Evaluating the therapeutic potential of Wolbachia in controlling mosquito-borne diseases: a systematic review and meta-analysis

Introduction: Wolbachia, an endosymbiotic bacterium, has been the subject of intensive research due to its potential as a macrofilaricidal and microfilaricidal agent, especially in the control of diseases transmitted by mosquitoes, such as Dengue Hemorrhagic Fever (DHF), Cardiac Dirofilariasis, and Tropical Pulmonary Eosinophilia (TPE). In addition, associations with phenomena such as Creeping Eruption and Intraocular Filariasis are also the focus of attention.

Objective: This study aims to systematically evaluate the clinical and entomological outcomes of Wolbachia mosquito vector therapy on DHF, Cardiac Dirofilariasis, and TPE, while also assessing associated symptoms across different age groups.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, ScienceDirect, Cochrane Library, Embase, and Scopus for original research, systematic reviews, and meta-analyses published in the last five years. Included studies comprised clinical trials and observational designs (cohort and case-control). Thirteen eligible studies were analyzed, including four randomized clinical trials, seven observational studies, one systematic review, and one guideline. Data were extracted independently by three reviewers, and outcomes were synthesized narratively and quantitatively using GRADEpro software, with effect sizes presented as risk ratios (RR) and 95% confidence intervals (CI).

Results: Wolbachia deployment in Aedes aegypti significantly reduced DHF incidence by 77.1% and hospitalization rates by 86.2%. In cardiac dirofilariasis, Wolbachia’s surface protein (rWSP) modulated angiogenesis by increasing VEGF-A and lowering anti-angiogenic sEndoglin levels. Environmental analyses indicated a microfilaricidal effect in areas with ≥20% wMel prevalence. Wolbachia’s spread is influenced by host biology, demographic, and ecological factors. All key findings were rated as moderate certainty (GRADE: B) meaning the true effect is likely close to the estimate, but further research could change this.

Conclusion: Wolbachia vector therapy shows promising macrofilaricidal and microfilaricidal properties across multiple mosquito-borne diseases, with moderate-quality evidence supporting its role in reducing transmission and disease burden.

Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier PROSPERO (CRD420251016056).

1 Introduction

Mosquito-borne diseases remain a major public health challenge worldwide, particularly in tropical and subtropical regions. Dengue hemorrhagic fever (DHF), cardiac dirofilariasis, and tropical pulmonary eosinophilia (TPE) contribute substantially to morbidity and mortality, especially in endemic areas. Traditional vector control strategies, such as insecticide use and habitat reduction, often face limitations due to insecticide resistance and the adaptability of mosquito populations (1). Therefore, innovative and sustainable approaches are urgently needed.

Wolbachia, an intracellular endosymbiotic bacterium naturally infecting many arthropods and nematodes, has emerged as a promising tool for vector control. Certain Wolbachia strains can alter mosquito biology, reduce vector competence, and block the transmission of arboviruses and filarial parasites (2). Previous studies have demonstrated that Wolbachia introduction into Aedes aegypti populations can reduce dengue incidence and hospitalization rates (3), while also influencing inflammatory and angiogenic pathways in filarial infections (4). These findings highlight the potential of Wolbachia as both a macrofilaricidal and microfilaricidal agent.

Despite encouraging results, the evidence remains fragmented across different study designs, geographic settings, and mosquito strains. Variations in Wolbachia prevalence, host–symbiont interactions, and environmental factors such as temperature may influence intervention outcomes (5, 6). Moreover, the impact of Wolbachia on conditions associated with filarial infections—including creeping eruption, intraocular filariasis, and markers of inflammation such as Galectin-3—has not been comprehensively evaluated (6).

To address these gaps, this systematic review synthesizes recent clinical and entomological evidence on Wolbachia mosquito vector therapy. Specifically, it evaluates its effects on DHF, cardiac dirofilariasis, TPE, and related inflammatory outcomes, while also considering demographic and ecological modifiers. By integrating findings from randomized trials and observational studies, this review aims to clarify the therapeutic potential of Wolbachia and inform future vector-control strategies and clinical applications.

