Trichlorfon for treatment of cutaneous habronemosis - evaluation of intravenous regional perfusion in the distal equine limbs

Background: Equine cutaneous habronemiasis is common in the distal regions of the limbs. Organophosphates, appliedsystemically, one previously used treatment, which is highly effective, but currently in disuse, due to the risks of intoxication. Regional perfusion is a potential technique for distal limb wounds, since, in addition to being used in low doses, itprevents systemic circulation of the drug and possible intoxication, and has a lower treatment cost. The current work aimedto perform clinical, laboratory, and venography evaluations of the use of trichlorfon in regional intravenous perfusion, asa possible form of treatment for cutaneous habronemosis in the distal region of equine limbs.Materials, Methods & Results: Twelve equines were used, divided into 2 groups, with the left thoracic limb (LTL) beingthe test limb, and the right thoracic limb (RTL) the control limb. At moment zero (M0), distal radiography and venographywere performed. The tourniquet was then loosened and after 5 min, at moment one (M1), the tourniquet was repositionedfor 1.25 mg/kg (G1) and 5.5 mg/kg (G2) trichlorfon injections into the left thoracic limb, diluted in 20 mL of Ringer’s lactate solution, and 20 mL of Ringer’s lactate solution was applied to the right thoracic limb. The tourniquet was maintainedfor 30 min after infusion in both groups. At moment 2 (M2), 4 days later, blood tests, radiography, and venography wererepeated. Every day between M0 and M2, physical examinations were performed, including measurement of the pastern,fetlock, and coronet band, and a lameness examination. There were no significant alterations in clinical parameters, behavior, and appetite. In the blood cell count, there was an increase in leukocytes on D4 in G2, although remaining withinthe reference values for the species. The biochemical tests showed no alterations. There were no changes in the circumferences evaluated and 4 equines from G2 presented lameness in the LTL and...

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.

The efficacy of trichlorphon and naphthalophos against multiple anthelmintic-resistant nematodes of naturally infected sheep in Argentina.

An anthelmintic efficacy trial was conducted in sheep harbouring anthelmintic-resistant worms in Argentina. Seventy lambs were selected from a flock that had been grazed on pastures infected with trichostrongyles previously shown to be resistant to the main anthelmintic groups. Lambs were allocated to comparable groups of ten animals each and treated with trichlorphon (50 mg/kg body weight (b.w.) orally); naphthalophos (50 mg/kg b.w. orally); ivermectin (0.2 mg/kg b.w. subcutaneously); fenbendazole (5 mg/kg b.w. orally); levamisole (8 mg/kg b.w. subcutaneously) and closantel (10 mg/kg b.w. orally). There was also an untreated group. The dose selection was based on manufacturer's recommendations.Faecal samples were collected 0 and 10 days post treatment to estimate efficacy (faecal egg count reduction). Six animals from each group were necropsied at day 10 for enumeration/identification of worms from the abomasum, small and large intestines to determine the absolute efficacy of each agent (controlled efficacy test). Trichlorphon and naphthalophos were effective (> 99 %) against Haemonchus contortus (p < 0.05).Naphthalophos also showed efficacy against Trichostrongylus axei (99.3 %), Teladorsagia circumcincta (97.8 %), Trichostrongylus colubriformis (99.2 %), Cooperia punctata/curticei/pectinata (90.4 %), Nematodirus spathiger (89.2 %) and Oesophagostomum venulosum/columbianum (93.7 %). Fenbendazole and levamisole showed efficacy (> 95 %) against all nematodes except T. colubriformis. The efficacy of ivermectin was low against H. contortus (23 %) and Cooperia spp. (46.3 %). Closantel showed low efficacy against T. axei (64.4 %), H. contortus (80.6 %) and T. colubriformis (59.5 %).When anthelmintic resistance is widespread, trichlorphon treatment is appropriate if H. contortus is present; however, naphthalophos represents an effective therapeutic alternative for incorporation into worm control programmes.

Anthelmintic efficacy of oral trichlorfon solution against ivermectin resistant nematode strains in cattle.

