Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
PLoS Negl Trop Dis ; 17(5): e0011071, 2023 05.
Article in English | MEDLINE | ID: mdl-37196017

ABSTRACT

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.


Subject(s)
Helminthiasis , Helminths , Animals , Humans , Ascaris lumbricoides , Feces , Helminthiasis/drug therapy , Helminthiasis/diagnosis , Sensitivity and Specificity , Soil , Trichuris
2.
Parasit Vectors ; 15(1): 166, 2022 May 12.
Article in English | MEDLINE | ID: mdl-35549990

ABSTRACT

BACKGROUND: Due to high prevalence of anthelmintic resistance in equine helminths, selective treatment is increasingly promoted and in some countries a positive infection diagnosis is mandatory before treatment. Selective treatment is typically recommended when the number of worm eggs per gram faeces (epg) exceeds a particular threshold. In the present study we compared the semi-quantitative sedimentation/flotation method with the quantitative methods Mini-FLOTAC and FECPAKG2 in terms of precision, sensitivity, inter-rater reliability and correlation of worm egg counts to improve the choice of optimal diagnostic tools. METHODS: Using sedimentation/flotation (counting raw egg numbers up to 200), we investigated 1067 horse faecal samples using a modified Mini-FLOTAC approach (multiplication factor of 5 to calculate epgs from raw egg counts) and FECPAKG2 (multiplication factor of 45). RESULTS: Five independent analyses of the same faecal sample with all three methods revealed that variance was highest for the sedimentation/flotation method while there were no significant differences between methods regarding the coefficient of variance. Sedimentation/flotation detected the highest number of samples positive for strongyle and Parascaris spp. eggs, followed by Mini-FLOTAC and FECPAKG2. Regarding Anoplocephalidae, no significant difference in frequency of positive samples was observed between Mini-FLOTAC and sedimentation/flotation. Cohen's κ values comparing individual methods with the combined result of all three methods revealed almost perfect agreement (κ ≥ 0.94) for sedimentation/flotation and strong agreement for Mini-FLOTAC (κ ≥ 0.83) for strongyles and Parascaris spp. For FECPAKG2, moderate and weak agreements were found for the detection of strongyle (κ = 0.62) and Parascaris (κ = 0.51) eggs, respectively. Despite higher sensitivity, the Mini-FLOTAC mean epg was significantly lower than that with FECPAKG2 due to samples with > 200 raw egg counts by sedimentation/flotation, while in samples with lower egg shedding epgs were higher with Mini-FLOTAC than with FECPAKG2. CONCLUSIONS: For the simple detection of parasite eggs, for example, to treat foals infected with Parascaris spp., sedimentation/flotation is sufficient and more sensitive than the other two quantitative investigared in this study. Mini-FLOTAC is predicted to deliver more precise results in faecal egg count reduction tests due to higher raw egg counts. Finally, to identify animals with a strongyle epg above a certain threshold for treatment, FECPAKG2 delivered results comparable to Mini-FLOTAC.


Subject(s)
Ascaridoidea , Helminths , Animals , Feces/parasitology , Horses , Parasite Egg Count/methods , Parasite Egg Count/veterinary , Reproducibility of Results
3.
PLoS Negl Trop Dis ; 14(7): e0008296, 2020 07.
Article in English | MEDLINE | ID: mdl-32614828

