Animal diseases - current developments

The health of domesticated animals and wild animals is frequently threatened by animal illnesses. It typically receives less attention and information than illnesses that also impact humans, including the Corona virus. To be able to respond quickly, it is crucial to understand the epidemic's progression and transmission vectors. Numerous new diseases have been reported in the news over the past 20 years, the majority of which having an animal source (zoonoses). Examples from recent times include the West Nile virus, SARS, avian influenza, and monkeypox. Some developing diseases impact both humans and animals, whereas others only affect either animals or humans. All of these emerging or reemerging illnesses, however, have societal repercussions that are frequently connected to regional and global economy. Understanding the effects of newly emerging animal diseases is crucial, as is promoting closer veterinarian and medical professional collaboration, particularly in rural regions. The index cases for newly developing diseases may be illnesses that affect agricultural laborers.

West Nile Meningoencephalitis in a Patient with Leiomyosarcoma Presenting with Neutropenic Fever

Case Report: West Nile Virus (WNV) was first isolated from the West Nile district of Northern Uganda in 1937, but was first detected in the United States well over half a century later in 1999. The arthropod-borne virus has since persisted, with 2,401 cases reported to the CDC on average annually. The infection typically causes a nonspecific acute systemic febrile illness with occasional gastrointestinal and skin manifestations;however, in less than 1% of infected patients, it can cause severe and potentially fatal neuroinvasive disease, presenting as meningitis, encephalitis or acute flaccid paralysis. Immunosuppression is one of the risk factors associated with the development of neuroinvasive disease, and chemotherapy thus places patients at risk. Uterine leiomyosarcoma is a rare gynecological malignancy. Palliative chemotherapy is common in late stage disease, but may predispose patients to conditions that present as neutropenic fever, leading to a diagnostic conundrum. This is the first case report where patient with neutropenic fever was found to have West Nile neuroinvasive disease, so it is important to include West Nile disease in the differential diagnosis. Case Description: This is a case of a 45-year-old female with history of diabetes, hypothyroidism and recently diagnosed uterine leiomyosarcoma status post tumor debulking with metastasis on palliative chemotherapy with gemcitabine that presented to the Emergency Room for a fever of 103.8 degrees Fahrenheit. Given the history of advanced leiomyosarcoma, the patient was admitted for neutropenic fever with an absolute neutrophil count of 1000. During the hospitalization, the patient became acutely altered and confused. CT head without contrast and lumbar puncture were performed. Due to clinical suspicion of meningitis, she was started on broad spectrum antibiotics. Lumbar puncture revealed leukocytosis of 168 with lymphocytic predominance and elevated protein level in the cerebrospinal fluid, therefore acyclovir was started due to high suspicion of viral meningoencephalitis. An EEG showed severe diffuse encephalopathy as the patient was persistently altered. A broad workup of infectious etiology was considered including HIV, syphilis, hepatitis A, B, C, COVID-19, adenovirus, pertussis, influenza, WNV, HHV6, coccidiomycosis, aspergillus, and tuberculosis. Patient was ultimately found to have elevated IgM and IgG titers for West Nile Virus. Discussion(s): It is important to consider a broad spectrum of diagnosis in patients with metastatic carcinoma presenting with new-onset fever and acute encephalopathy. This includes working up for other causes of altered mental status including cardiac, neurologic, psychiatric, endocrine, metabolic, electrolyte, drug, and infectious etiology. While uncommon in the healthy population, WNV encephalitis should be on the radar for any patient who is immunocompromised or on immunosuppressive therapy, especially those who present with a neutropenic fever.

A Perspective on Current Flavivirus Vaccine Development: A Brief Review.