Infected calves from two different rural estates in Brazil were studied to assess the anthelmintic efficacy of oral trichlorfon against naturally occurring ivermectin resistant parasitic nematode strains. In experiment I, infected animals were from a region where ivermectin resistant populations of Haemoncus placei, Cooperia punctata, Cooperia spatulata and Trichuris discolor have recently been identified. Six calves with natural gastrointestinal nematode infections were treated with 48.5mg/kg aqueous trichlorfon administered orally and six calves acted as a non-treated control group. In experiment II 24 naturally infected calves were selected to enter one of four treatment groups, six animals each received: 48.5mg/kg oral trichlorfon; 200 microg/kg subcutaneous 1% ivermectin; 630 microg/kg subcutaneous 3.15% ivermectin; or no treatment (control group). Gastrointestinal helminths were counted and identified post-mortem at 7 days (trichlorfon and 1% ivermectin treated and untreated animals) or 14 days (3.15% ivermectin treated and untreated animals) after administration of the test agents. Experiment I identified a high level efficacy for oral trichlorfon against four helminth species that have previously been shown to be ivermectin resistant in this geographical region: percentage efficacy was 99.82% against adult H. placei, 99.18% against C. punctata, 99.33% against C. spatulata, 81.06% against T. axei, 98.46% against Oesophagostomum radiatum and 100% against T. discolor. Trichlorfon also showed activity against the ivermectin (1% and 3.15%) resistant helminth species identified in experiment II, attaining efficacy levels of 99.17% against H. placei, 98.46% against C. punctata and 100.00% against T. discolor. These findings indicate that oral trichlorfon is an effective treatment option in the management of cattle infected with ivermectin resistant helminths.

WITHDRAWN: Drugs for treating neurocysticercosis (tapeworm infection of the brain).

BACKGROUND: Anthelminthic drugs may shrink brain cysts in neurocysticercosis, but can also cause severe adverse effects. OBJECTIVES: The objective of this review was to assess the effects of drug treatment in human neurocysticercosis in relation to survival, cyst persistence, subsequent seizures and hydrocephalus. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (September 2002), The Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2002), MEDLINE (1966 to September 2002), EMBASE (1980 to August 2002), LILACS (September 2002). We contacted researchers and experts in the field, and pharmaceutical companies. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing a cysticidal drug with a placebo or a control group receiving symptomatic therapy, in patients with neurocystercosis. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and data extraction was done independently by two reviewers. MAIN RESULTS: Four studies involving 305 people met the inclusion criteria. None reported on withdrawal of anticonvulsant therapy, headache relief, disability or death as outcomes. A difference just approaching significance was detected between cysticidal therapy and placebo in relation to cyst persistence up to six months (relative risk 0.83, 95% confidence interval 0.70 to 0.99). Two trials reported on seizures after one to two years follow-up and found no difference (relative risk 0.95, 95% 0.59 to 1.51). There was no difference detected for hydrocephalus (relative risk 2.19, 95% confidence interval 0.29 to 16.55). AUTHORS' CONCLUSIONS: There is insufficient evidence to assess whether cysticidal therapy in neurocysticerosis is associated with beneficial effects.

Drugs for treating neurocysticercosis (tapeworm infection of the brain).

BACKGROUND: Anthelminthic drugs may shrink brain cysts in neurocysticercosis, but can also cause severe adverse effects. OBJECTIVES: The objective of this review was to assess the effects of drug treatment in human neurocysticercosis in relation to survival, cyst persistence, subsequent seizures and hydrocephalus. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group trials register and Medline. We contacted researchers and experts in the field and drug manufacturers. SELECTION CRITERIA: Randomised or quasi-randomised trials comparing a cysticidal drug with a placebo or a control group receiving symptomatic therapy, in patients with neurocystercosis. DATA COLLECTION AND ANALYSIS: Assessment of trial quality and data extraction was done independently by two reviewers. MAIN RESULTS: Four studies involving 305 people met the inclusion criteria. None reported on withdrawal of anticonvulsant therapy, headache relief, disability or death as outcomes. A difference just approaching significance was detected between cysticidal therapy and placebo in relation to cyst persistence up to six months (relative risk 0.83, 95% confidence interval 0.70 to 0.99). Two trials reported on seizures after one to two years follow-up and found no difference (relative risk 0.95, 95% 0.59 to 1.51). There was no difference detected for hydrocephalus (relative risk 2.19, 95% confidence interval 0.29 to 16.55). REVIEWER'S CONCLUSIONS: There is insufficient evidence to assess whether cysticidal therapy in neurocysticerosis is associated with beneficial effects.

