Nitrobenzylthioinosine 5'-monophosphate (
NBMPR-P) inhibits the transport of
nucleosides, including
tubercidin, in mammalian systems but not in Schistosoma mansoni. Administration of
NBMPR-P with high doses of
tubercidin (lethal doses if injected alone) by
intraperitoneal injection into S. mansoni-infected mice was highly toxic to the parasite but not to the host. Combination
therapy resulted in a striking decrease in the number and copulation of worms. The few worms that could be found were so stunted that it was difficult to identify their sex. Mice receiving the combination of
tubercidin plus
NBMPR-P appeared healthy and had normal-sized livers and spleens. Combination
therapy also caused a drastic decrease in the number of eggs in the liver (from 32,500 to 1,800 eggs per liver) and in the intestine (from 1,295 to 2 eggs per cm2). All eggs found were dead, indicating the termination of oviposition. Very few
granulomas were detected in livers of treated animals. Sections of these livers showed lesions containing dead worms and what appeared to be a process of regeneration of normal tissue around old
granulomas. Thus, combination
therapy reduced the number and the progress of the primary pathological lesions associated with
schistosomiasis. These results demonstrate that through combination
therapy, highly selective toxicity against a parasite can be achieved. The effectiveness, simplicity, and practicality of host protection afforded by this method may yield a promising chemotherapeutic approach for the treatment of
schistosomiasis and other
parasitic diseases.