[Opsoclonus-myoclonus syndrome associated with West Nile virus]. / Opsoklonus-mioklonus sindrom, obuslovlennyi likhoradkoi Zapadnogo Nila.

Opsoclonus is oculomotor dyskinesia characterized by rapid, repetitive conjugate eye movements that are involuntary, arrhythmic, chaotic, and multidirectional (horizontal, vertical, and torsional components). Most common cause of the symptom is paraneoplastic process. It is combined with myoclonus usually with the development of opsoclonus-myoclonus syndrome. Viral etiology is one of the possible causes of the of this syndrome, which is presented in the following case. A 26-year-old man was admitted to an infectious hospital suspected by encephalitis. After a 2-day febrile fever the patient developed balance problem, nausea, vomiting, tremors in the limbs and head, sensations of jerking of eyeballs. The neurological examination revealed opsoclonus, myoclonic jerking in the limbs, neck and trunk muscles, severe static and dynamic ataxia, there was no consciousness changes or altered mental stature. Cerebrospinal fluid examination revealed a pleocytosis (24 cells), increased protein levels (1.1 g/l). MRI of the brain was normal. After excluding of typical neuroinfections the patient was tested for West Nile fever. Elevated titers of IgG and IgM for West Nile fever virus were detected, as well as positive PCR for virus RNA in the cerebrospinal fluid. Patient was treated by acyclovir, an antibiotic and dexamethasone but severe neurological symptoms were persisted for 2 weeks with inability of sitting and walking. Then the symptoms gradually began to improve, rehabilitation was included with total recovery during the next 2 months. The doctors should be aware for possibility of neuroinvasive form of West Nile fever as the etiology of opsoclonus-myoclonus syndrome.

Early rise of West Nile fever in Israel, June 2024.

This report describes an unusual surge of West Nile fever in Israel in June 2024, during which 125 cases were diagnosed, compared with 4 cases on average during June in previous years (2014-23). Of the cases, 64 (62.1%) had neuroinvasive disease and 12 (9.6%) died; the 2024 case fatality rate was not significantly elevated vs the average rate in 2014-23. The early rise could be related to a temperature increase in spring and early summer of 2024.

Cross-sectional serosurvey of selected infectious diseases in wild ruminants in Serbia.

The role of wildlife in maintaining infectious diseases in veterinary medicine is often neglected, although the disease eradication process in domestic animals is continuously affected by the risk of pathogens transmission from wildlife as a primary source. The main aim of this paper was to estimate the prevalence and distribution of selected infectious diseases in wild ruminants in Serbia. In total, 259 sera from wild ruminants were tested for specific antibodies to bluetongue virus, Schmallenberg virus, Bovine viral diarrhea/border disease virus, Capripox virus, West Nile fever virus, Bovine herpes virus-1, Coxiella burnetii, Brucella spp., and Leptospira spp. Specific Capripox virus and Leptospira spp. antibodies were not detected in any of the 259 wild ruminant samples. Although one animal was detected positive for BVDV/BDV specific antibodies, with 99.8% confidence, the prevalence of BVD within this population could be very low i.e. essentially free from BVD infection. One and three positive animals were detected for Brucella spp. and Coxiella burnetii antibodies, respectively. Bovine herpes virus-1 specific antibodies were detected in 20.85% of the samples. The estimated seroprevalence of vector-borne diseases was 20.5% for Schmallenberg disease, 34.3% for West Nile fever, and 38.6% for Bluetongue. Considering the reported results, wildlife health status is a result of different factors in complex relation, such as the presence of disease in domestic animals, disease nature, pathogen characteristics, environmental factors, presence, and vector competence. Wildlife should be considered not only as a risk but as a source of important information on disease distribution and its indicators.

West Nile virus in India: An update on its genetic lineages.

