BackgroundThe three major soil-transmitted helminths (STH) Ascaris
lumbricoides, Trichuris trichiura and
Necator americanus/Ancylostoma duodenale are among the
most widespread parasites worldwide. Despite the global expansion of
preventive anthelmintic treatment, standard operating procedures to monitor
anthelmintic drug efficacy are lacking. The objective of this study,
therefore, was to define the efficacy of a single 400 milligram dose of
albendazole (ALB) against these three STH using a standardized protocol.Methodology/Principal FindingsSeven trials were undertaken among school children in Brazil, Cameroon,
Cambodia, Ethiopia, India, Tanzania and Vietnam. Efficacy was assessed by
the Cure Rate (CR) and the Fecal Egg Count Reduction (FECR) using the
McMaster egg counting technique to determine fecal egg counts (FEC).
Overall, the highest CRs were observed for A. lumbricoides
(98.2%) followed by hookworms (87.8%) and T.
trichiura (46.6%). There was considerable variation in
the CR for the three parasites across trials (country), by age or the
pre-intervention FEC (pre-treatment). The latter is probably the most
important as it had a considerable effect on the CR of all three STH.
Therapeutic efficacies, as reflected by the FECRs, were very high for
A. lumbricoides (99.5%) and hookworms
(94.8%) but significantly lower for T. trichiura
(50.8%), and were affected to different extents among the 3 species
by the pre-intervention FEC counts and trial (country), but not by sex or
age.Conclusions/SignificanceOur findings suggest that a FECR (based on arithmetic means) of
>95% for A. lumbricoides and >90% for
hookworms should be the expected minimum in all future surveys, and that
therapeutic efficacy below this level following a single dose of ALB should
be viewed with concern in light of potential drug resistance. A standard
threshold for efficacy against T. trichiura has yet to be
established, as a single-dose of ALB is unlikely to be satisfactory for this
parasite.Trial RegistrationClinicalTrials.gov NCT01087099
This protocol is an extension to: Nat. Protoc. 5, 503-515 (2010); doi: 10.1038/nprot.2009.235; published online 25 February 2010The FLOTAC is a sensitive, accurate, and precise technique for the diagnosis of protozoan and helminth infections in humans and animals. However, it requires centrifugation, and hence might be out of reach in resource-constrained settings. As an extension of the original FLOTAC protocol, this protocol describes the Mini-FLOTAC technique, a logical evolution of FLOTAC conceived to perform multivalent, qualitative, and quantitative diagnosis of helminth and protozoan infections in human and animal feces, and urine. This has been found to be of most use in the processing of large numbers of samples with rapid laboratory workup, and for veterinary applications directly on-farm. In addition to the Mini-FLOTAC apparatus, we describe the use of the Fill-FLOTAC, a closed system used to facilitate the performance of the first four consecutive steps of the Mini-FLOTAC technique: fecal sample collection and weighing, homogenization, filtration, and filling of the Mini-FLOTAC chambers. Processing of an individual sample using this protocol requires ∼12 min.
The major human soil-transmitted helminths (STH), Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura have a marked impact on human health in many parts of the world. Current efforts to control these parasites rely predominantly on periodic mass administration of anthelmintic drugs to school age children and other at-risk groups. After many years of use of these same drugs for controlling roundworms in livestock, high levels of resistance have developed, threatening the sustainability of these livestock industries in some locations. Hence, the question arises as to whether this is likely to also occur in the human STH, thereby threatening our ability to control these parasites. This is particularly important because of the recent increase in mass control programmes, relying almost exclusively on benzimidazole anthelmintics. It will be important to ensure that resistance is detected as it emerges in order to allow the implementation of mitigation strategies, such as use of drug combinations, to ensure that the effectiveness of the few existing anthelmintic drugs is preserved. In this review we address these issues by firstly examining the efficacy of anthelmintics against the human STH, and assessing whether there are any indications to date that resistance has emerged. We then consider the factors that influence the effect of current drug-use patterns in selecting for resistant parasite populations. We describe the tools currently available for resistance monitoring (field-based coprological methods), and those under development (in vitro bioassays and molecular tests), and highlight confounding factors that need to be taken into account when interpreting such resistance-monitoring data. We then highlight means to ensure that the currently available tools are used correctly, particularly with regard to study design, and we set appropriate drug-efficacy thresholds. Finally, we make recommendations for monitoring drug efficacy in the field, as components of control programmes, in order to maximise the ability to detect drug resistance, and if it arises to change control strategy and prevent the spread of resistance.
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