The flavivirus genus contains several clinically important pathogens that account for tremendous global suffering. Primarily transmitted by mosquitos or ticks, these viruses can cause severe and potentially fatal diseases ranging from hemorrhagic fevers to encephalitis. The extensive global burden is predominantly caused by six flaviviruses: dengue, Zika, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitis. Several vaccines have been developed, and many more are currently being tested in clinical trials. However, flavivirus vaccine development is still confronted with many shortcomings and challenges. With the use of the existing literature, we have studied these hurdles as well as the signs of progress made in flavivirus vaccinology in the context of future development strategies. Moreover, all current licensed and phase-trial flavivirus vaccines have been gathered and discussed based on their vaccine type. Furthermore, potentially relevant vaccine types without any candidates in clinical testing are explored in this review as well. Over the past decades, several modern vaccine types have expanded the field of vaccinology, potentially providing alternative solutions for flavivirus vaccines. These vaccine types offer different development strategies as opposed to traditional vaccines. The included vaccine types were live-attenuated, inactivated, subunit, VLPs, viral vector-based, epitope-based, DNA and mRNA vaccines. Each vaccine type offers different advantages, some more suitable for flaviviruses than others. Additional studies are needed to overcome the barriers currently faced by flavivirus vaccine development, but many potential solutions are currently being explored.

West Nile virus infections in Hungary: Epidemiological update and phylogenetic analysis of the Hungarian virus strains between 2015 and 2022.

Following the introduction of the West Nile virus (WNV) into Hungary in 2004, it has shortly become one of the most important human arbovirus infections, with a gradually increasing number of cases. The study aimed to summarize the current epidemiological situation in Hungary and sequence the WNV PCR-positive clinical specimens and virus isolates by next-generation whole genome sequencing (NGS) to obtain a detailed phylogenetic analysis of the circulating virus strains. Whole blood and urine samples from confirmed WNV-infected patients and WNV isolates were investigated by reverse transcription PCR assays. Genome sequencing was carried out by Sanger-method, followed by NGS on the Illumina MiSeq platform. Altogether 499 human infections were diagnosed between 2004 and 2022. A particularly remarkable increase in human WNV infections was observed in 2018, while the number of reported cases significantly decreased during the COVID-19 pandemic. Between 2015 and 2022, 15 WNV isolates, and 10 PCR-positive clinical specimens were investigated by NGS. Phylogenetic analysis revealed that the major European WNV lineage 2 clades, namely the Eastern European (or Russian) and the Central European (or Hungarian) clades, are presented in Hungary. Strains of the Balkan and other European clusters within the Central European clade are co-circulating in the country, following a characteristic geographical distribution. In Hungary, the presence and co-circulation of multiple lineage 2 WNV strains could be identified in the last few years. Therefore, in light of the 2018 WNV outbreak, sequence-based typing of the currently circulating strains could highly support outbreak investigations.

Severe West Nile Virus Neuroinvasive Disease: Clinical Characteristics, Short- and Long-Term Outcomes.

West Nile Virus Neuroinvasive Disease (WNV NID) requires prolonged intensive care treatment, resulting in high mortality and early disability. Long-term results are lacking. We have conducted an observational retrospective study with a prospective follow-up of WNV NID patients treated at the Intensive Care Unit (ICU), University Hospital for Infectious Diseases, Zagreb, Croatia, 2013-2018. Short-term outcomes were vital status, length of stay (LOS), modified Rankin Scale (mRS), and disposition at discharge. Long-term outcomes were vital status and mRS at follow-up. Twenty-three patients were identified, 78.3% males, median age 72 (range 33-84) years. Two patients (8.7%) died in the ICU, with no lethal outcomes after ICU discharge. The median ICU LOS was 19 days (range 5-73), and the median hospital LOS was 34 days (range 7-97). At discharge, 15 (65.2%) patients had moderate to severe/mRS 3-5, 6 (26.0%) had slight disability/mRS 2-1, no patients were symptom-free/mRS 0. Ten (47.6%) survivors were discharged to rehabilitation facilities. The median time to follow-up was nine months (range 6-69). At follow-up, seven patients died (30.5%), five (21.7%) had moderate to severe/mRS 3-5, one (4.3%) had slight disability/mRS 2-1, six (26.1%) had no symptoms/mRS 0, and four (17.4%) were lost to follow-up. Briefly, ten (43.5%) survivors improved their functional status, one (4.3%) was unaltered, and one (4.3%) aggravated. In patients with severe WNV NID, intensive treatment in the acute phase followed by inpatient rehabilitation resulted in significant recovery of functional status after several months.

