Search

A well defined model of T cell-mediated hypersensitivity-type granulomatous inflammation induced by Schistosoma mansoni eggs was used to assess the role of IL-4 and IFN-gamma in granuloma development. Synchronized pulmonary granulomas were induced and isolated from S. mansoni-infected mice during vigorous (8 wk) and modulated (20 wk) stages of the disease. The sequential production of IL-4 and IFN was determined and related to temporal changes in granuloma macrophage production of IL-1, TNF, and superoxide anion (O2-). During the vigorous stage, IL-4 was produced on days 1 and 2 of granuloma formation, whereas IFN was released in greatest amounts on days 4 to 8. The peak of IL-4 occurred in a window between the peak of IL-1 (1 day) and maximal TNF production (8 to 16 days). Maximal O2- release tended to parallel IFN production. During the modulated stage when the inflammatory response is attenuated, IL-4 production was dramatically reduced as were levels of IL-1 and TNF, but IFN production persisted and maximum O2(-)-producing capacity was only delayed in onset. mAb specific for IL-4 and IFN were used to examine the effect of in vivo depletion of these cytokines on granuloma development. Administration of a single 1.0-mg dose of anti-IL-4 antibodies to mice with synchronously developing granulomas dramatically reduced granuloma size (40 to 50% suppression of area) during an 8-day study period, whereas antibodies to IFN had no effect on size. However, the latter treatment reduced giant cell formation. Our results indicate that granuloma development involves an orchestrated production of cytokines possibly resulting from sequential participation of different Th cell populations. Moreover, IL-4 is a pivotal cytokine in anamnestic cellular recruitment and subject to endogenous regulation.

Spleen cell proliferative responses in BALB/c mice were assessed at varying intervals after vaccination or primary infection and subsequent cercarial challenge. Mice were vaccinated with 500 50-Krad-irradiated Schistosoma mansoni schistosomula or infected with 20 normal schistosomula. Prior to challenge, splenic responses in the two test groups to phytohemagglutinin (PHA) declined progressively while schistosomula (SMA)-driven responses increased. After challenge, PHA responses increased in both groups on day 3 then declined to significantly lower levels compared to normal controls. On day 3 after challenge, SMA responses in vaccinated mice were vigorous, and greater than twice the responses in infected mice. Thereafter, responses in vaccinated mice declined while responses in infected mice increased on days 7 through 25 but dropped markedly by day 39. For the infected group, in vitro depletion of plastic adherent cells or Lyt 2.2+ lymphocytes resulted in augmented SMA responses 3 days post-challenge by greater than 400% and greater than 100%, respectively. Depletion of either cell population in the vaccinated group had no significant effect. Protection assessed by total worm burdens showed a reduction of 62% in vaccinated mice and 43% reduction in infected mice. The post-challenge results indicate that these two models of anti-schistosomula immunity differed in the dynamics of their splenocyte antigen-specific proliferative responses. These findings may contribute to an understanding of the mechanisms by which resistance to S. mansoni is induced.

A cDNA that encodes Schistosoma mansoni tropomyosin, except for 10 amino acids at the amino terminus, has been cloned into a pOTSNCO plasmid vector. Induced expression resulted in a constant level of recombinant protein production. The recombinant S. mansoni tropomyosin was purified from preparative SDS-PAGE gel and by a combination of 20% ammonium sulfate fractionation and fast protein liquid chromatography-ion-exchange chromatography. The purified recombinant S. mansoni tropomyosin was tested as an immunodiagnostic reagent in Western blot and enzyme-linked immunosorbent assays. Sera from individual patients with chronic S. mansoni infection, but not S. haematobium, S. japonicum, parasitic infections other than schistosomiasis, and without infection reacted with the recombinant tropomyosin. The species specificity of S. mansoni tropomyosin suggests that further study of its potential as an immunodiagnostic reagent is warranted.

