Schistosomiasis (1990): Entire title

this video is based on the work of two research teams one led by Dr Owen standon at the welcome Laboratories of tropical medicine in the early ' 50s and the other led by Dr Diane McClaren in the late 80s at the National Institute for medical research Dr McLaren's scanning and transmission electron micrographs of the schistosome are featured in our video this is the image seen in the microscope which is enlarged still further when processed photographically it should be appreciated that these electron micrographs represent a wide range of magnifications for example this adult male schistosome is magnified about 35 times when viewed on a 50 cm television screen his ventral sucker 500 times and this spiny Inside Edge of the sucker 7,000 times some of our images are magnified around a quarter of a million times like this section showing the outer surface of a lval schistosome it was with the aid of this electron microscope that Dr McLaren was able to unravel one of the most puzzling stages in the life cycle of the Chism The crucial process is involved in the transformation from free living organism to a parasitic way of life these happy children are playing in water that is more than likely to be infected by one of the world's most damaging parasitic diseases schistosomes are parasitic flukes that live in the bloodstream of man they cause the disease schistosomiasis probably better known as bartsia a major health problem for hundreds of millions of people in many tropical and subtropical regions of the world a male schistosome is seen here with a female partly held in his gynecophoric Canal the male is about a centimet long and uses the lateral folds of his body to form the gynecophoric canal with which he Embraces the longer more slender female incidentally the scientific name chista means Clift bodied this is the anterior part of the Clift which surrounds the head end of the female here are the paired schistosomes in the portal vein of an experimentally infected hamster the flukes migrate as far as they can into the mesenteric veins and the female extend extends out of the gynecophoric canal to deposit her eggs into the smaller blood vessels the eggs then work through the tissues into the Lumen of the intestine in this species of schistosome the eggs pass out later with the feces here's an egg in a fecal smear the earliest records of urinary schistosomiasis are to be found in the EAS Papyrus dated around 1,900 BC although the ancient Egyptians did not know the cause of the disease they recognized and clearly Illustrated the urinary symptoms in their hieroglyphics calcified schistosome eggs have also been identified in the kidneys of mummies more than 3,000 years old it was not until 1851 that the German pathologist Theodore billhartz identified chistosa hematobium as the causative agent of urinary schistosomiasis in Egypt in 1904 katsurada described the life cycle of japonicum and in 197 sambon described menseni as a separate species in 1934 Fisher recorded the existence of intercalatum and as recently as 1978 Vogue Brookner and Bruce discovered mongi today 18 species are recognized of these mansai japonicum and he opium probably infect more people worldwide than any of the other species mansoni lives chiefly in the veins of the large intestine and this part of the portal circulation is also infected by a japonicum the passage of eggs through the intestinal tissues causes ulceration thickening and fibrosis of the bowel wall eggs can be seen in this much thickened region of The Superficial layers of the intestine also at the bases of the Villi those eggs which enter the Lumen of the gut are discharged with the feces chistosa hematobium differs from the other two species it inhabits the blood vessels of the bladder and its eggs are discharged with the urine the main clinical sign is hematuria But ultimately fibrotic lesions May develop throughout the whole of the urogenital system bladder cancer is not an uncommon development in advanced stages of the disease schistosomiasis is currently endemic in 75 countries hematobium is present in 53 countries mostly in Africa but also in the Eastern Mediterranean mansai shows a similar distribution except that it's also found in South America notably Brazil where it was probably carried with the slave trade japonicum on the other hand is confined to countries of the Far East China Indonesia and the Philippines Japan where the parasite was originally found has now been freed from the disease mongi occurs in Southeast Asia and intercalatum is found in Central and West Africa worldwide some 200 million people are infected with the schists and 500 to 6 100 million are at risk the highest infection rates are found in Brazil Egypt and the Sudan freshwater snails play an essential role in the transmission of the disease since each schistosome will spend part of its life cycle in the tissues of a snail species of bulinus are intermediate hosts for hematobium biomphalaria carries mansini and enom Melania carries japonicum wholesale destruction of the snail hosts with chemical MDES is one obvious method of reducing the incidence of schistosomiasis but since the snails are hemaphrodite possessing both male and female sexual organs it needs only one individual to survive a control program of this kind for an entire area to be repopulated within a single season moreover development projects such as hydroelectric schemes like the gigantic Kuba Dam on the zambesi have created large bodies of water and consequently enable the snails to flourish in recent years although most infected people carry only small numbers of schistosomes treatment with an effective drug not only reduces the prevalence of the disease it also reduces morbidity przi quantel is currently the drug of choice since a single dose affects all the main species of schistosome that infect man and it produces High cure rates oxamniquine is also used for mansen especially in South America while metrifonate is valuable for the treatment of hematobium it's man's primitive habits with regard to urination and defecation which maintain the disease in the community obviously the separation of urine and feces from Waters inhabited by the snails is vital in the control of infection in the third world this is easier said than done however in Zimbabwe the Blair Research Laboratories