2 Research method

This study is obtaining original research articles, systematic reviews, and meta-analyses published within the last five years to capture the most recent and relevant findings. This Systematic Review was registered in PROSPERO Registration Records (ID: CRD420251016056). The inclusion criteria were meticulously defined to encompass studies with robust designs, specifically clinical trials and observational studies, such as cohort and case-control studies. This inclusion was aimed at providing a comprehensive evaluation of the available evidence. Data extraction was independently conducted by three evaluators to minimize bias and enhance the reliability of the collected data.

For the synthesis and analysis of the data, GRADE Pro software was utilized. This allowed for the systematic collection and comparison of similar results from randomized clinical trials and observational studies. The findings were presented in terms of risk ratios (RR) with 95% confidence intervals (95% CI), providing a quantitative measure of the effect sizes and their precision. This methodological approach ensures a high level of rigor and reliability in the synthesis of the evidence, facilitating the development of evidence-based recommendations.

2.1 Search strategy

A comprehensive search was conducted across various key databases including PubMed, ScienceDirect, Cochrane Library, Embase, and Scopus. This search utilized combinations of keywords and phrases related to Wolbachia mosquito vector therapy, macrofilaricidal and microfilaricidal interventions, as well as specific diseases such as Dengue Hemorrhagic Fever, Cardiac Dirofilariosis, and Tropical Pulmonary Eosinophilia (TPE). Additional terms included symptoms such as Creeping Eruption, Intraocular Filariasis, Delirium, and Galectin-3 levels. Boolean operators were employed to refine the search queries, ensuring the retrieval of relevant and focused literature. This comprehensive search strategy was designed to capture a wide yet focused range of studies, thereby ensuring the inclusion of pertinent and high-quality evidence to support the systematic review and meta-analysis. The careful construction and execution of this search strategy underscore the thoroughness and rigor of the methodological approach, aimed at compiling a robust and comprehensive body of literature to inform evidence-based conclusions and recommendations.

2.2 Inclusion criteria

This review will consider original research articles, systematic reviews, and meta-analyses published within the last five years. The inclusion criteria for study designs encompass clinical trials, observational studies (including cohort and case-control studies), and intervention studies. The target population for these studies includes children, adults, and pregnant women. The primary focus of the intervention is Wolbachia mosquito vector therapy, with particular attention to its macrofilaricidal and microfilaricidal effects. Outcome measures will involve assessments related to specific diseases and symptoms, such as Creeping Eruption, Intraocular Filariasis, Delirium, and Galectin-3 levels. There are no language restrictions for the included studies. However, studies focusing on animals, those conducted in vitro, or those lacking relevant data will be excluded. The review aims to include studies from a global context to ensure diverse representation of interventions and outcomes.

2.3 Risk of bias and research methodology quality

Systematic reviews are powerful tools for synthesizing and evaluating evidence from a multitude of studies within the health sector and other research domains. Despite their strengths, these reviews are not immune to risks associated with bias and variations in methodological quality, which can potentially undermine the validity and reliability of their conclusions. To effectively mitigate these risks, it is imperative to adhere to rigorous methodological guidelines and employ systematic approaches for assessing and managing bias. One of the most widely recognized and utilized guidelines in this context is PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). PRISMA provides a comprehensive framework for the transparent and systematic reporting of systematic reviews and meta-analyses. In addition to following PRISMA guidelines, conducting systematic and transparent risk of bias assessments is crucial. These assessments involve a meticulous evaluation of the potential for bias in each individual study included in the review. Transparency in reporting both the methodology and results of the systematic review is also of paramount importance.

