RESUMEN
This study aims to formulate a mathematical framework to examine how the Lassa virus spreads in humans of opposite genders. The stability of the model is analyzed at an equilibrium point in the absence of the Lassa fever. The model's effectiveness is evaluated using real-life data, and all the parameters needed to determine the basic reproduction number are estimated. Sensitivity analysis is performed to pinpoint the crucial parameters significantly influencing the spread of the infection. The interaction between threshold parameters and the basic reproduction number is simulated. Control theory is employed to devise and evaluate strategies, such as awareness campaigns, advocating condom usage, and deploying rodenticides to reduce the possibility of virus transmission efficiently.
Asunto(s)
Fiebre de Lassa , Virus Lassa , Humanos , Fiebre de Lassa/transmisión , Fiebre de Lassa/prevención & control , Fiebre de Lassa/epidemiología , Virus Lassa/fisiología , Femenino , Masculino , Número Básico de Reproducción , Epidemias/prevención & control , Modelos TeóricosRESUMEN
Lassa fever is a West African rodent-borne viral haemorrhagic fever that kills thousands of people a year, with 100 000 to 300 000 people a year probably infected by Lassa virus (LASV). The main reservoir of LASV is the Natal multimammate mouse, Mastomys natalensis. There is reported asynchrony between peak infection in the rodent population and peak Lassa fever risk among people, probably owing to differing seasonal contact rates. Here, we developed a susceptible-infected-recovered ([Formula: see text])-based model of LASV dynamics in its rodent host, M. natalensis, with a persistently infected class and seasonal birthing to test the impact of changes to seasonal birthing in the future owing to climate and land use change. Our simulations suggest shifting rodent birthing timing and synchrony will alter the peak of viral prevalence, changing risk to people, with viral dynamics mainly stable in adults and varying in the young, but with more infected individuals. We calculate the time-average basic reproductive number, [Formula: see text], for this infectious disease system with periodic changes to population sizes owing to birthing using a time-average method and with a sensitivity analysis show four key parameters: carrying capacity, adult mortality, the transmission parameter among adults and additional disease-induced mortality impact the maintenance of LASV in M. natalensis most, with carrying capacity and adult mortality potentially changeable owing to human activities and interventions.
Asunto(s)
Fiebre de Lassa , Virus Lassa , Murinae , Animales , Fiebre de Lassa/epidemiología , Fiebre de Lassa/transmisión , Fiebre de Lassa/virología , Virus Lassa/fisiología , Murinae/virología , Humanos , Modelos Biológicos , Reservorios de Enfermedades/virología , África Occidental/epidemiología , Estaciones del Año , FemeninoRESUMEN
Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.
Asunto(s)
Virus Lassa , Genética Inversa , Virus Lassa/genética , Virus Lassa/fisiología , Genética Inversa/métodos , Humanos , Animales , Antivirales/farmacología , Chlorocebus aethiops , Línea Celular , Replicación Viral , Fiebre de Lassa/virología , Ribavirina/farmacología , Células Vero , Contención de Riesgos Biológicos , Genoma Viral , Virión/genética , Virión/metabolismoRESUMEN
The black rat (Rattus rattus) is a globally invasive species that has been widely introduced across Africa. Within its invasive range in West Africa, R. rattus may compete with the native rodent Mastomys natalensis, the primary reservoir host of Lassa virus, a zoonotic pathogen that kills thousands annually. Here, we use rodent trapping data from Sierra Leone and Guinea to show that R. rattus presence reduces M. natalensis density within the human dwellings where Lassa virus exposure is most likely to occur. Further, we integrate infection data from M. natalensis to demonstrate that Lassa virus zoonotic spillover risk is lower at sites with R. rattus. While non-native species can have numerous negative effects on ecosystems, our results suggest that R. rattus invasion has the indirect benefit of decreasing zoonotic spillover of an endemic pathogen, with important implications for invasive species control across West Africa.
