Comparison between the efficacy of oxamniquine and praziquantel in the treatment of Schistosoma mansoni infections on a sugar estate in Ethiopia

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.     

不同剂量吡喹酮治疗埃及血吸虫病1627例的临床观察

本文报道在马里共和国某医院工作期间，采用不同剂量吡喹酮治疗１６２７例埃及血吸虫病患者的临床疗效。甲组１１８７例，给以４０ｍｇ／ｋ，顿服；乙组３２１例，给以１０ｍｇ／ｋｇ，日服３次，连服２ｄ；丙组１１９例，给以５０ｍｇ／ｋｇ，顿服。治疗后３个月，镜检尿内虫卵，３组比较，以乙组疗法的疗效为最佳，虫卵阴转率达９６．６％，表明吡喹酮分次给药的方案较单次顿服为佳，且无药物副作用。     

The effectiveness of metrifonate in reducing hookworm infection in Kenyan school children

The reduction in hookworm egg counts was determined in children treated with 1 and 2 doses of metrifonate. Kenyan primary school children were allocated to receive either 10.0 mg (n = 53) or 7.5 mg (n = 53) of metrifonate per kg of body weight (mg/kg) or a placebo (n = 26). Two doses of 10.0 mg/kg reduced hookworm egg counts (from arithmetic means of 4,177 to 438 eggs per gram of feces [epg]) more than did 2 doses of 7.5 mg/kg (from 4,329 to 1,392 epg; P less than 0.01). Two doses of metrifonate reduced egg counts more than did 1 dose (P less than 0.0001). The placebo group did not show a significant change in egg counts. The single dose of 10.0 mg/kg led to a 78% reduction in hookworm egg counts (from 4,177 to 918 epg), a level unlikely to cause iron deficiency anemia. This was as effective as 2 doses of 7.5 mg/kg, and was more easily administered than 2 or 3 doses. The further reduction after a second dose of 10.0 mg/kg (to 438 epg) is probably not of practical importance. This study shows that metrifonate, even in a single dose for treatment of S. haematobium, is also useful in reducing hookworm egg counts.     

Single dose metrifonate or praziquantel treatment in Kenyan children. I. Effects on Schistosoma haematobium, hookworm, hemoglobin levels, splenomegaly, and hepatomegaly

The relationships between S. haematobium, hookworm, malaria, hemoglobin level, splenomegaly, and hepatomegaly before and 8 months after treatment with a single dose of metrifonate or praziquantel were studied in Kenyan primary schoolchildren in an area where anemia, S. haematobium, and hookworm are common and malaria is holoendemic. Children with light to moderate S. haematobium infection were examined (Exam 1), assigned at random to groups receiving placebo (PL, n = 104), metrifonate (MT, n = 103, dose 10 mg/kg body weight) or praziquantel (PR, n = 105, dose 40 mg/kg body weight), treated, and examined 8 months later (Exam 2). At Exam 2, 62% of the MT group still passed S. haematobium eggs vs. 13% in the PR group. Egg reduction rates were substantial in both groups, but greater in the PR group; geometric mean egg counts in both groups were very low. Prevalence and intensity in the PL group had not changed between exams. Hookworm egg counts were significantly reduced in the MT group (59% egg reduction rate); malarial infection had increased in all 3 groups, presumably due to the long rainy season between exams. Hookworm egg count was the most significant predictor of initial hemoglobin level, followed by S. haematobium egg count and presence of malarial infection. Treatment with a single dose of MT or PR can produce substantial decreases in S. haematobium infection 8 months later.     

Chemotherapy-based control of schistosomiasis haematobia. II. Metrifonate vs. praziquantel in control of infection-associated morbidity

