Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia. Single dose oral treatment in urinary schistosomiasis: a double blind trial. Randomized comparison of low-dose versus standard-dose praziquantel therapy in treatment of urinary tract morbidity due to Schistosoma haema tobium infection. Chemotherapy-based control of schistosomiasis haematobia. I. Metrifonate versus praziquantel in control of intensity and prevalence of infection. A comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium. Randomized comparative trials of single doses of the newer antischistosomal drugs at Mwanza, Tanzania. I. Praziquantel and oxamniquine for the treatment of schistosomiasis mansoni. Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya. Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil. Single dose metrifonate or praziquantel treatment in Kenyan children. II. Effects on growth in relation to Schistosoma haematobium and hookworm egg counts. Comparison between the efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infections on a sugar estate in Ethiopia. Mixed Schistosoma haematobium and S. mansoni infection: effect of different treatments on the serum level of circulating anodic antigen (CAA). A field trial using praziquantel (BiltricideR) to treat Schistosoma mansoni and Schistosoma haematobium infection in Gezira, Sudan. Dosage trial of a combination of oxamniquine and praziquantel in the treatment of schistosomiasis in Zimbabwean schoolchildren. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni. Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial. Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis. Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths. A community-based randomized trial of praziquantel to control schistosomiasis morbidity in schoolchildren in Zambia. Preliminary trials with praziquantel in human infections due to Schistosoma mansoni. Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households. Field trial of metrifonate in the treatment and prevention of schistosomiasis infection in man. Praziquantel: a new schistosomicide against Schistosoma haematobium.
Alternative regimes for the treatment of Schistosoma haematobium infection were compared in two trials. Praziquantel at a dose of 40 mg kg-1 appeared to cure 63% of a random sample of heavily infected subjects; significantly more than the 18% cured by three fortnightly doses of metrifonate at 10 mg kg-1. However, praziquantel led to a greater incidence of mild, transient side-effects. A single dose of metrifonate was found to be an inadequate treatment in the same group of subjects as it left 53% with an egg count of at least 100 ova/10 ml. A combination of 10 mg kg-1 of metrifonate and 25 mg kg-1 of niridazole had a similar effect to that of a single dose of metrifonate alone and it had more side-effects. Reduced doses of praziquantel had less effect on egg counts than the standard regime, but the difference was not significant in the case of 20 mg kg-1. Although a combination of metrifonate and praziquantel, each at 10 mg kg-1, had a greater effect than either constituent alone, the difference was not significant. Factors affecting the choice of drug for use in mass treatment of urinary schistosomiasis in The Gambia are discussed. The present findings suggest that the standard regime of praziquantel should be used or, if this is not possible, a three-dose metrifonate regime. A double blind trial of three oral preparations given in single doses for the treatment of Schistosoma haematobium infection was carried out in schoolchildren; selection was biased towards those who excreted large quantities of eggs. Praziquantel 40 mg/kg was the most effective drug giving a greater than 97% reduction in egg output six months after treatment; combined treatment with niridazole 25 mg/kg and metrifonate 10 mg/kg gave a reduction of greater than 92% and metrifonate 10 mg/kg alone a reduction of greater than 86%. Fewer children continued to have moderate to heavy infections (excretion greater than 124 ova/10 ml urine) six months after treatment with praziquantel (5%) and the combined regimen (7%) than with metrifonate (16%). Though our findings show that praziquantel appears to be the most effective and convenient drug available for individuals with S haematobium infection, the combined regimen is a cheaper alternative for treatment where cost is important and parasitological cure not an essential objective. At present, anthelmintic therapy with praziquantel at a dose of 40 mg/kg of body weight is the recommended treatment for control of urinary tract morbidity caused by Schistosoma