Preparation for the Next Potential Pandemic—Chikungunya, Dengue, Zika and Other Viruses

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Human Virology and Viral Diseases".

Deadline for manuscript submissions: 31 December 2025 | Viewed by 10360

Special Issue Editor

Special Issue Information

Dear Colleagues,

Pandemics have claimed millions of lives over the centuries and millennia. The bubonic plague, smallpox, cholera, and, more recently, the Spanish flu devastated the world, causing enormous impacts on the population. With the advancement of medical knowledge, especially in infectious diseases and microbiology, it may appear that the importance of pandemics and the damage caused by them will be much less concerning in the future. However, the 2009–10 swine flu and, even more so, the COVID-19 pandemics served as wake-up calls, pointing out that even with advances in medicine, some aspects of our modern lifestyles, such as urbanization, massive sports events, or concerts, with tens of thousands of people concentrating in small areas, large indoor malls, and travel habits actually may increase the likelihood of future pandemics, lowering the effects of the advances we have made in epidemiology. Newly emerging, or mutating, variants of previously known microorganisms, may continue to present potential for further pandemics. This Special Issue focuses on such viruses, including chikungunya, dengue, Zika, and others with pandemic potential. We encourage discussing public health, epidemiological, pharmaceutical, immunological, and other measures that might help to avoid or at least mitigate future pandemics, to prevent the loss of lives and decrease the economic burden.

Dr. Zoltan Vajo
Guest Editor

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Keywords

  • chikungunya
  • dengue
  • zika
  • next pandemic
  • epidemiology
  • pharmaceutics
  • immunology

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Published Papers (6 papers)

