ScienceWeek

MEDICAL BIOLOGY: ON SCHISTOSOMIASIS

The following points are made by Christoph G. Grevelding (Current Biology 2004 14:R545):

1) Helminthes of the genus Schistosoma are the cause of schistosomiasis, originally termed bilharzia in honor of Theodor Bilharz (1829-1862), who first described these worm parasites in 1851. Aside from malaria, schistosomiasis is the most prevalent parasitic infection in the world, affecting over 200 million people in 76 countries of the tropics and subtropics. The blood flukes live in the abdominal veins of their vertebrate definitive hosts and produce eggs. About 50% pass through the intestinal wall to enter the gut lumen. Eggs retained in the gut wall induce inflammation, hyperplasia, ulceration, microabscess formation and polyposis. The remaining 50% are mainly deposited in spleen and liver resulting in presinusoidal inflammation and periportal fibrosis.

2) The adult worms are not infectious for humans, but one of the larval forms is the infectious entity. The complex life cycle starts with the eggs that are deposited with the feces of infected humans in the water and give rise to the miracidia, which penetrate a species-specific water snail. In this intermediate host, the parasite multiplies asexually to produce a high number of aquatic cercariae that leave the snail as infectious agents. Following penetration into the skin of humans, cercariae transform into schistosomula, which are transported in the bloodstream via the lungs and heart to the liver to become adults.

3) Schistosomes are unusual because they are the only members of the trematodes (flukes) that have evolved separate sexes. Males and females pair in the liver and migrate as couples to the abdominal veins. Permanently paired, they can live here for decades, surviving the attacks of the immune system. An even more astonishing peculiarity is that pairing is mandatory not only for the fertilization of eggs but also for the sexual maturation of the female, a phenomenon unique in nature.

4) If paired, a female starts a proverbial assembly-line production to deliver compound eggs, each composed of one oocyte from the ovary and 30-40 vitelline cells from the vitellarium. To achieve the daily production of 300 eggs, more than 10,000 vitelline cells have to be generated, providing yolk and egg-shell proteins. This efficiency depends on the maturation status of the female that is induced and maintained by the male.

5) A continuously supplied, as yet unknown male stimulus initiates the mitoses and differentiation processes of the reproductive organs of the female, especially the vitellarium. Upon separation from the partner, the vitellarium degenerates and egg production stops. These processes are reversible upon remating. Virgin females, however, are stunted and sexually immature: instead of a fully developed vitellarium, they contain undifferentiated precursor vitelline cells. Molecular studies demonstrated that the male even governs the transcriptional activity of female-specific genes expressed in the reproductive organs, such as those encoding egg shell precursor proteins.[1-5]

References (abridged):

1. Basch, P. (1997). Schistosomes Development, Reproduction and Host Relations. (Oxford University Press)

2. Grevelding, C.G., Sommer, G. and Kunz, W. (1997). Female-specific gene expression in Schistosoma mansoni is regulated by pairing. Parasitology 115, 635-640

3. Kunz, W. (2001). Schistosome male-female interaction: induction of germ-cell differentiation. Trends Parasitol. 17, 227-231

4. LoVerde, P.T. (2002). Sex and schistosomes: an interesting biological interplay with control implications. J. Parasitol. 88, 3-13

5. McManus, D.P., Hu, W., Brindley, P.J., Feng, Z. and Han, Z.G. (2004). Schistosome transcriptome analysis at the cutting edge. Trends Parasitol. 20, 301-304

Current Biology http://www.current-biology.com

--------------------------------

Related Material:

ON SCHISTOSOMIASIS

The following points are made by A.G. Ross et al (New Engl. J. Med. 2002 346:1212):

1) In 1851, Theodor Bilharz (1829-1862) described a parasitic infection (bilharzia) that would later be termed schistosomiasis. Currently, 200 million people in 74 countries have this disease; 120 million of them have symptoms, and 20 million have severe illness. Schistosomiasis is caused by parasitic trematode worms (schistosomes) that reside in the abdominal veins of their vertebrate definitive hosts.

