Cited by 172Parasitic Diseases Research and TreatmentHelminth infection and controlResearch on Leishmaniasis Studies

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Combined ivermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimentally infected dogs

Bazzocchi, C., Mortarino, M., Grandi, G., Kramer, L.H., Genchi, C., Bandi, C., Genchi, M., Sacchi, L., McCall, J.W.·2008·International Journal for Parasitology

DOI 10.1016/j.ijpara.2008.03.002

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Abstract

There is still a pressing need for effective adulticide treatment for human and animal filarial infections. Like many filarial nematodes, Dirofilaria immitis, the causative agent of canine heartworm disease, harbours the bacterial endosymbiont Wolbachia, which has been shown to be essential for worm development, fecundity and survival. Here the authors report the effect of different treatment regimens in dogs experimentally infected with adult D. immitis on microfilariemia, antigenemia, worm recovery and Wolbachia content. Treatment with ivermectin (IVM; 6 microg/kg per os weekly) combined with doxycycline (DOXY; 10 mg/kg/day orally from Weeks 0-6, 10-12, 16-18, 22-26 and 28-34) resulted in a significantly faster decrease of circulating microfilariae and higher adulticidal activity compared with either IVM or DOXY alone. Quantitative PCR analysis of ftsZ (Wolbachia DNA) and 18S rDNA (nematode DNA) absolute copy numbers showed significant decreases in Wolbachia content compared with controls in worms recovered from DOXY-treated dogs that were not, however, associated with worm death. Worms from IVM/DOXY-treated dogs, on the other hand, had Wolbachia/nematode DNA ratios similar to those of control worms, suggesting a loss of both Wolbachia and nematode DNA as indicated by absolute copy number values. Histology and transmission electron microscopy of worms recovered from the IVM/DOXY combination group showed complete loss of uterine content in females and immunohistochemistry for Wolbachia was negative. Results indicate that the combination of these two drugs causes adult worm death. This could have important implications for control of human and animal filarial infections.

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Jacobson, L. S., DiGangi, B. A., Serrano, M. A., Friedman, J., Cuccinello, M. K., Garcia, H. M., & Levy, J. K. (2026) · Parasites & Vectors · doi:10.1186/s13071-026-07344-x · Cited by 1
The history of Wolbachia and heartworm
Vismarra, A., Fozzer, M., McCall, J. W., Genchi, M., Venco, L., García, R. M., Bazzocchi, C., Genchi, C., Kramer, L., & Bandi, C. (2026) · Parasites & Vectors · doi:10.1186/s13071-026-07397-y
Self-citation
Blocking Dirofilaria immitis transmission by treatment of heartworm microfilaremic dogs with doxycycline
McCall, J. W., Mansour, A., DiCosty, U., Fricks, C., McCall, S. D., Carson, B., Dzimianski, M. T., Nelson, C. T., & Moorhead, A. R. (2026) · Parasites & Vectors · doi:10.1186/s13071-026-07383-4
Self-citation
Estudo retrospetivo da prevalência de cardiopatias adquiridas no cão: comparação entre Hospital Veterinário da UTAD e Hospital Veterinário Clinicão
Pinto, I. F. T. (2013) · Repository of UTAD (Universidad De Tras-os Montes e Alto Douro)

Authors: Bazzocchi, C., Mortarino, M., Grandi, G., Kramer, L. H., Genchi, C., Bandi, C., Genchi, M., Sacchi, L., & McCall, J. W.
Affiliations: University of Milan (IT)
University of Parma (IT)
University of Pavia (IT)
University of Georgia (US)
Corresponding author: Kramer, L.H.
ORCID: Bazzocchi, C.
Mortarino, M.
Grandi, G.
Kramer, L.H.
Bandi, C.
Genchi, M.
Sacchi, L.
Venue: International Journal for Parasitology
Publisher: Elsevier BV
Published: 2008-10
Volume: 38
Issue: 12
Pages: 1401-1410
ISSN: 0020-7519 (ISSN-L)
DOI: 10.1016/j.ijpara.2008.03.002
OpenAlex: W2157661246
Cited by: 170
References: 12
Citations by year: 2026: 8 · 2025: 9 · 2024: 5 · 2023: 13 · 2022: 8 · 2021: 8 · 2020: 17 · 2019: 9 · 2018: 8 · 2017: 12 · 2016: 5 · 2015: 11 · 2014: 9 · 2013: 10 · 2012: 5
FWCI: 7.04
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: International Journal for Parasitology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Life Sciences › Immunology and Microbiology › Parasitology › Helminth infection and control
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Research on Leishmaniasis Studies
Keywords: Dirofilaria immitis, canine heartworm disease, ivermectin, doxycycline, combination therapy, adulticidal activity, microfilaricidal activity, Wolbachia, endosymbiotic bacteria, filarial nematodes, antigenemia, FtsZ, 18S rDNA
MeSH terms: Animals, Anti-Bacterial Agents, Antigens, Helminth, Dirofilaria immitis, Dirofilariasis, Dog Diseases, Dogs, Doxycycline, Filaricides, Immunohistochemistry, Ivermectin, Microfilariae, Polymerase Chain Reaction, Wolbachia

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Combined ivermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimentally infected dogs

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