Serological and molecular screening of arenaviruses in suspected tick-borne encephalitis cases in Finland.

Lymphocytic choriomeningitis virus (LCMV) is one of the arenaviruses infecting humans. LCMV infections have been reported worldwide in humans with varying levels of severity. To detect arenavirus RNA and LCMV-reactive antibodies in different geographical regions of Finland, we screened human serum and cerebrospinal fluid (CSF) samples, taken from suspected tick-borne encephalitis (TBE) cases, using reverse transcriptase polymerase chain reaction (RT-PCR) and immunofluorescence assay (IFA). No arenavirus nucleic acids were detected, and the overall LCMV seroprevalence was 4.5%. No seroconversions were detected in paired serum samples. The highest seroprevalence (5.2%) was detected among individuals of age group III (40-59 years), followed by age group I (under-20-year-olds, 4.9%), while the lowest seroprevalence (3.8%) was found in age group IV (60 years or older). A lower LCMV seroprevalence in older age groups may suggest waning of immunity over time. The observation of a higher seroprevalence in the younger age group and the decreasing population size of the main reservoir host, the house mouse, may suggest exposure to another LCMV-like virus in Finland.

Transmission, seroprevalence, and maternal-fetal impact of lymphocytic choriomeningitis virus.

Congenital infections can have devastating short- and long-term impacts on the developing fetus. Lymphocytic choriomeningitis virus (LCMV) is a zoonotic pathogen of concern that causes a severe congenital syndrome but is under-recognized and under-studied. Herein we review data on the natural animal reservoirs of LCMV, modes of transmission to humans, seroprevalence of LCMV worldwide in both pregnant and non-pregnant individuals, mechanisms of viral dissemination to placenta and fetus, and impact of climate change on viral transmission. We highlight opportunities to enhance awareness of congenital LCMV and provide recommendations for prevention and monitoring among at-risk pregnant people. IMPACT: Key message of the article: LCMV is a zoonotic virus that poses a major threat to maternal-fetal health. Adds to the existing literature: We comprehensively address transmission of LCMV from the natural reservoir to the pregnant individual, placenta, and fetus. Impact: Available data call for enhanced patient and provider awareness about congenital LCMV during pregnancy, as well as a need for efforts to better define the seroprevalence and impact of congenital LCMV worldwide.

Human cases of lymphocytic choriomeningitis virus (LCMV) infections in Hungary.

Lymphocytic choriomeningitis (LCM) is a "neglected" rodent-borne viral zoonotic disease caused by lymphocytic choriomeningitis virus (LCMV) (family Arenaviridae). The aim of this retrospective clinical and laboratory study was to detect LCMV RNA, using RT-PCR, in cerebrospinal fluid samples collected from patients with central nervous system (CNS) infections of unknown aetiology from over a 12-year period in Hungary. Between 2009 and 2020, a total of 74 cerebrospinal fluid samples were tested using an in-house LCMV-specific RT-PCR-based method at the Department of Medical Microbiology and Immunology, University of Pécs. The mean age of the 74 patients included in our study was 24 years (min. 5, max. 74), with a predominance of men (44 [59.5%]; women, 30 [40.5%]). Two (2.7%) cerebrospinal fluid samples were found to be positive for LCMV RNA by RT-PCR and sequencing. The first LCMV case was a 5-year-old preschool boy who had a hamster bite on his left-hand finger, and the second LCMV case was a 74-year-old man who was living in a village and had incipient dementia and a previous permanent functional CNS impairment. The two detected LCMV strains (MW558451 and OM648933) from the year 2020 belonged to two different genetic lineages (I and II). These two cases of CNS inflammation of unknown origin represent the first published human LCMV infections confirmed by molecular methods in Hungary.

Locally acquired lymphocytic choriomeningitis virus infections in South-East Queensland: an outbreak of a pathogen rarely described in Australia.

Lymphocytic choriomeningitis virus (LCMV) is a zoonotic virus that can cause clinically significant illnesses in humans. Although cases of LCMV infection are well described globally, and there is evidence that the virus is present in Australian rodent populations, there has been only one case of domestically acquired LCMV infection published previously. Here, we describe a cluster of LCMV infections in South-East Queensland identified in early 2021, and the diagnostic testing processes implemented. This identifies LCMV as an under-recognised human pathogen in Australia.

Lymphocytic Choriomeningitis Virus Infection, Australia.

