Arthropod-borne Infections Research Articles

Prior influenza virus infection alleviates an arbovirus encephalitis by reducing viral titer, inflammation, and cellular infiltrates in the central nervous system.

Influenza viruses are medically important human pathogens that caused epidemics and pandemics throughout history. Conversely, encephalitic arthropod-borne virus (arboviral) diseases affect both humans and domestic animals, creating massive public health issues. Influenza viruses circulate globally while arboviruses dominate tropical regions. Given both influenza virus and encephalitic arboviruses, such as alphaviruses, circulate in many regions globally, co-infections are likely to occur. In addition, arthropod-borne neurotropic infections are generally mild or asymptomatic, hence are likely to be unnoticed as a risk factor during influenza infection. However, the consequences of such co-infections are unclear. Our recent study showed that alphavirus infection preceding Influenza A virus (IAV) infection negatively impacted immune responses to the influenza virus in mice. Here, we aim to investigate the immune responses when the order of sequential infection with IAV and alphavirus are swapped. Altogether, our findings will provide key insights to improved diagnostics, preventative vaccines, and antiviral therapies.

Low-density Lipoprotein Receptor is an important host factor in flaviviral entry and replication in neurons.

Flaviviruses, which are transmitted by mosquitoes, are arthropod-borne infections that are pathogenic to both humans and animals, posing a significant global threat to public health. So far, various endocytic pathways have been reported for flaviviral entry; however, the role of cellular factors in viral replication and entry remains uncertain. Here in this study, we identified the role of Low-density lipoprotein receptor, which has long been established as a cholesterol carrier for neurons but remained unexplored as an essential host factor for JEV/WNV replication. To explore this, we utilized 10-day old BALB/c pups and two neuronal cell lines, NSC34 and HT22, both of different origin, as experimental models. Transient knockdown of LDLR gene in vitro using siRNA-mediated gene silencing drastically reduced viral specific transcripts and proteins upon viral incubation. Moreover, flaviviral binding and internalization were significantly compromised upon infection in LDLR-transfected cells when compared with non-specific eGFP-transfected cells. Antibody neutralization experiments using LDLR-specific polyclonal antibody significantly reduced viral entry in vitro, suggesting the role of LDLR as an important cell attachment factor for JEV and WNV uptake. Furthermore, ectopic expression of LDLR via plasmid transfection led to significant increase in virus replication in cells, indicating significant role of LDLR in flavivirus replication beside acting as an active attachment factor for JEV and WNV. Overall, our results indicate that LDLR act as novel host factor involved in both flaviviral entry and replication, thus serving as a suitable candidate for antiviral research.

Research progress toward arthropod salivary protein vaccine development for vector-borne infectious diseases.

Hematophagous arthropods, including mosquitoes, ticks, and flies, are responsible for the transmission of several pathogens to vertebrates on whom they blood feed. The diseases caused by these pathogens, collectively known as vector-borne diseases (VBDs), threaten the health of humans and animals. In general, attempts to develop vaccines for pathogens transmitted by arthropods have met with moderate success, with few vaccine candidates currently developed. Nowadays, there are vaccine candidates under clinical trials, including different platforms, like mRNA, DNA, recombinant viral vector-based, virus-like particles (VLPs), inactivated-virus, live-attenuated virus, peptide and protein-based vaccines, all of them based on the presentation of pathogen antigens to the host immune system. A new approach to prevent VBDs has arose during the last decades, based on the design of vaccines that target vector-derived antigens. The salivary secretions of arthropods, in addition of causing allergic reactions and harbor pathogens, are also involved in the transmission and infection establishment in the host, altering its immune responses. In this review, we summarize the achievements in the arthropod salivary-based vaccine development for different vector-borne infectious diseases. This provides a rationale for creating vaccines against different types of arthropod salivary proteins, such as mosquitoes, ticks, and sand flies. Using salivary proteins of clinically important vectors might contribute to achieve protection against and control multiple arthropod-borne infection diseases.

A Scoping Review of Arthropod-Borne Flavivirus Infections in Solid Organ Transplant Recipients.

