In vitro effect of metrifonate on the indices of oxidative stress in Gigantocotyle explanatum.

Helminth infections in general and digenetic trematodes in particular cause a huge economic loss globally to our livestock. Gigantocotyle explanatum is a digenetic amphistome that infects the bile ducts of water buffalo and are highly prevalent in tropical and sub-tropical countries. In the present study, effects of an organophosphate compound, Metrifonate (MF) in three doses, viz., 9.4 × 10-5 M (Dose I), 14.4 × 10-5 M (Dose II), and 19.4 × 10-5 M (Dose III), have been studied in vitro, on the motility and on some enzymatic and non-enzymatic oxidative stress indices in G. explanatum. The worm's motility and their non-enzymatic oxidative stress biomarkers like lipid peroxides measured as thiobarbituric acid-reactive substances (TBARS) and reduced glutathione (GSH) were disrupted significantly in a dose-dependent manner. However, the enzymatic oxidative stress biomarkers like glutathione-S-transferase (GST) and superoxide dismutase (SOD) were affected by MF treatment in a biphasic manner. Exposure to Dose I significantly stimulated the activities of both GST and SOD, whereas exposure to Doses II and III resulted into significant inhibition in a dose-dependent manner. Our findings suggest that MF has potential to be a strong and effective anthelmintic, however, further studies in vitro as well as in vivo are needed to explore further these observations and understand the exact mode of MF action in G. explanatum and other trematodes of veterinary economic importance.

Oxidative stress and hepatotoxicity in the frog, Rana chensinensis, when exposed to low doses of trichlorfon.

Trichlorfon is an organophosphate insecticide that is widely used in aquaculture and agriculture against parasitic infestations and has caused aquatic toxicity to non-target organisms. To evaluate the effects of low doses of trichlorfon on the oxidative stress and hepatotoxicity in amphibians, Chinese brown frogs (Rana chensinensis) were exposed to trichlorfon at concentrations of 0, 0.01, 0.1, and 1.0 mg/L for 2 and 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of malondialdehyde (MDA) in hepatic tissue were examined to evaluate the effects of oxidative stress and lipid peroxidation. The histopathological alternations to the liver were observed through light and transmission electron microscopy (TEM). The results showed that SOD and CAT activities were increased in the livers of frogs exposed to various concentrations of trichlorfon. The GST activity showed no significant changes at any concentration after 2 weeks of exposure, whereas there was an initial increase after exposure to 0.1 mg/L of trichlorfon at 4 weeks. The content of MDA revealed a significant decrease after exposure. Histopathological and ultrastructural studies showed that trichlorfon induced hyalinization, vacuolation, nucleus necrosis, and cellular swelling in hepatocytes. These results suggest that low doses of trichlorfon could induce oxidative stress, lipid peroxidation, and hepatic lesions in frogs, which shows that even lower, non-lethal doses of trichlorfon are potentially toxic to amphibians.

Trichlorfon-induced haematological and biochemical changes in Cyprinus carpio: ameliorative effect of propolis.

Trichlorfon is among the most commonly used products to treat fish parasites in aquaculture. We investigated the effectiveness of propolis in alleviating the toxicity of trichlorfon on haematological and oxidant/antioxidant parameters in carp Cyprinus carpio. Fish were exposed to sublethal concentrations (11 and 22 mg l-1) of trichlorfon, and propolis (10 mg kg-1 of fish weight) was simultaneously administered. At the end of 14 d administration, blood and tissue (liver, kidney, gill) samples were collected. Haematological changes (red and white blood cell count, haemoglobin concentration, haematocrit level and erythrocyte indices: mean corpuscular volume, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration) were determined in the blood samples, while antioxidant parameters (malondialdehyde and reduced glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities) were evaluated in the liver, kidney and gill samples. Trichlorfon led to negative alterations in the haematological and antioxidant parameters investigated. The administration of propolis alleviated this effect and suggests that fish treated with trichlorfon improve their physiological status when fed a propolis-supplemented diet.

Pesticide-contaminated feeds in integrated grass carp aquaculture: toxicology and bioaccumulation.

