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.
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.
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.