The extent of eosinophil and neutrophil cell-mediated cytotoxicity on Brugia malayi microfilariae by sera from an area endemic for bancroftian filariasis in Andhra Pradesh, India, has been studied in vitro in terms of the clinical status of the subjects. At physical examination, 66 serum samples were collected. Group "A" included patients with various disease manifestations like lymphoedema, hydrocoele, lymphangitis and elephantiasis. Group "B" had microfilaraemia ranging from 1-300/ml of blood. Subjects with no history of infection past or present (endemic normals) were studied as Group "C". Out of 38 sera tested individually with eosinophils, 14/18 of Group A, 10/11 of Group B and 7/9 of Group C promoted higher (21-97%), moderate (18-88%) and highest (51-95%) range of cytotoxicity, respectively. The age, clinical status and duration of disease among the infected subjects appeared to correlate with the microfilarial mortality. In Group B, we observed the highest microfilarial count (16-300/ml) in lower (1-20 yrs) age groups. These individuals promoted higher (77-83%) cytotoxicity compared to the older age group (21-40 or 41-60) with low (1-36/ml) microfilaraemia. Group C sera were highly toxic to microfilariae. All those that were positive promoted greater than 50% mortality. Eighteen nonendemic normal sera had no effect on microfilariae. The overlapping but differential toxicity of the sera indicates that various clinical manifestations are associated with different types of cellular and humoral responses. These studies should help focus identification of the target epitopes of various immune responses of the host.

The role of T cells in immunity to murine schistosomiasis was examined through the use of T cell clones that recognize the live schistosomulum stage of Schistosoma mansoni. T cell clones of three different phenotypes were isolated and expanded into long term culture from lymph nodes of C57B1/6J mice vaccinated with irradiated S. mansoni larvae. They were characterized by surface markers, lymphokine production, and functional assays. The m.w. range of the Ag recognized by one clone was identified through nitrocellulose blotting and confirmed with a preparation of the putative protein made by immunoaffinity purification. All but one of the clones were CD4+, CD5+, Th cells. One clone, 35, produced Il-2 and IFN-gamma and was designated a TH1 clone. The others were designated TH2 clones because of Il-4 production. One clone was CD8+ and failed to show help. Clone 35 recognized live schistosomula and produced Il-2 when presented a 27-kDa protein from nitrocellulose. It proliferated in response to purified Ag. Clone 35 participated along with macrophages to induce up to 98% killing of live schistosomula in vitro. IFN-gamma and TNF-alpha were essential to the killing mechanism whereas Il-1, Il-2, and Il-4 were not required. This study has approached Ag identification for vaccine development from the point of view of T cells and showed that TH1 cells are essential to in vitro macrophage killing of schistosomula in murine schistosomiasis.

Forty-five children with Schistosoma haematobium infections were studied utilizing a whole-blood culture technique to assay lymphocyte blast transformation responses. The mitogenic lectins, phytohaemagglutinin (PHA) and pokeweek mitogen (PWM), and heterologous schistosomal antigens from adult worms and eggs were used. Responsiveness to PHA was intact but PWM responses were significantly impaired. Varying responses to schistosomal adult worm antigens were evident. Responses to soluble egg antigens were consistently low. No correlation of lymphocyte transformation responses was evident with egg excretion rates or clinical data. Treatment, primarily with niridazole, resulted in augmented cellular immune responses to PHA, PWM and adult worm antigens and two and eight weeks post-therapy. Anti-egg antigen responses did not significantly change. It was evident that niridazole did not induce cellular immunodepression. The role of schistosome-specific immune modulation is discussed.

CBA/J mice undergoing pulmonary granulomatous inflammation exhibited depressed NK cytolytic activity. Granulomas induced by i.v. embolization of Schistosoma mansoni eggs (hypersensitivity type) or Sephadex beads (foreign body type) both caused reduced NK activity, although hypersensitivity granulomas induced a significantly higher level of NK suppression. Kinetic analysis of hypersensitivity lesions at 4, 8, 16, and 32 days post-embolization indicated that NK activity was significantly suppressed by day 8, maximally suppressed by day 16 (at the peak of the inflammatory response) then returned to near control values by day 32 (as the granulomas resolved). Suppression of NK activity ranged from three- to 15-fold in different experiments. NK cells obtained from both spleen and peripheral blood demonstrated reduced NK activity with kinetic patterns similar to the granuloma NK cells. Suppression was not due to reduced splenic NK cells as the frequency of YAC-1 binding cells, as well as asialo GM1+ or laminin+ cells remained constant over the entire study period. Suppression of NK activity did not appear to be due to serum components or suppressor cells present in the spleen preparations. However, the suppression of NK activity could be reversed by overnight incubation of spleen cells at 25 or 37 degrees C or daily treatment of the mice with indomethacin. Suppression also appeared relatively specific for NK cells as the generation and expression of cytotoxic T lymphocyte activity was not affected.

