Hepatosplenic Disease Research Articles

Disseminated Cat Scratch Disease With Vertebral Osteomyelitis and Epidural Abscess

A 5-year-old boy with cat scratch disease presented with fever of unknown origin and osteomyelitis of the thoracic spine and epidural abscess. He did not have localizing signs or symptoms. Computed tomography of the abdomen, which was initially negative, showed hepatosplenic disease. Cat scratch disease has variable systemic presentations and should be included in the differential diagnosis of fever of unknown origin if an epidemiologic risk factor is present.

Evaluation of some Cytokine Responses in Ascitic Fluid; Their Relation to Circulating Immune Complexes

There is no clear consensus about the pattern of cytokine production and regulation that causes patients with chronic schistosomiasis to develop severe hepatosplenic disease, which is characterized by peri-portal fibrosis and portal hypertension. Circulating immune complexes [CICs], play an important role in the pathogenesis of many clinical syndromes during the course of hepatic schistosomiasis. Therefore, the aim of this study was to estimate interleukin-6 [IL-6] and tumor necrosis factor-α] levels in serum and ascetic fluid [AF] of schistosomal patients and to evaluate these cytokines response in relation to circulating immune complexes. Material and methods: The study enrolled 40 patients with hepatic schistosomiasis forming two groups; 20 patients with ascites [group I] and the other 20 patients without ascites [group II]. Apart from complete history taking, clinical examination, and routine laboratory work, blood and ascetic fluid [AF] samples were collected from the patients after hospital admission. Estimation of IL-6 and TNF-α in serum and AF according to the manufacturer instructions. Moreover, serum circulating immune complexes [CICs] were assayed as well. Results: The mean serum level of IL-6 was 156.9±150.82 pg/ml in schistosomal ascetic patients and 121.63±68.47 pg/ml in non-ascetic cases. The mean serum concentration of TNF-α was 88.5±70.59 pg/ml in group I and 66±46.76 pg/ml in group II patients. IL-6 concentration in the ascetic fluid of schistosomal patients had a mean of 284.4±280.08 pg/ml while ascetic fluid TNF-α had a mean of 113.25±58.97 pg/ml. Schistosomal patients with ascites were shown to have significantly higher levels of IL-6 and TNF-α in their ascetic fluid than in serum. A significant positive correlation was detected between the serum and AF concentrations of IL-6 [r-=0.559], and TNF-α [r-=0.556*], P<0.05 in each case. Ascitic patients had a significantly higher mean CIC [21.33±5.4 μg Eq/ml] than the non-ascitic cases [15.51±5.27 μg Eq/ml]. There was a significant positive correlation between serum level of IL-6 and CICs in schistosomal patients with ascites [r-=0.446*, P<0.05], and another significant positive correlation was demonstrated between ascetic fluid TNF-α and CICs in the same patients [r-=0.448*, P<0.05]. Conclusion: The study concluded that schistosomal patients with ascites had significantly higher levels of IL-6 and TNF-α in their ascetic fluid than in serum, while there was no significant difference between their serum levels in the ascetic and non-ascitic groups. Moreover, a significant positive correlation was detected between CICs and serum IL-6 in patients with ascites.

Potential Role of the Chemokine Macrophage Inflammatory Protein 1α in Human and Experimental Schistosomiasis

In human schistosomiasis, the concentrations of the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha/CCL3) is greater in the plasma of patients with clinical hepatosplenic disease. The objective of the present study was to confirm the ability of CCL3 to detect severe disease in patients classified by ultrasonography (US) and to evaluate the potential role of CCL3 in Schistosoma mansoni-infected mice. CCL3 was measured by enzyme-linked immunosorbent assay in the plasma of S. mansoni-infected patients. CCL3-deficient mice were infected with 25 cercariae, and various inflammatory and infectious indices were evaluated. The concentration of CCL3 was higher in the plasma of S. mansoni-infected than noninfected patients. Moreover, CCL3 was greater in those with US-defined hepatosplenic than with the intestinal form of the disease. In CCL3-deficient mice, the size of the granuloma and the liver eosinophil peroxidase activity and collagen content were diminished compared to wild-type mice. In CCL3-deficient mice, the worm burden after 14 weeks of infection, but not after 9 weeks, was consistently smaller. The in vitro response of mesenteric lymph node cells to antigen stimulation was characterized by lower levels of interleukin-4 (IL-4) and IL-10. CCL3 is a marker of disease severity in infected humans, and experimental studies in mice suggest that CCL3 may be a causative factor in the development of severe schistosomiasis.