Asunto(s)
Reservorios de Enfermedades , Especies Introducidas , Fiebre de Lassa , Virus Lassa , Murinae , Zoonosis , Animales , Virus Lassa/patogenicidad , Virus Lassa/fisiología , Fiebre de Lassa/transmisión , Fiebre de Lassa/epidemiología , Fiebre de Lassa/virología , Fiebre de Lassa/veterinaria , Reservorios de Enfermedades/virología , Humanos , Ratas , Murinae/virología , Zoonosis/virología , Zoonosis/transmisión , Zoonosis/epidemiología , Sierra Leona/epidemiología , Guinea/epidemiología , Ecosistema , Enfermedades de los Roedores/virología , Enfermedades de los Roedores/epidemiología , Enfermedades de los Roedores/transmisiónRESUMEN
Lassa virus (LASV) is a mammarenavirus that can cause lethal Lassa fever disease with no FDA-approved vaccine and limited treatment options. Fatal LASV infections are associated with innate immune suppression. We have previously shown that the small matrix Z protein of LASV, but not of a nonpathogenic arenavirus Pichinde virus (PICV), can inhibit the cellular RIG-I-like receptors (RLRs), but its biological significance has not been evaluated in an infectious virus due to the multiple essential functions of the Z protein required for the viral life cycle. In this study, we developed a stable HeLa cell line (HeLa-iRIGN) that could be rapidly and robustly induced by doxycycline (Dox) treatment to express RIG-I N-terminal effector, with concomitant production of type I interferons (IFN-Is). We also generated recombinant tri-segmented PICVs, rP18tri-LZ, and rP18tri-PZ, which encode LASV Z and PICV Z, respectively, as an extra mScarlet fusion protein that is nonessential for the viral life cycle. Upon infection, rP18tri-LZ consistently expressed viral genes at a higher level than rP18tri-PZ. rP18tri-LZ also showed a higher level of a viral infection than rP18tri-PZ did in HeLa-iRIGN cells, especially upon Dox induction. The heterologous Z gene did not alter viral growth in Vero and A549 cells by growth curve analysis, while LASV Z strongly increased and prolonged viral gene expression, especially in IFN-competent A549 cells. Our study provides important insights into the biological role of LASV Z-mediated RIG-I inhibition and implicates LASV Z as a potential virulence factor. IMPORTANCE Lassa virus (LASV) can cause lethal hemorrhagic fever disease in humans but other arenaviruses, such as Pichinde virus (PICV), do not cause obvious disease. We have previously shown that the Z protein of LASV but not of PICV can inhibit RIG-I, a cytosolic innate immune receptor. In this study, we developed a stable HeLa cell line that can be induced to express the RIG-I N-terminal effector domain, which allows for timely control of RIG-I activation. We also generated recombinant PICVs encoding LASV Z or PICV Z as an extra gene that is nonessential for the viral life cycle. Compared to PICV Z, LASV Z could increase viral gene expression and viral infection in an infectious arenavirus system, especially when RIG-I signaling is activated. Our study presented a convenient cell system to characterize RIG-I signaling and its antagonists and revealed LASV Z as a possible virulence factor and a potential antiviral target.
Asunto(s)
Virus Lassa , Proteínas Virales/metabolismo , Células HeLa , Humanos , Fiebre de Lassa/virología , Virus Lassa/patogenicidad , Virus Lassa/fisiología , Virus Pichinde/genética , Factores de VirulenciaRESUMEN
Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.
Asunto(s)
Reservorios de Enfermedades/veterinaria , Fiebre de Lassa/veterinaria , Virus Lassa/fisiología , Murinae/virología , Enfermedades de los Roedores/virología , Zoonosis Virales/virología , Esparcimiento de Virus , Animales , Reservorios de Enfermedades/virología , Femenino , Humanos , Fiebre de Lassa/transmisión , Fiebre de Lassa/virología , Virus Lassa/genética , Masculino , Murinae/fisiología , Enfermedades de los Roedores/transmisión , Zoonosis Virales/transmisiónRESUMEN
Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fusion, we examined cell-cell fusion induced by the Old World Lassa virus (LASV) GPC complex. LASV GPC-mediated cell fusion is more efficient and occurs at higher pH with target cells expressing human LAMP1 compared to cells lacking this cognate receptor. However, human LAMP1 is not absolutely required for cell-cell fusion or LASV entry. We found that GPC-induced fusion progresses through the same lipid intermediates as fusion mediated by other viral glycoproteins-a lipid curvature-sensitive intermediate upstream of hemifusion and a hemifusion intermediate downstream of acid-dependent steps that can be arrested in the cold. Importantly, GPC-mediated fusion and LASV pseudovirus entry are specifically augmented by an anionic lipid, bis(monoacylglycero)phosphate (BMP), which is highly enriched in late endosomes. This lipid also specifically promotes cell fusion mediated by Junin virus GPC, an unrelated New World arenavirus. We show that BMP promotes late steps of LASV fusion downstream of hemifusion-the formation and enlargement of fusion pores. The BMP-dependence of post-hemifusion stages of arenavirus fusion suggests that these viruses evolved to use this lipid as a cofactor to selectively fuse with late endosomes.