Infective stage larvae (L3) of Loa loa and Brugia malayi upon in vitro incubation with normal human serum activated the alternative complement pathway. C3 conversion products were detected on larval cuticles by eosinophil adherence and by immunofluorescence with C3c antiserum. No evidence for cuticle binding of IgG, IgA, IgM, Clq, or C4 was found by immunofluorescence. L3-induced C3 activation was inhibited by 10 mM EDTA but unaffected by 10 mM Mg++-EGTA. Human sera deficient in C2, C4, or C6 incubated with L3 resulted in C3 activation. However, sera treated with zymosan or heated for 1 h, 56 degrees C were unreactive with L3. Immunoelectrophoresis of fresh serum exposed to L3 for 1 h at 37 degrees C showed C3 cleavage products. The results indicate that these nematode L3 activate the alternative complement cascade via cuticular surface components. Larval viability was unaffected by complement activation or by adherence of eosinophils.

Immunodiagnostic tests for human protozoan and helminthic infections are reviewed. The need for immunodiagnostic tests varies with each infection but is of paramount importance in those infections that cannot be parasitologically diagnosed readily such as toxoplasmosis, pneumocystosis, Chagas' disease, trichinosis, hydatidosis, cysticercosis, and visceral larva migrans. Immunoassays are also needed for those worldwide highly prevalent infections with severe morbidity to be used in seroepidemiology and in the follow-up evaluation of control programs. The most important are malaria, schistosomiasis, onchocerciasis, lymphatic filariasis, and trypanosomiasis. Major advances have been made in the use of enzyme-linked immunosorbent assay (ELISA) as a practical and rapid test for use in endemic countries and in the identification and isolation of diagnostic parasite antigens aided in particular by the use of monoclonal antibodies. Development of immunodiagnostic tests for specific parasite antigens in body fluids for many infections is being actively pursued.

Disease concepts and medical treatment practices surrounding schistosomiasis haematobium were studied among males in Upper Egyptian villages and towns using interview methods. Most informants considered bilharzia to be a serious disease for which they commonly sought treatment. Its occurrence was attributed primarily to natural causes, particularly various aquatic worms and insects, dirts, excrement, dead animals, toxins and stagnant and vegetated waters, mostly large canals. Contact with water from the Nile river was generally thought to be quite safe. Drug treatment was weakly associated with amount of education. All groups reported use of antischistosomal drugs and plant medicines. Seventy-four per cent of the sample had a treatment history, 64% having taken oral drugs and/or injections, 40% plant medicines and 29% both. Drinking decoctions of damsissa (Ambrosia maritima) was the most commonly used household remedy. Plant materials were usually obtained from fields, gardens and local markets and patent medicines from nearby clinics and private physicians in towns. Recommendations are made for the national mass chemotherapy programme.

In an ongoing study of obscure fevers in Cairo, Egypt which is presently in its 6th year, 12 cases of hepatic amebiasis have been diagnosed. Three were diagnosed during the period 1971-1974. With the introduction of amebic serologic techniques, particularly counterimmunoelectrophoresis, nine additional cases have been diagnosed in 1975-1976. Of 9 patients treated with metronidazole 6 were rapidly cured, 2 had a recurrence of fever necessitating surgical drainage of the abscess, and 1 died suddenly on the 3rd day of therapy.

This report describes two Egyptian patients who presented with the nephrotic syndrome and concurrent infections with Schistosoma mansoni and Salmonella paratyphi A. Unlike similar cases previously reported from this unit, these patients did not respond to antimicrobial and antischistosomal therapy, and their renal biopsies demonstrated amyloidosis. These two case reports and several experimental observations suggest that chronic schistosomiasis and salmonellosis may lead to secondary amyloidosis in susceptible individuals.