ABSTRACT

The World Health Organization (WHO) has defined moderate-to-heavy intensity (M&HI) infections with soil-transmitted helminths (Ascaris lumbricoides, Trichuris trichiura and the two hookworms, Ancylostoma duodenale and Necator americanus) based on specific values of eggs per gram of stool, as measured by the Kato-Katz method. There are a variety of novel microscopy and DNA-based methods but it remains unclear whether applying current WHO thresholds on to these methods allows for a reliable classification of M&HI infections. We evaluated both WHO and method-specific thresholds for classifying the M&HI infections for novel microscopic (FECPAKG2, McMaster and Mini-FLOTAC) and DNA-based (qPCR) diagnostic methods. For this, we determined method-specific thresholds that best classified M&HI infections (defined by Kato-Katz and WHO thresholds; reference method) in two multi-country drug efficacy studies. Subsequently, we verified whether applying these method-specific thresholds improved the agreement in classifying M&HI infections compared to the reference method. When we applied the WHO thresholds, the new microscopic methods mainly misclassified M&HI as low intensity, and to a lesser extent low intensity infection as M&HI. For FECPAKG2, applying the method-specific thresholds significantly improved the agreement for Ascaris (moderate → substantial), Trichuris and hookworms (fair → moderate). For Mini-FLOTAC, a significantly improved agreement was observed for hookworms only (fair → moderate). For the other STHs, the agreement was almost perfect and remained unchanged. For McMaster, the method-specific thresholds revealed a fair to a substantial agreement but did not significantly improve the agreement. For qPCR, the method-specific thresholds based on genome equivalents per ml of DNA moderately agreed with the reference method for hookworm and Trichuris infections. For Ascaris, there was a substantial agreement. We defined method-specific thresholds that improved the classification of M&HI infections. Validation studies are required before they can be recommended for general use in assessing M&HI infections in programmatic settings.


Subject(s)
Helminthiasis/classification , Microscopy/methods , Real-Time Polymerase Chain Reaction/methods , Soil/parasitology , Helminthiasis/diagnosis , Helminthiasis/transmission , Humans , World Health Organization
4.
PLoS Negl Trop Dis ; 13(8): e0007446, 2019 08.
Article in English | MEDLINE | ID: mdl-31369558

ABSTRACT

BACKGROUND: Because the success of deworming programs targeting soil-transmitted helminths (STHs) is evaluated through the periodically assessment of prevalence and infection intensities, the use of the correct diagnostic method is of utmost importance. The STH community has recently published for each phase of a deworming program the minimal criteria that a potential diagnostic method needs to meet, the so-called target product profiles (TPPs). METHODOLOGY: We compared the diagnostic performance of a single Kato-Katz (reference method) with that of other microscopy-based methods (duplicate Kato-Katz, Mini-FLOTAC and FECPAKG2) and one DNA-based method (qPCR) for the detection and quantification of STH infections in three drug efficacy trials in Ethiopia, Lao PDR, and Tanzania. Furthermore, we evaluated a selection of minimal diagnostic criteria of the TPPs. PRINCIPAL FINDINGS: All diagnostic methods showed a clinical sensitivity of ≥90% for all STH infections of moderate-to-heavy intensities. For infections of very low intensity, only qPCR resulted in a sensitivity that was superior to a single Kato-Katz for all STHs. Compared to the reference method, both Mini-FLOTAC and FECPAKG2 resulted in significantly lower fecal egg counts for some STHs, leading to a substantial underestimation of the infection intensity. For qPCR, there was a positive significant correlation between the egg counts of a single Kato-Katz and the DNA concentration. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the diagnostic performance of a single Kato-Katz is underestimated by the community and that diagnostic specific thresholds to classify intensity of infection are warranted for Mini-FLOTAC, FECPAKG2 and qPCR. When we strictly apply the TPPs, Kato-Katz is the only microscopy-based method that meets the minimal diagnostic criteria for application in the planning, monitoring and evaluation phase of an STH program. qPCR is the only method that could be considered in the phase that aims to seek confirmation for cessation of program. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.


Subject(s)
Diagnostic Tests, Routine/methods , Helminthiasis/parasitology , Helminthiasis/transmission , Helminths/isolation & purification , Molecular Diagnostic Techniques/methods , Real-Time Polymerase Chain Reaction/methods , Soil/parasitology , Adolescent , Animals , Brazil , Child , Diagnostic Tests, Routine/instrumentation , Ethiopia/epidemiology , Feces/parasitology , Female , Helminthiasis/diagnosis , Helminthiasis/epidemiology , Helminths/genetics , Humans , Laos/epidemiology , Male , Microscopy , Molecular Diagnostic Techniques/instrumentation , Parasite Egg Count/methods , Prevalence , Sensitivity and Specificity , Tanzania/epidemiology , World Health Organization
5.
PLoS Negl Trop Dis ; 13(8): e0007471, 2019 08.
Article in English | MEDLINE | ID: mdl-31369562

