Efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infection: a controlled trial. Randomized comparative trials of single doses of the newer antischistosomal drugs at Mwanza, Tanzania. I. Praziquantel and oxamniquine for the treatment of schistosomiasis mansoni. Oxamniquine cures Schistosoma mansoni infection in a focus in which cure rates with praziquantel are unusually low. 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). Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan. Two-year follow-up of Schistosoma mansoni infection and morbidity after treatment with different regimens of oxamniquine and praziquantel. Therapeutic evaluation of two different dose regimens of praziquantel in a recent Schistosoma mansoni focus in Northern Senegal. Preliminary trials with praziquantel in human infections due to Schistosoma mansoni. Praziquantel in the treatment of mixed S. haematobium and S. mansoni infections. Oxamniquine for treating Schistosoma mansoni infection in Sudan. Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium. Efficacy of oxamniquine, praziquantel and a combination of both drugs in schistosomiasis mansoni in Brazil. A field trial using praziquantel (BiltricideR) to treat Schistosoma mansoni and Schistosoma haematobium infection in Gezira, Sudan. Comparative randomised trial of high and conventional doses of praziquantel in the treatment of schistosomiasis mansoni. Single dose oral treatment in urinary schistosomiasis: a double blind trial. Efficacy of mirazid in comparison with praziquantel in Egyptian Schistosoma mansoni-infected school children and households. Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya. Field study of different oxamniquine dose for Schistosoma mansoni in Gezira, Sudan. Dosage trial of a combination of oxamniquine and praziquantel in the treatment of schistosomiasis in Zimbabwean schoolchildren. Dose-finding trials of oral oxamniquine in Rhodesia. A preliminary report on the treatment of intestinal schistosomiasis with oxamniquine. Randomized comparison of low-dose versus standard-dose praziquantel therapy in treatment of urinary tract morbidity due to Schistosoma haema tobium infection. Survey on the clinical trial results achieved in Brazil comparing praziquantel and oxamniquine in the treatment of mansoni schistosomiasis. Clinical experience with praziquantel in the treatment of Nigerian patients infected with S. haematobium. Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia. Single dose metrifonate or praziquantel treatment in Kenyan children. II. Effects on growth in relation to Schistosoma haematobium and hookworm egg counts. A double blind trial with oxamniquine in chronic schistosomiasis mansoni. Double-blind clinical trial comparing praziquantel with oxamniquine in the treatment of patients with schistosomiasis mansoni. Praziquantel side effects during treatment of Schistosoma mansoni infected pupils in Kibwezi, Kenya. Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on intensity of infection and antibody responses to schistosome antigens: results of a randomised, placebo-controlled trial. Praziquantel: a new schistosomicide against Schistosoma haematobium. The impact of Schistosoma haematobium infection and of praziquantel treatment on the growth of primary school children in Bertoua, Cameroon. A community-based randomized trial of praziquantel to control schistosomiasis morbidity in schoolchildren in Zambia. A multicentre randomized controlled trial of the efficacy and safety of single-dose praziquantel at 40 mg/kg vs. 60 mg/kg for treating intestinal schistosomiasis in the Philippines, Mauritania, Tanzania and Brazil. Chemotherapy-based control of schistosomiasis haematobia. I. Metrifonate versus praziquantel in control of intensity and prevalence of infection. Double-blind clinical trial comparing praziquantel with oxamniquine in schistosomiasis mansoni. Treatment of patients with schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine. What is the effect of combining artesunate and praziquantel in the treatment of Schistosoma mansoni infections? A comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium.
