rel="nofollow" href="#ulink_4da080f1-a3d3-5e28-9615-ab25afcf2a9e">1 Several other minor species make up the remaining 1% of the cases. Almost all of the people infected with schistosomiasis live in Africa, with 29 African nations each harboring 1 million or more cases (Fig. 3.1).1 Outside Africa, only the nations of Brazil and Yemen have 1 million or more cases of schistosomiasis.1 In Brazil and elsewhere in the Americas, S. mansoni infection was likely introduced by a flourishing slave trade with sub-Saharan Africa that began in the 1600s.12
Humans contract schistosomiasis through freshwater contact with free-swimming cercariae (Fig. 3.2). Therefore, poor rural populations whose everyday activities involve fishing, bathing, or swimming in schistosome-contaminated waters or working in agricultural areas irrigated by contaminated waters are at the highest risk of infection.10,13 Almost 800 million people in developing countries live in proximity to either irrigated agricultural fields or dam reservoirs, where the risk of acquiring schistosomiasis is the highest.1
Schistosome cercariae have a forked tail that allows them to swim and ultimately to directly penetrate human skin. Following skin penetration, the cercariae lose their tail and undergo a number of biochemical changes that allow them to resist attack by the human immune system. The larval schistosomes (also known as schistosomulae) migrate through the lungs and over a period of approximately 1 to 2 months make their way to the portal vein of the liver, where they mature into adult male and female schistosomes.13 The paired worms ultimately migrate to their final destination, which for S. haematobium, the cause of urogenital schistosomiasis, is the small veins that drain the bladder and other pelvic organs, while S. mansoni and S. japonicum live in the mesenteric veins that drain the intestine.13 While living in the blood vessels, the adult schistosomes feed on blood, breaking down the hemoglobin components by using enzymes similar to those found in hookworms. Through evolution, the adult male and female schistosomes living in the bloodstream have developed remarkable mechanisms for masking their identity, including the accretion of host molecules on their surface. In this way, the schistosomes avoid attack by antibodies and cells of the human immune system.
Figure 3.2 Life cycle of human schistosomes. (From Public Health Image Library, CDC [http://phil.cdc.gov].)
The female worms subsequently produce hundreds of eggs daily.13 In order to continue the schistosome life cycle, the eggs ultimately require a mechanism to exit from the body. In the case of hookworm infection and other soil-transmitted helminth infections in which the parasites live in the gastrointestinal tract, the feces provide a straightforward path for the eggs to escape into the environment. In contrast, schistosome eggs have a more formidable challenge because they are present in the human blood vessels. As shown in Fig. 3.3, schistosome eggs are equipped with an ominous-looking spine that permits them to bore their way through the blood vessels and then into either the bladder or intestine from the outside. Through a combination of mechanical boring and the release of tissue-dissolving enzymes, the eggs gain access to either the lumen of the bladder or the intestine; they exit the body in urine or feces, respectively. When deposited in freshwater, the eggs live for about a week. They hatch and give rise to free-swimming ciliated forms known as miracidia, which seek out a suitable snail species. Upon entry into the appropriate snail, each miracidium can give rise to multiple progeny through asexual reproduction. Eventually, these progeny develop into cercariae that exit the snail.13
Figure 3.3 Spined eggs of S. haematobium (top) and S. mansoni (bottom). (Images from Public Health Image Library, CDC [http://phil.cdc.gov].)
Unfortunately, egg migration through human body tissues is not an efficient process, so many eggs become trapped in either the bladder and reproductive organs (S. haematobium) or intestine and liver (S. mansoni and S. japonicum). The trapped eggs cause mechanical damage and the rupture of small blood vessels, which lead to bleeding and the appearance of blood in either urine or feces. The eggs also trigger an inflammatory response composed of masses of human white cells and other host-derived components (known as granulomas), which can obstruct urine or blood flow. Because schistosomes can live for years in the small veins of the bladder and intestine, their constant release of eggs is associated with chronic blood loss leading to anemia, as well as damage to the bladder, kidneys, and reproductive organs (S. haematobium) or to the intestine and liver (S. mansoni). The combination of long-standing anemia, inflammation, and target organ damage causes growth retardation, undernutrition, and cognitive delays in children, as well as chronic abdominal pain, exercise intolerance, poor school performance, and reduced work capacity.13,14 Anemia and chronic inflammation also partially account for the developmental delays occurring in chronic pediatric soil-transmitted helminth infections.
Sub-Saharan Africa bears the greatest burden of disease caused by the schistosomes and almost all of the cases of S. haematobium infection. Figure 3.4 shows several children, each holding a cup of his or her reddened urine (schistosomiasis is sometimes known locally as “red-water fever,” as well as “snail fever”). Endemic hematuria from schistosomiasis was first recorded by a Western physician in 1798, by J. Renoult, a French army surgeon who accompanied Napoleon on his invasion of Egypt.2 Just as hookworm causes chronic blood loss in the intestine, leading to anemia, the chronic blood loss resulting from S. haematobium egg deposition in the bladder is a significant cause of anemia in Africa, particularly among adolescent children, who on average harbor larger numbers of schistosomes than do any other age group.13,14 We saw previously how chronic intestinal blood loss and anemia resulting from hookworm were associated with physical and mental delays in children. For urogenital schistosomiasis, the anemia results not only from urinary blood loss but also from other factors, including chronic inflammation. These processes also contribute to inhibition of physical and mental growth for the child. Other important contributors to the morbidity of urogenital schistosomiasis are the inflammatory granulomas that develop in the bladder. Severe bladder wall pathology occurs in an estimated 18 million people in Africa.11 When the bladder granulomas coalesce, they can obstruct urine flow and cause distension of the ureter and kidneys. This condition is known as hydronephrosis and occurs in approximately 20 million people in Africa as a result of S. haematobium infection.11 Long-standing hydronephrosis can lead to renal failure; this progression probably accounts for a significant number of the estimated 280,000 annual deaths from schistosomiasis.11 Another major consequence of chronic S. haematobium infection is its ability to predispose people to acquiring an unusual form of bladder cancer. Whereas most bladder carcinomas in the industrialized world are adenocarcinomas, S. haematobium infection is associated with a unique squamous cell carcinoma of the bladder. It is conjectured that the schistosome
