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Editorial

Borrelia, Leishmania, and Babesia: An Emerging Triad of Vector-Borne Co-Infections?

by
Elianne Piloto-Sardiñas
1,2,*,
Ana Laura Cano-Argüelles
3 and
Alejandro Cabezas-Cruz
2,*
1
Direction of Animal Health, National Center for Animal and Plant Health, Carretera de Tapaste y Autopista Nacional, Apartado Postal 10, San José de las Lajas 32700, Cuba
2
ANSES, INRAE, Ecole Nationale Vétérinaire d’Alfort, UMR BIPAR, Laboratoire de Santé Animale, F-94700 Maisons-Alfort, France
3
Parasitology Laboratory, Institute of Natural Resources and Agrobiology of Salamanca (IRNASA, CSIC), Cordel de Merinas, 40-52, 37008 Salamanca, Spain
*
Authors to whom correspondence should be addressed.
Pathogens 2025, 14(1), 36; https://doi.org/10.3390/pathogens14010036
Submission received: 25 December 2024 / Accepted: 3 January 2025 / Published: 6 January 2025
(This article belongs to the Section Parasitic Pathogens)
Canine leishmaniosis (CanL), caused by the protozoan Leishmania infantum and transmitted primarily by phlebotomine sand flies, poses significant challenges for zoonotic disease management [1], with dogs serving as reservoirs, facilitating transmission to humans [2]. Host exposure to sand fly vectors, as well as ticks carrying other pathogens, increases the risk of co-infection with Leishmania, Borrelia, and Babesia [3]. These co-infections may exacerbate CanL progression due to synergistic interactions between pathogens that manipulate host immune responses [3].
The dynamics of zoonotic diseases are increasingly influenced by the overlapping habitats of vectors such as sand flies and ticks [4,5,6]. Climate change and habitat alterations are driving these vectors into new territories [7,8], creating conditions in which ticks (carrying Borrelia and Babesia) and sand flies (carrying Leishmania) can coexist [9,10,11,12,13,14,15]. This overlap enhances the likelihood of hosts, particularly dogs, becoming co-infected with multiple pathogens [9,10,11,12,13,14,15,16]. Pathogen interactions during co-infections—synergistic, antagonistic, or neutral—affect virulence, pathogenicity, and colonization success [17,18], affecting disease progression, and ultimately the risk of human infection [11,19].
A recent study by Pessôa-Pereira et al. [4] highlights how Borrelia burgdorferi, the agent of Lyme disease, exacerbates Leishmania infection in co-infected dogs. This study underscores the broader implications of co-infections involving vector-borne pathogens with overlapping hosts and/or vectors. Babesia, a protozoan parasite transmitted by ticks, causes babesiosis [20] and has been reported in co-infections with Leishmania in dogs [3,9,21]. Similarly, in humans, co-infection with Babesia and Borrelia worsens the clinical course of both Lyme disease and babesiosis [22]. Given these findings, it raises the possibility that co-infection with Borrelia might similarly affect dogs with Leishmania, potentially enhancing CanL progression. This hypothesis is supported by the study of Pessôa-Pereira et al. [4], which showed that Borrelia co-infection increases Leishmania survival in macrophages by altering immune responses. Combined immune modulation by Borrelia, Leishmania, and Babesia—each employing different mechanisms to evade or manipulate host defenses [3]—could amplify disease severity and complicate treatment.
Despite their structural differences and distinct pathogenesis mechanisms, bacteria and protozoa can establish ecological interactions within biological systems [23,24]. In terrestrial (e.g., soil) or aquatic ecosystems, bacterial communities can interfere with protozoan colonization or predation, often fostering antagonistic relationships [23,24,25]. These antagonisms arise through intracellular mechanisms (e.g., survival and replication within protozoan cells) or extracellular adaptations (e.g., altered cell morphology, increased motility, or biofilm formation) [26], as well as the production of bacteriocins with antiprotozoal activity [27]. However, these interactions differ significantly when subjected to the biology, physiology, and immune pressures of hosts and vectors.
