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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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Examination of N. americanus egg output data from Hill [18].A = egg output per female worm for the 93 human cases; x  = cases with <500 females (n = 82); ▪ = cases with >500 females (n = 11) (see text for details). B: Relationship between % FECR in response to treatment with a drug of known efficacy for the human cases in the < or > 500 female groups; ▪ dotted line: cases with pretreatment female numbers <500 (assuming no increase in egg output per female after treatment) (n = 82); ▾solid line: cases with pretreatment female numbers >500 (assuming post treatment egg output per female equals the median of the <500 group) (n = 11); ○ dashed line: all cases combined (n = 93). % FECR is based on a simple model in which the worms surviving the drug treatment in the >500 group from A are able to increase their egg output to match the median output of the <500 group from A, while the <500 output group show no change in output following drug treatment. Each data point represents mean±SE (n = 82, 11 or 93) (see text for details).
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pntd-0000297-g002: Examination of N. americanus egg output data from Hill [18].A = egg output per female worm for the 93 human cases; x  = cases with <500 females (n = 82); ▪ = cases with >500 females (n = 11) (see text for details). B: Relationship between % FECR in response to treatment with a drug of known efficacy for the human cases in the < or > 500 female groups; ▪ dotted line: cases with pretreatment female numbers <500 (assuming no increase in egg output per female after treatment) (n = 82); ▾solid line: cases with pretreatment female numbers >500 (assuming post treatment egg output per female equals the median of the <500 group) (n = 11); ○ dashed line: all cases combined (n = 93). % FECR is based on a simple model in which the worms surviving the drug treatment in the >500 group from A are able to increase their egg output to match the median output of the <500 group from A, while the <500 output group show no change in output following drug treatment. Each data point represents mean±SE (n = 82, 11 or 93) (see text for details).

Mentions: The production of eggs per day per female worm from the study of Hill [18] is shown in Figure 2A. The two trends noted earlier as common to such egg output data are apparent, namely, 1) as the number of worms harboured increases there is a decrease in the number of eggs produced per female, with no cases of high egg production per female occurring at high worm densities (>500 females per person), and 2) at lower densities (<500 females per person) there is a large degree of variation in egg production between females. Egg production per day per female at densities less than 500 females varied from 351 to 11,904.


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)

Examination of N. americanus egg output data from Hill [18].A = egg output per female worm for the 93 human cases; x  = cases with <500 females (n = 82); ▪ = cases with >500 females (n = 11) (see text for details). B: Relationship between % FECR in response to treatment with a drug of known efficacy for the human cases in the < or > 500 female groups; ▪ dotted line: cases with pretreatment female numbers <500 (assuming no increase in egg output per female after treatment) (n = 82); ▾solid line: cases with pretreatment female numbers >500 (assuming post treatment egg output per female equals the median of the <500 group) (n = 11); ○ dashed line: all cases combined (n = 93). % FECR is based on a simple model in which the worms surviving the drug treatment in the >500 group from A are able to increase their egg output to match the median output of the <500 group from A, while the <500 output group show no change in output following drug treatment. Each data point represents mean±SE (n = 82, 11 or 93) (see text for details).
© Copyright Policy
Related In: Results  -  Collection

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

pntd-0000297-g002: Examination of N. americanus egg output data from Hill [18].A = egg output per female worm for the 93 human cases; x  = cases with <500 females (n = 82); ▪ = cases with >500 females (n = 11) (see text for details). B: Relationship between % FECR in response to treatment with a drug of known efficacy for the human cases in the < or > 500 female groups; ▪ dotted line: cases with pretreatment female numbers <500 (assuming no increase in egg output per female after treatment) (n = 82); ▾solid line: cases with pretreatment female numbers >500 (assuming post treatment egg output per female equals the median of the <500 group) (n = 11); ○ dashed line: all cases combined (n = 93). % FECR is based on a simple model in which the worms surviving the drug treatment in the >500 group from A are able to increase their egg output to match the median output of the <500 group from A, while the <500 output group show no change in output following drug treatment. Each data point represents mean±SE (n = 82, 11 or 93) (see text for details).
Mentions: The production of eggs per day per female worm from the study of Hill [18] is shown in Figure 2A. The two trends noted earlier as common to such egg output data are apparent, namely, 1) as the number of worms harboured increases there is a decrease in the number of eggs produced per female, with no cases of high egg production per female occurring at high worm densities (>500 females per person), and 2) at lower densities (<500 females per person) there is a large degree of variation in egg production between females. Egg production per day per female at densities less than 500 females varied from 351 to 11,904.

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