Lassa Virus Isolation from Mastomys natalensis Rodents during an Epidemic in Sierra Leone

Natural hosts of most arenaviruses are rodents. The human-pathogenic Lassa virus and several non-pathogenic arenaviruses such as Morogoro virus (MORV) share the same host species, namely Mastomys natalensis (M. natalensis). In this study, we investigated the history of infection and virus transmission within the natural host population. To this end, we infected M. natalensis at different ages with MORV and measured the health status of the animals, virus load in blood and organs, the development of virus-specific antibodies, and the ability of the infected individuals to transmit the virus. To explore the impact of the lack of evolutionary virus–host adaptation, experiments were also conducted with Mobala virus (MOBV), which does not share M. natalensis as a natural host. Animals infected with MORV up to two weeks after birth developed persistent infection, seroconverted and were able to transmit the virus horizontally. Animals older than two weeks at the time of infection rapidly cleared the virus. In contrast, MOBV-infected neonates neither developed persistent infection nor were able to transmit the virus. In conclusion, we demonstrate that MORV is able to develop persistent infection in its natural host, but only after inoculation shortly after birth. A related arenavirus that is not evolutionarily adapted to M. natalensis is not able to establish persistent infection. Persistently infected animals appear to be important to maintain virus transmission within the host population.

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Lassa Virus Circulation in Small Mammal Populations in Bo District, Sierra Leone

Biology ◽

10.3390/biology10010028 ◽

2021 ◽

Vol 10 (1) ◽

pp. 28

Author(s):

Umaru Bangura ◽

Jacob Buanie ◽

Joyce Lamin ◽

Christopher Davis ◽

Gédéon Ngiala Bongo ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Sierra Leone ◽

Small Mammal ◽

Hemorrhagic Fever ◽

Lassa Fever ◽

Lassa Virus ◽

Sierra Leonean ◽

Bayesian Phylogenetic Analysis ◽

Prevalent Species ◽

Lineage Iv

Lassa fever is a viral hemorrhagic fever caused by the Lassa virus LASV, which was first isolated in the rodent Mastomys natalensis in 1974 in Kenema, Sierra Leone. As little is known about the abundance and the presence of LASV in rodents living in the Bo area, we carried out a small mammal longitudinal population survey. A standardized trapping session was performed in various habitats and seasons in six villages over two years (2014–2016) and samples collected were tested for arenavirus IgG and LASV. A Bayesian phylogenetic analysis was performed on sequences identified by PCR. A total of 1490 small mammals were collected, and 16 rodent species were identified, with M. natalensis (355, 24%) found to be the most prevalent species. Forty-one (2.8%) samples were IgG positive, and 31 of these were trapped in homes and 10 in surrounding vegetation. Twenty-nine of 41 seropositive rodents were M. natalensis. We detected four LASV by PCR in two villages, all found in M. natalensis. Phylogenetic analysis showed that the sequences were distributed within the Sierra Leonean clade within lineage IV, distinguishing a Bo sub-clade older than a Kenema sub-clade. Compared to other settings, we found a low abundance of M. natalensis and a low circulation of LASV in rodents in villages around Bo district.

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Identification of Common CD8+ T Cell Epitopes from Lassa Fever Survivors in Nigeria and Sierra Leone

Journal of Virology ◽

10.1128/jvi.00153-20 ◽

2020 ◽

Vol 94 (12) ◽

Author(s):

Saori Sakabe ◽

Jessica N. Hartnett ◽

Nhi Ngo ◽

Augustine Goba ◽

Mambu Momoh ◽

...

Keyword(s):

T Cell ◽

West Africa ◽

Sierra Leone ◽

T Cell Responses ◽

Lassa Fever ◽

Health Concern ◽

Lassa Virus ◽

T Cell Epitopes ◽

Virus Surface ◽

Cell Responses

ABSTRACT Early and robust T cell responses have been associated with survival from Lassa fever (LF), but the Lassa virus-specific memory responses have not been well characterized. Regions within the virus surface glycoprotein (GPC) and nucleoprotein (NP) are the main targets of the Lassa virus-specific T cell responses, but, to date, only a few T cell epitopes within these proteins have been identified. We identified GPC and NP regions containing T cell epitopes and HLA haplotypes from LF survivors and used predictive HLA-binding algorithms to identify putative epitopes, which were then experimentally tested using autologous survivor samples. We identified 12 CD8-positive (CD8+) T cell epitopes, including epitopes common to both Nigerian and Sierra Leonean survivors. These data should be useful for the identification of dominant Lassa virus-specific T cell responses in Lassa fever survivors and vaccinated individuals as well as for designing vaccines that elicit cell-mediated immunity. IMPORTANCE The high morbidity and mortality associated with clinical cases of Lassa fever, together with the lack of licensed vaccines and limited and partially effective interventions, make Lassa virus (LASV) an important health concern in its regions of endemicity in West Africa. Previous infection with LASV protects from disease after subsequent exposure, providing a framework for designing vaccines to elicit similar protective immunity. Multiple major lineages of LASV circulate in West Africa, and therefore, ideal vaccine candidates should elicit immunity to all lineages. We therefore sought to identify common T cell epitopes between Lassa fever survivors from Sierra Leone and Nigeria, where distinct lineages circulate. We identified three such epitopes derived from highly conserved regions within LASV proteins. In this process, we also identified nine other T cell epitopes. These data should help in the design of an effective pan-LASV vaccine.

