Parasitology Course BIOL 2272 Part 3

1. Parasitology Course BIOL 2272Part 3 By Fred Opperdoes

2. Schistosomiasis • Schistosomiasis is also known as bilharzia after Theodor Bilharz, a German pathologist, who first identified the parasite in Egypt in 1851. Infection is widespread with a relatively low mortality rate, but a high morbidity rate, causing severe debilitating illness in millions of people. The disease is often associated with water resource development projects, such as • dams and irrigation schemes, • fresh water reservoirs, • artificial lakes, • cultivation of rice, • where the snail intermediate hosts of the parasite breed. 

3. Global status • People at risk: 600 million • Number Infected: > 200 million • Symptomatic patients: 120 million • Severely infected: 20 million • Deaths: 14,000 annually • Disease burden: 1.93 million Disability Adjusted Life Years (DALY)

4. Distribution Responsible organismsRegions Schistosoma haematobium Africa, East Mediterranean Schistosoma mansoni Africa, South America Schistosoma japonicum Asia • 600 million people are exposed to the risks of schistosomiasis of whom 200 million are infected. Schistosomiasis is after malaria the most important parasitic disease of mankind. Endemic in 74 developing countries with more than 80% of infected people living in sub-Saharan Africa (courtesy WHO/TDR).

5. Causative agent • Trematode flatworms (flukes) of the genus Schistosoma. • S. haematobium is the most prevalent and widespread species in Africa and the Middle East • S. intercalatum occurs in 10 countries in the rainforest belt of Africa • S. mansoni is found in Africa and is the only species seen in Latin America • S. japonicum is restricted to the Pacific region including China and the Philippines • S. mekongi is found in limited areas of Laos and Cambodia. Adult male and female Schistosoma haematobium (courtesy WHO/TDR) • S. mansoni adult female worms have a very long longevity of between 10 and 30 years • male worms are 10-15 mm long and 1 mm large • female worms are 15-18 mm long and less than 1 mm large

6. Life cycle • Cercaria (500 per year per snail) • Sporocysts (several per miracidium) • Miracidium in water • Schistosomula • Adult worms in: • blood vessel around rectum (mansoni) • bladder (haematobium) • mesenteric veins and pulmonary arteries (japonicum) • Egg production (10-30 per day)

7. Transmission  • Occurs in freshwater when intermediate snail hosts release infective forms of the parasite. People are infected by contact with water where infected snails live.Intermediate hosts are molluscsschistosome • Bullinus globususS. haematobium • Bullinus truncatus • Biomphalaria pfeifferiS. mansoni • Biomphalaria glabratta • Larval forms of the parasites (known as cercariae), released by the snails, penetrate the skin of people in the water. The snails themselves become infected by another larval stage of the parasite, known as a miracidium, which develops from eggs passed out in the urine or faeces of infected people. Bulinus globosus, the intermediate host snail for Schistosoma haematobium (courtesy WHO/TDR)

8. Symptoms • Adult male and female schistosomes pair and live together in human blood vessels. The females release eggs, some of which are passed out in the urine (in S. haematobium infection) or stools (S. mansoni, S. japonicum), but some eggs are trapped in body tissues. Immune reactions to eggs lodged in tissues are the cause of disease.  Adult male and female schistosome worms (courtesy WHO/TDR) Calcified eggs in the tissues Calcified eggs in the tissuesHepato-splenomegaly in S. mansoni schistosomiasis (courtesy WHO/TDR) Formation of granulomas

9. Types of disease • S. haematobium (urogenital)In urinary schistosomiasis damage to the urinary tract is revealed by blood and schistosome eggs in the urine. Eggs which get stuck in the tissues may calcify and lead to the formation of granulomas and superinfections. Urination becomes painful and is accompanied by progressive damage to the bladder, ureters and then the kidneys. Bladder cancer is common in advanced cases.   Schistosoma haematobium:eggs (Differential Interference Contrast microscopy) Macrohematuria: A sample of normal urine and blood-containing urine from a child suffering from urinary schistosomiasis.

10. Types of disease (2) • In intestinal schistosomiasis (infection with S. mansoni, S. japonicum, S. mekongi) disease is slower to develop. There is progressive enlargement of the liver and spleen, intestinal damage due to fibrotic lesions around eggs lodged in these tissues, and hypertension of the abdominal blood vessels. Bleeding from these vessels leads to blood in stools, and can be fatal. Sufferers become seriously weakened by the disease and, in some cases, the functioning of organs such as spleen and kidneys becomes impaired. • Death is mostly due to bladder cancer associated with urinary schistosomiasis and to bleeding from varicose veins in the oesopahagus associated with intestinal schistosomiasis. Children are especially vulnerable to infection, which develops into chronic disease if not treated.  