Synchronous models of T-cell-mediated and foreign body granulomas were induced in mice by intravenous embolization of Schistosoma mansoni eggs and Sephadex beads, respectively. The authors then performed flow-cytometric analysis of lymphocytes from dispersed granulomas, spleens, and peripheral blood at 4, 8, 16, and 32 days corresponding to the induction, growth, and maintenance, and resolution of these lesions. Lymphocytes were identified on the basis of light scatter characteristics, and the nature of the cells was confirmed by cell sorting and electron-microscopic examination. Lymphocyte subpopulations were characterized with antibodies to lymphocyte surface markers, specifically Ig, Thy 1.2, Lyt 1, Lyt 2, and L3T4. Natural killer cells were identified with anti-asialo GM1. Egg-induced granulomas had more lymphocytes of all phenotypes at all time points. Surprisingly, there was a significant number of cells staining positive for asialo GM1. On Day 16 after embolization there was a greater percentage of helper T cells, as defined by positive staining with L3T4, in the egg model, compared with the bead model. There was no obvious shift of lymphocytes from either the blood or spleen into the granuloma. These data confirm the importance of T cells in the direct participation of granulomatous inflammation, and the large numbers of asialo GM1-positive cells suggest a role for natural killer cells.

This study assessed in vivo and in vitro parameters of cell-mediated immunity in 45 tuberculous meningitis patients. Delayed-type hypersensitivity responses to purified protein derivative of tuberculin (PPD), Candida albicans and streptokinase-streptodornase antigens were lacking in 34 patients compared to 2 of 54 normal volunteers. Circulating T lymphocyte subpopulations (E-rosetting active and total T cells) were diminished in 41 patients studied compared to 41 normal donors (p less than 0.001). Lymphocyte blast responses to PPD (25 micrograms-500 micrograms/ml) were positive but quantitatively depressed in all 34 patients studied compared to PPD positive normal donors (p less than 0.001). Phytohemagglutinin responses were significantly depressed (p less than 0.001). Repeat studies in 20 patients 4-5 months post-therapy resulted in reversals of all parameters to control values with heightened blastogenic responses to all PPD concentrations.

The humoral and cellular immune response to filarial parasites is complex. Numerous studies have shown that antibodies to a large number of protein and non-protein antigens may be produced over the course of infection and that immune recognition of any given antigen may vary by disease manifestation and by immunoglobulin class. We have used the techniques of molecular cloning to attempt to dissect this complex interaction, and describe here two clones, isolated from an expression library constructed from Brugia malayi genomic DNA, whose products are recognized by distinct immunoglobulin classes. A lambda gt11 fusion protein containing part of the B. malayi myosin tail region is recognized by antibodies of the IgG class from a high percentage of bancroftian filariasis patients. A fusion protein containing a collagen-like sequence is less frequently and weakly recognized under the same experimental conditions, but is almost universally recognized when the developing reagent is specific for IgE. We thus identify specific filarial proteins against which the infected human host responds preferentially with antibodies of a specific immunoglobulin class.

Various arachidonic acid (AA) metabolites are known to regulate immune cell function(s) and dictate the progression of both acute and chronic inflammatory reactions. Using a model of Schistosoma mansoni egg-induced hypersensitivity granulomas, we have delineated the in vivo effects of inhibitors of cyclooxygenase (CO) and lipoxygenase (LO) pathways on granuloma development and granuloma macrophage I-region-associated (Ia) antigen expression. In addition, by high performance liquid chromatography (HPLC) we have profiled the metabolism of AA by macrophages that are isolated from granulomatous foci, and have biochemically characterized the in vitro specificity and activity of selected CO and LO inhibitors. The development of hypersensitivity-type pulmonary granulomas in mice was dramatically suppressed by inhibitors with anti-LO activity (nordihydroguairetic acid (NDGA), nafazatrom, and BW755c) in a dose-dependent manner, while indomethacin, which is primarily CO-selective, had no significant effect. Furthermore, NDGA and nafazatrom profoundly arrested the normal progression of preformed granulomatous lesions. The inhibitors of the LO pathway also suppressed the in vivo kinetics of Ia antigen expression by granuloma macrophages. In contrast, indomethacin augmented Ia-antigen expression. The major AA metabolites that were synthesized by the granuloma macrophages were shown to be leukotriene C4 and mono-hydroxyeicosatetraenoic acids. HPLC analysis of AA metabolites from granuloma macrophages that were treated with the various inhibitors confirmed that indomethacin was most CO-selective and NDGA most LO-selective. Nafazatrom and BW755c inhibited AA metabolism by both pathways. Notably, high concentrations of the compounds (5 X 10(-5) M) tended to suppress all products. Our results suggest that LO products may be important in the generation and maintenance of immune granulomatous inflammatory responses.

