Field trial of the efficacy of a simplified and standard metrifonate treatments of Schistosoma haematobium. Artesunate and praziquantel for the treatment of Schistosoma haematobium infections: a double-blind, randomized, placebo-controlled study. Praziquantel: a new schistosomicide against Schistosoma haematobium. Proteinuria, hematuria, and leukocyturia in children with mixed urinary and intestinal schistosomiasis. The impact of Schistosoma haematobium infection and of praziquantel treatment on the growth of primary school children in Bertoua, Cameroon. Epidemiology of helminth infections: implications for parasite control programmes, a South African perspective. Dose-finding study for praziquantel therapy of Schistosoma haematobium in Coast Province, Kenya. Chemotherapy-based control of schistosomiasis haematobia. I. Metrifonate versus praziquantel in control of intensity and prevalence of infection. Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan. [Comparison of 3 metrifonate dosages in mass chemotherapy of Schistosoma haematobium]. The impact of population level deworming on the haemoglobin levels of schoolchildren in Tanga, Tanzania. Comparative trials of regimes for the treatment of urinary schistosomiasis in The Gambia. Single dose oral treatment in urinary schistosomiasis: a double blind trial. Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths. Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium. Relationships of Schistosoma haematobium, hookworm and malarial infections and metrifonate treatment to growth of Kenyan school children. Praziquantel in the treatment of mixed S. haematobium and S. mansoni infections. Clinical experience with praziquantel in the treatment of Nigerian patients infected with S. haematobium. Single dose metrifonate or praziquantel treatment in Kenyan children. II. Effects on growth in relation to Schistosoma haematobium and hookworm egg counts. Field trial of metrifonate in the treatment and prevention of schistosomiasis infection in man. A comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium. Tolerance and efficacy of praziquantel in phase II A and II B therapeutic trials in Zambian patients. Randomized comparison of low-dose versus standard-dose praziquantel therapy in treatment of urinary tract morbidity due to Schistosoma haema tobium infection.
In a randomized double-blind study, the percentage egg reduction and cure rate after the standard schedule of metrifonate treatment of Schistosoma haematobium (3 doses of 7.5 mg.kg-1 at two-weekly intervals; A) and an abbreviated regimen (3 doses of 5 mg.kg-1 in one day; B) were compared in five villages in Somalia. 300 patients who were excreting 20 or more eggs of S. haematobium in 10 ml urine were recruited. The patients were classified according to their home villages and were then, randomly allocated to treatment A or B. They had similar ages, weights and egg output. Each patient received 3 doses of metrifonate and 2 doses of identical appearing placebo. Group A received metrifonate on the 1st, 4th and 5th dosing occasions and placebo on the 2nd and 3rd times. Group B received metrifonate on the 1st, 2nd and 3rd dosing times and placebo on the 4th and 5th times. Two hundred and one patients were followed up from 1 to 6 months. The remaining 99 (33%) patients either did not complete treatment or were lost during follow up. Egg reduction in the groups 1, 2, 3 and 6 months after treatment were 97, 97, 95 and 93% in Group A and 96, 96, 94 and 92% in Group B (NS). Corresponding cure rates for Group A were 52, 50, 48 and 44%, and in Group B they were 47, 48, 43 and 40% (NS). Seven patients from Group A and 9 from Group B complained of minor side-effects.(ABSTRACT TRUNCATED AT 250 WORDS) 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 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. Quantitative parasitological assessment and quantitative analysis of proteinuria, hematuria, and leukocyturia were carried out in 182 Sudanese schoolboys with mixed urinary and intestinal schistosomiasis. Pathological proteinuria was found in 73% of patients (median = 380, 95% confidence limits = 200 to 500 mg/liter). The median protein/creatinine ratio was 0.54. SDS polyacrylamide gel electrophoresis showed an excretion of albumin, transferrin, and IgG consistent with a postrenal pattern of proteinuria. Pathological erythrocyturia occurred in 84% of patients (median = 255, 95% CL = 95 to 629 cells/microliter) and leukocyturia in 77% of patients (median = 148, 95% CL = 93 to 246 cells/microliter). Phase contrast microscopy revealed intact erythrocytes, suggestive of postrenal hemorrhage. Proteinuria, erythrocyturia, and leukocyturia correlated significantly with the ova excretion in the urine, but not with egg excretion in the stool. Oxamniquine reduced ova excretion in the stool but did not influence pathological urine findings. In patients treated effectively with Praziquantel or Metrifonate, pathological PU, EU, and LU decreased markedly 1 month post treatment. PU in severely proteinuric patients reached physiological values 5 months post therapy. We suggest that the proteinuria, erythrocyturia, and leukocyturia in mixed schistosomiasis were of postrenal origin. 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. To determine the epidemiology of helminthic infections and the efficacy of parasite treatment among rural South African primary school children in the province of KwaZulu-Natal. To assess the South African government's parasite control policy.
