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14 pages, 957 KB  
Article
Improving Management of Viral Febrile Illness and Reducing the Need for Empiric Antibiotics Using VIDAS® Immunoassay for Dengue and Chikungunya: A West African Multicentric Study
by Fanette Ravel, Solenne Robert, Diakourga Arthur Djibougou, Kigninlman Horo, Aristophane Tanon, Privat Ango, Palpouguini Félix Lompo, Faustine Meynier, Ludovic Brossault, Umit Guler, Jacques Simpore and Potiandi Serge Diagbouga
Diagnostics 2025, 15(17), 2269; https://doi.org/10.3390/diagnostics15172269 - 8 Sep 2025
Abstract
Background: Dengue and chikungunya are endemic in West Africa, posing significant public health issues. The aim of this study was to evaluate the impact of differential and systematic diagnosis of dengue and chikungunya on patient management and on antibiotic use in Burkina Faso [...] Read more.
Background: Dengue and chikungunya are endemic in West Africa, posing significant public health issues. The aim of this study was to evaluate the impact of differential and systematic diagnosis of dengue and chikungunya on patient management and on antibiotic use in Burkina Faso and Ivory Coast. Methods: A multicenter prospective cohort study was conducted in both countries involving patients with suspected dengue and/or chikungunya viremia. VIDAS® diagnostic tests (bioMérieux SA, Marcy-l’Étoile, France) were provided to the intervention sites, while the control sites initially followed standard of care before testing at the end of the study. The primary outcome was defined as antibiotic prescription or non-initiation/discontinuation, and the secondary endpoints included hospital resource use, patient satisfaction, and health-related quality of life (HRQoL), analyzed through Chi-square and logistic regression using SAS software v9.4. Results: Out of 775 enrolled patients, 767 had corresponding VIDAS® Dengue and VIDAS® Chikungunya results, with 570 having recorded antibiotic therapy (initiated, non-initiated or discontinued). Both Burkina Faso and Ivory Coast observed an increase in antibiotic discontinuation (or non-initiation) rates at the intervention sites compared to control sites: increased from 60% to 78% in Burkina Faso and from 36% to 83% in Ivory Coast. Hospitalization rates within seven days following inclusion were also lower in intervention sites than in the control sites: Burkina Faso 41% as compared with 97% and Ivory Coast 24% as compared with 98%. Patient-reported antibiotic use within seven days post-inclusion was also significantly lower in intervention sites. Conclusions: The results showed a reduction in potential antibiotic overuse and hospital admissions (i.e., hospitalization rates within seven days) in both the Burkina Faso and Ivory Coast interventions sites. These findings emphasize the importance of enhanced diagnostic strategies for the improvement of patient outcomes and the fight against antibiotic resistance. This study also highlights the need for implementing systematic and differential diagnosis of dengue and chikungunya in West Africa where febrile infections are endemic. Further studies are warranted to explore the economic benefits of these diagnostic strategies. Full article
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8 pages, 4689 KB  
Case Report
Ischemic Cerebellar Infarct During Recovery from Secondary Dengue Fever—A Case Report and Literature Review
by Boon Ping Ting, Corinne Yee Lyn Lau, Puneet Seth, Jean Mui Hua Lee and Shao Hui Koh
Emerg. Care Med. 2025, 2(3), 43; https://doi.org/10.3390/ecm2030043 - 3 Sep 2025
Viewed by 263
Abstract
Background: Dengue fever is a global health problem and is endemic in Singapore, with a high economic burden. Neurological manifestations of dengue fever, although rare, are being increasingly reported. Ischemic stroke as a complication of dengue fever has rarely been reported. Methods: [...] Read more.
