Seroprevalence of hantavirus infection in non-epidemic settings over four decades: a systematic review and meta-analysis.

INTRODUCTION: Hantavirus infection is a zoonotic disease from rodents to humans, necessitating seroprevalence assessment for disease burden clarification and control measure implementation. This study aimed to estimate global hantaviruses seroprevalence, examining variations by regions, populations or settings. METHODS: A comprehensive database search identified studies on human hantaviruses seroprevalence using IgG detection until january 2024. A random-effects meta-analysis estimated pooled seroprevalence, with subgroup analyses for geographical region, population, setting or occupation. RESULTS: Out of 3,382 abstracts reviewed, 110 studies were selected, comprising 81,815 observations and 3207 events. The global seroprevalence was calculated at 2.93% (2.34%-3.67%). In terms of geographical distribution, our analysis encompassed 61 studies from the Americas, where the seroprevalence was estimated at 2.43% (95% CI: 1.71%-3.46%), 33 studies from Europe indicating a seroprevalence of 2.98% (95% CI: 2.19%-4.06%), 10 studies from Asia revealing a seroprevalence of 6.84% (95% CI: 3.64%-12.50%), and 6 studies from Africa demonstrating a seroprevalence of 2.21% (95% CI: 1.82%-2.71%). Subgroup analysis underscored varying seroprevalence rates across different populations, settings, and occupations, highlighting the necessity for targeted interventions and preventive measures. CONCLUSION: The analysis reveals a moderate global hantaviruses seroprevalence, emphasizing the viral family's complex transmission dynamics influenced by exposure and geographical factors. This highlights the need for targeted prevention and control strategies.

Distribution and genetic characterization of hantaviruses in bats and rodents from Yunnan.

Hemorrhagic fever with renal syndrome caused by hantaviruses has long been a serious public health issue in Yunnan Province. Hantaviruses exhibit a high extent of biodiversity in their natural hosts, particularly in mammalian hosts. This study was conducted to screen for hantaviruses in bats and rodents in Yunnan Province and elucidate their genetic characteristics and possible zoonotic disease risk. Hantaviruses were detected in 202 bats and 372 rodents with the positive rates 27.49% and 1.25% respectively. A novel lineage (named Lineage 10) of the Seoul virus (SEOV) from rodents and the geographic clustering of hantavirus in bats were identified using phylogenetic analyses of the full-length M- and S-segments. Our study suggest a high cross-species transmissibility of hantaviruses in bats and existence of a new lineage of SEOV in rodents differing significantly from other SEOVs. These results provide data to support the prevention and control of hantavirus-associated diseases in Yunnan Province.

Orthohantavirus infections in South America: a systematic review and meta-analysis.

Orthohantaviruses are zoonotic pathogens that cause acute and severe syndromes in humans. This review was performed to estimate the occurrence of human orthohantaviruses in South America between 2010 and 2022. A careful evaluation of the eligibility and quality of the articles was carried out after a systematic bibliographic search of four databases. The pooled frequency of human orthohantaviruses was calculated using a random effects model meta-analysis. The heterogeneity of estimates (resulting from the chi2 test and I2 statistics) was investigated by subgroup analysis and meta-regression. 1,962 confirmed cases of orthohantavirus infections were diagnosed among 35,548 individuals from seven South American countries. The general occurrence of orthohantaviruses was estimated to be 4.4% (95% confidence interval: 2.9-6.2%) based on general pooling of human cases from 32 studies. In a subgroup analysis considering the study design and method of diagnosis, the percentages of diagnosed orthohantavirus infections differed substantially (I2 = 97.8%, p = 0.00) among South American countries. Four genetic variants of orthohantavirus have been identified circulating in Argentina, Brazil, Bolivia, Chile, Colombia, and Peru. Although laboratory diagnosis of orthohantaviruses is not performed in many countries in South America, there is evidence that four different orthohantaviruses are circulating in the region. The pooled occurrence of viral infection was approximately 4.0% in more than half of the South American countries. Updated information on the occurrence of human infections is essential for monitoring the territorial spread and determining the frequency of this zoonosis.