haematobium. Although this standard regimen is effective, drug cost may represent a significant barrier to implementation of large-scale schistosomiasis control programs in developing areas. Previous comparison trials have established that low-dose (20-30 mg/kg) praziquantel regimens can effectively suppress the intensity of S. haematobium infection in endemic settings. However, the efficacy of these low-dose regimens in controlling infection-related morbidity has not been determined in a randomized field trial. The present random allocation study examined the relative efficacy of a 20 mg/kg dose versus a 40 mg/kg dose of praziquantel in control of hematuria and bladder and renal abnormalities associated with S. haematobium infection in an endemic area of Coast Province, Kenya. After a nine-month observation period, the results indicated an advantage to the standard 40 mg/kg praziquantel dose in terms of reduction of infection prevalence and hematuria after therapy (P < 0.01 and P < 0.005, respectively). However, the two treatment groups were equally effective in reducing structural urinary tract morbidity detected on ultrasound examination. We conclude that in certain settings, a 20 mg/kg dose of praziquantel may be sufficient in providing control of morbidity due to urinary schistosomiasis in population-based treatment programs. To determine the effect of targeted field administration of oral chemotherapeutic agents on the prevalence, intensity, and morbidity of Schistosoma haematobium infections, we initiated a long-term school-based program in the Msambweni area of Kwale District, Coast Province, Kenya. Prior to treatment, 69% of the children examined (ages 4-21, n = 2,628) were infected; 34% had moderate or heavy infections (greater than 100 eggs/10 ml urine). Infected individuals were randomized to receive, during one year, either metrifonate (10 mg/kg x 3 doses) or praziquantel, (40 mg/kg x 1 dose). At the end of the first year, prevalence of infection fell to 19%; only 2% of the pupils remained in the moderately and heavily infected groups. Corresponding decreases in the prevalence of hematuria (54% in 1984 vs. 16% in 1985) and proteinuria (56% in 1984 vs. 26% in 1985) were noted. These were associated with significant declines in bladder thickening and irregularities noted during ultrasound examinations, but not with decreases in hydronephrosis. There was no significant difference in the post-treatment prevalence or intensity of infection after treatment with metrifonate as compared with praziquantel. These results demonstrate that field-applied chemotherapy with either agent offers a practical strategy for the control of S. haematobium infection and its associated morbidity. Praziquantel administered in a single oral dose of 30 mg kg-1 to subjects infected with Schistosoma haematobium produced minimal side effects and was more effective than established regimes of niridazole and metrifonate. Praziquantel should prove a major tool in schistosomiasis control programmes. Randomized single-blind comparative trials of the newer antischistosomal drugs praziquantel and oxamniquine were undertaken at Mwanza, Tanzania, an area coendemic for schistosomiasis mansoni and haematobium. The objective was to compare praziquantel, having broad-spectrum activity, with oxamniquine when administered in single doses for levels of tolerance, symptomatic relief, and reduction in schistosome egg output in schistosomiasis mansoni. Whereas the single oral doses of 40 mg/kg and 15 mg/kg for praziquantel and oxamniquine respectively were nearly equally well tolerated, praziquantel showed significantly better efficiency to commend it as a drug of choice for chemotherapy for control programmes, besides its acknowledged place in the clinical management of individual patients. To assess the efficacy of low dose praziquantel regimens in comparison with standard 40 mg/kg dosing in the treatment of urinary schistosomiasis, a random allocation dose-finding trial was performed in children and adults from a Schistosoma haematobium endemic region in Coast Province, Kenya. Following an initial screening, 280 individuals with greater than or equal to 50 eggs/10 ml urine were randomly assigned to receive either 10, 20, 30, or 40 mg/kg of the drug in a single oral dose. Two to three months later, cure rates of 26%, 68%, 78%, and 84% were found for the 10, 20, 30, and 40 mg/kg doses, respectively. The results of 10 mg/kg oral dosing were significantly worse than for all other doses in terms of cure rate and of post-treatment prevalence of morbidity. The 40 mg/kg dosing resulted in a significantly