Schistosoma mansoniin Family 5 Years after Safari

<i>Schistosoma mansoni</i>in Family 5 Years after Safari

Comparative clinical and ultrasound study of egg-negative and egg-positive individuals from Schistosoma mansoni low morbidity endemic areas, and hospitalized patients with hepatosplenic disease

Two hundred and twenty three subjects from a Schistosoma mansoni low morbidity endemic area and nine hospitalized hepatosplenic patients were submitted to stool test and clinical examination and abdomen ultrasound assessments. According to stool examination and ultrasound results, they were grouped as follows: G1 -- 63 Schistosoma mansoni egg-negative individuals; G2 -- 141 egg-positive patients and without evidence of periportal fibrosis; G3 -- 19 egg-positive patients with periportal echogenicity (3-6 mm); and G4 -- 9 hepatosplenic patients with periportal echogenicity (> 6 mm). Hepatomegaly detected by physical examination of the abdomen evaluated in the midclavicular line was verified in G1, G2 and G3, respectively, in 11.1, 12.1 and 26.3%. In G1, G2 and G3, periportal thickening occurred only in schistosomal patients (8.5%). Mild pathological alterations in patients that cannot yet be detected by clinical examination were detectable in the liver by ultrasound and can be due to fibrosis. The degree of mild periportal fibrosis was diminished in 57.9% of patients 12 months after treatment of schistosomiasis with oxamniquine. At ultrasonography, the mean liver left lobe measurement of G3 was larger than that of G1, and that of G4 larger than that of G1 and G2. The mean size of the spleen of G4 was significantly larger than that of the other three groups, and that of G3 larger than that of G1 and G2.

Schistosomal hepatopathy.

Gross anatomical features and a complex set of vascular changes characterize schistosomal hepatopathy as a peculiar form of chronic liver disease, clinically known as "hepatosplenic schistosomiasis". It differs from hepatic cirrhosis, although clinical and pathological aspects may sometimes induce confusion between these two conditions. Intrahepatic portal vein obstruction and compensatory arterial hypertrophy render the hepatic parenchyma vulnerable to ischemic insult. This may lead to focal necrosis, which may give place to focal post-necrotic scars. These events are of paramount importance for the clinico-pathological evolution of schistosomal hepatopathy. Although portal fibrosis due to schistosomiasis sometimes reveals numerous myofibroblasts, it does not mean that such fibrosis belongs to a peculiar type. Damage to the muscular walls of the portal vein may be followed by dissociation of smooth muscle cells and their transition toward myofibroblasts, which appear only as transient cells in schistosomal portal fibrosis. Studies made with plastic vascular casts, especially those with the murine model of "pipestem" fibrosis have helped to reveal the mechanisms involved in systematized portal fibrosis formation. However, the factors involved in the pathogenesis of hepatosplenic disease remain poorly understood. A process of chronic hepatitis is a common accompaniment of portal fibrosis in schistosomiasis. Most of the times it is caused by concomitant viral infection. However, no special interaction seems to exist between schistosomal hepatopathy and viral hepatitis.

Detailed clinical and ultrasound examination of children and adolescents in a Schistosoma mansoni endemic area in Kenya: hepatosplenic disease in the absence of portal fibrosis.

Hepatosplenic schistosomiasis involving organomegaly, portal fibrosis and portal hypertension has been observed in autopsy studies. Here, we have tested the hypothesis that hepatosplenic disease including organomegaly and markers of increased portal pressure can occur in school aged children in the absence of fibrosis. A case-only study of 96 children aged 7-20 years defined by ultrasound detectable hepatomegaly was undertaken in Makueni district, Kenya. A novel method of clinical examination that involved a consensus scoring by three or four examiners was used to classify children as presenting with severe or moderate hepatosplenic disease after palpation of livers and spleens. Ultrasound examination of livers and spleens was based on the Niamey protocol. Clinical measurements included spleen enlargement along the mid-clavicular and mid-axillary lines, liver enlargement along the mid-sternal (MSL) and mid-clavicular lines, as well as organ consistency. The clinical examination indicated that 9% and 60% of the children had severe or moderate hepatosplenomegaly, respectively. Amongst egg-positive children, all clinical measurements, except MSL liver enlargement, correlated with egg count, as did portal vein diameter, spleen length and liver length measured by ultrasound. Peri-portal fibrosis was not observed in any child, whereas 28% of the children were classified as having increased portal pressure according to World Health Organization criteria. There was no effect of malaria parasitaemia or hepatitis seropositvity on any of the observed parameters. These results indicate that hepatosplenic disease in school-aged children attributable to S. mansoni infection, involving hepatosplenomegaly and increased portal vein diameter, can occur in the absence of peri-portal fibrosis.

