Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects — mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea — were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls — three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs — despite their different chemical structures, pharmacological properties and mechanisms-of-action — induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.

Avaliação terapêutica duplo-cega baseada na técnica do oograma quantitativo, comparando praziquantel com oxamniquine na esquistossomose mansônica humana

Um total de 54 pacientes adultos, com esquistossomose mansônica crônica, nas formas intestinal ou hepatintestinal, participou de um ensaio clínico duplo-cego, para comparar o praziquantel com a oxamniquine. De acordo com uma distribuição aleatória, 27 casos receberam o praziquantel (65 mg/kg de peso corporal) e 27 a oxamniquine (18 mg/kg), administrados em dose oral única. A incidência, intensidade e duração dos efeitos colaterais foram similares para os dois medicamentos A avaliação da eficácia terapêutica baseou se na técnica do oograma quantitativo por biópsia da mucosa retal, realizada ao final de um, dois, quatro e seis meses depois do tratamento. Nessas mesmas ocasiões foram feitos exames de fezes pelos métodos de HOFFMAN, PONS e JANER e de KATO-KATZ, com a finalidade de confrontar seu resultados com os achados do oograma. Para averiguar o efeito imediato do tratamento sobre a atividade ovipositora do parasito, um número restrito de pacientes foi submetido a biópsias retáis no 6,° e 18.° dias subsequentes a administração da medicação. Ambas as drogas provaram ser ativas contra o esquistossoma, vez que os respectivos coeficientes de variação, determinados a partir de oogramas efetuados imediatamente após o tratamento, foram superiores a 60%. Ademais, dentre os 27 pacientes de cada grupo, 24 tratados com praziquantel e 22 com oxamniquine completaram o período de seis meses, requerido para controle parasitológico. Os índices de cura, segundo os achados do oograma e dos exames de fezes pelos métodos de HPJ e KK, foram, respectivamente, 29%,— 50% e 92% com o praziquantel; 23%, 50% e 86% com a oxamniquine. Apesar do baixo percentual de cura, observou-se nos oogramas pós tratamento, uma pronunciada queda no número de ovos vivos por grama de tecido. Esses resultados revelam que ambas as drogas foram semelhantemente eficazes, embora já se tenha comprovado que a susceptibilidade do S. mansoni não seja sempre igual para cada um desses medicamentos, pois linhagens resistentes à oxamniquine evidenciaram ser 100% sensíveis ao praziquantel. Por outro lado, constatou-se uma nítida diferença nos percentuais de cura em função do método utilizado para controle parasitológico. O oograma foi o mais preciso, seguido pelo HPJ e, finalmente, pelo K-K. Tendo ocorrido uma correlação direta entre o número de ovos vivos no oograma e a positividade dos exames de fezes, a percentagem de resultados falso-negativos aumentou acentuadamente após o tratamento, alcançando 47,3% com o HPJ e 92,9% com o K-K. Antes da medicação esses índices eram, respectivamente, 0% e 64,8%. Os autores depreendem que a diferença de precisão da metodologia aplicada para avaliar a eficácia terapêutica pode explicar a divergência encontrada entre o índice de cura obtido neste - ensaio clínico e os relatados por outros investigadores, tanto com o praziquantel quanto com a oxamniquine.

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.

Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil

A randomized clinical trial was carried out to compare the efficacy of a low-dosage combination of oxamniquine (7.5 mg/kg) plus praziquantel (20 mg/kg) against either agent, oxamniquine (15 mg/kg) or praziquantel (40 mg/kg) alone, in the treatment of schistosomiasis mansoni in the Brazilian north-east. The drugs were randomly administered per os to 91 patients. Six and twelve months after treatment 89% of those admitted to the trial were reexamined by Kato-Katz method (ten slides) and MIF technique (one gram of stool) The achieved cure rates, as defined by absence of S. mansoni eggs in the faeces of individual patients at all points during the parasitological follow-up, were 81.8%, 81.2% and 67.6% for praziquantel, oxamniquine and the combination respectively. The reduction of eggs excretion in non cured patients six months after therapy ranged from 93.8-96.8% with praziquantel, 32.5-97% with oxamniquine and 76.9-99.5% with the combination. It is concluded that, at the used dosages, the three therapeutical regimens give similar and satisfactory results in the treatment of uncomplicated S. mansoni infection in Brazil.

Seizures and Praziquantel. A case report

A 27 year Old male developed seizures after receiving a single 20 mg/kg dose of praziquantel for the treatment of an intestinal Hymenolepis nana infection. On further clinical and laboratorial evaluations, he was found to suffer from an until then asymptomatic parenchymal brain cysticercosis. Praziquantel must be used with caution in those areas where cysticercosis represents a mayor public health problem. The occurrence of unexpected seizures in an individual being treated with the compound, must prompt clinicians to rule out cysticercosis of the CNS.

Infecção por clonorchis sinensis em imigrantes asiáticos no Brasil: tratamento com praziquantel

Estudaram-se quinze pacientes com infecção assintomática por Clonorchis sinensis, revelada através de exame parasitológico de fezes. Todos eram de origem asiática e procuraram o Laboratório Central do Instituto Adolfo Lutz para se submeterem a exames laboratoriais necessários à regularização de sua situação, face à nova legislação sobre imigrantes. Eram todos indivíduos adultos, seis pertencendo ao sexo feminino e nove ao masculino. Os quinze pacientes com clonorquíase foram internados no Hospital das Clínicas da FMUSP e tratados com Praziquantel, na dosagem de 60 mg/kg de peso corporal, dividida em duas tomadas. Foram realizados exames coprológicos quantitativos (método de Kato-Katz), antes do tratamento específico e no 15º, 30º e 60º dias após a terapêutica. Na última avaliação (60? dia após terapêutica), em nove pacientes (60,0%) não se encontraram ovos do trematódeo nas fezes e nos seis (40,0%), que continuavam eliminando ovos, notou-se redução na quantidade eliminada (superior a 90% em cinco e a 30% no paciente restante). Os pacientes foram também submetidos a exames subsidiários, para avaliação do estado geral e função hepática, antes da administração de Praziquantel e, posteriormente, no seguimento ambulatorial. A medicação foi relativamente bem tolerada pelos pacientes, verificando-se a ocorrência de efeitos colaterais representados por náuseas e vômitos (dois casos), vertigens e tonturas (dois casos), epigastralgia (dois casos) e diarréia no 3? dia após tratamento (um caso).