Background: Dengue fever is a global health problem and is endemic in Singapore, with a high economic burden. Neurological manifestations of dengue fever, although rare, are being increasingly reported. Ischemic stroke as a complication of dengue fever has rarely been reported. Methods: This case report describes a case of ischemic cerebellar infarct during the recovery phase of secondary dengue fever with a review of similar cases previously described in the literature. Results: This is the first known case report of cerebellar ischemic stroke in Singapore following dengue fever, where Magnetic Resonance Angiography (MRA) demonstrated a possible occlusion or severe stenosis of a cerebral artery as the underlying pathophysiology of dengue-associated stroke. Dengue fever has been shown to increase the incidence of stroke. Conclusions: Physicians in dengue-endemic areas need to have a high index of suspicion to consider this diagnosis, especially in patients with dengue fever who present with neurologic deficits. Full article
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15 pages, 1205 KB  
Review
Dengue-Related Ocular Complications: Spectrum, Diagnosis, and Management
by Jiaxin Deng, Yaru Zou, Mingming Yang, Jing Zhang, Zizhen Ye, Yuan Zong, Kyoko Ohno-Matsui and Koju Kamoi
Pathogens 2025, 14(9), 872; https://doi.org/10.3390/pathogens14090872 - 2 Sep 2025
Viewed by 330
Abstract
Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients [...] Read more.
Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients develop eye-related symptoms. Furthermore, studies confirm a higher risk of new uveitis cases following dengue infection. Breakdown of the blood–ocular barrier—driven by antibody-mediated enhancement, complement activation and release of inflammatory mediators—leads to vascular leakage, tissue injury and ischemia. Diagnosis relies on clinical examination supplemented by imaging (OCT, angiography) and laboratory confirmation of dengue. Mild anterior inflammation often responds to topical steroids, while sight-threatening posterior disease requires systemic corticosteroids and, in refractory cases, immunomodulatory agents. Visual outcomes depend on the initial severity; anterior uveitis typically resolves without sequelae, whereas vasculitis or foveal involvement may leave lasting deficits. This review integrates the current understanding of dengue-related eye disease, emphasizing its varied presentations and the importance of early recognition. Further research into targeted, mechanism-based therapies is needed to optimize visual outcomes. Full article
(This article belongs to the Special Issue Dengue Virus: Transmission, Pathogenesis, Diagnostics, and Vaccines)
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10 pages, 851 KB  
Article
Introduction and Spatial–Temporal Distribution of Oropouche Virus in Rio de Janeiro State, Brazil
by Fábio Burack da Costa, Andrea Cony Cavalcanti, Rafael Santos Erbisti, Vanessa Zaquieu Dias, Cristiane Gomes de Castro Moreira, Mateus Marques Grifo, Maria Carmelita dos Santos Vaz, Adriana Cardoso Camargo, Leandro Magalhães de Souza, Flávia Barreto dos Santos, Mário Sérgio Ribeiro, Viviana Malirat, Nildimar Alves Honório and Renata Campos Azevedo
Pathogens 2025, 14(8), 833; https://doi.org/10.3390/pathogens14080833 - 21 Aug 2025
Viewed by 496
Abstract
The Oropouche virus (OROV) has been circulating in the Amazon region since the 1960s, with a progressive increase in outbreaks and human cases reported in Brazil and neighboring countries. In the Rio de Janeiro state, there has been a significant rise in suspected [...] Read more.
