Introduction
Schistosomiasis, or bilharziasis, is a preventable parasitic disease found in tropical regions of developing countries that is caused by infection from five trematode species of blood-dwelling fluke worms called schistosomes. The term “bilharziasis” comes from the German pathologist, Theodor Biharz, who first identified the parasite in 1852. Schistosomiasis is typically a rural disease, but it has been found in urban areas. [1][2][3] Schistosomiasis is one of the most prevalent diseases in the world and is second only to malaria in terms of public health and socioeconomic importance. [4][5][6] Schistosomiasis is frequently neglected because it primarily impacts poor rural areas of developing countries. This neglect exacerbates the poverty levels of developing regions, especially sub-Saharan Africa and Asia. [3][7][8]
Adult schistosomes are white or grey worms that can grow from 7 to 20 mm in length. Schistosomes have separate sexes, which are unlike other trematodes. [1] On average, the lifespan of an adult schistosome is 3 to 5 years, but they can live for as long as 30 years. [9] Human infection occurs through direct contact with freshwater sources that are infested with cercariae, the free-living larval form of schistosomes. Freshwater is contaminated in poor rural areas with inadequate sanitation practices. The eggs of the parasite are excreted in the feces and urine of humans. Once in the water, the eggs release another form of the parasite called miracidium. The miracidium penetrate into their intermediate host, freshwater snails, and multiply into cercariae. The snails excrete the cercariae into the water where they can live up to 48 hours without a host. The cercariae find their definitive human host and penetrate the skin. After penetration, the cercariae lose their tails and become schistosomulae and travel through the blood stream and lungs to the liver. In the liver, the parasites sexually mature, pair off, and travel to the intestines or the bladder where they lay eggs. Female worms can lay from 200 to 2000 eggs per day, depending on the species. Although most eggs are excreted through the intestines, some become trapped in the tissues. The morbidity that is associated with schistosomiasis is caused by the presence of these trapped eggs in the intestines, bladder, or liver and not the worms themselves. [5]
Agricultural and recreational contact with freshwater, the building of dams and reservoirs, and the migration of refugees all contribute to the spread of the disease. For example, an intestinal form of schistosomiasis was introduced into Mauritania and Senegal when the Diama dam was built on the Senegal River, and the movement of refugees in the Horn of Africa introduced intestinal schistosomiasis to Somalia and Djibouti. [5]
There are five species of schistosomes that infect humans:
- Schistosoma mansoni infects Biomphalaria snails and causes intestinal and hepatic schistosomiasis. S. mansoni only infects humans and rodents and is found in most of sub-Saharan Africa, parts of Egypt, the Arabian Peninsula, parts of the Caribbean, Brazil, Suriname, and Venezuela.
- S. haematobium infects Bulinus snails, causes urinary schistosomiasis, and is found in the Arabian Peninsula, sub-Saharan Africa, including Madagascar and Mauritis, and the Nile valley of Egypt and Sudan.
- S. intercalatum infects Bulinus snails, causes intestinal schistosomiasis, and is found in central Africa. [1][2][5]
- S. japonicum infects amphibious Oncomelania snails and causes intestinal and hepatosplenic schistosomiasis in China, Indonesia, and the Philippines. S. japonicum is a zoonotic parasite, which means that it infects many different animals, more than 40 species, including cattle, dogs, pigs, and rodents; however, humans are the main host. This “persistent zoonotic reservoir” perpetuates the transmission of the parasite, making it more difficult to control. Domestic water buffaloes can contribute up to 90% of S. japonicum transmission. S. japonicum has the greatest risk for infection-related illness. [4][7]
- S. mekongi infects Neotricula snails and causes intestinal schistosomiasis. This parasite is found along the Mekong River in Cambodia and Laos.
Statistic
- Approximately 207 million people are currently infected with schistosomiasis, where of those infected 120 million display symptoms, 20 million suffer serious consequences. [3]
- Schistosomiasis is endemic in 74 countries and 650 million people currently live in endemic areas.
- 165 million people are infected in sub-Saharan Africa, nearly 112 million of those infected have urinary schistosomiasis and nearly 54 million have intestinal schistosomiasis. [10]
- Annually, approximately 280,000 deaths caused by schistosomiasis occur in sub-Saharan Africa. [11]
- Approximately 60 million people are at risk for the disease in China, 6 million in the Philippines, and 140,000 in Cambodia and Lao People’s Democratic Republic. [12]
Signs and Symptoms
The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.