During co-infections in hosts or vectors, pathogens may interact at various stages of their life cycles, targeting the same cells or eliciting overlapping immune responses. For instance, shared immune cell tropism between vector-borne bacteria and protozoa or the modulation of immune functions, such as macrophage activity, can allow bacterial infections to enhance protozoal infections [11]. This overlap enables Borrelia, Leishmania, and Babesia to exploit host immune systems, exacerbating disease severity. For instance, Borrelia promotes a skewed Th17 immune response that is inflammatory but insufficient for clearance [28], Leishmania inhibits macrophage reactive oxygen species (ROS) production [29], and Babesia suppresses adaptive immunity against Borrelia, worsening Lyme disease severity [30]. Together, these immune evasion strategies create a feedback loop of suppression, chronic infection, and increased zoonotic risk.
The proactive monitoring of co-infections in regions with vector overlap is vital. The surveillance of multi-pathogen exposure in dogs and wildlife can provide an early warning of zoonotic threats, aiding veterinarians and public health officials in mitigating risks. Dogs are sentinel hosts in zoonotic disease ecology [31], moving between environments shared with humans and wildlife. Co-infections in dogs highlight potential spillover risks to humans [19,32], especially in regions where expanding tick and sand fly populations overlap.
Managing co-infections involving Leishmania, Borrelia, and Babesia necessitates an integrated, multi-vector approach targeting both sand fly and tick populations. Effective measures, such as vector control, habitat management, and innovative immune-modulating therapies that address the compounded effects of co-infections, are crucial to mitigating disease severity in dogs and reducing zoonotic transmission risks. The study by Pessôa-Pereira et al. [4] highlights the critical implications of co-infections among vector-borne pathogens that share vectors and hosts, emphasizing how these interactions accelerate disease progression and complicate treatment. In an era of shifting ecological boundaries, understanding these pathogen interactions within hosts like dogs is vital for anticipating and mitigating zoonotic risks. By integrating vector control strategies, expanding pathogen surveillance in dogs and wildlife, and advancing targeted treatment approaches for co-infected hosts, we can better manage the complex dynamics of vector-borne diseases. This holistic approach is essential to protecting the health of both animal populations and the human communities with whom they share their environments.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Morales-Yuste, M.; Martín-Sánchez, J.; Corpas-Lopez, V. Canine leishmaniasis: Update on epidemiology, diagnosis, treatment, and prevention. Vet. Sci. 2022, 9, 387. [Google Scholar] [CrossRef] [PubMed]
  2. Ribeiro, R.R.; Michalick, M.S.M.; da Silva, M.E.; Dos Santos, C.C.P.; Frézard, F.J.G.; da Silva, S.M. Canine leishmaniasis: An overview of the current status and strategies for control. BioMed Res. Int. 2018, 1, 3296893. [Google Scholar] [CrossRef] [PubMed]
  3. Beasley, E.A.; Pessôa-Pereira, D.; Scorza, B.M.; Petersen, C.A. Epidemiologic, clinical and immunological consequences of co-infections during canine leishmaniosis. Animals 2021, 11, 3206. [Google Scholar] [CrossRef]
  4. Pessôa-Pereira, D.; Scorza, B.M.; Cyndari, K.I.; Beasley, E.A.; Petersen, C.A. Modulation of Macrophage Redox and Apoptotic Processes to Leishmania infantum during Coinfection with the Tick-Borne Bacteria Borrelia burgdorferi. Pathogens 2023, 12, 1128. [Google Scholar] [CrossRef] [PubMed]
  5. LaDeau, S.L.; Allan, B.F.; Leisnham, P.T.; Levy, M.Z. The ecological foundations of transmission potential and vector-borne disease in urban landscapes. Funct. Ecol. 2015, 29, 889–901. [Google Scholar] [CrossRef]
