Immune response and pathogenesis of neuroschistosomiasis mansoni

The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosome infection. Considering the symptomatic form, Schistosoma mansoni causes almost always spinal cord disease. Cerebral and spinal cord disorders in S. mansoni infections are inflammatory conditions of the CNS that cause mild-moderate impairment of the blood-brain barrier and intrathecal synthesis of antibodies against schistosomal antigens. Little is known about the pathogenesis of NS, but available evidence strongly suggests that it depends basically on the presence of parasite eggs in the nervous tissue and on the host's immune response against the trapped eggs. Numerous eggs surrounded by granulomas lodged together in circumscribed areas of the CNS damage the nervous tissue by both the mass effect and the egg-induced inflammatory reaction. Vasculitis of immune etiology, which causes isquemic lesions, may also play an important role in the genesis of the neurological symptoms. Although the mechanisms involved in the immunophatogenesis of NS are largely unknown, initial investigations on cerebrospinal fluid (CSF) and serum cytokine profiles suggest the occurrence of inflammation as well as a skewed Th2 immune response that probably occur both locally and systemically.     

Clinical characterization of neuroschistosomiasis due to Schistosoma mansoni and its treatment

The involvement of the central nervous system (CNS) by Schistosoma mansoni may or may not cause clinical manifestations. When symptomatic, neuroschistosomiasis mansoni (NSM) is one of the most severe presentations of this infection. The neurological manifestations are due to numerous granulomas grouped in confined areas of the spinal cord or the brain. Considering the symptomatic form, myelopathy is far more frequent than the cerebral disease. Spinal cord NSM presents as a low cord syndrome of acute/subacute progression usually associated with involvement of the cauda esquina roots. Lower limbs pain, weakness and sensory disturbance, and autonomic dysfunctions, particularly bladder dysfunction, are often present. Cerebrospinal fluid (CSF) examination generally shows an inflammatory pattern with or without eosinophils and/or IgG against schistosomal antigens. Magnetic resonance imaging (MRI) demonstrates signs of inflammatory myelopathy. Cerebral NSM presents as a slow-expanding intracranial tumor-like lesion. Its clinical manifestations are variable and depend on the increased intracranial pressure and on the site of the lesion. The diagnosis of spinal cord NSM is based on clinical evidence whereas the cerebral disease is usually diagnosed by biopsy of the nervous tissue. There is no consensus on the treatment of NSM. We discuss the literature data on this topic, and suggest a therapeutic approach based on our experience with 69 spinal cord NSM patients who have been followed up by a long period of time. Outcome is largely dependent on early treatment, particularly in the medullar disorder, and is better in cerebral NSM.     

The relation between involvement of the central nervous system in schistosomiasis mansoni and the clinical forms of the parasitosis. A review

A review of the available literature on the involvement of the central nervous system (CNS) in schistosomiasis mansoni was undertaken to assess the schistosomal lesions in the spinal cord and brain and the clinical forms of the disease that are associated with these lesions. In almost all clinically symptomatic cases of neuroschistosomiasis mansoni (NSM), involvement of the CNS starts in the early stages of infection (non-toxaemic form), during evolution of the disease to its chronic forms, or concomitantly with the (oligo or asymptomatic) chronic intestinal and hepatointestinal forms. In-situ ova deposition following the anomalous migration of adult worms appears to be the main, if not the only, mechanism by which Schistosoma mansoni may reach the CNS in patients with the intestinal and hepatointestinal forms of the parasitosis. The mass effect produced by the heavy concentration of ova and granulomas in circumscribed areas of the spinal cord and brain explains the severe neurological symptoms observed in most of these patients. Though more frequent, CNS involvement associated with the hepatosplenic and cardiopulmonary forms is almost always asymptomatic. The random distribution of ova in the CNS of patients with these forms suggests that ova are carried there mainly as emboli via the arterial system or through retrograde venous flow. Because of the discrete inflammatory reaction elicited by the sparsely distributed ova, neurological symptoms attributable to ova deposition are not present in most NSM patients with the hepatosplenic and cardiopulmonary forms.     

