Are poor responses to praziquantel for the treatment of Schistosoma mansoni infections in Senegal due to resistance? An overview of the evidence

This paper summarizes and concludes in-depth field investigations on suspec ted resistance of Schistosoma mansoni to praziquantel in northern Senegal. Praziquantel at 40 mg/kg usually cures 70-90% of S. mansoni infections. In an initial trial in an epidemic S. mansoni focus in northern Senegal, only 18% of the cases became parasitological ly negative 12 weeks after treatmen t, although the reduction in mean egg counts was within normal ranges (86%) . Among other hypotheses to explain the observed low cure rate in this focu s, the possibility of drug resistance or tolerance had to be considered. Su bsequent field trials with a shorter follow-up period (6-8 weeks) yielded c ure rates of 31-36%. Increasing the dose to 2 x 30 mg/kg did not significan tly improve cure rates, whereas treatment with oxamniquine at 20 mg/kg resu lted in a normal cure rate of 79%. The efficacy of praziquantel in this foc us could be related to age and pre-treatment intensity but not to other hos t factors, including immune profiles and water contact patterns. Treatment with praziquantel of individuals from the area residing temporarily in an u rban region with no transmission, and re-treatment after 3 weeks of non-cur ed individuals within the area resulted in normal cure rates (78-88%). The application of an epidemiological model taking into account the relation be tween egg counts and actual worm numbers indicated that the low cure rates in this Senegalese focus could be explained by assuming a 90% worm reductio n after treatment with praziquantel; in average endemic situations, such a drug efficacy would result in normal cure rates. Laboratory studies by othe rs on the presence or absence of praziquantel resistance in Senegalese schi stosome strains have so far been inconclusive. We conclude that there is no convincing evidence for praziquantel-resistant S. mansoni in Senegal, and that the low cure rates can be attributed to high initial worm loads and in tense transmission in this area.