Systemic Candidiasis

HomeRadioGraphicsVol. 23, No. 5 PreviousNext AFIP ARCHIVESSystemic CandidiasisNicholas J. E. Moore, Johnsey L. Leef, III, Yijun PangNicholas J. E. Moore, Johnsey L. Leef, III, Yijun PangAuthor Affiliations1From the Departments of Radiology and Pathology, University of Vermont School of Medicine, 111 Colchester Ave, Burlington, VT 05401. Received November 13, 2002; revision requested January 15, 2003 and received February 28; accepted March 5. Address correspondence to N.J.E.M. (e-mail: [email protected]).Nicholas J. E. MooreJohnsey L. Leef, IIIYijun PangPublished Online:Sep 1 2003https://doi.org/10.1148/rg.235025162MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In References 1 Lee GR, Foerster J, Lukens J, et al. eds. Wintrobe’s clinical hematology 10th ed. Baltimore, Md: Williams & Wilkins, 1999. Google Scholar2 Anttila VJ, Elonen E, Nordling S, Sivonen A, Ruutu T, Ruutu P. Hepatosplenic candidiasis in patients with acute leukemia: incidence and prognostic implications. Clin Infect Dis 1997; 24:375-380. Crossref, Medline, Google Scholar3 Rossetti F, Brawner DL, Bowden R, et al. Fungal liver infection in marrow transplant recipients: prevalence at autopsy, predisposing factors, and clinical features. Clin Infect Dis 1995; 20:801-811. Crossref, Medline, Google Scholar4 van Burik JH, Leisenring W, Myerson D, et al. The effect of prophylactic fluconazole on the clinical spectrum of fungal diseases in bone marrow transplant recipients with special attention to hepatic candidiasis: an autopsy study of 355 patients. Medicine (Baltimore) 1998; 77:246-254. Crossref, Medline, Google Scholar5 Schwartz RS, Mackintosh FR, Schrier SL, et al. Multivariate analysis of factors associated with invasive fungal disease during remission induction therapy for acute myelogenous leukemia. Cancer 1984; 53:411-419. Crossref, Medline, Google Scholar6 Kontoyiannis DP, Luna MA, Samuels BI, Bodey GP. Hepatosplenic candidiasis: a manifestation of chronic disseminated candidiasis. Infect Dis Clin North Am 2000; 14:721-739. Crossref, Medline, Google Scholar7 Sallah S, Semelka RC, Wehbie R, Sallah W, Nguyen NP, Vos P. Hepatosplenic candidiasis in patients with acute leukaemia. Br J Haematol 1999; 106:697-701. Crossref, Medline, Google Scholar8 Lamminen AE, Anttila VJ, Bondestam S, Ruutu T, Ruutu PJ. Infectious liver foci in leukemia: comparison of short-inversion-time inversion-recovery, T1-weighted spin-echo, and dynamic gadolinium-enhanced MR imaging. Radiology 1994; 191:539-543. Link, Google Scholar9 Semelka RC, Kelekis NL, Sallah S, Worawattanakul S, Ascher SM. Hepatosplenic fungal disease: diagnostic accuracy and spectrum of appearances on MR imaging. AJR Am J Roentgenol 1997; 169:1311-1316. Crossref, Medline, Google Scholar10 Sallah S, Semelka R, Kelekis N, Worawattanakul S, Sallah W. Diagnosis and monitoring response to treatment of hepatosplenic candidiasis in patients with acute leukemia using magnetic resonance imaging. Acta Haematol 1998; 100:77-81. Crossref, Medline, Google ScholarArticle HistoryPublished in print: Sept 2003 FiguresReferencesRelatedDetailsCited ByCurrent Problems in Diagnostic Radiology, Vol. 51, No. 1Abdominal Radiology, Vol. 46, No. 6Journal of the American Academy of Dermatology, Vol. 80, No. 4Seminars in Roentgenology, Vol. 52, No. 2Multimodality Imaging of Liver Infections: Differential Diagnosis and Potential PitfallsPablo Bächler, María José Baladron, Christine Menias, Ignacio Beddings, Ron Loch, Eugenio Zalaquett, Matías Vargas, Sarah Connolly, Sanjeev Bhalla, Álvaro Huete, 27 May 2016 | RadioGraphics, Vol. 36, No. 4Current Radiology Reports, Vol. 4, No. 1Clinical Imaging, Vol. 40, No. 4Seminars in Roentgenology, Vol. 50, No. 4Ultrasound Quarterly, Vol. 24, No. 4Radiología, Vol. 49, No. 6Fungal Liver Infection in Immunocompromised Patients: Depiction with Multiphasic Contrast-enhanced Helical CT1Ur Metser, , Masoom A. Haider, , Marcus Dill-Macky, , Mostafa Atri, , Gina Lockwood, , and Mark Minden, 1 April 2005 | Radiology, Vol. 235, No. 1Recommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 23, No. 5 Metrics Downloaded 8,670 times Altmetric Score PDF download

