Aspectos clínico-patológicos da intoxicação por ivermectina em suínos / Clinical and pathological aspects of the intoxication by ivermectin in pigs

A ivermectina é um derivado semi-sintético das avermectinas. Essas lactonas macrocíclicas são obtidas como compostos da fermentação do actinomiceto Streptomyces avermitilis, apesar de sua ampla margem de segurança, casos de intoxicação iatrogênica tem sido observados em diversas espécies animais. O objetivo do presente trabalho é relatar o primeiro surto de intoxicação por ivermectina em suínos no Brasil. Os casos descritos neste estudo foram observados em uma propriedade rural no Município de Catingueira, Estado da Paraíba. O rebanho era composto por 103 suínos, destes 32 foram medicados com ivermectina a 1% por via subcutânea para tratamento de ecto e endoparasitose. A dose utilizada foi cinco vezes superior a recomendada para espécie. Os animais apresentaram anorexia, tremores, ataxia, paresia dos membros posteriores, depressão, coma e morte. 96,9% dos animais evoluiram a óbito. Os sinais clínicos foram observados em média oito horas após administração do fármaco e o período de evolução que culminou com o óbito variou de 10 a 48 horas. O presente estudo chama atenção para a necessidade de se calcular com precisão a dose de ivermectina a ser utilizada em suínos, em especial para animais jovens, uma vez que é possível que nos mesmos a barreira hematoencafálica seja mais permeável ao fármaco em relação aos adultos.

Ivermectin is a semi-synthetic derivative of avermectins. These macrocyclic lactones are obtained as fermentation compounds of the actinomycete Streptomyces avermitilis, despite their wide safety margin, cases of iatrogenic intoxication have been observed in several animal species. The objective of the present study is to report the first outbreak of ivermectin intoxication in swine in Brazil. The cases described in this study were observed in a rural property in the Municipality of Catingueira, State of Paraíba. The herd was composed of 103 pigs, of these 32 were medicated with 1% ivermectin subcutaneously for treatment of ecto and endoparasitosis. The dose used was five times higher than that recommended for the species. The animals presented anorexia, tremors, ataxia, paresis of the hind limbs, depression, coma and death. 96.9% of the animals evolved to death. Clinical signs were observed on average eight hours after drug administration and the evolution period that culminated with death ranged from 10 to 48 hours. The present study draws attention to the need to accurately calculate the dose of ivermectin to be used in pigs, especially for young animals, since it is possible that the blood-brain barrier is more permeable to the drug compared to adults.

Postmortem Redistribution of Avermectin in Acute Poisoning death of Rabitts / 中国法医学杂志

Objective To investigate the postmortem redistribution of Avermectin in acute poisoning death of rabitts. Methods According to the minimum lethal dose intragastric of 250mg/kg avermectin, the avermectin contents in the heart blood and major organs and tissues of the rabitts after death of 0h~72h were assayed by HPLC method. Results Determination of clinical death time was 120.6±9.2min(x±s, n=10)by intragastric 250mg/kg avermectin to the rabitts; Lethal blood concentrations and lethal tissue concentrations of Avermectin were determined; Presence of postmortem redistribution of avermectin contents in the heart blood and major organs and tissues of the rabitts after death of 0h~72h were proved; Determination of the liver, kidney and lung were the best tissue samples for toxicological anaysis. Conclusion The data of Avermectin postmortem redistribution in the rabbits have important reference value for the forensic management of such cases.

Historical story on natural medicinal chemistry: Avermectin and ivermectin / 中草药

Microorganisms have provided abundant sources of natural products, which have been developed as commercial products for human medicine, animal health, and plant crop protection. Avermectin discovered from Streptomyces avermectinius was the first macrocyclic lactones against parasitic worms. The semi-synthetic derivative of avermectin, ivermectin, was used to treat onchocerciasis and lymphatic filariasis in human. Two scientists were awarded the Nobel Prize for the great contribution to the discovery and research of these drugs. This paper reviewed the study and development of avermectins and ivermectin. This is one of the series papers about historical story on natural medicinal chemistry.

