124 Schistosomiasis

Schistosomiasis (bilharzia), known also by many lo­cal names such as “red-water fever,” “snail fever,” “big-belly,” and “Katayama disease,” is an “immu­nologic disease” induced by eggs of blood-vessel­inhabiting worms of the class Trematoda, genus Schistosoma.

There are three major human schistosome species: Schistosoma haematobium, which inhabit the veins of the bladder area and whose eggs are discharged in the urine; and Schistosoma mansoni and Schisto­soma japonicum, which inhabit the mesenteric veins supplying the intestines and whose eggs are dis­charged in the feces. In every case, however, the worms may also be found in the liver and portal system. There are also a few other species that can parasitize humans. These include the japonicum- Iike Schistosoma mekongi from the lower Mekong River basin, and some African schistosomes, such as Schistosoma intercalatum, that normally parasitize cattle and wild animals.

Terminology

The terminology of this disease is very confusing. Theodor Bilharz, the discoverer of the trematode worm responsible for the disease, placed it in the genus Distoma, a broad genus that was soon aban­doned as more trematode species were discovered. Numerous generic names were thereafter invented to label the worm, including Schistosoma in 1858 (the name that must stand according to the rules of zoolog­ical nomenclature), Gynaecophorus in 1858, Bilhar-

zia in 1859, and Thecosoma in 1860. Before World War II, however, in an understandable desire to honor the name of Bilharz, the disease was commonly called bilharziasis. But in 1949, members of the World Health Organization’s Study Group on Bilharziasis in Africa, ignorant of the tight rules of zoological nomenclature, recommended that the name Bilhar­zia be used for the worm and “bilharziasis” for the disease.

This ruling makes little sense. The name bilhar­ziasis would be used only for the disease if the ge­neric name of the worm were Bilharzia, just as trypanosomiasis is used to denote the disease caused by protozoans of the genus Trypanosoma. But be­cause the generic name Schistosoma must be re­tained, the term “bilharziasis” becomes invalid, al­though the word “bilharzia” could be used to denote the disease.

Logic, however, has frequently ruled over histori­cal awareness, and since World War II, the Ameri­cans, in particular, have used the word “schistoso­miasis,” or even its ugly derivative, “schisto,” to denote a disease whose causal agent belongs to the genus Schistosoma.

Distribution and Prevalence

The disease has an almost worldwide tropical distri­bution, but is mercifully absent from the Indian sub­continent. S. haematobium is highly endemic in the Nile Valley, and has an irregular distribution in the Middle East and North Africa (Map VIII. 124.1). It occurs in most West and Central African countries, along the coastal countries of East Africa from So­malia to Natal, and in the islands off the east coast. S. mansoni is highly endemic in the Nile Delta and now seems to be spreading into the Nile Valley (Map VIIL 124.2). In Africa it has a distribution similar to (although more irregular than) that of S. haema­tobium. But, unlike S. haematobium, S. mansoni also occurs in South America (Brazil, Surinam, and Venezuela) and in some islands in the Caribbean (Dominican Republic, Puerto Rico, St. Lucia, and others) (Map VIIL 124.3); the parasite was trans­ported from Africa to the New World as an unin­tended by-product of the slave trade. Oriental schis­tosomiasis, caused by S. japonicum, is endemic to the Yangtze Valley and many coastal provinces of mainland China (Map VΠI.

Map VIII.124.1. Distribution of Schistosoma haematobium in Africa and the Middle East. (From Far­ley 1991.)

Map VIΠ. 124.2. Distribution of Schistosoma mansoni in

Africa and the Middle East. (From Farley 1991.)

Map VIII.124.3. Distribution of Schistosoma mansoni in the Western Hemisphere. (From Farley 1991.)

Map VIII.124.4. Distribution of Schistosoma japonicum and Schistosoma mekongi. (From Farley 1991.)

a series of smaller foci in Malaysia, Thailand, and Japan.

Over 200 million people are said to be infected with the disease, although the data on which such figures are based are extremely variable and unreli­able. There is little doubt, however, that in villages of the Nile Delta and other areas where there is constant contact of the human host with water, the prevalence can be as high as almost 100 percent. On a worldwide scale, a recent World Health Organiza­tion survey revealed that in 42 countries surveyed, 21 percent of the population was infected.

Etiology

The worms are acquired in fresh water by contact with their larval stages. The worm eggs, which are highly diagnostic for each species, are shed in the urine or feces of the human host and hatch to pro­duce a minute short-lived larval stage called a miracidium. The miracidium of each species invades the tissues of a specific snail host where it undergoes asexual reproduction, eventually to produce the fi­nal larval stage. The final stage, the cercaria, is released daily in very large numbers from the snail, swims freely in the water, and then bores into the skin of the human host.