To determine the relative efficacy of metrifonate and praziquantel in controlling urinary tract morbidity due to Schistosoma haematobium infection, a random allocation treatment trial was performed among 1,813 school age S. haematobium-infected children from the Msambweni area of Coast Province, Kenya. Following baseline examination for infection, hematuria, proteinuria, and ultrasonographic urinary tract abnormalities, oral treatment with either metrifonate (10 mg/kg, repeated at 4 month intervals) or praziquantel (1 dose of 40 mg/kg) was given to infected subjects. Prevalence of morbidity was reassessed 12 months later for each treatment group. Results indicated equivalent patient improvement in response to either regimen: prevalence of hematuria fell from 75% to 17% after either praziquantel or metrifonate therapy. Similarly, prevalence of proteinuria was significantly reduced from 73% to 29% (metrifonate) or 27% (praziquantel) after therapy. Metrifonate and praziquantel caused similar reductions in bladder granulomata and bladder thickening; however, no reduction in hydronephrosis was noted with either drug. Analysis of outcomes in population subgroups defined by age, sex, pretreatment intensity of infection, or severity of pretreatment morbidity showed no consistent advantage for either drug. In this endemic area, both agents provide effective control of morbidity due to urinary schistosomiasis.     

Eighteen-month follow-up on the treatment of urinary schistosomiasis with a single dose of metrifonate

Egg excretion of school children with urinary schistosomiasis treated with a single 10 mg/kg dose of metrifonate was monitored over a period of 18 months. At 18 months 68.8% of infected children showed a greater than 90% reduction in egg excretion and 23.7% had ceased excreting eggs. During the study period 25% of children with no evidence of infection at the start of the trial had become infected, while 45.5% of children apparently cured by the metrifonate treatment had recommenced egg excretion. The evidence suggested that reinfection rather than recovery of adult worms was responsible. Children with scanty or light infections, in general, showed increasing egg excretion rates during the following period, while those with heavy or severe infections showed a sustained reduction. In view of this, single dose metrifonate may be a useful approach to mass treatment in a schistosomiasis control program, resulting in significant reduction in egg excretion in those most likely to be important sources of transmission.     

Efficacy of metrifonate in urinary schistosomiasis in light and heavy infections

In a prospective clinical trial, patients with urinary schistosomiasis from the Sudan and from other African countries were treated with two or three doses of metrifonate (10 mg/kg), respectively, in two weeks' intervals. Patients seen in the Sudan (n = 37) were followed up for 3 months, those seen in Hamburg (n = 17) up to 20 months. Each dose of metrifonate led to a decrease of almost 90% in egg excretion independently of the pretreatment intensity of infection so that after three doses a reduction of almost 99.9% was achieved. The estimated proportion of parasitological cure after two doses of metrifonate was in the order of 24% in the lightly infected patients seen in Hamburg, and in the order of 8% in the heavily infected Sudanese patients. Almost 59% of the patients who received a complete metrifonate treatment of three doses stopped to excrete ova of S. haematobium. Drug failure was found in almost the same proportion in the two patient groups (17.5% and 16.2%, respectively) and could not be overcome by additional doses of metrifonate. The considerable reduction in egg excretion after a single dose of metrifonate might have a remarkable benefit in large scale programmes where the aim is drastic reduction of worm burden rather than complete cure.     

Efficacy of low doses of praziquantel for Schistosoma mansoni and S. haematobium

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.     

Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals

Praziquantel and artemether are safe and efficacious antischistosomal drugs that act against different developmental stages of the parasite: praziquantel against adult worms and artemether against schistosomula. A combined treatment has been suggested as a strategy for transmission control. Recent laboratory experiments with rabbits with a mixed infection of Schistosoma japonicum parasites of different ages confirmed the effectiveness of a combination therapy. In the present work, we assessed the effect of a combined treatment on adult worms of S. japonicum and found significantly higher worm reduction rates than with a single dose of praziquantel. In a next step, we extended the study of the combined treatment to Schistosoma mansoni. A combined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was administered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, resulted in significantly higher worm reduction rates than a single treatment with praziquantel. A combination therapy with increased doses of 100 mg/kg praziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined treatment experiments, suggesting that these drug concentrations were too high. We conclude that a combined treatment with praziquantel and artemether at the lower doses is safe and more effective than praziquantel alone, which forms a foundation for designing respective clinical trials in humans.     