Effects of dissolved pesticides on fish are widely described, but little is known about effects of pesticide-contaminated feeds taken up orally by fish. In integrated farms, pesticides used on crops may affect grass carp that feed on plants from these fields. In northern Vietnam, grass carp suffer seasonal mass mortalities which may be caused by pesticide-contaminated plants. To test effects of pesticide-contaminated feeds on health and bioaccumulation in grass carp, a net-cage trial was conducted with 5 differently contaminated grasses. Grass was spiked with 2 levels of trichlorfon/fenitrothion and fenobucarb. Unspiked grass was used as a control. Fish were fed at a daily rate of 20% of body mass for 10 d. The concentrations of fenitrothion and fenobucarb in pond water increased over time. Effects on fish mortality were not found. Fenobucarb in feed showed the strongest effects on fish by lowering feed uptake, deforming the liver, increasing blood glucose and reducing cholinesterase activity in blood serum, depending on feed uptake. Fenobucarb showed increased levels in flesh in all treatments, suggesting bio-concentration. Trichlorfon and fenitrothion did not significantly affect feed uptake but showed concentration-dependent reduction of cholinesterase activity and liver changes. Fenitrothion showed bioaccumulation in flesh which was dependant on feed uptake, whereas trichlorfon was only detected in very low concentrations in all treatments. Pesticide levels were all detected below the maximum residue levels in food. The pesticide-contaminated feeds tested did not cause mortality in grass carp but were associated with negative physiological responses and may increase susceptibility to diseases.

Comparative efficacy of trichlorphon and trichlorphon/ivermectin combination treatment against anthelmintic-resistant cattle nematodes in Argentina.

Twenty-four Holando Argentino male calves were treated orally with 50 mg/kg body weight trichlorphon (TCF); 0.2 mg/kg body weight subcutaneous ivermectin (IVM); a combination of TCF+IVM at the same doses and administration routes; or remained untreated (control group). All calves were necropsied at day 14 post treatment for counting and identification of worms from abomasum, small and large intestines and lungs to determine the absolute efficacy (controlled efficacy test) for each treatment. Using the faecal egg count reduction test, the efficacy was 63.7 % for TCF, 72.3 % for IVM and 99.2 % for TCF+IVM. The absolute efficacy of IVM and IVM+TCF was 100 % against Haemonchus placei, Trichostrongylus axei and Ostertagia ostertagi (p < 0.05). TCF showed a similar level of efficacy except against O. ostertagi (84.7 %). Efficacy of the treatments against Cooperia oncophora/pectinata/mcmasteri was 80.4 % for IVM, 95.7 % for TCF and 99.6 % for TCF+IVM; against Trichostrongylus colubriformis was 79 % for IVM, 86.2 % for TCF and 94.1 % for TCF+IVM; against Nematodirus helvetianus was 0 % for IVM, 100 % for TCF and 93.8 % for TCF+IVM. The efficacies of TCF, IVM and TCF+IVM were 100 % against Oesophagostomum radiatum and Trichuris spp. The efficacy of TCF against Dictyocaulus viviparus was 52 % and 100 % for IVM and IVM+TCF, respectively. This is the first report of Trichostrongylus colubriformis and Nematodirus helvetianus resistant to ivermectin treatment in cattle of Argentina. The TCF+IVM combination could be an alternative for the control and treatment of nematode infections including IVM-resistant strains.

Metrifonate alters antioxidant levels and caspase activity in cerebral cortex of Wistar rats.

Metrifonate (trichlorfon) is an inhibitor of acetylcholinesterase (AChE). It was used as an Alzheimer's disease (AD) drug; however, the application was withdrawn due to adverse effects. Implication of metrifonate for the antioxidant status and regulation of apoptotic processes was evaluated in the present study. Wistar rats (six per group) were exposed subcutaneously to either 60 or 120 mg/kg of body weight of metrifonate and compared with the controls treated with saline only. Cerebral cortex and liver tissues were collected from animals 40 min after exposure. Activities of AChE, glutathione reductase, glutathione-S-transferase, caspase 3, total protein level, thiobarbituric acid reactive substances, reduced glutathione level and ferric reducing antioxidant power (FRAP) were assayed in the tissue samples. Metrifonate had only lower impact on oxidative stress in the liver. Cerebral cortex tissues had decreased AChE and increased caspase 3 activities as well as the FRAP level. Owing to the novel findings, suitability of metrifonate for AD therapy is discussed.