Amugulang virus, a novel hantavirus harboured by small rodents in Hulunbuir, China.

The Hulunbuir region, known for its diverse terrain and rich wildlife, is a hotspot for various natural epidemic diseases. Between 2021 and 2023, we collected 885 wild rodent samples from this area, representing three families, seven genera, and eleven species. Metagenomic analysis identified three complete nucleic acid sequences from the S, M, and L segments of the Hantaviridae family, which were closely related to the Khabarovsk virus. The nucleotide coding sequences for S, M, and L (1392 nt, 3465 nt, and 6491 nt, respectively) exhibited similarities of 82.34%, 81.68%, and 81.94% to known sequences, respectively, while protein-level analysis indicated higher similarities of 94.92%, 94.41%, and 95.87%, respectively. Phylogenetic analysis placed these sequences within the same clade as the Khabarovsk, Puumala, Muju, Hokkaido, Topografov, and Tatenalense viruses, all of which are known to cause febrile diseases in humans. Immunofluorescence detection of nucleic acid-positive rodent kidney samples using sera from patients with hemorrhagic fever and renal syndrome confirmed the presence of viral particles. Based on these findings, we propose that this virus represents a new member of the Hantaviridae family, tentatively named the Amugulang virus, after its primary distribution area.

Molecular evolution of Hokkaido virus, a genotype of Orthohantavirus puumalaense, among Myodes rodents.

Viruses in the genus Orthohantavirus within the family Hantaviridae cause human hantavirus infections and represent a threat to public health. Hokkaido virus (HOKV), a genotype of Orthohantavirus puumalaense (Puumala virus; PUUV), was first identified in Tobetsu, Hokkaido, Japan. Although it is genetically related to the prototype of PUUV, the evolutionary pathway of HOKV is unclear. We conducted a field survey in a forest in Tobetsu in 2022 and captured 44 rodents. Complete coding genome sequences of HOKVs were obtained from five viral-RNA-positive rodents (four Myodes rufocanus bedfordiae and one Apodemus speciosus). Phylogenetic analysis revealed a close relationship between the phylogenies and geographical origins of M. rufocanus-related orthohantaviruses. Comparison of the phylogenetic trees of the S segments of orthohantaviruses and the cytochrome b genes of Myodes species suggested that Myodes-related orthohantaviruses evolved in Myodes rodent species as a result of genetic isolation and host switching.

The role of health mediation in investigation of Hantavirus cases among informal settlements inhabitants of Cayenne area, French Guiana, 2022-2023.

Context: In 2022, four severe cases of Hantavirus pulmonary syndrome (HPS) were reported in patients from informal settlements around Cayenne, the main city in French Guiana. Regional Health Agency (RHA) was commissioned by the French Public Health Agency to estimate the seroprevalence of Hantavirus infections in the neighborhoods of confirmed cases of HPS. RHA then commissioned the French Red Cross (FRC) mobile public health team, providing support in environmental health issues to the population living in informal settlements by health mediators, to facilitate the investigation. The objective of this study was to describe the health mediators' activities set up to improve the efficiency of the investigation. Methods: The health mediators' team was specifically trained by virologist and infectiologist specialized in HPS. They helped the investigating team and health workers at various steps of the investigation. These interventions are then described in the results section. Results: The investigation took place between Nov. 2022 and March 2023 in three neighborhoods. During the pre-investigation activities, the mediators raised awareness about HPS of 343 people, among whom 319 (93%) planned to participate in the investigation. Altogether, 274 people finally participated in the investigation, including, i.e., 30.8% of the estimated population living in the three concerned settlements. The global proportion of patients with positive IgG anti-Hantavirus was 5.1%. The health mediators team supported the following steps: preliminary meetings and training modules, identification of resource persons, field visits and awareness and information campaigns (pre-investigation); on field data collection in informal settlements (per-investigation) and communication of individual results, public feedback meeting (post-investigation). Discussion/Conclusion: The involvement of mediators was probably a factor in the success of the public health response to socially vulnerable people living in the investigated neighborhoods. The preliminary prevention activities helped to raise awareness of the health risk and to enroll participants. Health mediation and outreach activities seem relevant tools of epidemiological field investigations in diseases affecting inhabitants of informal settlements.