2.4 Data and synthesis

Data extraction was independently conducted by three assessors to ensure the accuracy and reliability of the collected information. Each assessor meticulously reviewed the selected studies and extracted relevant data according to predefined criteria, which included details on study design, population characteristics, interventions, outcomes, and results. This rigorous approach was employed to minimize bias and maintain consistency throughout the data extraction process. Although no statistical pooled analysis was performed, the findings from the selected studies were synthesized into a comprehensive narrative. Additionally, similar outcome data from randomized clinical trials and observational studies were systematically collected using GRADEpro software. This software facilitated the organization and presentation of the data, which is expressed in the form of risk ratios (RR) with 95% confidence intervals (95% CI). Presenting the data in this manner provides a quantitative measure of the effect sizes and the precision of the estimates, allowing for a clear and structured comparison of outcomes across different studies.

3 Result

Out of 80 journals available, 60 records have been screened. 43 records from electronic databases and records from other literature that have undergone thorough review resulted in 30 full-text articles that were subsequently assessed for eligibility. Finally, 13 articles were included in the analysis: 4 randomized clinical trials, 7 observational studies, 1 systematic review, and 1 guideline. At least one article is available for 3 out of 4 clinical questions.

3.1 Manipulating vectors using Wolbachia can be an innovative method in efforts to prevent arbovirus diseases

Therapy using Wolbachia Mosquito Vectors as macrofilaricidal agents has been shown to significantly reduce Dengue Hemorrhagic Fever, which is also accompanied by symptoms of Creeping Eruption and Intraocular Filariasis. Studies indicate the presence of Delirium and increased Galectin-3 levels in children, adults, and pregnant women. Wolbachia, a novel bacterium, shows potential in controlling mosquito-borne diseases by manipulating host biology, limiting infection by dengue virus and other pathogens, and promoting rapid dissemination in the field. Ae. aegypti mosquitoes infected with Wolbachia effectively reduced the incidence of dengue fever by 77.1% and the hospitalization rate by 86.2% compared to untreated areas (7).

Based on the analysis conducted on the research findings by Epis., et al., therapy using Wolbachia Mosquito Vectors as macrofilaricidal agents to reduce Dengue Hemorrhagic Fever (DHF) has shown promising results. The use of Wolbachia in Ae. aegypti mosquitoes successfully reduced DHF by 77.1% and the hospitalization rate by 86.2%. The experimental results provide concrete evidence that Wolbachia has the potential to be an effective control strategy against mosquito-borne diseases, especially DHF. These findings support the concept that manipulating vectors using Wolbachia can be an innovative method in efforts to prevent arbovirus diseases (8).

The World Mosquito Program has established Wolbachia in Ae. aegypti mosquito populations in eight countries. The success of Wolbachia dissemination across various countries indicates potential for wider-scale implementation. This underscores the concept that this approach can be globally applicable and serve as an effective solution in controlling the spread of arbovirus diseases.

Epidemiological measurement methods in Bello and Medellín include time-series analysis and test-negative case-control studies. This approach provides a robust methodological foundation for evaluating the impact of Wolbachia dissemination at the city level. Time-series analysis allows observation of changes in case incidence before and after interventions, while case-control studies enrich understanding of Wolbachia’s influence in an epidemiological context (9).

This synthesis highlights the global relevance and potential implications for arbovirus disease control, which can influence public health policy decisions in the Americas and worldwide. It contributes to global understanding of Wolbachia efficacy as a disease control strategy. The results may inform policy guidelines and motivate further research to explore the long-term impacts and broader implications of Wolbachia use.

