tribendimidine and Intestinal-Diseases--Parasitic

China was once a country plagued by parasitic diseases. At the beginning of the founding of the People's Republic of China, nearly 80% of the population suffered from parasitic diseases because of poverty and poor sanitary conditions. After nearly 70 years of development, China has made remarkable achievements in the prevention and control of parasitic diseases, and the prevalence of parasitic diseases has been greatly reduced. In addition to organizational leadership from the government and various preventive measures, drug treatment and drug research & development are important and irreplaceable links in prevention and control work. Since the 1950s, China has begun to introduce, produce and imitate antiparasitic drugs from abroad, such as santonin, benzimidazole, and praziquantel. Chinese scientists have also contributed to the optimization of production techniques, improvements in drug formulation, the application in the clinic and the mechanisms of actions of generic drugs. At the same time, China has independently developed tribendimidine (TrBD, a broad spectrum anthelminthic), and its anthelminthic spectrum has been comprehensively studied. It is active against almost 20 parasites, is especially superior to benzimidazoles against Necator americanus, and surpasses the effectiveness of praziquantel against Clonorchis sinensis. In the treatment of tapeworm disease, the traditional Chinese medicines pumpkin seeds and betel nuts have good curative effects for taeniasis. Chinese scientists have explored the action modes and clinical administration methods of pumpkin seeds and betel nuts, which is still the main clinical regimen for the disease. This paper reviews the history and progress of the study of anthelmintics in intestinal helminth infections since the founding of the People's Republic of China and aiming to support clinicians and drug researchers in China and other countries.

Topics: Animals; Anthelmintics; Cestode Infections; China; Clonorchis sinensis; Helminthiasis; History, 20th Century; History, 21st Century; Humans; Intestinal Diseases, Parasitic; Parasitic Diseases; Phenylenediamines; Praziquantel; Taeniasis

We review, for the first time, a 20-year Chinese story of research and development pertaining to tribendimidine, a promising anthelmintic agent that is safe and exhibits a broad spectrum of activity. Tribendimidine was first synthesized at the National Institute of Parasitic Diseases in Shanghai in the mid 1980s. In laboratory studies, tribendimidine showed high efficacy against Nippostrongylus braziliensis in rats, Necator americanus in hamsters, Ancylostoma caninum and Toxocara canis in dogs, and Syphacia mesocriceti in mice. Activity was also found against several species of cestodes in chicken. In clinical trials, a single oral dose of 400 mg tribendimidine, administered to patients infected only with N. americanus, or with N. americanus and Ancylostoma duodenalis, resulted in cure rates of 85.7% (132/154) and 89.8% (53/59), respectively. In comparison, a single oral dose of 400 mg albendazole resulted in significantly lower cure rates, namely 65.5% (91/139; chi(2) = 16.47, P < 0.001) and 71.7% (43/60; chi(2) = 6.29, P = 0.012), respectively. Single oral doses of tribendimidine (300 mg) and albendazole (400mg) were equally effective against Ascaris lumbricoides infections; cure rates were 96.0% (97/101) and 98.1% (101/103), respectively. In 5-14-year-old children with an Enterobius vermicularis infection, treated with a single oral dose of 200 mg tribendimidine, a cure rate of 81.6% (93/114) was observed. Tribendimidine was well-tolerated as only mild and transient side effects were observed. It would be of great public health significance if these findings are confirmed in other epidemiological settings, as more than one-quarter of the world population is currently affected by intestinal nematodes, with only very few drugs currently available on the market.

Topics: Animals; Anthelmintics; China; Humans; Intestinal Diseases, Parasitic; Molecular Structure; Phenylenediamines; Randomized Controlled Trials as Topic; Strongylida; Strongylida Infections

Topics: Animals; Anthelmintics; Cricetinae; Female; Helminthiasis; Humans; Intestinal Diseases, Parasitic; Male; Mice; Phenylenediamines; Rats; Rats, Sprague-Dawley