Arthropod-borne flaviviruses (ABFs), transmitted by mosquitoes or ticks, are increasing due to climate change and globalization. This scoping review examines the epidemiology, clinical characteristics, diagnostics, treatment, and outcomes of ABF infection in solid organ transplant recipients (SOTRs). A database search up to January 25, 2024, focused on ABFs such as West Nile virus (WNV), dengue virus (DENV), Japanese encephalitis virus (JEV), Powassan virus (POWV), yellow fever virus (YFV), and Zika virus (ZIKV), limited to SOTRs. We identified 173 WNV cases from 84 studies, with 28 donor-derived infections (DDIs). Common clinical features included fever (78.5%), altered mental status (65.1%), and weakness or paralysis (45.6%). Treatment involved reducing immunosuppression (IS) in 93 cases, with intravenous immunoglobulin (IVIG), interferon alfa-2b, and ribavirin used in 75 cases. Seven cases involved graft loss or rejection post-infection. WNV infection had a 23.7% mortality rate, with severe neurological complications in 43.9% For DENV infection, 386 cases from 47 studies were identified, including 14 DDI cases. Symptoms included fever (85%), myalgias (56.4%), and headache or retro-orbital pain (34.6%). Severe dengue occurred in 50 cases (13.0%). IVIG was administered in six cases. Reduction in IS was reported in 116 patients. DENV mortality rate was 4.9%. Additionally, 26 cases of less common ABFs such as JEV, POWV, YFV, and ZIKV were described. In summary, ABF infections among SOTRs are associated with higher morbidity and mortality compared to the general population, emphasizing the need for improved preventive strategies, timely diagnosis, and optimized management protocols.

Positive feedback regulation between RpoS and BosR in the Lyme disease pathogen.

Lyme disease is the most prevalent arthropod-borne infection in the United States. The etiological agent, Borreliella (or Borrelia ) burgdorferi , is maintained in nature through an enzootic cycle involving a tick vector and a mammalian host. RpoS, the master regulator of differential gene expression, plays a crucial role in tick transmission and mammalian infection of B. burgdorferi . This study reveals a positive feedback loop between RpoS and a Fur/PerR homolog. Elucidating this regulatory network is essential for identifying potential therapeutic targets to disrupt B. burgdorferi 's enzootic cycle. The findings also have broader implications for understanding the regulation of RpoS and Fur/PerR family in other bacteria.

La Crosse virus encephalitis in children.

La Crosse virus encephalitis (LACV-E) is among the most common neuroinvasive arthropod-borne viral infections of childhood in North America. Children are uniquely predisposed to symptomatic disease, whereas symptomatic adult infections remain uncommon. Infection results frequently in neurologic symptomatology including headaches, seizures, and altered mentation, often necessitating hospitalization and significant diagnostic evaluation. The purpose of this review is to provide a contemporary assessment of clinical, laboratory, and neurobehavioral outcomes of children with LACV-E. Common clinical manifestations at presentation, specifically seizure activity and altered mental status, are independent predictors of disease severity. Epileptiform discharges on electroencephalogram (EEG) during hospitalization may predict long-term epilepsy diagnosis. Lastly, long-term neurologic sequelae from acute infection is persistent and likely under-recognized among children with LACV-E. As climate change alters the geographic distribution of mosquito borne illnesses, a possibility of regional expansion of La Crosse virus (LACV) endemicity exists. The above data highlight readily identifiable features and testing modalities for clinicians who may encounter this viral infection. Importantly, an emphasis on long term neurobehavioral follow up is necessary to better identify and provide support of affected individuals. Future research in identifying host immune responses to LACV infection, as well as therapeutic options, are needed.

The curious case of subcutaneous dirofilariasis mimicking a fibroma - Report of a rare disease from North India.

Human dirofilariasis is a rare arthropod-borne zoonotic infection caused by a filarial nematode of the genus Dirofilaria. It typically manifests in humans as pulmonary, ocular, or subcutaneous lesions. In India, the disease is predominantly seen in the southern states, especially Kerala. Cases documented from India are mostly of ocular infection, and very few cases of subcutaneous dirofilariasis (SD) are reported. We hereby present a case of SD in a 25-year-old male, clinically diagnosed to have fibroma of the left forearm. Histopathology confirmed the diagnosis of SD. We present this case to reiterate that SD, though very rare in North India, should always be considered as a differential for subcutaneous swellings.

