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 five years we have continued to conduct field studies mapping the geographic distribution of Lassa virus in peridomestic settings across sub-Saharan Mali (Sogoba, Feldmann, Safronetz, Zoonoses Pub Health 2012; Safronetz et al., PLoS Negl Trop Med 2013). With a better understanding of the regions endemic 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. A proof-of-concept study showed that the animals can be persistently infected with Lassa without showing obvious clinical signs but virus shedding through different routes (Rosenke et al., unpublished data). Thus, this colony provides a unique tool for future studies Lassa virus infection in the natural host. We also have started to define the incidence rates of Lassa virus infection in humans in Southern Mali. A first human serosurvey study was conducted at three sites and data are currently being analyzed. Seroprevalence was found at all sites ranging from 16-44% (Safronetz et al., unpublished data). As there are no reports of Lassa fever, the disease caused by Lassa virus infection, this indicates that asymptomatic and mild infections are frequently occurring. Future studies at different sites need to confirm this preliminary results. Diagnostic testing has been implemented to identify human infections in future to determine the public health importance of Lassa virus infections. As mentioned above, we do have a Lassa virus isolate from Mali (designated Soromba) (Safronetz et al., Emerg Infect Dis 2010). Multiple studies have been performed at Rocky Mountain Laboratories defining the pathogenic potential in animal models as well as the efficacy of vaccines and antivirals. Lassa-Soromba seems to be less virulent in animal models and presents with an atypical clinical disease in the cynomolgus macaque model (Safronetz et al., J Infect dis 2013) supporting the idea of the circulation of a distinct and less pathogenic Lassa strain in Southern Mali. A live-attenuated recombinant vaccine platform expressing the Lassa virus glycoproteins was cross-protective against several Lassa isolates including Lassa-Soromba (Garbutt et al., J Virol 2004; Geisbert et al., PLoS Med 2005; Marzi et al., Emerg Infect Dis 2015; Safronetz et al., PLoS Negl Trop Dis 2015). Ribavirin and favipiravir are effective as antivirals even when given post onset of symptoms with favipiravir being superior over ribavirin (Safronetz et al., unpublished data). The Mali field program has expanded to include other zoonotic viruses including surveillance for additional arenaviruses, hantaviruses, MERS-CoV, and CCHFV, as well as rodent-specific pathogens including cytomegalovirus (Zivcec et al., Emerg Infect Dis 2013). In the future we will include testing 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. This program also includes education and training of young Malian scientists. References: 1: Safronetz D, et al. A recombinant vesicular stomatitis virus-based Lassa fever vaccine protects guinea pigs and macaques against challenge with geographically and genetically distinct Lassa viruses. PLoS Negl Trop Dis. 2015 Apr 17;9(4):e0003736. 2: Marzi A, et al. Vesicular stomatitis virus-based vaccines against Lassa and Ebola viruses. Emerg Infect Dis. 2015 Feb;21(2):305-7. 3: Rasmussen AL, et al. Delayed inflammatory and cell death responses are associated with reduced pathogenicity in Lujo virus-infected cynomolgus macaques. J Virol. 2015 Mar;89(5):2543-52. 4: Safronetz D, et al. Geographic distribution and genetic characterization of Lassa virus in sub-Saharan Mali. PLoS Negl Trop Dis. 2013 Dec 5;7(12):e2582. 5: Sogoba N, Feldmann H, Safronetz D. Lassa fever in West Africa: evidence for an expanded region of endemicity. Zoonoses Public Health. 2012 Sep;59 Suppl 2:43-7. 6: Safronetz D, et al. A recently isolated Lassa virus from Mali demonstrates atypical clinical disease manifestations and decreased virulence in cynomolgus macaques. J Infect Dis. 2013 Apr 15;207(8):1316-27. 7: Safronetz D, et al. Detection of Lassa virus, Mali. Emerg Infect Dis. 2010 Jul;16(7):1123-6. 8: Geisbert TW, et al. Development of a new vaccine for the prevention of Lassa fever. PLoS Med. 2005 Jun;2(6):e183. 9: Garbutt M, et al. Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses. J Virol. 2004 May;78(10):5458-65. 10. Zivcec M, et al. Unique strain of Crimean-Congo hemorrhagic fever virus, Mali. Emerg Infect Dis. 2014 May;20(5):911-3.