Organophosphate pesticide trichlorfon induced neurotoxic effects in freshwater silver catfish Rhamdia quelen via disruption of blood-brain barrier: Implications on oxidative status, cell viability and brain neurotransmitters.

The aim of this study was to evaluate whether rupture on blood-brain barrier (BBB) can be a pathway for trichlorfon-induced neurotoxic effects, and to investigate its implications on oxidative status, cell viability and brain neurotransmitters in silver catfish (Rhamdia quelen). The BBB permeability was increased in fish exposed for 24 h to 22 mg/L of trichlorfon compared to the control group, as well as in those exposed to 11 and 22 mg/L of trichlorfon for 48 h. Compared to the control group, brain reactive oxygen species and lipid peroxide levels were higher when exposed to 22 mg/L of trichlorfon and 11 and 22 mg/L of trichlorfon after 24 h and 48 h, respectively, while the antioxidant capacity against peroxyl radical levels was lower. Exposure to 22 mg/L of trichlorfon for 24 h reduced brain cell viability compared to the control group, together with 11 and 22 mg/L of trichlorfon for 48 h. Also, brain AChE, Na+ and K+-ATPase activities were reduced in those fish exposed to trichlorfon compared to the control group. Thus, the rupture of BBB can be considered an important pathway involved in trichlorfon-induced neurotoxic effects, which contributes to brain oxidative damage and important changes on brain neurotransmitters.

Trichlorfon effects on mouse oocytes following in vivo exposure.

Trichlorfon (TCF) is a widely used pesticide, which according to some epidemiological and experimental data, is suspected of being aneugenic in human and mouse cells. In particular, in vitro studies in mouse oocytes showed the induction of aneuploidy and polyploidy at the first meiotic division and of severe morphological alterations of the second meiotic spindle. We have tested the hypothesis that an acute treatment of mice with TCF might similarly affect chromosome segregation in maturing oocytes. Superovulated MF-1 mice were intraperitoneally injected with 400mg/kg TCF or orally administered with 600mg/kg TCF either at the time of or 4h after human chorionic gonadotrophin (HCG) injection. Oocytes were harvested 17h after HCG and metaphase II chromosomes were cytogenetically analyzed. No significant increase of aneuploid or polyploid cells was detected at any treatment condition. A significant (p<0.001) decrease of metaphases showing premature chromatid separation or premature anaphase II in all TCF-treated groups with respect to controls suggested that TCF treatment may have delayed the first meiotic division. To evaluate possible effects of the pesticide upon the second meiotic division, a group of females orally treated with 600mg/kg TCF at resumption of meiosis was mated with untreated males and zygotes were collected for cytogenetic analysis. No evidence of aneuploidy induction was obtained, but the frequency of polyploid zygotes was increased fivefold over the control level (p<0.01). Such polyploid embryos might have arisen from fertilization of oocytes that were either meiotically delayed and still in metaphase I at fertilization or progressed through anaphase II without cytokinesis. These findings show that in vivo studies on aneuploidy induction in oocytes may yield results different from those obtained by in vitro experiments and that both kinds of data may be necessary for risk assessment of environmentally relevant exposures.

Spatial discrimination deficits by excitotoxic lesions in the Morris water escape task.

The effects of the cholinesterase inhibitors (ChEI) metrifonate and donepezil were assessed on spatial performance of rats with bilateral lesions of the entorhinal cortex (EC), which is thought to model early changes in the brains of patients suffering from Alzheimer's disease. In the present study, we found that spatial discrimination deficits in rats, induced by bilateral ibotenic acid (IBO) lesions of the EC region can partially be antagonised by treatment with the cholinesterase inhibitors metrifonate (30 mg kg(-1)) and donepezil (0.3 and 3 mg kg(-1)). Performance was improved in the spatial discrimination task compared with that of the EC-lesioned control group. It is concluded that the rat with bilateral EC lesions is a suitable deficit model for the assessment of effects of putative Alzheimer therapeutics.

A comparison of the effects of two inhibitors on brain cholinesterase.

