The Potential Impact of Density Dependent Fecundity on the Use of the Faecal Egg Count Reduction Test for Detecting Drug Resistance in Human Hookworms
The Potential Impact of Density Dependent Fecundity on the Use of the Faecal Egg Count Reduction Test for Detecting Drug Resistance in Human Hookworms
复制标题
DOI：
10.1371/journal.pntd.0000297
复制
发表时间：
2008-10-01
影响因子：
3.8
通讯作者：
Kopp, Steven R.
中科院分区：
文献类型：
--
作者：
Kotze, Andrew C.;Kopp, Steven R.
目前控制人类土壤传播蠕虫（STH）感染的努力涉及使用苯并咪唑和咪唑类药物对所有流行地区的人群，特别是儿童进行定期大规模治疗。鉴于家畜蛔虫对这些药物产生了高度耐药性，因此有必要监测药物在人类STH中的疗效。粪便虫卵计数减少试验（FECRT）是在药物治疗前后测量粪便虫卵排出量的一种方法，目前正在接受世卫组织的审查，作为检测耐药性出现的一种手段。我们已经研究了密度依赖的繁殖力FECRT数据的潜在影响。最近的证据与犬钩虫表明，密度依赖性产卵现象显示动态特性，在药物治疗的反应。这将影响药物疗效的测量，从而影响耐药性。在某些人类病例中，在FECRT药物治疗后存活的雌性蠕虫可能会通过与其治疗前水平相比显著增加其卵产量来响应密度依赖性限制对卵产量的放松。因此，这些病例将低估FECRT中的药物疗效。低估的程度将取决于特定宿主内蠕虫增加其卵产量的能力，这反过来又取决于药物治疗前其卵产量受到限制的程度。由于在拟定的FECRT之前，不同人类病例中的蠕虫可能以完全不同的密度存在，因此这种现象对药物疗效测量的影响可能在任何潜在的FECRT候选者组中差异很大。通过尝试确保参与单独FECRT的人群中一致的低估程度，可以改善相对药物疗效的测量。这可能部分是通过从FECRT中省略感染最严重的病例来实现的，因为这些病例在去除密度依赖性限制后可能最有可能增加其产蛋量。蠕虫生殖生物学的潜在影响的实用性的FECRT作为一种耐药检测工具，突出了需要开发新的耐药监测方法，检查直接药物作用于孤立的蠕虫与体外表型测定，或蠕虫基因型的变化。
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.