Hantavirus Expansion Trends in Natural Host Populations in Brazil.

Hantaviruses are zoonotic agents responsible for causing Hantavirus Cardiopulmonary Syndrome (HCPS) in the Americas, with Brazil ranking first in number of confirmed HCPS cases in South America. In this study, we simulate the monthly spread of highly lethal hantavirus in natural hosts by conjugating a Kermack-McCormick SIR model with a cellular automata model (CA), therefore simultaneously evaluating both in-cell and between-cell infection dynamics in host populations, using recently compiled data on main host species abundances and confirmed deaths by hantavirus infection. For both host species, our models predict an increase in the area of infection, with 22 municipalities where no cases have been confirmed to date expected to have at least one case in the next decade, and a reduction in infection in 11 municipalities. Our findings support existing research and reveal new areas where hantavirus is likely to spread within recognized epicenters. Highlighting spatial-temporal trends and potential expansion, we emphasize the increased risk due to pervasive habitat fragmentation and agricultural expansion. Consistent prevention efforts and One Health actions are crucial, especially in newly identified high-risk municipalities.

Recurrent Occupational Hantavirus Infections Linked to Feeder Rodent Breeding Farm, Taiwan, 2022.

We investigated 2 acute cases and 1 previous case of Seoul hantavirus infection in workers in a feeder rodent breeding farm in Taiwan. Prevalence of hantavirus IgG among the tested feeder rats was 37.5%. Appropriate prevention measures, including using disinfection protocols and personal protective equipment, are crucial to lowering risk.

In silico design of multi-epitope vaccines against the hantaviruses by integrated structural vaccinology and molecular modeling approaches.

Hantaviruses are single-stranded RNA viruses belonging to the family Bunyaviridae that causes hantavirus cardiopulmonary syndrome (HCPS) and hemorrhagic fever with renal syndrome (HFRS) worldwide. Currently, there is no effective vaccination or therapy available for the treatment of hantavirus, hence there is a dire need for research to formulate therapeutics for the disease. Computational vaccine designing is currently a highly accurate, time and cost-effective approach for designing effective vaccines against different diseases. In the current study, we shortlisted highly antigenic proteins i.e., envelope, and nucleoprotein from the proteome of hantavirus and subjected to the selection of highly antigenic epitopes to design of next-generation multi-epitope vaccine constructs. A highly antigenic and stable adjuvant was attached to the immune epitopes (T-cell, B-cell, and HTL) to design Env-Vac, NP-Vac, and Com-Vac constructs, which exhibit stronger antigenic, non-allergenic, and favorable physiochemical properties. Moreover, the 3D structures were predicted and docking analysis revealed robust interactions with the human Toll-like receptor 3 (TLR3) to initiate the immune cascade. The total free energy calculated for Env-Vac, NP-Vac, and Com-Vac was -50.02 kcal/mol, -24.13 kcal/mol, and -62.30 kcal/mol, respectively. In silico cloning, results demonstrated a CAI value for the Env-Vac, NP-Vac, and Com-Vac of 0.957, 0.954, and 0.956, respectively, while their corresponding GC contents were 65.1%, 64.0%, and 63.6%. In addition, the immune simulation results from three doses of shots released significant levels of IgG, IgM, interleukins, and cytokines, as well as antigen clearance over time, after receiving the vaccine and two booster doses. Our vaccines against Hantavirus were found to be highly immunogenic, inducing a robust immune response that demands experimental validation for clinical usage.

