The study by Kopp et al. 
suggests that the reproductive behaviour of adult hookworms before and after a drug treatment will likely be far from static. The significant increase in egg production by the worms following drug treatment is most likely a consequence of the relaxation of density dependent constraints on their egg output. The degree to which egg output increased coincided with the extent to which the worm populations were reduced by the drug treatment in the dogs harbouring the two worm isolates showing different levels of resistance to the drug. Given the widespread occurrence of density dependent worm fecundity constraints in human STHs 
it is most likely that the phenomenon noted here with the canine hookworm will apply more widely to the human STHs.
The effect of the host immune response on fecundity in S. ratti
has been demonstrated to be reversible 
, with the immune mediated constraints on egg production being quickly reversed upon removal or suppression of the host immune effects. The time scale of the reversibility in these studies is similar to that in the report of Kopp et al. 
(6 days), and as would occur in a FECRT (approximately 10 days between drug treatment and faecal egg count). However, the role of host immune mechanisms in the increased fecundity observed by Kopp et al. 
is unclear as no specific suppression or removal of host immunity was imposed as in the experiments described above for S. ratti
It is likely that among a group of people involved in a FECRT will be some cases in which female worms are producing more eggs post-treatment than they did prior to the drug treatment due to the relaxation of density constraints following the drug treatment. Therefore epg in these cases would be expected to decrease by a lower percentage than worm burden in response to the drug. Hence, a comparison of epg before and after drug treatment will underestimate efficacy. For dogs 3 and 4 from Kopp et al. 
removal of 71% of the worm burden by the drug was associated with an increase in epg of 41%. The degree to which an increase in fecundity can distort FECRT data will depend on the extent to which the egg production of female worms is constrained prior to the FECRT. It is clear that while worms which are constrained in their egg output by density-dependent effects prior to the treatment will have the potential for increasing their egg output per worm as worm numbers decrease, cases whose worms are at low densities and hence may be producing eggs at nearer to their reproductive potential within that host prior to the drug, will have a significantly lower scope to further increase egg output. It can be seen from that the overall FECR data from a pool of cases will depend on the relative proportions of worms that are able to increase egg output significantly in response to drug treatment, compared to those which do show little or no change, and the extent of any output increases in individual cases. For FECRT data to be a useful tool for detecting changes in drug efficacy (that is, drug resistance), it is important for such population based variables to be minimised. If FECRTs are conducted on populations with similar balances of cases which show a presence or absence of relaxation of egg output constraints, then they will be comparable despite the % FECR values underestimating actual drug efficacy. However, if the degree of pre-treatment constraint is different between two populations, then the potential exists for % FECR values to falsely indicate different drug efficacy between the two populations.
Removal of the most heavily infected human cases whose worm populations are significantly constrained by density dependent effects from a FECRT study would seem desirable in order to reduce the potential distorting effects that relaxation of the constraints in these cases may have on the FECRT data. Anderson and Schad 
, working with mixed infections of N. americanus
and A. duodenale
, showed that, although density dependent fecundity resulted in a poor relationship between epg and worm burden, it was possible to discriminate between people with very low and very high infections on the basis of epg. This indicates that omission of high burden cases with potential to distort FECRTs would be possible. However, our analysis of the Hill  N. americanus
data set in this regard shows that such selection of suitable candidates for a FECRT may not always be so clear. For the Hill 
dataset, omission of the highest epg cases would not result in preferential removal of the highest worm burden cases (from ). It is apparent that the increase in fecundity seen at lower worm burdens is of such a magnitude that the total egg output by these less dense populations (as measured by epg) can greatly exceed that of populations containing significantly higher numbers of worms. However, for the Hill 
data set, as the epg cut-off for omission from a FECRT was further reduced, the removal of most heavy infections was evident (). A negative outcome is that many lighter infection cases were also removed. The cost, in terms of necessitating the omission of many apparently ‘unconstrained’ populations, may be outweighed by the benefit of removing the potential distorting effects of the heavy infection cases. Decisions on omission of cases for FECRTs may depend on local infection levels, and availability of suitable numbers of people to satisfy the statistical requirements of the test. Further study may identify epg cut-off values that could be applied widely to FECRTs.
The FECRT is used in livestock industries as a measure of drug resistance. The question arises as to whether the density dependent effects we have described will have a significant potential to distort FECRTs with the human parasites given the acceptance of the utility of the test for livestock. While reports on some livestock species have shown an absence of density dependent effects 
, other livestock species show strong density dependence (for example, Teladorsagia circumcincta 
). A difference in the application of FECRTs to livestock and humans, which may influence the impact of density dependency, is the efficacy levels of anthelmintics in the two systems. In livestock, the expected drug efficacy for susceptible parasites is greater than 99%. Resistance is suspected if this value drops below 95% (and if the lower 95% confidence interval is below 90%) 
. Hence, very little of a susceptible worm population within each host is expected to survive the drug treatment, leaving little scope for egg output in the remaining worms to be significantly amplified by relaxation of density dependent constraints. Hence, a susceptible worm population is clearly indicated by the test. The effect of a relaxation of density dependent fecundity constraints in amplifying egg counts from worms remaining after drug treatment may only be expected if a significant proportion of the population is drug resistant. In humans, however, the situation is quite different. Efficacies for some human anthelmintics would never have originally met the criteria required by the livestock FECRT as indicating susceptibility, suggesting the use of suboptimal dosing regimes in some cases. While egg reduction rates for A. lumbricoides
after treatment with albendazole or mebendazole are generally close to 100%, the values for hookworms and Trichuris
are much lower 
. For example, in the analysis of a number of studies by Keiser and Utzinger 
, hookworm egg reduction rates in response to albendazole varied form 64.2% to 100%, with an overall cure rate of 78.4%. Hence, with significant proportions of susceptible worms expected to survive current treatment regimes, the capacity for the relaxation of fecundity constraints in drug susceptible worms to distort efficacy measurements may be significantly greater than would be expected for the livestock parasite species.
Given the potential for distortion of FECRT data by density dependent fecundity, it may be difficult to identify apparent drug efficacy changes (that is, the development of drug resistance) amongst a background of dynamic female worm reproductive biology. The impact of worm biology on the utility of the FECRT as a resistance detection tool highlights the need to remove this influence by developing methods which examine either direct drug effects on isolated worms with in vitro phenotypic assays, or changes in worm genotypes, as drug resistance monitoring tools.