Immunity to schistosomiasis: glycans are potential antigenic targets for immune intervention

The major humoral immune responses in animals infected with Schistosoma mansoni are directed toward carbohydrate antigens. Among these antigens are complex-type N-glycans expressing LDN [GalNAcβ1–4GlcNAc-R], LDNF [GalNAcβ1–4(Fucα1–3)GlcNAc-R], and polymeric Lewis x (Le x) [Galβ1–4(Fucα1–3)GlcNAc] n -R epitopes. We have now evaluated the potential of the three glycan antigens as targets for immune-mediated intervention of infections and serodiagnosis. A variety of approaches were employed, including ELISA, Western blot, immunohistology, and in vitro complement lysis assays, to determine the immunogenicity of the glycans in infected humans, their localization on the parasites and their efficacy as targets for parasite lysis. Our results show that S. mansoni-infected patients, with either intestinal or hepatosplenic disease, generate predominantly IgM, but also IgG and IgA, antibodies to LDN, LDNF, and Le x. However, immune responses to Le x are generally lower than responses to LDN and LDNF and less specific to schistosome infections. Western blot analysis with monoclonal antibodies (mAb) to LDN, LDNF, and Le x determinants show that the glycan antigens occur on multiple glycoproteins from cercariae, 3-h, 48-h, and lung stage schistosomula, as well as adults and eggs. Immunohistological studies demonstrate that LDN, LDNF, and Le x are expressed on the parasite surface at all stages of development in the vertebrate host. Importantly, a mAb to LDN in the presence of complement efficiently kills schistosomula in vitro, as demonstrated by flow-cytometric assays that quantify cytolysis by propidium iodide uptake into damaged parasites. These findings raise the possibility that LDN and LDNF may be targets for vaccination and/or serodiagnosis of chronic schistosomiasis in humans. Abbreviations used: LDN—LacdiNAc, GalNAcβ1 → 4GlcNAc; LDNF, fucosylated lacdiNAc, GalNAcβ1 → 4(Fucα1 → 3)GlcNAc; Le x—Lewis x, Galβ1 → 4(Fucα1 → 3)GlcNAc; LDNT—lacdiNActetraose, GalNAcβ1 → 4GlcNAcβ1 → 3Galβ1 → 4GlcNAc; LDNFP—lacdiNAc fucopentaose GalNAcβ 1 → 4(Fucα1 → 3)GlcNAcβ1 → 3Galβ1 → 4GlcNAc; LNFPIII—lacto- N-fucopentaose III, Galβ1 → 4(Fucα1 → 3)GlcNAcβ1 → 3Galβ1 → 4GlcNAc; SEA, soluble egg antigen; PBS, phosphate-buffered saline; BSA, bovine serum albumin; BCA, bicinchoninic acid; SDS–PAGE, sodium dodecyl sulfate–polyacrylamide gel electrophoresis; ASGP-R, asialoglycoprotein receptor

Plasma concentrations and role of macrophage inflammatory protein-1alpha during chronic Schistosoma mansoni infection in humans.