Crude polysaccharide antigen was extracted from Schistosoma mansoni egg homogenate by 44% aqueous phenol. The aqueous soluble polysaccharide extract was subjected to affinity chromatography with concanavalin A-Sepharose 4B. Two fractions (bound and unbound) were obtained; both of them gave precipitin lines with serum obtained from mice infected with S. mansoni. These precipitin lines gave partial identity. Further fractionation with wheat germ agglutinin-sepharose of the unbound fraction resulted in three antigenic fractions. These different antigens were eluted with different N-acetylglucosamine molarities (0, 0.05) and 0.5) and gave lines of identity when reacted against infected mouse serum. When the four antigenic materials were subjected to polyacrylamide gel electrophoresis and stained for proteins and polysaccharides no migration bands were observed. The chemical analysis of the two initial fractions showed a small percentage of amino acids in both fractions. Sugar analysis with gas-liquid chromatography showed different sugar composition of the two initial fractions.

An immunofluorescent study was carried out on skin biopsies from 12 leprosy patients who had been suffering from the disease for periods of one to 30 years; all were treated with dapsone and clofazimine at one stage. Skin biopsies made from reactive nodular lesions showed that all 12 had IgG deposits and seven had IgM deposits in the dermal-epidermal junction. No IgA, IgE, C3 and fibrinogen were found deposited in any biopsy. All patients had significantly raised levels of serum immunoglobulins and rheumatoid factor. Anti-epithelial (eight patients) and anti-nuclear (three patients) antibodies were also found. The possible role of autoantibodies in the present findings is discussed.

Larval ascarid nematodes recently discovered in fresh salmon were identified as Anisakis larval Type I, this roundworm is the etiologic agent of anisakiasis, a parasitic disease characterized by eosinophilic granulomas affecting the human gastrointestinal tract. Infection may occur following ingestion of raw or poorly cooked fish. Patients generally present with an acute abdominal syndrome mimicking a wide variety of clinical conditions, thus creating a diagnostic dilemma. Unselected samples of fresh salmon tested by the University of Michigan Clinical Microbiology Laboratory and School of Public Health were all infected, the mean worm burden calculated as 79.3 larvae per kilogram of fish. The significance of this infection and the implications for morbidity in the United States are discussed.

The effect of parenteral administration of prostaglandins, 15-(s)-15-methyl PGE1 (M-PGE) and PGF2 alpha (PGF) on the pathophysiologic manifestations of active murine Schistosoma mansoni infection was examined. Both M-PGE and PGF resulted in a nearly 50% suppression of granuloma size following a 7-day course of treatment. M-PGE and PGF appeared to act by different mechanisms. The former caused a broad-spectrum immunosuppression manifested as reduced splenomegaly, B-cell proliferation, and antigen-specific interleukin-2 (IL-2) production as well as decreased granuloma macrophage Ia antigen expression, superoxide anion (O2-) production, and interleukin-1 (IL-1) production. In contrast, PGF did not ameliorate splenomegaly, but caused increases in splenic asialo-GM1 (natural killer cells) and L3T4 (helper) positive T cells. Prostaglandin F also reduced IL-2 production, but to a lesser extent that M-PGE. Although PGF caused reduced granuloma macrophage Ia expression and O2- production, it did not suppress IL-1 production. Overall, these data show that PGs can significantly modulate immunopathologic events in chronic granulomatous disease states.