To further evaluate the efficacy and safety of tribendimidine in treatment of adult patients with intestinal nematode infections.. An open and multi-center clinical trial was conducted in the provinces of Hainan, Sichuan and Guizhou. A total of 1,292 infected cases aged 15-70 years were enrolled in the study. Modified Kato-Katz method was used to diagnose the cases with intestinal nematode infections and assess the efficacy 3-4 weeks post treatment. Patients with Ascaris lumbricoides infection were treated orally with tribendimidine enteric coated tablets at a single dose of 300 mg, while in the patients with Ancylostoma duodenale, mixed A. duodenale and A. lumbricoides, or with other helminth infections, a single dose of 400 mg was administered.. The cure rate and effective rate of the patients with Ancylostoma infection were 88.4% (1,009/1,141) and 99.1% (1,131/1,141), respectively, while in patients with A. lumbricoides infection, they were 95.0% (419/441) and 99.8% (440/441), respectively. The cure rate of tribendimidine enteric coated tablet given to patients with Trichuris trichiura infection at a single dose of 400 mg was 76.8% (109/142). The adverse effect induced by tribendimidine was light and transient with a rate of 3.3% (42/1,292). No apparent impact was seen on blood and urine routine examinations, hepatic and renal functions as well as ECG examination.. It is further confirmed that under the used dosage for expanding treatment in larger sample of patients with various ages and infected with Ancylostoma duodenale, A. lumbricoides and other helminths, tribendimidine enteric coated tablet is safe with satisfactory efficacy.

Topics: Adolescent; Adult; Aged; Animals; China; Humans; Intestinal Diseases, Parasitic; Male; Middle Aged; Nematode Infections; Phenylenediamines; Rhabditida; Tablets, Enteric-Coated; Treatment Outcome; 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

Nematode parasites may be controlled with drugs, but their regular application has given rise to concerns about the development of resistance. Drug combinations may be more effective than single drugs and delay the onset of resistance. A combination of the nicotinic antagonist, derquantel, and the macrocyclic lactone, abamectin, has been found to have synergistic anthelmintic effects against gastro-intestinal nematode parasites. We have observed in previous contraction and electrophysiological experiments that derquantel is a potent selective antagonist of nematode parasite muscle nicotinic receptors; and that abamectin is an inhibitor of the same nicotinic receptors. To explore these inhibitory effects further, we expressed muscle nicotinic receptors of the nodular worm, Oesophagostomum dentatum (Ode-UNC-29:Ode-UNC-63:Ode-UNC-38), in Xenopus oocytes under voltage-clamp and tested effects of abamectin on pyrantel and acetylcholine responses. The receptors were antagonized by 0.03 μM abamectin in a non-competitive manner (reduced Rmax, no change in EC50). This antagonism increased when abamectin was increased to 0.1 μM. However, when we increased the concentration of abamectin further to 0.3 μM, 1 μM or 10 μM, we found that the antagonism decreased and was less than with 0.1 μM abamectin. The bi-phasic effects of abamectin suggest that abamectin acts at two allosteric sites: one high affinity negative allosteric (NAM) site causing antagonism, and another lower affinity positive allosteric (PAM) site causing a reduction in antagonism. We also tested the effects of 0.1 μM derquantel alone and in combination with 0.3 μM abamectin. We found that derquantel on these receptors, like abamectin, acted as a non-competitive antagonist, and that the combination of derquantel and abamectin produced greater inhibition. These observations confirm the antagonistic effects of abamectin on nematode nicotinic receptors in addition to GluCl effects, and illustrate more complex effects of macrocyclic lactones that may be exploited in combinations with other anthelmintics.

Topics: Acetylcholine; Allosteric Site; Animals; Anthelmintics; Cloning, Molecular; Dose-Response Relationship, Drug; Gastrointestinal Tract; Gene Expression Regulation; Haemonchus; Helminthiasis; Indoles; Intestinal Diseases, Parasitic; Ivermectin; Nematoda; Nicotinic Antagonists; Oocytes; Oxepins; Patch-Clamp Techniques; Phenylenediamines; Pyrantel; Receptors, Nicotinic; Xenopus laevis

Golden hamsters infected with Necator americanus were treated orally with a new anthilmintic tribendimidin (N, N'-[bis-4'-(1-dimethyl amino ethylidene amino)phenyl] 1,4-phenyene dimethylidyne amine) at a single dose of 150 mg/kg. One h after medication, some worms showed cuticular swelling, fusion of transverse striations and attachment of host leucocytes onto the worm's damaged cuticular surface. Four h post treatment, the cuticle revealed a moderate swelling or even erosion. Meanwhile, the ventral cutting plates appeared to be swollen. After 8-24 h, severe cuticular swelling, erosion and peeling in female worm tails and male copulatory bursa were seen. No increases in lesions in the small intestinal mucosa of infected golden hamsters were observed 4-8 h after medication.

Topics: Animals; Anthelmintics; Cricetinae; Female; Intestinal Diseases, Parasitic; Intestinal Mucosa; Male; Mesocricetus; Microscopy, Electron, Scanning; Necator; Necatoriasis; Phenylenediamines