Pediatric Schistosomiasis

Pediatric schistosomiasis is principally caused by one of the following 6 species of parasitic worms:

• Schistosoma haematobium

• Schistosoma intercalatum

• Schistosoma japonicum

• Schistosoma malayensis

• Schistosoma mansoni

• Schistosoma mekongi

Other species of animal schistosomes cause human infection, including schistosomes of birds and small mammals that cannot mature in the human host but die in the skin where they cause dermatitis.

Schistosomes are blood flukes and belong to the class Trematoda. Unlike other trematodes, schistosomes are elongated but become round as they adapt to residing in blood vessels of the genitourinary or gastrointestinal (GI) tract. They require a vertebrate and an intermediate water-dwelling snail host to complete their life cycle. Geographic distribution and maintenance of human infection by schistosomes depends on and is limited by the presence of a suitable snail host.

Clinical features of human schistosomiasis depend on the species, developmental stage, and site of infection in the body. Schistosomiasis comprises the following 3 major syndromes:

• Cercarial dermatitis

• Acute schistosomiasis or Katayama fever

• Chronic fibro-obstructive disease

Schistosomes are digenetic, which means that mature adult worms reproduce sexually in the definitive human host with asexual reproduction in the larval forms (common to all trematodes or flukes). They are also diecious, which means that adults are sexually distinct and that male and female genitals do not occur within the same individual (a characteristic that separates them from other flukes).

Life cycle of human schistosomes

The life cycle of schistosomes differs from that of other trematodes in that humans become infected through penetration of the skin by cercariae rather than through oral ingestion. Human schistosomes can infect other vertebrates and provide an animal reservoir of infection, though this is of epidemiologic significance only for S japonicum and, possibly, S mekongi. Snails of the genera Biomphalaria, Bulinus, Neotricula, and Oncomelania are the principal intermediate hosts for S mansoni, S haematobium, S mekongi, and S japonicum, respectively.

Once cercariae have entered the human body through the skin, they are referred to as schistosomula. These organisms migrate through the tissues to invade blood vessels. They are transported to the lungs and then to the liver, where they mature into adult worms within 6 weeks before descending to their final positions in the venous circulation.

Adult S haematobium organisms are mostly found in the venous plexuses of the bladder, prostate, and uterus, whereas adult S intercalatum, S japonicum, S mansoni, and S mekongi organisms are observed in the portal, inferior, and superior mesenteric veins. The maturity of female worms depends on the presence of a mature male because the 2 worms are paired, with the female lying enclosed within a groove formed by the male.

Adult worms have a mean life span of 5-10 years, with females releasing 300-3000 eggs per day. Eggs are deposited in the terminal venules of the bladder (S haematobium), intestine, and rectum (S intercalatum, S japonicum, S mansoni, and S mekongi), where they mature over the next 10 days into a larval form known as a miracidium. The miracidium releases proteolytic enzymes, which facilitate larval movement through the tissues into either the genitourinary tract or the GI tract.

Schistosome eggs contain spines in various positions, depending on the species (see the images below). Eggs are passed in human urine and excrement, and motile miracidia are released upon contact with fresh water. Miracidia then actively seek out snail hosts, in which they develop first into mother and daughter sporocysts by asexual division and then into cercariae over 4-6 weeks. Cercariae then leave the snail and penetrate the human skin on contact, with the assistance of their glandular secretions.

Immune response and granuloma formation

Not all schistosome eggs are excreted from the body. As many as 50% can embolize to other body areas, leading to a host immune reaction and granuloma formation (see the images below). Granulomas begin to form with maturation of the miracidium at 6 days and are focal within 2 weeks. The most common sites are the liver for S intercalatum, S japonicum, and S mansoni and the bladder for S haematobium. Other areas less commonly affected include the lungs, central nervous system (CNS), and kidneys.

The immune response to schistosomiasis is highly regulated and of the delayed hypersensitivity type, including type 1 (Th1) and type 2 (Th2) helper T cell responses with local cytokine production. Granulomata are notable for the presence of eosinophils and lead to the development of widespread collagen deposition and scar tissue. This causes major lesions of chronic schistosomiasis with blood flow obstruction in affected tissues.

Human skin appears to be a critical site where the initial events of the host and parasite interaction occur and where the immune response is commenced. Induction and modulation of granuloma formation is under the control of clones of CD4 and CD8 T cells. Cytokines produced in response to the parasite, such as interleukin (IL)–7 in the skin and interferon-gamma (IFN-γ) in the liver, also seem to influence the development of schistosomal immunity.

The diagnosis of schistosomiasis should be considered in any individuals who have resided in endemic areas with significant freshwater contact.

S mekongi is thought to be the principal human schistosome pathogen of Cambodia and Laos. It has smaller eggs than S japonicum does, as well as a different intermediate snail host (Neotricula aperta). Hepatosplenomegaly, portal hypertension, or both are the main clinical findings in infected individuals.

S intercalatum (localized to West and Central Africa) is of less epidemiologic importance in these regions than S haematobium and S mansoni are. Observed symptoms include abdominal pain and bloody diarrhea.

Cercarial dermatitis is more commonly observed in human infection with avian schistosomes, cercarial demise, and immediate hypersensitivity reactions occurring at skin invasion sites.

Katayama fever occurs with the onset of egg production. The syndrome includes lymphadenopathy and diarrhea, with symptoms and signs similar to those of a serum sickness reaction. Katayama fever is commonly associated with S japonicum infection and is probably due to the larger number of eggs released by this species. It is less common with S mansoni infestation and is rare with S haematobium. Onset of symptoms is 20-40 days after exposure, and temperatures may reach 105°F. Fevers spontaneously subside 2-10 weeks after onset.