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. 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. An outbreak of Schistosoma mansoni in northern Senegal was observed in 1988, and chemotherapy with praziquantel in this recently established focus resulted in very low parasitologic cure rates. Among other explanations, the emergence of a praziquantel-tolerant parasite strain was feared. To study this hypothesis further, 138 persons with endemic S. mansoni infection were randomly allocated to treatment with either 20 mg/kg oxamniquine or 40 mg/kg praziquantel. Parasitologic cure rates at 6 weeks were significantly higher in the oxamniquine group (79%) compared with those in the praziquantel group (36%; P = .0043). The reduction in egg counts was generally good, but 12% less reduced in the praziquantel group. These results confirm that cure rates with praziquantel were abnormally low, whereas oxamniquine performed satisfactorily, as in other areas in which S. mansoni is endemic. The possibility of a praziquantel-tolerant S. mansoni strain must therefore be studied carefully. 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 Sudan to evaluate the acceptability and efficacy of praziquantel given to schoolchildren aged 7-11 years who were all infected with both Schistosoma mansoni and S. haematobium. Two dosage regimes were compared, a single dose of 40 mg/kg bodyweight, and a divided dose 2 X 20 mg/kg given 4-6 h apart. When interviewed 24 h after treatment, 80% of the children complained of drug-induced abdominal pain, diarrhoea, nausea or vomiting. However none of the side-effects persisted beyond the day of treatment. More children complained of side-effects from the divided dose than from the single dose. The cure rate in the divided-dose group was slightly better than in the single-dose group but the differences were not significant at any follow-up, nor when results were expressed in terms of cumulative failures. The initial cure rates were 66.3% and 61.8% at 1 month, and 73.2% and 64.7% at 3 months for the divided and single doses respectively. After 12 months there had apparently been considerable reinfection with S. mansoni and 73% of the children were passing eggs. Reinfection with S. haematobium was negligible. Three study groups in the Rusizi plain (Burundi) were examined parasitologically (duplicate 28 mg Kato slides) and clinically (history, abdominal palpation) 0, 1.5, 3, 6, 12 and 24 months after treatment for Schistosoma mansoni infection. Infected subjects in Maramvya (n = 430) were treated randomly with oxamniquine 20, 30 or 40 mg/kg; those in Bulinga (n = 457) with praziquantel, 20, 30 or 40 mg/kg; those in Bulamata (n = 333) with praziquantel, 30 or 40 mg/kg. In children (less than 20 years) in Maramvya and Bulamata, infection rates and intensities returned almost to pretreatment levels one to 2 years after treatment. In Bulinga, reinfection in children was much less intense. Hardly any reinfection occurred in adults in Bulinga and Maramvya; in Bulamata, half of the cured adults were reinfected, most of them lightly, 2 years after treatment. The initial parasitological advantage of the higher dosages of both drugs disappeared generally 3-12 months after treatment. There was no indication of predisposition to heavy reinfection after treatment of subjects with initial high egg counts. Little relation between pre-treatment egg count and morbidity was observed. The impact of chemotherapy on hepatomegaly was limited and observed only in adults treated with 40 mg/kg of either drug. Spleen rates in children and adults were not affected. Abdominal pain was reduced in almost all treatment groups for 3 to 24 months. The frequency of bloody diarrhoea decreased dramatically in children and adults from all 3 villages. This effect lasted 24 months in Maramvya, 12 months in Bulinga and 6 months in Bulamata, and was not dose-dependent. It is concluded that: (i) repeated population chemotherapy combined with sanitation is necessary to achieve lasting impact on infection rates; (ii) retreatment intervals should be adapted to age group and, possibly, local endemicity levels; (iii) the morbidity impact of population chemotherapy in these conditions was greater on intestinal than on hepatosplenic disease; (iv) lower, cheaper treatment schedules may in the long term be as effective as those with high cure rates. A therapeutic trial, involving 130 Schistosoma mansoni-infected children, with no previous history of antischistosomal treatment, was carried out to evaluate the efficacy of two different dose regimens of praziquantel. The study was carried out because low cure rates were described in this recently established (1990) S. mansoni focus in northern Senegal, following treatment with a standard dosage of 40 mg/kg. The subjects were randomly allocated into two groups: one group (1) received 40 mg/kg in one oral dose, the other group (2) was treated with two oral doses of 30 mg/kg at a 6-hr interval. Parasitologic examination and circulating anodic antigen (CAA) detection were performed before, 10 days, three, six, and 21 weeks after chemotherapy. No significant differences in cure rates were found between the two groups. Six weeks after treatment, 34% and 44% of the individuals were found to be stool negative in group 1 and group 2, respectively. However, only 10-15% became completely negative according to the serum CAA antigen assay. Mean egg counts were reduced by 99% in both groups. Antigen detection confirmed the parasitologic results. Fewer side effects were observed in the group treated with 2 x 30 mg/kg, which may be explained by split dosage administration. Our study shows that the low cure rates observed in this area could not be improved by using a higher dosage of praziquantel. 