11. Diagnosis • Diagnosis using urine filtration and faecal smear techniques: • Haematobium search for eggs in urine • Mansoni search for eggs in stool • Antigen detection in endemic areas • Antibody tests in non-endemic areas Urine is collected in empty beer bottles for further analysis (courtesy WHO/TDR) Schistosoma eggs in the stool

12. Drug treatment • Drug treatment is the only way to reduce disease symptoms and improve the situation of the patients. Drugs available are: • praziquantel: effective in a single dose against all species • oxamniquine: effective in a single dose, but only against S. mansoni

13. Snail control through focal mollusciciding China, Jiangsu province: Molluscicide (niclosamide) to kill intermediate host snails (Oncomelania) involved in the transmission of Schistosoma japonicum, being sprayed over riverbank and flood-prone land using a high-pressure hose (courtesy WHO/TDR). An irrigation canal can create ideal habitats for the freshwater snails that are intermediate hosts of schistosomes (courtesy WHO/TDR).

14. Other measures of prophylaxis • Health education 

15. Provision of safe, adequate water supply and sanitation A scoop being used to collect freshwater snails which are intermediate hosts in the schistosomiasis cycle A researcher using a scoop to search for freshwater snails which are intermediate hosts in the schistosomiasis cycle.

16. Onchocerciasis • Onchocerciasis is the world's second leading infectious cause of blindness. • Rarely life-threatening, the disease causes chronic suffering and severe disability. • In Africa, it constitutes a serious obstacle to socio-economic development. • It is often called river blindness because of its most extreme manifestation and because the blackflies that transmit the disease abound in riverside areas, where they breed in fast-flowing waters. • Fertile riverine areas are frequently abandoned for fear of the disease. • 78 millon people are estimated to be at risk • 300 000 people are blind The blackfly, Simulium damnosum, the vector of Onchocerca volvulus, the parasite which causes onchocerciasis (river blindness). Fast-flowing water, a typical breeding site for larvae of the blackfly

17. Distribution • 35 countries in total. • 28 in tropical Africa, where 99% of infected people live. • Isolated foci in Latin America (6 countries) and • Yemen.

18. Causative agent • A parasitic worm, Onchocerca volvulus, of the family filariidae, which lives in the human body for up to 14 years. Onchocerca volvolus is a helminthic worm • male: 2-3 cm long • female: 60 cm long • Adults occur in the subcutaneous tissues and in nodules • microfilariae: 300 x 8 micrometer, 1000-3000 produced per day per adult female worm • Adult worms have a longevity of 10-15 years Onchocerca volvulus (adult worms)

19. The vector and transmission of the disease • The vector is Simulium damnosum or blackfly. • Blackflies deposit their eggs in the highly oxygenated water of rivers where also larvae develop. • The young flies feed on the blood of humans and pick up the microfilariae from infected people. • The development in the fly takes about 7 days and occurs in the fly's proboscis. • When the fly feeds again the larvae are transmitted. • Man is the only definitive host of this parasite.

20. The disease • Each adult female worm produces millions of microscopic larvae (microfilariae) (1000-3000 per day), that migrate throughout the body to cause a variety of symptoms. • SymptomsAdult worms lodge in nodules under the skin, releasing large numbers of microfilariae into surrounding tissues. Immature worms move through the body and after dying, cause a variety of conditions including: • serious visual impairment and blindness, • skin rashes, • lesions, • intense itching and depigmentation of the skin, • lymphadenitis (resulting in hanging groins and elephantiasis of the genitals) and • general debilitation.

21. The disease (2)

22. Diagnosis • Search for the presence of microfilaria in blood urine and eyes • Search for adult worms (macrofilaria) examination of a young Yanomami indian child

23. Prevention and control

24. Drug treatment • Drugs: • Diethylcarbamazine (DEC) only kills microfilaria • Ivermectin (150 microgram/kg single dose) only kills microfilaria • Suramin only kills macrofilaria • The development of ivermectin in the 1980s provided a safe, effective drug for killing microfilariae in infected people. A single dose of the drug (being supplied free by the manufacturer, Merck & Co. Inc.) needs to be taken annually. Masindi district: A Community-directed distributor (CDD) dispensing ivermectin tablets to a young girl during a central point distribution in her village

25. Onchocerciasis Control Programme (OCP) • Vector control: has proved successful in certain areas. • Temephos as larvicide is effective but resistance develops • Applying insecticides via aerial spraying over breeding sites in fast-flowing rivers. • Following interruption of transmission, the reservoir of adult worms dies out in humans after 14 years. • To complement vector control activities, OCP also distributes ivermectin. • OCP, a major control initiative • Launched in 1974 in an area encompassing originally 7 countries in West Africa. • In 1986, the programme was extended to include a further 4 countries, • A total operational area of 1.23 million sq. km, • A combined human population of 30 million. • Jointly sponsored by the • WHO, • World Bank, • UNDP, • FAO, • And a coalition of 20 donor countries and agencies, • Scheduled to come to an end by 2002.

