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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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Related in: MedlinePlus

An examination of epg prior to drug treatment as a predictor of the level of density dependent fecundity constraint imposed on worm populations using the data set of Hill [18].Parts A, B, C highlight cases with epg >10,000, >5,000, or >2,500, respectively, as ▪; all other cases are shown as x.
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pntd-0000297-g003: An examination of epg prior to drug treatment as a predictor of the level of density dependent fecundity constraint imposed on worm populations using the data set of Hill [18].Parts A, B, C highlight cases with epg >10,000, >5,000, or >2,500, respectively, as ▪; all other cases are shown as x.

Mentions: Figure 3 highlights the cases from Hill [18] which fall into various epg groupings in order to demonstrate the effect of using such pre-treatment epg values to select appropriate candidates for a FECRT. It is apparent that the highest epg cases (epg >10,000, n = 10) do not coincide with the heaviest infection levels (Figure 3A). As the epg cut-off decreases, the highest infection level cases are mostly highlighted, alongside many cases with much lower infection levels (Figures 3B, 3C). For this data set, removal of most of the heaviest infections (ie. >500 females) from a FECRT would require the omission of all cases with epg >2,500, representing the additional omission of many low infection (<500 female) cases. It is clear that the relationship between egg output for each human case (ie, epg) and infection level (number of females) is poor due to the extent to which egg output per female can increase at low worm densities.


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)

An examination of epg prior to drug treatment as a predictor of the level of density dependent fecundity constraint imposed on worm populations using the data set of Hill [18].Parts A, B, C highlight cases with epg >10,000, >5,000, or >2,500, respectively, as ▪; all other cases are shown as x.
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000297-g003: An examination of epg prior to drug treatment as a predictor of the level of density dependent fecundity constraint imposed on worm populations using the data set of Hill [18].Parts A, B, C highlight cases with epg >10,000, >5,000, or >2,500, respectively, as ▪; all other cases are shown as x.
Mentions: Figure 3 highlights the cases from Hill [18] which fall into various epg groupings in order to demonstrate the effect of using such pre-treatment epg values to select appropriate candidates for a FECRT. It is apparent that the highest epg cases (epg >10,000, n = 10) do not coincide with the heaviest infection levels (Figure 3A). As the epg cut-off decreases, the highest infection level cases are mostly highlighted, alongside many cases with much lower infection levels (Figures 3B, 3C). For this data set, removal of most of the heaviest infections (ie. >500 females) from a FECRT would require the omission of all cases with epg >2,500, representing the additional omission of many low infection (<500 female) cases. It is clear that the relationship between egg output for each human case (ie, epg) and infection level (number of females) is poor due to the extent to which egg output per female can increase at low worm densities.

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