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. A randomized single blind stratified study involving 153 patients with mixed S. mansoni and S. haematobium infection showed that 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) is effective in giving high cure rates in each infection separately, 66% (64 patients) and 77% (94 patients), respectively. The complete clearance of both infections (i.e., no eggs whether dead or alive) 6 months after treatment was 29% (43 patients). The side effects of the drug were minimal and transient, the most common being gastrointestinal ones. The assessment of the objective tolerability by clinical, haematological and biochemical tests showed also that the drug was very safe. It is thus concluded that the drug is a promising useful tool in the control of schistosomiasis in general and the treatment of the individual. The efficacy and acceptability of oral oxamniquine were assessed in Sudanese patients infected with Schistosoma mansoni. Cure rates, determined by the absence of viable eggs in the stools six months after treatment, were 94.9% in patients treated with a total of 60 mg/kg, 78.8% in patients treated with 40 mg/kg, and 68.9% in patients treated with 30 mg/kg. All treatment regimens considerably reduced the egg count in those patients not cured. The drug was well tolerated and the side effects were minimal and transient, the most common being dizziness. Most of the patients noticed a reddish discoloration of their urine, which was probably caused by a metabolite of the drug. In patients who received 60 mg/kg oxamniquine there were transient rises in eosinophil counts and in serum alanine aminotransferase concentrations. Though 60 mg/kg was by far the most effective dose in terms of cure rate, egg counts were significantly reduced on all three doses. The lower doses could therefore be useful in a low-cost control programme in reducing transmission of S mansoni infection. The shortage of available information on the impact of low doses of praziquantel was remedied by a trial of 0, 10, 20, 30 and 40 mg kg-1 against double infections of Schistosoma haematobium and S. mansoni in a rural area of Zimbabwe. No significant differences were found in egg reduction between 20-40 mg kg-1 for S. haematobium and between 30-40 mg kg-1 for S. mansoni. It is suggested that morbidity control can be achieved with lower dosages of praziquantel than currently recommended. nan 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. 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. 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. 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. 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. Two hundred and ninety-six individuals of whom 126 were children and 170 adults with positive stool for Schistosoma mansoni were randomly given oxamniquine treatment in a dose of either 20, 40 or 60 mg/kg body wt. They were followed in the field for ova excretion at 1, 3 and 6 months for adults and at 1, 3, 6 and 8 months for children. The cure rates in adults at 6 months are 93%, 87% and 73% for the 60, 40, 20 mg/kg-1 treatments in order. For children the cure rates at 6 months are 36%, 58% and 63% and at 8 months are 16%, 21% and 26% for corresponding doses. There is no difference in egg reduction for those not cured between the three treatments at 6 months. It is concluded that oxamniquine need not be given in the previously recommended 60 mg/kg body wt. A choice between 40 and 20 mg/kg body wt is suggested with the 40 mg/kg body wt to be reserved for individuals leaving the endemic area, and the 20 mg/kg body wt for those continuing to stay there with substantial exposure for reinfection. The overall proper cure rates for children with a possible advantage of the low treatment in the long term for this age group is noted. nan Oral oxamniquine at a total dose of 60 mg/kg (given in 4 equal doses morning and evening over 2 days, after food) is an efficient and apparently very safe drug for the treatment of Schistosoma mansoni infections. Lower doses, or shorter schedules of treatment, are less efficient. The drug has little or no effect on S. haematobium infections. Side-effects are mild and infrequent. Oxamniquine proved to be an efficient drug for the treatment of Schistosoma mansoni in adults. The cure rate obtained with a single oral dose of 15 mg/kg was 81.3 per cent. With 15 mg given b.d. for a single day the cure rate was 90 per cent. Post-treatment reduction of egg count was 93.7 and 95 per cent respectively within three months follow-up period. The drug, given by the oral route, was well tolerated, non-toxic, and side-effects were evanescent. Further studies are needed to indicate its use for mass treatment and control of schistosomiasis. 