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Research

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35 pages, 654 KB  
Article
Time Series Analysis of Dengue, Zika, and Chikungunya in Ecuador: Emergence Patterns, Epidemiological Interactions, and Climate-Driven Dynamics (1988–2024)
by José Daniel Sánchez, Carolina Álvarez Ramírez, Emilio Cevallos Carrillo, Juan Arias Salazar and César Barros Cevallos
Viruses 2025, 17(9), 1201; https://doi.org/10.3390/v17091201 - 31 Aug 2025
Viewed by 1217
Abstract
Background: Ecuador presents a unique epidemiological laboratory for studying arboviral dynamics due to its diverse ecological zones and exposure to climatic variability. Methods: We conducted a comprehensive 36-year analysis (1988–2024) of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) using national surveillance data from [...] Read more.
Background: Ecuador presents a unique epidemiological laboratory for studying arboviral dynamics due to its diverse ecological zones and exposure to climatic variability. Methods: We conducted a comprehensive 36-year analysis (1988–2024) of dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) using national surveillance data from Ecuador’s Ministry of Public Health. Statistical analyses included time series decomposition, change-point detection, correlation analysis, and climate association studies. Results: Ecuador reported 387,543 arboviral cases, with dengue comprising 91.3% (353,782 cases). Dengue exhibited endemic–epidemic cycles with major peaks during El Niño events (1994: 10,247 cases; 2000: 22,937 cases; 2015: 42,483 cases; 2024: 23,156 cases through week 26). CHIKV emerged explosively in 2015 (29,124 cases, incidence 181.10 per 100,000), followed by ZIKV in 2016 (2947 cases). Both showed rapid decline post-epidemic. Severe dengue cases paradoxically decreased from 2–4% of total cases in early 2000s to <0.1% post-2016, suggesting immunological modulation. Cross-correlation analysis revealed significant associations between climatic indices and epidemic timing (r=0.67, p<0.001), particularly for the El Niño-Southern Oscillation. Conclusions: Arboviral diseases in Ecuador function as an integrated epidemiological system with evidence of viral interactions, cross-protective immunity, and strong climate forcing. These findings emphasize the need for integrated surveillance and adaptive control strategies. Full article
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13 pages, 240 KB  
Article
Unexpected Predictors of Mortality During a DENV-3 Outbreak in Western Mexico: Seizures, Polyserositis, and Renal Dysfunction Without Severe Thrombocytopenia
by Martha A. Mendoza-Hernandez, Janet Diaz-Martinez, Gustavo A. Hernández-Fuentes, Fabian Rojas-Larios, Katya A. Cárdenas-Cárdenas, Paulina García de León-Flores, David A. Rojas-Cruz, Roberto Aceves-Calvario, Ernesto Gómez-Sandoval, Montserrat Árciga-García, José Guzmán-Esquivel, Valery Melnikov, Francisco Espinoza-Gómez and Iván Delgado-Enciso
Viruses 2025, 17(7), 950; https://doi.org/10.3390/v17070950 - 4 Jul 2025
Viewed by 744
Abstract
Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue [...] Read more.
Dengue mortality has traditionally been associated with severe thrombocytopenia and hemorrhagic complications. However, during 2024, dengue virus serotype 3 (DENV-3) increased significantly in western Mexico, leading to the emergence of a distinct clinical pattern. We conducted a retrospective cohort study of hospitalized dengue patients at the General Hospital of Colima (January–August 2024). Clinical features, laboratory parameters, and outcomes were compared between survivors and non-survivors. Among 201 hospitalized patients, 6 (3.0%) died. All deceased patients presented with generalized seizures, polyserositis (pleural effusion and/or ascites), and required mechanical ventilation. Contrary to classical patterns, they did not have severe thrombocytopenia. Instead, they showed significantly higher white blood cell counts and notably increased levels of serum urea and BUN, suggesting early renal impairment. ROC analysis indicated that BUN (AUC 0.904) and urea (AUC 0.906) were good to excellent discriminators of mortality. During 2024, with an increase in DENV-3 circulation, mortality was associated with neurological and systemic complications, including seizures and polyserositis, as well as biochemical evidence of renal dysfunction—but not with severe thrombocytopenia. These findings challenge current paradigms and highlight the need for early recognition of atypical clinical patterns. Full article
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12 pages, 1794 KB  
Article
Lineage B Genotype III of Dengue Virus Serotype 3 (DENV-3III_B) Is Responsible for Dengue Outbreak in Dire Dawa City, Ethiopia, 2023
by Abebe Aseffa Negeri, Dawit Hailu Alemayehu, Saro Abdella Abrahim, Tsigereda Kifle Wolde, Gutema Bulti Tura, Alemnesh Hailemariam Bedasso, Danile Tsega Geretsion, Ebise Abose Djirata, Eyilachew Zenebe Awule, Diana Rojas-Gallardo, Asefa Konde Korkiso, Kalkidan Melaku, Raffael Joseph, Abaysew Ayele, Mesfin Mengesha Tsegaye, Anne Piantadosi, Getachew Tollera, Alemseged Abdissa, Mesay Hailu Dangiso, Adane Mihret, Andargachew Mulu and Tesfaye Gelanewadd Show full author list remove Hide full author list
Viruses 2025, 17(3), 346; https://doi.org/10.3390/v17030346 - 28 Feb 2025
Cited by 1 | Viewed by 1463
Abstract
The eastern parts of Ethiopia, including Dire Dawa City, have experienced annual dengue fever (DF) outbreaks since 2013, leading to significant healthcare and economic impacts. However, comprehensive evidence on the specific dengue virus (DENV) serotypes and genotypes involved remains limited. During the 2023 [...] Read more.
The eastern parts of Ethiopia, including Dire Dawa City, have experienced annual dengue fever (DF) outbreaks since 2013, leading to significant healthcare and economic impacts. However, comprehensive evidence on the specific dengue virus (DENV) serotypes and genotypes involved remains limited. During the 2023 DF outbreak, the National Arbovirus Laboratory received seventy serum samples from suspected DF patients. Positive samples underwent sequencing of the CprM region of the DENV genome, and the obtained sequences were analyzed phylogenetically. Among the patients, 32 (45.7%) displayed early warning signs of severe dengue, and 13 were hospitalized, most showing symptoms indicative of severe dengue. Out of 67 adequate samples, 44 (65.6%) tested positive for DENV RNA by RT-PCR, and 17 successfully underwent CprM sequencing. All sequenced samples were identified as DENV-3, genotype III, major lineage B (DENV-3III_B), with two distinct minor lineages (DENV-3III_B.2 and DENV-3III_B.3). Phylogenetic analysis showed that these lineages were closely related to sequences from the Afar region, suggesting interconnected outbreaks with multiple co-circulating lineages. This study identifies DENV-3III_B as the cause of the 2023 DF outbreak in Dire Dawa City and highlights the need for enhanced viral genomic surveillance in Africa. Full article
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7 pages, 253 KB  
Communication
Factors Associated with Chronic Chikungunya in Vitória, Espírito Santo State, Brazil, Between 2016 and 2020
by Creuza Rachel Vicente, Luana Santos Louro, Nicolli Ribeiro de Jesus, Danielle Torres dos Santos Lopes, Aline Souza Areias Cabidelle, Crispim Cerutti Junior, Angelica Espinosa Barbosa Miranda, Iuri Drumond Louro, Debora Dummer Meira and Kuan Rong Chan
Viruses 2024, 16(11), 1679; https://doi.org/10.3390/v16111679 - 28 Oct 2024
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Abstract
Chikungunya patients may develop chronic joint pain that can persist for months to years. This study aimed to determine the factors associated with Chikungunya chronicity. This case–control study involved data from patients with laboratory-confirmed Chikungunya reported from March 2016 to December 2020 in [...] Read more.
Chikungunya patients may develop chronic joint pain that can persist for months to years. This study aimed to determine the factors associated with Chikungunya chronicity. This case–control study involved data from patients with laboratory-confirmed Chikungunya reported from March 2016 to December 2020 in Vitória, Espírito Santo state, Brazil. The data were accessed from compulsory notification databases (SINAN and eSUS VS) and electronic medical reports (Rede Bem-Estar). For each patient who developed chronic symptoms, we included a control patient who did not develop chronic symptoms by random sampling. A total of 183 chronic and 183 non-chronic patients were included in the study. Most of them were female (73.2%), with a median age of 49.5 years (interquartile range = 37–61), and presented fever (89.6%), myalgia (89.6%), arthralgia (89.3%), and headache (82.0%). Chronic patients were older (median = 53; interquartile range = 41–61) than non-chronic cases (median = 46; interquartile age = 31–61) (OR = 0.979, 95% CI = 0.968–0.991) and more frequently presented nausea (58.5% vs. 40.4%; OR = 2.109, 95% CI = 1.374–3.238), and leukopenia (20.2% vs. 10.9%; OR = 2.060, 95% CI = 1.122–3.779). Therefore, these characteristics should be monitored for the better clinical management of cases prone to chronicity. Full article
18 pages, 4926 KB  
Article
Comparison of Chikungunya Virus-Induced Disease Progression and Pathogenesis in Type-I Interferon Receptor-Deficient Mice (A129) and Two Wild-Type (129Sv/Ev and C57BL/6) Mouse Strains
by Victoria A. Graham, Linda Easterbrook, Emma Rayner, Stephen Findlay-Wilson, Lucy Flett, Emma Kennedy, Susan Fotheringham, Sarah Kempster, Neil Almond and Stuart Dowall
Viruses 2024, 16(10), 1534; https://doi.org/10.3390/v16101534 - 27 Sep 2024
Viewed by 1559
Abstract
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing a debilitating febrile illness with rheumatic disease symptoms of arthralgia and arthritis. Since its spread outside of Africa in 2005, it continues to cause outbreaks and disseminates into new territories. Intervention strategies are urgently required, [...] Read more.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus causing a debilitating febrile illness with rheumatic disease symptoms of arthralgia and arthritis. Since its spread outside of Africa in 2005, it continues to cause outbreaks and disseminates into new territories. Intervention strategies are urgently required, including vaccination and antiviral approaches. To test efficacy, the use of small animal models is required. Two mouse strains, A129, with a deficiency in their type-I interferon (IFN) receptor, and C57BL/6 are widely used. A direct comparison of these strains alongside the wild-type parental strain of the A129 mice, 129Sv/Ev, was undertaken to assess clinical disease progression, viral loads in key tissues, histological changes and levels of sera biomarkers. Our results confirm the severe disease course in A129 mice which was not observed in the parental 129Sv/Ev strain. Of the two wild-type strains, viral loads were higher in 129Sv/Ev mice compared to C57BL/6 counterparts. Our results have established these models and parameters for the future testing of vaccines and antiviral approaches. Full article
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Review