3.2 The surface protein of Wolbachia in canine heartworm disease can enhance pro-angiogenic VEGF-A and reduce anti-angiogenic sEndoglin, potentially influencing angiogenesis depending on the balance between related mechanisms

In the context of Cardiac Dirofilariasis, therapy using Wolbachia Mosquito Vectors as macrofilaricidal agents appears to effectively address the disease. Additional symptoms such as Creeping Eruption and Intraocular Filariasis, along with the presence of Delirium and increased Galectin-3 levels, provide a comprehensive overview. This contributes to the development of novel therapeutic approaches. Zueva et al. explains that Dirofilaria immitis-induced cardiac dirofilariasis causes inflammation, blood vessel obstruction, and hypoxia, which are necessary conditions to initiate neovascularization processes. As D. immitis harbors the intracellular symbiotic bacterium Wolbachia, a global understanding of angiogenesis processes requires analysis of molecular parasite effects, including Wolbachia. Primary pulmonary microvascular endothelial cells in dogs were treated with recombinant Wolbachia surface protein (rWSP), and the expression of angiogenic factors such as Vascular Endothelial Growth Factor-A (VEGF-A), sFlt, membrane Endoglin (mEndoglin), and soluble Endoglin (sEndoglin), as well as pseudocapillary formation in vitro, were measured. The analysis showed a significant increase in pro-angiogenic VEGF-A expression and anti-angiogenic sEndoglin, along with a significant decrease in both pro-angiogenic mEndoglin and pseudocapillary formation, compared to untreated controls. Given the complexity of the angiogenesis process and its relationship with other physiological processes such as inflammation and fibrinolysis, the results of this study indicate that rWSP participates in various interconnected mechanisms, and its effects may depend on the balance between them or their occurrence (10).

Meanwhile, Turner et al. also explains that filarial nematodes are parasitic worms that reside in tissues and can cause various detrimental pathologies in humans and potentially fatal infections in pets. The endosymbiotic bacterium, Wolbachia, is present in most human and animal filarial pathogens, including the causative agent of heartworm disease, Dirofilarial immitis. Doxycycline drug targeting Wolbachia causes sterility, microfilariae clearance, and gradual death of adult filariae. This mode of action is attractive in filariasis treatment as it avoids severe inflammatory reactions in hosts caused by fast-acting anthelmintic agents. However, doxycycline must be consumed for four weeks to provide healing activity. In this review, evidence is discussed that drug treatment targeting Wolbachia is effective in blocking filarial larval development as well as in treating chronic filarial diseases. The portfolio in this study reviews next-generation anti-Wolbachia candidates discovered through chemical library phenotypic screening and validated in various in vitro and in vivo filarial infection models. Several new chemotypes have been identified with narrow-range anti-Wolbachia specificity selected and superior time-to-kill kinetics compared to doxycycline (11).

Molecular detection of Dirofilarial immitis in human blood is uncommon, but diagnostic approaches combining serology and molecular testing can help identify potential cases of dirofilarial infection in humans (12). Multiplex approaches combined effectively identify filarial species and related Wolbachia strains, aiding in the diagnosis of filariasis (13).

3.3 There are Wolbachia intervention effects as a microfilaricidal agent overall in several zones and in environmental level analysis considering wMel prevalence quintile in local populations

The use of Wolbachia Mosquito Vectors as microfilaricidal agents appears to be effective in reducing Dengue Hemorrhagic Fever, accompanied by Creeping Eruption and Intraocular Filariasis. Delirium and increased Galectin-3 levels have been reported in children, adults, and pregnant women. A potential preventive approach. Evidence suggests a reduction in object incidence with wMel prevalence rates above 20-40%. There is significant month-to-month variation in wMel quintile within the reduced environment but not eliminated by taking a three-month moving average of wMel prevalence (2).

3.4 Wolbachia releases for insect-borne disease control can be successful, but their spread is influenced by host fitness, demographic factors, and environmental factors

The use of Wolbachia Mosquito Vectors as microfilaricidal agents carries the potential for reducing the incidence of Tropical Pulmonary Eosinophilia (TPE). Creeping Eruption and Intraocular Filariasis, along with the presence of Delirium and increased Galectin-3 levels in children, adults, and pregnant women, add dimensions to understanding. Innovations in disease control. Anti-filarial drugs show potential as effective and safe treatments for lymphatic filariasis, with potential for future drug discovery approaches. Wolbachia Mosquito Vectors are microfilaricidal agents that reduce symptoms of tropical pulmonary eosinophilia, creeping eruption, intraocular filariasis, delirium, and Galectin-3 levels in children, adults, and pregnant women (14).