Asunto(s)
Endosomas/metabolismo , Fiebre de Lassa/metabolismo , Virus Lassa/fisiología , Lisofosfolípidos/metabolismo , Monoglicéridos/metabolismo , Internalización del Virus , Animales , Células COS , Chlorocebus aethiops , Células HEK293 , Humanos , Proteínas del Envoltorio Viral/metabolismoRESUMEN
While investigating a signal of adaptive evolution in humans at the gene LARGE, we encountered an intriguing finding by Dr. Stefan Kunz that the gene plays a critical role in Lassa virus binding and entry. This led us to pursue field work to test our hypothesis that natural selection acting on LARGE-detected in the Yoruba population of Nigeria-conferred resistance to Lassa Fever in some West African populations. As we delved further, we conjectured that the "emerging" nature of recently discovered diseases like Lassa fever is related to a newfound capacity for detection, rather than a novel viral presence, and that humans have in fact been exposed to the viruses that cause such diseases for much longer than previously suspected. Dr. Stefan Kunz's critical efforts not only laid the groundwork for this discovery, but also inspired and catalyzed a series of events that birthed Sentinel, an ambitious and large-scale pandemic prevention effort in West Africa. Sentinel aims to detect and characterize deadly pathogens before they spread across the globe, through implementation of its three fundamental pillars: Detect, Connect, and Empower. More specifically, Sentinel is designed to detect known and novel infections rapidly, connect and share information in real time to identify emerging threats, and empower the public health community to improve pandemic preparedness and response anywhere in the world. We are proud to dedicate this work to Stefan Kunz, and eagerly invite new collaborators, experts, and others to join us in our efforts.
Asunto(s)
Planificación en Desastres , Fiebre de Lassa/epidemiología , Virus Lassa/fisiología , África Occidental/epidemiología , Planificación en Desastres/métodos , Humanos , Fiebre de Lassa/genética , Fiebre de Lassa/prevención & control , Fiebre de Lassa/virología , Virus Lassa/genética , N-Acetilglucosaminiltransferasas/genética , N-Acetilglucosaminiltransferasas/inmunología , Nigeria/epidemiología , Pandemias , Polimorfismo Genético , Receptores Virales/genética , Receptores Virales/inmunologíaRESUMEN
Defective interfering particles (DIPs) are naturally occurring products during virus replication in infected cells. DIPs contain defective viral genomes (DVGs) and interfere with replication and propagation of their corresponding standard viral genomes by competing for viral and cellular resources, as well as promoting innate immune antiviral responses. Consequently, for many different viruses, including mammarenaviruses, DIPs play key roles in the outcome of infection. Due to their ability to broadly interfere with viral replication, DIPs are attractive tools for the development of a new generation of biologics to target genetically diverse and rapidly evolving viruses. Here, we provide evidence that in cells infected with the Lassa fever (LF) vaccine candidate ML29, a reassortant that carries the nucleoprotein (NP) and glycoprotein (GP) dominant antigens of the pathogenic Lassa virus (LASV) together with the L polymerase and Z matrix protein of the non-pathogenic genetically related Mopeia virus (MOPV), L-derived truncated RNA species are readily detected following infection at low multiplicity of infection (MOI) or in persistently-infected cells originally infected at high MOI. In the present study, we show that expression of green fluorescent protein (GFP) driven by a tri-segmented form of the mammarenavirus lymphocytic choriomeningitis virus (r3LCMV-GFP/GFP) was strongly inhibited in ML29-persistently infected cells, and that the magnitude of GFP suppression was dependent on the passage history of the ML29-persistently infected cells. In addition, we found that DIP-enriched ML29 was highly attenuated in immunocompetent CBA/J mice and in Hartley guinea pigs. Likewise, STAT-1-/- mice, a validated small animal model for human LF associated hearing loss sequelae, infected with DIP-enriched ML29 did not exhibit any hearing abnormalities throughout the observation period (62 days).