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Fluctuation of Abundance and Lassa Virus Prevalence in Mastomys natalensis in Guinea, West Africa

Vector-Borne and Zoonotic Diseases ◽

10.1089/vbz.2006.0520 ◽

2007 ◽

Vol 7 (2) ◽

pp. 119-128 ◽

Cited By ~ 63

Author(s):

Elisabeth Fichet-Calvet ◽

Emilie Lecompte ◽

Lamine Koivogui ◽

Barré Soropogui ◽

Amadou Doré ◽

...

Keyword(s):

West Africa ◽

Lassa Virus ◽

Mastomys Natalensis ◽

Virus Prevalence

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Public health response to two imported, epidemiologically related cases of Lassa fever in the Netherlands (ex Sierra Leone), November 2019

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.15.2000265 ◽

2020 ◽

Vol 25 (15) ◽

Author(s):

Femke Overbosch ◽

Mark de Boer ◽

Karin Ellen Veldkamp ◽

Pauline Ellerbroek ◽

Chantal P Bleeker-Rovers ◽

...

Keyword(s):

Public Health ◽

The Netherlands ◽

Sierra Leone ◽

Healthcare Facility ◽

Lassa Fever ◽

Low Risk ◽

Lassa Virus ◽

Public Health Response ◽

Health Response

On 20 November 2019, Lassa fever was diagnosed in a physician repatriated from Sierra Leone to the Netherlands. A second physician with suspected Lassa fever, repatriated a few days later from the same healthcare facility, was confirmed infected with Lassa virus on 21 November. Comprehensive contact monitoring involving high- and low-risk contacts proved to be feasible and follow-up of the contacts did not reveal any case of secondary transmission in the Netherlands.

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A Sporadic and Lethal Lassa Fever Case in Forest Guinea, 2019

Viruses ◽

10.3390/v12101062 ◽

2020 ◽

Vol 12 (10) ◽

pp. 1062

Author(s):

N’Faly Magassouba ◽

Enogo Koivogui ◽

Sory Conde ◽

Moussa Kone ◽

Michel Koropogui ◽

...

Keyword(s):

Sierra Leone ◽

Lassa Fever ◽

Regional Hospital ◽

Health Centers ◽

Lassa Virus ◽

Fever Case ◽

Internal Bleeding ◽

Facial Edema ◽

Frequent Vomiting ◽

Generation Sequencing

Lassa fever is a rodent-borne disease caused by Lassa virus (LASV). It causes fever, dizziness, vertigo, fatigue, coughing, diarrhea, internal bleeding and facial edema. The disease has been known in Guinea since 1960 but only anectodical acute cases have been reported to date. In January 2019, a 35-year-old man, a wood merchant from Kissidougou, Forest Guinea, presented himself at several health centers with persistent fever, frequent vomiting and joint pain. He was repeatedly treated for severe malaria, and died three weeks later in Mamou regional hospital. Differential diagnosis identified LASV as the cause of death. No secondary cases were reported. The complete LASV genome was obtained using next-generation sequencing. Phylogenetic analysis showed that this strain, namely the Kissidougou strain, belongs to the clade IV circulating in Guinea and Sierra Leone, and is thought to have emerged some 150 years ago. Due to the similarity of symptoms with malaria, Lassa fever is still a disease that is difficult to recognize and that may remain undiagnosed in health centers in Guinea.

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Biological Species in Praomys (Mastomys) Natalensis (Smith), a Rodent Carrier of Lassa Virus and Bubonic Plague in Africa

American Journal of Tropical Medicine and Hygiene ◽

10.4269/ajtmh.1978.27.627 ◽

1978 ◽

Vol 27 (3) ◽

pp. 627-629 ◽

Cited By ~ 23

Author(s):

Christopher Alan Green ◽

D. H. Gordon ◽

N. F. Lyons

Keyword(s):

Biological Species ◽

Lassa Virus ◽

Mastomys Natalensis ◽

Bubonic Plague

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Diagnosis and Clinical Virology of Lassa Fever as Evaluated by Enzyme-Linked Immunosorbent Assay, Indirect Fluorescent-Antibody Test, and Virus Isolation

Journal of Clinical Microbiology ◽

10.1128/jcm.38.7.2670-2677.2000 ◽

2000 ◽

Vol 38 (7) ◽

pp. 2670-2677 ◽

Cited By ~ 101

Author(s):

D. G. Bausch ◽

P. E. Rollin ◽

A. H. Demby ◽

M. Coulibaly ◽

J. Kanu ◽

...