The role of oxygen reactive species in granulomatous hypersensitivity was explored using a model of pulmonary granulomas induced by intravenous injection of eggs from the parasite Schistosoma mansoni. Macrophages from sychronously developing lesions spontaneously released significant quantities of superoxide anion (26 nmoles/10(6)/2h) by 8 days of development. In contrast, the non-T cell foreign body (Sephadex bead) granuloma macrophages produced only (2 nmoles/10(6)/2h) small quantities. Daily administration of the oxygen scavenger, alpha-tocopherol, by either oral or parenteral routes caused up to 60% suppression of granuloma size. Moreover, parenteral administration of specific inactivators of 0-2 and H2O2, superoxide dismutase and catalase respectively, resulted in a 30 to 40% reduction in granuloma size. These data suggest that oxygen reactive species take part in the generation of hypersensitivity granulomas.

It has previously been shown that Salmonella paratyphi A associates with adult Schistosoma mansoni worms in animal models and in patients with schistosomiasis, resulting in Salmonella infections that are difficult to manage unless the helminthic parasite is eliminated. In the present study, characteristics of this association were explored. In vitro, fresh serum, but not heat-inactivated (56 degree C, 30 minutes) serum, from normal hamsters (NH) and schistosome-infected hamsters (SIH) equally inhibited bacterial growth. When either group of animals was given S. paratyphi A intracardially, there was a decline in recoverable bacteria in the blood for 3 days, but after the third day, the number of bacteria increased in SIH whereas NH blood became sterile. Co-cultivation of S. paratyphi A in Earle's medium with live worms yielded more bacterial growth than occurred in the medium without worms, suggesting that nutritional factors are involved in the relationship. An intimate association in vivo of bacteria and trematodes was confirmed by culturing Salmonella from both worm surfaces and homogenized worms, with more bacteria being recovered from female worms. Although the bacterial infection induced a significant hepatic shift of adult worms in SIH, oogram analyses were normal and no lethal effect of bacteria on worms was noted.

Thirty-five male patients with decompensated hepatosplenic schistosomiasis were longitudinally studied and divided into 3 Groups; with hepatitis B surface antigen (HBsAg) or antibody (anti-HBs) and a control group negative to both. Patients with HBsAg were persistently carrying the antigen as estimated by radioimmunoassay (RIA) for up to 3 years and when compared with the other 2 groups, they had significantly higher serum glutamic transaminases, their liver biopsy showed more destructive liver cell lesions in the form of chronic active hepatitis or liver cirrhosis, they were refractory to diuretic treatment and had higher mortality rate (64% in 3 years compared to 22% and 33% in the other 2 groups). The majority of patients with dual infection are at greater risk in spreading hepatitis B as they proved to carry the 'e' antigen.

An epidemiologic survey to assess the prevalence of bacteriuria in urinary schistosomiasis was carried out in a region endemic for urinary schistosomiasis in Egypt. Twenty of 390 (5.1%) school boys aged 5--16 years were bacteriuric. This prevalence rate is more than 10 times greater than that found in comparable surveys in areas non-endemic for urinary schistosomiasis. In this endemic population bacteriuria was found in 6.5% of active egg excreters and 2.3% of non-egg excreters.

Numerous species of Meriones have been incriminated as natural reservoir hosts of Leishmania major in Mongolia, Soviet Asia, Afghanistan, the Middle East, and North Africa. However, little is known about the immunological response or course of infection in these small rodents. In this study, 40 commercially obtained inbred Meriones unguiculatus were divided into equal groups and injected in the right hind footpad with various doses of L. major promastigotes or with medium only. At regular intervals, blood was collected from the animals for subsequent evaluation of the kinetics of anti-L. major serum antibody production. Footpad lesions were measured periodically for 13 wk, beginning just before infection. The humoral response to infection and the course and severity of disease were dose related. However, metastasis lymph nodes, liver, spleen, and secondary cutaneous sites occurred at each of the doses tested.