During a mouse plague in early 2021, a farmer from New South Wales, Australia, sought treatment for aseptic meningitis and was subsequently diagnosed with locally acquired lymphocytic choriomeningitis virus infection. Whole-genome sequencing identified a divergent and geographically distinct lymphocytic choriomeningitis virus strain compared with other published sequences.

New Perspective on the Geographic Distribution and Evolution of Lymphocytic Choriomeningitis Virus, Central Europe.

Lymphocytic choriomeningitis virus (LCMV) is an Old World mammarenavirus found worldwide because of its association with the house mouse. When LCMV spills over to immunocompetent humans, the virus can cause aseptic meningitis; in immunocompromised persons, systemic infection and death can occur. Central Europe is a strategic location for the study of LCMV evolutionary history and host specificity because of the presence of a hybrid zone (genetic barrier) between 2 house mouse subspecies, Mus musculus musculus and M. musculus domesticus. We report LCMV prevalence in natural mouse populations from a Czech Republic-Germany transect and genomic characterization of 2 new LCMV variants from the Czech Republic. We demonstrate that the main division in the LCMV phylogenetic tree corresponds to mouse host subspecies and, when the virus is found in human hosts, the mouse subspecies found at the spillover location. Therefore, LCMV strains infecting humans can be predicted by the genetic structure of house mice.

Identification of potential novel hosts and the risk of infection with lymphocytic choriomeningitis virus in humans in Gabon, Central Africa.

OBJECTIVES: Lymphocytic choriomeningitis virus (LCMV), a human pathogenic arenavirus, is distributed worldwide. However, no human cases have been reported in Africa. This study aimed to investigate the current situation and potential risks of LCMV infection in Gabon, Central Africa. METHODS: A total of 492 human samples were screened to detect LCMV genome RNA and anti-LCMV IgG antibodies using reverse transcription-quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. ELISA-positive samples were further examined using a neutralization assay. Viral RNAs and antibodies were also analyzed in 326 animal samples, including rodents, shrews, and bushmeat. RESULTS: While no LCMV RNA was detected in human samples, the overall seroprevalence was 21.5% and was significantly higher in male and adult populations. The neutralization assay identified seven samples with neutralizing activity. LCMV RNA was detected in one species of rodent (Lophuromys sikapusi) and a porcupine, and anti-LCMV IgG antibodies were detected in four rodents and three shrews. CONCLUSIONS: This study determined for the first time the seroprevalence of LCMV in Gabon, and revealed that local rodents, shrews, and porcupines in areas surrounding semi-urban cities posed an infection risk. Hence, LCMV infection should be considered a significant public health concern in Africa.

Lymphocytic Choriomeningitis Virus Infections and Seroprevalence, Southern Iraq.

Acute febrile neurological infection cases in southern Iraq (N = 212) were screened for lymphocytic choriomeningitis virus (LCMV). Two LCMV IgM-positive serum samples and 2 cerebrospinal fluid samples with phylogenetically distinct LCMV strains were found. The overall LCMV seroprevalence was 8.8%. LCMV infections are common and associated with acute neurological disease in Iraq.

Wild Red Foxes (Vulpes vulpes) as Sentinels of Rodent-Borne Hantavirus and Lymphocytic Choriomeningitis Virus in the Province of Soria, Northern Spain.

Three hundred and fourteen red foxes (Vulpes vulpes) in the province of Soria, Spain, were examined for hantavirus and lymphocytic choriomeningitis virus (LCMV) infection (and were likely to have been infected by feeding on infected rodents). Immunofluorescence and western blot assays confirmed 3.5% (11/314) to have antibodies to hantaviruses, and the immune fluorescence assay showed 2.2% (7/314) to have antibodies to LCMV. The serologic status of the animals showed no statistically significant association with sex or age. Although studies on the prevalence of hantaviruses and LCMV normally focus on rodents, our results showed that foxes can provide complementary information in determined areas.

Seroprevalence of lymphocytic choriomeningitis virus and Ljungan virus in Finnish patients with suspected neurological infections.