have produced some interesting designs for simple water pumps and lavatories this one is a strong shelter built over a deep pit it has an odor pipe fly traps and is easy to keep clean and here are some variations on the basic design the Blair water pumps are ingenious this one uses the pipe that delivers the water as the pump handle in the playground of a Village School these girls are enjoying their swing pump official notices pamplets and posters are also used in an attempt to increase local awareness in endemic areas the most desirable control measure would undoubtedly be a oneshot vaccine and it's towards this goal that current research is mainly directed all species of human schisms have essentially the same life cycle we've chosen mens andai for discussion here as it's the easiest to maintain and investigate under laboratory conditions the flukes live paired in the hepatic portal and mesenteric veins the male is light in color with a dark central line the gut just visible the female partly held in his gynecophoric Canal appears very dark in comparison because her gut is more obvious the dark color is hematin a product of hemoglobin digestion derived from Red cells of the host's blood which fills the double zigzag line of the gut if you look closely you'll see individual blood cells moving through the narrower passages this female has an egg in her uterus above the egg is the spiraled vitaline duct the female is cylindrical and has a relatively smooth surface but the dorsal surface of the male Bears many spiny bosses or tubic that are thought to Anchor came in position by catching against the walls of the blood vessels there are numerous pits between the tubic which presumably serve to increase the absorptive surface area while sensory organel are abundantly distributed over the entire body these ensure that the schistosome is aware of minute changes in its micro environment each fluke has two suckers at the anterior end of its body the ventral sucker is used by the fluke to attach itself to the walls of the blood vessels the very spiny surface of the sucker ensures a firm grip the oral sucker is important for feeding and is used to ingest the red blood cells of the host the orifice is spiny and its outer margin is well endowed with sense organs in this electron micrograph we can can see two blood cells inside the oral sucker here the well anchored pair seem to be traversed by continuous peristaltic waves which are probably associated with the rate of blood flow female schistosomes produce many hundreds of eggs a day and these are deposited into a venule of the intestinal wall where they become tightly lodged the egg shell is covered with hundreds of needlelike spines which abaid the tissue and enable the eggs to work their way across the bowel wall and through the Villi here are two eggs in tissue at the bases of the intestinal villi they're making their way towards and into the Lumen of the gut later they'll pass out of the body with the feces some eggs are inevitably swept back past the flukes and carried in the portal blood to the liver where they eventually provoke an immune reaction and become encapsulated in a granuloma these granulomas are clearly visible as white spots on the liver of an infected Mouse an egg is at the center of this mass of infiltrating lucaites mainly mononuclear cells and eosinophils these cells ultimately destroy many eggs they've already started to invade the shell of this one in severe chronic infections the liver becomes filled with granulomas and this leads to portal obstruction hypertension aites and massive enlargement of the liver and spleen compare the size of the organs in a normal mouse and a mouse harboring a chronic schistosome infection these features of pathology accurately mimic the clinical symptoms of the human disease schistosome eggs are easily detected in fecal smears they're about a sth of a millimeter long and are comparatively large as helminth eggs go The prominent lateral spine is the characteristic feature of chistosa manen the spine is terminal in hematobium and although lateral in japonicum the spine is very small the japonicum egg is much rounder and is therefore easily distinguished from the oval-shaped Egg of mansoni when PED in the feces each egg contains a fully formed midium whose surface is covered with hundreds of cyia the midium also possesses two pairs of flame cells which can be recognized by their flickering movement they form part of the simple excretory system and their activity shows that the organism is alive in fresh water the egg expands by osmosis and as its contents become diluted the midium is stimulated into activity the movements of its surface cyia set up currents in the liquid which appears to Bubble suddenly the shell is fractured and the midium half emerges together with fluid from the egg but the midium is still contained within the vitaline membrane which surrounded it in the egg and it has to struggle hard for a time before it finally manages to free itself then in a moment it's on its way in search of a particular species of snail the miridia are propelled by vibrating the thousands of minute hairlike cyia covering their elongated bodies this is a critical period for them they must find their particular species of snail within a few hours or they'll die the snail shown here is biom Feria gor from South America the miridia adhere to its exposed surfaces they burrow their way in by a combination of enzymic digestion and mechanical movement it takes about an hour for a midium to penetrate completely once this is accomplished the midium transforms to a primary sporocyst which migrates towards the liver of the snail and begins a process of a sexual multiplication in this way many secondary or daughter sporocysts develop independently and grow into long thin bodies that eventually become convoluted they give rise to Sakari that bud off in continuous sequence finally the liver tissue of the snail is almost completely replaced by sporocysts and free Sakari this is a secondary sporocyst which has been dissected out of the liver of an infected snail it contains mature Sakari which are struggling to get out they have developed in the sporocyst with their tails folded back along their bodies this one is struggling very vigorously to free itself remember we are watching Sakari with space around them if they were still