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33 pages, 1491 KB  
Review
The Evolving Role of Zika Virus Envelope Protein in Viral Entry and Pathogenesis
by Ashkan Roozitalab, Jiantao Zhang, Chenyu Zhang, Qiyi Tang and Richard Y. Zhao
Viruses 2025, 17(6), 817; https://doi.org/10.3390/v17060817 - 6 Jun 2025
Cited by 1 | Viewed by 2453
Abstract
Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of [...] Read more.
Zika virus (ZIKV) was first discovered in Uganda’s Zika Forest in 1947. The early African viruses posed little or no health risk to humans. Since then, ZIKV has undergone extensive genetic evolution and adapted to humans, and it now causes a range of human diseases, including neurologically related diseases in adults and congenital malformations such as microcephaly in newborns. This raises a critical question as to why ZIKV has become pathogenic to humans, and what virological changes have taken place and enabled it to cause these diseases? This review aims to address these questions. Specifically, we focus on the ZIKV envelope (E) protein, which is essential for initiating infection and plays a crucial role in viral entry. We compare various virologic attributes of E protein between the ancestral African strains, which presumably did not cause human diseases, with epidemic strains responsible for current human pathogenesis. First, we review the role of the ZIKV E protein in viral entry and endocytosis during the viral life cycle. We will then examine how the E protein interacts with host immune responses and evades host antiviral responses. Additionally, we will analyze key differences in the sequence, structure, and post-translational modifications between African and Asian lineages, and discuss their potential impacts on viral infection and pathogenesis. Finally, we will evaluate neutralizing antibodies, small molecule inhibitors, and natural compounds that target the E protein. This will provide insights into the development of potential vaccines and antiviral therapies to prevent or treat ZIKV infections and associated diseases. Full article
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