Directly-transmitted rodent-borne zoonotic viruses, such as lymphocytic choriomeningitis virus (LCMV) can cause nervous system infections. Rodent-borne Ljungan virus (LV) is considered potentially zoonotic possibly causing neurological symptoms. Our objective was to understand the role of these two viruses compared to other pathogens in causing neurological infections in Finnish patients. Routine screening data were available for 400 patients aged 5-50 years, collected from December 2013 to December 2014 with suspected neurological infection. Depending on symptoms, patients were variously tested for herpesviruses, enteroviruses, varicella zoster virus, and Mycoplasma pneumoniae, while those suspected of tick bite were further tested for Borrelia spp. and tick-borne encephalitis virus using antibody and/or nucleic acid tests. For 380 patients, we also screened the RNA and antibody prevalence of LCMV and LV in order to test if either of these viruses were the causative agent. Data collected indicated that the causative microbial agent was confirmed in only 15.5% of all Finnish patients with neurological symptoms, with M. pneumoniae (26 cases) being the most common causative agent found in sera, whereas Borrelia spp. (15), herpes simplex viruses (7), and enteroviruses (5) were the most common agents confirmed in the CSF. The seroprevalences for LV and LCMV were 33.8% and 5.0%, respectively, but no samples were PCR-positive. In this study, M. pneumoniae and Borrelia spp. were the most common causative agents of neurological infections in Finland. No LCMV or LV infections were detected. We conclude there was no association of LV with neurological diseases in this patient cohort.

The impact of illegal waste sites on a transmission of zoonotic viruses.

BACKGROUND: Illegal waste disposal impacts public health and causes aesthetic and environmental pollution. Waste disposed in places without permitted and controlled facilities can provide a ready source of nutrition and shelter for rodents and thus promote the spread of their ecto- and endoparasites. The presence of two distinct zoonotic viruses, lymphocytic choriomeningitis virus (LCMV) and tick-borne encephalitis virus (TBEV), was searched at illegal waste sites. The aim of this study was to determine the prevalence of infection with both viruses in rodents and to discuss the virus-rodent relations in such environments. METHODS: Rodents sampled between October 2011 and April 2013 at 7 locations in the Istrian peninsula, were identified morphologically and genetically to minimize misidentification. Serological and molecular techniques were used to determine seroprevalence of infection in rodents and to detect viral RNAs. Serological testing was performed by immune fluorescence assay for detection of LCMV and TBEV specific antibodies. Real-time RT PCR was used for the detection of LCMV nucleoprotein gene and TBEV 3' non-coding region. Data were statistically analysed using SPSS statistic v2.0. RESULTS: Out of 82 rodent sera tested, the presence of LCMV antibodies was demonstrated in 24.93%. The highest prevalence of LCMV infection was found in commensal Mus musculus (47.37%), followed by 11.53%, 19.04% and 25% prevalence of infection in A. agrarius, A. flavicolis and A. sylvaticus, respectively. The highest prevalence of infection in rodents (53.33%) was found in locations with large waste sites and high anthropogenic influence. LCMV seroprevalence was significantly lower in rodents sampled from natural habitats. Viral nucleic acids were screened in 46 samples but yielded no amplicons of LCMV or TBEV. In addition, TBEV specific antibodies were not detected. CONCLUSIONS: Illegal waste sites have considerable impact on the area where they are located. Results have shown that the transmission of human pathogens can be significantly increased by the presence of waste sites. However, the pathogen must be endemic in the environment where the waste site is located. The introduction of a human pathogen as a consequence of the waste site in the area of interest could not be proven.

Lymphocytic choriomeningitis, Ljungan and orthopoxvirus seroconversions in patients hospitalized due to acute Puumala hantavirus infection.

BACKGROUND: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. OBJECTIVE: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity. STUDY DESIGN: We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care. RESULTS: A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively. CONCLUSION: Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients.

Serological survey of rodent-borne viruses in Finnish field voles.

In northern Europe, rodent populations display cyclic density fluctuations that can be correlated with the human incidence of zoonotic diseases they spread. During density peaks, field voles (Microtus agrestis) become one of the most abundant rodent species in northern Europe, yet little is known of the viruses they host. We screened 709 field voles, trapped from 14 sites over 3 years, for antibodies against four rodent-borne, potentially zoonotic viruses or virus groups-hantaviruses, lymphocytic choriomeningitis virus (LCMV), Ljungan virus (LV), and orthopoxviruses (OPV). Antibodies against all four viruses were detected. However, seroprevalence of hantaviruses, LV, and LCMV was low. OPV antibodies (most likely cowpox) were more common but restricted geographically to southeastern Finland. Within these sites, antibody prevalence showed delayed density dependence in spring and direct density dependence in fall. Higher seroprevalence was found in spring than fall. These results substantially increase knowledge of the presence and distribution of viruses of field voles in Finland, as well as CPXV infection dynamics.