Asunto(s)
Fiebre de Lassa/prevención & control , Virus Lassa/inmunología , Vacunas Virales/inmunología , Animales , Femenino , Genoma Viral , Cobayas , Humanos , Fiebre de Lassa/genética , Fiebre de Lassa/inmunología , Fiebre de Lassa/virología , Virus Lassa/genética , Virus Lassa/fisiología , Ratones , Ratones Endogámicos CBA , ARN Viral/genética , ARN Viral/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/genética , Replicación ViralRESUMEN
Lassa fever is an haemorrhagic fever caused by Lassa virus (LASV). There is no vaccine approved against LASV and the only recommended antiviral treatment relies on ribavirin, despite limited evidence of efficacy. Recently, the nucleotide analogue favipiravir showed a high antiviral efficacy, with 100% survival obtained in an otherwise fully lethal non-human primate (NHP) model of Lassa fever. However the mechanism of action of the drug is not known and the absence of pharmacokinetic data limits the translation of these results to the human setting. Here we aimed to better understand the antiviral effect of favipiravir by developping the first mathematical model recapitulating Lassa viral dynamics and treatment. We analyzed the viral dynamics in 24 NHPs left untreated or treated with ribavirin or favipiravir, and we put the results in perspective with those obtained with the same drugs in the context of Ebola infection. Our model estimates favipiravir EC50 in vivo to 2.89 µg.mL-1, which is much lower than what was found against Ebola virus. The main mechanism of action of favipiravir was to decrease virus infectivity, with an efficacy of 91% at the highest dose. Based on our knowledge acquired on the drug pharmacokinetics in humans, our model predicts that favipiravir doses larger than 1200 mg twice a day should have the capability to strongly reduce the production infectious virus and provide a milestone towards a future use in humans.
Asunto(s)
Amidas , Antivirales , Fiebre de Lassa/virología , Virus Lassa , Pirazinas , Ribavirina , Amidas/farmacocinética , Amidas/farmacología , Amidas/uso terapéutico , Animales , Antivirales/farmacocinética , Antivirales/farmacología , Antivirales/uso terapéutico , Femenino , Interacciones Huésped-Patógeno/efectos de los fármacos , Fiebre de Lassa/tratamiento farmacológico , Virus Lassa/efectos de los fármacos , Virus Lassa/patogenicidad , Virus Lassa/fisiología , Macaca fascicularis , Modelos Biológicos , Pirazinas/farmacocinética , Pirazinas/farmacología , Pirazinas/uso terapéutico , Ribavirina/farmacocinética , Ribavirina/farmacología , Ribavirina/uso terapéutico , Carga Viral/efectos de los fármacosRESUMEN
The zoonotic Old World mammarenavirus Lassa (LASV) causes severe hemorrhagic fever with high mortality and morbidity in humans in endemic regions. The development of effective strategies to combat LASV infections is of high priority, given the lack of a licensed vaccine and restriction on available treatment to off-label use of ribavirin. A better understanding of the fundamental aspects of the virus's life cycle would help to improve the development of novel therapeutic approaches. Host cell entry and restriction factors represent major barriers for emerging viruses and are promising targets for therapeutic intervention. In addition to the LASV main receptor, the extracellular matrix molecule dystroglycan (DG), the phosphatidylserine-binding receptors of the Tyro3/Axl/Mer (TAM), and T cell immunoglobulin and mucin receptor (TIM) families are potential alternative receptors of LASV infection. Therefore, the relative contributions of candidate receptors to LASV entry into a particular human cell type are a complex function of receptor expression and functional DG availability. Here, we describe the role of two receptor tyrosine kinases (RTKs), Axl and hepatocyte growth factor receptor (HGFR), in the presence and absence of glycosylated DG for LASV entry. We found that both RTKs participated in the macropinocytosis-related LASV entry and, regardless of the presence or absence of functional DG, their inhibition resulted in a significant antiviral effect.