Schistosoma mansoni: assessment of morbidity before and after control

The literature on the assessment of morbidity due to Schistosoma mansoni infection is updated. Imaging techniques such as ultrasonography, echodoppler cardiography, computerized tomography (CT scan) and magnetic resonance imaging (MRI) introduced a new perspective, and expanded our knowledge on morbidity. Three well-defined syndromes caused by schistosomiasis mansoni have been described: the stage of invasion, acute schistosomiasis (Katayama fever), and chronic schistosomiasis. Complications of the acute and chronic syndromes have also been reported: pulmonary hypertension, neuroschistosomiasis, association with Salmonella, association with Staphylococci, viral hepatitis B, glomerulonephritis. In most individuals with hepatosplenic schistosomiasis the spleen is increased in size. Hepatosplenic schistosomiasis can, however, occur without splenomegaly. The definition of hepatosplenic schistosomiasis in endemic areas as the finding of S. mansoni eggs in the stools in an individual with hepatosplenomegaly is not satisfactory anymore. Many aspects of morbidity are expected to change after schistosomiasis control. Some are expected to change quickly (worm burden, Salmonella bacteremia, hepatosplenic schistosomiasis in children) whereas others shall remain for years (pulmonary hypertension, glomerulonephritis, neuroschistosomiasis). Intestinal schistosomiasis in individuals with low worm burdens is very difficult to diagnose and therefore laborious to control.     

Schistosomiasis

Schistosomiasis is a common intravascular trematode infection. The snail/human lifecycle is illustrated. Travellers who acquire the infection are often asymptomatic, but nearly always give a history of fresh water exposure in endemic countries when asked. The various manifestations of symptomatic schistosomiasis are described, including the rare but important complication of neuroschistosomiasis. Guidelines for diagnostic tests, treatment with praziquantel and management of complications are given. Prospects for disease control in endemic countries by improvement in public health and mass treatment are discussed. Various vaccines are in development, but none are in clinical use yet.     

Successful vaccination against murine Schistosoma mansoni infection with a purified 12 Kd Fasciola hepatica cross-reactive antigen

A 12 Kd antigen was isolated from Fasciola hepatica adult worm extracts by gel filtration in Sephadex G-50 and ion exchange chromatography using DEAE Sephadex A-120. Mice immunized with this Fasciola-derived 12 Kd antigen developed antibodies to Schistosoma mansoni adult worm extracts, demonstrating its cross-reactivity with schistosomes. Vaccination of mice with microgram amounts of the antigen in Freund's adjuvant induced up to 77% reduction in worm burdens after challenge with S. mansoni cercariae. F. hepatica 12 Kd degraded by proteinase K to lower molecular weight polypeptides which still retain their antigenicity as determined by the enzyme-linked immunoelectrotransfer blot technique. Treatment with either Endoglycosidase H, neuraminidase, or dithiothreitol had no effect on its mobility in sodium dodecyl sulfate polyacrylamide gels, or in its recognition by antibody, suggesting the absence of carbohydrate moieties or disulphide bonds in relation to its antigenic determinants and also suggesting that the antigen is a pure polypeptide. These studies establish that a molecularly defined cross-reactive component of one parasitic trematode (F. hepatica) induces resistance to challenge infection with another parasitic trematode (S. mansoni). Its polypeptide nature makes recombinant DNA technology an alternative for the manufacture of a vaccine.     

Antibodies to Schistosoma mansoni in human cerebrospinal fluid

Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested, 55% were reactive to SEA (26% were reactive only to SEA and 29% to both SEA and SWAP), 34% were reactive to SWAP (5% only to SWAP and 29% to both SEA and SWAP), and 40% were not reactive with any antigen. Cases that tested positive for SWAP in CSF and negative in serum were not found. Samples with high specific IgG antibody titers were selected for immunoglobulin isotype profiling. In the CSF samples, the antibodies against SEA and SWAP were mainly IgM, IgG1, and IgG4, although other immunoglobulins were also detected. Interestingly, nine patients had high levels of IgG1 only in the CSF. These results suggest that there is local synthesis of IgG1, and that this isotype could be an important immunologic marker in the diagnosis of NS.     

Pseudotumoral form of neuroschistosomiasis: report of three cases in Ganzi, China

The authors report three rare cases of neuroschistosomiasis lacking extracranial involvement. No parasitic eggs were detected in the stool with the Kato-Katz thick smear methods. Computed tomography of the brains showed hypodense signals, and magnetic resonance imaging showed isointense signals on T1-weighted images, hyperintense signals on T2-weighted images, and intensely enhancing nodules in the brain after intravenous administration of gadolinium. High-grade gliomas were suspected, and operations or radiosurgery was performed. Cerebral schistosomiasis was confirmed in all cases by biopsy of the brain lesions, revealing granulomas containing embedded Schistosoma japonicum eggs. All cases were definitively diagnosed as brain schistosomiasis japonica. Praziquantel and corticosteroids were administered, and the prognoses were good for all case patients. Although the aforementioned pattern of imaging examinations is not present in all cases of neuroschistosomiasis, a diagnosis of neuroschistosomiasis should be considered when this pattern of imaging is observed; cerebrospinal fluid serological exams are also recommended.     

