Artemether and Praziquantel: Origin, Mode of Action, Impact, and Suggested Application for Effective Control of Human Schistosomiasis

Abstract

The stumbling block for the continued, single-drug use of praziquantel (PZQ) against schistosomiasis is less justified by the risk of drug resistance than by the fact that this drug is inactive against juvenile parasites, which will mature and start egg production after chemotherapy. Artemisinin derivatives, currently used against malaria in the form of artemisinin-based combination therapy (ACT), provide an opportunity as these drugs are not only active against malaria plasmodia, but surprisingly also against juvenile schistosomes. An artemisinin/PZQ combination would be complementary, and potentially additive, as it would kill two schistosome life cycle stages and thus confer a transmission-blocking modality to current chemotherapy. We focus here on single versus combined regimens in endemic settings. Although the risk of artemisinin resistance, already emerging with respect to malaria therapy in Southeast Asia, prevents use in countries where ACT is needed for malaria care, an artemisinin-enforced praziquantel treatment (APT) should be acceptable in regions of North Africa (including Egypt), the Middle East, China, and Brazil that are not endemic for malaria. Thanks to recent progress with respect to high-resolution diagnostics, based on circulating schistosome antigens in humans and molecular approaches for snail surveys, it should be possible to keep areas scheduled for schistosomiasis elimination under surveillance, bringing rapid response to bear on problems arising. The next steps would be to investigate where and for how long APT should be applied to make a lasting impact. A large-scale field trial in an area with modest transmission should tell how apt this approach is.

Prevalence and correlates of intestinal schistosomiasis infection among school-aged children in North-Western Tanzania

“…The high prevalence of intestinal schistosomiasis infection found in the current study and in the previously reported studies indicate an urgent need for targeted interventions in addition to the current mass praziquantel treatment program for prevention and control of schistosomiasis around the Lake Zone and other endemic settings in the SSA region. Re-evaluation of the preventive chemotherapy being deployed by the National NTD Control Programs in SSA including the mode of delivery of annual mass praziquantel treatment such as giving repeated praziquantel doses may be considered [40] or research on alternative regimens such as combining praziquantel with artemisinin-based combination therapy targeting both the adult and juvenile parasites is recommended [41]. Apart from preventive chemotherapy, the provision of clean and safe water, improvement in sanitation and hygiene, and practical health education to school-aged children and the community is equally important in the study area.…”

Efficacy and Safety of Praziquantel for Treatment of Schistosoma mansoni Infection among School Children in Tanzania

“…The poor efficacy of praziquantel against juvenile schistosomes is well recognized, and hence, the need for further treatment optimization research is evident. To enhance praziquantel performance, randomized clinical trials (RCTs) to investigate the combination of praziquantel with other drugs that are active against the juvenile worms (such as artemisinins) [32], or the use of repeated praziquantel doses, may be considered in endemic settings [16,31].…”

Faculty Opinions recommendation of Efficacy and safety of praziquantel and dihydroartemisinin piperaquine combination for treatment and control of intestinal schistosomiasis: A randomized, non-inferiority clinical trial.

“…PZQ is efficacious against adults matured parasites but is less effective against juvenile worms [14]. We hypothesized that combining ACTs with PZQ would complement and potentially add to the killing effect of both immature and matured stages of the parasite to prevent transmission as suggested previously [31,47]. Several ACTs exist, but DHP was chosen in this study due to its multifactorial advantages including: (i) DHP has not been extensively used for malaria treatment in Tanzania compared to other first-line antimalarial drugs such as ALU, (ii) costeffectiveness and easy schedule of DHP administration (once a day) compared to ALU and (iii) its long duration of post-treatment prophylaxis which will offer protection to children against malaria who remain to be a vulnerable population in SSA.…”