Effect of praziquantel on the eggs of Schistosoma mansoni, with a note on the implications for managing central nervous system schistosomiasis

The morphology of Schistosoma mansoni eggs in intestinal tissues (oograms), and egg hatching in faeces, were studied after parenteral administration of praziquantel (PZQ) to infected mice. PZQ was given parentally in doses of 60 mg kg-1 for one day, five days or 10 days. Eleven days after initiation of therapy, oograms from all groups receiving PZQ showed more dead eggs than controls; a dose response was also observed. Depression of faecal egg hatching occurred within 24 hours of PZQ administration. Our observations suggest that PZQ kills most S. mansoni eggs in host tissues when administered in higher doses than are routinely recommended for treatment of intestinal schistosomiasis mansoni. In order to reduce the lifespan of metabolically active eggs in sensitive tissues, prolonged courses of PZQ could be used when treating central nervous system schistosomiasis.     

Clinical experience with metrifonate. Review with emphasis on its use in endemic areas

Metrifonate is an excellent drug for the treatment of urinary schistosomiasis in areas with S. haematobium monoinfection. Toxicity apparently is negligible. Side effects due to the inhibition of acetylcholinesterase are usually scarce, light and transient in nature. At the recommended dosage of 3 times 10 mg/kg the chemotherapeutic potential of metrifonate to cure can be expected to range between 60 and 90%. Each dose of metrifonate reduces egg excretion by almost 90%. Treatment with metrifonate clearly reverses lower and upper renal tract pathology. An intermittent course of metrifonate may be administered by minimally trained health personnel. When appropriately timed with regards to local transmission dynamics the minimal requirement to achieve 99% reduction of egg excretion may be as low as three or four doses spaced over a period of two years.     

Chemotherapy-based control of schistosomiasis haematobia. I. Metrifonate versus praziquantel in control of intensity and prevalence of infection

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.     

Chemotherapy-based control of schistosomiasis haematobia. IV. Impact of repeated annual chemotherapy on prevalence and intensity of Schistosoma haematobium infection in an endemic area of Kenya

To determine the effect of repeated, annual, age-targeted therapy on prevalence and intensity of Schistosoma haematobium infection in an endemic area, we treated all available, infected, school-age children (n = 2, 493) in the Msambweni area of Coast Province, Kenya with a randomized protocol of oral metrifonate (10 mg/kg for three doses each year) or praziquantel therapy (40 mg/kg as a single dose each year) for a period of one to three years. During 1984-1987, 1, 101 children completed three years of therapy, 550 received two years, and 842 received a single year. Annual followup revealed significant long-term suppression of S. haematobium infection in the targeted school-age population. Both cross-sectional analysis and study of individual outcomes suggested maximal suppression of infection after two years of therapy. Suppression lasted more than two years after cessation of treatment, and was associated with reduced community transmission (gauged by decreased prevalence among new study entrants and decreasing negative-to-positive conversion on annual parasitologic examinations). Comparison of metrifonate and praziquantel outcomes indicated greater suppression of infection and longer infection-free intervals for some subgroups given praziquantel. We conclude that annual population-based therapy targeted to schoolchildren has direct and indirect beneficial effects for endemic communities. In some specific situations, repeat therapy may not suppress transmission, and reduced drug efficacy may be observed after one to three years, suggesting the need for additional non-drug control measures in highly endemic villages.     

Praziquantel for treatment of schistosomiasis in patients with advanced hepatosplenomegaly

We evaluated praziquantel for therapy of active Schistosoma mansoni infection in 15 rural Egyptian males with hepatosplenic schistosomiasis. Criteria for inclusion in this study were two pre-treatment S. mansoni egg counts with a mean of greater than 100 eggs g-1 faeces and an enlarged spleen. Fourteen of 15 patients had hepatomegaly, five had ascites, and six had serum albumin below 3 g dl-1. Schistosoma haematobium infection (less than 10 eggs ml-1 urine) was present in three patients. Praziquantel was administered in a single oral dose of 30 mg kg-1 body weight. Eight of the 15 patients (53%) had mild and transient reactions in the form of fever (usually one day), gastrointestinal symptoms, headache and skin rash. Criteria for parasitological cure were the absence of live eggs in two stool samples and a negative rectal snip biopsy three months after therapy. Ten patients ceased to pass live eggs (cure rate 67%). For the five who were still passing live eggs there was a mean egg reduction of 95%. The three patients with S. haematobium demonstrated parasitological cures. We conclude that praziquantel is an effective and well tolerated drug for treatment of S. mansoni infection in patients with advanced hepatosplenic schistosomiasis, and it is the drug of choice for patients with coexisting S. haematobium infection.     