Keyword(s):

Gold Standard ◽

Virus Isolation ◽

Fluorescent Antibody ◽

Lassa Fever ◽

Virus Antigen ◽

Lassa Virus ◽

Indirect Fluorescent Antibody ◽

Rt Pcr ◽

Prognostic Information ◽

Course Of Illness

The Lassa virus (an arenavirus) is found in West Africa, where it sometimes causes a severe hemorrhagic illness called Lassa fever. Laboratory diagnosis has traditionally been by the indirect fluorescent-antibody (IFA) test. However, enzyme-linked immunosorbent assays (ELISAs) for Lassa virus antigen and immunoglobulin M (IgM) and G (IgG) antibodies have been developed that are thought to be more sensitive and specific. We compared ELISA and IFA testing on sera from 305 suspected cases of Lassa fever by using virus isolation with a positive reverse transcription-PCR (RT-PCR) test as the “gold standard.” Virus isolation and RT-PCR were positive on 50 (16%) of the 305 suspected cases. Taken together, Lassa virus antigen and IgM ELISAs were 88% (95% confidence interval [CI], 77 to 95%) sensitive and 90% (95% CI, 88 to 91%) specific for acute infection. Due to the stringent gold standard used, these likely represent underestimates. Diagnosis could often be made on a single serum specimen. Antigen detection was particularly useful in providing early diagnosis as well as prognostic information. Level of antigenemia varied inversely with survival. Detection by ELISA of IgG antibody early in the course of illness helped rule out acute Lassa virus infection. The presence of IFA during both acute and convalescent stages of infection, as well as significant interobserver variation in reading the slides, made interpretation difficult. However, the assay provided useful prognostic information, the presence of IFA early in the course of illness correlating with death. The high sensitivity and specificity, capability for early diagnosis, and prognostic value of the ELISAs make them the diagnostic tests of choice for the detection of Lassa fever.

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Lethal Infection of Lassa Virus Isolated from a Human Clinical Sample in Outbred Guinea Pigs without Adaptation

mSphere ◽

10.1128/msphere.00428-19 ◽

2019 ◽

Vol 4 (5) ◽

Cited By ~ 4

Author(s):

Junki Maruyama ◽

John T. Manning ◽

Elizabeth J. Mateer ◽

Rachel Sattler ◽

Natalya Bukreyeva ◽

...

Keyword(s):

Public Health ◽

Sierra Leone ◽

Guinea Pigs ◽

Lassa Fever ◽

West African ◽

Lassa Virus ◽

African Countries ◽

Successful Development ◽

Public Health Perspective ◽

Lethal Infection

ABSTRACT Lassa virus (LASV), a member of the family Arenaviridae, is the causative agent of Lassa fever. Lassa virus is endemic in West African countries, such as Nigeria, Guinea, Liberia, and Sierra Leone, and causes outbreaks annually. Lassa fever onset begins with “flu-like” symptoms and may develop into lethal hemorrhagic disease in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few licensed vaccines or therapeutics against Lassa fever. The fact that animal models are limited and the fact that mostly laboratory-derived viruses are used for studies limit the successful development of countermeasures. In this study, we demonstrated that the LASV isolate LF2384-NS-DIA-1 (LF2384), which was directly isolated from a serum sample from a fatal human Lassa fever case in the 2012 Sierra Leone outbreak, causes uniformly lethal infection in outbred Hartley guinea pigs without virus-host adaptation. This is the first report of a clinically isolated strain of LASV causing lethal infection in outbred guinea pigs. This novel guinea pig model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics. IMPORTANCE Lassa virus, the causative agent of Lassa fever, is a zoonotic pathogen causing annual outbreaks in West African countries. Human patients can develop lethal hemorrhagic fever in severe cases. Although Lassa virus is one of the most alarming pathogens from a public health perspective, there are few available countermeasures, such as antiviral drugs or vaccines. Moreover, the fact that animal models are not readily accessible and the fact that mostly laboratory viruses, which have been passaged many times after isolation, are used for studies further limits the successful development of countermeasures. In this study, we demonstrate that a human isolate of Lassa virus causes lethal infection uniformly in Hartley guinea pigs. This novel animal model of Lassa fever may contribute to Lassa fever research and the development of vaccines and therapeutics.

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