In the present paper various routes of administration (i.m., i.v. and i.c.v.) of physostigmine are compared and the effect of two drugs producing inhibition of cholinesterase, physostigmine and metrifonate, on the activity of cholinesterase in the brain of the rat and on levels of acetylcholine (ACh) and choline (Ch). After intramuscular administration of physostigmine (500 micrograms/kg), the activity of cholinesterase in brain was maximally inhibited (76%) at 5 min and recovered to 50% at 40 min. At 5 min, areas of the brain such as the striatum and medulla oblongata showed 49 and 67% inhibition, respectively. Levels of physostigmine in brain peaked at 5 min (1.28 nmol/g). With the exception of the cerebellum, there was a direct correlation between the concentration of physostigmine and inhibition of cholinesterase in a given area. With the intravenous route of administration (100 micrograms/kg), the activity of cholinesterase in brain was maximally inhibited (67%) at 3 min and recovered to 50% at 12 min. At 60 min, the activity of cholinesterase was 90% of control. Levels of physostigmine in brain peaked at 2 min (0.47 nmol/g). At 15 min, with intraventricular administration (4 micrograms), the activity of cholinesterase was 73% and 31% inhibited in the hippocampus and striatum, respectively. Other areas of brain showed intermediate values of inhibition. Levels of acetylcholine were increased 18 and 22% above control in the striatum and hippocampus, respectively and did not change in the medulla. After intramuscular administration of metrifonate (80 mg/kg), the activity of cholinesterase decreased to 26% at 30 min, recovered to 50% at 180 min and returned to 74% at 360 min. Levels of acetylcholine increased by 45% at 45 min, then returned to normal by 120 min. When metrifonate (2.5 mg) was given intraventricularly the activity of cholinesterase decreased in the left side injected at 30 min to 20% in hippocampus; 22% in the medulla; 50% in the cerebellum; 58% in the striatum and 72% in cortex. Levels of acetylcholine increased maximally at 45 min in hippocampus and cortex and peaked in the striatum at 60 min. The greatest increases were seen in the hippocampus and cortex with 60 and 55%, respectively. The results of this study reveal some major differences between the effects of the two substances in brain. Four major conclusions are apparent from this study. First, based on these results, it is concluded that metrifonate is more likely to produce a therapeutic effect in humans.(ABSTRACT TRUNCATED AT 400 WORDS)

Dipterex teratogenicity in the rat, hamster, and mouse when given by gavage.

Dipterex was teratogenic after administration by gavage (t.i.d.) at a dose level of 480 mg/kg-day to the CP rat on days 6 through 15 of gestation, but not when administered only on days 8 or 10 of gestation. A positive teratogenic response also occurred in the hamster after administration on days 7 through 11 of gestation at 400 mg/kg-day; the apparent no-effect level for the criteria studied was 200 mg/kg-day. Embryotoxicity, but not teratogenicity, occurred after administration of 400 mg/kg-day on day 8 of gestation. In both species, the teratogenicity seen was not merely due to reduced maternal food consumption during the period of exposure. The mouse was less susceptible to Dipterex than were the rat and hamster, but a significant increase in the incidence of cleft palates resulted from exposure on days 10 through 14, or on days 12 through 14 of gestation.

Evaluating response to metrifonate.

Metrifonate, administered orally to patients with probable Alzheimer's disease in a once-daily dose, readily enters the brain and inhibits brain acetylcholinesterase (AChE) activity in a dose-dependent fashion. Metrifonate is a prodrug, converted non-enzymatically to 2,2-dichlorovinyl dimethyl phosphate, a long-acting inhibitor of AChE that produces stable enzyme inhibition over time. In combination, these pharmacologic characteristics lead to a reduced side effect profile in comparison with several other cholinesterase inhibitors. Both preliminary and confirmatory pivotal studies have shown that significant cognitive improvement is achieved with this medication in comparison with placebo in patients with probable Alzheimer's disease. Moreover, these studies also have demonstrated that metrifonate benefits the global function--a measure comprising domains of cognition, function, activities of daily living, and behavior--of patients with Alzheimer's disease. The medication is generally well tolerated, and no significant laboratory abnormalities occur. Therefore, metrifonate is a useful treatment for the symptoms of Alzheimer's disease.

Metrifonate: update on a new antidementia agent.