Pseudotumoral form of neuroschistosomiasis: report of three cases.

Central nervous system (CSN) involvement in schistosomiasis is an ectopic manifestation with a large variety of clinical forms, including pseudotumoral, which occurs in isolated cases and is rare. Three patients with epidemiological indications of this pathology were examined; the clinical picture included lower-back pain irradiating to lower limbs, associated with progressive flaccid paraparesis and sphincterial disturbances in cases in which the spinal chord was involved; while in cases with encephalitic impairment, headache, dizziness and cerebellar syndrome, characterized by dysarthria and right-side dysgraphia, were present. Magnetic resonance imaging (MRI) showed a growing process in all cases; cerebrospinal fluid (CSF) characteristics and biological markers were compatible with neuroschistosomiasis (NS). Biopsy of the lesions confirmed this diagnosis in one case. After specific treatment with schistosomicides and corticosteroids, clinical, radiological and laboratorial improvement was observed.     

Hamadryas baboons Papio hamadryas as maintenance hosts of Schistosoma mansoni in Saudi Arabia

Free ranging hamadryas baboons ( Papio hamadryas ) in four localities in the west and north of Saudi Arabia were examined for natural infection with Schistosoma mansoni . Faecal examination revealed infection with S. mansoni on four occasions within one year (at a prevalence rate of 2.5–4.0%) in only one locality, the Al‐Baha area. The eggs were viable, as shown by miracidial hatching tests, and were recorded at a density of 140–280 eggs/g of faeces (7000–14 000 eggs/day). Post‐mortem examination of 13–24 baboons from each locality revealed infection with S. mansoni (adult worms and eggs in tissue) in only one locality, the Al‐Baha area, at a prevalence rate of 4.16%. Viable eggs were found in the faeces and tissue of the infected baboons. The low prevalence rate of S. mansoni in hamadryas baboons in Saudi Arabia is in accordance with the low prevalence rate of S. mansoni in humans in the area. This natural baboon isolate was highly infective to snail intermediate hosts and mammalian hosts under experimental conditions. The epidemiological significance of the role of P. hamadryas (considering their large overall population of 250 000) as maintenance hosts of S. mansoni in Saudi Arabia is discussed.     

Intramedullary tuberculomas of the spinal cord: case report and review

Intramedullary spinal tuberculomas are a rare cause of spinal cord compression. We report a recent case and review 17 cases described in the literature since 1960. Intramedullary spinal tuberculomas occurred in relatively young patients (mean age, 28.6 years) and more frequently in women (63% of cases) than in men. The commonest symptoms were those of subacute spinal cord compression (mean duration, 2.3 months) with progressive lower-limb weakness (94%), paresthesia, and bowel and bladder dysfunction. The major physical finding was paraplegia, either spastic (61%) or flaccid (33%). The majority of patients (55%) had a thoracic sensory level. Extraspinal tuberculous disease, predominantly pulmonary, occurred in 69% of reported cases. Myelography efficiently localized the lesion. The diagnosis was made surgically in 16 patients (89%) and clinically in two (11%). Eleven (65%) of 17 patients improved. Four deaths occurred, three in the perioperative period. Though rare, intramedullary spinal cord tuberculoma should be considered in the differential diagnosis of spinal cord compression, particularly when clinical disease compatible with tuberculosis is present.     

Absence of cervical schistosomiasis among women from two areas of north-eastern Brazil with endemic Schistosoma mansoni

Genital manifestations in schistosomiasis haematobium are common and are associated with considerable morbidity. Although Schistosoma mansoni may also cause genital disease, the frequency of this complication is not known. Cervical biopsies (N=401) and Pap smears (N=981) were therefore collected from women living in two S. mansoni-endemic areas (in the states of Alagoas and Ceará, in north-eastern Brazil). The women were screened for the presence of sexually transmitted diseases and for the presence, in their cervical smears and/or biopsies, of S. mansoni eggs. Attempts at schistosomiasis control, which began in both study areas in 1977, have led to generally low intensities of infection (<30 eggs/g faeces in 99% of infections) and community prevalences of infection that range between 1% and 52%. As no schistosome ova were detected in any of the biopsies or smears, it appears that the risk, among women, of genital manifestations of S. mansoni infection is small in areas where the parasite load in the population is low (as the result of interventions to control intestinal schistosomiasis).     