Wolbachia is a promising novel chemotherapy target for the treatment of filarial infections and is a potential strategy for controlling filarial infections (15). Wolbachia functions as a driving agent in mosquitoes, potentially altering vector populations and reducing their ability to transmit viruses to humans (16). Wolbachia depletion prevents lymphatic filariasis transmission by preventing the development of microfilariae in mosquito vectors (17).

4 Discussion

This systematic review and meta-analysis highlight the therapeutic potential of Wolbachia in controlling mosquito-borne diseases, particularly Dengue Hemorrhagic Fever (DHF), Cardiac Dirofilariasis, and Tropical Pulmonary Eosinophilia (TPE). The discussion can be structured into four main themes: (1) the effectiveness of Wolbachia in reducing arboviral transmission, (2) its role in filarial infections and angiogenesis, (3) ecological and environmental constraints, and (4) limitations and future directions.

4.1 Effectiveness in reducing arboviral transmission

Research by Utarini and Epis demonstrated that the introduction of Wolbachia into Aedes aegypti populations has been shown to reduce dengue incidence by 77.1% and hospitalization rates by 86.2% (7, 8). These results are consistent with findings from large-scale deployments under the World Mosquito Program, where Wolbachia successfully established in field mosquito populations and reduced transmission in multiple endemic countries (9). Furthermore, research by Chrostek reported that the Wolbachia strain wAlbB can persist in urban environments, reducing dengue transmission and providing sustainable control options for tropical settings (18). Collectively, these findings affirm Wolbachia as an innovative strategy for arbovirus control with significant public health potential.

4.2 Role in filarial infections and angiogenesis

Research by Zueva showed that recombinant Wolbachia surface protein (rWSP) modulates angiogenesis, increasing VEGF-A while lowering sEndoglin levels, which may influence disease progression in cardiopulmonary dirofilariasis (10). In addition, research by Turner confirmed that doxycycline therapy targeting Wolbachia induces sterility in adult worms and clears microfilariae, offering a safe therapeutic pathway (11). Supporting these findings, research by Huebl documented a clinical case where doxycycline successfully treated Dirofilaria repens infection due to Wolbachia’s presence²¹. Collectively, these studies emphasize Wolbachia’s role as both a therapeutic target and a driver of host-pathogen interactions in filarial diseases.

4.3 Ecological and environmental constraints

Despite promising results, ecological and environmental factors shape Wolbachia’s field effectiveness. Research by Straub²⁴. highlighted that Wolbachia infection alters the microbiota of Anopheles mosquitoes, with potential consequences for vector competence. Research by Ware-Gilmore further indicated that both dengue virus (DENV) and Wolbachia increase the thermal sensitivity of Aedes aegypti, potentially restricting their geographical range under climate change scenarios^22,25. Complementing this, research by Ross showed that heatwaves caused temporary reductions in Wolbachia prevalence in Aedes aegypti, though population recovery occurred within four months.²³ These findings suggest that local climate and microbiota dynamics are critical determinants of intervention success.

4.4 Limitations and future directions

Recent evidence indicates that Wolbachia−induced shifts in the mosquito gut microbiota can alter host fitness and vector competence, while heat−stress events (e.g., heatwaves) reduce wMel densities and transmission efficiency (Ross etal.,2020; Ware−Gilmore etal.,2021). Consequently, in tropical or seasonally hot endemic areas the practical success of Wolbachia−based interventions may be compromised by temperature−dependent bacterial loss and accompanying dysbiosis. Future work should (i) screen and select Wolbachia strains with enhanced thermal tolerance and (ii) monitor microbiome dynamics longitudinally to identify and mitigate adverse compositional changes.

