Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

M. Mamman, G. Gettinby, N.B. Murphy, S. Kemei, A.S. Peregrine

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These findings indicate that the majority of the relapse trypanosomes were susceptible to the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size, Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.
LanguageEnglish
Pages1107-1113
Number of pages6
JournalAntimicrobial Agents and Chemotherapy
Volume39
Issue number5
Publication statusPublished - May 1995

Fingerprint

Diminazene
Trypanosoma congolense
Trypanosomiasis
Population
Pharmaceutical Preparations
Body Weight
diminazene aceturate
Likelihood Functions
Recurrence
Infection
Parasites

Keywords

  • trypanzoon brucei brucei
  • pentamidine transport
  • cattle
  • mice
  • pharmacokinetics
  • clones
  • diamidines

Cite this

@article{97e2d6150d364356958b3d1dc4500ecc,
title = "Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate",
abstract = "The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100{\%} infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These findings indicate that the majority of the relapse trypanosomes were susceptible to the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size, Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.",
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author = "M. Mamman and G. Gettinby and N.B. Murphy and S. Kemei and A.S. Peregrine",
year = "1995",
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Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate. / Mamman, M.; Gettinby, G.; Murphy, N.B.; Kemei, S.; Peregrine, A.S.

In: Antimicrobial Agents and Chemotherapy , Vol. 39, No. 5, 05.1995, p. 1107-1113.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate

AU - Mamman, M.

AU - Gettinby, G.

AU - Murphy, N.B.

AU - Kemei, S.

AU - Peregrine, A.S.

PY - 1995/5

Y1 - 1995/5

N2 - The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These findings indicate that the majority of the relapse trypanosomes were susceptible to the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size, Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.

AB - The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These findings indicate that the majority of the relapse trypanosomes were susceptible to the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size, Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.

KW - trypanzoon brucei brucei

KW - pentamidine transport

KW - cattle

KW - mice

KW - pharmacokinetics

KW - clones

KW - diamidines

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M3 - Article

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EP - 1113

JO - Antimicrobial Agents and Chemotherapy

T2 - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 5

ER -