higher cure rate than the 20 mg/kg doses; nevertheless, there was no significant difference between 20 mg/kg and 40 mg/kg doses in terms of mean post-treatment intensity of infection or post-treatment prevalence of hematuria or proteinuria. For large-scale control programs, oral 20 mg/kg praziquantel therapy for urinary schistosomiasis may prove as effective as the standard oral 40 mg/kg dosing for control of infection-associated morbidity and reduction of parasite transmission. nan We studied the growth of comparable groups of children with light to moderate Schistosoma haematobium infections who received a single dose of metrifonate (MT, 10 mg/kg), praziquantel (PR, 40 mg/kg), or a placebo (PL). Children were re-examined 8 months later. The MT and PR groups gained significantly more than the placebo group in weight, percent weight for age, percent weight for height, arm circumference, and in triceps and subscapular skinfold thicknesses. The MT and PR groups did not differ significantly from each other. The placebo group showed statistically significant decreases or no change between exams in percent weight for age, percent weight for height, percent arm circumference, and both skinfold thicknesses; the MT and PR groups exhibited highly significant increases in these parameters (P less than 0.0002). The intensity of S. haematobium infection had decreased significantly in both the MT and PR groups, but especially in the PR group. Multiple regression analyses showed that a decrease in the intensity of S. haematobium infection was by far the most important predictor of growth rate after treatment for all 5 anthropometric measures tested; decreases in the intensity of hookworm infection was also significant for 2 of the 5 measures. The efficacy of the antischistosomal drugs praziquantel and oxamniquine was tested on four groups of Ethiopian sugar estate workers. The cure rates, determined by the absence of eggs in stools, were 96, 93 and 74% at one, three and six months post-treatment for patients receiving a single dose (40 mg kg-1 body weight) of praziquantel, and 82, 78 and 78% for patients on a single dose (15 mg kg-1 body weight) of oxamniquine. When split doses of these drugs were used, praziquantel achieved cure rates of 96, 95 and 89%, while the corresponding cure rates for oxamniquine were 98, 96 and 88% at one, three and six months post-treatment. In general, there were no statistically significant differences within the single and split doses of each drug, nor between the two drugs except that single doses of praziquantel had significantly higher cure rates than oxamniquine at one and three months post-treatment. Although both drugs produced mild and transient side-effects such as dizziness, abdominal discomfort and diarrhoea, serious side-effects such as seizures were seen only among patients on oxamniquine. As praziquantel is also effective against other forms of schistosomiasis as well as against cestodes, we recommended the use of this drug in mass chemotherapy and in the ambulatory treatment of schistosomiasis in Ethiopia. In this study, levels of circulating anodic antigen (CAA) in serum were investigated after differential treatment of 160 Sudanese patients with mixed Schistosoma haematobium and S. mansoni infections. The patients were randomly divided into four groups, which were treated with metrifonate (two doses of 10 mg/kg bodyweight), oxamniquine (60 mg/kg), praziquantel (40 mg/kg), or a multivitamin preparation, respectively. Serum, stool and urine samples were taken prior to treatment as well as one month and five months after chemotherapy. Before chemotherapy CAA levels were similar in the four groups. Antigenemia remained unchanged in the control group. In patients treated with praziquantel or oxamniquine the concentration of CAA decreased to a similar extent. However, whereas in the praziquantel group absence of CAA was already observed one month after treatment, clearing of CAA from the circulation seemed to take longer in patients treated with oxamniquine. Treatment with metrifonate did not result in a reduction of the CAA titres. A field trial was conducted in the Gezira, Sudan, to evaluate the acceptability and efficacy of praziquantel, a new schistosomicide. In one Arab village 350 patients with Schistosoma mansoni were randomly assigned to two treatment groups and given 1 X 40 mg kg-1 (Group A) or 2 X 20 mg kg-1 given four to six hours apart (Group B). In two small settlements (camps) 2 km distant from the Arab village 38 patients with S. mansoni and 43 with concurrent S. mansoni and S. haematobium infections were given 