Chronic abdominal pain and eosinophilia in a young African patient

A 20-year-old African female was hospitalized several times for diffuse chronic abdominal pain. The following exclusions were made: Acute adnexitis (by laparoscopy), acute appendicitis (by appendectomy), gastric ulcerations (by esophagogastroduodenoscopy) as well as Crohn's disease and ulcerative colitis. However, once taking a closer microscopical look at the mucosa, that otherwise appeared colonoscopically to be normal, multiple eggs of schistosomiasis mansoni (S. mansoni) were found in the colon as well as the rectum. Thus, the diagnosis of an intestinal bilharziosis was finely established. In retrospect even the sample taken for the appendix could have indicated this diagnosis already earlier on. Both the antibodies (ELISA/IFAT) and the specific immunoglobulins (IgE) for S. mansoni proved significantly positive. Therapy of choice was a single oral dosage of praziquantel. Migration and tourism have considerably increased the range of tropical and infectious diseases that need to be included into differential diagnosis. This case report focuses on intestinal bilharziosis as a potential underlying cause of chronic abdominal pain in immigrants of endemically affected areas. Direct diagnosis is the most important diagnostic method. The adult worms are usually inaccessible, so the method of choice to assess both diagnosis and the degree of activity of a chronic infection is evidence of living eggs in the stool. Alternatively, in case of lack of direct evidence diagnosis can be established by endoscopy and rectal biopsy.     

Moderate- and low-intensity co-infections by intestinal helminths and Schistosoma mansoni, dietary iron intake, and anemia in Brazilian children

To determine the role of moderate- and low-intensity infections with Schistosoma mansoni and intestinal helminths (hookworm, Trichuris trichiura, Ascaris lumbricoides) on the prevalence of anemia and their relationship to iron consumption, a cross-section of 1,709 children in rural Brazil was studied. All participants were selected for infection with one or multiple helminthic parasites, and demographic, anthropometric, and dietary intake were surveyed. The prevalence and intensity were as follows: hookworm infection, 15.7% and 8.6 eggs/g; T. trichiura, 74.8% and 190.5 eggs/g; A. lumbricoides, 63% and 1,905.5 eggs/g; S. mansoni, 44.5% and 60.3 eggs/g. There was no increase in odds ratio for anemia with any combination of intestinal helminths without S. mansoni infection. By logistic regression, the odds ratio for having anemia when infected with S. mansoni and two intestinal helminths was 1.7 (95% CI, 1.1-2.5) and for S. mansoni and three intestinal helminths was 2.4 (95% CI, 1.2-4.6) compared with children with a single parasite species. Children with an adequate intake of iron had no increased odds of anemia independent of the combination of parasite infections.     

曼氏迭宫绦虫动物模型的建立和生活史观察

目的建立曼氏迭宫绦虫动物模型,观察其生活史。方法从感染蛇体内分离曼氏裂头蚴,感染终宿主（猫）和中间宿主（剑水蚤、蝌蚪）,以观察其从虫卵孵出幼虫、感染第一、二中间宿主剑水蚤、蝌蚪和终宿主猫的生活史过程。结果感染猫12d后粪检发现虫卵,经解剖猫获得成虫、虫卵;虫卵在室温培养12d孵出钩球蚴,感染剑水蚤6d后发育为原尾蚴;感染蝌蚪后第28d发现裂头蚴。结论成功建立曼氏迭宫绦虫动物模型,裂头蚴在猫体内成熟时间仅12d。     

淮南地区曼氏迭宫绦虫病流行的危险因素调查

目的：探讨淮南地区曼氏迭宫绦虫病流行现状及其危险因素,为曼氏迭宫绦虫病的预防提供理论基础。方法：采用现场流行病学调查的方法,对淮南市各辖区水域剑水蚤原尾蚴感染状况、青蛙肌肉曼氏裂头蚴感染状况及各辖区家猫或家犬粪便曼氏迭宫绦虫卵感染状况进行随机抽样,分析剑水蚤原尾蚴感染率、青蛙肌肉曼氏裂头蚴感染率及各辖区家猫或家犬粪便曼氏迭宫绦虫卵感染率,另外采用问卷调查的方法调查曼氏迭宫绦虫病流行的环境及社会因素。结果：淮南地区6个市辖区或县剑水蚤原尾蚴感染率：田家庵区、谢家集区、八公山区、潘集区、大通区及凤台县分别为2%、1%、1%、2%、2%、3%;淮南地区青蛙曼氏裂头蚴总感染率为7.33%;家猫和家犬粪便中虫卵的检获率分别为0%~15%和0%~5%。问卷调查结果显示农民曼氏迭宫绦虫病预防知识知晓率为为0%,受调查农民中,有捕食青蛙的习俗的占14.77%,曾食过半生熟青蛙者占3.13%,曾用蛙喂猫或喂犬者占36.29%。结论：淮南地区剑水蚤原尾蚴感染率和青蛙曼氏裂头蚴总感染率均高,终宿主受到虫卵感染,农民对曼氏迭宫绦虫病预防知识知晓率低,应加强对农民曼氏迭宫绦虫病防治知识的教育,以达到有效控制曼氏迭宫绦虫病的发生、传播和流行的目的。     