During infection by S haematobium, eggs are deposited in the mucosa and submucosa of the bladder and lower ureters. Granulomas are highly cellular and form intraluminal polyploidal lesions that can lead to hydronephrosis. Lesions tend to necrotize, ulcerate, and bleed.

With age, the lesions become acellular, fibrose, and calcify and are termed sandy patches. Calcification may lead to bladder deformation, ureteric obstruction, secondary infections, hydronephrosis, chronic pyelonephritis, and renal failure. Carcinoma of the bladder is a long-term sequela of chronic infection.

In acute schistosomiasis, the enlarged liver and spleen are initially soft as a result of passive venous congestion and granuloma cellular proliferation. In chronic disease, the liver and spleen remain large, nodular, and nontender. Stigmata of liver disease and cirrhosis (eg, ascites, spider nevi, peripheral edema, testicular atrophy, and feminization) are usually absent. However, a small number of patients decompensate and show the above signs of chronic liver disease.

Focal epilepsy is secondary to a localized brain granuloma or generalized encephalopathy. It constitutes 3% of the complications of chronic disease. In transverse myelitis, spinal cord lesions are the result of the retrograde flow of eggs and granuloma formation in either S mansoni or S haematobium infection.

Pulmonary involvement (ie, cor pulmonale) is most commonly observed with S haematobium infection because ectopic egg deposition can occur more readily from the vesical plexus to the lungs via the inferior vena cava, bypassing the liver. Pulmonary complications with S japonicum and S mansoni are usually observed only after the development of collateral circulation secondary to severe hepatosplenic disease. ^[1]

United States statistics

The prevalence of schistosomiasis in the United States has been estimated to exceed 400,000 persons, principally as a consequence of immigration from endemic areas. Transmission of the disease cannot occur in the United States, because of the lack of suitable snail hosts. Epidemics of acute schistosomiasis have been reported in Americans traveling in or returning from endemic areas. ^[2] Cercarial dermatitis due to avian schistosomes has been reported in the Great Lakes region of the United States.

International statistics

Worldwide, human schistosomes currently infect more than 200 million people in 74 countries, including the endemic areas of Africa, the Caribbean, Central America, South America, East Asia, and the Middle East. ^{[3, 4]} The prevalence of schistosomiasis is thought to be increasing. A meta-analysis found that more than 4 million school-aged children in Zambia have schistosomiasis. The disease primarily affects those living in rural communities, owing to unsafe water and inadequate sanitation facilities. ^[5]

The most severely affected countries in Africa include Angola, Chad, Congo, Egypt, Ghana, Kenya, Madagascar, Malawi, Mali, Mozambique, Nigeria, Senegal, Sudan, Tanzania, Uganda, Zambia, and Zimbabwe. Yemen has the most infected people in the Middle East. Brazil is the most severely affected country in the Americas, with 25 million people living in endemic areas and an estimated 3 million infected.

S mansoni is found in 54 countries, including the Arabian Peninsula (especially Yemen), Egypt, Libya, Mauritania, Somalia, Sudan, sub-Saharan Africa, Brazil, the Caribbean (except Antigua, Guadeloupe, Martinique, Montserrat, and St. Lucia), Suriname, and Venezuela.

S haematobium is endemic in 53 countries in the Middle East and most of the African continent, including the islands of Madagascar and Mauritius. The infection is unlikely to be of public health significance in Lebanon, Mauritius, Oman, Syria, Tunisia, and Turkey, because transmission is low or nonexistent. A disputed and ill-defined focus is noted in India and requires further confirmation.

S japonicum is endemic in China, the Sulawesi province of Indonesia, and the Philippines. China is the most severely affected country, with an estimated 900,000 people infected. The parasite has been eradicated from Japan since 1982.

S intercalatum has been reported in 10 countries in central and western Africa. S mekongi is confined to Cambodia and Laos, where the borders run along the Mekong River. Neotricula snails have been reported in southern China, but S mekongi has not been reported in these areas. S malayensis has been reported among aboriginal people in a small jungle focus in Malaysia.

Age-related demographics

People of all ages are susceptible. Immune responses are heightened and more intense with secondary and subsequent exposures to schistosome cercariae. Surveys in endemic areas have demonstrated that severity and prevalence of infection takes several years to peak in children and that both decrease with age.

Most manifestations of disease occur in the second decade of life, apparently related to peak egg output. Evidence points to a partial and acquired immunity to schistosomes that is determined by specific antibodies and eosinophils, and the immunity targets immature adult worms.

Sex-related demographics

The 2 sexes are equally susceptible to schistosomiasis. Because of different local and cultural work and social practices, either sex may be more exposed to infection.

Cure rates for oral medical treatment range from 70-100%, depending on the drug used. Mortality from human schistosomiasis is related to complications of fibro-occlusive disease (secondary to the immune stimulus of schistosome eggs) and end-organ damage.

The morbidity of schistosomiasis correlates well with the worm burden as calculated by fecal and urinary egg counts. The disease significantly disrupts the nutritional status and growth from middle childhood to adolescence. Prevalence of infection in endemic communities demonstrates a negative binomial distribution, with most infected individuals having low worm burdens and only a small percentage with heavy infestations.

A possible genetic link has been observed between human leukocyte antigen (HLA) antigens and the occurrence of end-stage liver disease in S japonicum and S mansoni infections.