ABSTRACT

BACKGROUND: Preventive chemotherapy (PC) with benzimidazole drugs is the backbone of soil-transmitted helminth (STH) control programs. Over the past decade, drug coverage has increased and with it, the possibility of developing anthelmintic resistance. It is therefore of utmost importance to monitor drug efficacy. Currently, a variety of novel diagnostic methods are available, but it remains unclear whether they can be used to monitor drug efficacy. In this study, we compared the efficacy of albendazole (ALB) measured by different diagnostic methods in a head-to-head comparison to the recommended single Kato-Katz. METHODS: An ALB efficacy trial was performed in 3 different STH-endemic countries (Ethiopia, Lao PDR and Tanzania), each with a different PC-history. During these trials, stool samples were evaluated with Kato-Katz (single and duplicate), Mini-FLOTAC, FECPAKG2, and qPCR. The reduction rate in mean eggs per gram of stool (ERR) and mean genome equivalents / ml of DNA extract (GERR) were calculated to estimate drug efficacy. PRINCIPAL FINDINGS AND CONCLUSIONS: The results of the efficacy trials showed that none of the evaluated diagnostic methods could provide reduction rates that were equivalent to a single Kato-Katz for all STH. However, despite differences in clinical sensitivity and egg counts, they agreed in classifying efficacy according to World Health Organization (WHO) guidelines. This demonstrates that diagnostic methods for assessing drug efficacy should be validated with their intended-use in mind and that other factors like user-friendliness and costs will likely be important factors in driving the choice of diagnostics. In addition, ALB efficacy against STH infections was lower in sites with a longer history of PC. Yet, further research is needed to identify factors that contribute to this finding and to verify whether reduced efficacy can be associated with mutations in the ß-tubulin gene that have previously been linked to anthelmintic resistance. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.


Subject(s)
Albendazole/therapeutic use , Anthelmintics/therapeutic use , Helminthiasis/diagnosis , Helminthiasis/drug therapy , Soil/parasitology , Administration, Oral , Albendazole/administration & dosage , Animals , Brazil , Child , Diagnostic Tests, Routine/methods , Ethiopia , Feces/parasitology , Female , Helminths/genetics , Humans , Laos , Male , Parasite Egg Count/methods , Sensitivity and Specificity , Tanzania , Tubulin/genetics , World Health Organization
7.
PLoS Negl Trop Dis ; 12(11): e0006912, 2018 11.
Article in English | MEDLINE | ID: mdl-30388108

ABSTRACT

BACKGROUND: To work towards reaching the WHO goal of eliminating soil-transmitted helminth (STH) infections as a public health problem, the total number of children receiving anthelmintic drugs has strongly increased over the past few years. However, as drug pressure levels rise, the development of anthelmintic drug resistance (AR) is more and more likely to appear. Currently, any global surveillance system to monitor drug efficacy and the emergence of possible AR is lacking. Consequently, it remains unclear to what extent the efficacy of drugs may have dropped and whether AR is already present. The overall aim of this study is to recommend the best diagnostic methods to monitor drug efficacy and molecular markers to assess the emergence of AR in STH control programs. METHODS: A series of drug efficacy trials will be performed in four STH endemic countries with varying drug pressure (Ethiopia and Brazil: low drug pressure, Lao PDR: moderate drug pressure and Tanzania: high drug pressure). These trials are designed to assess the efficacy of a single oral dose of 400 mg albendazole (ALB) against STH infections in school-aged children (SAC) by microscopic (duplicate Kato-Katz thick smear, Mini-FLOTAC and FECPAKG2) and molecular stool-based diagnostic methods (quantitative PCR (qPCR)). Data will be collected on the cost of the materials used, as well as the time required to prepare and examine stool samples for the different diagnostic methods. Following qPCR, DNA samples will also be submitted for pyrosequencing to assess the presence and prevalence of single nucleotide polymorphisms (SNPs) in the ß-tubulin gene. These SNPs are known to be linked to AR in animal STHs. DISCUSSION: The results obtained by these trials will provide robust evidence regarding the cost-efficiency and diagnostic performance of the different stool-based diagnostic methods for the assessment of drug efficacy in control programs. The assessment of associations between the frequency of SNPs in the ß-tubulin gene and the history of drug pressure and drug efficacy will allow the validation of these SNPs as a marker for AR in human STHs. TRIAL REGISTRATION: The trial was retrospectively registered the 7th of March 2018 on Clinicaltrials.gov (ID: NCT03465488).


