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PubMed2000

Anthelmintic drugs for treating worms in children: effects on growth and cognitive performance.

BACKGROUND: Helminth (worm) infections are widespread and are thought to contribute to poor nutritional status, anaemia, and impaired growth and learning in children. OBJECTIVES: To summarise the effects of anthelmintic drug treatment in children in relation to their growth and cognitive performance. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and the reference lists of articles. We also contacted experts in the field. SELECTION CRITERIA: Randomised and quasi-randomised trials of drug treatment compared with placebo or no drug treatment for intestinal helminths in children. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for additional information. MAIN RESULTS: Thirty trials involving more than 1500 children were included. There was potential for bias from inadequate concealment of allocation. Studies varied in relation to target groups, drugs administered and treatment regimens. Compared to placebo or no drug treatment, drug treatment for helminths was associated with some positive effects on change in weight, height and skinfold thickness. However there was significant heterogeneity between the results of the trials. There were some positive effects on mean weight change in the trials reporting this outcome; after a single dose (any anthelminth) the pooled estimate was 0.24 kg, (95% CI 0.15 to 0.32; fixed effects model assumed); and 0.38 kg (95% CI 0.00 to 0.77; random effects model assumed). Results from trials giving multiple doses showed mean weight change under one year of follow up of 0.10 kg (95% CI 0.04 to 0.17; fixed effects assumed); or 0.15 (95% CI 0.00 to 0.30; random effects assumed). At more than one year of follow up, mean weight change was 0.12 kg (95% CI -0.02 to 0.26; fixed effects assumed) and 0.43 (95% CI -0.61 to 1.47; random effects model assumed). Results from studies of cognitive performance were mixed and inconclusive. REVIEWER'S CONCLUSIONS: There is some limited evidence that routine treatment of children in areas where helminths are common has small effects on weight gain, but this is not consistent between trials. There is insufficient evidence to know whether this intervention improves cognitive performance. Our interpretation of these results is that the current public health programme investments in this intervention, based on the expectation that there will be an improvement in growth and learning, are not based on consistent or reliable evidence.

Adolescent↗
PubMed1981

Synthesis and biological activities of quinoline hydrochlorides as anthelmintics.

In the present paper twenty five benzene substituted-4-amino quinoline derivatives were synthesized by condensation of 4-chloroquinolines with alkyl p-aminobenzoate or salicylate. The compounds were screened for antiacetylcholinesterase activity and also anthelmintic activity against Hymenolepis nana. Some of these compounds have shown interesting results.

Animals↗
PubMed1977

Anthelmintic dihydroquinoxalino[2,3-b]quinoxalines.

A series of dihydroquinoxalino[2,3-b]quinoxalines was synthesized and tested for anthelmintic activity in a model assay. The most promising compound, 5,12-diacetyl-5,12-dihydroquinoxalino[2,3-b]quinoxaline, was orally effective in sheep at a dose of 200 mg/kg against a broad range of helminths.

Animals↗
PubMed1991

Electrochemical reduction of arylethenylpyridinium salts: relation to structure and anthelmintic activity.

Cyclic voltammetry data were obtained for a series of 1(1-)- and 1(2-arylethenyl)pyridinium salts. The 1(1-arylvinyl) salts exhibited more negative reduction potentials than their N-beta-styryl counterparts. Rationalizations of the reduction values are provided. Differences in reduction potentials within a series are discussed utilizing substituent constant effects. Correlations exist for the electrochemical data and anthelmintic activity.

Animals↗
PubMed2001

Synthesis and anthelmintic activity of thioamide analogues of cyclic octadepsipeptides such as PF1022A.

The tetra- and mono-thionated cyclic octadepsipeptides represent novel cyclic octadepsipeptide derivatives with broad-spectrum activity against parasitic nematodes in mice and sheep. Some of these show better activity than the potent natural anthelmintic cyclic octadepsipeptide PF1022A against Hymenolepis nana, Heterakis spumosa and Trichinella spiralis larvae in mice. In particular, they show improved efficacy against Haemonchus contortus and Trichostrongylus colubriformis in sheep compared with PF1022A. Here we report on two different and simple synthetic pathways for this new class of thionated cyclic octadepsipeptides.

Animals↗
PubMed2002

Synthesis of anthelmintically active N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A.

The N-methylated amidoxime analogues of the cyclic octadepsipeptide PF1022A represent novel derivatives with activity against Trichinella spiralis Owen and Nippostrongylus brasiliensis Lane in vitro and against parasitic nematodes in mice and sheep. Some of them show better activity against Hymenolepis nana Siebold, Heterakis spumosa Schneider and Heligmosomoides polygyrus Dujardin in mice than the natural product PF1022A. In particular an improved efficacy against Haemonchus contortus Rudolphi and Trichostrongylus colubriformis Giles in sheep compared to the potent cyclic octadepsipeptide PF1022A and its mono-thionated derivative has been observed. Here we report on a specific modification at the N-methyl amide linkage by using the mono-thionated PF1022A, resulting in novel anthelmintically active backbone analogues of PF 1022A.

