Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.Uma pesquisa clínica compreendendo 80 pacientes de ambos os sexos, de 15 a 55 anos de idade, portadores de esquistossomose mansônica crônica, formas intestinal ou hepatintestinal, foi efetivada para avaliar a eficácia do praziquantel em diferentes esquemas posológicos. Os pacientes foram distribuídos aleatoriamente em quatro grupos, com igual número de casos, sendo tratados com uma das seguintes dosagens: 60 mg/kg em um dia, 60 mg/kg diários por dois dias, 60 mg/kg diários por três dias e 30 mg/kg diários por seis dias. A avaliação da cura parasitológica baseou-se na técnica do oograma quantitativo mediante biópsias da mucosa retal, realizadas antes, bem como um, dois, quatro e seis meses após o tratamento. Concomitantemente, efetuaram se exames de fezes segundo os métodos qualitativo de Hoffman, Pons & Janer e quantitativo de Kato-Katz. A melhor tolerabilidade foi verificada com 30 mg/kg diários durante seis dias, enquanto a maior incidência de efeitos colaterais, em especial tontura e náusea, ocorreu com 60 mg/kg diários durante três dias. Nenhuma reação adversa grave foi observada com o medicamento. Alcançaram se os seguintes índices de cura: 25% com 60 mg/kg em um dia; 60% com 60 mg/kg diários por dois dias; 89,5% com 60 mg/kg diários por três dias e 90% com 30 mg/kg diários por seis dias. Paralelamente houve uma queda de, respectivamente, 64%, 73%, 87% e84% no número mediano de ovos viáveis de S. mansoni por grama de tecido. Assim, constatou se uma correlação direta entre dose e efeito. Os correspondentes índices de cura, segundo os exames de fezes, foram 39%, 80%, 100% e 95% com o método de Hoffman, Pons & Janer e com o de Kato-Katz 89%, 100%, 100% e 100%. A discrepância encontrada nos resultados entre os três métodos parasitológicos decorre da desigualdade na precisão dos mesmos. Quando o número de ovos viáveis por grama de tecido caiu abaixo de 5000, a diferença no percentual de achados falso-negativos entre Hoffmann, Pons & Janer (28%) e Kato-Katz (80%) tornou-se significativa. Quando esse número baixou para menos de 2000, a percentagem de resultados falso-negativos encontrada com Hoffman, Pons & Janer (49%) também passou a ser significativa em relação ao oograma. Em conclusão, ficou provado que o praziquantel é altamente eficaz na infecção pelo S. mansoni. Administrado na dose total de 180 mg/kg, dividida em três ou seis dias, o praziquantel proporcionou 90% de cura. Provavelmente, poderia atingir 100% se a dose total fosse aumentada para 240 mg/kg. Ademais, confirmou-se que o oograma quantitativo consiste no método mais fidedigno para avaliar a eficácia terapêutica de novas drogas na esquistossomose mansônica

Investigation of the therapeutical efficacy and the morphological alterations induced on the Hymenolepis nana eggs, administering praziquantel in two dose schedules

Twenty children with hymenolepiasis, living at a close community and having more than 1000 eggs/g of feces, were selected for the investigation of the therapeutical efficacy and the morphological alterations induced on the H. nana eggs, following the oral administration of praziquantel in two posologies. The patients were allocated into two groups having equal number of cases. Group "A" was treated with a single dose of 25 mg/kg BWT and group "B" with the same dose but repeated 10 days afterwards. From the third day on until the 19th day it was found, in both groups, the uprising, with a peak around the seventh day, of distorted eggs. The normal eggs decreased gradually. They disappeared in 100% of the cases in group "B", from the 19th day on, but remained present in 20% of the cases in group "A". The tolerance to the drug was excellent with either dose schedule. It was concluded that praziquantel is highly efficaceous in the treatment of hymenolepiasis and that this drug should be administered in two doses of 25 mg/kg, 10 days apart, for those patients presenting intense worm burden and living in close communities.Foram selecionadas, numa comunidade fechada, 20 crianças com himenolepíase, apresentando carga parasitária acima de 1 000 ovos/g de fezes, visando a averiguar a eficácia terapêutica do praziquantel e as alterações morfológicas induzidas nos ovos de H. nana por sua administração oral, em dois esquemas posológicos. Os pacientes foram alocados em dois grupos com igual número de casos. O grupo "A" foi tratado com uma única dose de 25 mg/kg de peso corporal e o grupo "B" com a mesma dose, porém repetida 10 dias depois. A partir do terceiro dia até o 19.°, verificou-se, em ambos os grupos, o surgimento, com um pico em torno do sétimo dia, de ovos distorcidos do parasita. Os ovos normais decresceram gradativamente, desaparecendo em 100% dos casos do grupo "B", do 19° dia em diante, mas mantendo-se presentes em 20% dos casos no grupo "A". A tolerância ao medicamento mostrou-se igualmente excelente com as duas posologias empregadas. Conclui-se pela elevada eficácia terapêutica do praziquantel na himenolepíase, sugerindo-se administrá-lo em duas doses de 25 mg/kg, com um intervalo de dez dias, nos pacientes intensamente parasitados e que convivam em comunidades fechadas