Lethal effect of oxamniquine and praziquantel on mice experimentally infected with Schistosoma mansoni

Lethality caused by administration of oxamniquine and praziquantel to mice infected with Schistosoma mansoni, and their respective controls (uninfected), has been studied. As the results indicate, the infected animals clearly showed higher mortality rates when praziquantel was used. Surprisingly, it may be noted that exactly the contrary occurs in relation to the use of oxamniquine, inasmuch as marked higher mortality rates were seen in the control animals (uninfected). These observations lead to the conclusion that further toxicological studies of antischistosomal drugs using. S. mansoni infected animals are needed.

Synergistic action of praziquantel and host specific immune response against Schistosoma mansoni at different phases of infection

The interaction between specific immune response to Schistosoma mansoni and praziquantel (PZQ) was studied in mice. In mice harboring concomitant immunity, 6-day-old parasites treated with PZQ were more effectively removed than 24h treated parasites despite both had a significant worm burden reduction when compared with respective treated controls. These results show that PZQ can be effective at the skin and lung stages of parasite's development mainly acting with a established specific immune response, and particularly at the lung phase.

Schistosomiasis haematobia: histopathological course determined by cystoscopy in a patient in whom praziquantel treatment failed

Schistosomiasis haematobia or urinary schistosomiasis is one of the main public health problems in Africa and the Middle East. A single dose of 40 mg praziquantel per kg body weight continues to be the treatment of choice for this infection. The aims of this follow-up were to study the post-treatment course of a patient infected with S. haematobium and not submitted to re-exposure, and to identify complications of the disease and/or therapeutic failure after praziquantel treatment by histopathological analysis. Treatments were repeated under medical supervision to ensure the correct use of the drug. In view of the suspicion of lesions in cystoscopy, the patient was submitted to bladder biopsy. The histopathological characteristics observed in biopsies obtained, after each treatment, indicated viability of parasite eggs and activity of granulomas.

THE SUSCEPTIBILITY OF RECENT ISOLATES OF Schistosoma mansoni TO PRAZIQUANTEL

Introduction: Schistosomiasis is a chronic disease caused by trematode flatworms of the genus Schistosoma and its control is dependent on a single drug, praziquantel (PZQ), but concerns over PZQ resistance have renewed interest in evaluating the in vitro susceptibility of recent isolates of Schistosoma mansoni to PZQ in comparison with well-established strains in the laboratory. Material and methods: The in vitro activity of PZQ (6.5-0.003 µg/mL) was evaluated in terms of mortality, reduced motor activity and ultrastructural alterations against S. mansoni. Results: After 3 h of incubation, PZQ, at 6.5 µg/mL, caused 100% mortality of all adult worms in the three types of recent isolates, while PZQ was inactive at concentrations of 0.08-0.003 µg/mL after 3 h of incubation. The results show that the SLM and Sotave isolates basically presented the same pattern of susceptibility, differing only in the concentration of 6.5 µg/mL, where deaths occurred from the range of 1.5 h in Sotave and just in the 3 h range of SLM. Additionally, this article presents ultrastructural evidence of rapid severe PZQ-induced surface membrane damage in S. mansoni after treatment with the drug, such as disintegration, sloughing, and erosion of the surface. Conclusion: According to these results, PZQ is very effective to induce tegument destruction of recent isolates of S. mansoni.

Comparação entre praziquantel e oxamniquine no tratamento da esquistossomose mansoni

Tratamos 120 pacientes masculinos com idade de 17 a 19 anos, portadores de esquistossomose mansoni nas formas intestinal e hepatointestinal, pareados de acordo com o número de ovos por grama de fezes. Um membro de cada par tomou oxamniquine na dose de 15mg/kg e o outro, praziquantel na dose de 55mg/kg, em cápsulas. Dos 106 pacientes avaliados com pelo menos dois exames de fezes, negativaram-se 44 (83%) dos que tomaram praziquantel e 41 (77,3%) dos que tomaram oxamniquine. Ambas as drogas foram relativamente bem toleradas, com ligeira vantagem da oxamniquine.

Baixa eficácia da associação oxamniquine e praziquantel na cura da esquistossomose mansônica

Em uma área endêmica onde havia interrupção da transmissão, foram tratados 164 esquistossomóticos com a associação oxamniquine e praziquantel em doses reduzidas. Cada indivíduo tomou de uma só vez uma cápsula de 250mg de oxamniquine e um comprimido de 300mg de praziquantel, ingeridos na nossa presença. As doses de oxamniquine variaram de 3,5 a 16,6mg/kg de peso corporal e as de praziquantel de 4,2 a 20mg. O controle de cura constou de oito exames parasitológicos de fezes de cada paciente, pelo método de Kato-Katz, num período de 6 meses. Os índices de cura variaram de 30% a 56,6%. A percentagem total de cura foi de 39,6%. A tolerância à associação foi boa. Nossos resultados mostraram baixo percentual de cura e aparente ausência de sinergismo da associação oxamniquine epraziquantel em doses reduzidas no tratamento da esquistossomose mansônica no Brasil.