Epidemiology

The disease has a very complex epidemiology, result­ing in part from a quite intricate relationship be­tween the parasite and the snail intermediate host. Not only are there strains of each schistosome spe­cies, but also there are a multiplicity of snails that vary in their susceptibility to these strains and have a taxonomy that is in a constant state of revi­sion. Historically this has long been a source of to­tal confusion.

In very general terms, the snail hosts of S. haema­tobium belong to the genus Bulinus, which has been divided into two subgenera: one with three species complexes, including the Bulinus truncatus-tropicus group; and the other with one species complex, the Bulinus africanus group. The B. truncatus-tropicus species complex act as intermediate hosts to S. haematobium in Egypt and other countries north of the Sahara, whereas the B. africanus species complex generally serve as the most important intermediate hosts south of the Sahara. The genus Biomphalaria acts as the intermediate host for S. mansoni. As in

Bulinus, the genus has been divided into species com­plexes, with the Biomphalaria pfeifferi group acting as the most important complex in Africa south of the Sahara and in the Middle East, and Biomphalaria alexandrina the host in the Nile Delta. In the Ameri­cas, Biomphalaria glabrata acts as the most effective host. Whereas S. haematobium and S. mansoni are transmitted by species of pulmonate freshwater snails, S. japonicum is transmitted by amphibious prosobranch snails belonging to the species Oncome- Iania hupensis, of which there are six geographic subspecies. The aquatic prosobranch snail, Tricula aperta, endemic to the Mekong River, acts as the intermediate host of S. mekongi.

Schistosomiasis can be a serious chronic disease in poor rural areas, where children and adults, because of recreational, domestic, religious, and occupational reasons, come regularly into contact with fresh wa­ter contaminated with the schistosome cercariae.

Reservoir hosts play an important role in Oriental schistosomiasis, where the parasite is naturally transmitted between humans and other vertebrates, including many domesticated animals such as cat­tle, pigs, and dogs. Although animals are believed to play little if any role in the transmission of the two schistosome species in Africa, rodents are thought to act as important reservoirs of S. mansoni in South America.

The human schistosomes belong to a large family of trematodes, the Schistosomatidae, which also para­sitize birds and mammals. In many parts of the world, particularly in the lake country of the central and western United States and Canada, the cercariae of these nonhuman schistosomes can penetrate the skin ofhumans by accident. Although these cercariae are destroyed in the skin, they nevertheless cause a harmless but very irritating rash - “swimmer’s itch” or “schistosome dermatitis.”

Pathology

Disease pathology is due to embolized eggs that in­duce inflammatory reactions in various body organs, from which arise the classic symptoms of chronic schistosomiasis. This pathology is, however, very variable and is generally related to the intensity of infection. There are also pathological differences among the various species and among strains of the same species.

In S. haematobium lesions occur in the bladder and ureter around the entrapped and calcifying eggs, with the eventual laying down of fibrous con­nective tissue.

Immunology

The post-teenage decline in the disease has often been taken as evidence for a gradually acquired im­munity, but this probably plays a less significant role in the decline than do changing patterns of water contact. However, “concomitant immunity” is known to occur in experimental animals. The adult worms induce an immune response that has no effect on the adult worms but that protects the host from reinfec­tion by destroying many of the invading cercariae. The adult worms, themselves, are able to circumvent this immune response 2 to 3 days after boring into the skin by acquiring host antigens that become bound to the surface of the parasite; the host is no longer able to recognize the worms as foreign organ­isms. Whether concomitant immunity plays any sig­nificant role in humans has yet to be determined.

History

Pre-World WarI

Human schistosome worms were first described from Egypt by Theodor Bilharz in 1851, and their presence was related to disease symptoms by Wil­helm Griesinger shortly thereafter. Both men natu­rally assumed the worm to be a single species, Distoma haematobium (later named S. haemato­bium), occurring in the blood vessels of the gut or bladder. That there were two Egyptian species with different egg types was first suggested by Louis Sambon in 1907, who named the second species S. mansoni. A year later, Piraja da Silva in Brazil gave the first description of S. mansoni, but unfortu­nately assumed it to be another species distinct from both S. mansoni and haematobium. A long and testy controversy over the existence of two spe­cies in Egypt, with different morphologies and egg types, was finally resolved by Robert Leiper in 1915. Meanwhile, in 1905 Fujiro Katsurada had de­scribed eggs and worms from patients and cats in the Yamanashi district of Japan, and named them Schistosoma haematobium japonicum.