Asunto(s)
Virus Lassa/fisiología , Proteínas Proto-Oncogénicas c-met/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Receptores Virales/metabolismo , Internalización del Virus , Antivirales/farmacología , Antivirales/uso terapéutico , Benzocicloheptenos/farmacología , Benzocicloheptenos/uso terapéutico , Línea Celular Tumoral , Membrana Celular/metabolismo , Interacciones Farmacológicas , Distroglicanos/metabolismo , Glicosilación , Humanos , Fiebre de Lassa/tratamiento farmacológico , Fiebre de Lassa/virología , Virus Lassa/efectos de los fármacos , Pinocitosis , Proteínas Proto-Oncogénicas/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-met/antagonistas & inhibidores , Proteínas Tirosina Quinasas Receptoras/antagonistas & inhibidores , Triazoles/farmacología , Triazoles/uso terapéutico , Internalización del Virus/efectos de los fármacos , Tirosina Quinasa del Receptor AxlRESUMEN
With the COVID-19 officially declared a pandemic, Nigeria alongside other countries is directing all its resources and manpower to contain this pandemic. However, the existence of Lassa fever (LF), a more severe, zoonotic, endemic and viral haemorrhagic fever caused by Lassa virus with higher case fatality ratio (CFR) rages on across Nigeria while receiving little or no public health attention. The simultaneously increasing cases of COVID-19 and LF across Nigeria would be catastrophic unless infection prevention and control measures toward both LF and COVID-19 outbreaks are considered alongside.
Asunto(s)
Betacoronavirus/fisiología , Infecciones por Coronavirus/epidemiología , Brotes de Enfermedades , Fiebres Hemorrágicas Virales/epidemiología , Fiebre de Lassa/epidemiología , Virus Lassa/fisiología , Pandemias , Neumonía Viral/epidemiología , COVID-19 , Infecciones por Coronavirus/virología , Fiebres Hemorrágicas Virales/virología , Humanos , Fiebre de Lassa/virología , Nigeria/epidemiología , Neumonía Viral/virología , Salud Pública , SARS-CoV-2RESUMEN
Ever since it was established that rodents serve as reservoirs of the zoonotic Lassa virus (LASV), scientists have sought to answer the questions: which populations of rodents carry the virus? How do fluctuations in LASV prevalence and rodent abundance influence Lassa fever outbreaks in humans? What does it take for the virus to adopt additional rodent hosts, proliferating what already are devastating cycles of rodent-to-human transmission? In this review, we examine key aspects of research involving the biology of rodents that affect their role as LASV reservoirs, including phylogeography, demography, virus evolution, and host switching. We discuss how this knowledge can help control Lassa fever and suggest further areas for investigation.
Asunto(s)
Ecología , Virus Lassa/fisiología , Enfermedades de los Roedores/virología , Roedores/virología , África Occidental/epidemiología , Animales , Evolución Biológica , Brotes de Enfermedades , Reservorios de Enfermedades/virología , Humanos , Fiebre de Lassa/epidemiología , Fiebre de Lassa/virología , Filogeografía , Prevalencia , Zoonosis Virales/epidemiología , Zoonosis Virales/virologíaRESUMEN
Interferons (IFNs) control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. We report herein that gamma-interferon-inducible lysosomal thiol reductase (GILT), a lysosome-associated ISG, restricts the infectious entry of selected enveloped RNA viruses. Specifically, we demonstrated that GILT was constitutively expressed in lung epithelial cells and fibroblasts and its expression could be further induced by type II interferon. While overexpression of GILT inhibited the entry mediated by envelope glycoproteins of SARS coronavirus (SARS-CoV), Ebola virus (EBOV) and Lassa fever virus (LASV), depletion of GILT enhanced the entry mediated by these viral envelope glycoproteins. Furthermore, mutations that impaired the thiol reductase activity or disrupted the N-linked glycosylation, a posttranslational modification essential for its lysosomal localization, largely compromised GILT restriction of viral entry. We also found that the induction of GILT expression reduced the level and activity of cathepsin L, which is required for the entry of these RNA viruses in lysosomes. Our data indicate that GILT is a novel antiviral ISG that specifically inhibits the entry of selected enveloped RNA viruses in lysosomes via disruption of cathepsin L metabolism and function and may play a role in immune control and pathogenesis of these viruses.