West Nile virus (WNV) is a rapidly spreading mosquito-transmitted zoonotic flavivirus. Mosquitoes belonging to the genus Culex are incriminated as the principal vectors of the virus, which causes West Nile fever (WNF) in humans. Manifestations of WNF include a mild, self-limiting, flu-like illness, which in severe cases (rare) may progress to encephalitis, resulting in life-threatening consequences. WNV is geographically distributed worldwide, covering Africa, the Americas, Europe, and Asia (except Antarctica). The virus exists in a bird-mosquito transmission cycle in nature, with humans and horses as incidental/accidental hosts. The virus can infect a large variety of hosts worldwide, i.e., about 300 birds and around 70 different mosquito species belonging to several genera. For a long time, it was believed that WNV was not highly virulent and caused only mild infection globally. However, the recent frequent and increasing incidence of clinically severe WNV infections, such as encephalitis in humans and horses with significant mortality, has been reported in the Americas, Europe, and several East Asian countries. The emergence of lineage 2 strains endemic to Africa, with epidemic potential in humans and horses in Europe, is considered a serious global health concern. Although WNV is known to circulate in India since 1952, its re-emergence with severe neuro-invasive pathogenic potential in humans in Assam, Kerala, West Bengal and Tamil Nadu states signals urgent efforts to understand the dynamics of circulating strains with regard to its vector, hosts, and environment. This could be done by prioritizing "One Health" approach for developing effective preventive and control strategies. In view of the global interest, we present an overview of the circulating genetic lineages of WNV in India in comparison with the global scenario. In addition, we stress on holistic approaches of "One Health" strategy as the current need of the hour for designing effective preventive and control strategies in the country.

Mechanism of Immune Evasion in Mosquito-Borne Diseases.

In recent decades, mosquito-borne illnesses have emerged as a major health burden in many tropical regions. These diseases, such as malaria, dengue fever, chikungunya, yellow fever, Zika virus infection, Rift Valley fever, Japanese encephalitis, and West Nile virus infection, are transmitted through the bite of infected mosquitoes. These pathogens have been shown to interfere with the host's immune system through adaptive and innate immune mechanisms, as well as the human circulatory system. Crucial immune checkpoints such as antigen presentation, T cell activation, differentiation, and proinflammatory response play a vital role in the host cell's response to pathogenic infection. Furthermore, these immune evasions have the potential to stimulate the human immune system, resulting in other associated non-communicable diseases. This review aims to advance our understanding of mosquito-borne diseases and the immune evasion mechanisms by associated pathogens. Moreover, it highlights the adverse outcomes of mosquito-borne disease.

West Nile Virus Infection: A Cross-Sectional Study on Italian Medical Professionals during Summer Season 2022.

West Nile virus (WNV) has progressively endemized in large areas of continental Europe, and particularly in Northern Italy, in the Po River Valley. During summer season 2022, Italy experienced an unprecedented surge in incidence cases of WNV infections, including its main complications (West Nile fever (WNF) and West Nile neuroinvasive disease (WNND)). As knowledge, attitudes, and practices (KAP) of medical professionals may be instrumental in guaranteeing a prompt diagnosis and an accurate management of incident cases, we performed a cross-sectional study specifically on a sample of Italian medical professionals (1 August 2022-10 September 2022; around 8800 potential recipients). From a total of 332 questionnaires (response rate of 3.8%), 254 participating medical professionals were eventually included in the analyses. Knowledge status of participants was unsatisfying, as most of them exhibited knowledge gaps on the actual epidemiology of WNV, with similar uncertainties on the clinical features of WNF and WNND. Moreover, most of participants substantially overlooked WNV as a human pathogen when compared to SARS-CoV-2, TB, and even HIV. Interestingly, only 65.4% of respondents were either favorable or highly favorable towards a hypothetical WNV vaccine. Overall, acknowledging a higher risk perception on WNV was associated with individual factors such as reporting a seniority ≥ 10 years (adjusted odds ratio [aOR] 2.39, 95% Confidence interval [95%CI] 1.34 to 4.28), reporting a better knowledge score (aOR 2.92, 95%CI 1.60 to 5.30), having previously managed cases of WNV infections (aOR 3.65, 95%CI 1.14 to 14.20), being favorable towards a hypothetic vaccine (aOR 2.16, 95%CI 1.15 to 4.04), and perceiving WNV infections as potentially affecting daily activities (aOR 2.57, 95%CI 1.22 to 5.42). In summary, substantial knowledge gaps and the erratic risk perception collectively enlighten the importance and the urgency for appropriate information campaigns among medical professionals, and particularly among frontline personnel.

