moxidectin and Trichuriasis

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

Preventive chemotherapy is the main strategy to control soil-transmitted helminth (STH) infections. Albendazole and mebendazole are ubiquitously used, but they are not sufficiently effective against Trichuris trichiura. Moxidectin might be a useful addition to the small drug armamentarium. However, the optimal dosage of moxidectin alone and in combination with albendazole against T. trichiura and other STHs has not yet been determined.. A Phase II, randomized, placebo-controlled, dose-finding trial was conducted in 2 secondary schools on Pemba Island, Tanzania. Using a computer-generated list, T. trichiura-infected adolescents were randomly assigned to 7 treatment arms: 8, 16, or 24 mg of moxidectin monotherapy; 8, 16, or 24 mg of moxidectin plus 400 mg of albendazole combination therapy; or placebo. The primary outcome was cure rate (CR) against T. trichiura, analyzed 13 to 20 days after treatment by quadruple Kato-Katz thick smears.. A total of 290 adolescents were enrolled (41 or 42 per arm). CRs against T. trichiura were 43, 46, and 44% for 8, 16, and 24 mg of moxidectin alone, respectively; 60, 62, and 66% for the same moxidectin dosages plus 400 mg of albendazole, respectively; and 12% for placebo. The moxidectin-albendazole arms also revealed higher CRs and egg reduction rates against hookworm than the monotherapy arms. Moxidectin and its combination with albendazole were well tolerated.. Moxidectin-albendazole is superior to moxidectin. There is no benefit of using doses above 8 mg, which is the recommended dose for onchocerciasis. The moxidectin-albendazole combination of 8 mg plus 400 mg should be investigated further to develop recommendations for appropriate control of STH infections.. NCT03501251.

Topics: Adolescent; Albendazole; Animals; Anthelmintics; Feces; Humans; Macrolides; Tanzania; Trichuriasis; Trichuris

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

Separate controlled trials were conducted to evaluate the efficacy of two formulations of moxidectin (1% non-aqueous injectable solution and 0.5% pour-on (Cydectin) against larval or adult stages of Oesophagostomum radiatum and Trichuris discolor infecting cattle. Fifty-three strongylate-free dairy breed steer calves were obtained from commercial sources. After a brief acclimation period, calves were randomly divided into two pools to evaluate the efficacy of the moxidectin formulations against targeted larval (n = 27 calves) or adult (n = 26 calves) parasites. Calves in the larvacidal trial were inoculated on Day -16 relative to treatment with approximately 1000 embryonated Trichuris spp. eggs and approximately 640 infective Oesophagostomum spp. larvae. Calves were allocated by lottery to one of three treatment groups (n = 8 per group), which included: Group 1--moxidectin 0.5% pour-on (0.5 mg/kg body weight (BW)) applied topically; Group 2--moxidectin 1% non-aqueous injectable (0.2 mg/kg BW) administered subcutaneously; Group 3--untreated controls. Treatments were administered on Day 0 and calves were housed by group with no contact among animals of different treatments. Three sentinel calves were necropsied on Day 0 of the larvacidal trial to assess viability of larval inocula. On Days 14, 15 and 16 after treatment, calves were euthanatized (two or three from each group per day) and samples of gut contents were collected for determination of total worm counts. On Day -63 relative to treatment, calves in the adulticidal efficacy trial were inoculated with approximately 1000 embryonated Trichuris eggs and then on Day -35 with approximately 2500 infective Oesophagostomum spp. larvae. Fecal samples were collected on Day -7 and the 24 calves with the highest egg counts were assigned by lottery to the following three treatment groups (n = 8 per group): Group 4--moxidectin 0.5% pour-on; Group 5--moxidectin 1% injectable; Group 6--untreated controls. Details of experimental treatments, calf housing and necropsy scheduling were similar to the larvacidal trial. In both the larvacidal and adulticidal trials, inocula contained a variety of parasites in addition to the targeted species. Based on geometric means, both moxidectin 0.5% pour-on and moxidectin 1% non-aqueous injectable significantly reduced (P < 0.05) numbers of Oesophagostomum spp. and Trichuris spp. with anthelmintic efficacies of >99% when used against adult or larval stages of infection. In addition,

Topics: Administration, Topical; Animals; Anthelmintics; Anti-Bacterial Agents; Cattle; Cattle Diseases; Dose-Response Relationship, Drug; Feces; Injections, Subcutaneous; Larva; Macrolides; Male; Oesophagostomiasis; Oesophagostomum; Parasite Egg Count; Treatment Outcome; Trichuriasis; Trichuris