Reversible parkinsonism post combined infection with COVID- 19 and typhoid

Objective: To describe a case of levo-dopa responsive parkinsonism secondary to combined COVID-19 and Enteric fever in a patient Background: The first link between viruses and parkinsonism comes from the possible relationship between lethargic encephalitis and the Spanish flu of 1918.In addition, other viruses, including West Nile virus, herpes viruses, influenza A virus, and human immunodeficiency virus (HIV), have been associated with parkinsonism Methods: A 31 years old presented with fever ,headache for 5 days followed by altered sensorium. At presentation he had neck rigidity ,was localizing to pain ,not fully oriented and not following verbal command but he had hypoxia and need nasal oxygen support.He had D-Dimer 12506,COVID-19 RTPCR positive and was treated with Remdesivir,ceftriaxone ,dexamethasone after which he had improvement in sensorium.At day 6 of illness he had generalized rigidity,bradykinesia with slow hypophonic speech and was needing support to sit and walk . A provisional diagnosis of infection related parkinsonism was considered and Cerebrospinal fluid study,MRI Brain and spine ,Blood culture were done .His Cerebrospinal fluid study has normal protein , glucose,cells, stains and culture and negative autoimmune and paraneoplastic plane . His urine culture,blood culture was positive for salmonella typhi and serum widal titre was 1:640.MRI Brain and spine does not show any new abnormalities except old trauma sequalae. He was treated with Levo-dopa carbidopa and titrated to a dose of 675 mg/day and had sustained improvement with levo-dopa carbidopa .There are 6 other case of COVID-19 associated parkinsonism in literature .There are also few case of typhoid associated case of parkinsonism described in literature . Our patient had combined infection of both COVID-19 and typhoid associated parkinsonism. Result(s): We report a case of Infection related parkinsonism secondary to combined COVID-19 plus typhoid infection Conclusion(s): Exploring the potential relationship of co-infection SARS-CoV-2 and Salmonella typhi infection with development of parkinsonism is essential because of the epidemiological implications,as well as to gain a better understanding of the pathophysiological aspects of these disorders.

Innate immune pathway modulator screen identifies STING pathway activation as a strategy to inhibit multiple families of arbo and respiratory viruses.

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses.

Type I IFN stimulates lymph node stromal cells from adult and old mice during a West Nile virus infection.

Advanced age is a significant risk factor during viral infection due to an age-associated decline in the immune response. Older individuals are especially susceptible to severe neuroinvasive disease after West Nile virus (WNV) infection. Previous studies have characterized age-associated defects in hematopoietic immune cells during WNV infection that culminate in diminished antiviral immunity. Situated amongst immune cells in the draining lymph node (DLN) are structural networks of nonhematopoietic lymph node stromal cells (LNSCs). LNSCs are comprised of numerous, diverse subsets, with critical roles in the coordination of robust immune responses. The contributions of LNSCs to WNV immunity and immune senescence are unclear. Here, we examine LNSC responses to WNV within adult and old DLNs. Acute WNV infection triggered cellular infiltration and LNSC expansion in adults. Comparatively, aged DLNs exhibited diminished leukocyte accumulation, delayed LNSC expansion, and altered fibroblast and endothelial cell subset composition, signified by fewer LECs. We established an ex vivo culture system to probe LNSC function. Adult and old LNSCs both recognized an ongoing viral infection primarily through type I IFN signaling. Gene expression signatures were similar between adult and old LNSCs. Aged LNSCs were found to constitutively upregulate immediate early response genes. Collectively, these data suggest LNSCs uniquely respond to WNV infection. We are the first to report age-associated differences in LNSCs on the population and gene expression level during WNV infection. These changes may compromise antiviral immunity, leading to increased WNV disease in older individuals.

Elsberg Syndrome with Mixed Presentation as Meningitis Retention Syndrome: A Pediatric Case Report and Comprehensive Review of the Literature.

