The Power of Plagues. Irwin W. Sherman

3.2G). But there remained a puzzle: how was the infection transmitted? Bilharz and others were aware that flukes closely related to Schistosoma had intermediate stages in snails, but when Harley examined snails from a region where schistosomiasis was prevalent, he found no evidence of larval stages. Despite this failure, the suspicion remained that humans acquired the infection either by eating infected snails or by drinking water containing the ciliated larva called miracidia. In 1870, Spencer Cobbold, working in London, obtained eggs from a young girl living in the Cape of Good Hope and found that although the eggs would not hatch in urine, they did so in fresh or brackish water. Then, in about 1904, Japanese physicians found that a related blood fluke, named Schistosoma japonicum, could also infect humans, but this species had eggs without a spine. In 1905, Patrick Manson discovered another type of schistosome egg, one with a spine on its side (Fig. 3.2D); this was in the feces of an Englishman who had lived in the West Indies but had never visited Africa; this new type was duly named Schistosoma mansoni. Now there were three known species of human-infecting blood flukes.

The life cycle and mode of transmission of the schistosome to a human were first demonstrated between 1908 and 1910 in Japan. Fujinama and Nakamura found that when the tails of mice were immersed in water from rice fields known to have a high incidence of bilharzia, they became infected with S. japonicum. Shortly thereafter it was possible to show that the miracidia were able to penetrate freshwater snails in the rice paddies, and Ogata found that a tailed larva (called a cercaria) emerged from infected snails and could directly penetrate the skin of mice (Fig. 3.2G). This suggested that species other than S. japonicum might have a similar life cycle. At the outbreak of World War I the British became concerned about the potential deleterious effects of schistosomiasis on their troops in Egypt. In 1915 the British War Office sent Robert Leiper to Cairo “to investigate bilharzia … and advise as to preventive measures to be adopted.” Leiper collected freshwater snails, identified them, and determined whether they were infected, either by allowing the snails to release cercaria or by dissecting the snails to find other larval stages (called sporocysts). Within weeks he and his team identified the snails Bulinus and Biomphalaria as the vectors. (Because the snail vector is critical to transmission, schistosomiasis is called “snail fever.”) Leiper went on to show, by placing the tails of the mice in cercaria-infested water, that the skin of mice could be directly invaded by the cercaria. This suggested that the infection was acquired by bathing in infested water. But could the infection also be acquired by ingestion? Because Leiper was able to show that when cercaria were placed in dilute hydrochloric acid (similar in concentration to that found in the human stomach) they were killed, this route of infection seemed most unlikely. Leiper was also able to show that the adult S. mansoni and S. haematobium were different from one another and that cercaria hatched from Biomphalaria produced eggs with lateral spines whereas those from Bulinus produced eggs with a terminal spine. The pathology of the two species was also found to differ: S. mansoni remained in the liver and laid its eggs there, whereas S. haematobium early in its development left the liver for the veins surrounding the bladder. Thus, 65 years after the discovery of the adult worm by Bilharz, the life cycle of snail fever was known. The discharged eggs, on reaching freshwater, release a swimming larva, the miracidum. Miracidia are short-lived, but if they encounter a suitable snail, they penetrate the soft tissues (usually the foot), migrate to the liver, and change in form (sporocyst); and for 6 to 7 weeks, by asexual reproduction, the numbers of parasites increase. During this time the snail sheds thousands of fork-tailed cercaria, which can swim and directly penetrate human skin, and in 5 to 8 weeks they develop into adult worms.

       Snail fever, the disease

      Schistosomes differ from other flukes (trematodes) in that the sexes are separate and they inhabit the blood vessels. The adult worms are ~10 mm in length, and the stouter males have a groove running lengthwise, called the gynecophoric canal, where the female normally resides (Fig. 3.2E). It is this groove in the male that is the basis for the worm’s generic name Schistosoma, meaning “split body.” Both males and females have two suckers at the head end of the worm, and the more anterior one surrounds the mouth. (Bilharz mistakenly took the two suckers for two mouths, and thus he called the worm Distomum, “two mouths.”) The schistosome adults, in sexual union, live in blood vessels (veins) close to the bladder and small intestine. Mating occurs in the gynecophoric canal, and then the paired worms move “upstream” into smaller veins, where the female worm deposits the fertilized eggs. The pathology of schistosomiasis is due not to the adult worms themselves but to the eggs. Each day hundreds of embryo-containing eggs move across the walls of the veins into the bladder or intestine, aided by the host’s inflammatory response, and in the process eggs become enclosed in a small tumor called a granuloma. It is the passage of eggs through the bladder wall that results in bleeding and gives the telltale sign of hematuria. Once in the bladder or intestine, the egg becomes freed of the granuloma and is eliminated from the body either with the urine or in the feces.

More than two-thirds of the eggs, however, fail to work their way out of the body and are washed back in the veins, and by means of the bloodstream they scatter throughout the body, where they accumulate in various organs. Accumulation is greatest in the liver and spleen. The piling-up of eggs blocks the normal blood flow, and this leads to tissue death. The egg also acts as an irritating foreign substance that the body attempts to wall off by surrounding it with a fibrous capsule. The egg-laden liver eventually becomes filled with scar tissue. In the bladder blood fluke, S. haematobium, the scarred areas block the migration of eggs through the lower bowel tissues, and more eggs are swept back into other sites. The earliest signs of infection, fever, chills, sweating, headache, and cough, occur within 1 or 2 months. Six months to a year later the accumulation of eggs produces organ enlargement, especially the liver and spleen; the enlarged and cirrhotic liver causes the abdomen to become bloated, appetite diminishes, blood loss leads to anemia, and there is dysentery (Fig. 3.3).

Figure 3.3 Two young boys infected with blood flukes

      Schistosomiasis is an arithmetic disease: the severity of its symptoms and cumulative damage are directly related to the number of worms present, and the latter depends on the degree of exposure. In heavy cases there may be hundreds of worms, and the adults may live for 20 or 30 years. Clearly, with time and increased invasion by cercaria, a person becomes more and more debilitated. Yet over the centuries the adult inhabitants of areas where the disease is endemic, such as Africa, developed some measure of immunity largely as a result of continuous exposure; Europeans and Americans with no such immunity suffer more-severe symptoms as a result of higher burdens of worms.

       Where snail fever is found

Wars and human migrations carried the blood flukes of the East African lakes to the Nile River, and from there it was distributed along the trade routes to most of the continents of the world. Although in 1902 Manson believed schistosomiasis to be a disease unique to Africa, he had to revise his thinking when he discovered an Englishman, who had resided in the West Indies but had never been to Africa, passing eggs with a lateral spine. In 1908, Piraja da Silva, living in Bahia, Brazil, wrote that the schistosome common in the Americas was probably introduced from Africa by West African slaves beginning as early as 1550. Indeed, Bahia was one of the ports of entry for the African slaves, and more recently it has been suggested that, under the Dutch (1630-1654), Recife may also have been an important slave entry point. Although snails native to the Caribbean and South America have been found to be effective vectors (and different from the snail species in Africa), snails introduced from Africa have also been important in transmission.

      Schistosomiasis has not been eliminated. It is estimated that at present there are 240 million