Dataset Information

Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.

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 ?-tubulin gene that have previously been linked to anthelmintic resistance. TRIAL REGISTRATION:ClinicalTrials.gov NCT03465488.

SUBMITTER: Vlaminck J

PROVIDER: S-EPMC6675043 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.

Vlaminck Johnny J Cools Piet P Albonico Marco M Ame Shaali S Ayana Mio M Cringoli Giuseppe G Dana Daniel D Keiser Jennifer J Maurelli Maria P MP Matoso Leonardo F LF Montresor Antonio A Mekonnen Zeleke Z Mirams Greg G Corrêa-Oliveira Rodrigo R Pinto Simone A SA Rinaldi Laura L Sayasone Somphou S Thomas Eurion E Vercruysse Jozef J Verweij Jaco J JJ Levecke Bruno B

PLoS neglected tropical diseases 20190801 8

<h4>Background</h4>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 ...[more]

PMID: 31369562

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Project description:In Malaysia, soil-transmitted helminth (STH) infections still persist among indigenous communities. In the past, local studies have focused mostly on epidemiologic aspects of STH infections with a scarcity of information on the efficacy of deworming treatment. The present study consisted of 2 phases: a cross-sectional phase on current epidemiological status and risk factors of STH infections and a longitudinal study over 6 weeks on triple dose albendazole efficacy against STH infections. A total of 253 participants were recruited at baseline and a pre-tested questionnaire was administered to obtain information on socio-demographics, environmental and behavioural risk factors. Stool samples were evaluated using a modified Kato-Katz technique. Cure rate (CR) and egg reduction rate (ERR) were assessed at 3 weeks following a 3-day course of 400mg albendazole treatment and infection status were observed again at 6 weeks. Baseline positivity of trichuriasis, ascariasis and hookworm infections were 56.1%, 11.9% and 20.2%, respectively. Multivariate analysis showed age below 18 years old (P = 0.004), without latrine in house (P = 0.042) and indiscriminate defecation (P = 0.032) were associated with STH infections. In the longitudinal study (N = 89), CR for trichuriasis was 64.6%, while CR of 100% was observed for both ascariasis and hookworm. ERR was above 90% for all three STH species. A rapid increased of Trichuris trichiura egg output was observed at 6 weeks. In conclusion, STH infections are highly prevalent among indigenous communities. Children and teenagers, poor sanitation and hygiene behaviour were determinants for STH infections. Triple dose albendazole is found to be efficacious against Ascaris lumbricoides and hookworm infections but has moderate curative effect with high ERR against T. trichiura. Although triple dose albendazole regimen has logistic challenges and may not be a routine option, consideration of this treatment regime may still be necessary in selective communities to reduce high intensity of T. trichiura infection.

Project description:The current treatments against Trichuris trichiura, albendazole and mebendazole, are only poorly efficacious. Therefore, combination chemotherapy was recommended for treating soil-transmitted helminthiasis. Albendazole-mebendazole and albendazole-oxantel pamoate have shown promising results in clinical trials. However, in vitro and in vivo drug interaction studies should be performed before their simultaneous treatment can be recommended. Inhibition of human recombinant cytochromes P450 (CYPs) CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was tested by exposure to albendazole, albendazole sulfoxide, mebendazole, and oxantel pamoate, as well as albendazole-mebendazole, albendazole sulfoxide-mebendazole, albendazole-oxantel pamoate, and albendazole sulfoxide-oxantel pamoate. A high-pressure liquid chromatography (HPLC)-UV/visible spectroscopy method was developed and validated for simultaneous quantification of albendazole sulfoxide, albendazole sulfone, mebendazole, and oxantel pamoate in plasma. Albendazole, mebendazole, oxantel pamoate, albendazole-mebendazole, and albendazole-oxantel pamoate were orally applied to rats (100 mg/kg) and pharmacokinetic parameters calculated. CYP1A2 showed a 2.6-fold increased inhibition by albendazole-oxantel pamoate (50% inhibitory concentration [IC50] = 3.1 ?M) and a 3.9-fold increased inhibition by albendazole sulfoxide-mebendazole (IC50 = 3.8 ?M) compared to the single drugs. In rats, mebendazole's area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) were augmented 3.5- and 2.8-fold, respectively (P = 0.02 for both) when coadministered with albendazole compared to mebendazole alone. Albendazole sulfone was slightly affected by albendazole-mebendazole, displaying a 1.3-fold-elevated AUC compared to albendazole alone. Oxantel pamoate could not be quantified, translating to a bioavailability below 0.025% in rats. Elevated plasma levels of albendazole sulfoxide, albendazole sulfone, and mebendazole in coadministrations are probably not mediated by CYP-based drug-drug interaction. Even though this study indicates that it is safe to coadminister albendazole-oxantel pamoate and albendazole-mebendazole, human pharmacokinetic studies are recommended.

Project description:BackgroundBased on two national surveys, the prevalence of soil-transmitted helminthiasis (STH) in China had decreased from 53.58% in 1988-1992 to 19.56% in 2001-2004. To update the epidemiology and characteristics of STH in China, a third national survey was implemented in 2014-2015.Methodology/principal findingsThis survey covered rural areas in 31 provinces in mainland of China. Multiple-stage stratified cluster sampling was employed, which included three levels (provinces, ecozones and economical levels). Stool samples were collected and the Kato-Katz method was applied for helminth eggs detection. Samples with hookworm eggs were selected and hatched to differentiate the species based on larval morphology. Between June 2014 and May 2015, a total of 484,210 participants from 604 counties were enrolled. The weighted prevalence of STH overall was 4.49% (95% confidential interval (CI): 2.45%-6.53%), including 2.62% (95% CI: 0.86%-4.38%) hookworm infections, 1.36% (95% CI: 0.49%-2.23%) ascariasis, and 1.02% (95% CI: 0.15%-1.89%) trichuriasis. The estimated population infected was 29.12 million (95% CI: 15.88 million-42.32 million) for all STH; 16.97 million (95% CI: 5.57 million-28.39 million) for hookworm infections; 8.83 million (95% CI: 3.18 million-14.45 million) for ascariasis; and 6.60 million (95% CI: 0.97 million-12.25 million) for trichuriasis. Overall, the prevalence of ascariasis and trichuriasis was relatively high in children, while hookworm infections were more common in the older population, especially those over 60. STH was highly prevalent in western China, and moderately in central areas, but low in eastern and northern regions. Out of 3,579 hookworm cases with species differentiation, 479 cases (13.38%) were infected with only Ancylostoma spp., 2,808 cases (78.46%) with only Necator americanus, and another 292 cases (8.16%) with both species.Conclusions/significanceThis survey demonstrated the continuous decrease of STH in rural China. However, endemicity still prevails in the western areas of the country. Hookworm, especially N. americanus, is becoming the predominant species. Older farmers in western China should be prioritized for control due to the high prevalence of hookworm.

Project description:BackgroundControl efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date.MethodsWithin the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy.ResultsEgg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively.ConclusionsBased on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections.Trial registrationNCT03527732.

Dataset Information

Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.

Publications

Therapeutic efficacy of albendazole against soil-transmitted helminthiasis in children measured by five diagnostic methods.

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