inside the snail they would be tightly packed and their movements greatly restricted at about 4 weeks after infection the first Sakari emerge from the snail and they're soon escaping daily in swarms they're about half a millimeter long and are actively swimming organisms that travel through the water with characteristic movements usually tail first their life is short about 48 hours at most for they have no functional gut and their rapidly expended energy reserves cannot be replaced the sakaria has an elongated body region and a long forked tail it also has an oral and a ventral sucker by which it adheres to any substrate the external surface of the secaria is covered with spines that are back w l directed these help it to penetrate the skin of its next host since they ensure that the organism can only travel in a forward Direction each secaria has a secretory complex comprising three types of unicellular glands which open through the oral sucker this electron micrograph shows the folded gland openings the glands contain powerful proteolytic enzymes which help the secaria to digest Gest its way through the skin of the host here sari are penetrating the tail skin of a mouse they attach with their suckers digest and wriggle their way through the skin once the body is inside the tail drops off but remains active the parasite now called the schistosomulum is safely within its new host the sequence is now repeated in diagram a Saria attaches and makes a hole in the epidermis it deepens the aperture and enters it by elongating its body shedding its tail it migrates through the dir and fat layer where it turns seeking a blood vessel on finding one it enters and starts its Journey around the body of the host it's carried in the bloodstream first to the lungs by this time it's become longer and considerably more slender and lost its mid bodies spines although spines are retained at both ends the spines together with rhythmic activity enable it to migrate along the tiny lung capillaries which are often smaller in diameter than the lava itself the flukes leave the lungs through the pulmonary veins and pass via the left side of the heart to the liver the earliest migrants arrive in the liver 6 to 8 days after after infection they become short and squat begin to feed and their intestines fill with dark hematin pigment 2 to 3 week old juvenile flukes are now more recognizable as schistosomes but they have a convoluted system of folds and ridges on the surface by week four however these folds are less conspicuous and dome-shaped elevations appear on the dorsal surface of males they clearly represent early stages in the development of surface tubic male and female flukes pair at around week five and the male tubic take on their characteristic spiny appearance the paired flukes migrate through the portal vein to the mesenteric veins and egg laying begins that completes the life cycle of the schistosome we now have some observations on one of the most intriguing features of the life cycle the transition from free swimming sircaria to parasitic schistosomulum the sircaria has to adapt very rapidly to its move from fresh water to body fluid a temperature change of about 20° and a hostile environment the most dramatic changes take place at the outer surface of the secaria this is a diagrammatic section through a secaria the surface is spiny and totally covered by a typical three- layered membrane the outer layer is the glyco calx this is an electron micrograph of the three- layered membrane under the membrane is the tegument a citium with no cell walls its nuclei are located in deeper cell bodies joined to the tment by narrow Twisted connections these are layers of muscle cells this is how the section appears under the electron microscope when the Saria enters the tissues of its new host large numbers of membranous secretion granules are synthesized in the subtegumental cells and pass up into the tegument the bodies join together and then connect with the surface of the lava to liberate their membranes to the exterior the original trilaminate membrane and the glyco calx are cast off in a mass of microvilli this action not only serves to distract the host's immune system it also sensitizes the host against subsequent schistosome infection the parasite rapidly covers itself with a new seven layered membrane derived from the membranous bodies the lava further confuses the host by disguising its surface with proteins derived from the host's red blood cells at an early stage of infection it's also thought that the host produces a class of antibodies which attach to the invading parasites their function is rather puzzling in that they're not aggressive towards the parasite furthermore they serve to block the killing of the Parasite by other toxic antibodies later there's a switch so that the toxic antibodies predominate this could explain the finding that young children playing in infected water have no resistance to schistosomiasis and may become heavily infected but but as they get older they develop an effective immune response that kills newly invading parasites and thus limits the number of chisms they carry because man eventually develops this partial immunity concerted efforts are being made in many Research Laboratories to analyze the mechanisms responsible for killing the flukes and to characterize the parasite antigens against which the host's responses are directed present research gives hope that it will be possible to design and produce a vaccine for human use it would be an acceptable and desirable first step in Disease Control if the vaccine could reduce the debilitating pathology caused by schistosome eggs schistosomes like many other parasites have a variety of ways of avoiding the lethal effects of immunity shedding of microvilli using host protein as a disguise and the development of blocking antibodies these are but three of their many tricks a really successful vaccine will have to be several jumps ahead of these highly sophisticated evasive strategies until that time comes we must rely on improved standards of hygiene to break the life cycle of the parasite and drugs to reduce the infection but the problems of expense the need for repeated Drug Administration and the everpresent threat of drug resistance mean that researchers are working against the clock to develop an effective vaccination program