Chemokines play an important role during granulomatous inflammation in murine models of Schistosoma mansoni infection. Here, the expression and possible roles of chemokines during human S. mansoni infection were examined. Compared with uninfected individuals, infected patients had elevated plasma concentrations of macrophage inflammatory protein (MIP)-1alpha, RANTES (regulated on activation, normally T cell-expressed and secreted), and eotaxin. Concentrations of macrophage-derived chemokine, eotaxin-2, monocyte chemotactic protein-1, growth-related oncogene, and interleukin-8 were similar between the 2 groups. When subjects were grouped according to disease severity, individuals with a plasma MIP-1alpha concentration >400 pM had a 10-times greater risk of having the more severe hepatosplenic form of disease. In the in vitro granuloma reaction, greater concentrations of MIP-1alpha were produced by cells of patients with hepatosplenic disease than cells of patients with intestinal disease. Pretreatment with a chemokine receptor antagonist attenuated the enhanced in vitro reaction seen with cells derived from patients with hepatosplenic disease. MIP-1alpha may not only mark a subset of patients with a greater risk of having more severe disease but also play a relevant pathophysiological role in human schistosomiasis.

Enhanced interleukin-12 and CD40 ligand activities but reduced Staphylococcus aureus Cowan 1-induced responses suggest a generalized and progressively impaired type 1 cytokine pattern for human schistosomiasis.

Whole-blood-cell cultures from schistosomiasis patients were stimulated with a variety of T-cell-dependent and T-cell-independent stimuli to determine whether the defect in type 1 cytokine expression observed following helminth infection is associated with alterations in interleukin-12 (IL-12) or CD40 ligand (CD40L) responsiveness. Cultures from uninfected individuals produced abundant gamma interferon in response to Staphylococcus aureus Cowan 1 (SAC), while patients with intestinal and hepatosplenic disease displayed intermediate and weak responses, respectively. Importantly, the decrease in type 1 cytokine expression was not attributed to defects in IL-12- or CD40L-induced activity. Indeed, schistosomiasis patients displayed heightened responses and even produced more biologically active IL-12 when stimulated with SAC and CD40L than did uninfected controls. Finally, additional studies suggested only a partial role for IL-10, since intestinal patients were the only group that overproduced this downregulatory cytokine. Together, these studies demonstrate that the type 1 deficiency in chronic hepatosplenic schistosomiasis is not related to specific defects in IL-12, IL-10, or CD40L activity, although changes in the functional status of antigen-presenting cells appear to be involved.

P38 mitogen-activated protein kinase influence on the production of IL-10 in human schistosomiasis mansoni.

Schistosomiasis mansoni remains a significant public health problem in many parts of the tropics and subtropics. Clinical manifestations range from the asymptomatic intestinal form through to the hepatosplenic form of the disease, a potentially lethal clinical condition in a subsection of the exposed population. In this study, we investigated the mechanisms by which interleukin (IL)-10 production could be differentially controlled in patients with the intestinal and hepatosplenic forms of the disease, as IL-10 may play a fundamental role in the development of the hepatosplenic disease state. It is reported that p38 mitogen-activated protein (MAP) kinase signalling, and in particular p38 MAPK activation, is central to IL-10 production of cells from patients with schistosomiasis. Furthermore, the difference in the levels of activated p38 MAPK and the activation transcription factor (ATF-2), may explain the difference in the amount of IL-10 produced by cells from intestinal and hepatosplenic patients. We suggest that the type of immune response triggered in patients with hepatosplenomegaly could be influenced by the levels of phosphorylated p38 MAPK.

Geographic differences in hepatosplenic complications of schistosomiasis mansoni and explanatory factors of morbidity.

In a study in three neighbouring villages of southern Madagascar, where Schistosoma mansoni is hyperendemic, ultrasound examination using the Niamey protocol showed marked differences in the burden of disease from one village to another. Hepatosplenic schistosomiasis was more frequent in the village with the highest geometric mean egg counts and the earliest onset of infections, demonstrating that the morbidity induced by S. mansoni may vary greatly within a given area. True representativeness of study populations, a keystone of epidemiological studies, is mandatory to obtain a clear picture of a wide area. Ultrasound examinations in a small number of villages, or even a single one, may be a questionable approach. Using logistic regression analysis, the explanatory variables found to be significantly associated with a risk of severe hepatosplenic disease in our study were sex, age, village of residence and S. mansoni egg counts. On the other hand, a concurrent infection with an intestinal helminth seems to reduce the risk of severe hepatosplenic disease. Further studies should assess the role and possible impact of intestinal helminths on S. mansoni associated-morbidity.

Gastrointestinal complications of schistosomiasis.