Avaliação da associação de abamectina e ivermectina no controle das helmintoses gastrointestinais em ovinos / Evaluation of the association of abamectin and ivermectin in the control of gastrointestinal helminthes in sheep / Evaluación de la asociación de abamectina e ivermectina en el control de helmintos gastrointestinales en ovinos

A helmintose gastrointestinal em ovinos é um problema crescente, devido a presença da resistência anti-helmíntica, o que dificulta sobremaneira o controle. Assim sendo, o presente trabalho teve como objetivo testar a eficácia da associação de Abamectina e Ivermectina injetável para ovinos na concentração de 3,5% em duas propriedades norte do Paraná. As ovelhas foram randomizadas pela OPG e divididas em dois grupos, sendo T1 - Controle, T2 - associação de Abamectina e Ivermectina. Os animais foram monitorados pelo método de OPG e coprocultura no dia zero e 14, para determinar a eficácia da associação, por comparação da redução da contagem de OPG, antes e após o tratamento, e os parasitos resistentes. Os resultados encontrados foram a redução de OPG pela associação Ivermectina e Abamectina de 33,89% e 93,74% na primeira e segunda propriedade, respectivamente, demonstrando a eficácia do produto somente na segunda propriedade. Concluiu-se que a associação Abamectina e Ivermectina 3,5% pode ser utilizada em propriedades na região norte do Paraná para controle da verminose, após testes de eficácia. O parasito mais incidente e, portanto o de maior resistência encontrado na análise das larvas na coprocultura foi o Haemonchus sp.(AU)

Gastrointestinal helminthes in sheep is a growing problem due to the presence of anthelmintic resistance, which greatly complicates its control. Therefore, this study aims to test the efficiency of the combination of injectable abamectin and ivermectin in sheep at a concentration of 3.5% in two properties in the northern region of Parana. The sheep were randomly assigned by OPG and divided into two groups, where T1 - control, T2 - association of abamectin and ivermectin. The animals were monitored by the OPG method and fecal culture on day zero and fourteen to determine the effectiveness of the combination by comparing the reduction in OPG before and after treatment and the resistant parasites. Ivermectin and abamectin presented a reduction of 33.89% and 93.74% in the first and second property, respectively, demonstrating the effectiveness of the product only in the second property. It could be concluded that the association of Abamectin and Ivermectin 3.5% can be used in properties in the northern Paraná to control parasitic helminths, after efficacy tests. The most prevalent parasite and therefore, the one presenting greater resistance in the analysis of the larvae during fecal culture was Haemonchus spp.(AU)

Los helmintos gastrointestinales en ovejas es un problema creciente debido a la presencia de la resistencia antihelmíntica, lo que complica en gran medida el control. Así, este estudio ha tenido como objetivo evaluar la eficacia de la asociación de Abamectina e Ivermectina inyectable para ovejas a una concentración de 3,5% en dos propiedades al norte de Paraná. Las ovejas fueron separadas por OPG y divididas en dos grupos: T1 - control, T2 - Asociación Abamectina e Ivermectina. Los animales fueron controlados por el método OPG y coprocultura en el día cero y 14, para determinar la eficacia de la combinación, por comparación de la reducción del conteo de OPG, antes y después del tratamiento, y los parásitos resistentes. Los resultados encontrados fueron la reducción de OPG por asociación de Ivermectina y Abamectina de 33,89% y 93,74% en la primera y segunda propiedad, respectivamente, lo que demuestra la eficacia del producto sólo en la segunda propiedad. Se concluyó que la asociación Abamectina e Ivermectina 3.5% puede ser utilizada en propiedades en la región norte de Paraná para controlar gusanos, después de los ensayos de eficacia. El parásito más común y por lo tanto el de mayor resistencia encontrado en el análisis de las larvas en el cultivo fecal fue el Haemonchus spp.(AU)

Resistência anti-helmíntica em rebanhos caprinos nos biomas Caatinga e Mata Atlântica / Anthelmintic resistance in goat herds in the Caatinga and Mata Atlântica biomes