The life cycles of the worms long remained a mys­tery, although it was usually assumed that an inter­mediate host was involved. But Arthur Looss, the foremost authority on the disease at the turn of the century, argued in 1894 that there was no intermedi­ate host, and that the miracidia bored directly back into human beings. This bizarre theory likewise gen­erated a controversy that was finally resolved by experimental work in Japan. There, in 1913 Keino- suke Miyairi and Masatsuga Suzuki discovered the snail host into which the miracidia penetrated, and for the first time described the fork-tailed schisto­some cercariae emerging from the snails a few weeks later.

Leiper had been sent to China at this time to uncover the mysterious life cycle of the worm, and, hearing of the Japanese success, had hurried to Ja­pan to confirm the life cycle. In 1914 he was posted to Egypt, where he quickly resolved the life-cycle problem in that country, distinguishing the two spe­cies of schistosome worm in Egypt not only by their morphologies and egg types but also by their differ­ent snail hosts.

With these problems resolved, interest in schisto­somiasis subsided a bit, particularly because the dis­ease was thought curable by the drug antimony tartrate and preventable by the snail-killing chemi­cal copper sulfate.

The Interwar Years

Between the two world wars, campaigns against the disease using these chemicals were carried out in Egypt, the Gezira irrigated area of the Sudan, South­ern Rhodesia, and South Africa, particularly after schistosomiasis was found among the children of “poor whites” in rural Transvaal. In addition, the high prevalence of the disease among African mine laborers recruited for the South African mines gener­ated research on the disease by members of the South African Institute for Medical Research. The interwar years also witnessed the first involvement with the disease by the International Health Divi­sion of the Rockefeller Foundation, which financed an attempted eradication campaign against hook­worm and schistosomiasis in Egypt between 1929 and 1940. Moreover, in 1924 Ernest Faust and E. Meleney, two faculty members at the Rockefeller- funded Peking Union Medical College, first discov­ered the life cycle of S. japonicum in China.

Post-World WarII

After World War II, interest in the disease dramati­cally increased, especially in the British, French, and Belgian colonies in Africa. By 1950, schistoso­miasis, previously considered to be unimportant out­side Egypt, Sudan, South Africa, and to some extent China, was recognized as the most important tropi­cal disease in the world, after malaria. In America this interest followed from an outbreak of the infec­tion among American troops in Leyte, in the Philip­pines, where in 1944 over 1,000 troops of combat engineering companies involved in bridge building and road construction came down with the disease. The scientists and physicians, who were posted to Leyte to deal with the problem, brought the disease to the attention of American academics immediately after the war and initiated the growth in schisto­somiasis research.

In British Africa, where medical work had long been hampered by the policies of a penny-pinching empire, a series of Colonial Development and Wel­fare Acts passed every 5 years between 1940 and 1955 transformed the Colonial Office into an agent of colonial development. Money was made available for medical research, most of which was allocated for work on trypanosomiasis and the tsetse fly. But a helminth subcommittee of the Medical Research Ad­visory Committee was also formed, which began to stress the danger of schistosomiasis, particularly as new irrigation schemes, built as part of the new em­phasis on colonial agricultural development, threat­ened to spread the disease. The subcommittee initi­ated, for example, testing of a new drug, Miracil D, discovered by the British after occupation of the Bayer laboratories in Elberfeld toward the end of World War II.

The first major British work on the epidemiology of the disease in colonial Africa took place between 1955 and 1965, a period that saw the East Africa Medical Survey conducted while the Nationalist Gov- eminent of South Africa initiated surveys of the disease and supported laboratory research on experi­mental schistosomiasis in animals.

The 1950s also witnessed the first mass campaign against the disease that involved more than the usual introduction of latrines, drugs, and mollusc-killing chemicals by foreign experts. In 1958, as part of the Great Leap Forward, the Schistosomiasis Subcom­mittee of the Chinese Communist Party initiated an­other such campaign against schistosomiasis. Utiliz­ing a host of methods including the mass reclamation of swamp land, the Chinese eradicated the disease from many areas of the country. In 1949 perhaps 10 million Chinese were heavily infected with S.japoni- cuτn, whereas today the number is reported to have dropped to 2.4 million lightly infected cases.

The threat posed by irrigation schemes led to the postwar development of better molluscicides to re­place the ineffective copper sulfate. Niclosamide, selling under the trade name OfBayluscide₁ became the chemical of choice, but results were disappoint­ing. Chemotherapy has now become the favored weapon, particularly after the important 15-year ex­perimental control campaign in St. Lucia (1966-81), sponsored by the Rockefeller Foundation, and after the development of single-dose drugs to replace the highly toxic antimony compounds and Miracil-D, used earlier. Oral Oxamniquine proved effective against S. mansoni, and metrifonate against S. haematobium, whereas the newly developed prazi­quantel is emerging as a “wonder drug” effective against all schistosome species.

Today, with major support from the McConnnell Clark Foundation, a great deal of emphasis is being placed on problems of schistosome immunity and the development of vaccines.

John Farley

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