Lymphocytic choriomeningitis virus in employees and mice at multipremises feeder-rodent operation, United States, 2012.

We investigated the extent of lymphocytic choriomeningitis virus (LCMV) infection in employees and rodents at 3 commercial breeding facilities. Of 97 employees tested, 31 (32%) had IgM and/or IgG to LCMV, and aseptic meningitis was diagnosed in 4 employees. Of 1,820 rodents tested in 1 facility, 382 (21%) mice (Mus musculus) had detectable IgG, and 13 (0.7%) were positive by reverse transcription PCR; LCMV was isolated from 8. Rats (Rattus norvegicus) were not found to be infected. S-segment RNA sequence was similar to strains previously isolated in North America. Contact by wild mice with colony mice was the likely source for LCMV, and shipments of infected mice among facilities spread the infection. The breeding colonies were depopulated to prevent further human infections. Future outbreaks can be prevented with monitoring and management, and employees should be made aware of LCMV risks and prevention.

Trace-forward investigation of mice in response to lymphocytic choriomeningitis virus outbreak.

During follow-up of a 2012 US outbreak of lymphocytic choriomeningitis virus (LCMV), we conducted a trace-forward investigation. LCMV-infected feeder mice originating from a US rodent breeding facility had been distributed to >500 locations in 21 states. All mice from the facility were euthanized, and no additional persons tested positive for LCMV infection.

Lymphocytic choriomeningitis virus: an underrecognized cause of neurologic disease in the fetus, child, and adult.

Lymphocytic choriomeningitis virus (LCMV) is an important cause of neurologic disease in humans. Carried and secreted principally by wild mice, LCMV covers a large geographic range and infects great numbers of people. Humans acquire LCMV disease when they come into contact with the secretions of infected mice. Because it has a strong neurotropism, the clinical signs and symptoms of LCMV infection are mostly neurologic. When the virus is acquired postnatally by children or adults, the clinical manifestations are usually those of aseptic meningitis. Most people who acquire LCMV infection during childhood or adulthood are moderately symptomatic for several weeks, but have a full recovery. A much more severe disease ensues when the infection occurs prenatally. LCMV can infect the fetal brain and retina, where it leads to substantial injury and permanent dysfunction. The possibility of LCMV infection should be considered in all babies with evidence of congenital infection, especially those with prominent neurologic signs, such as microencephaly, periventricular calcifications, and hydrocephalus.

Notes from the field: lymphocytic choriomeningitis virus infections in employees of a rodent breeding facility--Indiana, May-June 2012.

In late April 2012, an infectious disease physician contacted CDC regarding a patient with aseptic meningitis who worked at a rodent breeding facility in Indiana. Lymphocytic choriomeningitis virus (LCMV) infection was suspected, and LCMV-specific antibody was detected in blood and cerebrospinal fluid from the patient, confirming the diagnosis. LCMV is an arenavirus carried by the common house mouse. Persons become infected through close contact with infected rodents, through infected organ transplantation, or from mother to fetus. In immunocompetent adults, symptoms can range from mild febrile illness to meningeal symptoms (e.g., headache, stiff neck, or sensitivity to light). Congenitally infected infants can have a range of severe birth defects including hydrocephalus, chorioretinitis, blindness, and mental retardation (1). Infections in organ recipients, who are immunosuppressed, can have a case-fatality rate approaching 90% (2).

Epidemiology of viral encephalitis in 2011.

Encephalitis is an inflammation of the brain structures: neurons, vessels or glial cells. However, a consensual definition of the syndrome is difficult to obtain, and it is even more difficult to define encephalitis due a specific agent. Most viruses can be responsible for infectious encephalitis, but the number of encephalitis cases is very limited with regards of the incidence of benign infections from these pathogens. Viruses responsible for encephalitis can be animal-borne, vector-borne or human-to-human transmitted, they can infect preferentially immunocompetent or immunosuppressed patients, and some of them have demonstrated their epidemic potential. Herpes simplex encephalitis is recognized worldwide as the most frequent infectious encephalitis, and the only one with a validated specific treatment. Encephalitis following some viral infections such as measles or rabies can be prevented by vaccination. Unfortunately, effective treatment currently lacks for most encephalitic viral agents identified so far.