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American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility?
J Infect Dis. 2006 Oct 15; 194(8):1168-75.JI

Abstract

BACKGROUND

Antimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes.

METHODS

Thirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined.

RESULTS

We observed 29 SbV-resistant isolates among 4 species of subgenus Viannia, most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy.

CONCLUSION

Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors.

Authors+Show Affiliations

London School of Hygiene and Tropical Medicine, Department of Infectious and Tropical Diseases, London, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16991093

Citation

Yardley, Vanessa, et al. "American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility?" The Journal of Infectious Diseases, vol. 194, no. 8, 2006, pp. 1168-75.
Yardley V, Ortuno N, Llanos-Cuentas A, et al. American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility? J Infect Dis. 2006;194(8):1168-75.
Yardley, V., Ortuno, N., Llanos-Cuentas, A., Chappuis, F., Doncker, S. D., Ramirez, L., Croft, S., Arevalo, J., Adaui, V., Bermudez, H., Decuypere, S., & Dujardin, J. C. (2006). American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility? The Journal of Infectious Diseases, 194(8), 1168-75.
Yardley V, et al. American Tegumentary Leishmaniasis: Is Antimonial Treatment Outcome Related to Parasite Drug Susceptibility. J Infect Dis. 2006 Oct 15;194(8):1168-75. PubMed PMID: 16991093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - American tegumentary leishmaniasis: Is antimonial treatment outcome related to parasite drug susceptibility? AU - Yardley,Vanessa, AU - Ortuno,Nimer, AU - Llanos-Cuentas,Alejandro, AU - Chappuis,Francois, AU - Doncker,Simonne De, AU - Ramirez,Luis, AU - Croft,Simon, AU - Arevalo,Jorge, AU - Adaui,Vanessa, AU - Bermudez,Hernan, AU - Decuypere,Saskia, AU - Dujardin,Jean-Claude, Y1 - 2006/09/08/ PY - 2006/05/11/received PY - 2006/06/27/accepted PY - 2006/9/23/pubmed PY - 2006/11/15/medline PY - 2006/9/23/entrez SP - 1168 EP - 75 JF - The Journal of infectious diseases JO - J Infect Dis VL - 194 IS - 8 N2 - BACKGROUND: Antimonials are the first drug of choice for the treatment of American tegumentary leishmaniasis (ATL); however, their efficacy is not predictable, and this may be linked to parasite drug resistance. We aimed to characterize the in vitro antimony susceptibility of clinical isolates of Peruvian patients with ATL who were treated with sodium stibogluconate and to correlate this in vitro phenotype with different treatment outcomes. METHODS: Thirty-seven clinical isolates were obtained from patients with known disease and treatment histories. These isolates were typed, and the susceptibility of intracellular amastigotes to pentavalent (SbV) and trivalent (SbIII) antimonials was determined. RESULTS: We observed 29 SbV-resistant isolates among 4 species of subgenus Viannia, most of which exhibited primary resistance; isolates resistant only to SbIII; and 3 combinations of in vitro phenotypes: (1) parasites sensitive to both drugs, (2) parasites resistant to both drugs, and (3) parasites resistant to SbV only (the majority of isolates fell into this category). There was no correlation between in vitro susceptibility to both antimonials and the clinical outcome of therapy. CONCLUSION: Antimony insensitivity might occur in a stepwise fashion (first to SbV and then to SbIII). Our data question the definition of true parasite resistance to antimonials. Further studies of treatment efficacy should apply standardized protocols and definitions and should also consider host factors. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/16991093/American_tegumentary_leishmaniasis:_Is_antimonial_treatment_outcome_related_to_parasite_drug_susceptibility L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/507710 DB - PRIME DP - Unbound Medicine ER -