Animals↗
PubMed2006

In vitro anthelmintic activity of Melia azedarach naturalized in Argentina.

The anthelmintic activity of the drupe extracts of Melia azedarach L. (Meliaceae) growing in Argentina was tested against tapeworms, hookworms, nodular worms and earthworms, and was shown to be better than the standards piperazine phosphate and hexylresorcinol against tapeworms and hookworms, respectively.

Ancylostomatoidea↗
PubMed1977

Mutagenicity studies with praziquantel, a new anthelmintic drug: tissue-, host-, and urine-mediated mutagenicity assays.

Praziquantel, a new anthelmintic drug with activity against all species of schistosomes pathogenic to man, and against a wide range of Cestodes, was tested for mutagenic potential. For the detection of both base substitutions and frameshift mutations, Salmonella typhimurium TA 100 and TA 98 were used as tester strains. Using the plate assay with and without added S-9, host-mediated assay and urine-mediated assay without and after incubation with beta-glucuronidase/arylsulfatase, no mutagenic activity could be detected.

Administration, Oral↗
PubMed1993

Comparative effects of anthelmintics on c-MDH from Molinema dessetae (Nematoda: Filarioidea) and from a mammal.

Malate dehydrogenase (MDH) (E.C.1.1.1.37) activity was detected in the filaria Molinema dessetae at a level similar to those found in other filariae. In M. dessetae, the cytoplasmic form (c-MDH) predominated and the study was performed on partially purified fractions. The pH optimum for oxaloacetate reduction was 6.1, with maximal activity at 7811 nmol min-1 mg protein-1, but high concentrations of oxaloacetate inhibited MDH activity. The Km value for oxaloacetate was determined as 22 microM for M. dessetae c-MDH and 33 microM for mammalian c-MDH. Anthelmintic drugs were compared as potential inhibitors of filarial and mammalian c-MDH. Among the compounds evaluated, amocarzine showed a specific inhibitory effect on filarial c-MDH through only at high concentrations. Suramin alone showed an inhibitory effect at low concentrations (Ki = 1.15 microM) but without selective action towards filarial c-MDH. The suramin type of inhibition was found to be competitive. Suramin probably acts on both enzymes in the same manner. Nevertheless, M. dessetae c-MDH is proposed as a suitable enzyme assay model to screen MDH inhibitors as potential filaricides.

Animals↗
PubMed1984

The fumarate reductase system as a site of anthelmintic attack in Ascaris suum.

Various benzimidazole compounds have been shown to be highly effective as inhibitors (up to 50% reduction of activity) in vitro of the helminth-specific enzyme, fumarate reductase, of Ascaris suum. Anthelmintically active and inactive benzimidazoles were similarly effective as inhibitors of enzyme activity. Albendazole-induced inhibition of fumarate reductase was not observed when the enzyme was preincubated with NADH.

Animals↗
PubMed1983

Pharmacokinetic behaviour and anthelmintic efficacy of 1-n-butyl carbamoyl oxfendazole given by intramuscular injection.

Oxfendazole (OFZ) was chemically modified to 1-n-butyl carbamoyl OFZ (C4-OFZ) in an attempt to improve the solubility of OFZ and enable it to be administered by injection. After intramuscular injection to sheep and cattle, C4-OFZ was metabolised to OFZ which resulted in higher plasma OFZ concentrations that persisted for a considerably longer period than those observed following administration of OFZ orally. The anthelmintic efficacy of injected C4-OFZ was tested, in sheep, against strains of Trichostrongylus colubriformis, Haemonchus contortus and Ostertagia circumcincta, which were highly resistant to benzimidazoles. In all cases, the C4-OFZ treatment showed a significant improvement in efficacy over the conventional oral OFZ drench.

Animals↗
PubMed1979

Oxfendazole--anthelmintic activity in Egyptian goats artificially infected with gastrointestinal nematodes.

The recently developed benzimidazole anthelmintic, oxfendazole, was tested against artificial nematode infestations in Egyptian goats using oral dosing at 4.5 and 2.8 mg/kg. A 100% clearance of mature and immature Haemonchus contortus, Trichostrongylus axei, Ostertagia circumcincta, Coopera curticei, Bunostomum trigonocephalum and Chabertia ovina was obtained at the 4.5 mg/kg level. Very high levels of clearance against the mature worms were obtained at 2.8 mg/kg but the drug was less effective against immature worms at the lower dose rate. PCV, hemoglobin concentration and total erythrocyte counts declined after infection but became significantly (P less than 0.001) raised in treated animal.