Elsberg syndrome is a typically infectious syndrome that may cause acute or subacute bilateral lumbosacral radiculitis and sometimes lower spinal cord myelitis. Patients often present with various neurological symptoms involving the lower extremities, including numbness, weakness, and urinary disturbances such as retention. A 9-year-old girl with no significant past medical history presented with altered mental status, fever, urinary retention, and anuria and was found to have encephalomyelitis. An extensive diagnostic workup led to ruling out possible etiologies until identifying Elsberg syndrome. In this report, we describe a case of Elsberg syndrome caused by West Nile virus (WNV). To the best of our knowledge, this is the first reported case of its kind in the pediatric population. Utilizing PubMed and Web of Science databases, we reviewed the literature to describe the neurogenic control of the urinary system in correlation to a multitude of neurologic pathologies.

Summary of global surveillance data of infectious diseases in December 2022

In December 2022, a total of 68 infectious diseases were reported globally, affecting 235 countries and regions. Except for influenza, the top five infectious diseases affecting greatest number of countries and regions were COVID-19 (235), monkeypox (110), dengue fever (28), measles (27) and cholera (14). The top five infectious diseases with highest case fatality rates were Ebola virus disease (47.0%), Rift Valley fever (44.2%), Crimean-Congo haemorrhagic fever (40.0%), Lassa fever (17.6%) and West Nile fever (7.6%). The top five infectious diseases with greatest number of deaths were COVID-19, malaria, cholera, dengue fever and measles. The prevalent infectious diseases in Asia were COVID-19, cholera and dengue fever, the prevalent infectious diseases in Africa were COVID-19, cholera, yellow fever, Lassa fever, monkeypox, malaria and measles, the prevalent infectious diseases in America were COVID-19, cholera, monkeypox, dengue fever and chikungunya fever, the prevalent infectious disease in Europe were COVID-19, monkeypox and invasive group A streptococcus infection.

Enhancing vaccination of key populations: lessons and actions

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

Human Arboviral Infections in Italy: Past, Current, and Future Challenges.

Arboviruses represent a public health concern in many European countries, including Italy, mostly because they can infect humans, causing potentially severe emergent or re-emergent diseases, with epidemic outbreaks and the introduction of endemic circulation of new species previously confined to tropical and sub-tropical regions. In this review, we summarize the Italian epidemiology of arboviral infection over the past 10 years, describing both endemic and imported arboviral infections, vector distribution, and the influence of climate change on vector ecology. Strengthening surveillance systems at a national and international level is highly recommended to be prepared to face potential threats due to arbovirus diffusion.

Human microglial models to study host-virus interactions.

Microglia, the resident macrophage of the central nervous system, are increasingly recognized as contributing to diverse aspects of human development, health, and disease. In recent years, numerous studies in both mouse and human models have identified microglia as a "double edged sword" in the progression of neurotropic viral infections: protecting against viral replication and cell death in some contexts, while acting as viral reservoirs and promoting excess cellular stress and cytotoxicity in others. It is imperative to understand the diversity of human microglial responses in order to therapeutically modulate them; however, modeling human microglia has been historically challenging due to significant interspecies differences in innate immunity and rapid transformation upon in vitro culture. In this review, we discuss the contribution of microglia to the neuropathogenesis of key neurotropic viral infections: human immunodeficiency virus 1 (HIV-1), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We pay special attention to recent work with human stem cell-derived microglia and propose strategies to leverage these powerful models to further uncover species- and disease-specific microglial responses and novel therapeutic interventions for neurotropic viral infections.

The Role of NS1 Protein in the Diagnosis of Flavivirus Infections.

