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The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms.

Kotze AC, Kopp SR - PLoS Negl Trop Dis (2008)

Bottom Line: It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels.As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates.The potential impact of worm reproductive biology on the utility of the FECRT as a resistance detection tool highlights the need to develop new drug resistance monitoring methods which examine either direct drug effects on isolated worms with in vitro phenotypic assays, or changes in worm genotypes.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Livestock Industries, St. Lucia, Brisbane, Queensland, Australia. andrew.kotze@csiro.au

ABSTRACT
Current efforts to control human soil-transmitted helminth (STH) infections involve the periodic mass treatment of people, particularly children, in all endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that high levels of resistance have developed to these same drugs in roundworms of livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg count reduction test (FECRT), in which faecal egg output is measured pre- and post-drug treatment, is presently under examination by WHO as a means of detecting the emergence of resistance. We have examined the potential impact of density dependent fecundity on FECRT data. Recent evidence with the canine hookworm indicates that the density dependent egg production phenomenon shows dynamic properties in response to drug treatment. This will impact on measurements of drug efficacy, and hence drug resistance. It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels. These cases will therefore underestimate drug efficacy in the FECRT. The degree of underestimation will depend on the ability of the worms within particular hosts to increase their egg output, which will in turn depend on the extent to which their egg output is constrained prior to the drug treatment. As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates. Measurement of relative drug efficacy may be improved by attempting to ensure a consistent degree of underestimation in groups of people involved in separate FECRTs. This may be partly achieved by omission of cases with the heaviest infections from a FECRT, as these cases may have the greatest potential to increase their egg output upon removal of density dependent constraints. The potential impact of worm reproductive biology on the utility of the FECRT as a resistance detection tool highlights the need to develop new drug resistance monitoring methods which examine either direct drug effects on isolated worms with in vitro phenotypic assays, or changes in worm genotypes.

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Increased egg output by canine hookworms surviving a drug treatment.Analysis of the data of Kopp et al. [7] to indicate changes in egg production by A. caninum worms surviving a treatment of their host animals with pyrantel. Dogs 1 and 2 were infected with an isolate of high level resistance to the drug, while dogs 3 and 4 were infected with an isolate showing low level resistance; * = prior to drug treatment, x = 6 days after treatment.
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pntd-0000297-g001: Increased egg output by canine hookworms surviving a drug treatment.Analysis of the data of Kopp et al. [7] to indicate changes in egg production by A. caninum worms surviving a treatment of their host animals with pyrantel. Dogs 1 and 2 were infected with an isolate of high level resistance to the drug, while dogs 3 and 4 were infected with an isolate showing low level resistance; * = prior to drug treatment, x = 6 days after treatment.

Mentions: Figure 1 shows an analysis of the egg output and adult worm numbers for the 4 dogs before and after treatment with pyrantel using the data of Kopp et al. [7]. Dogs 1 and 2 were infected with worms from an isolate with a high level of resistance to the drug, while dogs 3 and 4 were infected with an isolate which showed only a low level of resistance. All four dogs had similar worm burdens before the drug treatment, and all showed very similar rates of egg production per adult worm. Following drug treatment, all dogs showed an increase in their egg output per worm alongside reductions in worm numbers. The change in worm reproductive output was most dramatic for dogs 3 and 4 which increased egg output per worm by 4.2- and 3.6-fold, respectively.


The potential impact of density dependent fecundity on the use of the faecal egg count reduction test for detecting drug resistance in human hookworms.

Kotze AC, Kopp SR - PLoS Negl Trop Dis (2008)

Increased egg output by canine hookworms surviving a drug treatment.Analysis of the data of Kopp et al. [7] to indicate changes in egg production by A. caninum worms surviving a treatment of their host animals with pyrantel. Dogs 1 and 2 were infected with an isolate of high level resistance to the drug, while dogs 3 and 4 were infected with an isolate showing low level resistance; * = prior to drug treatment, x = 6 days after treatment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2553282&req=5

pntd-0000297-g001: Increased egg output by canine hookworms surviving a drug treatment.Analysis of the data of Kopp et al. [7] to indicate changes in egg production by A. caninum worms surviving a treatment of their host animals with pyrantel. Dogs 1 and 2 were infected with an isolate of high level resistance to the drug, while dogs 3 and 4 were infected with an isolate showing low level resistance; * = prior to drug treatment, x = 6 days after treatment.
Mentions: Figure 1 shows an analysis of the egg output and adult worm numbers for the 4 dogs before and after treatment with pyrantel using the data of Kopp et al. [7]. Dogs 1 and 2 were infected with worms from an isolate with a high level of resistance to the drug, while dogs 3 and 4 were infected with an isolate which showed only a low level of resistance. All four dogs had similar worm burdens before the drug treatment, and all showed very similar rates of egg production per adult worm. Following drug treatment, all dogs showed an increase in their egg output per worm alongside reductions in worm numbers. The change in worm reproductive output was most dramatic for dogs 3 and 4 which increased egg output per worm by 4.2- and 3.6-fold, respectively.

Bottom Line: It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels.As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates.The potential impact of worm reproductive biology on the utility of the FECRT as a resistance detection tool highlights the need to develop new drug resistance monitoring methods which examine either direct drug effects on isolated worms with in vitro phenotypic assays, or changes in worm genotypes.

View Article: PubMed Central - PubMed

Affiliation: CSIRO Livestock Industries, St. Lucia, Brisbane, Queensland, Australia. andrew.kotze@csiro.au

ABSTRACT
Current efforts to control human soil-transmitted helminth (STH) infections involve the periodic mass treatment of people, particularly children, in all endemic areas, using benzimidazole and imidothiazole drugs. Given the fact that high levels of resistance have developed to these same drugs in roundworms of livestock, there is a need to monitor drug efficacy in human STHs. The faecal egg count reduction test (FECRT), in which faecal egg output is measured pre- and post-drug treatment, is presently under examination by WHO as a means of detecting the emergence of resistance. We have examined the potential impact of density dependent fecundity on FECRT data. Recent evidence with the canine hookworm indicates that the density dependent egg production phenomenon shows dynamic properties in response to drug treatment. This will impact on measurements of drug efficacy, and hence drug resistance. It is likely that the female worms that survive a FECRT drug treatment in some human cases will respond to the relaxation of density dependent constraints on egg production by increasing their egg output significantly compared to their pre-treatment levels. These cases will therefore underestimate drug efficacy in the FECRT. The degree of underestimation will depend on the ability of the worms within particular hosts to increase their egg output, which will in turn depend on the extent to which their egg output is constrained prior to the drug treatment. As worms within different human cases will likely be present at quite different densities prior to a proposed FECRT, there is potential for the effects of this phenomenon on drug efficacy measurements to vary considerably within any group of potential FECRT candidates. Measurement of relative drug efficacy may be improved by attempting to ensure a consistent degree of underestimation in groups of people involved in separate FECRTs. This may be partly achieved by omission of cases with the heaviest infections from a FECRT, as these cases may have the greatest potential to increase their egg output upon removal of density dependent constraints. The potential impact of worm reproductive biology on the utility of the FECRT as a resistance detection tool highlights the need to develop new drug resistance monitoring methods which examine either direct drug effects on isolated worms with in vitro phenotypic assays, or changes in worm genotypes.

Show MeSH
Related in: MedlinePlus