1 X 40 mg kg-1. Side effects were mild and limited to the first 24 hours after treatment. The main complaints were abdominal pain, diarrhoea, urticaria and/or vomiting and were most common in the camp residents (79%) with 60% of Group A and 45% of Group B having one or more side effects. One month after treatment 'cure' rates were: Camps 63%, Group A 84% and Group B 96%, and the reduction in egg output was over 95%. After 12 months re-infection was greater in the camps. As there was no significant difference in the egg output reduction between the two treatment regimes, praziquantel is recommended for mass chemotherapy in Gezira at the logistically simpler regimen of 1 X 40 mg kg-1. nan Recently, artemisinin derivatives have been shown to be efficacious in chemoprophylaxis of and chemotherapy for Schistosoma japonicum and S. mansoni infections. Therefore, a double-blind, randomized, placebo-controlled study was carried out to investigate the efficacy and tolerability of artesunate plus placebo and the combination of artesunate and praziquantel in the treatment of S. haematobium infections in Gabon. The 300 infected schoolchildren included in the study were randomized to receive artesunate plus placebo (n=90), praziquantel plus placebo (n=90), artesunate and praziquantel (n=90), or only placebo (n=30). End points were efficacy, assessed as cure on day 56, and tolerability. All treatment regimens were well tolerated. The praziquantel plus placebo-treated group attained a cure rate of 73%, artesunate plus placebo a rate of 27%, the combination of artesunate and praziquantel a rate of 81%, and placebo alone a rate of 20%. In summary, earlier findings of efficacy of artemisinin derivitives against S. mansoni and S. japonicum could not be confirmed in S. haematobium infections. The efficacy of oral praziquantel in the treatment of schistosomiasis has been considered low by most public health institutions. In this paper, we compared the efficacy of two dosages of praziquantel (80 mg/kg vs. 50 mg/kg) in patients with chronic schistosomiasis mansoni. Two hundred eighty-eight patients with schistosomiasis from a community in Brazil were randomly divided into two groups: 145 patients (Group 1) received 80 mg/kg body weight of oral praziquantel divided in two equal doses with 1 h interval and 143 patients (Group 2) received 50 mg/kg body weight of oral praziquantel. To keep the study masked, patients in Group 2 received placebo 1 h after the first dose. All patients were subjected to clinical and ultrasonographic examination. Cure assessment was performed by repeating two stool examinations, by a quantitative method, at 30, 90 and 180 days after treatment. The morbidity of schistosomiasis was low, with a few cases of light periportal thickening and 16 cases of mild splenomegaly. The cure rates were 89.7% for Group 1 and 83.9% for Group 2. There was no difference in the efficacy of both therapeutic dosages of praziquantel assayed. The adverse reactions were more frequent with higher dosage. To evaluate the therapeutic efficacy of oxamniquine and praziquantel, the two most clinically important schistosomicide drugs, and to compare the accuracy of faecal examination with the accuracy of oogram in testing for Schistosoma mansoni infection.
                In a triple-masked and randomized controlled trial, 106 patients infected with S. mansoni were randomly allocated to one of three statistically homogeneous groups. One group was given 60 mg/kg praziquantel per day for three consecutive days, another was given two daily doses of 10 mg/kg oxamniquine, and the placebo group received starch. Faecal examinations (days 15, 30, 60, 90, 120, 150, and 180 after treatment) and biopsy of rectal mucosa by quantitative oogram (days 30, 60, 120, and 180) were used for the initial diagnosis and for evaluating the degree of cure. The chi2 test and the Kruskal-Wallis test were used to compare variables in the three groups. Survival analysis (Kaplan-Meier) and the log-rank test were used to evaluate the efficacy of the treatments.
                The sensitivity of stool examinations ranged from 88.9% to 94.4% when patients presented with >5000 S. mansoni eggs per gram of tissue (oogram); when the number of eggs dropped to <1000 eggs per gram, sensitivity was reduced (range, 22.7-34.0%). When cure was evaluated by stool examination, oxamniquine and praziquantel had cure rates of 90.3% and 100%, respectively. However, when the oogram was used as an indicator of sensitivity, the oxamniquine cure rate dropped dramatically (to 42.4%), whereas the rate for praziquantel remained high, at 96.1%.