The Oropouche virus (OROV) has been circulating in the Amazon region since the 1960s, with a progressive increase in outbreaks and human cases reported in Brazil and neighboring countries. In the Rio de Janeiro state, there has been a significant rise in suspected cases of arboviruses, with only 30% of laboratory tests confirming infections with dengue, Zika, or chikungunya viruses. The investigation of OROV virus circulation in the Rio de Janeiro state was initiated and confirmed in April 2024. Our study aimed to retrospectively investigate OROV infections in dengue-suspected cases with inconclusive diagnosis in order to better understand the temporal and geographic introduction of OROV in the Rio de Janeiro state. Municipalities from Rio de Janeiro with arbovirus-like fever cases but a low percentage of dengue-positive RT-PCR test confirmations were identified in the laboratory database. Samples were selected for testing OROV infections using real-time RT-PCR as recommended by the Brazilian Ministry of Health. Municipalities in the Middle Paraíba region of the state showed 93% negative tests results for dengue, Zika, and chikungunya starting in September 2023. A total of 118 positive cases of Oropouche were recorded in the state of Rio de Janeiro between March and July 2024. Moreover, by genome sequencing of eight strains, it was shown that OROV circulating in Rio de Janeiro belongs to recently emergent M1L2S2 lineage. Our findings retrospectively revealed a concentration of cases in the Middle Paraíba region and an outbreak in the rural village of Cacaria, located in the municipality of Piraí. According to our data, this region is the first area with sustained transmission in the Rio de Janeiro state. Full article
(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Control, and Future Directions)
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10 pages, 684 KB  
Article
Cardiovascular Manifestations and Outcomes in Patients with Scrub Typhus Admitted to a Tertiary Care Center in the Coastal Karnataka Region in India
by Mugula Sudhakar Rao, Jyothi Samanth, Swathi Poojary, Krishnananda Nayak, Shubha Srinivas and Thrupthi Naik
Diseases 2025, 13(8), 270; https://doi.org/10.3390/diseases13080270 - 20 Aug 2025
Viewed by 920
Abstract
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data [...] Read more.
Introduction: Scrub typhus is a mite-borne infectious disease caused by “Orientia tsutsugamushi”, a bacterium that was formerly classified under the genus Rickettsia. It is transmitted to humans through the bites of infected chigger mites (larval trombiculid mites). However, clinical data on the cardiac manifestations of scrub typhus and their outcomes remain limited. Methods: This research was retrospectively conducted at a tertiary care hospital in South India. The study included all patients admitted from January 2016 to September 2021 who fulfilled the clinical criteria for a diagnosis of scrub typhus. Data were collected for 426 patients. Patients with previously diagnosed heart disease and mixed infections (leptospirosis, dengue fever, blood culture positivity, and COVID-19 positivity) were excluded. Comprehensive assessments of clinical presentation, electrocardiography (ECG), 2D echocardiography, and outcomes, including all-cause mortality and probable myocarditis, were performed. Multivariate regression analysis was performed to identify independent predictors of all-cause mortality and probable myocarditis. Results: Out of 426 patients, 200 (46.9%) were male and 226 (53.1%) were female. The mean age at presentation was 49.29 ± 14.43 years. A total of 108 (25.4%) patients had diabetes and 82 (19.25%) had hypertension. Sinus tachycardia (29.3%) was the most frequent ECG finding. Echocardiographic evidence of probable myocarditis was observed in 20 (4.7%) patients, while 6 (1.4%) patients had isolated RV dysfunction, 4 (0.9%) had biventricular dysfunction, 7 (1.6%) had significant pulmonary hypertension, and 40 (9.4%) had trivial pericardial effusion. A total of 78 (18.3%) patients had acute respiratory distress syndrome. All-cause mortality was observed in 12 (2.8%) patients. A total of 56 (13.1%) patients developed multiorgan dysfunction syndrome (MODS) during their hospitalization. A total of 78 (18.3%) patients were documented to have acute kidney injury (AKI), and 22 (5.2%) patients underwent hemodialysis. Multivariable binary logistic regression analysis revealed that probable myocarditis and MODS were independent predictors of mortality among patients with scrub typhus, and age, female gender, and LV systolic dysfunction were identified as predictors of overall complications, including mortality, probable myocarditis, congestive heart failure, MODS, AKI, and the need for hemodialysis. Conclusions: Probable myocarditis was the most frequent cardiac manifestation noted in patients with scrub typhus, and in addition to MODS, probable myocarditis was an independent predictor of mortality in this cohort. Thus, it is crucial to maintain clinical vigilance regarding the cardiac status of such patients. Full article
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10 pages, 561 KB  
Article
Prognostic Indicators of Severe Dengue Infection in Adult Patients in Thailand
by Patcharin Khamnuan, Surangrat Pongpan, Pantitcha Thanatrakolsri, Supa Vittaporn, Punnaphat Daraswang and Sirawan Samsee
Trop. Med. Infect. Dis. 2025, 10(8), 233; https://doi.org/10.3390/tropicalmed10080233 - 18 Aug 2025
Viewed by 583
Abstract
Background: Dengue infection is a spreading vector borne disease with most severe infection-related fatalities occurring in adults. This study was conducted to explore prognostic indicators of dengue infection severity. Methods: This study included patients aged over 15 years who were diagnosed with dengue [...] Read more.
