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      Drug trials for treatment of human angiostrongyliasis Translated title: Ensaios com drogas para o tratamento da angiostrongilíase humana

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          Abstract

          Abdominal and cerebral angiostrongyliasis are two important infections produced by metastrongylid worms, the former occurring in Central and South America and the later in Asia and Pacific Islands. Drug treatment is a challenge since the worms and its evolving larvae live or migrate inside vessels and efficient killing of the parasites may produce more severe lesions. Larvicidal effect of certain drugs appears to be more easily accomplished but this outcome is not useful in abdominal angiostrongyliasis since clinical manifestations appear to result from sexual maturation of the worms. We review the drug trials in murine experimental models and conclude that most of them could not be considered good candidates for treatment of human infection, except for PF1022A, pyrantel and flubendazole.

          Translated abstract

          Angiostrongilíase abdominal e cerebral são duas infecções importantes produzidas por metastrongilídeos, a primeira delas ocorrendo nas Américas Central e do Sul e a segunda, na Ásia e Ilhas do Pacífico. O tratamento é complicado pelo fato das larvas e vermes adultos viverem e migrarem dentro dos vasos sanguíneos, sendo que as lesões podem se agravar com a morte desses parasitos. Os efeitos larvicidas de determinadas drogas parecem ser mais eficazes, porém não são úteis no tratamento em angiostrongilíase abdominal, onde as manifestações clínicas podem resultar da maturidade sexual dos vermes. Este estudo faz uma revisão das drogas utilizadas para o tratamento de ambas as parasitoses, em modelos experimentais murinos, realizados antes e depois da maturação dos vermes. A maioria das drogas testadas não pode ainda ser considerada candidata a ensaios de tratamento em infecções humanas, com exceção do PF1022A, pirantel e flubendazol.

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          Most cited references55

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          Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma.

          Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.
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            Angiostrongilíase abdominal: Um problema de Saúde Pública?

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              Avermectin B1a, a paralyzing anthelmintic that affects interneurons and inhibitory motoneurons in Ascaris.

              Avermectin B1a (AVM) is an antiparasitic agent that paralyzes nematodes without causing hypercontraction or flaccid paralysis. Using selective stimulation techniques, we have shown that AVM blocks transmission between interneuron(s) and excitatory motorneurons in the ventral nerve cord of Ascaris. It also inhibits transmissin between inhibitory motoneurons and muscle but has little effect on excitatory neuromuscular transmission. Picrotoxin can reverse the AVM-induced block of interneuron-excitatory motoneuron transmission but has no effect on the inhibitory motoneuronal synapse in either the presence or absence of AVM. Our results provide an explanation of how AVM may cause paralysis of nematodes.
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                Author and article information

                Journal
                rimtsp
                Revista do Instituto de Medicina Tropical de São Paulo
                Rev. Inst. Med. trop. S. Paulo
                Instituto de Medicina Tropical de São Paulo (São Paulo, SP, Brazil )
                1678-9946
                August 2003
                : 45
                : 4
                : 179-184
                Affiliations
                [01] orgnameUniversidade Federal do Rio Grande do Sul orgdiv1Instituto de Ciências Básicas da Saúde orgdiv2Departamento de Microbiologia
                [02] orgnamePontifícia Universidade Católica do Rio Grande do Sul
                Article
                S0036-46652003000400001 S0036-4665(03)04500401
                485e286c-f115-45bc-adac-b86e96c065dc

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 23 May 2003
                : 10 July 2003
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 55, Pages: 6
                Product

                SciELO Brazil

                Categories
                Review

                Zoonosis,Tissue-dwelling parasites,Angiostrongyliasis,Eosinophilia,Anthelmintic drugs

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