Praziquantel is a major advance in the treat- ment of schistosomiasis and of other fluke. (trematode) and tapeworm (cestode) infections. It is taken by mouth, ...
Journal of Antimicrobial Chemotherapy (1985) 15, \-%
Leading articles Praziquantel More recently, trials comparing praziquantel Praziquantel is a major advance in the treat- with established regimes have demonstrated its ment of schistosomiasis and of other fluke greater efficacy. A comparison of praziquantel (trematode) and tapeworm (cestode) infections with metrifonate and niridazole in Schist, It is taken by mouth, usually as a single dose, haematobium in Tanzania showed a 98% cure rate at four months compared to 59% and 68% and lacks serious toxicity. Praziquantel is a pyrazino-isoquinoline with metrifonate and niridazole respectively derivative supplied in 600 mg tablets which are (McMahon, 1983). In those not cured tiere was easily quartered. Pharmacokinetic studies in 99% reduction in egg count with praziquantel human volunteers have shown that the drug is (cf. 98% with metrifonate and 75% with rapidly absorbed and peak serum levels are niridazole). In Malawi, in a comparison of reached after 1-2 h. There is considerable first- praziquantel with metrifonate and niridazole, pass metabolism. Praziquantel and its singly and in combination, praziquantel produmetabolites have a half-life of 4-5 h and are ced a 97% egg reduction compared to 92% for excreted by the kidneys, over 70% appearing in the combination and lower levels for the two other drugs individually. (Pugh & Teesdale, the urine in thefirst24 h. 1983). How praziquantel kills helminths is unclear Studies with radio-labelled drug show that it Schist, mekongt, a hitherto virtually untreatis taken up by both adults and larvae, is dis- able parasitic disease in Laos and other parts of tributed evenly but not metabolised, and leads South-east Asia also seems amenable to treatto the appearance of vacuoles in the tegument ment with praziquantel (Nash et at., 1982). of the parasite (Thomas, Andrews & Successful use of praziquantel in Mehlhorn, 1982). schistosomiasis led to trials in other fluke infecIt is estimated that over 200 million people in tions. There has previously been no effective Africa, South America and the Far East are treatment for the liver fluke Clonorchis sinensis. infected by Schistosoma haematobium. mansoniPraziquantel in three doses of 25 mg/kg in a or japonicum. They may present with disorders single day produced a 100% cure rate (60 day of bladder, bowel or liver. The lungs and cen- follow-up) and a single dose of 40 mg/kg while tral nervous system are less commonly affected. only curing 50% of patients, produced a 99% Hitherto, therapy of schistosomiasis has reduction in egg count. (Rim et al., 1981). been unsatisfactory. Niridazole was supplanted Other trials have shown good results against by metrifonate for the treatment of infection the lung flukes Paragonimus westermani in South-east Asia) Par. with Schist, haematobium and by oxamniquine (endemic for Schist, mansoni but these newer agents have uterobilateralis (Cameroon and eastern no activity against Schist, japonicum. All three Nigeria) (Monson, Koenig & Sachs, 1983) and against a species, possibly Par. kellicoti, which agents are more toxic than praziquantel. Multicentre trials of praziquantel in has recently been reported in Missouri, U.S.A. schistosomiasis have been carried out under the (Pachucki et al., 1984). Trials arc underway to auspices of the World Health Organization determine the efficacy of praziquantel against using standard protocols. In Zambian children Fasciola hepatica. affected by Schist, haematobium there was only There is little information available about one treatment failure in 79 patients. (Davis, the treatment of intestinal flukes although Biles & Ulrich, 1979). In Brazil, praziquantel infestations with these parasites were often incicured 25 of 28 patients with Schist, mansoni dentally found and cured during trials of infection (Katz, Rocha & Chavas, 1979), and, praziquantel against other helminths. in the Philippines, 60 of 75 people affected by PTaziquantel has been found to be active Schist, japonicum (Santos, Bias & Noseman, against both adult and larval tapeworms. 1979) Cure was defined as complete cessation Taenia saginata, T. soltum, Hymenolepis nana of excretion of viable eggs. and Diphyllobothrium latum have been elimm1