  6. Martina, B.E.; Barzon, L.; Pijlman, G.P.; de la Fuente, J.; Rizzoli, A.; Wammes, L.J.; Takken, W.; van Rij, R.P.; Papa, A. Human to human transmission of arthropod-borne pathogens. Curr. Opin. Virol. 2017, 22, 13–21. [Google Scholar] [CrossRef] [PubMed]
  7. Sutherst, R.W. Global change and human vulnerability to vector-borne diseases. Clin. Microbiol. Rev. 2004, 17, 136–173. [Google Scholar] [CrossRef] [PubMed]
  8. Ortiz, D.I.; Piche-Ovares, M.; Romero-Vega, L.M.; Wagman, J.; Troyo, A. The impact of deforestation, urbanization, and changing land use patterns on the ecology of mosquito and tick-borne diseases in Central America. Insects 2021, 13, 20. [Google Scholar] [CrossRef] [PubMed]
  9. Cardoso, L.; Yisaschar-Mekuzas, Y.; Rodrigues, F.T.; Costa, Á.; Machado, J.; Diz-Lopes, D.; Baneth, G. Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections. Parasites Vectors 2010, 3, 27. [Google Scholar] [CrossRef] [PubMed]
  10. Ortuño, M.; Nachum-Biala, Y.; García-Bocanegra, I.; Resa, M.; Berriatua, E.; Baneth, G. An epidemiological study in wild carnivores from Spanish Mediterranean ecosystems reveals association between Leishmania infantum, Babesia spp. and Hepatozoon spp. infection and new hosts for Hepatozoon martis, Hepatozoon canis and Sarcocystis spp. Transbound. Emerg. Dis. 2022, 69, 2110–2125. [Google Scholar] [CrossRef] [PubMed]
  11. Toepp, A.J.; Monteiro, G.R.; Coutinho, J.F.; Lima, A.L.; Larson, M.; Wilson, G.; Grinnage-Pulley, T.; Bennett, C.; Mahachi, K.; Anderson, B.; et al. Comorbid infections induce progression of visceral leishmaniasis. Parasites Vectors 2019, 12, 54. [Google Scholar] [CrossRef] [PubMed]
  12. Little, S.; Braff, J.; Place, J.; Buch, J.; Dewage, B.G.; Knupp, A.; Beall, M. Canine Infection with Dirofilaria immitis, Borrelia burgdorferi, Anaplasma spp., and Ehrlichia spp. in the United States, 2013–2019. Parasites Vectors 2021, 14, 10. [Google Scholar] [CrossRef] [PubMed]
  13. Attipa, C.; Solano-Gallego, L.; Leutenegger, C.M.; Papasouliotis, K.; Soutter, F.; Balzer, J.; Carver, S.; Buch, J.S.; Tasker, S. Associations between Clinical Canine Leishmaniosis and Multiple Vector-Borne Co-Infections: A Case-Control Serological Study. BMC Vet. Res. 2019, 15, 331. [Google Scholar] [CrossRef]
  14. Miró, G.; Montoya, A.; Roura, X.; Gálvez, R.; Sainz, A. Seropositivity Rates for Agents of Canine Vector-Borne Diseases in Spain: A Multicentre Study. Parasites Vectors 2013, 6, 117. [Google Scholar] [CrossRef] [PubMed]
  15. Evaristo, A.M.C.; Santos, P.T.T.; Sé, F.S.; Collere, F.C.M.; Silva, B.B.; Cardoso, E.R.; Kakimori, M.T.A.; Vieira, T.S.W.J.; Krawczak, F.S.; Moraes-Filho, J.; et al. Co-infection by tick-borne pathogens and Leishmania spp. in dogs with clinical signs suggestive of leishmaniasis from an endemic area in northeastern Brazil. Pesqui. Veterinária Bras. 2024, 44, e07437. [Google Scholar] [CrossRef]
  16. De Sousa, K.C.M.; André, M.R.; Herrera, H.M.; de Andrade, G.B.; Jusi, M.M.G.; dos Santos, L.L.; Barreto, W.T.G.; Machado, R.Z.; de Oliveira, G.P. Molecular and Serological Detection of Tick-Borne Pathogens in Dogs from an Area Endemic for Leishmania infantum in Mato Grosso Do Sul, Brazil. Rev. Bras. Parasitol. Vet. 2013, 22, 525–531. [Google Scholar] [CrossRef] [PubMed]
  17. Blondel, J. Guilds or functional groups: Does it matter? Oikos 2003, 100, 223–231. [Google Scholar] [CrossRef]
  18. Lello, J.; Hussell, T. Functional group/guild modelling of inter-specific pathogen interactions: A potential tool for predicting the consequences of co-infection. Parasitology 2008, 135, 825–839. [Google Scholar] [CrossRef]
  19. Baxarias, M.; Álvarez-Fernández, A.; Martínez-Orellana, P.; Montserrat-Sangrà, S.; Ordeix, L.; Rojas, A.; Nachum-Biala, Y.; Baneth, G.; Solano-Gallego, L. Does co-infection with vector-borne pathogens play a role in clinical canine leishmaniosis? Parasites Vectors 2018, 11, 135. [Google Scholar] [CrossRef] [PubMed]
  20. Homer, M.J.; Aguilar-Delfin, I.; Telford III, S.R.; Krause, P.J.; Persing, D.H. Babesiosis. Clin. Microbiol. Rev. 2000, 13, 451–469. [Google Scholar] [CrossRef] [PubMed]