Evaluating climate-dependent distribution of orthohantaviruses with monitoring wild rodents: One Health Perspective†.

Orthohantaviruses, cause hemorrhagic fever with renal syndrome, nephropathia epidemica, and hantavirus pulmonary syndrome, are major public health problems all over the world. Wild rodent surveillance for orthohantaviruses is of great importance for the preparedness against these human infections and the prediction of possible outbreak regions. Thus, we aimed to screen orthohantaviruses in wild rodents in Southern Anatolia, where the area has some of the glacial period refugia in the Mediterranean Basin, and interpret their current epidemiology with climatic biovariables in comparison with previously positive regions.We trapped muroid rodents between 2015 and 2017, and screened for orthohantaviruses. Then, we evaluated the relationship between orthohantavirus infections and bioclimatic variables. In spite of the long-term and seasonal sampling, we found no evidence for Orthohantavirus infections. The probable absence of orthohantaviruses in the sampling area was further evaluated from the climatic perspective, and results led us suggest that Orthohantavirus epidemiology might be relatively dependent on precipitation levels in driest and warmest quarters, and temperature fluctuations.These initial data might provide necessary perspective on wild rodent surveillance for orthohantaviruses in other regions, and help to collect lacking data for a such habitat suitability study in a bigger scale in the future.

Orthohantaviruses in Misiones Province, Northeastern Argentina.

Few cases of hantavirus pulmonary syndrome have been reported in northeastern Argentina. However, neighboring areas show a higher incidence, suggesting underreporting. We evaluated the presence of antibodies against orthohantavirus in small rodents throughout Misiones province. Infected Akodon affinis montensis and Oligoryzomys nigripes native rodents were found in protected areas of Misiones.

Use of a diagnostic Puumala virus real-time RT-PCR in an orthohantavirus endemic region in the Netherlands.

Laboratory diagnosis of orthohantavirus infection is primarily based on serology. However, for a confirmed serological diagnosis, evaluation of a follow-up serum sample is essential, which is time consuming and causes delay. Real-time reverse transcription polymerase chain reaction (RT-PCR) tests, if positive, provide an immediate and definitive diagnosis, and accurately identify the causative agent, where the discriminative nature of serology is suboptimal. We re-evaluated sera from orthohantavirus-suspected clinical cases in the Dutch regions of Twente and Achterhoek from July 2014 to April 2016 for the presence of Puumala orthohantavirus (PUUV), Tula orthohantavirus (TULV), and Seoul orthohantavirus (SEOV) RNA. PUUV RNA was detected in 11% of the total number (n = 85) of sera tested, in 50% of sera positive for anti-PUUV/TULV IgM (n = 16), and in 1.4% of sera negative or indeterminate for anti-PUUV/TULV IgM (n = 69). No evidence was found for the presence of TULV or SEOV viral RNA. Based on these findings, we propose two algorithms to implement real-time RT-PCR testing in routine orthohantavirus diagnostics, which optimally provide clinicians with early confirmed diagnoses and could prevent possible further invasive testing and treatment. IMPORTANCE: The addition of a real-time reverse transcription polymerase chain reaction test to routine orthohantavirus diagnostics may better aid clinical decision making than the use of standard serology tests alone. Awareness by clinicians and clinical microbiologists of this advantage may ultimately lead to a reduction in over-hospitalization and unnecessary invasive diagnostic procedures.

Development and standardization of an enzyme-linked inmunosorbent for the detection of orthohantavirus infection in Argentina based on its bacterial-expressed nucleocapside protein.

