tribendimidine and Hookworm-Infections

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 global strategy to control soil-transmitted helminthiasis is mainly focused on preventive chemotherapy with albendazole and mebendazole. We assessed the efficacy and safety of ascending tribendimidine doses against hookworm infections in African school-aged children, key information for the development of tribendimidine.. We performed a single blind, randomized, controlled trial in Côte d'Ivoire between June and August 2017. Eligible participants were randomly assigned to placebo, 100, 200, or 400 mg tribendimidine. Cure rates (CRs, primary outcome) and egg reduction rates (ERRs) were determined 14-21 days after treatment. Clinical symptoms were assessed before treatment and adverse events monitored 3 and 24 hours posttreatment.. CRs calculated for 130 children dose-dependently increased. The observed CRs were 20.6% (7/34), 21.2% (7/33), 38.7% (12/31), and 53.1% (17/32) for placebo, 100, 200, and 400 mg of tribendimidine, respectively. The Emax model predicted a placebo corrected net effect of 34.3 percentage points (95% confidence interval [CI], 13.3-54.4) for the 400-mg tribendimidine dose. The ERRs (geometric mean) were 30.6% (95% CI, -24.7 to 64.1), 65.4% (95% CI, 24.5-85.9), 82.1% (95% CI, 58.4-92.5) and 92.2% (95% CI, 81.0-97.1) for placebo, 100, 200, and 400 mg tribendimidine, respectively. The Emax model predicted an ERR of 95% at 500 mg. Only mild adverse events and no abnormal biochemical parameters were observed.. A 400-mg dose of tribendimidine yielded the highest efficacy and was well tolerated. Because children were mostly lightly infected, further investigations with tribendimidine against moderate/heavy hookworm infection are needed.. The trial is registered at www.isrctn.com number ISRCTN81391471.

Topics: Child; Cote d'Ivoire; Dose-Response Relationship, Drug; Feces; Female; Hookworm Infections; Humans; Male; Parasite Egg Count; Phenylenediamines; Prospective Studies; Single-Blind Method; Treatment Outcome

To study the efficacy of tribendimdine in the treatment of hookworm infection.. Forty-seven cases of hookworm infection detected in a cross-sectional study were selected and randomly divided into two groups, one was experimental group (23 cases) treated with tribendimdine and the other was control group (24 cases) treated with albendazole. The negative conversion rates and the incidence rates of adverse effects in the two groups were observed and compared.. The negative conversion rates and the incidence rates of adverse effects of the two groups were 95.65% and 95.83%, 8.70% and 8.33%, respectively, there were no statistical differences (both P values > 0.05).. The efficacy of tribendimdine in the treatment of hookworm infection is similar to albendazole.

Topics: Adolescent; Adult; Aged; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Child; Female; Hookworm Infections; Humans; Male; Middle Aged; Phenylenediamines; Young Adult

To evaluate the efficacy and safety of tribendimidine in treatment of children with hookworm and Ascaris lumbricoides infections.. An open and multi-center clinical trial was conducted in the provinces of Hainan, Sichuan and Guizhou. 899 children aged 4-14 years were enrolled in the study. Hookworm, A. lumbricoides or other helminth infections were diagnosed by improved Kato-Katz method. All the patients were treated orally with tribendimidine enteric coated tablet at a single dose of 200 mg. The efficacy was evaluated by stool examination 3-4 weeks post treatment.. The cure rate and effective rate of the children with hookworm infection were 82.0% (433/528) and 99.2% (524/528), respectively, while in children with A. lumbricoides infection, they were 95.0% (576/639) and 99.8% (637/639), respectively. The efficacy of tribendimidine enteric coated tablet given to the children with Trichuris trichiura infection at a single dose of 200 mg was 36.8% (112/304). The adverse effect induced by tribendimidine, such as dizziness, nausea and vomiting, was light and transient with an adverse effect rate of 1.6% (14/899). No apparent impact was seen on the blood and urine routine examination, hepatic and renal function as well as ECG examination. Conclusion Tribendimidine given at a single dose of 200 mg exhibits lower adverse effect rate and potential efficacy in the treatment of children with hookworm and A. lumbricoides infections.