  21. Krawczak, F.D.S.; Reis, I.A.; Silveira, J.A.D.; Avelar, D.M.; Marcelino, A.P.; Werneck, G.L.; Labruna, M.B.; Paz, G.F. Leishmania, Babesia and Ehrlichia in urban pet dogs: Co-infection or cross-reaction in serological methods? Rev. Soc. Bras. Med. Trop. 2015, 48, 64–68. [Google Scholar] [CrossRef] [PubMed]
  22. Swanson, S.J.; Neitzel, D.; Reed, K.D.; Belongia, E.A. Coinfections acquired from Ixodes ticks. Clin. Microbiol. Rev. 2006, 19, 708–727. [Google Scholar] [CrossRef]
  23. Snelling, W.J.; Moore, J.E.; McKenna, J.P.; Lecky, D.M.; Dooley, J.S. Bacterial–protozoa interactions; an update on the role these phenomena play towards human illness. Microbes Infect. 2006, 8, 578–587. [Google Scholar] [CrossRef]
  24. Eriksson, K.I.; Thelaus, J.; Andersson, A.; Ahlinder, J. Microbial interactions—Underexplored links between public health relevant bacteria and protozoa in coastal environments. Front. Microbiol. 2022, 13, 877483. [Google Scholar] [CrossRef]
  25. Clarholm, M. Protozoan grazing of bacteria in soil—Impact and importance. Microb. Ecol. 1981, 7, 343–350. [Google Scholar] [CrossRef] [PubMed]
  26. Song, C.; Mazzola, M.; Cheng, X.; Oetjen, J.; Alexandrov, T.; Dorrestein, P.; Watrous, J.; van der Voort, M.; Raaijmakers, J.M. Molecular and chemical dialogues in bacteria-protozoa interactions. Sci. Rep. 2015, 5, 12837. [Google Scholar] [CrossRef]
  27. Gupta, R.; Rajendran, V.; Ghosh, P.C.; Srivastava, S. Assessment of anti-plasmodial activity of non-hemolytic, non-immunogenic, non-toxic antimicrobial peptides (AMPs LR14) produced by Lactobacillus plantarum LR/14. Drugs R&D 2014, 14, 95–103. [Google Scholar]
  28. Strle, K.; Sulka, K.B.; Pianta, A.; Crowley, J.T.; Arvikar, S.L.; Anselmo, A.; Sadreyev, R.; Steere, A.C. T-Helper 17 Cell Cytokine Responses in Lyme Disease Correlate with Borrelia burgdorferi Antibodies during Early Infection and with Autoantibodies Late in the Illness in Patients with Antibiotic-Refractory Lyme Arthritis. Clin. Infect. Dis. 2017, 64, 930–938. [Google Scholar] [CrossRef]
  29. Saha, S.; Basu, M.; Guin, S.; Gupta, P.; Mitterstiller, A.-M.; Weiss, G.; Jana, K.; Ukil, A. Leishmania donovani Exploits Macrophage Heme Oxygenase-1 To Neutralize Oxidative Burst and TLR Signaling–Dependent Host Defense. J. Immunol. 2019, 202, 827–840. [Google Scholar] [CrossRef]
  30. Djokic, V.; Akoolo, L.; Primus, S.; Schlachter, S.; Kelly, K.; Bhanot, P.; Parveen, N. Protozoan parasite Babesia microti subverts adaptive immunity and enhances Lyme disease severity. Front. Microbiol. 2019, 10, 1596. [Google Scholar] [CrossRef] [PubMed]
  31. Bowser, N.H.; Anderson, N.E. Dogs (Canis familiaris) as sentinels for human infectious disease and application to Canadian populations: A systematic review. Vet. Sci. 2018, 5, 83. [Google Scholar] [CrossRef] [PubMed]
  32. Cevidanes, A.; Di Cataldo, S.; Muñoz-San Martín, C.; Latrofa, M.S.; Hernández, C.; Cattan, P.E.; Otranto, D.; Millán, J. Co-infection patterns of vector-borne zoonotic pathogens in owned free-ranging dogs in central Chile. Vet. Res. Commun. 2023, 47, 575–585. [Google Scholar] [CrossRef] [PubMed]
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MDPI and ACS Style

Piloto-Sardiñas, E.; Cano-Argüelles, A.L.; Cabezas-Cruz, A. Borrelia, Leishmania, and Babesia: An Emerging Triad of Vector-Borne Co-Infections? Pathogens 2025, 14, 36. https://doi.org/10.3390/pathogens14010036

AMA Style

Piloto-Sardiñas E, Cano-Argüelles AL, Cabezas-Cruz A. Borrelia, Leishmania, and Babesia: An Emerging Triad of Vector-Borne Co-Infections? Pathogens. 2025; 14(1):36. https://doi.org/10.3390/pathogens14010036

Chicago/Turabian Style

Piloto-Sardiñas, Elianne, Ana Laura Cano-Argüelles, and Alejandro Cabezas-Cruz. 2025. "Borrelia, Leishmania, and Babesia: An Emerging Triad of Vector-Borne Co-Infections?" Pathogens 14, no. 1: 36. https://doi.org/10.3390/pathogens14010036

APA Style

Piloto-Sardiñas, E., Cano-Argüelles, A. L., & Cabezas-Cruz, A. (2025). Borrelia, Leishmania, and Babesia: An Emerging Triad of Vector-Borne Co-Infections? Pathogens, 14(1), 36. https://doi.org/10.3390/pathogens14010036

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