                Praziquantel was significantly more effective than oxamniquine in treating S. mansoni infection. The oogram was markedly more sensitive than stool examinations in detecting S. mansoni eggs and should be recommended for use in clinical trials with schistosomicides. nan A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains of Schistosoma japonicum, and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment. A community-based, double-blind, randomized trial of praziquantel was carried out in an area of Zambia endemic for schistosomiasis. The aim of the study was to assess the impact of the treatment on Schistosoma mansoni morbidity. A total of 377 infected children, aged seven to 19 years, was randomized into two groups: one of 190 (group A) and one of 187 (group B). All children were treated with 40 mg praziquantel/kg at the start of the study. Six months later, the children in group A were re-treated with the same dose of praziquantel, while the children in group B were given placebos. All children were followed up three, six and 12 months after the initial treatment, morbidity being clinically evaluated at the six- and 12-month follow-ups. The results show that, in both groups of children, there were significant reductions in splenomegaly, hepatomegaly, and subjective symptoms of morbidity six and 12 months after initial treatment. However, there were no significant differences, between the two groups, in the prevalences of these symptoms of morbidity. It therefore appears that once-yearly treatment of children, in this and similar endemic areas, is sufficient to reduce schistosomiasis morbidity to, and maintain it at, a tolerable level. As part of a programme of multicentre trials of the tolerance and therapeutic effect of praziquantel, clinical trials were carried out in Brazil in patients with active Schistosoma mansoni infections, each of whom had a minimum geometric mean egg output of 100 eggs per gram of faeces calculated from multiple pretreatment stool examinations.The first stage was a double-blind assessment of tolerance and efficacy of oral doses of 1 x 20, 2 x 20, or 3 x 20 mg of praziquantel per kg of body weight. Subsequently, single-blind trials explored the effects of 3 x 20 mg/kg at 4-hourly intervals, and a single dose of 50 mg/kg.Side effects increased in frequency as dosage increased. Nausea, epigastric pain, headache, dizziness, and drowsiness were all noted but their severity was mild or moderate and they disappeared in 48 hours. In general, monitoring laboratory tests showed little change.Following a stringent parasitological follow-up, 96% of 28 patients followed at 1 year after treatment with either 3 x 20 mg/kg or 1 x 50 mg/kg were cured. Praziquantel seems to be a very promising drug against S. mansoni and further clinical trials should be strongly encouraged. This trial investigated the anti-schistosomal activity of mirazid in comparison with that of praziquantel in Schistosoma mansoni-infected Egyptian patients. The sample population was composed of 1,131 individuals (459 school children and 672 household members). Screening for S. mansoni was conducted using the standard Kato Katz technique. Four slides from a single stool sample were examined before treatment, and four slides per sample from stool samples obtained on three consecutive days were examined post-treatment. All positive eligible subjects were randomly assigned into two groups, the first received mirazid at a dose of 300 mg/day for three consecutive days, and the second received praziquantel at a single dose of 40 mg/kg. All treated subjects were examined 4-6 weeks post-treatment. Mirazid showed low cure rates of 9.1% and 8.9% in S. mansoni-infected school children and household members, respectively, compared with cure rates of 62.5% and 79.7%, respectively, in those treated with praziquantel. Therefore, we do not recommend mirazid as an agent to control schistosomiasis. A field trial was set up to test the prophylactic properties of the organophosphorous drug metrifonate (Bilarcil Bayer AG). Subjects were rural African children living in an area of Rhodesia where Schistosoma haematobium and S. mansoni are highly endemic. The trial was conducted in three stages, a preliminary period of therapy followed by two six-month periods of prophylaxis. Parasitological and haematological tests were carried out monthly and major assessments (including clinical examinations) were carried out prior to the start of the trial and at the end of each of the three stages. Drug was given to the appropriate groups at a dose rate of 7-5 mg/kg once per fortnight for three doses during the therapy stage and four-weekly during the prophylaxis stage. Results with S. haematobium were very good. A 60% cure-rate was observed six weeks aection was obtained in those children continuing to receive the drug as a prophylactic, even during the season of highest transmission; intensities of infection in those who became infected were very low. Infection rates in the treated but unprotected group rose steadily from 40% at week 11 to 95% at week 70. There was a sigificant effect upon the intensity of S. mansoni infections only when pre- and post-trial data were compared. Apart from the anticipated (and previously reported) depression of plasma cholinesterase values no side effects were recorded. Drug tolerance and acceptibility were very high. It is likely that the costs of a year's protection against S. Haematobium using metrifonate will be significantly lower than protection by molluscicidal techniques or single courses of treatment with established drugs. The effectiveness of the new schistosomicide praziquantel was assessed in African schoolchildren infected with Schistosoma haematobium. They were stratified according to the severity of their infection and were then randomly allocated to treatment with two single-dose regimens (30 and 40 mg/kg) and a split regimen of two doses of 20 mg/kg given four hours apart. All three regimens were highly effective and produced few side effects. Children who initially had very high pretreatment egg loads showed a poorer therapeutic response at all dose levels, and further investigations are necessary to find the optimum dose. Because of its effectiveness in a single dose and lack of toxicity, praziquantel may prove to be the ideal schistosomicide.
Praziquantel and metrifonate are effective treatments for urinary schistosomiasis and have few adverse events. Metrifonate requires multiple administrations and is therefore operationally less convenient in community-based control programmes. Evidence on the artemisinin derivatives is currently inconclusive, and further research is warranted on combination therapies. We suggest metrifonate be reconsidered for the WHO Model List of Essential Medicines.