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The prophylactic and curative effects of praziquantel and oxamniquine on a Saudi Arabian strain of Schistosoma mansoni in MF-1 mice were assessed. The drugs were administered orally. At 240 mg/kg praziquantel, there was a reduction of 89.1% in adult worm recovery and a marked reduction in tissue deposited eggs. The reduction in adult worm recovery after dosing with 50 mg/kg oxamniquine was 89.2%. At low doses (40 mg/kg praziquantel and 30 mg/kg oxamniquine) administered at 11 days, 5 days and 3 h before and 5, 21 and 49 days after infection, the reduction in adult worm recovery was 0.0%, 65.1%, 58.8%, 33.6%, 0.0% and 76.0% for praziquantel and 0.0%, 66.0%, 60.0%, 41.3%, 10.8% and 79.0% for oxamniquine. Numbers of lung schistosomula and the size of hepatic granulomata were also reduced.

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.

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.

Blood samples from 24 patients infested with Schistosoma mansoni were drawn immediately before and 2 days after the administration of a single therapeutic dose of 12-15 mg/kg oral oxaminiquine. Two-day lymphocyte cultures were obtained and about 100 mitoses from each blood sample were analyzed for chromosome aberrations. No significant differences were observed between the "before" and "after" cultures in the frequencies of aberrations resulting from spindle, chromatidic, or chromosome events. It is concluded that there is no reason to fear harmful effects on the chromosomes of patients from treatment with oxaminiquine.

The best therapeutic approach to acute schistosomiasis (Katayama fever) is still unsettled. In this paper we report a synergistic effect between schistosomicides and steroids in the treatment of the early stages of Schistosoma mansoni infection in the mouse. CBA mice infected with 150 S. mansoni cercariae were treated with oxamniquine or praziquantel and dexamethasone or prednisolone. The rate of parasite egg excretion by treated mice and appropriate controls was monitored, and the mice were perfused 43 d after infection for estimation of worm burdens and tissue egg densities. Mice treated with schistosomicides alone or with schistosomicides plus steroids had worm burdens of similar size. Significant reductions in egg counts were, however, recorded in faeces, and in the intestines and livers (with consequent reduction in liver pathology), of mice treated with schistosomicide and steroid, when compared to mice treated with schistosomicide alone or steroid alone. The apparent inhibition of fecundity of S. mansoni by combining these drugs has clear implications for treatment of the Katayama syndrome.

Mice experimentally infected with Schistosoma curassoni were treated with different dose regimens of praziquantel, metrifonate, oxamniquine and hycanthone. Praziquantel was the most effective drug; a dose of 100 mg/kg given orally for 5 days resulted in a 95% reduction in worm burdens. The drug produced oogram changes in all animals. Metrifonate did not result in a reduced worm burden but caused oogram changes even on a low-dose (150 mg/kg during 2 consecutive days) schedule. Oxamniquine proved to be ineffective; no reduction in worm burdens or alterations in oograms were observed. Hycanthone (80 mg/kg for 1 day) resulted in a significant reduction in worm burdens.

One hundred sixteen male patients with uncomplicated Schistosoma mansoni infection were randomized to treatment with oxamniquine (20 mg/kg a day for 3 days) or niridazole (15 mg/kg a day for 8 days) in an in-hospital study. Fifty-four patients were treated with oxamniquine; no serious drug side effects were noted. Twenty-six percent of children 16 years old and younger were cured, while 85% of adults were cured. Egg reduction was 89%. Sixty-two patients were treated with niridazole; four patients (one child and three adults) had serious side effects which necessitated discontinuing the drug. Seventy-one percent of children and 84% of adults were cured. Egg reduction was 84%. Minor clinical side effects occurred during therapy with both drugs (26% with oxamniquine, 48% with niridazole) but cleared after completion of therapy. Niridazole is the more effective drug for the child with uncomplicated Schistosomiasis mansoni, but oxamniquine is advised for the adult with this disease.