A pilot study investigating severe community-acquired febrile illness through implementation of an innovative microbiological and nucleic acid amplification testing strategy in Timor-Leste (ISIN-MANAS-TL)

ObjectivesAcute febrile illness (AFI) causes significant health-seeking, morbidity, and mortality in Southeast Asia. This pilot study aimed to describe presentation, etiology, treatment, and outcomes of patients with AFI at one hospital in Timor-Leste and assessing the feasibility of conducting larger studies in this setting. MethodsPatients attending Hospital Nacional Guido Valadares with tympanic or axillary temperature ≥37.5°C in whom a blood culture was taken as part of routine clinical care were eligible. Participants were followed up daily for 10 days and again after 30 days. Whole blood was analyzed using a real-time quantitative polymerase chain reaction assay detecting dengue virus serotypes 1-4 and other arthropod-borne infections. ResultsA total of 82 participants were recruited. Polymerase chain reaction testing was positive for dengue in 14 of 82 (17.1%) participants and blood culture identified a bacterial pathogen in three of 82 (3.7%) participants. Follow-up was completed by 75 of 82 (91.5%) participants. High rates of hospital admission (58 of 82, 70.7%), broad-spectrum antimicrobial treatment (34 of 82, 41.5%), and mortality (9 of 82, 11.0%) were observed. ConclusionsPatients with AFI experience poor clinical outcomes. Prospective observational and interventional studies assessing interventions, such as enhanced diagnostic testing, clinical decision support tools, or antimicrobial stewardship interventions, are required and would be feasible to conduct in this setting.

Epidemiological Profile of Communicable Diseases in Childhood within the Babylon Governorate, Iraq from 2017 to 2021

Background: Notifiable communicable diseases are a significant public health issue in Iraq, particularly among children. Aims: This study aimed to comprehensively assess the epidemiological profile of childhood communicable diseases in Babylon Governorate, Iraq, over the period 2017–2021 Methods and Material: Data from 11,925 cases of notifiable communicable diseases were collected from the health department in AL-Hilla City, Iraq, between 2017 and 2021. The data were analysed according to the mode of transmission, type of infection, and age and sex patterns. Results: The majority of the reported communicable diseases (85.4%) were droplet and airborne infections, with pneumonia being the most frequently reported respiratory infection (76.8%). The reported cases of pertussis, viral meningitis, bacterial meningitis, chickenpox, and mumps showed a significant decrease during the study period, while the incidence of measles had two peaks in 2019 and 2020. Viral hepatitis A and typhoid fever were the most frequently reported foodborne infections. Kala-azar was the most common arthropod-borne infection, while brucellosis and rabies were the most common zoonotic infections. Pneumonia and meningitis affected infants and children aged 1-4 years more commonly than other age groups, while pertussis affected infants and children aged 1-4 years more frequently than other age groups, with a female predominance. Measles affected infants and children aged 1-4 years more commonly than older age groups, with a male predominance. Conclusions: This study provides a comprehensive overview of the occurrence and trends of notifiable communicable diseases among children in AL-Hilla City, Iraq, between 2017 and 2021. The findings highlight the need for improved surveillance and prevention measures.

Effects of human mobility on the spread of Dengue in the region of Caldas, Colombia.

According to the World Health Organization (WHO), dengue is the most common acute arthropod-borne viral infection in the world. The spread of dengue and other infectious diseases is closely related to human activity and mobility. In this paper we analyze the effect of introducing mobility restrictions as a public health policy on the total number of dengue cases within a population. To perform the analysis, we use a complex metapopulation in which we implement a compartmental propagation model coupled with the mobility of individuals between the patches. This model is used to investigate the spread of dengue in the municipalities of Caldas (CO). Two scenarios corresponding to different types of mobility restrictions are applied. In the first scenario, the effect of restricting mobility is analyzed in three different ways: a) limiting the access to the endemic node but allowing the movement of its inhabitants, b) restricting the diaspora of the inhabitants of the endemic node but allowing the access of outsiders, and c) a total isolation of the inhabitants of the endemic node. In this scenario, the best simulation results are obtained when specific endemic nodes are isolated during a dengue outbreak, obtaining a reduction of up to 2.5% of dengue cases. Finally, the second scenario simulates a total isolation of the network, i.e., mobility between nodes is completely limited. We have found that this control measure increases the number of total dengue cases in the network by 2.36%.

