Controlling schistosomiasis with praziquantel: How much longer without a viable alternative?

Abstract

The current approach of morbidity control of schistosomiasis, a helminth disease of poverty with considerable public health and socioeconomic impact, is based on preventive chemotherapy with praziquantel. There is a pressing need for new drugs against this disease whose control entirely depends on this single drug that has been widely used over the past 40 years. We argue that a broader anthelminthic approach supplementing praziquantel with new antischistosomals targeting different parasite development stages would not only increase efficacy but also reduce the risk for drug resistance. Repositioning drugs already approved for other diseases provides a shortcut to clinical trials, as it is expected that such drugs rapidly pass the regulatory authorities. The antischistosomal properties of antimalarial drugs (e.g., semisynthetic artemisinins, synthetic trioxolanes, trioxaquines and mefloquine) and of drugs being developed or registered for other purposes (e.g., moxidectin and miltefosin), administered alone or in combination with praziquantel, have been tested in the laboratory and clinical trials. Another avenue to follow is the continued search for new antischistosomal properties in plants. Here, we summarise recent progress made in schistosomiasis chemotherapy, placing particular emphasis on repositioning of existing drugs against schistosomiasis.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-017-0286-2) contains supplementary material, which is available to authorized users.

Sm‐p80‐based schistosomiasis vaccine: double‐blind preclinical trial in baboons demonstrates comprehensive prophylactic and parasite transmission‐blocking efficacy

“…The disease is endemic in 79 countries, and 200 million people are infected, with up to 800 million more being at risk of doi: 10.1111/nyas.13942 acquiring the infection. [1][2][3] These estimates are based on partially sensitive egg retrieval/detection techniques. Apparent "egg-negative" individuals may be carrying infections that are indiscernible using current schistosome egg detection procedures in feces/urine.…”

“…Dependence on mass drug administration (MDA) alone with praziquantel (PZQ) for the past several decades has not yielded satisfactory results, and infection rates continue to be high despite global PZQ coverage in 2016 of 54%. 1,2,6,7 Furthermore, large-scale PZQ use may lead to drug resistance in the parasite. 4 An efficacious vaccine inducing prolonged protection would result in a substantial decrease in transmission of infection and morbidity, particularly if deployed concurrently with existing control measures.…”

Chemotherapy for Fighting Schistosomiasis: Past, Present and Future

“…The insensitivity of juvenile worms to PZQ contributes to treatment failures and the re‐emergence of symptoms after treatment . The use of a single drug, however, constitutes a selection pressure that might favor resistance development . Oxamniquine preceded PZQ and represents a possible alternative, but it is only active against S. mansoni and is currently unavailable .…”

Sm‐p80‐based vaccine trial in baboons: efficacy when mimicking natural conditions of chronic disease, praziquantel therapy, immunization, and Schistosoma mansoni re‐encounter

“…Efforts to control schistosomiasis in endemic areas have largely been based on mass drug administration (MDA) of praziquantel (PZQ), control of intermediate snail host populations and improved sanitation. Although these control strategies have shown some promise in certain areas, evident limitations such as sustained reinfection rates, emergence of drug‐resistant parasites, and a lack of adequate infrastructure, necessitate the development of a schistosomiasis vaccine to supplement (or even supplant) existing control strategies . Additionally, PZQ is nonprophylactic and only effective against adult parasites; repeated treatments are therefore required to alleviate the burden of schistosomiasis in endemic areas …”

“…Although these control strategies have shown some promise in certain areas, evident limitations such as sustained reinfection rates, emergence of drug-resistant parasites, and a lack of adequate infrastructure, necessitate the development of a schistosomiasis vaccine to supplement (or even supplant) existing control strategies. [11][12][13][14][15][16][17] Additionally, PZQ is nonprophylactic and only effective against adult parasites; repeated treatments are therefore required to alleviate the burden of schistosomiasis in endemic areas. 18,19 A Schistosoma mansoni calpain (Sm-p80)-based vaccine has consistently shown protection against schistosomiasis in rodent and nonhuman primate models of infection and disease, making it a leading vaccine candidate; it is currently being prepared for Phase I/II human clinical trials in 2019.…”