Efficacy of a Single Oral Dose of Artesunate plus Sulfalene-Pyrimethamineversus Praziquantel in the Treatment of Schistosoma mansoni in Kenyan Children: An Open-Label, Randomized, Exploratory Trial.

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.

The effects of artemether-lumefantrine vs amodiaquine-sulfalene-pyrimethamine on the hepatomegaly associated with Plasmodium falciparum malaria in children.

An open randomized controlled study of artemether-lumefantrine (AL) and amodiaquine-sulfalene-pyrimethamine (ASP) for the treatment of uncomplicated Plasmodium falciparum malaria was carried out in 181 children. In 79 children, the hepatomegaly reduction ratios (HRR) and the speed of resolution of hepatomegaly, the hepatomegaly resolution rates (HRSR), were calculated and compared between the two treatment groups. HRR and HRSR were similar in the two treatment groups. HRSR was 71% and 62% in AL- and ASP-treated children, respectively, 14 days after commencing treatment. There was no significant correlation between HRR and parasite reduction ratio in the same patient. In children in whom parasitaemia cleared and hepatomegaly resolved within 14 days, recurrence of parasitaemia was associated with reoccurrence of hepatomegaly, suggesting that the propensity for recurrence of infection drives the malaria-attributable hepatomegaly in children from this endemic area. Combination therapy may provide additional beneficial effects on pathophysiological processes and changes associated with falciparum malaria by rapid clearing of asexual parasitaemia and reducing the propensity for recurrence of infection.

An in vivo evaluation of the induction of abnormal sperm morphology by sulphamethoxypyridazine: pyrimethamine (Metakelfin).

The effects of sulphamethoxypyridazine: Pyrimethamine (Metakelfin) a combination antimalarial drug on mouse sperm head morphology were evaluated in University of Ibadan Veterinary F1 mice. Five different dose levels of 3.85:0.19; 7.7:0.38; 15.4:0.76; 23.1:1.13 and 30.8:1.54 mg kg(-1) body weight of sulphamethoxypridazine:pyrimetamine, respectively were administered to the animals by a schedule of 5 consecutive daily intraperitoneal (i.p.) injections. The sperm of the mice from the cauda epididymis were examined 5 weeks after treatment. Metakelfin induced sperm head abnormalities; however, of the 5 doses sampled; only the 7.7:0.38 mg kg(-1) dose, corresponding to 0.5x the human therapeutic dose (HTD0), gave a statistically significant (p > 0.05) increase over the negative control value of 2.53% abnormality. All the other dose level treatments did not yield statistically significant increase over the negative control value. The 15.4:0.77 mg kg(-1) dose showed 3.5% abnormality and fewer abnormalities than the preceding lower dose. The drug is probably not mutagenic as induction of sperm head abnormality was not dose dependent.

Plasmodium falciparum: drug-resistant malaria complicating leukemias and lymphomas in children.

The present communication deals with drug-resistant Plasmodium falciparum malaria complicating hematologic malignancies (leukemias, n = 24, and lymphomas, n = 7) in children. Of 50 cases of hematologic malignancies, 31 patients were microscopically diagnosed as having P. falciparum infection (MP +). Initially, all the patients were treated with chloroquine. The results of primary treatment showed chloroquine resistance in 16 (51. 62%) cases. Of these 16 chloroquine-resistant cases, 13 were secondarily treated with a combination of pyrimethamine plus sulfamethopyrazine. The results of secondary treatment also revealed resistance to pyrimethamine plus sulfamethopyrazine in 6 of 13 (46. 10%) cases. The 6 pyrimethamine plus sulfamethopyrazine-resistant P. falciparum cases were finally cured by quinine therapy, against which no resistance was encountered. Conversely, in the control group comprising 38 cases of P. falciparum without malignancy, the incidence of chloroquine resistance was found in only 9 cases, which is rather low (23.70%). Of these 7 chloroquine-resistant cases, 5 were found to be sensitive to pyrimethamine plus sulfamethopyrazine treatment, while the 2 nonresponders were finally cured with quinine. The overall results of this study show a high prevalence of chloroquine resistance among clinical cases of falciparum malaria (25/69; 30.6%). Among the nonresponders (n = 20) 40% of cases were also resistant to the pyrimethamine plus sulfamethopyrazine combination. There was no resistance to quinine.