Dried Serum Samples for Antibody Detection in Arthropod-Borne Virus Infections Are an Effective Alternative to Serum Samples.

The disease burden of arthropod-borne infections is particularly high in low- and middle-income countries, where the availability of resources for surveillance and testing is limited. The lack of local infrastructure demands that biological samples be sent to central laboratories by refrigerated transport, which increases costs and the risk of sample degradation. Dried blood spot samples are an alternative for ensuring sample integrity during transportation and storage. They can be used for the detection of nucleic acids and proteins, such as antigens or antibodies. Here, we compared anti-chikungunya IgM, anti-dengue IgM, anti-dengue IgG, and anti-Zika IgG detection between paired serum and dried serum samples (DSSs); the agreement between results was found to be 90.6%, 94.1%, 85.9%, and 95.5%, respectively, indicating a strong correlation. Our results suggest that DSSs provide a reliable alternative for detection of specific antibodies in arthropod-borne infections.

Multisystem Failure in Fatal Dengue: Associations between the Infectious Viral Serotype and Clinical and Histopathological Findings.

Dengue is the most important arthropod-borne viral infection of humans. However, its viral pathogenesis is still unknown. The information collected from dengue fatal cases is crucial for understanding the complex interactions between virulence and host factors. This study aimed to establish possible associations between the clinical characteristics, histopathological changes, replication, and tissue location of viral serotypes in dengue fatal cases. Clinical and histopathological characterizations, antigen localization in tissue, and detection of the infecting serotype and replication using real-time polymerase chain reaction were all performed on the dengue fatal cases. The majority of the cases involved people under the age of 20. Bleeding (48.3%), abdominal pain (44.8%), myalgia (52.9%), and headache (48.3%) were the most common clinical manifestations in the cases. There was multiorgan pathology, with histopathological changes primarily in the liver, spleen, and lung. Similarly, the viral antigen was found primarily in these organs; however, there were no associations between tissue changes, viral location, infecting serotypes, and replication processes. Dengue infection should be considered a multiorgan disease, the outcome of which is possibly not associated with the infecting viral serotype.

Seroprevalence of arthropod-borne bacterial infections in homeless individuals in Hamburg in 2020

PurposeThe number of homeless people in Germany is steadily increasing. Due to their often precarious living conditions, this specific population may be increasingly exposed to ectoparasites that can transmit various pathogens. To assess the prevalence and thus the risk of such infections, we analyzed the seropositivity of rickettsiosis, Q fever, tularemia and bartonellosis in homeless individuals.MethodsA total of 147 homeless adults from nine shelters in Hamburg, Germany, were included. The individuals underwent questionnaire-based interviewing, physical examination, and venous blood was drawn between May and June 2020. Blood samples were analyzed for antibodies against rickettsiae (Rickettsia typhi and R. conorii), Coxiella burnetii, Francisella tularensis and bartonellae.Results and conclusionA very low seroprevalence of R. typhi and F. tularensis infection was found (0–1%), while antibodies against R. conorii and C. burnetii were more common (7% each), followed by a relatively high seroprevalence of 14% for bartonellosis. Q fever seroprevalence was associated with the country of origin, whereas bartonellosis seroprevalence was associated with the duration of homelessness. Preventive measures targeting ectoparasites, especially body lice, should be put in place continuously.

Tetrahydroquinazoline N-oxide derivatives inhibit reproduction of tick-borne and mosquito-borne flaviviruses.

Tick-borne encephalitis virus (TBEV), yellow fever virus (YFV), and West Nile virus (WNV) are flaviviruses causing emerging arthropod-borne infections of a great public health concern. Clinically approved drugs are not available to complement or replace the existing vaccines, which do not provide sufficient coverage. Thus, the discovery and characterization of new antiflaviviral chemotypes would advance studies in this field. In this study, a series of tetrahydroquinazoline N-oxides was synthesized, and the antiviral activity of the compounds was assessed against TBEV, YFV, and WNV using the plaque reduction assay along with the cytotoxicity to the corresponding cell lines (porcine embryo kidney and Vero). Most of the studied compounds were active against TBEV (EC50 2 to 33 μM) and WNV (EC50 0.15 to 34 μM) and a few also demonstrated inhibitory activity against YFV (EC50 0.18 to 41 μM). To investigate the potential mechanism of action of the synthesized compounds, time-of-addition (TOA) experiments and virus yield reduction assays were performed for TBEV. The TOA studies suggested that the antiviral activity of the compounds should affect the early stages of the viral replication cycle after cell entry. Compounds with tetrahydroquinazoline N-oxide scaffold show a broad spectrum of activity against flaviviruses and represent a promising chemotype for antiviral drug discovery.