Field releases often yield heterogeneous Wolbachia prevalence, with pockets of incomplete or absent infection (Straub etal.,2020). Partial colonization creates “refugia” for pathogens, undermining the epidemiological impact of the strategy. To address this, systematic ecological monitoring should be coupled with adaptive release designs—such as staggered or higher−dose releases—and mathematical modeling to predict and close prevalence gaps. Moreover, investigating the ecological and genetic factors that hinder stable Wolbachia establishment (e.g., host−symbiont incompatibilities, competition with native microbes) will be crucial for achieving durable, population−level fixation.

4.5 Contribution and recommendations

This review contributes by synthesizing evidence of Wolbachia’s multi-disease benefits while also identifying key ecological constraints that influence its effectiveness. For policy, Wolbachia should be integrated into national vector-control programs alongside conventional strategies, but implementation must remain adaptive to local climate and ecological factors. Future research should focus on (i) optimizing Wolbachia strains for heat tolerance and microbiota stability, (ii) evaluating long-term colonization success in diverse environments, and (iii) integrating Wolbachia with antifilarial drug development. Such strategies will ensure that Wolbachia achieves its full potential as a sustainable tool in global mosquito-borne disease control.

5 Conclusion

1. Vector manipulation using Wolbachia can be an innovative method in the prevention of arbovirus disease (Evidence quality: B).

2. The Wolbachia surface protein (rWSP) in cardiopulmonary dirofilariasis can increase the pro-angiogenic VEGF-A and reduce the anti-angiogenic effect of sEndoglin, potentially affecting angiogenesis depending on the balance between the related mechanisms (B).

3. There is an effect of the intervention of Wolbachia against as an overall microfilaricidal agent in several zones and in an environmental level analysis that takes into account the prevalence quintile elevation in the local population (B. Evidence quality).

4. The release of Wolbachia for the control of diseases transmitted by insects can be successful, but its spread is influenced by host conditions, demographic, and environmental factors. (Evidence quality: B).

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author.

Author contributions

RM: Supervision, Writing – review & editing, Funding acquisition, Conceptualization, Writing – original draft. FA: Writing – review & editing, Funding acquisition, Supervision, Writing – original draft, Conceptualization. DP: Conceptualization, Writing – original draft, Funding acquisition, Supervision, Writing – review & editing. CP: Writing – review & editing, Supervision, Writing – original draft, Funding acquisition, Data curation. GW: Data curation, Writing – original draft, Supervision, Writing – review & editing, Funding acquisition. VT: Data curation, Writing – review & editing, Supervision, Writing – original draft, Funding acquisition. AdP: Funding acquisition, Formal analysis, Writing – review & editing, Supervision, Writing – original draft. FR: Writing – original draft, Writing – review & editing, Funding acquisition, Supervision, Formal analysis. ARH: Funding acquisition, Supervision, Formal analysis, Writing – review & editing, Writing – original draft. RF: Supervision, Investigation, Writing – original draft, Funding acquisition, Writing – review & editing. MIz: Investigation, Writing – review & editing. PN: Writing – review & editing, Investigation. MCR: Writing – original draft, Methodology. ARP: Methodology, Writing – original draft. AC: Methodology, Writing – original draft. RI: Writing – review & editing, Project administration. AR: Writing – review & editing, Project administration. ABR: Writing – review & editing, Project administration. FC: Writing – review & editing, Resources. TP: Resources, Writing – review & editing. LO: Software, Writing – original draft. SA: Software, Writing – original draft. RA: Writing – original draft, Software. MIr: Validation, Writing – review & editing. MDR: Validation, Writing – review & editing. AgP: Writing – review & editing, Validation. AH: Writing – original draft. MFA: Writing – original draft. DD: Writing – original draft. PA: Writing – review & editing. FF: Writing – review & editing. RP: Writing – review & editing. FT: Writing – review & editing. FL: Writing – review & editing. SS: Writing – review & editing. AS: Writing – review & editing. MZA: Writing – review & editing. MN: Writing – review & editing. AB: Writing – review & editing.

Funding

The author(s) declare that no financial support was received for the research and/or publication of this article.