Background: Dengue infection is a spreading vector borne disease with most severe infection-related fatalities occurring in adults. This study was conducted to explore prognostic indicators of dengue infection severity. Methods: This study included patients aged over 15 years who were diagnosed with dengue viral infection. Data were collected from nine hospitals across all regions of Thailand between January 2019 and December 2022. Diagnosis of dengue infection was confirmed by a positive result for the NS-1 antigen via RT–PCR, IgM antibody, or IgG antibody tests. Data including gender, age, BMI, underlying disease, clinical characteristics and laboratory findings were collected. Multivariable logistic regression with backward elimination was used to identify a set of prognostic factors. Results: The prognostic indicators of severe dengue were age < 55 years (OR = 6.13, p = 0.054), severe bleeding (bleeding from the gastrointestinal tract, hematemesis, melena, menorrhagia, or hematuria) (OR = 20.75, p < 0.001), pleural effusion (OR = 10.23, p < 0.001), and platelet ≤ 100,000 (/µL) (OR = 3.62, p = 0.035). These predictors were able to accurately estimate the severity of dengue infection with an area under the receiver operating curve (AuROC) of 0.836. Conclusions: The proposed four prognostic factors can be applied to predict severe dengue infections. These findings may inform the development of a risk scoring system to forecast severe dengue infection, early detection, and appropriate treatment during sickness. Full article
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17 pages, 2112 KB  
Article
Direct Detection of Orthoflavivirus via Gold Nanorod Plasmon Resonance
by Erica Milena de Castro Ribeiro, Bruna de Paula Dias, Cyntia Silva Ferreira, Samara Mayra Soares Alves dos Santos, Rajiv Gandhi Gopalsamy, Estefânia Mara do Nascimento Martins, Cintia Lopes de Brito Magalhães, Flavio Guimarães da Fonseca, Luiz Felipe Leomil Coelho, Cristiano Fantini, Luiz Orlando Ladeira, Lysandro Pinto Borges and Breno de Mello Silva
Sensors 2025, 25(15), 4775; https://doi.org/10.3390/s25154775 - 3 Aug 2025
Viewed by 504
Abstract
Dengue, Zika, yellow fever, chikungunya, and Mayaro arboviruses represent an increasing threat to public health because of the serious infections they cause annually in many countries. Serological diagnosis of these viruses is challenging, making the development of new diagnostic strategies imperative. In this [...] Read more.
Dengue, Zika, yellow fever, chikungunya, and Mayaro arboviruses represent an increasing threat to public health because of the serious infections they cause annually in many countries. Serological diagnosis of these viruses is challenging, making the development of new diagnostic strategies imperative. In this study, we investigated the effectiveness of gold nanorods (GNRs) functionalized with specific anti-dengue and anti-orthoflavivirus antibodies in detecting viral particles. GNRs were created with a length-to-width ratio of up to 5.5, a size of 71.4 ± 6.5 nm, and a light absorption peak at 927 nm, and they were treated with 4 mM polyethyleneimine. These GNRs were attached to a small amount of monoclonal antibodies that target flaviviruses, and the viral particles were detected by measuring the localized surface plasmon resonance using an UV-Vis/NIR spectrometer. The tests found Orthoflavivirus dengue and Orthoflavivirus zikaense in diluted human serum and ground-up mosquitoes, with the lowest detectable amount being 100 PFU/mL. The GNRs described in this study can be used to enhance flavivirus diagnostic tests or to develop new, faster, and more accurate diagnostic techniques. Additionally, the functionalized GNRs presented here are promising for supporting virological surveillance studies in mosquitoes. Our findings highlight a fast and highly sensitive method for detecting Orthoflavivirus in both human and mosquito samples, with a detection limit as low as 100 PFU/mL. Full article
(This article belongs to the Section Biosensors)
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14 pages, 667 KB  
Review
Hemophagocytic Lymphohistiocytosis Triggered by Dengue: A Narrative Review and Individual Patient Data Meta-Analysis
by Angelos Sourris, Alexandra Vorria, Despoina Kypraiou, Andreas G. Tsantes and Petros Ioannou
Viruses 2025, 17(8), 1047; https://doi.org/10.3390/v17081047 - 27 Jul 2025
Viewed by 697
Abstract
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and [...] Read more.
Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome that may be triggered by infections such as dengue virus. Due to overlapping features with severe dengue and sepsis, diagnosis of HLH in dengue-infected patients remains challenging. Methods: We conducted a narrative review and individual patient data meta-analysis of published cases of dengue-associated HLH. Eligible studies were identified through a search of PubMed and Scopus databases up to 5 March 2025. Clinical, laboratory, microbiological, treatment, and outcome data were extracted and analyzed. Results: A total of 133 patients from 71 studies were included. The median patient age was 18 years, and 56.8% were male. Common clinical features included fever (96.9%), cytopenias, organomegaly, and liver dysfunction. ALT elevation, jaundice, and hypofibrinogenemia were associated with mortality. DENV-1 was the most common serotype (57.4%) and was negatively associated with death. Overall, 19.3% of patients died. Multivariate analysis did not identify independent mortality predictors. Conclusions: Dengue-associated HLH predominantly affects young individuals and carries significant mortality. Key indicators of poor prognosis include hepatic dysfunction and the presence of shock or organ failure. Early recognition and prompt immunomodulatory treatment, particularly corticosteroids, may improve outcomes. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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9 pages, 650 KB  
Case Report
Beyond the Fever: A Serial Report on Moderate to Severe Murine Typhus Cases and Diagnostic Hurdles in Indonesia
by Velma Herwanto, Sandra Utami Widiastuti, Gunawan and Khie Chen Lie
Trop. Med. Infect. Dis. 2025, 10(8), 204; https://doi.org/10.3390/tropicalmed10080204 - 23 Jul 2025
Viewed by 542
Abstract
(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with [...] Read more.
(1) Background: Murine typhus, caused by Rickettsia typhi, is a neglected rickettsial disease and an underdiagnosed cause of acute febrile illness (AFI), particularly in endemic regions such as Indonesia. (2) Case description: We report a case series of four patients presenting with AFI of less than seven days in duration. Three patients were admitted with moderate disease, while one presented with septic shock with the macrophage activation-like syndrome (MALS) phenotype. Common clinical features included myalgia and headache; additional symptoms included cough, sore throat, and abdominal pain. Laboratory findings revealed bicytopenia, elevated transaminases, and raised inflammatory and bacterial infection markers. Common tropical infections—dengue, typhoid fever, and leptospirosis—and other potential sources of infection were excluded early during hospitalization. Diagnosis was confirmed by nucleic acid amplification testing (NAAT), which detected R. typhi in all patients. Doxycycline was initiated following confirmation, leading to defervescence within 36–48 h. (3) Conclusions: Murine typhus remains an underrecognized cause of febrile illness in Indonesia. In the near future, the inclusion of rickettsial testing in the diagnostic protocol of AFI will be crucial, as it enables timely administration of effective, low-cost treatment. Full article
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20 pages, 853 KB  
Review
Dengue and Flavivirus Co-Infections: Challenges in Diagnosis, Treatment, and Disease Management
by Rosmen Sufi Aiman Sabrina, Nor Azila Muhammad Azami and Wei Boon Yap
Int. J. Mol. Sci. 2025, 26(14), 6609; https://doi.org/10.3390/ijms26146609 - 10 Jul 2025
Viewed by 1017
Abstract
Co-infections of dengue serotypes and dengue with other flaviviruses pose substantial hurdles in disease diagnosis, treatment options, and disease management. The overlapping geographic distributions and mosquito vectors significantly enhance the probability of co-infections. Co-infections may result in more severe disease outcomes due to [...] Read more.