Mixed Schistosoma haematobium and S. mansoni infection: effect of different treatments on the serum level of circulating anodic antigen (CAA)

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 comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium

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.     

Treatment with praziquantel of schoolchildren with concurrent Schistosoma mansoni and S. haematobium infections in Gezira, Sudan

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.     

Evaluation of albendazole, pyrantel, bephenium, pyrantel-praziquantel and pyrantel-bephenium for single-dose mass treatment of necatoriasis

An effective drug for single-dose mass treatment of necatoriasis was sought by testing three drugs and two drug combinations in Ethiopian immigrants to Israel found to have light infections. The drugs tested sequentially in single-doses were pyrantel pamoate (20 mg kg-1, 81 subjects); bephenium hydroxynaphthoate (2.5-5 g, 65 subjects); combined pyrantel and bephenium (25 subjects); combined pyrantel (20 mg kg-1) and praziquantel (40 mg kg-1) (16 subjects); and albendazole (400 mg, 77 subjects). Follow-up under conditions without likelihood of reinfection was by one stool examination. Cure rates with albendazole, pyrantel-bephenium and pyrantel-praziquantel were 84, 80 and 81% respectively; these rates were significantly higher than the 49% found for bephenium and the 51% for pyrantel (P less than 0.05). Egg reductions in those not cured were pyrantel (22%), bephenium (6%), pyrantel-bephenium (34%), pyrantel-praziquantel (3%) and albendazole (6%). Albendazole was the most promising single drug treatment; unexpected was the high effectiveness of pyrantel-praziquantel in combination.     

吡喹酮对小鼠卫氏并殖吸虫童虫的疗效及T淋巴细胞的变化

目的 探讨吡喹酮对转续宿主体内滞育童虫的杀虫效果以及吡喹酮有效治疗后感染小鼠T淋巴细胞及其亚群的变化。 方法 将不同数量的江西二倍体型卫氏并殖吸虫囊蚴感染小鼠,10 d后用不同剂量、不同疗程吡喹酮进行治疗。治疗结束后7 d,剖杀检虫观察疗效以及小鼠T淋巴细胞及其亚群的变化。 结果 当小鼠感染30个囊蚴,用吡喹酮400、500和600 mg/(kg·d),连续3 d给药,其减虫率分别为71.01％±10.38％、82.29％±7.92％和95.83％±3.24％;当小鼠感染80个囊蚴时,用吡喹酮600 mg(kg·d),连续3 d给药,减虫率仅为84.49％±10.91％。小鼠经吡喹酮治疗1wk后,T淋巴细胞及其亚群开始升高,在第8周恢复正常。 结论 吡喹酮对卫氏并殖吸虫童虫的疗效比成虫差,其疗效与药物剂量和小鼠感染度有关,增加剂量或增加疗程可增强杀虫效果。     

Albendazole plus praziquantel versus albendazole alone as a pre-operative treatment in intra-abdominal hydatidosis caused by Echinococcus granulosus

Summary objective  To compare the effects of a combined medication of albendazole (10 mg/kg/day) plus praziquantel (25 mg/kg/day) to those of albendazole alone at different doses (10 and 20 mg/kg/day).
method  The protoscoleces9 viability was studied in a consecutive series of patients affected by intra-abdominal hydatidosis caused by Echinococcus granulosus . In all cases the drugs were given during the month prior to surgery.
results  A significant increase of patients with nonviable protoscoleces was observed in the group treated with the scolicides combination compared to those treated with albendazole alone, both at a dose of 10 mg/kg/day ( P = 0.004) and at a dose of 20 mg/kg/day ( P = 0.03). Albendazole sulphoxide levels in serum and in cyst fluid were higher in patients given the combined therapy than in those who received only albendazole (10 mg/kg/day: P = 0.016; 20 mg/kg/day: P = 0.034). Levels in the cysts were not significantly different probably due to the sample size; nevertheless a lineal relation between the values obtained in serum and inside the cysts could be discerned in the patients treated with the combined medication.
conclusion  Albendazole plus praziquantel is more effective than monotherapy with albendazole in the preoperative treatment of intra-abdominal hydatidosis.