Acute schistosomiasis, also called Katayama fever, resulted from a “hypersensitivity reaction against the migrating schistosomulae” within the body. This reaction can occur months after the initial infection. Symptoms occur suddenly and include fever, rash, myalgia, malaise, cough, eosinophila, and rash. Individuals with this mild form of schistosomiasis may later develop abdominal symptoms. Typically, individuals who have acute schistosomiasis recover within 2 to 10 weeks. Some individuals may develop a more serious infection that results in weight loss, dyspnea, diarrhea, abdominal pain, toxemia, hepatosplenomegaly, and rash. [9]
Schistosomiasis is a chronic inflammatory disease that has a lasting effect on the daily lives of those who are infected including anemia, malnutrition, and inability to perform at work or school. Children under the age of 14 represent a large proportion of those infected with the disease.3 The fibrotic organ damage and the continuous granulomatous inflammation caused by the lodged eggs of the parasite leads to many complications. [4]
S. haematobium eggs that remain lodged in the vesical and ureteral walls of the body cause granulomatous inflammation, ulceration, and pseudopolyposis. Symptoms of urinary schistosomiasis include blood in the urine, pain or difficulty when urinating, and frequent urination. Iron deficiency anemia can occur with blood loss associated with this form of the disease. Chronic infection can lead to fibrosis or calcification of the bladder and lower ureters, parenchymal damage, kidney failure, and bladder cancer.2,,9 The schistosome eggs that are lodged in the intestinal wall cause an immune response called a granulomatous reaction. This reaction can cause obstruction of the colon and blood loss. The eggs of the parasite can also lodge in the liver and cause high blood pressure, enlarged spleen, portal hypertension, and swollen esophagus or gastrointestinal tract, which can lead to tearing and bleeding. Intestinal schistosomiasis may also affect the central nervous system, although this is rare. [2]
Treatment Options
Conventional
Currently the World Health Organization (WHO) recommends morbidity control of schistosomiasis by utilizing preventative chemotherapy with praziquantel (PZQ). The WHO strategy is the mass drug administration of PZQ to all school-aged children once every 2 years in communities where schistosomiasis prevalence is more than 10% and once every year in communities with a prevalence of more than 50%. [13] PZQ is the only available treatment for all forms of the disease and has only a few transient side effects. PZQ is also inexpensive; the average treatment cost is $0.20 to $0.30. PZQ has been successfully used to control schistosomiasis in Brazil, Cambodia, China, Egypt, Morocco, and Saudi Arabia. Chemotherapy does not prevent relapse, but it does diminish or reverse severe organ damage. [3]
Although there is currently no definitive evidence of resistant strains of the disease, there are concerns that parasitic resistance will develop. [1] Because of the high re-infection rate of the disease and the concern of resistant strands developing, health officials are working towards the development of a vaccine. Organizations, such as the Egyptian-based Schistosomiasis Vaccine Development Programme, are attempting to create a vaccine using antigens from schistosomules and schistosomes; however, no effective human vaccine has been developed. Another method for the development of a vaccine involves reducing egg excretion by targeting the productivity of the female schistosome. Researchers have been successful with this method in animal reservoir hosts, such as mice, pigs, and water buffaloes. It is hoped that vaccination of the reservoir host might lead to the significant reduction of schistosomiasis in humans. [5]
There is current evidence that schistosomiasis may affect the transmission of HIV/AIDS. In particular, researchers have found that female genital schistosomiasis may cause susceptibility to HIV/AIDS infection. A cross-sectional study conducted in a Zimbabwean village showed that women aged 20 to 49 years who had female genital schistosomiasis had a threefold risk for developing HIV compared with women who did not have that form of the disease. Researchers believe that a potential AIDS-prevention strategy may develop if female genital schistosomiasis is prevented in young, at-risk girls by the administration of PZQ. [13]
The London-based Schistosomiasis Control Initiative (SCI) is an organization that offers technical and financial support to sub-Saharan African countries to control schistosomiasis and other diseases. Specifically, SCI worked with Burkina Faso, a land-locked country in Africa, to reduce the infection of urinary schistosomiasis by the biennial distribution of PZQ to school-aged children. In 2005, with the help of SCI, Burkina Faso became the first country to reach full national coverage by treating more than 90% of school-aged children with PZQ. Results from a longitudinal cohort study of this biennial treatment showed that a single round of PZQ treatment reduced the prevalence of S. haematobium by 87% and the “intensity of infection” by 92.8% (ie, 94.2 to 6.8 eggs/10 ml of urine). [10]
An integrated approach to reduce the burden of schistosomiasis by eliminating reinfection is recommended. Integrated control efforts include a combination of drug therapy, water management, snail control, and sewage control. With S. japonicum, the reduction of animal reservoir hosts is also needed. [4] This strategy worked for China with a reduction in schistosomiasis infection rates by 55% in humans and 50% in livestock after a 10-year World Bank Loan Project in the 1990s. The control program consisted of chemotherapy in humans and livestock, snail surveillance and control, community health education, disease monitoring, regular training for schistosomiasis-control workers, and operational research management. [14]
Nutritional Supplementation
Nutritional status and parasitic infections are intertwined where each exacerbating the progression of the other. Inadequate micronutrient intake in regions of the world where schistosomiasis is prevalent is both a risk factor for the disease and as a result the progression of the disease. [15] Micro-nutrient and antioxidant status in infected populations have been studied as causal and as a result of the progression of the disease. [16][17][18][19]
Vitamin A
Vitamin A belongs to a class of compounds called retinoids, which only occur in animal products. Retinoids with vitamin A activity occur in nature in three different forms: a) the alcohol, retinol, b) the aldehyde, retinal or retinaldehyde, and c) the acid, retinoic acid. Vitamin A requires fats as well as minerals in order to be properly absorbed from the digestive tract. Substantial amounts of vitamin A are stored in the liver, and therefore, it does not need to be supplied in the diet on a daily basis.