Efficacy of moxidectin injection (ProHeart 6 Sustained Release Injectable for Dogs, Fort Dodge Animal Health) against naturally acquired infections of Trichuris vulpis was compared with that of milbemycin oxime/lufenuron tablets (Sentinel Flavor Tabs, Novartis Animal Health). Eighteen dogs infected with T. vulpis were ranked by egg counts and randomly allocated to treatment with moxidectin (170 micro g/kg), milbemycin (500 micro g/kg)/lufenuron (10 mg/kg), or to an untreated control group (six dogs per treatment). Dogs were euthanized for worm counting 7 days after treatment. Efficacy of milbemycin/lufenuron against T. vulpis was 99.6 %, compared with 67.5 % for moxidectin. The commercial formulation of milbemycin oxime/lufenuron provided excellent control of whipworm infection, whereas moxidectin demonstrated variable efficacy against this parasite.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Autopsy; Benzamides; Delayed-Action Preparations; Dog Diseases; Dogs; Drug Combinations; Female; Injections; Macrolides; Male; Tablets; Trichuriasis; Trichuris

The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs.

Topics: Ancylostomiasis; Animals; Anthelmintics; Anti-Bacterial Agents; Dog Diseases; Dogs; Feces; Female; Intestinal Diseases, Parasitic; Macrolides; Male; Parasite Egg Count; Trichuriasis

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

Forty pigs with induced infections of Ascaris suum, Trichuris suis, Metastrongylus spp., Oesophagostomum dentatum and O. quadrispinulatum were assigned to five-dose groups of moxidectin 0.5% pour-on with eight pigs per dose group. The doses were: moxidectin, 0 (vehicle control), 0.75, 1.00, 1.25, and 1.50 mg/kg(-1) body weight. Worm egg counts (EPG) were made from fecal samples collected on Day 2 pretreatment and on Day 14 or 15 post-treatment. Animals were ranked according to the descending order of A. suum egg counts made on Day 2 and blocked in groups of five. Pigs in blocked groups were assigned randomly to each of the five dose groups. Treatment doses were calculated on the basis of weights taken on Day 1 and were administered topically from the neck to the base of the tail. Pigs were housed by pairs in individual pens provided with self-feeders and automatic waterers. Necropsies were performed on equal numbers of pigs from each treatment group on days 14 and 15 post-treatment. Adult and larval worms were collected, identified and counted by standard parasitological techniques. All counts were transformed by Y=log10 (count+1) transformation prior to analysis. A two-way analysis of variance was conducted and treatment effect was tested for significance at the 5% level. Efficacies based on geometric means and optimal doses were as follows: Ascaris suum, 98.3% at 1.25; Metastrongylus spp., 100% at 0.75; Oesophagostomum quadrispinulatum, 100% at 1.50; and Trichuris suis, 93.5% at 0.75. Efficacy for O. dentatum was from 81.3% to 100%; however, the average number of O. dentatum (30) was too small for significance. Two species of lungworms were present, Metastrongylus apri and M. pudendotectus but they were not speciated at necropsy. As reported for several anthelmintics, the efficacy of moxidectin was variable for Trichuris. The highest efficacy was in the 0.75 dose group with six pigs harboring a few or no worms. The lowest efficacy was in the 1.25 group with only two pigs harboring a few or no worms.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Ascariasis; Ascaris suum; Feces; Female; Intestines; Macrolides; Male; Metastrongyloidea; Nematoda; Nematode Infections; Oesophagostomiasis; Oesophagostomum; Parasite Egg Count; Random Allocation; Stomach; Strongylida Infections; Swine; Swine Diseases; Trichuriasis; Trichuris

Previous work indicated that adult Ancylostoma caninum can be removed from experimentally infected dogs, using a formulation of milbemycin oxime at dosage of 0.5 mg/kg of body weight. To determine the efficacy of this treatment in dogs naturally infected with adult hookworms, 24 mixed-breed dogs with patent hookworm infections were purchased from an out-of-state vendor, and 6 male and 6 female dogs were assigned to either a control group or a group that would be treated. Dogs were treated 10 days after their arrival and were euthanatized 1 week after treatment. Beginning 3 days before treatment, fecal samples were collected daily from all dogs, and the number of Ancylostoma eggs per gram of dry weight of feces was determined from each sample. By 1 week after treatment, the mean number of eggs being passed by the treated dogs had dropped from 12,700 to 10 eggs/g of dried feces; there was no apparent change in fecal egg counts for dogs of the control group. At necropsy, the mean number of adult A caninum in dogs of the treated and control groups was 1.3 and 56, respectively; in these naturally infected dogs, efficacy of treatment was calculated to be 97.8%. The mean number of adult Trichuris vulpis recovered in dogs of the control and treated groups at necropsy was 24 and 0, respectively, which yielded treatment efficacy of 100%. Although Uncinaria stenocephala and Toxocara canis appeared also to be removed by use of this dosage, too few dogs were in the study to calculate meaningful efficacies.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ancylostomiasis; Animals; Anti-Bacterial Agents; Dogs; Feces; Female; Macrolides; Male; Parasite Egg Count; Random Allocation; Toxocariasis; Trichuriasis