Co-infections of dengue serotypes and dengue with other flaviviruses pose substantial hurdles in disease diagnosis, treatment options, and disease management. The overlapping geographic distributions and mosquito vectors significantly enhance the probability of co-infections. Co-infections may result in more severe disease outcomes due to elevated viral loads, modulation of the immune response, and antibody enhancement. Cross-reactivity in serological assays and the likeness of clinical presentations add to the ongoing challenges in disease diagnosis. Molecular diagnostics such as reverse transcription polymerase chain reaction (RT-PCR) and next-generation sequencing (NGS) are, therefore, employed for more specific disease diagnosis although requiring substantial resources. Despite the advancements, specific anti-flaviviral therapy is still limited, hence the urgency for further investigative research into various therapeutic approaches, including peptide inhibitors, host-targeted therapies, and RNA-based interventions. This review discusses the epidemiology, clinical ramifications, and diagnostic obstacles associated with flavivirus co-infections whilst assessing prospective strategies for better disease prevention, treatment, and management. Addressing these critical gaps is essential for disease mitigation whilst improving patient management especially in regions where co-circulation of flaviviruses is common and their diseases are highly endemic. Full article
(This article belongs to the Section Molecular Microbiology)
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10 pages, 788 KB  
Article
Key Laboratory Markers for Early Detection of Severe Dengue
by Kumar Sivasubramanian, Raj Bharath R, Leela Kakithakara Vajravelu, Madan Kumar D and Aritra Banerjee
Viruses 2025, 17(5), 661; https://doi.org/10.3390/v17050661 - 30 Apr 2025
Viewed by 1112
Abstract
Dengue virus is the most prevalent arthropod-borne viral disease in humans. Severe dengue, defined by hemorrhagic fever and dengue shock syndrome, can develop quickly in people who have warning indications such as abdominal pain, mucosal bleeding, and a significant decrease in platelet count. [...] Read more.
Dengue virus is the most prevalent arthropod-borne viral disease in humans. Severe dengue, defined by hemorrhagic fever and dengue shock syndrome, can develop quickly in people who have warning indications such as abdominal pain, mucosal bleeding, and a significant decrease in platelet count. Laboratory markers such as hematocrit, platelet count, liver enzymes, and coagulation tests are critical for early diagnosis and prognosis. This retrospective study was carried out from January 2023 to December 2024 at a super-specialty tertiary care hospital. There were 283 adult patients with dengue with warning signs, who were categorized into 102 with platelet transfusion and 181 with no platelet transfusion. Data on patient demographics, clinical history, laboratory values, and radiological findings were systematically obtained from hospital records at the time of admission. Laboratory parameters such as white blood cell (OR = 2.137), hemoglobin (OR = 2.15), aPTT (OR = 5.815), AST2/ALT (OR = 2.431), platelet count (OR = 26.261) and NS1 (OR = 4.279) were found to be significantly associated (p < 0.01) with platelet transfusion. Similarly, an increased prothrombin time (OR = 2.432) contributed to prolonged hospital stays and the presence of ascites (OR = 5.059), gallbladder wall thickening (OR = 4.212), and pleural effusion (OR = 2.917), contributing to the severity of the dengue infection. These significant laboratory markers help with identifying patients with dengue who may develop severe dengue, requiring platelet transfusion, thereby prioritizing patient care and enabling the implementation of targeted interventions. Full article
(This article belongs to the Special Issue Arboviruses and Global Health: A PanDengue Net Initiative)
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16 pages, 3144 KB  
Review
The Emerging Role of Circulating T Follicular Helper Cells in Dengue Virus Immunity: Balancing Protection and Pathogenesis
by Paola N. Flores-Pérez, José A. Collazo-Llera, Fabiola A. Rodríguez-Alvarado and Vanessa Rivera-Amill
Viruses 2025, 17(5), 652; https://doi.org/10.3390/v17050652 - 30 Apr 2025
Viewed by 3383
Abstract
Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic [...] Read more.