Oxylog studies of energy expenditure and schistosomiasis in the Sudan

The effects of varying intensities of S. mansoni infection on physical work performance in agricultural tasks were studied in 269 male farmers living in the highly endemic Gezira area of the Sudan. The subjects were in the age range 18-50 years, and they were subdivided into four infection groups: non-infected (passing no S. mansoni eggs in their faeces), lightly infected (egg excretion 1-499), moderately infected (egg excretion 500-999), and heavily infected (egg excretion 1000+ eggs g-1 faeces). The Oxylog, a portable oxygen analyser, was used to measure energy expenditure throughout the field studies. The investigations showed that heavy S. mansoni infection significantly lowered oxygen intake by 20-30% during agricultural work tasks. There was a clear relationship between the intensity of S. mansoni infection and both the aerobic power output and morbidity in those populations. Anti-schistosomal treatment (praziquantel) given over a period of 1 year produced a marked improvement in working capacity and reduced morbidity.     

Induction of immunity in mice to Fasciola hepatica with a Fasciola/Schistosoma cross-reactive defined immunity antigen

The paradox of schistosomiasis is that infection confers immunity to its host, yet immunization with subcellular antigens of the parasite does not, in general, induce protective immunity. Infection or immunization with subcellular antigens of Fasciola hepatica confers high levels of immunity to a challenge infection with another trematode, Schistosoma mansoni. We have isolated by antibody affinity chromatography a Fasciola hepatica/Schistoma mansoni cross-reactive antigen, designated FhSmIII(M), and also have shown that this antigen confers immunity in mice to a challenge infection with S. mansoni. This antigen was compared with a crude F. hepatica worm extract (FhWWE) as to its ability to induce an IgG antibody response in mice, and to determine whether it had a protective effect in mice to a challenge infection with F. hepatica metacercariae. Mice immunized with FhSmIII(M) or FhWWE, and subsequently infected with F. hepatica, developed higher IgG antibody levels to FhSmIII(M), as measured by ELISA, than F. hepatica-infected controls. Mice immunized with FhWWE did not develop significant levels of resistance to challenge with F. hepatica metacercariae. Mice immunized with FhSmIII(M) and infected with F. hepatica metacercariae developed 69%-78% less worms than controls. An F. hepatica/S. mansoni cross-reactive, cross-protective defined immunity antigen confers in mice significant levels of protection to a challenge infection with F. hepatica.     

Interactions between Schistosoma haematobium and Schistosoma mansoni in humans in north Cameroon

OBJECTIVES: To analyse the relationships between the frequency of ectopic localizations of Schistosoma haematobium and S. mansoni eggs. METHODS: Studies were conducted in 11 villages in north Cameroon, around Bessoum, a village where an epidemic of bloody diarrhoea caused by S. mansoni occurred in 1997. RESULTS: The results revealed infection prevalence rates of 70.5% for S. haematobium and 30.8% for S. mansoni. Interestingly, S. mansoni eggs were found in 14.5% of the urine samples and S. haematobium eggs in 3% of the stool samples. These ectopic eliminations of schistosome eggs resulted from sexual interactions between the two species of schistosomes, and from a spill-over of high infection loads. The clinical study showed that the morbidity was lower in individuals with mixed infections and high loads of S. haematobium than in those with S. mansoni infections only, suggesting a possible lowering effect of S. haematobium infection on S. mansoni morbidity. DISCUSSION: The results obtained in human populations are discussed in relation to the known schistosome interspecific interactions in animal models.     

Serum and cerebral spinal fluid levels of chemokines and Th2 cytokines in Schistosoma mansoni myeloradiculopathy

Schistosomal myeloradiculopathy (SMR) is the most common neurological form of Schistosoma mansoni infection. In this study we investigated the expression of chemokines and Th2 cytokines in serum and cerebral spinal fluid (CSF) of SMR patients. SMR patients presented increased serum levels of CCL11/eotaxin and CCL24/eotaxin-2 when compared to controls. SMR patients also had higher levels of IL-13 in CSF. Thus, SMR patients present enhancement of both IL-13 and CCR3 acting chemokines, both of which may facilitate the expression of a Th2 response and Th2-dependent damage to the spinal cord. As this cytokine is responsible for promoting Th2 responses, this finding is in accordance to the view that Th2 cells are important in the immunological process against the S. mansoni.