**1. Introduction**

Schistosomiasis is a debilitating disease caused by dioecious (having separate sex) trematode worms of the genus Schistosoma. Three members, *Schistosoma mansoni*, *Schistosoma haematobi‐ um*, and *Schistosoma japonicum*, are responsible for the great majority of human infections. Schistosomiasis is also called snail fever as the schistosomes' life cycle comprises asexual reproduction in an appropriate, fresh water snail. Actually, it is the presence of the specific snail vector that determines the prevalence of the disease, as infection is exclusively caused by the larvae (termed cercariae) shed by infected snails. The cercariae of *S. mansoni*, *S. haematobi‐ um*, and *S. japonicum* swim in fresh water and soon die if they fail to land on the skin of humans or other suitable mammalian hosts. The cercariae then penetrate the epidermis, linger there for one (*S. japonicum*) to three (*S. mansoni*, *S*. *haematobium*) days or more until extensive biochemical changes end by setting a protective, outer double-lipid bilayer armor. The larvae, now termed schistosomula, exit to the dermis and then make their way into dermal venous capillaries, en route to the lung and then liver. There the parasites start to feed and rapidly grow and mature, and the male carrying the female into its ventral gynecophoric groove or "schist" migrate to permanent residence in the inferior mesenteric (*S. mansoni*, *S*. *japonicum*) or the peri-vesical (*S. haematobium*) venous plexus. Until then, the worms are nearly innocuous causing very limited harm, especially in endemic regions. With the onset of female parasite egg deposition, harm starts and progresses into overt diseases [1-5].

To continue the life cycle, the ova must egress the mammalian host vasculature to the exterior to locate the intermediate snail host where asexual reproduction takes place. The parasite dwelling is nearest to the outlets of the lower colon and rectum via feces and the urinary bladder with urine. Eggs release proteolytic and other hydrolytic enzymes to transit the blood capillaries, and thereafter the large intestine (or urinary bladder) wall into the lumen. Besides releasing host matrix digestive enzymes, *S. mansoni* and *S. haematobium* additionally depend on the sharp, lateral and terminal spine, respectively. The massive daily egg migration, trapping, and calcification lead to edema, congestion, ulcers, lesions, petechial hemorrhage, necrosis, hyperplastic and hypertrophic changes, fibrosis, and excessive nodules and polyps formation in the intestine, symptoms collectively known as intestinal schistosomiasis [1, 2]. Continuous egg transit via the wall of the lower urinary tract to the lumen causes even more damage to the urinary tract and bladder, the severe symptoms of urinary schistosomiasis [3]. Beside the egg-induced overt mechanical injury and lesions, the presence of parasite molecules within the extracellular matrix signals danger and expectedly contributes to intense and prolonged generation of inflammatory mediators [4].

The "plat de resistance" is still away, as the most severe injury does not result from the eggs that escape to the exterior but from the eggs that fail to do so. Eggs trapped in the wall of the intestine or urinary tract drift and eventually accumulate in tissues of other organs, namely the liver, where they remain viable for approximately three weeks, and release soluble egg antigens (SEA) via their microscopic pores. The host responds to these insults through vigorous immunologic reactions. These intense immunological reactions are injurious to the host, not the egg that remains unscathed, until its viability becomes exhausted. Lymphocytes, eosino‐ phils, basophils, and macrophages accumulate around the egg in attempt to prevent its contents from seeping and disseminating, thus forming large granulomas. The granulomas gradually begin to encompass the entire organ, progressing to fibrosis with excessive accu‐ mulation of collagen and extracellular matrix proteins, obstructive vascular lesions, vascular hypertension, neo angiogenesis, splenomegaly, esophageal varices, and signs of hepatocellular (*S. mansoni*) or kidney (*S. haematobium*) failure [1-3, 5].

The transiting eggs-induced mechanical injury and the immunological reactions to the entrapped eggs manifest into colitis, diarrhea, blood in stool or urine, abdominal discomfort and pain, urodynamic abnormalities, fatigue, lower exercise and work tolerance, impaired cognitive capacities, and retarded development. Chronic infection leads to organ dysfunction, intense vascular complications, and additionally, predisposes to other even more severe viral and bacterial infections, cancer development, and ultimately death [1-3, 5].

Detection of eggs in stool specimens is the gold standard for diagnosis of the infection. In chronic infections, i.e., in adults residing in endemic areas, continuous egg deposition and migration via the wall of the lower intestine and the urinary bladder and tracts generate fibrosis in the submucosa and hypertrophy in the muscularis mucosa, and consequently, a barrier is raised to the usual route of ova transit from the surrounding veins to the lumen of the gut or urinary bladder [2, 3]. Expectedly, the gold standard method of egg detection is entirely unreliable in chronic infections. Diagnostic methods based on serological detection of anti‐ bodies to the parasite antigens do not lack sensitivity, but lack specificity and additionally may not be used to monitor the outcome of therapy or to differentiate between present and past infection. Diagnostic methods based on antigen detection in serum, urine or stool, and saliva lack both sensitivity and specificity and together with the methods based on molecular biology advances are cumbersome, costly, and none has been adapted for routine screening in endemic regions, all situated in the developing world [5 and references therein, 6]. Epidemiological surveys are costly and require thorough scientific and political involvement, both often failing in developing countries. Based on the above, it may be foreseen that the figures on the prevalence of schistosomiasis, namely 252 million infected, are a gross underestimate. Yet, it is certain that the figures of 800 million persons, namely children, residing in rural areas are at risk of the infection, and yearly deaths as high as 200,000 are correct [6-9]. Schistosomiasis is widespread in sub-Saharan Africa, several countries of the Middle East, South America, and South-East Asia [6-10]. 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 an unmet clinical need. Praziquantel is the only drug considered for schistosomiasis treatment as it is effective against the major human schistosomes, commercially available, costaffordable, and elicits limited side-effects [reviewed in 5, 11, 12].
