Discussion
Schistosomiasis is an infectious disease caused by blood flukes, also known as trematodes. More than 230 million people are estimated to be infected, although the true figure is probably much higher (1) . In humans, schistosomes exist as 1 – 2 cm long worm-like parasites in perivascular locations within the venous system or in the mesentery, but may also be found elsewhere. Male and female flukes live paired together and can move within the vascular tree. The flukes can live for up to 40 years, but their normal lifespan does not exceed 3 – 10 years (1) .
Each pair lays thousands of eggs that are excreted via the urinary bladder or the intestines. Eggs can remain lodged in tissue and cause significant problems for the infected host. The tissue may react against the eggs, with a subsequent humoral and cell-mediated response generating granulomas many times larger than the egg itself.
The prevalence of schistosomiasis is highest in sub-Saharan Africa. The disease also occurs in South America and Asia, and a total of five different species cause disease in humans (1) .
Fresh water is essential for the parasite to complete its life cycle. The eggs are excreted into the water via the host’s urine or faeces. Once there, the parasite continues its development using a snail as an intermediate host, and releases a cercaria which can infect humans upon contact with the skin. The cercaria penetrates the skin and moves by passive intravascular migration via the lungs to the liver. After 1 – 3 months, the parasite will have developed into an adult fluke. Male and female flukes form a pair and move to the species’ preferred final niche (Fig. 2). For Schistosoma mansoni and Schistosoma japonicum , this is the inferior mesenteric veins and colon, whereas Schistosoma haematiobium makes its way to veins surrounding the urinary bladder. The flukes can also move to other organs, however.
Figure 2 The life cycle of the Schistosoma parasite
Ectopic flukes are most often found in the central nervous system, in the perivertebral venous plexus or cortical cerebral veins. Egg deposition in the central nervous system may trigger a cell-mediated periocular granulomatous reaction, leading to neurological complications. The mass effect of tens of thousands of eggs plus the large granulomas in the brain or spinal cord can account for symptoms such as increased intracranial pressure, myelopathy, radiculopathy and subsequent sequelae. Myelopathy in the lumbosacral region is the most common complication of S. mansoni and S. haematobium infection, whereas acute encephalitis in the cortex, subcortical white matter, basal ganglia or internal capsule is typical for S. japonicum (2, 3) .
Neurological complications have been described in numerous case reports with small numbers of patients. The majority describe patients from endemic regions, but there is also a report of a tourist who developed symptoms four years after bathing in fresh water while travelling in West Africa (4) .
Neuroschistosomiasis is a consequence of central nervous system involvement in schistosome infection and requires prompt treatment if symptoms emerge. Complete remission of symptoms after treatment has been described in several case reports (5) – (7) . There are three main forms of the condition. One is acute schistosomal encephalopathy, for which the direct aetiology remains unknown. Headache, altered sensation, seizures, ataxia and cerebellar symptoms are seen most frequently (2) .
A granulomatous reaction in brain tissue may give rise to a pseudotumour leading to increased intracranial pressure. Headache, visual disturbances, seizures and altered mental status are the main symptoms.
A granulomatous reaction in the spinal cord is the earliest described and best known form of neuroschistosomiasis. Patients often have no other symptoms, but symptoms in such cases may also vary greatly. Back pain is often the first symptom with radiating pain in the lower extremities. Others may present with weakness of the lower extremity muscles, bowel and urinary bladder dysfunction, paraesthesia, impotence in men and altered reflexes in the lower extremities (2) .
Direct diagnostic methods, which aim to detect living eggs, are the only way to unequivocally confirm an ongoing schistosomiasis infection. The various Schistosoma species that have been identified have different eggs. Microscopy of normal and filtered urine is used in areas where schistosomiasis is widespread. Direct microscopy of stools has insufficient sensitivity, although this can be increased via special concentration techniques. The presence of eggs in a biopsy can also confirm the diagnosis (1) .
There are a number of immunological tests that detect circulating anti-schistosomal antibodies. However, these reveal nothing about the degree of infection, do not differentiate between previous and current infection, and are not species-specific. The cost of these tests and a lack of technology means that they are not available to the most relevant patients in countries with the highest disease burden. These tests are not performed in Norway either; samples are sent to a laboratory in Sweden. The Public Health Agency of Sweden conducts tests using immunofluorescence against gut-associated antigen (GAA) and somatic antigen (SA). If at least one of these two is positive, ELISA is used to test for soluble egg antigen (SEA). Gut-associated antigen comes from the parasite’s gut and is regurgitated by the fluke after it has digested a blood meal. It is typically the first test to show a positive result after infection, and may be positive even before eggs can be detected in the urine or faeces. Soluble egg antigen, as the name suggests, shows positive only once egg production has started. Somatic antigen is a bodily antigen from the fluke itself and is typically seen in chronic infections where some flukes have begun to die, or following treatment (senior consultant Tore Lier, personal communication).
Assessment of schistosomiasis infection in hepatosplenic and urogenital organs can be performed using ultrasound, CT and MRI. Ultrasound can be used at the bedside and in the field and requires significantly less financial investment than the other modalities (8) . CT scanning is particularly good for showing calcification of the urinary tract, which is typical of urogenital schistosomiasis (9) . For ectopic infection with cerebral involvement or myeloradiculopathy, MRI is the optimal method. However, this modality is rarely available among the populations that are most at risk. In cases of neuroschistosomiasis, the distal medulla/conus is most frequently affected. On T2-weighted sequences, heterogeneous hyperintensities are seen along with expansion of the medulla, often over several segments. The presence of eggs and consequent granuloma formation may result in nodular contrast enhancement in the medulla and peripheral enhancement in the leptomeninges. In a number of cases there is also involvement of nerve roots and the cauda equina (10) – (12) .
Treatment is directed chiefly at eliminating the flukes. Treatment of immunopathological complications caused by the eggs may also be appropriate.
Praziquantel in a single dose of 40 mg/kg is sufficient for all Schistosoma species. No serious side effects have been reported.
In cases of neuroschistosomiasis, treatment with praziquantel may lead to exacerbation of the immunological response. Treatment with steroids is therefore recommended before the elimination of flukes.
Our patient had spent at least 11 years in countries free of schistosomiasis prior to being hospitalised. That flukes can survive for many years in the human body highlights the need to keep imported diseases in mind, even for persons who have been in Norway for a long time. Myelopathy due to schistosomiasis has been described in one patient 22 years after they were last exposed to infected water (13) .
Myeloradiculopathy caused by schistosomiasis is a serious and under-recognised complication (6) . The prevalence of this condition in centres in Brazil and Africa that handle cases of non-traumatic myelopathy is estimated to be 1 – 5 % (2, 14) .
Cerebrospinal fluid analysis shows increased protein concentration and mononuclear cell count in 90 % of patients with such myeloradiculopathy (14) , and this was also true for our patient. MRI-based diagnosis has proven particularly valuable for this patient population and led to the correct diagnosis in our case too.
Upon examination one year post-treatment, the MRI findings in the spinal canal had completely resolved. This shows that treatment is still effective, even long after the time of infection. This observation is important because very few persons with neuroschistosomiasis are examined using MRI.