Levantamento dos resultados das pesquisas clínicas realizadas no Brasil, comparando o praziquantel com a oxamniquina no tratamento da esquistossomose mansônica

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p ; 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p ; 0.05). Dentre os pacientes não curados, houve, após o tratamento, uma redução no número médio de ovos por grama de fezes de 88,6% e 74,6% com praziquantel e com oxamniquina, respectivamente, uma diferença estatisticamente significativa (p < 0.05). Em conclusão, apesar de serem substâncias com estruturas químicas diversas, de possuírem propriedades farmacológicas e toxicológicas distintas, bem como mecanismos de ação próprios, inclusive tendo o praziquantel já demonstrado ser 100% ativo contra linhagens de S. mansoni resistentes à oxamniquina, ambas as drogas evidenciaram tolerabilidade e eficácia terapêutica similares

Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis

A random, double-blind, parallel group clinical trial program was carried out to compare praziquantel, a recently developed anti-helmintic drug, and oxamniquine, an already established agent for treating mansoni schistosomiasis. Both drugs were administered orally as a single dose, on the average, praziquantel 55 mg/kg and oxamniquine 16 mg/kg BWT. The diagnosis and the parasitological follow-up lasting for a minimum of six months, were based on stool examinations according to Kato/Katz technique. A patient was considered cured if all results were negative and if he had performed at least three post-treatment controls, each one comprising three stool examinations. The finding of a single S. mansoni egg in any stool examination indicated, a therapeutical failure. A total of 267, cases were treated with praziquantel and 272 with oxamniquine. The two groups were homogeneous in regard to patients, age, clinical form of the disease, risk of reinfection and worm burden, relevant factors in the therapeutical response. The incidence and severity of untoward, effects were similar in both groups but abdominal distress and diarrhoea were more frequently reported under praziquantel and dizzines under oxamniquine (p < 0.05). In the former group a marked urticariform reaction was observed whereas in the latter one patient presented convulsion. The laboratory work-up. failed to disclose any significant alteration although the AST, ALT and y-GT mean values revealed a tendence to increase on the 7th day after oxamniquine intake. The overall parasitological cure rates were 75.5% (139/ 184) with praziquantel and 69.8% (134/192) with oxamniquine (p &gt; 0.05). Amongst the noncured aptients a reduction of 88.6% and 74.6% in the mean number of eggs/g of feces Was seen following the treatment with praziquantel and oxamniquine, respectively (p < 0.05). In conclusion, in spite of their different chemical, pharmacological and toxicological profiles as well as mechanisms-of-action, inclusively praziquantel already had proved to be 100% active against S. mansoni strains resistant to oxamniquine, both drugs showed comparable tolerance and therapeutical efficacy

Estudo da eficácia terapêutica do praziquantel e das alterações morfológicas nos ovos de Hymenolepis nana após sua administração em dois esquemas posológicos

Foram selecionadas, numa comunidade fechada, 20 crianças com himenolepíase, apresentando carga parasitária acima de 1 000 ovos/g de fezes, visando a averiguar a eficácia terapêutica do praziquantel e as alterações morfológicas induzidas nos ovos de H. nana por sua administração oral, em dois esquemas posológicos. Os pacientes foram alocados em dois grupos com igual número de casos. O grupo "A" foi tratado com uma única dose de 25 mg/kg de peso corporal e o grupo "B" com a mesma dose, porém repetida 10 dias depois. A partir do terceiro dia até o 19.°, verificou-se, em ambos os grupos, o surgimento, com um pico em torno do sétimo dia, de ovos distorcidos do parasita. Os ovos normais decresceram gradativamente, desaparecendo em 100% dos casos do grupo "B", do 19° dia em diante, mas mantendo-se presentes em 20% dos casos no grupo "A". A tolerância ao medicamento mostrou-se igualmente excelente com as duas posologias empregadas. Conclui-se pela elevada eficácia terapêutica do praziquantel na himenolepíase, sugerindo-se administrá-lo em duas doses de 25 mg/kg, com um intervalo de dez dias, nos pacientes intensamente parasitados e que convivam em comunidades fechadas