moxidectin and tribendimidine

Diagnosis of soil-transmitted helminths (STHs) in developing countries is commonly based on microscopic detection of eggs in stool samples, using the Kato-Katz (KK) method, which has a poor sensitivity for detecting light intensity infections. We compared the performance of the KK method and real-time PCR in the framework of a randomized trial, which evaluated four novel treatments against Trichuris trichiura and concomitant STH infections.. Two stool samples obtained from 320 participants were examined at baseline and follow-up with quadruplicate KK and PCR analyses of one of the two samples using "bead-beating" for DNA extraction. At follow-up, 80 samples were negative according to both PCR and KK and 173 were positive with both methods for any of the STHs. Relative to PCR, the calculated sensitivity of KK at follow-up was 83.6%, 43.0% and 53.8% for T. trichiura, for hookworm and for Ascaris lumbricoides, respectively. The sensitivity of PCR compared with KK at this time point was 89.1% for T. trichiura, 72.7% for hookworm and 87.5% for A. lumbricoides. Cure rates (CRs) for T. trichiura and A. lumbricoides were slightly lower with the PCR method. For hookworm CRs with KK were mostly significantly lower, namely 36.7%, 91.1%, 72.2% and 77.8% for moxidectin, moxidectin in combination with tribendimidine, moxidectin in combination with albendazole and albendazole in combination with oxantel pamoate, respectively, whereas with PCR the CRs were 8.3%, 82.6%, 37.1% and 57.1%, respectively.. In conclusion, a single real-time PCR is as sensitive as quadruplicate KK for T. trichiura and A. lumbricoides detection but more sensitive for hookworm, which has an influence on the estimated treatment efficacy. PCR method with DNA extraction using the "bead-beating protocol" should be further promoted in endemic areas and laboratories that can afford the needed equipment. The study is registered at ISRCTN (no. 20398469).

Topics: Adolescent; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Ascariasis; Ascaris lumbricoides; Child; Diagnostic Tests, Routine; DNA, Helminth; Feces; Female; Hookworm Infections; Humans; Macrolides; Male; Phenylenediamines; Pyrantel Pamoate; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Soil; Trichuriasis; Trichuris; Young Adult

The recommended anthelmintics show low efficacy in a single-dose regimen against Trichuris trichiura. Moxidectin, a new treatment for river blindness, might complement the drug armamentarium for the treatment and control of soil-transmitted helminthiasis. However, its efficacy against T trichiura has not yet been studied. The aim of the study was to assess the efficacy of moxidectin alone and in co-administrations against T trichiura infection.. A randomised, single-blind, non-inferiority trial was done in two primary schools and one secondary school in Pemba, Tanzania. Adolescents aged 12-18 years who tested positive for T trichiura were randomly assigned (5:5:3:3) with a computer-generated sequence to receive moxidectin (8 mg) plus albendazole (400 mg), albendazole (400 mg) plus oxantel pamoate (25 mg/kg; reference treatment), moxidectin (8 mg) plus tribendimidine (200 mg or 400 mg), or moxidectin (8 mg) alone. Study group assignments were masked from participants and laboratory technicians. The primary outcome was non-inferiority with a 2 percentage point margin for egg reduction rate (ERR) against T trichiura assessed as the relative change in the geometric mean egg counts from baseline to 14-21 days after treatment with the Kato-Katz method, based on the available case population. Cure rates (CR) and tolerability (assessed 3, 24, and 48 h post treatment) were secondary outcomes. The study is registered at ISRCTN (number 20398469) and is closed to accrual.. 701 students were enrolled between April 1, and Aug 7, 2017. Primary outcome data were available for 634 students. We observed ERRs of 98·5% for moxidectin plus albendazole and 99·8% for albendazole plus oxantel pamoate, resulting in an absolute difference of -1·2 percentage points (95% CI -1·8 to -0·8), meeting the non-inferiority margin. 100 (51%) of 197 students receiving moxidectin plus albendazole and 166 (83%) of 200 receiving albendazole plus oxantel pamoate were cured, indicating a difference of 32 percentage points (odds ratio 5·3, 95% CI 3·3 to 8·7). ERRs were 91·6% for moxidectin-tribendimidine and 83·2% for moxidectin. Only mild adverse events (mainly headache and stomach pain) were reported. The largest number of adverse events (126 [20%] of 632 students) was observed 24 h post treatment, with no difference among the individual treatment arms (ranging from 23 [19%] of 118 students treated with moxidectin to 38 [19%] of 199 with moxidectin plus albendazole).. Moxidectin plus albendazole showed non-inferiority to albendazole plus oxantel pamoate in terms of ERR; however, albendazole plus oxantel pamoate showed a considerably higher cure rate. Dose-optimisation studies with moxidectin and moxidectin plus albendazole should be considered since the efficacy of the dose used for the treatment of onchocerciasis (8 mg) in this study might not be optimal for the treatment of T trichiura infections.. Thrasher Foundation.

Topics: Administration, Oral; Adolescent; Albendazole; Animals; Anthelmintics; Child; Drug Therapy, Combination; Female; Humans; Macrolides; Male; Mebendazole; Phenylenediamines; Pyrantel Pamoate; Single-Blind Method; Trichuriasis; Trichuris

Topics: Albendazole; Humans; Macrolides; Phenylenediamines; Pyrantel Pamoate; Single-Blind Method; Trichuriasis