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

OBJECTIVE: To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. METHODS: Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. RESULTS: Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. CONCLUSIONS: There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

Quantitative evaluation of tuberculosis evolution in hamsters submitted to an eight-week Trichlorfon treatment and infected with Mycobacterium bovis, strain AN5

A evoluçäo da doença causada pela inoculaçäo intraperitoneal de Mycobacterium bovis (cepa AN5) foi avaliada em hamsters (Mesocricetus auratus) tratados de segundas a sextas-feiras, com doses subcutâneas de 30 mg/kg de Triclorfon, por um período de 8 semanas consecutivas. Os critérios adotados para essa avaliaçäo foram o tempo de sobrevivência após a inoculaçäo e a quantificaçäo do agente no baço, fígado, rim e pulmäo colhidos aos 1, 15, 29 e 45 dias após a inoculaçäo. Nessas oportunidades também foram realizados exames histopatológicos. Os animais do grupo tratado com Triclorfon e do grupo controle desenvolveram tuberculose progressiva. Os resultados da quantificaçäo do agente nos órgäos examinados, e do tempo de sobrevivência após a inoculaçäo, näo mostraram qualquer influência da administraçäo do Triclorfon

[Evaluation of chemotherapeutic agents against cichlidogyriasis in tilapia (Oreochromis hornorum) in Mexico]. / Evaluación de quimioterapéuticos contra la ciclidogiriasis en tilapia (Oreochromis hornorum) en México.

To evaluate the efficacy of seven compounds against the cichlidogyriasis of tilapia fish (Oreochromis hornorum), two experiments were carried out. In one, 160 naturally infected fish with a mean burden of 33.4 parasites/animal were used. In another, 1600 fish with a burden of 49.9 parasites/fish were used. Fish were randomly divided into eight equal groups and received three treatments as submersion baths: methylene blue, malachite green, potassium permanganate, sodium chloride, formaldehyde, copper sulfate and triclorfon, and a non-treated control. Five days after the last treatment, all fish were killed and dissected to quantify the remaining parasites. All data were submitted to an ANOVA analysis. All groups compared to the control showed statistical difference (P < 0.01), with better efficacy at higher doses. Sodium chloride, potassium permanganate and triclorfon are highly efficient in the control of cichlidogyriasis of tilapia fish, but care should be taken with the toxicity of the two first compounds.

[Evaluation of 4 vermifuges against Bothriocephalus acheilognathi in carp]. / Evaluación de cuatro vermicidas contra Bothriocephalus acheilognathi en carpas.

With the aim to evaluate the efficacy of four vermicides, praziquantel, mebendazole, nitroscanate and triclorfon in the control of Bothriocephalus acheilognathi in carps, one hundred and sixty, two year-old carps (Ctenopharyngodon idellus) with an average weight of 120 g and a mean parasitic burden of 115.5 parasites/fish were used. Five groups of 30 fish each were randomly formed. Each group was then subdivided in three groups, each of 10 individuals/pond. The three subgroups of group A received 30, 50 and 70 mg/Kg of praziquantel, respectively. Groups B and C received 2.2, 4.4, and 6.8 mg/Kg of mebendazole suspension and mebendazole solution respectively; groups D and E received 10, 30, 50 mg/Kg; and 2.0, 4.0, 6.0 mg/Kg of nitroscanate and trichlorfon respectively. Group F of 10 fish remained as non-treated control. Praziquantel showed 100% of efficacy for all doses, therefore it was excluded from the statistical analysis. The subgroups B, C, D and E compared with the non-treated control were statistically significant (P < 0.01); showing in all treatments an additive effect, the higher the dose the better efficacy, except trichlorfon which showed a different tendency, having no explanation on that matter.

Efficacy of pyrantel pamoate either alone or combined with trichlorfon for control of cyathostomes of horses

Através de estudo comparativo, objetivou-se avaliar a eficiência anti-helmíntica de pamoato de pirantel, isolado ou associado ao triclorfon, no controle de estrongilídeos de equinos da raça Puro Sangue Inglês. As coproculturas realizadas antes e após os tratamentos levaram consistentemente ao encontro de populaçöes puras de ciatostomíneos com oito células intestinais. As reduçöes de ovos por grama de fezes foram avaliadas do 7§ ao 45§ dias pós-tratamento. Comparando os valores médios de OPG dos equinos tratados com pamoato de pirantel (13,2 mg/kg) associado ao triclorfon (30 mg/kg) e com pamoato de pirantel isolado (13,2 mg/kg), observou-se diferença näo significante (P<0,05) ao longo do experimento, verificando-se, 7 dias após o tratamento, reduçöes médias de OPG de quase 100 por cento e, do 7§ ao 20§ dias, reduçöes ainda superiores a 90 por cento. Os resultados indicam que os dois produtos säo eficazes na reduçäo de ovos por grama de fezes de ciatostomíneos de equinos mantidos sob condiçöes a campo

Haemonchus contortus resistance to ivermectin and netobimin in Brazilian sheep.

