Forgotten People, Forgotten Diseases. Peter J. Hotez
Gorges Dam across the Yangtze River might help to establish new ecological niches for snails to thrive and reproduce, thereby causing a rebound in the number of cases of schistosomiasis, just as other dam projects on the Nile at Aswan and the Senegal and Volta rivers in sub-Saharan Africa have caused massive increases in snail populations and reemergence of the disease.8
In Egypt and elsewhere in East Africa, schistosomiasis has had an equally important historical impact. Schistosome eggs have even been recovered from Egyptian mummies dating from the 20th dynasty, around 1000 BCE.2 During the first half of the 20th century, more than half of the populations in some rural villages of the Nile Delta were infected with either Schistosoma haematobium or Schistosoma mansoni. Both forms of schistosomiasis were considered the scourge of the fellaheen, Egypt’s peasant agricultural laborers.9 It was said that hematuria, the bloody urine that results from S. haematobium infection, was so common among Egyptian children and adolescent boys that it was considered a form of male menstruation.9 The initial efforts to control schistosomiasis in Egypt and in neighboring Sudan (where the Gezira Scheme, one of the world’s largest irrigation projects, is located near the confluence of the Blue Nile and White Nile) were organized by the British, initially through multiple injections of toxic antimony compounds to cure the disease in humans and subsequently through widespread use of molluscicides, snail-destroying chemical agents distributed in the environment.10 During the 1960s, Bayluscide (known generically as niclosamide), a molluscicide developed by Bayer, was widely used but later largely abandoned because of price increases combined with a realization that it caused significant damage to fish and other wildlife. Subsequently, during the 1970s, newly discovered drugs, such as ambilhar and hycanthone, were used in large-scale treatment of schistosomiasis, but they too fell into disuse because of their toxicity and some unexplained deaths.10 Complicating Egypt’s schistosomiasis problem was the fact that many schistosome-infected individuals also contracted hepatitis C when contaminated needles and equipment were used to administer tartar emetic, an older and injectable antiparasitic drug that is now seldom used.10 Patients with schistosome and hepatitis C coinfections often suffered from a severe, progressive form of fibrotic liver disease.10 Finally, during the 1990s, widespread use of the anthelmintic drug praziquantel in a 14-year-long mass drug administration campaign, supported in part by the World Bank and the U.S. Agency for International Development (USAID), reduced the overall prevalence of schistosomiasis in Egypt to less than 10% of the population.10 In China, a 10-year World Bank initiative also supporting mass drug administration of praziquantel has resulted in similar dramatic reductions of schistosomiasis in the Yangtze River valley.10
Table 3.1 The major human schistosomes
Despite the successes in China and Egypt, today schistosomiasis still rivals hookworm infection as the most important helminth infection of humans. Urogenital schistosomiasis caused by S. haematobium is responsible for approximately 63% of the cases worldwide, while an intestinal and hepatic form caused by S. mansoni accounts for another 35% (Table 3.1).11 Less than 1% of the global burden of schistosomiasis results from the Cold War warrior S. japonicum.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