OBJECTIVE: To review preclinical and clinical studies of metrifonate, a cholinesterase inhibitor relevant to the treatment of Alzheimer's disease. DATA SOURCES: English-language literature identified by MEDLINE using the term metrifonate was reviewed, and bibliography-sorted searches were conducted. STUDY FINDINGS: Metrifonate is an organophosphate cholinesterase inhibitor effective in the treatment of the cognitive symptoms of Alzheimer's disease and currently under review by the U.S. Food and Drug Administration. The active metabolite of metrifonate, 2,2-dimethyldichlorovinyl phosphate (DDVP), irreversibly inhibits the acetylcholinesterase enzyme. Although the elimination half-life of DDVP is 2-3 hours, the half-life of cholinesterase inhibition by DDVP is stable (26 days). Metrifonate can be administered once daily. Animal studies demonstrate its efficacy in enhancing memory in animals that have cholinergic deficits. Double-blind, placebo-controlled studies have shown the benefit of metrifonate compared with placebo in improving scores on the Clinical Global Impression of Change scale, the Alzheimer's Disease Assessment Scale-cognitive subscale, and the Neuropsychiatric Inventory. CONCLUSION: Metrifonate is a useful addition to our limited armamentarium of agents helpful against the cognitive deficits of Alzheimer's disease.

AR-R 17779 improves social recognition in rats by activation of nicotinic alpha7 receptors.

RATIONALE: Nicotine and agonists at alpha(4)beta(2) and alpha(7) nicotinic acetylcholine receptors (nAChRs) improve learning and memory. The alpha(7)-nAChR subtype is of special interest, since it appears to play no role in the abuse liability of nicotine. OBJECTIVES AND METHODS: To further investigate the role of the alpha(7)-nAChR in learning and memory, the effects of the specific alpha(7)-nAChR agonist AR-R17779 on cognition were measured in the rat social recognition test (SRT) and the effect of the alpha(7)-nAChR antagonist methyllycaconitine (MLA) was studied. The SRT and a scopolamine-induced deficit version were validated with the acetylcholinesterase inhibitor metrifonate. Social memory was measured by the ability of an adult rat to recognize a juvenile rat after a delay. The difference in social interaction time (SIT) was measured between two encounters. The difference in SIT is expressed as percent reduction in social interaction time (%RSIT). RESULTS: Metrifonate (10 and 30 mg/kg PO) increased %RSIT in a behaviorally specific manner, employing a 24-h interval and reversed the scopolamine-induced deficit at a retention time of 15 min. Likewise, AR-R17779 increased %RSIT in unimpaired animals (1, 3, 10 and 30 mg/kg SC) employing a 24-h retention interval, and reversed the scopolamine-induced deficit (0.3 and 1 mg/kg SC) after a 15-min retention interval. The effects of AR-R17779 (1 mg/kg SC) in unimpaired animals were reversed by MLA (10 micro g ICV), which induced a decrease of %RSI at a 15-min retention interval when given alone. CONCLUSIONS: AR-R17779 increased social recognition memory by activation of alpha(7)-nAChRs, suggesting that alpha(7)-nAChR agonists possess cognitive-enhancing properties.

Teratogenic effects of trichlorfon (Metrifonate) on the guinea-pig brain. Determination of the effective dose and the sensitive period.

The conditions (sensitive period and doses) for producing hypoplasia in guinea-pig offspring after treatment of pregnant guinea-pigs with the organophosphorous agent trichlorfon (metrifonate, 0,0-dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate) were examined. The results showed that the minimal dose required was 100 mg/kg on three consecutive days. For the cerebellum the most sensitive period was 42-44 day of gestation, for cortex the most vulnerable period was gestational days 48-50. The doses could be given either per os or subcutaneously. Almost all regions of the brain were reduced in weight. Cerebellum was the most vulnerable region, but also the medulla and hypothalamus were greatly reduced in weight. The mechanism behind the teratogenic effect is not known, but alkylation of DNA or an effect on its repair mechanism are possible effects.

Effects of chronic metrifonate treatment on cholinergic enzymes and the blood-brain barrier.