Leading articles atcd. Of particular interest is the treatment of Bolero, D. & Castano, S (1982) Treatment of cysticercosis with praziquantel in Colombia. American cysticercosis. This disease occurs when the larvae of the pork tapeworm T. solium migrate Journal of Tropical Medicine and Hygiene 31, 811-21. from the intestinal lumen of affected humans Davis, A , Biles, J E & Ulnch, A. M (1979) Initial and encyst in the tissues. Recent trials in South experiences with praziquantel in the treatment of America using 30 mg/kg/day for six days have human infection due to schistosoma shown marked reduction of raised intracranial haematobium Bulletin WHO 57, 773-9. pressure and better control of epilepsy in Davis, A. & Wegner, D. H. G (1979) Multicentre patients with CNS cysticercosis (Bolero & trials of praziquantel in human schistosomiasis: Castano, 1982). Intraocular cysticercosis has design and techniques. Bulletin WHO 57, 767-71. proved less amenable (Santos, Chavarna & deGhetaldi, L. D , Norman, R M & Douville, A W. (1983). Cerebral cysticercosis treated biphasically Aquirre, 1984). In hydatid disease, the targets with dexamethasone and praziquantel. Annals of for chemotherapy are the larval stages of the dog tapeworm, Echinococcus granulosus. In one Internal Medicine 99,179-81. study, praziquantel failed to kill the germinal Katz, N., Rocha, R S & Chavas, A. (1979). Preliminary trials with praziquantel in human infection layer of hydatid cysts from which the larvae due to Schistosoma mansoni. Bulletin WHO SI, develop, despite killing protoscohces in the cyst 781-5. fluid (Marshall & Edwards, 1982). While it can- McMthon, J. E. (1983). A comparative trial of not, therefore, be used as the sole treatment of praziquantel, metrifonate and niridazole against inoperable hydatid cysts, it may yet prove to be Schistosoma haematobium. Annals of Tropical of value as an adjunct to surgical excision if it Medicine and Parasitology Tl, 139-42. kills germinal matter unprotected by mem- Marshall, I. & Edwards, G T (1982) The effects of sustained release praziquantel on the survival of branes, which may be spilled from cysts at protoscohces of Echinococcus granulosus equinus operation. in laboratory mice Annals of Tropical Medicine Praziquantel, when used in large hospitaland Parasitology 76,649-51. based studies, has been found to be well- Monson, M. H , Koenig, J. W. & Sachs, R. (1983) tolerated with only minor side-effects such Successful treatment with praziquantel of six as nausea, abdominal pain, headache and patients infected with the African lung fluke Paragonimus uterobilateralis. American Journal of transient fever. Studies on bacteria, yeasts and Tropical Medicine and Hygiene 32,371-5. mammalian cells have shown no increase in mutation rate (Bartsch el al., 1978). However, Nash, T. E , Hofstetter, M., Cheever, A W. & Ottesen, E A (1982). Treatment of Schistosoma the drug is not recommended for pregnant or mekongi with praziquantel A double-blind study lactating women. American Journal of Tropical Medicine and Praziquantel represents an important Hygiene 31,977-82. advance in the chemotherapy of several helmin- Pachucki, C. T., Levandowski, R. A , Brown, V. A , thic infections. It can be given in simple dosage Sonnenkalb, B. H & Vruon, M J (1984) Ameriregimens which are well tolerated. However, its can paragonimiasis treated with praziquantel. New cost (currently more than ten times the cost of England Journal of Medicine 311, 582—3. metrifonate) will limit its use in poorer Pugh, R. N H &Teesdale, C H. (1983) Single dose oral treatment in urinary schistosomiasis' A countries and in mass treatment programmes. double-blind trial British Medical Journal 286, C. P. CONLON 429. C J. ELLIS Department of Communicable and Tropical Diseases. East Birmingham Hospital, Bordesley Green East, Birmingham, B9 5ST, England
References Bartsch, H., Kuroki, T , Malaveille, C , Lopneno, N., Barole, R., Abbondandolo, A , Bonatti, S., Rainaldi, G., Vogel, E. & Davis, A (1978). Mutageniaty of praziquantel, a new effective aiitischistosomal drug in bacteria, yeasts, insects and mammalian cells. Mutation Research 58,133-42.
Rim, H. J , Lyu, K. S-, Lee, J. S. & Joo, K. H. (1981). Clinical evaluation of the efficacy of praziquantel against Clonorchis sinensis infection in man. Annals of Tropical Medicine and Parasitology 75, 27-33. Santos, A T , Bias, B L. & Nosenas, J S (1979) Preliminary clinical trials with praziquantel in Schistosoma japomcum infections in the Philippines Bulletin WHO 57, 793-9. Santos, R , Chavarria, M & Aguirre, A. E. (1984) Failure of medical treatment in two cases of intraocular cysticercosis. American Journal of Ophthalmology 97, 49-50. Thomas, H., Andrews, P & Mehlhorn, H (1982). New results on the effect of praziquantel in experimental cysticercosis. American Journal of Tropical Medicine and Hygiene 31, 803-10