We conducted a development and standardization of an IgG ELISA assay for serological detection of human orthohantavirus infections using the recombinant antigen rLECH13 produced in bacterial and derived from the LECHV. The evaluation and standardization were carried out by analyzing serum samples from a total of 50 patients with confirmed Hantavirus Pulmonary Syndrome (HPS) diagnosis through the reference technique, 50 negative sera, and 53 patients with other medical conditions. The data from the assay analysis showed a diagnostic sensitivity value of 95% and a diagnostic specificity of 80%. The high sensitivity of this novel assay leads us to conclude that rLECH13 is a feasible option for use in the immunodiagnostic of orthohantavirus infection. Additionally, it is crucial to have an antigen that can be produced under conditions that do not require highly complex laboratories. Furthermore, the new assay is cost-effective, reproducible, and demonstrates excellent performance.

Brno loanvirus (BRNV) in bats inhabiting the urban area of Brno, Czech Republic.

Bats are known reservoirs of various emerging pathogens, and have recently been found to host a novel hantavirus, named Brno loanvirus (BRNV), from the Mammantavirinae subfamily (family Hantaviridae, order Bunyavirales). Here we report BRNV detection in bats from the urban area of Brno, Czech Republic in March 2022. Specifically, we uncovered a high prevalence of BRNV (8.8%, 5/57) among hibernating bats (Nyctalus noctula) in urban area, which poses a risk of human exposure. The positive bats included adult females (3/9 positive), a juvenile female (1/32 positive), and an adult male (1/6 positive). All 10 juvenile males were negative. We used RT-qPCR to quantify the BRNV RNA levels in various bat organs, which yielded positive results for viral RNA in organs, including the kidneys, heart, spleen, brain, liver, lung, and gut, and in body cavity fluid. Among all tested organs, the liver showed the highest levels of viral RNA in 4 out of 5 animals examined (average Ct value of 20.8 ± 7.4).

Single-Domain Antibody-Gold Nanoparticle Bioconjugates as Immunosensors for the Detection of Hantaviruses.

INTRODUCTION: Hantavirus, a zoonotic pathogen, causes severe syndromes like hemorrhagic fever with renal syndrome (HFRS), sometimes fatal in humans. Considering the importance of detecting the hantavirus antigen, the construction of an immunosensor is essential. The structural and functional characteristics of camelid nanobodies (VHHs) encourage their application in the areas of nanobiotechnology, therapeutics, diagnostics, and basic research. Therefore, this study aimed to standardize stable bioconjugates using gold nanoparticles (AuNPs) and VHHs, in order to develop immunobiosensors for the diagnosis of hantavirus infection. METHODS: Immobilized metal affinity chromatography (IMAC) was performed to obtain purified recombinant anti-hantavirus nucleocapsid nanobodies (anti-prNΔ85 VHH), while AuNPs were synthesized for bioconjugation. UV-visible spectrophotometry and transmission electron microscopy (TEM) analysis were employed to characterize AuNPs. RESULTS: The bioconjugation stability parameters (VHH-AuNPs), analyzed by spectrophotometry, showed that the ideal pH value and VHH concentration were obtained at 7.4 and 50 µg/mL, respectively, after addition of 1 M NaCl, which induces AuNP aggregation. TEM performed before and after bioconjugation showed uniform, homogeneous, well-dispersed, and spherical AuNPs with an average diameter of ~ 14 ± 0.57 nm. Furthermore, high-resolution images revealed a thin white halo on the surface of the AuNPs, indicating the coating of the AuNPs with protein. A biosensor simulation test (dot blot-like [DB-like]) was performed in stationary phase to verify the binding and detection limits of the recombinant nucleocapsid protein from the Araucária hantavirus strain (prN∆85). DISCUSSION: Using AuNPs/VHH bioconjugates, a specific interaction was detected between 5 and 10 min of reaction in a dose-dependent manner. It was observed that this test was sensitive enough to detect prNΔ85 at concentrations up to 25 ng/µL. Considering that nanostructured biological systems such as antibodies conjugated with AuNPs are useful tools for the development of chemical and biological sensors, the stability of the bioconjugate indicates proficiency in detecting antigens. The experimental results obtained will be used in a future immunospot assay or lateral flow immunochromatography analysis for hantavirus detection.

