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.
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.
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.