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. nan A double-blind controlled trial of 2-cyclohexylcarbonyl-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a] isoquinolin-4-one (praziquantel, EMBAY 8440, Biltricide) in the treatment of vesical schistosomiasis has been carried out in 90 Nigerian schoolchildren of both sexes aged 9--16 years. Oral doses of 1 x 30, 1 x 40, and 2 x 20 mg/kg b.w. were assessed against placebo at 1 x 40 mg/kg, and the subjects followed up for up to twelve months after treatment. The results showed that the drug is very effective against S. haematobium infections and well tolerated. There were not significant differences between the three dosage groups, and the drug had no adverse haematological or biochemical effects. It is concluded that praziquantel widely meets the requirements necessary for use in large scale control of vesical schistosomiasis. 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. 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. Ninety-one children with chronic schistosomiasis mansoni were selected for this double blind trial. 48 (Group 1) were treated with a single oral dose of oxamniquine (20mg/kg body-weight) and 43 (Group 2) received the placebo. Clinical, laboratory and radiological examinations were performed before and after treatment. Dark urine and vomiting were observed only in the oxamniquine group. Pulmonary condensations with or without air bronchogram were observed in the chest X-ray of 15% of Group 1 patients, between days 3 and 5 after treatment. In the urinalysis made on the first day after treatment, a false positive reaction was reported for urobilinogen and bilirubin in up to 50% of the patients treated with oxamniquine. In Group 1, 69.6% of the patients were cured. No patient was cured in Group 2. There was a 4.4% incidence of infection in the control group. There was a 77.9% egg excretion reduction in the 14 Group 1 patients not cured by oxamniquine. The authors conclude that oral oxamniquine in the prescribed dosage, has low toxicity and good therapeutic efficacy in children with chronic schistosomiasis mansoni. nan Four hundred and thirty six pupils in two primary schools in Kibwezi, Kenya aged between seven and sixteen years and positive for S. mansoni were treated as follows: 320 pupils with a single dose of praziquantel at 40 mg/kg body weight and 116 controls with a placebo. Immediate and delayed side effects of praziquantel were observed. The main side-effects were abdominal pain (36.3%), headache (35.3%) and nausea (13.1%). There was correlation between frequencies of these side-effects and intensity of infection measured as eggs per gram of faeces. Other side-effects included dizziness (9.7%), fever (7.8%), urticaria and bloody diarrhoea. Overall, the side-effects of praziquantel were mild and transient, and did not require any intervention. For ethical reasons, all pupils who served as controls were treated with praziquantel after the study. 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. 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. Praziquantel treatment of schistosomiasis during pregnancy was only recommended in 2002; hence the effects of treatment during pregnancy are not fully known. We have therefore evaluated the effects on infection intensity and the immunological effects of praziquantel treatment against Schistosoma mansoni during pregnancy, compared with treatment after delivery.
                A nested cohort of 387 Schistosoma mansoni infected women was recruited within a larger trial of de-worming during pregnancy. Women were randomised to receive praziquantel or placebo during pregnancy. All women were treated after delivery. Infection intensity after treatment was assessed by a single Kato-Katz examination of stool samples with duplicate slides and categorised as undetected, light (1-99 eggs per gram (epg)), moderate (100-399 epg) or heavy (>or=400 epg). Antibodies against S. mansoni worm and egg antigens were measured by ELISA. Results were compared between women first treated during pregnancy and women first treated after delivery.
                At enrollment, 252 (65.1%) of the women had light infection (median (IQR) epg: 35 (11, 59)), 75 (19.3%) moderate (median (IQR) epg: 179(131, 227)) and 60 (15.5%) had heavy infection (median (IQR) epg: 749 (521, 1169)) with S. mansoni. At six weeks after praziquantel treatment during pregnancy S. mansoni infection was not detectable in 81.9% of the women and prevalence and intensity had decreased to 11.8% light, 4.7% moderate and 1.6% heavy a similar reduction when compared with those first treated after delivery (undetected (88.5%), light (10.6%), moderate (0.9%) and heavy (0%), p = 0.16). Parasite specific antibody levels were lower during pregnancy than after delivery. Praziquantel treatment during pregnancy boosted anti-worm IgG isotypes and to a lesser extent IgE, but these boosts were less pronounced than in women whose treatment was delayed until after delivery. Praziquantel had limited effects on antibodies against egg antigens.