Vitamin A deficiency is a common finding in patients diagnosed with parasitic infections. However, a causal relationship with urinary schistosomiasis has not been identified. [20] Numerous studies have investigated the relationship between the infection and vitamin A status with conflicting results. One study identified that the schistosomiasis infection interferes with Vitamin A transport, possibly through its impact on zinc status. [21] Additional research has indicated that this relationship may be due to overall antioxidant status in the patient. [19]
Vitamin C
Vitamin C cures the world’s oldest known nutritional deficiency disease, scurvy. It was first isolated by Albert Szent-Gyorgyi in 1928 from pork adrenal glands and called hexuronic acid. In 1933, its chemical structure was established. It was successfully synthesized, and the name was changed to ascorbic acid.
Vitamin C is a water-soluble vitamin that is stored in many tissues throughout the body, with the adrenal glands containing the highest concentration.
Vitamin C is necessary for iron absorption and supplementation of ascorbic acid improves iron status in various types of anemia, as commonly condition associated with schistosomiasis. [22]
Iron
Iron plays a role in many biochemical pathways. The primary functions of iron involve oxygen transport within blood and muscle, electron transfer in relation to the cellular uptake of oxygen, and the conversion of blood sugar to energy. Iron is also a part of many enzymes that are involved with making new cells, amino acids, hormones, and neurotransmitters. Iron exists in various forms in the body: in functional forms (in hemoglobin and in enzymes) and in transport and storage forms (ferritin, transferrin, and hemosiderin).
Anemia is commonly associated with Schistosomiasis, making iron supplementation necessary to improve or stabilize iron status. [16] [23]
Zinc
Zinc is necessary for the functioning of over 300 different enzymes and, as such, it plays a vital role in an enormous number of biological processes. Zinc is widely distributed in microorganisms, plants, and animals. In humans, the highest concentrations of zinc are found in the liver, pancreas, kidneys, bone, and muscles. Zinc is highly concentrated in parts of the eye, prostate gland, sperm, skin, hair, and nails.
Low zinc status has been identified in subjects infected with this parasite. Zinc status also affects the absorption of other micronutrients and is responsible for the transport of Vitamin A. [21] [24]
Herbal Supplementation
Herbal therapies for treating Schistosomiasis vary by region, with each region utilizing the botanicals that are indigenous to that particular area. Various herbal therapies include a Traditional Chinese Medicine formula known as heluoshugan (or heluo shugan) which has been studied in animals as a remedy for liver fibrosis that is associated with this particular parasitic infection. [24] Other regional remedies include Echinops ellenbeckii and Echinops longisetus as used in Ethiopia; [25] Phytolacca dodecandra also used in Ethiopia; [26][27] Berkheya speciosa (Asteraceae), Euclea natalensis (Ebenaceae) and Trichilia emetica (Meliaceae) used in South Africa; [28] Abrus precatorius (Leguminosae), Pterocarpus angolensis (Leguminosae) and Ozoroa insignis (Anacardiaceae) from Zimbabwe; [29] stem and root extracts from Abrus precatorius (Fabaceae) and stem bark from Elephantorrhiza goetzei (Mimosaceae) also in Zimbabwe; [30] Cissus quadrangularis and Stylosanthes erecta in Mali; [31] Ferula assafoetida in Egypt. [32]
Myrrh
Found in areas such as Ethiopia and Somalia, [33] myrrh can be traced back to the Arabian Peninsula. It has been associated with countries such as Yemen, Oman, and Egypt. [34] The myrrh shrub is very spiny and reaches upwards to 4 meters. The bark is whitish, silver or blue-grey. This bark peels, and reveals the green under bark which contains the resin. This resin is hard, translucent and yellowish in color. [35]
Studies have been published on a proprietary product produced in Egypt that has been shown to be protective against schistosomes. [36][37] Other research efforts have indicated that Myrrh in general has an inhibitory effect on the parasite and is safe to use in most individuals. [37][38]
Evodia
Evodia has been the subject of studies to identify the chemical constituents produced by the plant that exhibit anti-parasitic activity. [39]
Clinical Notes
Urinary schistosomiasis is commonly diagnosed microscopically with a filtration method that uses filter paper or polycarbonate or nylon filters. Chemical reagent strips may also be used to detect blood in the urine. Intestinal schistosomiasis can be diagnosed by microscopically detecting the eggs in fecal specimens with a method that uses cellophane soaked in glycerin. [3] The fecal thick smear or the Kato-Katz method may be used in the field. [9]
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