One hundred eighty-four patients with hepatosplenic schistosomiasis mansoni from the northeast of Brazil were studied. All were treated with a single dose of Oxamniquine or Praziquantel, and were observed over 6 to 12 months. Special attention was given to the evolution of severe hepatopathy. Favourable results were obtained, particularly with the compensated hepatosplenic form. Hepatic function showed great improvement. Hepatomegaly and splenomegaly were significantly reduced in size, to a greater or lesser extent, in the great majority of patients. The implications of the results obtained are considered below.

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.

The authors note a very high prevalence of schistosomiasis mansoni in the two foci studied in Togo (Lama Kara in the North and Kpalimé in the South-West); however, the prevalence is significantly higher in Lama Kara (79.5%) than in Klonou (54.7%); this was calculated on both coprological and serological basis. The parasite burden is identical in the two foci; but, the GMRT is higher in Lama Kara than in Klonou (31.7 and 8) which might be explained by a different immunogenicity of the two strains. It is noticed schistosomiasis mansoni might be responsible for hepatosplenomegaly found in the two foci, especially in Lama Kara, which might be explained by a higher virulence in this location. The treatment by oltipraz (RP 35972) had a 91.9% success rate in Klonou (similar to our results in Paris). However, in Lama Kara, even though the drug was taken with some food--increasing its biodisponibility--, the treatment was less effective at day 180 (76.5%). The authors wonder whether the difference of oltipraz efficiency between the two foci is based on a difference of biology between the two strains of Schistosoma mansoni in Lama Kara and in Klonou.

This prospective study has shown that oxamniquine treatment controlled endemic schistosomiasis mansoni in a defined rural population in Castro Alves, north-east Brazil. Data before and after treatment spanning 11 years were collected for a cohort of 191 residents. Before treatment (1974-77), the cohort was heavily infected and the prevalence of associated hepatomegaly (greater than 86%) and splenomegaly (greater than 17%) was stable. The cohort was treated when oxamniquine became available in 1977; during the next 8 years, over 80% received further treatments from the Brazilian programme for the control of schistosomiasis. With treatment, the incidence of splenomegaly fell (10% to 2%) and the splenomegaly regression rate increased (43% to 91%). Declining disease rates were coincident with substantial falls in the prevalence and intensity of Schistosoma mansoni infections. The final prevalence rates for hepatomegaly (31%) and splenomegaly (3%) in Castro Alves approached the corresponding rates of 10% and 1% in a comparable uninfected control population.

Although 30 mg/kg oxamniquine produced high levels (85.5 to 99.5%) of egg reduction in Kenyan children infected with Schistosoma mansoni after a single oral treatment, cure rates from children at Mwea in Kirinyaga district were lower than those from Machakos (58% v. 74%). Redosing uncured children confirmed this lower cure rate (36% v. 83%). Isolates from infected children were passaged into mice and dosed with oxamniquine. Lower than expected reductions in worm numbers were obtained, suggesting that oxaminiquine tolerant S. mansoni are present in the normal worm population in Kenya. It is concluded that mass use of oxamniquine at 30 mg/kg may produce problems of drug resistance.

The hepatic levels of thiamine, pantothenic acid and niacin in hamsters infected with S. mansoni were depressed, while the levels of riboflavin and pyridoxine remained unchanged. A single dose of oxamniquine, 10-50 mg/kg, brought the levels of thiamine, pantothenic acid and niacin to values not significantly different from those in non-infected controls, but lowered the concentrations of riboflavin and pyridoxine in infected hamsters.

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.

