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

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. +1 more·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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Crossref · 10.1016/j.ijpara.2008.03.002

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  • A combination of doxycycline (10 mg/kg die for 30 days) and ivermectin (6 mcg/kg every 15 days for 6 months) has a potential efficacy, as high as 73%, in the adulticide therapy in dogs infested with Dirofilaria immitis.

    “Therefore, it has been suggested that a combination of doxycycline (10 mg/kg die for 30 days) and ivermectin (6 mcg/kg every 15 days for 6 months) has a potential efficacy, as high as 73%, in the adulticide therapy in dogs infested with D. immitis[107,108].”

    From Vector-borne helminths of dogs and humans in Europe (2013) · cites this paper as [107]

  • Unnoticed cases of dirofilarial infections are very common in dogs due to a long prepotency and many asymptomatic courses.

    “As unnoticed cases of dirofilarial infections are very common in dogs due to a long prepotency and many asymptomatic courses, the zoonotic potential of D. immitis should not be underestimated [52,53].”

    From The Incidence of Dirofilaria immitis in Shelter Dogs and Mosquitoes in Austria (2021) · cites this paper as [52]

  • Dirofilariosis is a non-negligible risk to animal and human health.

    “Thus, it is a non-negligible risk to animal and human health (Bazzocchi et al. 2008; Kartashev et al. 2017).”

    From Current trends in canine dirofilariosis in Austria-do we face a pre-endemic status? (2020) · cites this paper as Bazzocchi et al. 2008

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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
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
  • Health Sciences › Veterinary › Small Animals › 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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