Flaviviruses are a group of viruses transmitted mainly by mosquitoes and ticks, causing severe diseases in humans. Examples include dengue, Zika, West Nile virus, and yellow fever. They primarily affect individuals in tropical and subtropical regions, causing public health problems such as epidemic outbreaks and significant economic burdens due to hospitalizations and treatments. They share antigens, leading to cross-reactivity where antibodies generated against one flavivirus can react with others, complicating the accurate diagnosis of individual infections and making the development of treatments or vaccines more challenging. The role of T cells in the immune response to flaviviruses is a complex topic debated by scientists. On one hand, T cells help control infection by eliminating infected cells and protecting against disease. However, there is evidence that an excessive or dysregulated T cell response can cause tissue damage and worsen the disease, as seen in severe dengue cases. This duality underscores the complexity of the immune response to flavivirus infections, posing a significant challenge for researchers. Gaining a deeper understanding of the immune response at the cellular level, particularly the role of T follicular helper cells, can reveal new avenues of investigation that could lead to novel strategies for disease management. This review explores the dynamics of T cell responses, focusing on circulatory T follicular helper cells (cTFH), to enhance our understanding of flavivirus immunity and inform future interventions. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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21 pages, 2478 KB  
Review
Beyond Infection: The Role of Secreted Viral Proteins in Pathogenesis, Disease Severity and Diagnostic Applications
by Luis Herrera-Moro Huitron, Víctor Javier Cruz-Holguin, José Manuel Ulloa-Aguilar, Luis Adrián De Jesús-González, Juan Fidel Osuna-Ramos, Mario Guzmán-Huerta, Mercedes Piedad de León-Bautista, Guadalupe León-Reyes, Julio García-Cordero, Leticia Cedillo-Barrón, Jorge Francisco Cerna-Cortes and Moisés León-Juárez
Cells 2025, 14(9), 624; https://doi.org/10.3390/cells14090624 - 22 Apr 2025
Viewed by 1494
Abstract
Secreted viral proteins are crucial in virus–host interactions, as they modify the host microenvironment to promote infection. These secreted proteins could alter immune and inflammatory responses, allowing viruses to evade defense mechanisms such as cytotoxic T cell activation and antibody neutralization. Some secreted [...] Read more.
Secreted viral proteins are crucial in virus–host interactions, as they modify the host microenvironment to promote infection. These secreted proteins could alter immune and inflammatory responses, allowing viruses to evade defense mechanisms such as cytotoxic T cell activation and antibody neutralization. Some secreted proteins mimic host molecules to suppress antiviral responses, making them valuable targets for antivirals and diagnostics. Notable examples include BARF1 from Epstein–Barr virus, associated with gastric cancer; vIL-10 from Epstein–Barr virus, which regulates immune responses and contributes to autoimmune diseases; NS1 from dengue virus, associated with vascular permeability and early diagnosis; and NSP4 from rotavirus as an enterotoxin, among others. The study of these proteins improves our understanding of viral pathogenesis and helps to develop innovative treatments for infectious and non-infectious diseases, taking advantage of the evolutionary adaptations of viruses. This review explores their impact on the infection cycle, disease progression, and key processes, such as cell cycle regulation, apoptosis, and cell signaling. Research on these proteins deepens our basic knowledge of virology and generates alternative methods for detecting biomarkers and creating more effective therapies, as well as implementing some emerging technologies, such as biosensors and plasmon resonance, for the diagnosis of viral diseases. Full article
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16 pages, 2711 KB  
Article
Ultrasensitive Peptide-Based Electrochemical Biosensor for Universal Diagnostic of Dengue
by Isis Campos Prado, João Pedro Rangel da Silva Carvalho, André Souza Araujo, Paloma Napoleão-Pêgo and Salvatore Giovanni De-Simone
Biosensors 2025, 15(4), 236; https://doi.org/10.3390/bios15040236 - 8 Apr 2025
Viewed by 1121
Abstract
Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, [...] Read more.
