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Review
. 2023 Dec 18:14:1281667.
doi: 10.3389/fimmu.2023.1281667. eCollection 2023.

Integrated control strategies for dengue, Zika, and Chikungunya virus infections

Nelson Côrtes #  1   2 , Aline Lira #  1   2 , Wasim Prates-Syed  1   2 , Jaqueline Dinis Silva  1   3 , Larissa Vuitika  1 , William Cabral-Miranda  4 , Ricardo Durães-Carvalho  5 , Andrea Balan  2   6 , Otavio Cabral-Marques  1   3   7 , Gustavo Cabral-Miranda  1   2   3
Affiliations
Review

Integrated control strategies for dengue, Zika, and Chikungunya virus infections

Nelson Côrtes et al. Front Immunol. .

Abstract

Arboviruses are a major threat to public health in tropical regions, encompassing over 534 distinct species, with 134 capable of causing diseases in humans. These viruses are transmitted through arthropod vectors that cause symptoms such as fever, headache, joint pains, and rash, in addition to more serious cases that can lead to death. Among the arboviruses, dengue virus stands out as the most prevalent, annually affecting approximately 16.2 million individuals solely in the Americas. Furthermore, the re-emergence of the Zika virus and the recurrent outbreaks of chikungunya in Africa, Asia, Europe, and the Americas, with one million cases reported annually, underscore the urgency of addressing this public health challenge. In this manuscript we discuss the epidemiology, viral structure, pathogenicity and integrated control strategies to combat arboviruses, and the most used tools, such as vaccines, monoclonal antibodies, treatment, etc., in addition to presenting future perspectives for the control of arboviruses. Currently, specific medications for treating arbovirus infections are lacking, and symptom management remains the primary approach. However, promising advancements have been made in certain treatments, such as Chloroquine, Niclosamide, and Isatin derivatives, which have demonstrated notable antiviral properties against these arboviruses in vitro and in vivo experiments. Additionally, various strategies within vector control approaches have shown significant promise in reducing arbovirus transmission rates. These encompass public education initiatives, targeted insecticide applications, and innovative approaches like manipulating mosquito bacterial symbionts, such as Wolbachia. In conclusion, combatting the global threat of arbovirus diseases needs a comprehensive approach integrating antiviral research, vaccination, and vector control. The continued efforts of research communities, alongside collaborative partnerships with public health authorities, are imperative to effectively address and mitigate the impact of these arboviral infections on public health worldwide.

Keywords: Chikungunya virus; Zika virus; arboviruses; climate change; dengue virus; public health; strategies control; tropical regions.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The arbovirus replication cycle and systematic infection. Arboviruses interact with multiple types of host attachment factors, including molecules that bind to the viral membrane or virion-associated N-linked carbohydrates. Virions are internalized by clathrin-dependent mechanisms that usurp host factors involved in the uptake of large macromolecules. Subsequently, viral RNA replication takes place, and infected cells migrate through skin into blood stream and lymphoid organs, such as lymph nodes, spleen, liver and brain. Host immune response, and each affected organ can trigger different sinptoms and pathologies.
Figure 2
Figure 2
The Arbovirus DENV, ZIKV, and CHIKV distribution around the world: The map shows the areas with the distribution of the risk of DENV throughout the world (A), the areas with the risk of ZIKV (B), and the areas of the risk of CHIKV (C). On (D), the incidence of DENV is shown in the Brazilian states, (E) ZIKV, and (F) CHIKV.
Figure 3
Figure 3
Genomic Organization and Viral Structure of Flavivirus and Alphavirus. Flavivirus comprise a single Open Reading Frame with the genes for the Structural Proteins followed by the Non-Structural Proteins transcribed and translated and the resulting polyprotein undergoes proteolytic processing. Alphavirusus are comprised of the genes for the Non-Structural Proteins followed by the Structural Proteins, transcribed from two distinct ORFs, and each resulting polyprotein undergoes further proteolytical processing. Flavivirus structure have a mature virions with capsid (C) and membrane (M) covered by 90 dimers of (E) proteins. The E proteins exhibit three domain: E-DI (dark blue), E-DII (light blue) and E-DIII (green) anchored to the viral membrane (purple). The Alphavirus virion have the envelope glycoproteins in a shape of 240 dr trimer of E1(dark green), E2 (light green) ancored in lipid membrane (M) and the capsid (C) protein (blue). Showing heterodimers interacting with capsid protein.
Figure 4
Figure 4
Chord Diagram with candidate vaccine in clinical trials to DENV, ZIKV and CHIKV. The chord diagram employed in this study depicts a central circle representing the target virus of the vaccines, including DENV (dark green), ZIKV (red), and CHIKV (yellow). The diverse segments of the circle are assigned to distinct vaccine development methodologies: 3 trials on VLP (brown), 5 trials on inactivated virus (gray), 6 trials on recombinant methods (orange), 1 mRNA trial (yellow), 12 trials on live attenuated (blue), and 1 trials involving DNA (red). The phases of the clinical trials are indicated by symbols: dash (Phase 1), plus (Phase 2), and star (Phase 3). The vaccines mentioned in the chord diagram are registered in the ClinicalTrials.gov - National Library of Medicine (U.S.) database.
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The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The authors acknowledge the support provided by The São Paulo Research Foundation – FAPESP: GC-M: 2019/14526-0, 2020/04667-3; GC-M and NC: 2021/03508-1 (PhD Scholarship); GC-M and AL: 2021/03102-5 (PhD Scholarship); (FAPESP Young Investigator Program, 2021/03684-4, RD-C); (FAPESP grants: 2020/01688-0 and 2020/07069-0 to OC-M).
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