Schistosomiasis is an important disease in many parts of the world and has affected the course of human history many times over. The parasitic infection is acquired during contact with infected water. A chronic inflammatory response to schistosome eggs, mediated by both cellular and humoral mechanisms, is the root of the pathology seen in schistosomiasis. Hepatosplenic disease results in intrahepatic presinusoidal portal hypertension. The resultant esophageal and gastric varices are an important cause of morbidity and mortality. Standard treatment guidelines for managing varices can be applied to patients with schistosomiasis. Coinfection with viral hepatitis results in liver disease that progresses more rapidly and is more difficult to treat. Intestinal schistosomiasis may be confused with other disease states and can be an important cause of morbidity, especially in heavily infected patients. Diagnosis relies on demonstration of schistosome eggs in feces or tissue. Praziquantel is the treatment of choice. The development of a vaccine for schistosomiasis is an important goal in the attempt to control this disease.

HLA class II antigens positively and negatively associated with hepatosplenic schistosomiasis in a Chinese population

To identify possible associations between host genetic factors and the onset of liver fibrosis following Schistosoma japonicum infection, the major histocompatibility class II alleles of 84 individuals living on an island (Jishan) endemic for schistosomiasis japonica in the Poyang Lake Region of Southern China were determined. Forty patients exhibiting advanced schistosomiasis, characterised by extensive liver fibrosis, and 44 age and sex-matched control subjects were assessed for the class II haplotypes HLA-DRB1 and HLA-DQB1. Two HLA-DRB1 alleles, HLA-DRB1*0901 ( P=0.012) and *1302 ( P=0.039), and two HLA-DQB1 alleles, HLA-DQB1*0303 ( P=0.012) and *0609 ( P=0.037), were found to be significantly associated with susceptibility to fibrosis. These associated DRB1 and DQB1 alleles are in very strong linkage disequilibrium, with DRB1*0901–DQB1*0303 and DRB1*1302–DQB1*0609 found as common haplotypes in this population. In contrast, the alleles HLA-DRB1*1501 ( P=0.025) and HLA-DQB1*0601 ( P=0.022) were found to be associated with resistance to hepatosplenic disease. Moreover, the alleles DQB1*0303 and DRB1*0901 did not increase susceptibility in the presence of DQB1*0601, indicating that DQB1*0601 is dominant over DQB1*0303 and DRB1*0901. The study has thus identified both positive and negative associations between HLA class II alleles and the risk of individuals developing moderate to severe liver fibrosis following schistosome infection.

Schistosomiasis: progress and problems.

Schistosomiasis, also commonly known as bilharziasis, is one of the most significant parasitic diseases of humans. A report of World Health Organization in 1996 estimated that over 200 million people were infested worldwide, mainly in rural agricultural and periurban areas. Of these, 20 million suffer severe consequences from the disease and 120 million are symptomatic. Symptoms range from fever, headache and lethargy, to severe sequelae including ascites, hepatosplenomegaly and even death[1]. More than 600 million people in the tropics are at risk for developing schistosomiasis. Schistosomiasis is the major public health problem in rural Egypt, with almost six million Egyptians are infested[2]. Schistosomiasis is caused by digenetic trematodes belong to phylum platyhelminthes, super family schistosmatoida, genus schistosoma. It is usually attributed to three species, subdivided into intestinal Schistosoma mansoni and Schist osoma japonicum or urinary Schistosoma hematobium types, according to the site preferred by the adult worms. In Egypt, the two species of bilharziasis are Schistosoma mansoni and hematobium whose intermediate hosts are fresh s nails, Biomphalaria alexandra, and Bulinus trancatus respectively[3]. In humans, these blood flukes reside in the mesenteric and vesical venules. They have a life span of many years and daily produce large numbers of eggs, which must traverse the gut and bladder tissues on their way to the lumens of the excretory organs. Many of the eggs remain in the host tissues, inducing immunologically mediated granulomatous inflammation and fibrosis. Heavy worm burdens may produce hepatosplenic disease in schistosomiasis mansoni and japonica and urinary tract disease in schistosomiasis hematobia. Because both the schistosomes and the eggs utilize host metabolites, and because the host responses to the parasite are affected by its nutritional status, malnutrition may strongly affect both the parasite and the complex host-parasite relationship[4].

Remote village survey for agents causing hepatosplenic disease in the Republic of Yemen.