Dengue is a neglected disease mainly affecting tropical and subtropical countries. The diagnosis of dengue fever is still a problem since most of it is made from whole or recombinant DENV proteins, which present cross-reactions with other members of the Flavivirus family. Therefore, there is still a huge demand for new diagnostic methods that provide rapid, low-cost, easy-to-use confirmation. Thus, in this study, we developed an affordable electrochemical biosensor for rapidly detecting immunoglobulin G (IgG) serological antibodies in the sera of DENV-infected patients. An identified linear B-cell epitope (DENV/18) specific for DENV 1–4 serotypes recognized by IgG in patient sera was selected as a target molecule after a microarray of peptides using the SPOT-synthesis methodology. After chemical synthesis, the DENV/18-peptide was immobilized on the surface of the working electrode of a commercially available screen-printed gold electrode (SPGE). The capture of DENV-specific IgG allowed for the formation of an immunocomplex that was measured by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) using a potassium ferrocyanide/ferricyanide ([Fe(CN)6]3−/4−) electrochemical probe. An evaluation of the biosensor’s performance showed a detection limit of 100 µg mL−1 for the synthetic peptides (DENV/18) and 1.21 ng mL−1 in CV and 0.43 ng mL−1 in DPV for human serum, with a sensitivity of 7.21 µA in CV and 8.79 µA in DPV. The differentiation of infected and uninfected individuals was possible even at a high dilution factor that reduced the required sample volumes to a few microliters. The final device proved suitable for diagnosing DENV by analyzing real serum samples, and the results showed good agreement with molecular biology diagnostics. The flexibility to conjugate other antigenic peptides to SPEs suggests that this technology could be rapidly adapted to diagnose other pathogens. Full article
(This article belongs to the Special Issue Biosensing and Diagnosis—2nd Edition)
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18 pages, 1778 KB  
Review
A Comprehensive Review of the Neglected and Emerging Oropouche Virus
by Fengwei Bai, Prince M. D. Denyoh, Cassandra Urquhart, Sabin Shrestha and Donald A. Yee
Viruses 2025, 17(3), 439; https://doi.org/10.3390/v17030439 - 19 Mar 2025
Cited by 3 | Viewed by 3249
Abstract
Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, [...] Read more.
Oropouche virus (OROV) is a neglected and emerging arbovirus that infects humans and animals in South and Central America. OROV is primarily transmitted to humans through the bites of infected midges and possibly some mosquitoes. It is the causative agent of Oropouche fever, which has high morbidity but low mortality rates in humans. The disease manifests in humans as high fever, headache, myalgia, arthralgia, photophobia, and, in some cases, meningitis and encephalitis. Additionally, a recent report suggests that OROV may cause fetal death, miscarriage, and microcephaly in newborns when women are infected during pregnancy, similar to the issues caused by the Zika virus (ZIKV), another mosquito-borne disease in the same regions. OROV was first reported in the mid-20th century in the Amazon basin. Since then, over 30 epidemics and more than 500,000 infection cases have been reported. The actual case numbers may be much higher due to frequent misdiagnosis, as OROV infection presents similar clinical symptoms to other co-circulating viruses, such as dengue virus (DENV), chikungunya virus (CHIKV), ZIKV, and West Nile virus (WNV). Due to climate change, increased travel, and urbanization, OROV infections have occurred at an increasing pace and have spread to new regions, with the potential to reach North America. According to the World Health Organization (WHO), over 10,000 cases were reported in 2024, including in areas where it was not previously detected. There is an urgent need to develop vaccines, antivirals, and specific diagnostic tools for OROV diseases. However, little is known about this surging virus, and no specific treatments or vaccines are available. In this article, we review the most recent progress in understanding virology, transmission, pathogenesis, diagnosis, host–vector dynamics, and antiviral vaccine development for OROV, and provide implications for future research directions. Full article
(This article belongs to the Special Issue Oropouche Virus (OROV): An Emerging Peribunyavirus (Bunyavirus))
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