Subject(s)
Anthelmintics/administration & dosage , Benzimidazoles/administration & dosage , Drug Resistance , Feces/parasitology , Helminthiasis/diagnosis , Helminthiasis/drug therapy , Helminths/drug effects , Adolescent , Animals , Biomarkers/chemistry , Brazil , Child , Child, Preschool , Clinical Protocols , Ethiopia , Female , Helminth Proteins/genetics , Helminthiasis/parasitology , Helminths/genetics , Helminths/physiology , Humans , Male , Parasite Egg Count , Polymorphism, Single Nucleotide , Schools/statistics & numerical data , Soil/parasitology , Tubulin/genetics
8.
PLoS Negl Trop Dis ; 12(10): e0006655, 2018 10.
Article in English | MEDLINE | ID: mdl-30321180

ABSTRACT

BACKGROUND: Standard diagnosis of human soil-transmitted helminth (STH) infections is based on the microscopic detection of helminth eggs in stool and supports programmatic decision making in control programs. However, the current standard diagnostic techniques still show a number of limitations. Recently, the FECPAKG2 method was developed to detect helminth infections and asses drug efficacy in sheep or cattle. It includes a device that takes digital images of helminth eggs that have been concentrated into one microscopic field of view and stores these images online for future evaluation. The goal of this study was to introduce a standard operating procedure (SOP) for the detection and quantification of human STH eggs using the FECPAKG2 and to optimize 2 crucial steps of the protocol, namely the sedimentation step (aimed at separating sinking eggs from floating debris) and the accumulation step (aimed at concentrating the eggs by flotation). METHODOLOGY/PRINCIPAL FINDINGS: A total of 55 stool samples from naturally infected children were used from 4 different geographical areas (Ethiopia, Laos, Tanzania and Brazil). The results showed that Trichuris eggs generally moved slower than eggs of the other two STH species during both sedimentation in water in the FECPAKG2 sedimenter as during accumulation in flotation solution in the FECPAKG2 cassettes. The highest number of eggs were present in the slurry of the sedimenter after overnight sedimentation (Ascaris: 95.7%, Trichuris: 89.8% and hookworm: 94.2% of the eggs). A minimum of 24 minutes were needed to ensure the accumulation of at least 80% of the eggs from all three STH species in the FECPAKG2 cassette (Ascaris: 96.1%; Trichuris: 88.2% and hookworm: 87.6%). CONCLUSIONS/SIGNIFICANCE: This study introduces for the first time a SOP for the FECPAKG2 method. Different aspects of the method for diagnosing human STH infections were optimized. Our study forms the basis for a thorough and objective evaluation of the system as a diagnostic tool that could be implemented in STH control programs.