Asunto(s)
Ebolavirus/fisiología , Fiebre Hemorrágica Ebola/inmunología , Fiebre de Lassa/inmunología , Virus Lassa/fisiología , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/inmunología , Síndrome Respiratorio Agudo Grave/inmunología , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/fisiología , Proteínas del Envoltorio Viral/metabolismo , Internalización del Virus , Catepsina L/genética , Catepsina L/inmunología , Línea Celular , Ebolavirus/genética , Fiebre Hemorrágica Ebola/genética , Fiebre Hemorrágica Ebola/virología , Humanos , Fiebre de Lassa/genética , Fiebre de Lassa/virología , Virus Lassa/genética , Lisosomas/genética , Lisosomas/inmunología , Lisosomas/virología , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genética , Coronavirus Relacionado al Síndrome Respiratorio Agudo Severo/genética , Síndrome Respiratorio Agudo Grave/genética , Síndrome Respiratorio Agudo Grave/virología , Proteínas del Envoltorio Viral/genética , Replicación ViralAsunto(s)
Células Dendríticas/inmunología , Evasión Inmune/inmunología , Virus Lassa/fisiología , Linfocitos T/inmunología , Tropismo Viral , Animales , Presentación de Antígeno , Arenaviridae/genética , Arenaviridae/inmunología , Arenaviridae/fisiología , Células Cultivadas , ADN Helicasas/fisiología , Células Dendríticas/citología , Reservorios de Enfermedades , Humanos , Mediadores de Inflamación/metabolismo , Virus Lassa/genética , Virus Lassa/inmunología , Activación de Linfocitos , Monocitos/citología , Murinae/microbiología , Virus Reordenados/inmunología , Receptores Virales/fisiología , Especificidad de la Especie , Especificidad del Receptor de Antígeno de Linfocitos T , Proteínas Virales/inmunologíaRESUMEN
BACKGROUND: Infectious disease prevention and control strategies require a coordinated, transnational approach. To establish core capacities of the International Health Regulations (IHR), the World Health Organization (WHO) developed the Integrated Diseases Surveillance and Response (IDSR) strategy. Epidemic-prone Lassa fever, caused by Lassa virus, is an endemic disease in the West African countries of Ghana, Guinea, Mali, Benin, Liberia, Sierra Leone, Togo and Nigeria. It's one of the major public health threats in these countries. Here it is reported an epidemiological investigation of a cross-border case of Lassa fever, which demonstrated the importance of strengthened capacities of IHR and IDSR. CASE PRESENTATION: On January 9th, 2018 a 35-year-old Guinean woman with fever, neck pain, body pain, and vomiting went to a hospital in Ganta, Liberia. Over the course of her illness, the case visited various health care facilities in both Liberia and Guinea. A sample collected on January 10th was tested positive for Lassa virus by RT-PCR in a Liberian laboratory. The Guinean Ministry of Health (MoH) was officially informed by WHO Country Office for Guinea and for Liberia. CONCLUSION: This case report revealed how an epidemic-prone disease such as Lassa fever can rapidly spread across land borders and how such threat can be quickly controlled with communication and collaboration within the IHR framework.