A Case Report of Parainfectious Opsoclonus-Myoclonus Syndrome after Powassan Virus Meningitis (P8-10.002)

<h3>Objective:</h3> To report a case of opsoclonus-myoclonus syndrome after Powassan virus meningitis. <h3>Background:</h3> Opsoclonus-myoclonus syndrome is rare in adults and has been associated with viral infection, including West Nile virus (WNV). Powassan virus (PWV) is a tick-borne flavivirus causing a spectrum of disease similar to other flaviviruses such as WNV, which is mosquito-borne. Most human cases in the United States occur in the northeastern and Great Lakes regions from Spring through Fall when ticks are most active. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> A 44-year-old man from Minnesota recovering from a meningitic syndrome characterized by fever, headache, and lymphocytic pleocytosis (860 cells/μL) presented with oscillopsia and gait instability. He reported a history of recent tick exposure. Exam demonstrated opsoclonus most prominent after gaze refixation, myoclonus, prominent tremor and dysmetria of the upper extremities, truncal ataxia, and a wide-based ataxic gait. Magnetic resonance imaging brain was normal. Lyme serology and serum testing for autoimmune/paraneoplastic autoantibodies were unremarkable. Serologic testing detected IgM antibodies against WNV in serum and cerebrospinal fluid. Given history of tick exposure, PWV serology was also performed and demonstrated the presence of IgM antibodies against the virus in both serum and cerebrospinal fluid. Confirmatory plaque reduction neutralization test (PRNT), however, detected neutralizing antibodies against PWV only. He received 5 days of 1g methylprednisolone and 2g/kg intravenous immune globulin, and his symptoms slowly resolved over three months. <h3>Conclusions:</h3> Opsoclonus-myoclonus is uncommon in adults and may be a rare complication of arthropod-borne viral infections, including PWV. Clinicians should consider testing for PWV in patients from endemic regions presenting with opsoclonus-myoclonus and potential tick exposure. <b>Disclosure:</b> Dr. Syc-Mazurek has nothing to disclose. Dr. Santilli has nothing to disclose. Dr. Hass has nothing to disclose. Dr. Skolka has nothing to disclose. Dr. Toledano has nothing to disclose. Dr. Eggers has received intellectual property interests from a discovery or technology relating to health care. Dr. Eggers has received publishing royalties from a publication relating to health care.

Year-round dengue fever in Pakistan, highlighting the surge amidst ongoing flood havoc and the COVID-19 pandemic: a comprehensive review.

Dengue fever (DF) is an arthropod-borne viral infection caused by four serotypes of dengue virus (DENV 1-4) transmitted to the host by the vector mosquito Aedes, which causes fever, vomiting, headache, joint pain, muscle pain, and a distinctive itching and skin rash, ultimately leading to dengue hemorrhagic fever and dengue shock syndrome. The first case of DF in Pakistan was documented in 1994, but outbreak patterns began in 2005. As of 20 August 2022, Pakistan has 875 confirmed cases, raising alarming concerns. Misdiagnosis due to mutual symptoms, lack of an effective vaccine, the weakened and overburdened health system of Pakistan, irrational urbanization, climate change in Pakistan, insufficient waste management system, and a lack of awareness are the significant challenges Pakistan faces and result in recurrent dengue outbreaks every year. The recent flood in Pakistan has caused massive destruction, and stagnant dirty water has facilitated mosquito breeding. Sanitization and spraying, proper waste management, an adequate and advanced diagnostic system, control of population size, public awareness, and promotion of medical research and global collaboration, especially amidst flood devastation, are recommended to combat this deadly infection in Pakistan. This article aims to comprehensively review the year-round DF in Pakistan, highlighting the surge amidst ongoing flood havoc and the coronavirus disease 2019 pandemic.