Animals↗
PubMed1986

Evaluation of three strategic anthelmintic programmes for the prophylaxis of parasitic gastroenteritis in cattle in Nigeria.

Three strategic anthelmintic programmes were evaluated for use in the prophylaxis of parasitic gastroenteritis in naturally infected N'Dama cattle aged 12 to 21 months at Nsukka, eastern Nigeria. Four groups A, B, C and D were used which grazed together and each consisted of seven animals. Group A was treated in April, July, August and December. Group B was dosed in April, August and December and Group C in July, August and September. Group D received no treatments. All three treatment programmes substantially reduced pasture contamination while programmes A and B also resulted in significantly improved weight gains. The potential net profit from the three programmes was 38 X 0 Naira, 33 X 10 Naira and 24 X 74 Naira per head respectively. The early dry season (December) treatment in Groups A and B contributed relatively little to their overall performance but would have minimised the carryover of infection to the following wet season.

Animals↗
PubMed2002

Analysis and partial reversal of multidrug resistance to anthelmintics due to P-glycoprotein in Haemonchus contortus eggs using Lens culinaris lectin.

Our previous work has shown that drug efflux pumps close to MDR1 P-glycoprotein (Pgp) can regulate anthelmintic efflux in nematodes in a way similar to that of the mutidrug resistance system (MDR) in vertebrate cancer cells. In the present study, the role of the glycosylation of Pgp was studied using a lectin specific for the alpha-mannosyl residues ( Lens culinaris agglutinin, LCA). Highly significant reversion (up to 50%) in the resistance to thiabendazole of eggs pre-treated with the lectin was obtained. Flow cytometric examinations were performed using FITC-labelled lectin. The results demonstrated that: (1) the number of Pgp sites was higher in resistant H aemonchus contortus, (2) resistance can also be associated with a decreased affinity of LCA for these sites, (3) eggs stained with LCA were also stained with specific MDR1 monoclonal antibodies. The implication of the glycosylation of Pgp in the activity and/or degradation of these pumps in eukaryotic cells is discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Anthelmintic efficacy of Flemingia vestita (Fabaceae): alteration in the activities of some glycolytic enzymes in the cestode, Raillietina echinobothrida.

The crude root-peel extract of Flemingia vestita, genistein and praziquantel were tested against some selected glycolytic enzymes--hexokinase (HK), phosphofructokinase (PFK), phosphoenolpyruvate carboxykinase (PEPCK), pyruvate kinase (PK), lactate dehydrogenase (LDH), malate dehydrogenase (MDH) and malic enzyme (ME)--of the fowl tape worm, Raillietina echinobothrida. Following exposure to the various treatments, the activities of HK, PFK, PEPCK and LDH increased by 33-39%, 41-125%, 44-49% and 55-67%, respectively, and that of PK decreased by 14-26% in the parasite at the time of paralysis. The MDH and ME activities of the tissue homogenate were also found to be higher by 22-43% and 28-59%, respectively, in the treatments. However, whereas the activity of both cytosolic and mitochondrial MDH increased by 33-58% and 43-73%, respectively, the cytosolic ME activity showed an increase of 33-39%, and there was no significant enhancement in the mitochondrial ME activity. Histochemically, the enhancement in the activities of HK, LDH and MDH was clearly discernible. The enhanced glycolytic activity seems to be a function of anthelmintic stress caused by the phytochemicals.

Animals↗
PubMed2005

Putative G protein-coupled receptors in parasitic nematodes--potential targets for the new anthelmintic class cyclooctadepsipeptides?

Parasitic nematodes cause major problems in livestock animals. Resistances to the most commonly used drugs are arising. The cyclooctadepsipeptide emodepside belongs to a new class of anthelmintics. A receptor for emodepside, Hc110-R, was previously identified in Haemonchus contortus. We have identified the complete coding sequences of putative orthologues in Cooperia oncophora and Ostertagia ostertagi, tri-chostrongyles in cattle. The putative receptors were named depsiphilins. The deduced amino acid sequence of C. oncophora depsiphilin has a similarity of 91% to the O. ostertagi sequence. The similarity of both the C. oncophora and O. ostertagi depsiphilin to Hc110-R is 89%, based on the amino acid sequence. The depsiphilins share 46% identity with the latrophilin-like protein 1 in Caenorhabditis elegans and 47% identity with a hypothetical protein in Caenorhabditis briggsae. Hc110-R and the latrophilin-like proteins of C. elegans were previously reported to be putative G protein-coupled receptors (GPCRs) and to be related to mammalian latrophilins. A seven transmembrane domain, a GPCR proteolytic site, and other conserved domains characteristic of receptors of the latrophilin group were identified within the depsiphilins. Therefore it seems reasonable to allocate the depsiphilins to the previously described latrophilins and latrophilin-like proteins.

Amino Acid Sequence↗