26. Wolbachia and onchocerciasis • Wolbachia bacteria are endosymbionts of Onchcerca • Wolbachia are killed by antibiotics • Antibiotics interfere with the life cycle of Onchcerca • Wolbachi protein extracts seem to be responsible for keratitis • Antibiotic treatment leads to cure Wolbachia (red) thrive in the filarial worms responsible for river blindness

27. Lymphatic filariasis • Rarely life-threatening, lymphatic filariasis causes widespread and chronic suffering, disability, and social stigma. It can lead to grotesquely swollen limbs - a condition known as elephantiasis.

28. Distribution • Endemic in over 80 countries in Africa, Asia, South and Central America and the Pacific Islands. More than 40% of all infected people live in India and one-third live in Africa. • W. bancrofti • China • Japan • Vietnam • India • Malaysia • B. malaya • India • China • Korea • Malaysia • Indonesia • Philippines

29. Causative agent • Parasitic nematode worms of the family filariidae. • Three species are of significance, • ParasiteDefinitive host • Wuchereria bancrofti Man only • Brugia malayi Man and animals • Brugia timori. Man and animals • Adult worms (Macrofilaria) 4-10 cm long, longevity 10-15 years • Microfilaria 300 micometers • Macrofilaria are present in the lymphe fluids • They give rise to a constant production of microfilaria • Adaptation to the intermediate host has led to the nocturnal appearance of of microfilaria in the blood (microfilaraemia)

30. Transmission • Via the bite of blood-feeding female mosquitoes which transmit immature larval forms of the parasitic worms from human to human. • Vectors: mosquitoes • Anopheles • Culex • Aedes • Mansonia • Only the female mosquitoes are haemotophgous and bite only at night • In humans, adult worms can live for many years, producing large numbers of larval forms (known as microfilariae) which circulate in the lymphatics and blood where they can be ingested by blood-feeding mosquitoes, so completing the transmission cycle. W. bancrofti parasites are mainly transmitted by Culex quinquefasciatus mosquitoes and some species of Anopheles. Brugia parasites are mainly transmitted by Mansonia mosquitoes.

31. Diagnosis • The disease can be diagnosed by the identification of microfilaria in a blood sample that has preferably taken at night.

32. Symptoms • Infective larvae develop into adult worms (known as macrofilariae) in the afferent lymphatic vessels, causing severe distortion of the lymphatic system. Adult Wuchereria are often lodged in the lymphatics of the spermatic cord, causing scrotal damage and swelling. Elephantiasis - painful, disfiguring swelling of the limbs - is a classic sign of late-stage disease. • There are three basic disease stages: • 1. Asymptomatic: patients have hidden damage to the lymphatic system and kidneys. • 2. Acute: attacks of 'filarial fever' (pain and inflammation of lymph nodes and ducts, often accompanied by fever, nausea and vomiting) increase with severity of chronic disease. • 3. Chronic: may cause elephantiasis and hydrocoele (swelling of the scrotum) in males or enlarged breasts in females. The foot of an elderly man who had to give up his job due to to his elephantiasis

33. Prevention and control • The global elimination strategy has two major components: • Mass administration of drugs to 'at-risk' populations with once-a-year, one-day treatment (to interrupt transmission) • Promotion of rigorous, simple hygiene techniques for lymphoedema (to alleviate and prevent suffering of affected individuals). • Interruption of transmission by the use of insecticides • Lymphatic filariasis used to be treated with a 12-day treatment regimen using the drug diethylcarbamazine (DEC), but recent work has shown that a single dose of DEC is equally effective. Ivermectin has also been registered for treatment of filariasis, and albendazole was shown to have additional antifilarial effects.  • Transmission can also be reduced by avoiding mosquito bites in endemic areas , e.g. through use of • repellents, • bednets, • insecticides. • Mosquito vectors often breed in polluted urban waters (such as blocked drains and sewers) so good sanitation and environmental management to minimize mosquito breeding places can play a major role in reducing the risk of the disease.

34. Chemotherapy • The treatment strategy is now based on annual, single-dose, 2-drug regimens of • ivermectin+albendazole in countries that are co-endemic for onchocerciasis, and of • DEC+albendazole in all other countries.  • A health worker dispensing DEC tablets at a local distribution point. Mass distribution of DEC tablets is being used to help control Bancroftian filariasis in favelas around Recife.