During a 5-year period (1975-1980), 171 male patients aged eight to 58 years infected with Schistosoma mansoni have been treated with oxamniquine on an in-hospital basis. The patients comprised three clinical groups--uncomplicated S. mansoni infection, colonic polyposis due to S. mansoni, and hepatic decompensation due to S. mansoni--all with active infection. After treatment all patients were observed for 12 weeks then evaluated for cure. In the uncomplicated group 40 of 73 children (55%) and 39 of 45 adults (87%) were cured. In the polyps group 24 of 29 patients (83%) were cured and in the decompensated group all 24 patients were cured. The only side effect was a febrile reaction occurring in 65 patients (38%) 3-4 days after treatment was started. This 5 years' experience showed that oxamniquine results in a low cure rate in children but is effective in adults with uncomplicated S. mansoni. In patients with colonic polyposis oxamniquine is safe and well tolerated as initial therapy, particularly in the very ill, debilitated patient. Oxamniquine is clearly the drug of choice in patients with decompensated liver disease and active S. mansoni infection.

A comparative study on the evolutive morbidity of schistosomiasis mansoni in treated and non-treated patients in an endemic area was carried-out with evaluation of the treatment after one and six years. In the first year after treatment there was both an improvement in the clinical conditions and a dramatic reduction in the number of S. mansoni eggs eliminated by the treated patients in relation to the controls. However, after six years of observations, although the number of S. mansoni eggs eliminated by the treated patients was still less than in the control group, it was nearly the same number as before treatment. In both treated and non-treated groups there was an increase in the severity of the clinical forms of schistosomiasis, with a certain tendency of greater severity in the control group. Therefore the authors recommend that the specific treatment of the population in endemic area should be done at intervals of two to three years, and that the treatment should be associated to the environmental sanitation, water supply and the education of the population.

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.

The efficacy of an association of oxamniquine and praziquantel in the patent phase of experimental schistosomiasis was studied. The mice were infected and divided in four groups in accordance to the following schedules with the use of single oral doses: I--Oxaminiquine (50 mg/kg); II--praziquantel (75 mg/kg); III--association of oxamniquine (50 mg/kg) and praziquantel (75 mg/kg); and IV--no drug. Efficacy was assessed by the oogram technique, studying and classifying the evolution of the output of eggs in fragments of the small intestine, and also by recovery of the worms by portal vein perfusion. In the animals of groups I and II, the drugs had a partial effect while in the group III sinergism was evident.

Forty-one Egyptian schoolchildren (36 boys and five girls; age, 12-16 years) who were heavily infected with Schistosoma mansoni were studied. Symptomatic subjects had swimmer's itch and hematochezia. Hepatomegaly was found in 39 and splenomegaly in 31 children. All subjects had eosinophilia, 13 had anemia, 31 had elevated levels of serum globulins, and nine had elevated levels of alkaline phosphatase. All but one subject had antibody to hepatitis A virus, and 26 had antibody to hepatitis B core antigen, antibody to hepatitis B surface antigen, or both. Oxamniquine was given in single daily doses of 20 mg/kg of body weight for either two or three days and cured 50% and 85%, respectively, of subjects treated; ova excretion was reduced by 86%-93% for up to 12 months. Morbidity was associated with heavy S. mansoni infection. Therapy with oxamniquine was safe and efficacious.

The various presentations of schistosomiasis mansoni are discussed, stressing the indications of parosites elimination. Parasitologic cure is necessary, although, when the infestation is recent (acute), the drug efficacy is lower than in the chronic forms. Surgery may be pertension, special care must be taken, and in the pseudotumoral form there is not enough diet regarding progression of the disease after treatment. Contraindications are linked to associated illness, and are due to toxic effects of the available drugs. The mechanism of action of such drugs are discussed, as well as the historical background. Hycantone, Oxamniquine and Praziquantel are detailed in separate, with the proposed drug schedules and possible side effects.

The therapeutic efficiency of oxamniquine against the local strain of Schistosoma mansoni was investigated in experimentally infected mice. The drug was administered orally using a human-equivalent dose of 20 mg kg-1 day-1 for 3 consecutive days (total dose of 60 mg kg-1). Oxamniquine proved to be very effective as indicated by hepatic shift, oogram changes, complete elimination of adult worms and eradication of faecal eggs.