Suffolk, Texel, Hampshire Down and Ile de France sheep from the municipalities of Porto Amazonas, Piraquara and Araucaria in the State of Paraná, and Bagé in the State of Rio Grande do Sul were brought to Sobral, State of Ceará, to be used in a cross-breeding project. On arrival they had clinical signs of nematode parasitosis, and one Suffolk female died. The animals were treated orally with ivermectin (0.2 mg kg-1) and fifteen days later with netobimin (20.0 mg kg-1). Neither drug reduced the egg counts (measured in eggs per gram, EPG) significantly, and this suggested that the nematodes in the sheep were resistant to the anthelmintics used. Haemonchus contortus was the species involved. The egg counts were reduced after oral treatment with trichlorfon (100.0 mg kg-1). Haemonchus contortus larvae obtained from these animals before trichlorfon treatment and passaged through two nematode-free sheep were used in a further experiment. Twenty 6- to 9-month-old nematode-free lambs were infected with the H. contortus larvae (10,000 per animal) and after the infection was confirmed, were randomly divided into four groups of five animals. Group I was orally treated with ivermectin at 0.2 mg kg-1, Group II with oral netobimin at 20.0 mg kg-1, Group III with oral trichlorfon at 100.0 mg kg-1 and Group IV was a non-treated control. Egg counts and faecal cultures were taken before dosing on the day of treatment and seven days later when all animals were necropsied and the nematodes were collected from the abomasa and counted.(ABSTRACT TRUNCATED AT 250 WORDS)

Age-targeted chemotherapy for control of urinary schistosomiasis in endemic populations.

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year 1, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P < 0.01), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5 yr) entering into the targeted age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trend. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on a population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects.

Age-targeted chemotherapy for control of urinary schistosomiais in endemic populations

Severity of urinary tract morbidity increases with intensity and duration of Schistosoma haematobium infection. We assessed the ability of yearly drug therapy to control infection intensity and reduce S. haematobium-associated disease in children 5-21 years old in an endemic area of Kenya. In year I, therapy resulted in reduced prevalence (66% to 22%, P < 0.001) and intensity of S. haematobium infection (20 to 2 eggs/10 mL, urine), with corresponding reductions in the prevalence of hematuria (52% to 19%, P < 0.001). There was not, however, a significant first-year effect on prevalence of urinary tract abnormalities detected by ultrasound. Repeat therapy in years 2 and 3 resulted in significant regression of hydronephrosis and bladder abnormalities (41% to 6% prevalence, P< 0.001), and further reductions in proteinuria. Repeat age-targeted therapy was associated with decreased prevalence of infection among young children (< 5yr) entering into the target age group. Two years after discontinuation of therapy, intensity of S. haematobium infection and ultrasound abnormalities remained suppressed, but hematuria prevalence began to increase (to 33% in 1989). Reinstitution of annual therapy in 1989 and 1990 reversed this trends. We conclude that annual oral therapy provides an effective strategy for control of morbidity due to S. haematobium on population basis, both through regression of disease in treated individuals, and prevention of infection in untreated subjects

Experimental treatment of cysticercosis with metrifonate.

Thirty cysticercous patients were treated with metrifonate in doses of 7.5 mg/kg given for five consecutive days, with intervals of two weeks until completion of six series. The symptoms originated by drug reaction were mild and transitory. The results obtained after treatment demonstrated the effectivity in cerebral ocular and musculocutaneous cysticercosis, corroborated by clinical evaluations like: neurological, ophtalmological and psychiatric examinations; routine laboratory tests; special examinations like indirect immunofluorescence and hemagglutination, immunoglobulin quantitation and cholinesterase activity and by special cabinet studies like electroencephalogram, retinal fluorangiography, axial computerized tomography. The postreatment observation time varied from six months to nine years; in no case reactivation was observed.