A Rare Case of West Nile Virus-Associated Cardiomyopathy.

A 68-year-old man presented in late summer 2021 with fever, myalgias, generalized weakness, dizziness, and headache. Past medical history included rheumatoid arthritis treated with infliximab, congestive heart failure with preserved ejection fraction, and recent travel to Alaska. He was febrile, tachycardic, and tachypneic on admission. Physical exam and admission labs were overall unremarkable. On day 4, he complained of shortness of breath and central chest discomfort. Troponin was mildly elevated, electrocardiogram was unremarkable, and echocardiogram showed new global wall motion abnormalities and ejection fraction of 40%, which was 55% months prior. Serum West Nile IgM antibodies resulted positive near the end of hospitalization. Testing for SARS-CoV-2, influenza as well as multiple other viral, bacterial, and fungal organisms was negative. Overall, the patient recovered clinically including improvement in ejection fraction on echocardiogram with conservative management. West Nile virus (WNV) is associated with a myriad of symptoms and complications, most notably, neuroinvasive disease. However, cardiomyopathy secondary to WNV as illustrated in this case has been infrequently described. Clinicians should be aware of this potential rare complication in patients with WNV to improve rapid detection and treatment of myositis, associated cardiomyopathy, and related complications.

Can Biomarkers of Oxidative Stress in Serum Predict Disease Severity in West Nile Virus Infection? A Pilot Study.

West Nile virus (WNV) can cause asymptomatic infection in humans, result in self-limiting febrile illness, or lead to severe West Nile Neuroinvasive disease (WNND). We conducted a pilot study to compare selected biomarkers of oxidative stress in sera of viremic West Nile virus patients and asymptomatic infected blood donors to investigate their potential as predictors of disease severity. We found that total oxidant status was elevated in WNND and in uncomplicated WNV infections (median 9.05 (IQR 8.37 to 9.74) and 7.14 (7.03 to 7.25) µmol H2O2 equiv./L, respectively) compared to asymptomatic infections (0.11 (0.07 to 0.19) µmol H2O2 equiv./L) (p = 0.048). MDA levels showed a similar trend to TOS, but differences were not significant at α = 0.05. Total antioxidant status did not differ significantly between different disease severity groups. Oxidative stress appears to be associated with more severe disease in WNV-infected patients. Our preliminary findings warrant prospective studies to investigate the correlation of oxidative stress with clinical outcomes and severity of WNV infection.

West Nile virus outbreak in Pakistan: Another potential public health threat in the pipeline?

West Nile virus (WNV), a single-stranded RNA virus belonging to the family of Flaviviridae, is an arbovirus transmitted to humans predominantly by mosquito bites. It exhibits a wide range of clinical findings ranging from asymptomatic presentation to severe several neurological disorders. WNV has afflicted several countries around the globe including Pakistan. News of yet another outbreak in the country by WNV is circulating again. Concerned authorities should act vigilantly before the endemic takes over completely and bring down the already bereaving healthcare of Pakistan.

Tick-borne encephalitis virus and West-Nile fever virus as causes of serous meningitis of unknown origin in Kazakhstan.

Flaviviruses are a family of viruses that cause many diseases in humans. Their similarity in the antigenic structure causes a cross-reaction, which complicates the precise diagnostic of disease causing agents. Tick-borne encephalitis virus (TBEV), a member of the flavivirus family, is the cause of tick-borne encephalitis (TBE). Worldwide the awareness of this disease is raising, however, in many countries such as the Republic of Kazakhstan (KZ) there is a lack of serological investigation of flaviviruses in humans. In our study, we focused on two TBE endemic regions of KZ (East Kazakhstan Oblast (EKO) and Almaty (AO)) and a region where TBE cases were registered only since 2010 (Akmola Oblast (AkO)). In KZ, up to 400 cases of serous meningitis of unknown origin were registered annually in the period from 2017 to 2019. Our goals were to calculate the prevalence of antibodies against TBEV in patients with suspected meningitis. We collected 179 sera and 130 cerebrospinal fluid (CSF) samples from patients and included a questionnaire with focus on socio-demographical factors and observed tick bites. The human samples were tested with TBEV and West-Nile fever virus (WNFV) IgM and IgG ELISA, by immunofluorescence assay using a flavivirus biochip, and TBEV-specific real-time RT-PCR. We found TBEV and WNFV antibodies in 31 samples by serological and molecular techniques. Seven serum samples out of 31 showed TBEV-specific antibodies, and three serum pairs had WNFV antibodies. Correlating the serological results with the information gained from the questionnaires it becomes apparent that the number of tick bites is a significant factor for a TBEV infection. This result has an impact on diagnostic in KZ and physicians should be aware that both flaviviruses play a role for serous meningitis of unknown origin in KZ.