Topics: Adolescent; Ascariasis; Child; Child, Preschool; China; Double-Blind Method; Female; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Male; Phenylenediamines; Tablets, Enteric-Coated; Treatment Outcome; Trichuriasis

To study the therapeutic effect and possible adverse effects of tribendimidine enteric coated tablets in the treatment of infections due to hookworms, Ascaris lumbricoides, Trichuris trichiura, Enterobius vermicularis.. According to the standard clinical trial design and protocol, persons infected with hookworms, Ascaris lumbricoides, Trichuris trichiura, or Enterobius vermicularis respectively, were treated with tribendimidine enteric coated tablets in four counties of Guangdong and Jiangsu Provinces, albendazole was used as control.. For hookworm infection, the curative rate (eggs negative in the faeces) were 89.5% (85/95) and 70.6% (60/85) with tribendimidine (400 mg) and albendazole(400 mg) respectively; for Ascaris infection, 97.4% (114/117) and 98.9% (91/92) with tribendimidine(300 mg) and albendazole(400 mg) respectively; for Trichuris infection, 33.3% (25/75) and 56.1% (23/41) with tribendimidine(400 mg/day for 3 days) and albendazole(400 mg/day for 3 days) respectively; for Enterobius infection in children, 74.1% (60/81) and 93.0% (40/43) with tribendimidine(200 mg) and albendazole(200 mg) respectively. No considerable side effect was found.. Tribendimidine is highly active in the treatment of hookworm, Ascaris lumbricoides infections, free of major adverse effect and easy to administer. It is more effective than albendazole for the infection of Necator americanus.

Topics: Adolescent; Adult; Aged; Albendazole; Ancylostomatoidea; Animals; Ascariasis; Ascaris lumbricoides; Child; Double-Blind Method; Enterobiasis; Enterobius; Hookworm Infections; Humans; Intestinal Diseases, Parasitic; Middle Aged; Necator americanus; Nematode Infections; Phenylenediamines; Tablets, Enteric-Coated; Treatment Outcome; Trichuriasis; Young Adult

Topics: Adolescent; Ancylostomatoidea; Animals; Anthelmintics; Hookworm Infections; Humans; Phenylenediamines

Tribendimidine has been successful in treating hookworm infections and may serve as an alternative to albendazole should resistance arise. Our aims were to (i) characterize the pharmacokinetics (PK) of tribendimidine's primary metabolite, deacetylated amidantel (dADT), and secondary metabolite, acetylated derivative of amidantel (adADT), in school-aged children and adolescents, (ii) link exposure to efficacy against hookworm, and (iii) evaluate whether tribendimidine pharmacotherapy in children could be further improved. First, a population PK model was developed based on dried-blood-spot samples collected from 155 school-aged children and adolescents with hookworm infections, following tribendimidine doses ranging from 100 to 400 mg. Second, an exposure-response analysis was conducted to link the active metabolite dADT to cure rates (CRs) and egg reduction rates (ERRs). Third, simulations were performed to identify a treatment strategy associated with >90% CRs. A two-compartmental model with transit compartments describing observed delay in absorption adequately described PK data of dADT and adADT. Allometric scaling was included to account for growth and development. The absorption rate was 56% lower with 200-mg tablets than with 50-mg tablets, while the extent of absorption remained unaffected. The identified

Topics: Adolescent; Albendazole; Ancylostomatoidea; Animals; Anthelmintics; Child; Hookworm Infections; Humans; Phenylenediamines; Treatment Outcome

Soil-transmitted helminths infect 1.5 billion people worldwide. Treatment with anthelminthics is the key intervention but interactions between anthelminthic agents and the gut microbiota have not yet been studied. In this study, the effects of four anthelminthic drugs and combinations (tribendimidine, tribendimidine plus ivermectin, tribendimidine plus oxantel-pamoate, and albendazole plus oxantel-pamoate) on the gut microbiota were assessed. From each hookworm infected adolescent, one stool sample was collected prior to treatment, 24 h post-treatment and 3 weeks post-treatment, and a total of 144 stool samples were analyzed. The gut bacterial composition was analyzed using 16S rRNA gene sequencing. Tribendimidine given alone or together with oxantel-pamoate, and the combination of albendazole and oxantel pamoate were not associated with any major changes in the taxonomic composition of the gut microbiota in this population, at both the short-term post-treatment (24 h) and long-term post-treatment (3 weeks) periods. A high abundance of the bacterial phylum Bacteroidetes was observed following administration of tribendimidine plus ivermectin 24 h after treatment, due predominantly to difference in abundance of the families Prevotellaceae and Candidatus homeothermaceae. This effect is transient and disappears three weeks after treatment. Higher abundance of Bacteroidetes predicts an increase in metabolic pathways involved in the synthesis of B vitamins. This study highlights a strong relationship between tribendimidine and ivermectin administration and the gut microbiota and additional studies assessing the functional aspects as well as potential health-associated outcomes of these interactions are required.

Topics: Adolescent; Albendazole; Anthelmintics; Ascariasis; Bacteria; Bacteroidetes; Biotin; DNA, Bacterial; Drug Therapy, Combination; Feces; Gastrointestinal Microbiome; Hookworm Infections; Humans; Ivermectin; Metabolic Networks and Pathways; Parasite Egg Count; Phenylenediamines; Pyrantel Pamoate; RNA, Ribosomal, 16S; Trichuriasis