Nonstructural protein 1 (NS1) is a glycoprotein among the flavivirus genus. It is found in both membrane-associated and soluble secreted forms, has an essential role in viral replication, and modulates the host immune response. NS1 is secreted from infected cells within hours after viral infection, and thus immunodetection of NS1 can be used for early serum diagnosis of dengue fever infections instead of real-time (RT)-PCR. This method is fast, simple, and affordable, and its availability could provide an easy point-of-care testing solution for developing countries. Early studies show that detecting NS1 in cerebrospinal fluid (CSF) samples is possible and can improve the surveillance of patients with dengue-associated neurological diseases. NS1 can be detected postmortem in tissue specimens. It can also be identified using noninvasive methods in urine, saliva, and dried blood spots, extending the availability and effective detection period. Recently, an enzyme-linked immunosorbent assay (ELISA) assay for detecting antibodies directed against Zika virus NS1 has been developed and used for diagnosing Zika infection. This NS1-based assay was significantly more specific than envelope protein-based assays, suggesting that similar assays might be more specific for other flaviviruses as well. This review summarizes the knowledge on flaviviruses' NS1's potential role in antigen and antibody diagnosis.

Emerging and reemerging viral infections in globe with special emphasis in India - A review

It has long been recognized that pathogens, such as viruses, parasites, and other microorganisms, emerge and change over time. Viruses are powerful infectious agents that have co-evolved with humans and are responsible for several serious illnesses in people. There is no herd immunity for most humans, making emerging viruses, particularly the RNA viruses, more dangerous. The high mistake rate of the polymerases that copy the RNA viruses' genomes gives them the ability to adapt to the quickly changing local and global environments. Through mutation (as in the case of Dengue viruses), reassortment (as in the case of influenza viruses), and recombination, they can evolve at a rapid rate (polioviruses). The influenza A viruses (such as H1N1 and H5N1), which have caused numerous outbreaks, epidemics, and pandemics around the world, are the finest example of viruses emerging and reemerging. The complex host-pathogen ecology and the co-evolution of microbes with their hosts are linked to the emergence and reemergence of novel diseases. Human viral illness emergence and reemergence is an ongoing problem that affects a nation's social and economic growth.

West Nile virus IgG antibodies among blood donors in Sudan: a cross-sectional study.

while the world is concentrated on fighting SARS-CoV-2, other viruses such as West Nile virus (WNV) attack the communities silently. West Nile Virus (WNV) is established as one of the infectious agents that transmissible blood transfusion. The present study is cross-sectional, conducted in the central blood bank, Khartoum state, Sudan, and aimed to determine WNV IgG antibodies among blood donors. METHODS: the antibodies of the IgG class against West Nile virus in the serum were determined using the ELISA technique. Ninety blood donors participated in this study. RESULTS: the results showed that 67(74.4%) of participants had positive IgG for WNV. The majority of positive participants 28/67(41.8%) had an age between 28-37 years followed by an age group 18-27 years 24/67(35.8), the dominant blood group of the positive WNV IgG participants was A+ 26/67 (38.8%) followed by O+ 19/67(28.4%). The result displayed that 40(59.7%) of the positive IgG had donated blood several times and 58 (86.6%) had a blood transfusion. Statistical analysis showed an insignificant association between age group, blood group, blood donation, blood transfusion, and West Nile Virus. CONCLUSIONS: the high IgG seroprevalence (which indicated previous infection) in the present study suggests high virus circulation in Sudan. This situation proposed that WNF screening test should be part of blood transfusion screening tests in Sudan.

An expanded role for blood donor emerging pathogens surveillance: CMAJ

From May 2020 (continuing until March 2023), Canadian Blood Services, in partnership with the COVID-19 Immunity Task Force, tested samples from all Canadian provinces (not Quebec and the territories) for SARS-CoV-2 antibodies.2,3 Monthly reports were openly and routinely distributed to provincial and national public health professionals, posted on the COVID-19 Immunity Task Force website (https://www.covid19immunitytaskforce.ca /seroprevalence-in-canada) and used to estimate the population prevalence of SARS-CoV-2 in mathematical models. Canadian Blood Services is undertaking a pilot study to link SARS-CoV-2 seroprevalence data to administrative data from at least 1 province. Canadian Blood Services has a long history of contributing to public health surveillance for vectorborne pathogens such as West Nile virus and Babesia microti, and food-borne illnesses such as hepatitis E.4 We believe it makes sense for blood donor surveillance to take on an expanded role in surveillance for emerging and re-emerging pathogens.

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.