Praziquantel, (2-cyclohexylcarbonyl)-1,2,3,6,7,11b-hexa-hydro-2H pyrazino[2,1a]isoquinolin-4-one, belongs to a new series of antischistosomal compounds. The results of a detailed study of the efficacy of praziquantel on Schistosoma mansoni in mice, Mastomys and Syrian hamsters are described. Praziquantel is effective after oral and all parenteral routes of administration tested. The amount of praziquantel required to achieve parasite reductions of at least 95% depends on the host species and on the routes and schedules of administration. Total doses range from 200–1,000 mg/kg in mice and from 100–500 mg/kg for Mastomys and hamsters. In all three species, splitting of the total dose into 3 or more fractional doses given within 1 day approximately doubles the efficacy over that achieved after a single oral administration of the same total dose. A single subcutaneous dose is only slightly more effective, whilst a single intramuscular injection in olive oil is about twice as effective as a single oral administration. Praziquantel is very effective against the invading stages and slightly less against schistosomules up to an age of 7 days. It is less effective against 2- to 4-week-old juveniles, but is effective again against 5-week-old and older schistosomes. Praziquantel is equally effective against both sexes of S. mansoni. It is less effective against unpaired and therefore juvenile female worms, but fully effective against single male worms. The efficacy of praziquantel on S. mansoni in mice is not influenced by the strain or the sex of the host, the worm burden or the age of the infection. Considering all data available, praziquantel promises to be a very potent antischistosomal drug.

Praziquantel, a new board-spectrum antischistosomal agent.

Schistosomiasis is a disease caused by parasitic trematode worms (schistosomes) that currently affects 200 million people living in tropical and subtropical environments. It is a chronic disease and the latest estimates for sub-Saharan Africa are that it kills > 200,000 people every year. Soil-transmitted helminthiasis (STH) is caused by intestinal nematodes. More than 2 billion people are infected worldwide and the disease burden might approach that of malaria. Recognising the enormous public health significance of schistosomiasis and STH, particularly among the poor, and in view of readily available drugs that are safe, efficacious and inexpensive, the World Health Assembly recently set forth a resolution for a combined approach for morbidity control of both diseases. This review briefly summarises the geographical distribution, life cycle and global burden of schistosomiasis and STH. The current arsenal of drugs available for morbidity control, including discovery, chemistry, pharmacological properties...

Schistosomiasis and soil-transmitted helminthiasis: common drugs for treatment and control

Antischistosomal drugs: Past, present … and future?

Schistosomiasis is a chronic and debilitating disease that is caused by parasitic trematode worms (schistosomes). It continues to threaten millions of people, particularly the rural poor in the developing world ([11][1], [24][2]). Of the estimated 200 million infected people, more than half have

Combination chemotherapy of schistosomiasis in laboratory studies and clinical trials

Praziquantel (EMBAY 8440, Droncit) is a new type of acylated isoquinoline-pyrazine. A single oral or subcutaneous dose of the compound is reliably effective against juvenile and adult cestodes in mice and rats. For the first time, with praziquantel a compound is available that is also effective on cestodes in the bile-duct. Using Hymenolepis nana in mice we were able to show that age, sex, strain and intensity of infestation of the host have no influence on the efficacy. The onset of the effect of praziquantel in vivo is rapid. Within 10 min the parasites were immobilized and contracted and excreted within a few hours with the faeces.

The efficacy of praziquantel against cestodes in animals.

In mice experimentally infected with Schistosoma mansoni, praziquantel (2-cyclohexylcarbonyl-1,3,4,6,7,11b-hexahydro-2H-pyrazino[2,1-a]isoquinoline-4-one), administered orally at the levels of 100 and 50 mg/kg, for 5 consecutive days, produced oogram changes in all animals and a pronounced hepatic shift of schistosomes (97.1 and 89.1, respectively). At lowest levels (12.5 and 6.3 mg/kg), alterations in the oogram could still be detected, although hepatic shift of schistosomes was no more evident. After a single intramuscular injection, the results obtained paralleled those observed with a single-dose oral treatment. The hepatic shift was only moderate at 200 and 100 mg/kg and the percentages of worms retained in the liver, after perfusion, were particularly low. When nasal route in a 1-day regimen was used, the results obtained were slightly less evident as compared with those observed by oral route (5-day schedule).

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Experimental Chemotherapy of Schistosomiasis mansoni

Groups of mice 2–6 days old were exposed by paddling to 35 or 50 cercariae of Schistosoma mansoni per animal. The mean worm burden from 115 baby mice exposed to 35 cercariae was 20·7 (59·2% of worm return). In 400 adult mice, weighing about 20 g. and exposed to 120 cercariae, worm return was only 18·6% (a mean worm burden of 22·3 schistosomes). 8–10 weeks after exposure of baby mice to S. mansoni cercariae, 70–85% of the schistosomes were found in the mesenteric veins, 5–10% in the liver, and 10–20% in the portal vein. The mortality rate among 662 baby mice exposed to 50 cercariae was found to increase sharply after the 6th week of infection. The percentages of the various schistosome elements (oogram) in the intestinal wall of infected baby mice, 53–60 days after exposure to S. mansoni cercariae, did not differ from the pattern already described for mice infected when adult. The therapeutic activity of 14 antischistosomal compounds was compared in groups of baby mice and adult animals experimentally infected with S. mansoni. No significant differences were found when the hepatic shift of worms and oogram changes were used for the assessment of activity. The infection of baby mice with S. mansoni cercariae represents a simple and reliable working model for chemotherapeutic studies.

J. Pellegrino

Papers

Experimental Chemotherapy of Schistosomiasis mansoni

Infection of baby mice with Schistosoma mansoni; some biological aspects in connection with experimental chemotherapy.

An attempt to obtain infertile live worms in mice infected with Schistosoma mansoni.