2) Five species of schistosoma are known to infect humans. Infection with Schistosoma mansoni, S. japonicum, S. mekongi, or S. intercalatum is associated with chronic hepatic and intestinal fibrosis. S. haematobium infection results in fibrosis, stricturing, and calcification of the urinary tract. All schistosoma infections follow direct contact with fresh water that harbors free-swimming larval forms of the parasite known as cercariae. Cercariae penetrate the skin of humans or, in the case of S. japonicum, humans and other mammalian hosts that act as reservoirs for infection. The cercariae shed their bifurcated tails, and the resulting schistosomula enter capillaries and lymphatic vessels en route to the lungs. After several days, the worms migrate to the portal venous system, where they mature and unite. Pairs of worms then migrate to the superior mesenteric veins (in the case of S. mansoni ), the inferior mesenteric and superior hemorrhoidal veins (in the case of S. japonicum), or the vesical plexus and veins draining the ureters (in the case of S. haematobium).

3) Egg production commences four to six weeks after infection and continues for the life of the worm ù usually three to five years. Eggs pass from the lumen of blood vessels into adjacent tissues, and many then pass through the intestinal or bladder mucosa and are shed in the feces (in the case of S. mansoni and S. japonicum) or urine (in the case of S. haematobium). The life cycle is completed when the eggs hatch, releasing miracidia that, in turn, infect specific freshwater snails (S. mansoni infects biomphalaria species, S. haematobium infects bulinus species, and S. japonicum infects oncomelania species). After two generations ù primary and then daughter sporocysts ù within the snail, cercariae are released.

4) Despite major advances in control and substantial decreases in morbidity and mortality, schistosomiasis continues to spread to new geographic areas. Furthermore, there are reports of resistance to praziquantel, the mainstay of medical treatment. The majority of Schistosoma haematobium, S. mansoni, and S. intercalatum infections are found in sub-Saharan Africa. S. mansoni remains endemic in parts of Brazil, Venezuela, and the Caribbean. S. japonicum infection still occurs in China, Indonesia, and the Philippines, despite substantial and largely successful control measures. S. mekongi is found in Cambodia and Laos, along the Mekong River.

5) Environmental changes that result from the development of water resources and the growth and migration of populations can facilitate the spread of schistosomiasis. For example, the construction of Diama Dam on the Senegal River led to the introduction of S. mansoni into Mauritania and Senegal. The movement of refugees and the displacement of populations resulted in the introduction of S. mansoni into Somalia and Djibouti. The presence of the Aswan Dam in Egypt has led to the virtual elimination of S. haematobium from the Nile Delta but has brought about the establishment of S. mansoni in upper Egypt. The Three Gorges Dam is currently being built on China's Yangtze River between two areas where schistosomiasis is endemic. The Chinese Ministry of Health is currently evaluating the potential effect of the dam on schistosomiasis transmission.

References (abridged):

1. Chitsulo L, Engels D, Montresor A, Savioli L. The global status of schistosomiasis and its control. Acta Trop 2000;77:41-51

2. Jordan P, Webbe G, Sturrock R. Human schistosomiasis. Wallingford, England: CAB, 1993.

3. Waine GJ, McManus DP. Schistosomiasis vaccine development --the current picture. Bioessays 1997;19:435-443

4. Morel C. Reaching maturity -- 25 years of the TDR. Parasitol Today 2000;16:522-528

5. Newman L. Worm infections fester as experts vie for fair share of funding. Lancet Infect Dis 2001;1:140.

New Engl. J. Med. http://www.nejm.org

--------------------------------

Related Material:

CURRENT PROGRESS IN MEDICAL HELMINTHOLOGY

The following points are made by D.G. Colley et al (Science 2001 293:1437):

1) Two billion people on Earth are infected by soil-transmitted helminths (such as Ascaris lumbricoides, hookworms, Trichuris trichiura) and schistosomes (a subgroup of human helminthic infections), and the public health burden is enormous. Together with other widespread medical helminthic infections, including onchocerciasis, lymphatic filariasis, Guinea worm disease, and food-borne nematode and tapeworm infections, these infections are largely diseases of chronic morbidity and debilitation, and so the suffering is difficult to quantify at the population level.

2) Nevertheless, schistosomes in Africa are responsible for some 45 million people with hematuria, 21 million people with dysuria, 14 million people with hydroureter, 7 million people with heptomegaly, and hookworms are now estimated to cause anemia in 33 million Africans. Overall, 300 million of the 2 billion infected people are estimated to have severe infections with one or more soil-transmitted helminths and schistosomes. Early childhood infections by soil-transmitted helminths contribute significantly to debilitation, since treatment clearly leads to increased physical and cognitive development. Unfortunately, during the past decade there has been a serious erosion of support for research in medical helminthology, and only a small proportion of graduate students trained in parasitology remain in that field after receiving their PhD.

Science http://www.sciencemag.org

ScienceWeek http://scienceweek.com