[Effects of sulfalene on the thymus, spleen and adrenals in an experiment]. / Vliianie sul'falena na timus, selezenku i nadpochechniki v éksperimente.

The effect of sulfalen on the weight and structure of the thymus, spleen and adrenal glands was studied. The findings were compared with the results observed in control rats. It was shown that after administration of sulfalen, the weight of the adrenal glands markedly decreased while their structure did not change. Thymus specimens showed a large number of hypertrophic epitheliocytes, in the medulla which was accompanied by a decrease in its weight.

[Effect of sulfalene and furosemide on benzylpenicillin kinetics in rats with aseptic inflammation]. / Vliianie sul'falena i furosemida na kinetiku benzilpenitsillina u krys s asepticheskim vospaleniem.

The effect of sulfalen and furosemide on benzylpenicillin kinetics in blood serum, intact tissues and aseptic inflammation foci was studied on rats. It was shown that under the action of sulfalen and furosemide protein binding of benzylpenicillin lowered by 30 per cent. The changes in the antibiotic kinetics after combined use with sulfalen and furosemide were of the same type: markedly increased concentrations in blood serum and tissues and retarded elimination.

[Macrolide antibiotics: characteristics of their interaction with organoids, intracellular distribution and the effect of sulfalene]. / Antibiotiki-makrolidy: osobennosti vzaimodeistviia s organoidami, vnutrikletochnoe raspredelenie i vliianie na nego sul'falena.

Interaction of erythromycin and oleandomycin with isolated subcellular fractions of rat liver homogenates and intracellular distribution of the antibiotics were studied. It was found that the macrolides were bound by the cell organoids. The binding was partially reversible. The intracellular distribution was characterized by accumulation of erythromycin and oleandomycin in the mitochondrial fraction while erythromycin preserved higher activity in cytosol as compared to oleandomycin. Sulfalen induced redistribution of the macrolides. It decreased absorption of the macrolides by the organoids and increased the concentration of free erythromycin and especially oleandomycin in cytosol.

[Pharmacodynamics of cephaloridine and cephalothin combined with sulfalene in rabbits]. / Farmakokinetika tsefaloridina i tsefalotina u krolikov pri kombinirovannom primenenii s sul'falenom.

The combined use of cephaloridin and cephalothin with sulfalen resulted in decreased binding of the cephalosporins by serum proteins and decreased rate of drug elimination in rabbits. It might be suggested that these two processes were interrelated. The decreased binding of the antibiotics by proteins in rabbits promoted an increase in the volume distribution of the drugs at the expense of a rise in the level of their penetration from the blood into the peripheral tissues.

The effect of sulfomethoxypyrazine-pyrimethamine therapy on the fine structure of Toxoplasma gondii-cysts in the brain of Mastomys natalensis. Scanning and transmission electron microscopical investigations.

Two month old chronically infected Mastomys natalensis, which had been treated for ten days with sulfomethoxypyrazine-pyrimethamine, were utilized for testing the effect of chemotherapy on the fine structure of Toxoplasma cysts (strain ALT). After completion of the therapy, cysts were examined from the brains of killed animals in scanning and transmission electron microscopes. The scanning electron microscopic experiments revealed no or only slight morphological differences between the cysts of the untreated controls (Fig. 1) and the treated animals (Fig 2). In transmission electron microscopic studies the cyst membrane appeared less rugged (see Fig. 3,7 and the untreated control Fig. 6). The cyst basic substance often produces an optically empty space (Fig. 3,4). The pellicle of individual parasites display an unusual affinity for the pellicle of neighboring parasites (Fig. 3,5,7). In direct contrast to the untreated cysts no endodyogeny could be observed on the treated cysts examined to this point.

Antimalarial drugs and reduced incidence of dental plaque.

Known antimalarial compunds from several chemical classes were tested for their ability to inhibit in vitro growth of microorganisms causing dental plaque and to prevent the development of plaque in a hamster model. Approximately a third of the compounds tested inhibited in vitro growth; however, none prevented development of plaque.