Invasive Pulmonary Aspergillosis in Critically Ill Patients with Hantavirus Infection, Austria.

We investigated a cohort of 370 patients in Austria with hantavirus infections (7.8% ICU admission rate) and detected 2 cases (cumulative incidence 7%) of invasive pulmonary aspergillosis; 1 patient died. Hantavirus-associated pulmonary aspergillosis may complicate the course of critically ill patients who have hemorrhagic fever with renal syndrome.

First clinical reports of acute hantavirus and dengue infections among pregnant women in the Caribbean.

BACKGROUND: Hantavirus and dengue virus infections lead to diseases causing economic and public health concerns. Acute hantavirus infections can lead to similar clinical haemorrhagic signs as other endemic diseases including dengue and leptospirosis. METHODS: Using a retrospective case analysis of pregnant dengue and hantavirus disease patients with clinical reports and compatible clinical laboratory information during pregnancy, we report the first evidence of dengue and hantavirus infections and a case of dual dengue and hantavirus infection among pregnant women in the Caribbean. Laboratory testing by enzyme-linked immunosorbent assay (ELISA) and non-structural protein 1 (NS1) for DENV and for hantavirus infection pseudotype focus reduction neutralisation tests (pFRNT), ELISA and immunochromatographic (ICG) strips. RESULTS: Four pregnant cases with acute DENV infections were identified; however, only one out of the four cases (25%) had a detailed medical record to permit abstraction of clinical data. Six hantavirus infected pregnant cases were identified with gestation periods ranged from 36 to 39 weeks; none of the reported patients exhibited previous pregnancy complications prior to hospitalisation and infection. Acute liver damage was observed in three of the six cases (AST readings) who were subsequently diagnosed with hepatitis in pregnancy and variable clinical outcomes were observed with term and pre-term deliveries. CONCLUSIONS: Whilst hantavirus infection in pregnancy is rare, consideration should be given to differential diagnosis with fever, kidney involvement, liver involvement, haemorrhagic symptoms and thrombocytopenia in endemic areas with clinically similar diseases such as dengue and leptospirosis.HighlightsFirst recorded case of hantavirus and dengue co-infection in a pregnant woman.First detailed report of clinical hantavirus infection in pregnant women in the Caribbean.First published report of clinical dengue infection in pregnant woman in the Caribbean.Possible complications of pregnancy following hantavirus infection.Pre-term birth and low birth weights.Clinical course of hantavirus infection in a Caribbean population.

Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study.

BACKGROUND: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. METHODS: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. FINDINGS: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). INTERPRETATION: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. FUNDING: National Institutes of Health and Agencia de Investigación y Desarrollo. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Hantavirus infection-related acute inflammatory demyelinative polyradiculoneuropathy: A case report and literature review.

RATIONALE: Hemorrhagic fever with renal syndrome (HFRS) is a common infectious disease in China. As a complication of post-Hantavirus infection, Guillain-Barre syndrome (GBS) was rarely previously reported. Here, we described a case of acute inflammatory demyelinative polyradiculoneuropathy secondary to Hantavirus infection in spring of 2023. We also made a summary of the clinical features from previous reported cases. PATIENT CONCERNS: A young male patient complained a fever with headache, who was subsequently diagnosed with HFRS with positive serum Hantavirus antibody IgM. Two weeks later, he presented sustained back pain, obvious numbness located in 4 extremities, chest and abdomen, facial dyskinesia and 4 extremities muscle weakness. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: He was rapidly diagnosed with GBS by typical cerebrospinal fluid change and the electromyography examination presentation, which was verified associated with hantavirus infection. He was treated with intravenous immunoglobulin infusion followed by rehabilitation treatment. He got a complete recovery within 4 months after disease onset. LESSONS: GBS was an uncommon manifestation of Hantavirus infection. GBS should be considered when acute limb weakness happens in cases with HFRS. A multidisciplinary team could make a rapid diagnosis and optimal treatment when nervous system disorders occurred.