                S mansoni antigen-specific antibody levels and praziquantel-induced boosts in antibody levels were broadly suppressed during pregnancy, but this was not associated with major reduction in the efficacy of praziquantel. Long-term implications of these findings in relation to resistance to re-infection remain to be explored. 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. Our objective was to determine in a Cameroonian school population the effect of mild to moderate S. haematobium infection intensity on growth and development of children before and 6 months after praziquantel treatment. Previous studies have yielded contradictory results. Children from Bertoua schools were divided into four study groups: heavily infected (> 500 eggs 10 ml-1), moderately infected (1-499 eggs 10 ml-1) treated with praziquantel, a similar group treated with placebo, and an uninfected control group. Anthropometric measures--height for age per cent median (HAPM), and weight for age per cent median (WAPM)--were significantly higher among the uninfected children. Stepwise regression analysis showed that S. haematobium and Ascaris infections were the strongest predictors of the HAPM with hookworm and malaria infections playing a lesser role. Post treatment comparison of the praziquantel treatment group and the placebo group showed no significant differences for the anthropometric indicators except for mid-arm circumference. Longer observations of growth after treatment as well as monitoring of the rate of reinfection would be necessary to understand better the effect of S. haematobium on growth. 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. Praziquantel at 40 mg/kg in a single dose is the WHO recommended treatment for all forms of schistosomiasis, but 60 mg/kg is also deployed nationally.
                Four trial sites in the Philippines, Mauritania, Tanzania and Brazil enrolled 856 patients using a common protocol, who were randomised to receive praziquantel 40 mg/kg (n  =  428) or 60 mg/kg (n  =  428). While the sites differed for transmission and infection intensities (highest in Tanzania and lowest in Mauritania), no bias or heterogeneity across sites was detected for the main efficacy outcomes. The primary efficacy analysis was the comparison of cure rates on Day 21 in the intent-to-treat population for the pooled data using a logistic model to calculate Odd Ratios allowing for baseline characteristics and study site. Both doses were highly effective: the Day 21 cure rates were 91.7% (86.6%-98% at individual sites) with 40 mg/kg and 92.8% (88%-97%) with 60 mg/kg. Secondary parameters were eggs reduction rates (ERR), change in intensity of infection and reinfection rates at 6 and 12 months. On Day 21 the pooled estimate of the ERR was 91% in both arms. The Hazard Ratio for reinfections was only significant in Brazil, and in favour of 60 mg/kg on the pooled estimate (40 mg/kg: 34.3%, 60 mg/kg: 23.9%, HR  =  0.78, 95% CI  = [0.63;0.96]). Analysis of safety could not distinguish between disease- and drug-related events. 666 patients (78%) reported 1327 adverse events (AE) 4 h post-dosing. The risk of having at least one AE was higher in the 60 than in the 40 mg/kg group (83% vs. 73%, p<0.001). At 24 h post-dosing, 456 patients (54%) had 918 AEs with no difference between arms. The most frequent AE was abdominal pain at both 4 h and 24 h (40% and 24%).
                A higher dose of 60 mg/kg of praziquantel offers no significant efficacy advantage over standard 40 mg/kg for treating intestinal schistosomiasis caused by either S. mansoni or S. japonicum. The results of this study support WHO recommendation and should be used to inform policy decisions in the countries. 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. nan nan A group of 110 individuals with Schistosoma mansoni infection was investigated. Patients were allocated to one of three treatment groups and given artesunate or praziquantel alone or both in combination. Combined artesunate-praziquantel significantly increased the number of individuals cured at 5 weeks post-treatment, but at 12 weeks was only better than artesunate alone and at 24 weeks there was no statistically significant difference between the three groups. Egg count reduction rate was similar to the rate obtained with praziquantel used alone. 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.
Praziquantel 40 mg/kg as the standard treatment for S. mansoni infection is consistent with the evidence. Oxamniquine, a largely discarded alternative, also appears effective.
Further research will help find the optimal dosing regimen of both these drugs in children.
Combination therapy, ideally with drugs with unrelated mechanisms of action and targeting the different developmental stages of the schistosomes in the human host should be pursued as an area for future research.