A utilização de anti-helmínticos por longos períodos como principal medida de controle das parasitoses gastrintestinais de ruminantes levou a ineficácia aos levamisol, benzimidazóis e avermectinas. Este estudo descreve a atividade anti-helmíntica in vivo em populações naturais de nematoides trichostrongilídeos de caprinos. Foram selecionados 18 rebanhos provenientes dos biomas Caatinga (n=12) e Mata Atlântica (n=6), do Estado da Bahia, Brasil, criados em pastagens comunais em região semiárida. Grupos de oito a 10 animais foram tratados com albendazol (ABZ), ivermectina (IVM), levamisol (LEV), moxidectina (MOX) e closantel (CLOS). Os resultados do Teste de Redução da Contagem de Ovos nas Fezes indicaram resistência simultânea dos gêneros Haemonchus sp. e Trichostrongylus spp. para o ABZ, IVM, LEV, MOX e CLOS. As percentagens de eficácia variaram de 0-92%, 0-75%, 0-91%, 69-97% e 0-85% para o ABZ, IVM, LEV, MXD e CLOS, respectivamente, no bioma Caatinga e 0-59% para o ABZ e 9-59% para o IVM no bioma Mata Atlântica. Verificou-se nos rebanhos eficácia inferior a 95% para estes anti-helmínticos, com exceção de um único rebanho no qual a eficácia para MOX foi de 97%, o que sugere a presença de NGIs resistentes aos principais classes de anti-helmínticos em rebanhos caprinos destes biomas...

The use of anthelmintic drugs for long periods as the main measure control of gastrointestinal nematodes (GINs) has led to the inefficacy of levamisole, benzimidazoles and macrocyclic lactones. This study describes the in vivo anthelmintic activity against natural trichostrongyle nematodes populations in goats. We selected 18 herds from the Caatinga (n=12) and Mata Atlântica (n=6) biomes, Bahia State, Brazil, raised in communal pastures in semiarid region. Groups of 8 to 10 goats were treated with albendazole (ABZ), ivermectin (IVM), levamisole (LEV), moxidectin (MOX), and closantel (CLOS). The results of the Fecal Egg Count Reduction Test indicated simultaneous resistance of Haemonchus sp. and Trichostrongylus spp. genera against albendazole (ABZ), ivermectin (IVM), levamisole (LEV), moxidectin (MOX), and closantel (CLOS). The efficacy percentages ranged from 0 to 92%, 0 to 75%, 0 to 91%, 69 to 97%, and 0 to 85% for ABZ, IVM, LEV, MXD and CLOS respectively in the Caatinga bioma, and 0 to 59% for ABZ and 9 to 59% for IVM in the Mata Atlântica biome. Most herds showed efficacy lower than 95% for anthelmintics, with the exception of one herd in which the efficacy for MOX was 97%. The results indicated the presence of GINs resistant to main anthelmintics classes in goat herds in these biomes...

Study on Clinical Efficacy of Avermectin A and Astragalus on the Treatment of Psoriasis and the Detection Of TNF-α / 国际中医中药杂志

Objective To observe the clinical efficacy of psoriasis treated with avermectin A and astragalus and detect the changes of TNF-a in serum. Preliminarily study the anti-inflammatory and immunomodulatory mechanism of avermectin A and astragalus in the treatment of psoriasis. Methods 20 patients were randomly recruited into a control group (9 cases) and a treatment group (11 cases). Another 20 healthy people were recruited for comparison. The control group was administrated with avermectin A orally, 0.2±0.6 mg/kg·d, with the symptoms turning better, reduced the dosage till the recovery, the treatment group was injected with astragalus injection on the therapeutic basis of the control group. Detect and compare the levels of TNF-α in the serum of the patients with psoriasis before and after the treatment in both groups, then make a contrast to the healthy people. Results 20 patients got clinical cure. The level of TNF-α in the serum of healthy persons is 11.7± 6.7 ng/L, and the level of TNF-α in the serum of psoriasis patients before treatment is (45.4±12.4) ng/L and (46.4±16.9) ng/L in the treatment group and the control group respectively. Compared with healthy control group, the difference is significant. After treatment, is the TNF-αlevels dropped to (13.8± 5.4) ng/L and (20.9±6.3) ng/L in the treatment group and the control group respectively, showing no significant difference compared with healthy control group. The difference between the two group is also significant. Conclusion The efficacy of treating psoriasis with avermectin A and astragalus is better than using avermectin A exclusively. The mechanism may lie in its inhibiting the formation of TNF-α and so thus exerting the anti-inflammatory and immune regulatory functions.