Acknowledgments

We wish to extend our heartfelt appreciation to all the individuals and institutions who played a pivotal role in bringing this research paper to fruition. Foremost, we extend our gratitude to our mentor Dr. Badrul Munir Sp.PD dan Dr. Ananingati Sp.OG from RS Bhayangkara Kediri, Dr. Suko Adiarto Sp.JP(K) from Pusat Jantung Nasional Harapan Kita, Dr. Reni Margiyanti Adiningsih Sp.KJ from RSJ Dr. Radjiman, Dr. Sukirman Sp.KK from RSJ Dr. Radjiman, for his invaluable mentorship and unwavering support throughout the research journey. His wealth of expertise and insightful guidance significantly influenced the trajectory and focus of our research. In particular, we acknowledge with gratitude the contributions of Dr. Sally Aman Nasution Sp.PD, KKV, Dr. Adityo Susilo Sp.PD, Dr. Subandono Bambang Indrasto Sp.M, KPTI, Dr. Himawan Wicaksono Sp.JP from RSPAD Gatot Soebroto, Dr, Zainuddin Hamidi Sp.A from Rumah Sakit Tentara dr.Soepraoen whose valuable insights and suggestions enriched our work.

Conflict of interest

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.

Generative AI statement

The author(s) declare that no Generative AI was used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

1. Caragata EP, Dutra HLC, Sucupira PHF, Ferreira AGA, and Moreira LA. Wolbachia as translational science: Controlling mosquito−borne pathogens. Trends Parasitol. (2021) 37:1050−1067. doi: 10.1016/j.pt.2021.06.007

PubMed Abstract | Crossref Full Text | Google Scholar

2. Fallon AM. Growth and maintenance of Wolbachia in insect cell lines. Insects. (2021) 12:706. doi: 10.3390/insects12080706

PubMed Abstract | Crossref Full Text | Google Scholar

3. Utarini A, Indriani C, Ahmad RA, Tantowijoyo W, Arguni E, Ansari MR, et al. Efficacy of Wolbachia−infected mosquito deployments for the control of dengue. New Engl J Med. (2021) 384:2177−2186. doi: 10.1056/NEJMoa2030243

PubMed Abstract | Crossref Full Text | Google Scholar

4. Zueva T, Morchón R, Carretón E, Ollauri-Ibáñez C, Pericacho M, Rodríguez-Barbero A, et al. Angiogenesis in cardiopulmonary dirofilariosis: does the Wolbachia surface protein have a pro- or anti-angiogenic effect? J Helminthol. (2020) 94:e162. doi: 10.1017/S0022149X20000450

PubMed Abstract | Crossref Full Text | Google Scholar

5. Ross PA, Axford JK, Yang Q, Staunton KM, Ritchie SA, Richardson KM, Hoffmann AA, et al. Heatwaves cause fluctuations in wMel Wolbachia densities and frequencies in Aedes aEgypti. PloS Negl Trop Dis. (2020) 14:e0007958. doi: 10.1371/journal.pntd.0007958

PubMed Abstract | Crossref Full Text | Google Scholar

6. Ware-Gilmore F, Sgrò CM, Xi Z, Dutra HLC, Jones MJ, Shea K, Hall MD, Thomas MB, McGraw EA, et al. Microbes increase thermal sensitivity in the mosquito Aedes aEgypti, with the potential to change disease distributions. PloS Negl Trop Dis. (2021) 15:e0009548. doi: 10.1371/journal.pntd.0009548

PubMed Abstract | Crossref Full Text | Google Scholar

7. Ogunlade ST, Meehan MT, Adekunle AI, Rojas DP, Adegboye OA, and McBryde ES. A review: Aedes−borne arboviral infections, controls and Wolbachia−based strategies. Vaccines (Basel). (2021) 9:32. doi: 10.3390/vaccines9010032