After an acute (4 h) treatment with an irreversible cholinesterase inhibitor organophosphate, metrifonate (100 mg/kg i.p.), the activities of both acetyl- and butyrylcholinesterase were inhibited (66.0-70.7% of the control level) in the rat brain cortex and hippocampus. There were no significant changes in the acetyl- and butyrylcholinesterase activities in the olfactory bulb, or in the choline acetyltransferase activity in all three brain areas. After chronic (2 or 5 week) metrifonate treatment (100 mg/kg daily i.p.), the activities of both cholinesterases were substantially inhibited in the rat brain cortex and hippocampus (15.8-31.8% of the control levels), but there was no inhibition of the choline acetyltransferase activity. Moreover, chronic metrifonate treatment did not have any effect on the distribution of the acetylcholinesterase molecular forms. In vitro, metrifonate proved to be a more potent inhibitor of butyryl- than of acetylcholinesterase in both the cortex and the hippocampus. In the hippocampus, the butyrylcholinesterase activity was twice as sensitive to metrifonate inhibition as that in the cortex (IC50 values 0.22 and 0.46 microM, respectively). The effects of chronic (5 week) metrifonate treatment on the blood-brain barrier of the adult rat were examined. The damage to the blood-brain barrier was judged by the extravasation of Evans' blue dye in three brain regions: the cerebral cortex, the hippocampus, and the striatum. No extravasation of Evans' blue dye was found in the brain by fluorometric quantitation. These data indicate that chronic metrifonate treatment may increase the extracellular acetylcholine level via cholinesterase inhibition, but it does not have any effects on the blood-brain barrier. Therefore, it appears reasonable to hypothesize that cholinesterase activities do not play a role in the blood-brain barrier permeability.

Eighteen-month follow-up on the treatment of urinary schistosomiasis with a single dose of metrifonate.

Egg excretion of school children with urinary schistosomiasis treated with a single 10 mg/kg dose of metrifonate was monitored over a period of 18 months. At 18 months 68.8% of infected children showed a greater than 90% reduction in egg excretion and 23.7% had ceased excreting eggs. During the study period 25% of children with no evidence of infection at the start of the trial had become infected, while 45.5% of children apparently cured by the metrifonate treatment had recommenced egg excretion. The evidence suggested that reinfection rather than recovery of adult worms was responsible. Children with scanty or light infections, in general, showed increasing egg excretion rates during the following period, while those with heavy or severe infections showed a sustained reduction. In view of this, single dose metrifonate may be a useful approach to mass treatment in a schistosomiasis control program, resulting in significant reduction in egg excretion in those most likely to be important sources of transmission.

The effectiveness of metrifonate in reducing hookworm infection in Kenyan school children.

The reduction in hookworm egg counts was determined in children treated with 1 and 2 doses of metrifonate. Kenyan primary school children were allocated to receive either 10.0 mg (n = 53) or 7.5 mg (n = 53) of metrifonate per kg of body weight (mg/kg) or a placebo (n = 26). Two doses of 10.0 mg/kg reduced hookworm egg counts (from arithmetic means of 4,177 to 438 eggs per gram of feces [epg]) more than did 2 doses of 7.5 mg/kg (from 4,329 to 1,392 epg; P less than 0.01). Two doses of metrifonate reduced egg counts more than did 1 dose (P less than 0.0001). The placebo group did not show a significant change in egg counts. The single dose of 10.0 mg/kg led to a 78% reduction in hookworm egg counts (from 4,177 to 918 epg), a level unlikely to cause iron deficiency anemia. This was as effective as 2 doses of 7.5 mg/kg, and was more easily administered than 2 or 3 doses. The further reduction after a second dose of 10.0 mg/kg (to 438 epg) is probably not of practical importance. This study shows that metrifonate, even in a single dose for treatment of S. haematobium, is also useful in reducing hookworm egg counts.

Single-dose metrifonate for the treatment of Schistosoma haematobium infection in an endemic area of Zimbabwe.

The excretion of Schistosoma haematobium eggs by school children in an endemic area of Zimbabwe was studied for 16 weeks following a single oral dose of 10 mg/kg body weight metrifonate. By 16 weeks, 40.7% of the children had ceased excreting eggs. The mean reduction in egg excretion was 75.1%, but over half the children showed a greater than 90% reduction. Of the treatment failures, the majority showed less marked or transient reductions in egg excretion, though evidence suggested that 17.5% of the failures may have been due to reinfection.

The effect of a single dose of metrifonate on Schistosoma haematobium infection in Egyptian school children.

Egyptian school children infected with Schistosoma haematobium and treated with a single dose of metrifonate, 10 mg/kg body weight, had a marked reduction in urine egg counts reaching 90% during a 30-week follow-up. While cure rate was higher among lightly infected persons, percentage reduction in egg counts was greater among the heavily infected. After a summer period of probable high risk exposure reinfection rate in those children who were treated and cured was 4.7% as compared to 6% in previously uninfected children.