Predicting Culex pipiens/restuans Population Dynamics Using a Weather-Driven Dynamic Compartmental Population Model.

Mosquitoes of the genus Culex are important vectors of a variety of arthropod-borne viral infections. In most of the northern parts of the USA, Cx. pipiens/restuans is the predominant representative of this genus. As vectors, they play a key role in the spreading of arboviruses and thus, knowledge of the population dynamic of mosquitoes is important to understand the disease ecology of these viruses. As poikilotherm animals, the vital rates of mosquitoes are highly dependent on ambient temperature, and also on precipitation. We present a compartmental model for the population dynamics of Cx. pipiens/restuans. The model is driven by temperature, precipitation, and daytime length (which can be calculated from the geographic latitude). For model evaluation, we used long-term mosquito capture data, which were averaged from multiple sites in Cook County, Illinois. The model fitted the observation data and was able to reproduce between-year differences in the abundance of the Cx. pipiens/restuans mosquitoes, as well as the different seasonal trends. Using this model, we evaluated the effectiveness of targeting different vital rates for mosquito control strategies. The final model is able to reproduce the weekly mean Cx. pipiens/restuans abundance for Cook County with a high accuracy, and over a long time period of 20 years.

Emerging and re-emerging viral diseases, predisposing risk factors, and implications of international travel: a call for action for increasing vigilance and imposing restrictions under the current threats of recently emerging multiple Omicron subvariants.

Emerging and re-emerging viral diseases, predisposing risk factors, and implications of international travel: a call for action for increasing vigilance and imposing restrictions under the current threats of recently emerging multiple Omicron subvariants.

Arthropod-Borne Pathogens in Wild Canids

Wild canids, as well as other wild animal species, are largely exposed to bites by ticks and other hematophagous vectors where the features favoring their presence and spread are found in wooded and semi-wooded areas. Much of the information about arthropod-borne infections concerns domestic and companion animals, whereas data about these infections in wild canids are not exhaustive. The present study is a narrative review of the literature concerning vector-borne infections in wild canids, highlighting their role in the epidemiology of arthropod-borne bacteria and protozoa.

NEUTROPHIL-LYMPHOCYTE RATIO AS A PROGNOSTIC INDICATOR IN DENGUE FEVER PATIENTS AT TERTIARY CARE HOSPITAL IN NORTHWEST-MAHARASHTRA

Introduction- Dengue is regarded as the most important arthropod-borne viral infection in humans and is the second most important re-emerging tropical disease. Dengue infections are increasing resulting in more illness and death and in 2012 World Health Organization (WHO) reclassified dengue as the most important mosquito-borne viral disease in the world. Given the heterogeneous nature of the clinical presentation of dengue, identifying robust and sensitive clinical or laboratory predictors of dengue fever and its severity has not been an easy task. Neutrophil-to-lymphocyte ratio (NLR) can be easily calculated based on a complete blood count by dividing the Neutrophil percentage by Lymphocyte percentage. There is enough literature to suggest that NLR has prognostic significance in various diseases. However, no studies have focussed on NLR as a prognostic marker for dengue. Aim- To study NLR in dengue patients and assess its role in relation with age, gender,serological tests for dengue and platelet count. Materials and Methods- This retrospective observational study was carried out at Tertiary care hospital in Northwest Maharashtra. 100 diagnosed and admitted cases of dengue were included in this study. Clinical data and laboratory data were reviewed and analysed. Chi Square test was done and its significance noted. Results- In our study, Ns1Ag dengue serology test was found to be more common in males indicating recent infection and Ns1Ag, IgM and IgG more common in females indicating recent and past infection. NLR &lt; 2 strongly correlates with low platelets indicating severity of disease and reversal of NLR &gt; 2 correlates with improvement of disease. NLR &lt; 2 was more common in 0-20 years age group, younger the age lesser the NLR and hence more severe the disease. Conclusion- From our study we found that there is a significant relation between NLR to the severity of dengue fever in adult patients and by keeping an eye on the NLR we can predict the prognosis and the severity of the disease in patient. Lower the NLR ratio severe the disease. Hence NLR can be used as a prognostic indicator in dengue patients.