Modelling the temperature suitability for the risk of West Nile Virus establishment in European Culex pipiens populations.

Increases in temperature and extreme weather events due to global warming can create an environment that is beneficial to mosquito populations, changing and possibly increasing the suitable geographical range for many vector-borne diseases. West Nile Virus (WNV) is a flavivirus, maintained in a mosquito-avian host cycle that is usually asymptomatic but can cause primarily flu-like symptoms in human and equid accidental hosts. In rare circumstances, serious disease and death are possible outcomes for both humans and horses. The main European vector of WNV is the Culex pipiens mosquito. This study examines the effect of environmental temperature on WNV establishment in Europe via Culex pipiens populations through use of a basic reproduction number ( R 0 ${R_0}$ ) model. A metric of thermal suitability derived from R 0 ${R_0}$ was developed by collating thermal responses of different Culex pipiens traits and combining them through use of a next-generation matrix. WNV establishment was determined to be possible between 14°C and 34.3°C, with the optimal temperature at 23.7°C. The suitability measure was plotted against monthly average temperatures in 2020 and the number of months with high suitability mapped across Europe. The average number of suitable months for each year from 2013 to 2019 was also calculated and validated with reported equine West Nile fever cases from 2013 to 2019. The widespread thermal suitability for WNV establishment highlights the importance of European surveillance for this disease and the need for increased research into mosquito and bird distribution.

Public Perceptions on Non-Pharmaceutical Interventions for West Nile Virus Infections: A Survey from an Endemic Area in Northern Italy.

During the last decade, cases of West Nile Virus (WNV) have occurred in the Emilia Romagna Region (ERR). Even though the notification rates remain relatively low, ranging from 0.06 to 1.83 cases/100,000 inhabitants, the persistent pathogen's circulation in settings characterized by favorable environmental characteristics suggests that WNV is becoming endemic to the Po River Valley. This study assesses knowledge, attitudes, and preventive practices toward WNV prevention among residents from 10 high-risk municipalities from the provinces of Parma and Reggio Emilia (total population: 82,317 inhabitants, census 2020). A web-based survey, based on the health belief model, was performed during the month of January 2021, with a convenience sampling of 469 participants from a series of closed discussion groups on social media (i.e., 2.1% of the potential responders). A total of 243 participants knew the meaning of WNV: Of them, 61.3% were aware of previous WNV infections in ERR, 76.5% acknowledged WNV infection as a severe one, but only 31.3% expressed any worry about WNV. Our results irregularly report preventive practices, either collective (e.g., draining standing water from items and the environment, 50.7%; spraying pesticides around the home, 33.0%) or individual (e.g., use of skin repellants when going outdoors, 42.6%). In a multivariate analysis, performed through binary logistic regression, participants reporting any worry towards WNV were more likely to characterize WNV as a severe disease (adjusted odds ratio [aOR] = 20.288, 95% confidence interval [CI] = 5.083-80.972). On the contrary, respondents supporting community mosquito control programs were more likely among people working with animals/livestock (aOR = 13.948, 95%CI = 2.793-69.653), and supporting tax exemptions for mosquito control programs (aOR = 4.069, 95%CI 2.098-7.893). In conclusion, our results suggest that future interventions promoting WNV prevention among residents in ERR should focus on perceptions of vulnerability to WNV, emphasizing the benefits of personal protective behaviors.