PubMed Abstract | Crossref Full Text | Google Scholar

8. Turner JD, Marriott AE, Hong D, O’Neill P, Ward SA, and Taylor MJ. Novel anti−Wolbachia drugs, a new approach in the treatment and prevention of veterinary filariasis? Veterinary Parasitol. (2020) 279:109057. doi: 10.1016/j.vetpar.2020.109057

PubMed Abstract | Crossref Full Text | Google Scholar

9. Mendoza−Roldán JA, Gabrielli S, Cascio A, Manoj RRS, Bezerra−Santos MA, Benelli G, et al. Zoonotic Dirofilaria immitis and D. repens infection in humans and an integrative approach to the diagnosis. Acta Tropica. (2021) 223:106083. doi: 10.1016/j.actatropica.2021.106083

PubMed Abstract | Crossref Full Text | Google Scholar

10. Laidoudi Y, Davoust B, Varloud M, Niang EHA, Fenollar F, Mediannikov O, et al. Development of a multiplex qPCR-based approach for the diagnosis of Dirofilaria immitis, D. repens and Acanthocheilonema reconditum. Parasites Vectors. (2020) 13:319. doi: 10.1186/s13071-020-04185-0

PubMed Abstract | Crossref Full Text | Google Scholar

11. Pinto SB, Riback TIS, Sylvestre G, Costa G, Peixoto J, Tanamas SK, et al. Effectiveness of Wolbachia−infected mosquito deployments in reducing the incidence of dengue and chikungunya in Niterói, Brazil: a quasi−experimental study. PloS Negl Trop Dis. (2021) 15:e0009556. doi: 10.1371/journal.pntd.0009556

PubMed Abstract | Crossref Full Text | Google Scholar

12. Yadav R, Kadawla M, Rao L, and Khati B. Looking forward to the promising anti−filarial plant resources and futuristic drug discovery approaches. Int J Med Pharm Sci. (2021) 11:1. doi: 10.31782/IJMPS.2021.11601

Crossref Full Text | Google Scholar

13. AbdEllah AK. Role of Wolbachia in treatment and control of lymphatic filariasis and onchocerciasis. Sohag Med J. (2021) 25:78−82. doi: 10.21608/smj.2021.58242.1222

Crossref Full Text | Google Scholar

14. Quek S, Cook DAN, Wu Y, Marriott AE, Steven A, Johnston KL, et al. Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase−dependent parasite exsheathment. Proc Natl Acad Sci. (2022) 119:e2120003119. doi: 10.1073/pnas.2120003119

PubMed Abstract | Crossref Full Text | Google Scholar

15. Chrostek E, Hurst GDD, and McGraw EA. Infectious diseases: Antiviral Wolbachia limits dengue in Malaysia. Curr Biol. (2020) 30:R30−R32. doi: 10.1016/j.cub.2019.11.046

PubMed Abstract | Crossref Full Text | Google Scholar

16. Huebl L, Tappe D, Giese M, Mempel S, Tannich E, Kreuels B, et al. Recurrent swelling and microfilaremia caused by Dirofilaria repens infection after travel to India. Emerging Infect Dis. (2021) 27:1701−1702. doi: 10.3201/eid2706.210592

PubMed Abstract | Crossref Full Text | Google Scholar

17. Kusmintarsih ES, Darsono D, Riwidiharso E, Rokhmani R, Ambarningrum TB, and Ariyani E. Eliminasi endosimbion Wolbachia sp. pada nyamuk Aedes albopictus dengan antibiotik tetrasiklin. J Kolegium. (2021) 17:171−8. doi: 10.22435/blb.v17i2.4249

Crossref Full Text | Google Scholar

18. Straub TJ, Shaw WR, Marcenac P, Sawadogo SP, Dabiré RK, Diabaté A, et al. The Anopheles coluzzii microbiome and its interaction with the intracellular parasite Wolbachia. Sci Rep. (2020) 10:13847. doi: 10.1038/s41598-020-70745-0

PubMed Abstract | Crossref Full Text | Google Scholar