The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Combined ivermectin and doxycycline treatment has microfilaricidal and adulticidal activity against Dirofilaria immitis in experimentally infected dogs
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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In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
Citations
Cites
Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis
Hoerauf, A. M., Volkmann, L., Hamelmann, C., Adjei, O., Autenrieth, I. B., Fleischer, B., & Büttner, D. W. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02095-x · Cited by 310
Hoerauf, A. M., Specht, S., Büttner, M., Pfarr, K. M., Mand, S., Fimmers, R., Marfo‐Debrekyei, Y., Konadu, P., Debrah, A. Y., Bandi, C., et al. (2007) · Medical Microbiology and Immunology · doi:10.1007/s00430-007-0062-1 · Cited by 253
Self-citationBandi, C., McCall, J. W., Genchi, C., Corona, S., Venco, L., & Sacchi, L. (1999) · International Journal for Parasitology · doi:10.1016/s0020-7519(98)00200-8 · Cited by 250
Self-citationIs heartworm disease really spreading in Europe?
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Self-citationReversal of P-glycoprotein-associated multidrug resistance by ivermectin
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Macrofilaricidal effect of 4 weeks of treatment with doxycycline on Wuchereria bancrofti
Debrah, A. Y., Mand, S., Marfo‐Debrekyei, Y., Debrah, L. B., Pfarr, K. M., Büttner, M., Adjei, O., Büttner, D. W., & Hoerauf, A. M. (2007) · Tropical Medicine & International Health · doi:10.1111/j.1365-3156.2007.01949.x · Cited by 111
Kramer, L., Passeri, B., Corona, S., Simoncini, L., & Casiraghi, M. (2003) · Parasitology Research · doi:10.1007/s00436-002-0765-6 · Cited by 79
Self-citationGilbert, J., Nfon, C. K., Makepeace, B. L., Njongmeta, L. M., Hastings, I. M., Pfarr, K. M., Renz, A., Tanya, V. N., & Trees, A. J. (2005) · The Journal of Infectious Diseases · doi:10.1086/462426 · Cited by 76
Kavallaris, M., Madafiglio, J., Norris, M. D., & Haber, M. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.1013 · Cited by 39
Rajan, T. V. (2004) · American Journal of Tropical Medicine and Hygiene · doi:10.4269/ajtmh.2004.71.24 · Cited by 25
Cited by
Sorted by citations
Wolbachia: master manipulators of invertebrate biology
Werren, J. H., Baldo, L., & Clark, M. E. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1969 · Cited by 2,830
Chapter 4 Heartworm Disease in Animals and Humans
McCall, J. W., Genchi, C., Kramer, L. H., Guerrero, J., & Venco, L. (2008) · Advances in Parasitology · doi:10.1016/s0065-308x(08)00204-2 · Cited by 609
Self-citationCanine and feline cardiopulmonary parasitic nematodes in Europe: emerging and underestimated
Traversa, D., Di Cesare, A., & Conboy, G. (2010) · Parasites & Vectors · doi:10.1186/1756-3305-3-62 · Cited by 351
Vector-borne helminths of dogs and humans in Europe
Otranto, D., Dantas-Torres, F., Brianti, E., Traversa, D., Petrić, D., Genchi, C., & Capelli, G. (2013) · Parasites & Vectors · doi:10.1186/1756-3305-6-16 · Cited by 336
Self-citationHeartworm Biology, Treatment, and Control
Bowman, D. D., & Atkins, C. E. (2009) · Veterinary Clinics of North America: Small Animal Practice · doi:10.1016/j.cvsm.2009.06.003 · Cited by 298
Metadata
- 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.
- Venue
- International Journal for Parasitology
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 38
- Issue
- 12
- Pages
- 1401-1410
- ISSN
- 0020-7519 (ISSN-L)
- 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
- 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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