

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 (Safronetz et al. Emerg Infect Dis 2010). Over the last fifteen 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 (RML). 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 et al. PNAS Nexus 2022, Prevost et al. J Infect Dis 2025). We have also shown that Mastomys can serve as a host species for Borrelia Crocidurae, a cause of relapsing fever (Boardman et al., Am J Trop Med Hyg 2019). 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). Over the past years, 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 (Sogoba et al. Emerg Infect Dis 2016; Safronetz et al. Am J Trop Med Hyg 2017). More recently, a two-part human study covering a larger geographic area has ended and we are drafting the initial manuscript. In this study we are examining a cross-section of the population 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. Results of the studies are currently being analyzed and will be published in FY25/26. The Mali ICER runs by the motto “from Field – to Bench – to Public health” which includes bench work at RML for the development of countermeasures to support public health responses in Mali. We have continued to test the preclinical efficacy of favipiravir for Crimean-Congo hemorrhagic fever virus (CCHFV) and Lassa virus in animal models (Rosenke et al., Emerg Infect Dis 2018; Hawman et al. Antiviral res 2018). In addition, we are expanding vaccine research Lassa virus using vectored vaccines based on vesicular stomatitis virus (VSV) for which we have a GMP produced product that is ready to enter clinical trials (Rosenke et al. manuscript in preparation). Since a few years we are establishing a novel approach to target Lassa virus with a disseminated vaccine concept based on cytomegalovirus vectors. For this, tissue samples collected in Mali were used to isolate and characterize new Cytomegaloviruses (CMV) in Mastomys natalensis, the natural reservoir for Lassa virus (Hansen et al. J Gen Virol, 2023). These new CMVs were used to generate a vaccine containing Lassa virus antigen for use as a disseminating vaccine (Steicker et al. Science 2024, Staliunaite et al. J Virol 2025, Nuismer et al. Nature Commun, under review). We have also used the Mastomys colony to begin testing this vaccine and have demonstrated transmission of the vaccine between animals (Rosenke et al. in preparation). 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 (Bane et al. Emerg Infect Dis 2021). We have also established high seroprevalence of Dengue virus, Zika virus and Chikungunya virus in the population of Southern Mali (Bane et al. Am J Trop Med Hyg 2024). These results implying that several of these zoonotic pathogens are widely distributed yet underreported throughout Mali. 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 and the newly emerged H5N1. The ICER site (Point G) continues to be one of 4 national diagnostic centers for infectious disease testing in Mali. This program continues to educate and train young Malian scientists. Sidy Bane recently graduated with his PhD degree from the University of Bamako and has remained with us to continue his work. Hamady Sissoko, who was a medical student in the program has graduated and remained with the lab. Hamady will continue his molecular biology training and will be working as a lab technician. The human study has now provided twelve Malian students the necessary work and experience to earn their medical degrees from the University of Bamako in 2023. We currently have four new students on the project and expect them to successfully defend their dissertations in the fall/winter of 2025.