Subject(s)
Feces/parasitology , Helminthiasis/diagnosis , Intestinal Diseases, Parasitic/diagnosis , Parasite Egg Count/methods , Adolescent , Africa , Animals , Asia , Brazil , Child , Child, Preschool , Female , Humans , Male , Parasite Egg Count/standards
9.
PLoS Negl Trop Dis ; 12(6): e0006562, 2018 06.
Article in English | MEDLINE | ID: mdl-29864132

ABSTRACT

BACKGROUND: Over one billion people are infected with soil-transmitted helminths (STH), i.e. Ascaris lumbricoides, hookworm and Trichuris trichiura. For estimating drug efficacy and monitoring anthelminthic drug resistance, accurate diagnostic methods are critical. FECPAKG2 is a new remote-diagnostic tool used in veterinary medicine, which produces an image of the stool sample that can be stored on an internet cloud. We compared for the first time FECPAKG2 with the recommended Kato-Katz method. METHODOLOGY/PRINCIPAL FINDINGS: Two stool samples were collected from adolescent participants (age 15-18 years) at baseline and 14 to 21 days after treatment in the framework of a randomized clinical trial on Pemba Island, Tanzania. Stool samples were analyzed with different diagnostic efforts: i) one or ii) two Kato-Katz thick smears from the first sample, iii) two Kato-Katz thick smears from two samples and iv) FECPAKG2 from the first sample. Parameters were calculated based on a hierarchical Bayesian egg count model. Complete data for all diagnostic efforts were available from 615 participants at baseline and 231 hookworm-positive participants at follow-up. At baseline FECPAKG2 revealed a sensitivity of 75.6% (72.0-77.7) for detecting A. lumbricoides, 71.5% (67.4-95.3) for hookworm and 65.8% (64.9-66.2) for T. trichiura, which was significantly lower (all p<0.05) than any of the Kato-Katz methods and highly dependent on infection intensity. Despite that the egg counts based on FECPAKG2 were relatively lower compared to Kato-Katz by a ratio of 0.38 (0.32-0.43) for A. lumbricoides, 0.36 (0.33-0.40) for hookworm and 0.08 (0.07-0.09) for T. trichiura, the egg reduction rates (ERR) were correctly estimated with FECPAKG2. CONCLUSIONS/SIGNIFICANCE: The sensitivity to identify any STH infection was considerably lower for FECPAKG2 compared to Kato-Katz. Following rigorous development, FECPAKG2 might be an interesting tool with unique features for epidemiological and clinical studies.


Subject(s)
Ascariasis/diagnosis , Feces/parasitology , Parasite Egg Count/methods , Soil/parasitology , Trichuriasis/diagnosis , Adolescent , Animals , Ascariasis/epidemiology , Ascariasis/parasitology , Ascariasis/transmission , Ascaris lumbricoides/isolation & purification , Bayes Theorem , Female , Helminthiasis/diagnosis , Helminthiasis/epidemiology , Helminthiasis/parasitology , Helminthiasis/transmission , Helminths/isolation & purification , Humans , Intestinal Diseases, Parasitic/diagnosis , Intestinal Diseases, Parasitic/epidemiology , Intestinal Diseases, Parasitic/parasitology , Male , Reagent Kits, Diagnostic , Sensitivity and Specificity , Specimen Handling/methods , Tanzania/epidemiology , Trichuriasis/epidemiology , Trichuriasis/parasitology , Trichuriasis/transmission , Trichuris/isolation & purification
10.
Parasit Vectors ; 11(1): 278, 2018 05 02.
Article in English | MEDLINE | ID: mdl-29716657

ABSTRACT

This study aimed to compare the FECPAKG2 and the McMaster techniques for counting of gastrointestinal nematode eggs in the faeces of alpacas using two floatation solutions (saturated sodium chloride and sucrose solutions). Faecal eggs counts from both techniques were compared using the Lin's concordance correlation coefficient and Bland and Altman statistics. Results showed moderate to good agreement between the two methods, with better agreement achieved when saturated sugar is used as a floatation fluid, particularly when faecal egg counts are less than 1000 eggs per gram of faeces. To the best of our knowledge this is the first study to assess agreement of measurements between McMaster and FECPAKG2 methods for estimating faecal eggs in South American camelids.


Subject(s)
Camelids, New World/parasitology , Feces/parasitology , Parasite Egg Count/methods , Animals , Gastrointestinal Tract/parasitology
SELECTION OF CITATIONS
SEARCH DETAIL
...