The objective of this study was to epidemiologically describe potential infectious agents among rural people in the Republic of Yemen. This would aid clinicians in designing empirical therapy and public health officials in planning disease prevention. We sought to examine evidence for the geographical distribution of pathogens causing human hepatic and splenic disease among villagers and domestic animals living in three remote areas with differing altitudes. In June 1992, a cross-sectional survey was conducted at three survey sites of differing altitudes: 3080, 1440 and 250 m above sea level. Questionnaires, parasitic and serological tests were administered to 627 human volunteers. Additionally 317 domestic animals were studied. Malaria, schistosomiasis, and hepatitis B and C infections were found to be likely causes of human hepatic or splenic disease. Additionally, evidence of human and animal infections with the agents of brucellosis and Q fever was found: IgG antibodies against hepatitis E virus were discovered in two (2.0%) of the 100 volunteers. The prevalence of markers for human and animal disease was often lowest at the village of highest elevation, suggesting that increasing altitude, as a surrogate or a true independent risk factor, was protective against infection with the agents studied.

Clinical forms of human Schistosoma mansoni infection are associated with differential activation of T-cell subsets and costimulatory molecules.

The current study has compared the activation status and the expression of the CD28 molecule on circulating CD4+ and CD8+ lymphocytes from patients with different clinical forms of schistosomiasis. The data show that patients with acute schistosomiasis have an increase on the mean percentage of CD4+ HLA-DR+ cells, whereas chronic asymptomatic patients exhibit an increased mean percentage of CD8+ HLA-DR+ cells. Patients with the hepatosplenic disease showed an increase in both CD4+ HLA-DR+ and CD8+ HLA-DR+ cells. Despite the high levels of CD8+ HLA-DR+ cells in hepatosplenic patients, they presented a decreased ratio of CD8+ CD28+/CD8+ cells. These findings of a different percentage of circulating CD8+ CD28+ cells might explain the different in vitro cellular reactivity of asymptomatic and hepatosplenic patients and the defects in the cytokine secretion patterns reported in individuals with hepatosplenic schistosomiasis.

HLA Class II antigens are associated with resistance or susceptibility to hepatosplenic disease in a Chinese population infected with Schistosoma japonicum

The major histocompatibility Class II alleles of 108 individuals living in an area endemic for schistosomiasis japonica in China were determined to identify possible immunogenetic associations with advanced schistosomiasis. Two alleles, HLA-DRB1 ∗1202 ( P=0.002) and HLA-DQA1 ∗0601 ( P=0.001) were strongly associated with resistance to advanced disease. In contrast, HLA-DQB1 ∗05031 ( P=0.02) was associated with susceptibility to advanced schistosomiasis. The remaining alleles showed no association with advanced disease. Allele DRB1 ∗1202 co-occurred with allele DQA1 ∗0601; therefore, their independent protective effects could not be ascertained. In contrast, alleles DQA1 ∗0601 and DQB1 ∗05031 never co-occurred and had opposite and significant effects on the occurrence of disease.

High Levels of TNF, Soluble TNF Receptors, Soluble ICAM-1, and IFN-γ, but Low Levels of IL-5, Are Associated with Hepatosplenic Disease in Human Schistosomiasis Mansoni

AbstractIn a case-control study based in two areas of Kenya, hepatosplenic schistosomiasis mansoni was shown to be linked with low levels of IL-5 and with correspondingly high IFN-γ, TNF, and circulating soluble TNF receptor I (sTNFR-I), sTNFR-II, and sICAM-1. PBMC from the hepatosplenic cases responded to in vitro Ag stimulation with significantly higher levels of IFN-γ and TNF, but lower levels of IL-5, compared with nonhepatosplenic controls matched for age and infection intensity. Most of these correlations were confounded by differences between geographical areas. However, principle component analysis identified a high IFN-γ and TNF, and low IL-5 axis in the data as the first principle component; this was significantly associated with hepatosplenomegaly (p &amp;lt; 0.0005) even after controlling for area. High plasma levels of sTNFR-I (p &amp;lt; 0.001), sTNFR-II, (p &amp;lt; 0.0001), and sICAM-1 (p &amp;lt; 0.009) were also significantly associated with hepatosplenomegaly, independently of area, in the case of the soluble forms of both TNF receptors. These parameters were negatively related to IL-5. These results suggest that proinflammatory cytokines are involved in the hepatosplenic disease process in infected individuals who have low anti-inflammatory Th2 responses and that sTNFR may be a useful circulating marker for this disease process, perhaps reflecting the level of TNF activity in hepatic tissues.