Praziquantel and Arachidonic Acid Combination — An Innovative Approach to the Treatment of Schistosomiasis

Abstract

Schistosomiasis is a debilitating disease caused by trematode worms of the genus Schistosoma. Three members Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum are responsible for the great majority of human infections.Schistosomiasis is widespread in sub-Saharan Africa, several countries of the Middle East, South America, and South-East Asia. Vaccination against the infection would be the most reliable way to combat the infection and decrease or interrupt its transmission, but a commercial vaccine is still unavailable. Praziquantel PZQ is the only drug considered for schistosomiasis treatment as it is effective against the major human schistosomes, commercially available, cost-affordable, and elicits limited side-effects. Several reports documented the highly significant PZQ efficacy in treatment of light infections in areas of low S. mansoni and S. haematobium endemicity and PZQ use. Chemotherapy with PZQ alone of patients residing in regions of high schistosome endemicity and afflicted with light, moderate, or heavy infection is not efficacious. Accordingly, we propose implementation of cost-affordable arachidonic acid ARA , a polyunsaturated omega-fatty acid and efficacious in vitro and in vivo schistosomicide, for oral therapy of children with Schistosoma mansoni and Schistosoma haematobium light infection, as adjunct to PZQ for cure of children with moderate and heavy infections, and for counteracting schistosome resistance to PZQ that arises in endemic areas exposed to repeated and intense PZQ mass treatment campaigns.

Synopsis of arachidonic acid metabolism: A review

“…Arachidonic acid is naturally found incorporated in the structural phospholipids in the cell membrane in the body or stored within lipid bodies in immune cells [13] . It is particularly abundant in skeletal muscle, brain, liver, spleen and retina phospholipids [14] . Local levels of esterified AA in resting cells like platelets, for example, are around 5 mM.…”

Arachidonic acid: Physiological roles and potential health benefits – A review

“…The chemotherapeutic activity of ARA and praziquantel (PZQ) was equally high in low infection settings and equally low in children with heavy infection living in high endemicity areas. The highest cure was consistently achieved in children with light or heavy infection when ARA was combined with PZQ [77] , [86] , [102] , [103] .…”

“…Decreased postnatal ARA and DHA blood levels in premature infants were found to be associated with neonatal morbidities, while adding DHA and ARA to preterm-infant formulas led to improved visual acuity, visual attention and cognitive development [82] , [83] , [84] , [85] . The ARA levels in human milk and ARA requirements, essentiality in pre- and neonatal life and during development, and inclusion in infant formulas have recently been reviewed [86] , [87] , [88] , challenged and discussed [89] .…”

“…In skeletal muscles, ARA has been found to make up to 15–17% of total fatty acids, thus explaining why ARA supplementation affected body composition, muscle function and power output in strength-training individuals [86] , [95] , [96] . It is also possible that ARA modulates neuromuscular signaling through its incorporation into cell membranes, and/or increases neurotransmitter firing from nerve cells [91] .…”

“…ARA is a major nSMase activator. Accordingly, it was straightforward to predict that ARA possesses potentially potent schistosomicidal activity [75] , [77] , [86] , [98] , [99] .…”