Serological evidence of equine infectious anaemia, West Nile fever, surra and equine piroplasmosis in a herd of horses in northern Argentina.

Northern Argentina hosts equine populations living under preserved natural areas and extensive breeding conditions, with limited access to veterinary care. Horses can be in contact with i) wildlife considered to be a potential reservoir of horse pathogens (e.g. capybara, coatis and pampas deer) and/or ii) potential disease vectors such as ticks, horse flies, Culicidae and vampire bats. In this context, the aim of this study was to assess the exposure of horses from a herd in northern Argentina to different vector-borne pathogens. Serum samples were collected from 20 horses on a farm in Chaco province. Most of these horses were in good health, but a few showed clinical signs such as fever, neurological signs or emaciation. Potential vectors (ticks, horse flies and Culicidae) were present and a fresh bite of a vampire bat (Desmodus rotundus) was observed on one horse. This serological survey revealed that 100% (20/20) were positive for equine infectious anaemia (EIA), 100% (18/18) for West Nile fever (WNF), 53% (10/19) for surra and 45% (9/20) for equine piroplasmosis (Babesia equi). Among these horses, four were found seropositive for all four infections. On the other hand, all the tested horses were seronegative for equine viral arteritis (EVA), Eastern equine encephalomyelitis (EEE), Venezuelan equine encephalitis (VEE), Western equine encephalomyelitis (WEE) and glanders. The data from this survey conducted on a small number of animals illustrate the need for an effective application of surveillance programmes and control measures for equine diseases in northern Argentina and constitute, to our knowledge, the first report of horses simultaneously seropositive for EIA, WNF, surra and equine piroplasmosis.

Unprecedented increase of West Nile virus neuroinvasive disease, Spain, summer 2020.

Cases of West Nile neuroinvasive disease (WNND) in Spain increased in summer 2020. Here we report on this increase and the local, regional and national public health measures taken in response. We analysed data from regional surveillance networks and the National Epidemiological Surveillance Network, both for human and animal West Nile virus (WNV) infection. During the 2020 season, a total of 77 human cases of WNV infection (median age 65 years; 60% males) were detected in the south-west of Spain; 72 (94%) of these cases developed WNND, presenting as meningoencephalitis, seven of which were fatal. In the previous two decades, only six human cases of WNND were detected in Spain. Reduced activities for vector control this season, together with other factors, might have contributed to the massive increase. Public health measures including vector control, campaigns to raise awareness among physicians and the general population, and interventions to ensure the safety of donations of blood products, organs, cells and tissues were effective to reduce transmission. Going forward, maintenance of vector control activities and an update of the vector-borne diseases response plan in Spain is needed.

Epidemiology of human West Nile virus infections in the European Union and European Union enlargement countries, 2010 to 2018.

BackgroundWest Nile virus (WNV) circulates in an enzootic cycle involving mosquitoes and birds; humans are accidental hosts.AimWe analysed human WNV infections reported between 2010 and 2018 to the European Centre for Disease Prevention and Control to better understand WNV epidemiology.MethodsWe describe probable and confirmed autochthonous human cases of WNV infection reported by European Union (EU) and EU enlargement countries. Cases with unknown clinical manifestation or with unknown place of infection at NUTS 3 or GAUL 1 level were excluded from analysis.ResultsFrom southern, eastern and western Europe, 3,849 WNV human infections and 379 deaths were reported. Most cases occurred between June and October. Two large outbreaks occurred, in 2010 (n = 391) and in 2018 (n = 1,993). The outbreak in 2018 was larger than in all previous years and the first cases were reported unusually early. The number of newly affected areas (n = 45) was higher in 2018 than in previous years suggesting wider spread of WNV.ConclusionReal-time surveillance of WNV infections is key to ensuring that clinicians and public health authorities receive early warning about the occurrence of cases and potential unusual seasonal patterns. Human cases may appear shortly after first detection of animal cases. Therefore, public health authorities should develop preparedness plans before the occurrence of human or animal WNV infections.

Antiviral Cytokine Response in Neuroinvasive and Non-Neuroinvasive West Nile Virus Infection.