Asunto(s)
Emigración e Inmigración , Fiebre de Lassa/diagnóstico , Virus Lassa/fisiología , Adulto , África Occidental/epidemiología , Monitoreo Epidemiológico , Femenino , Humanos , Reglamento Sanitario Internacional/normas , Fiebre de Lassa/epidemiología , Fiebre de Lassa/patología , Virus Lassa/genética , Organización Mundial de la SaludRESUMEN
OBJECTIVES: Lassa fever (LF) causes annual outbreaks in endemic regions with high mortality of symptomatic patients. Ribavirin is recommended as standard treatment for LF in national and international guidelines but the evidence base for this recommendation has been questioned recently. METHODS: We conducted a systematic review and included 6 studies providing efficacy data of ribavirin treatment for LF (PROSPERO protocol CRD42018103994). RESULTS: Besides retrospective case series, the evidence mostly relies on a single prospective clinical trial with critical risk of bias. In this trial, LF associated mortality is reduced for patients with elevated aspartate aminotransferase (AST) when treated with ribavirin (OR 0.41, 95% CI 0.23-0.73), while mortality is higher for patients without elevated AST (OR 2.37, 95% CI 1.07-5.25). CONCLUSIONS: Based on the available data, current treatment guidelines may therefore put patients with mild LF at increased risk of death. The role of ribavirin in the treatment of LF requires urgent reassessment.
Asunto(s)
Fiebre de Lassa/tratamiento farmacológico , Virus Lassa/efectos de los fármacos , Ribavirina/uso terapéutico , Aspartato Aminotransferasas/metabolismo , Ensayos Clínicos como Asunto , Humanos , Fiebre de Lassa/enzimología , Fiebre de Lassa/mortalidad , Fiebre de Lassa/virología , Virus Lassa/fisiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Lassa fever (LF) is a zoonotic disease that is widespread in West Africa and involves animal-to-human and human-to-human transmission. Animal-to-human transmission occurs upon exposure to rodent excreta and secretions, i.e. urine and saliva, and human-to-human transmission occurs via the bodily fluids of an infected person. To elucidate the seasonal drivers of LF epidemics, we employed a mathematical model to analyse the datasets of human infection, rodent population dynamics and climatological variations and capture the underlying transmission dynamics. The surveillance-based incidence data of human cases in Nigeria were explored, and moreover, a mathematical model was used for describing the transmission dynamics of LF in rodent populations. While quantifying the case fatality risk and the rate of exposure of humans to animals, we explicitly estimated the corresponding contact rate of humans with infected rodents, accounting for the seasonal population dynamics of rodents. Our findings reveal that seasonal migratory dynamics of rodents play a key role in regulating the cyclical pattern of LF epidemics. The estimated timing of high exposure of humans to animals coincides with the time shortly after the start of the dry season and can be associated with the breeding season of rodents in Nigeria. This article is part of the theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: approaches and important themes'. This issue is linked with the subsequent theme issue 'Modelling infectious disease outbreaks in humans, animals and plants: epidemic forecasting and control'.
Asunto(s)
Fiebre de Lassa/epidemiología , Fiebre de Lassa/veterinaria , Enfermedades de los Roedores/epidemiología , Roedores/virología , Animales , Humanos , Fiebre de Lassa/transmisión , Fiebre de Lassa/virología , Virus Lassa/fisiología , Modelos Teóricos , Nigeria/epidemiología , Enfermedades de los Roedores/transmisión , Enfermedades de los Roedores/virología , Roedores/fisiología , Estaciones del Año , Zoonosis/epidemiología , Zoonosis/transmisión , Zoonosis/virologíaRESUMEN
Lassa virus (LASV), a hemorrhagic fever virus endemic to West Africa, causes conjunctivitis in patients with acute disease. To examine ocular manifestations of LASV, we histologically examined eyes from infected guinea pigs. In fatal disease, LASV immunostaining was most prominent in the anterior uvea, especially in the filtration angle, ciliary body, and iris and in and around vessels in the bulbar conjunctiva and peripheral cornea, where it co-localized with an endothelial marker (platelet endothelial cell adhesion molecule). Antigen was primarily associated with infiltration of T-lymphocytes around vessels in the anterior uvea and with new vessel formation at the peripheral cornea. In animals that exhibited clinical signs but survived infection, eyes had little to no inflammation and no LASV immunostaining 6 weeks after infection. Overall, in this model, LASV antigen was restricted to the anterior uvea and was associated with mild chronic inflammation in animals with severe disease but was not detected in survivors.