                The study recruited 268 school children, aged 8 to 10, and randomly allocated them into treatment and placebo groups (treatment consisted of a single dose of albendazole (400 mg) and praziquantel (40 mg/kg)). Anthropometric measurements and the prevalence and intensity of helminth infections were taken at baseline (prior to treatment) and 16 weeks post treatment. Two weeks after treatment prevalence and intensity were again measured for an approximate 50% sub-sample of the children to investigate efficacy of treatment. An analysis of the South African government's policies concerning parasite control is assessed in the light of these epidemiological findings.
                Low levels of both stunting and wasting were observed throughout the study (approximately 10% and 1%, respectively), but did not vary significantly across either treatment group or time period (P >0.50). At baseline the observed prevalences for the three main helminths found in this study among the treated children were Ascaris lumbricoides 29.5%, Trichuris trichiura 51.9% and Schistosoma haematobium 22.3%. These prevalences declined significantly to 4.7% (P <0.0005), 38.0% (P < 0.03), and 3.3% (P < 0.0002), respectively, 16 weeks post treatment. The majority of infections observed at baseline were of light intensity, namely A. lumbricoides (50%), T. trichiura (80%) and S. haematobium (100%), and following treatment these levels were reduced significantly (P <0.0001, P< 0.05 and P < 0.005, respectively). The levels of both prevalence and intensity in the untreated group remained constant. The cure rates over the first two weeks of the study were found to be 94.4% for A. lumbricoides, 40% for T. trichiura and 72.2% for S. haematobium.
                The benefits of targeted, school-based treatment in reducing the prevalence and intensity of infection supports the South African government's focus of using school-based interventions as part of an integrated parasite control programme. These strategies and programmes are consistent with recommendations of the World Health Organization (WHO) and The United Nations Children's Fund (UNICEF). 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. 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. 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. The metrifonate standard cure consisted of three doses of 7.5 to 10 mg/kg at a fortnight interval. These repeated doses increase the total cost of the treatment and the number of incomplete cures. We wanted to verify whether a reduced cure gets still a good efficacy. 286 people from three villages situated near Niamey (Niger) where treated at random with either 1, 2 or 3 doses of 10 mg/kg metrifonate. Before treatment the mean egg-output was 40 eggs/10 ml; 4 months later the cure rate was different only between the 1 dose trial and the 3 doses one. Moreover, this rate is low (35.3%) and the mean egg-output is also low (40.3%) for one dose. These results are more significant according to the first mean egg-output level. Below 5 eggs/10 ml, the cure rate is good with 2 or 3 doses (62% and 70%, 4 months later treatment), between 6 and 50 eggs/10 ml the results are still acceptable (55 and 53%). On the other hand, above 50 eggs these results are insufficient even with 3 doses. The single dose does not give sufficient result even in low egg-output. The impact of albendazole (400 mg) and praziquantel (40 mg/kg body weight) treatment of schoolchildren was compared with placebo according to the presence of anaemia (haemoglobin concentration < 11. 0 g/dl) and heavy (> 5000 epg) or light (< 5000 epg) hookworm egg load. The study was conducted in rural Tanga. Medication was administered in September 1994 and children were followed-up in January 1995. Overall, anthelminthic treatment reduced the fall in haemoglobin concentration compared with that observed in the placebo group (- 0.11 g/dl vs. - 0.35 g/dl; P = 0.02). Anthelminthic treatment was of greatest benefit to the 9% of children with both anaemia and heavy hookworm egg load (+ 0.67 g/dl vs. - 0.67 g/dl) and was also of significant benefit to the 38% of children with anaemia and light hookworm egg load (+ 0.07 g/dl vs. - 0.21 g/dl). It was of no significant benefit to children who were not anaemic. This study suggests that single-dose anthelminthic treatment distributed in schools in this area achieves haematological benefits in nearly half of children infected with S. haematobium and geohelminths (37% of total population). 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. 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. 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. Relationships of S. haematobium, hookworm and malarial infections to growth 6 months after metrifonate treatment were studied in Kenyan primary school children in an area where poor growth, S. haematobium and hookworm were common and malaria was endemic. All children with light-moderate S. haematobium infections (1-500 eggs/10 ml adj) in 4 schools were examined (Exam 1), allocated at random to either placebo (MIP, n = 198) or metrifonate treatment (MIT, n = 201) groups, treated, and examined again 6 months later (Exam 2). An additional 19 heavily infected children (HIT group greater than 500 eggs/10 ml adj) were treated immediately after Exam 1 and also followed. The MIT and HIT groups exhibited more rapid growth between Exam 1 and 2 than did the placebo group. The MIT group gained significantly (P less than 0.001) more than the MIP group in weight (0.8 kg), percent weight for age (2.3 percentage points), weight for height squared (0.04 units), arm circumference (0.4 cm), percent arm circumference for age (1.7 percentage points) and in triceps and subscapular skinfold thicknesses. In addition, the placebo group showed statistically significant decreases between exams in percentage weight for age, percent arm circumference for age, both skinfold thicknesses for age and no significant increase in percent height for age while the MIT group exhibited highly significant increases in all anthropometric parameters.(ABSTRACT TRUNCATED AT 250 WORDS) 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. 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. 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. 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. 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. nan 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.
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.