Data on the immune response to West Nile virus (WNV) are limited. We analyzed the antiviral cytokine response in serum and cerebrospinal fluid (CSF) samples of patients with WNV fever and WNV neuroinvasive disease using a multiplex bead-based assay for the simultaneous quantification of 13 human cytokines. The panel included cytokines associated with innate and early pro-inflammatory immune responses (TNF-α/IL-6), Th1 (IL-2/IFN-γ), Th2 (IL-4/IL-5/IL-9/IL-13), Th17 immune response (IL-17A/IL-17F/IL-21/IL-22) and the key anti-inflammatory cytokine IL-10. Elevated levels of IFN-γ were detected in 71.7% of CSF and 22.7% of serum samples (p = 0.003). Expression of IL-2/IL-4/TNF-α and Th1 17 cytokines (IL-17A/IL-17F/IL-21) was detected in the serum but not in the CSF (except one positive CSF sample for IL-17F/IL-4). While IL-6 levels were markedly higher in the CSF compared to serum (CSF median 2036.71, IQR 213.82-6190.50; serum median 24.48, IQR 11.93-49.81; p < 0.001), no difference in the IL-13/IL-9/IL-10/IFN-γ/IL-22 levels in serum/CSF was found. In conclusion, increased concentrations of the key cytokines associated with innate and early acute phase responses (IL-6) and Th1 type immune responses (IFN-γ) were found in the CNS of patients with WNV infection. In contrast, expression of the key T-cell growth factor IL-2, Th17 cytokines, a Th2 cytokine IL-4 and the proinflammatory cytokine TNF-α appear to be concentrated mainly in the periphery.

Seroprevalence of West Nile Virus among Healthy Blood Donors from Different National Populations Residing in Qatar.

OBJECTIVE: To estimate the age- and nationality-specific West Nile virus (WNV) seroprevalence in select Middle East and North Africa (MENA) populations residing in Qatar. METHODS: Sera were collected from male blood donors attending Hamad Medical Corporation. A total of 1,948 sera were tested for anti-WNV antibodies using Serion ELISA classic IgG and IgM kits. RESULTS: Overall, seroprevalence estimates of WNV-specific IgG and IgM antibodies were 10.4% and 3.3%, respectively. Country-specific WNV-specific IgG seroprevalence was estimated to be 37.0% (34/92) in Sudanese, 33.0% in Egyptians (66/200), 13.0% (26/200) in Indians, 10.6% (11/104) in Iranians, 10.2% (14/137) in Yemenis, 9.2% (18/195) in Pakistanis, 7.0% (14/199) in Jordanians, 5.4% (6/111) in Filipinos, 2.5% (5/200) in Palestinians, 2.5% (5/200) in Syrians, 1.5% (3/200) in Qataris, and 0.9% (1/110) in Lebanese. Seroprevalence of WNV-specific IgM was lowest in Iranians (0/77), Lebanese (0/108), and Filipinos (0/107) at 0.0%, and was highest in Sudanese at 10.0% (8/80). While there seemed to be apparent trends in the prevalence of WNV-IgM and WNV-IgG antibodies, none of these trends were found to be statistically significant. CONCLUSION: The findings support the circulation of WNV in human populations in different countries of the MENA region. Seroprevalence was highest in Sudanese and Egyptians and lowest in Qataris and nationals of the Levant. The findings call for further animal, vector, and human studies, such as studying the actual prevalence of the viral RNA in blood donors to assess the risk of viral transmission through blood donation and for a better characterization of the epidemiology of this infection in this part of the world.

Arthropod-Borne Disease Control at a Glance: What's New on Drug Development?

Discovering and validating effective drugs to manage arthropod-borne diseases (ABD) is a timely and important research challenge with major impacts on real-world control programs at the time of quick resistance development in the targeted pathogens. This editorial highlights major research advances in the development of drugs for the control of vector-borne diseases, with a significant focus on malaria, Chagas disease, dengue, human African trypanosomiasis, leishmaniasis, and Zika. Broad reviews providing new insights on ABD recently published in Molecules have also been covered in "The Editors' pick" section.