Preliminary findings of a study of the role of microspatial behavior and local ecological circumstances in the persistence of Schistosoma haematobium infection in El Ayaisha village, Upper Egypt, are presented. Twelve types of water contact activities were studied in three cohorts of 274,324 and 392 male students aged 5-16 during a 2-year period. Swimming and playing resulted in more frequent and intensive contact with potentially infective water and in more pollution of snail habitats with schistosome eggs than any other type of activity. Irrigation was probably not a major cause of S. haematobium infection in schoolboys and drinking water and fishing carried the smallest risk for this age group. Mapping and discriminate analysis of infection and transmission indicators revealed spatial associations between water contact, schistosome transmission and infection among the various age groups. The highest egg excretion rates in individuals and the highest prevalence rates were noted in the neighborhoods nearest to the canals. Water contact and contamination of water by the heavily infected school age boys is seasonally concentrated during the summer, when intermediate host snails and infective cercariae are also most common in the water. Frequency, type and duration of water contact change with age together with types of water bodies used, causing corresponding changes in exposure risk. Nevertheless, other factors, including acquired immunity, preexisting infections, chemotherapy and the effect of the study on the normal water contact behavior of the study population must also be evaluated. Contact with the Nile and the canals by the general nonschool population of El Ayaisha was studied to verify the observations among the schoolboys and to study socially linked activities and the transmission potential of the various transmission sites. Results are evaluated in regard to the feasibility of various schistosomiasis control measures in El Ayaisha.

The ability of arachidonic acid (AA) metabolites to regulate I-region-associated (Ia) antigen expression on macrophages from schistosome-egg-induced pulmonary granulomas was examined. The prostaglandin (PG) analog 15-S-15-CH3-PGE1 (M-PGE1) and PGF2 alpha were found to modulate the kinetics of Ia expression when administered in vivo. Methyl-PGE1 significantly suppressed Ia antigen expression by hypersensitivity granuloma macrophages, while PGF2 alpha appeared to potentiate the expression. Lymphokine-induced Ia antigen expression by cultured granuloma macrophages was likewise dramatically inhibited by M-PGE1. Further analysis using systemically administered inhibitors of AA metabolism demonstrated that the cyclooxygenase inhibitor indomethacin caused augmentation of Ia expression. In contrast, lipoxygenase inhibitors significantly reduced both Ia expression and granuloma size. The role of AA metabolites in modulating chronic inflammation is discussed.

Vaccination of inbred jirds (Meriones unguiculatus) with 60cobalt radiation-attenuated Brugia malayi infective stage larvae (L3) protected against homologous challenge given either subcutaneously (sc) or by the intraperitoneal route (ip). At necropsy numerous nodules were recovered from the peritoneal cavities of jirds which had been vaccinated sc and challenged ip. Histopathologic analysis showed these to be granulomas containing dead and dying larvae and transmission electron microscopy showed that eosinophils were present in high numbers around and within the larvae. Structural damage to the L3 cuticle was apparent in discrete areas and eosinophils actively entering the breached cuticle at the time of fixation were observed. Coalescence of eosinophil secretion granules and the formation of degranulation vacuoles were seen in eosinophils throughout the granulomas. Degranulation resulted in the deposition of electron-dense material on the surface of the larval cuticle. The jird vaccine model for B. malayi thus appears to be a potentially useful tool for investigation of immune mechanisms in filariasis.

T-lymphocyte subpopulations in cerebrospinal fluid (CSF) and peripheral blood fo 20 tuberculous meningitis patients were enumerated by sheep erythrocyte rosette assays. There were fewer active and total T lymphocytes in peripheral blood in patients than in controls. But patient CSF T-lymphocyte subpopulations were significantly higher than their peripheral blood values and no different proportionally from normal peripheral blood values. The results support the concept of immunologic compartmentalization of the neuraxis from the rest of the body.

Vaccination of inbred jirds (Meriones unguiculatus) with 60cobalt radiation-attenuated Brugia malayi infective stage larvae (L3) protected against homologous challenge given either subcutaneously (sc) or by the intraperitoneal (ip) route. Groups of jirds vaccinated once sc with 75, 15 Krad L3 showed from 69% to 91% reduction in recovered worms after ip challenge infection compared to infection in non-vaccinated control jirds, while 75% reduction in mean worm burden was seen in jirds receiving sc challenge infection. A single sc vaccination with 75, 10 or 20 Krad L3 produced no protection (10 Krad) and 64% reduction in recovered worms (20 Krad). Therefore the 15 Krad dose appeared to be best. A marked increase in anti-B. malayi antibody in vaccinated jirds was seen (by ELISA) immediately after challenge infection and an immunofluorescence assay showed that L3 incubated in serum from vaccinated jirds were completely and uniformly covered with specific antibody. Eosinophil-rich granulomas containing dead and moribund L3 were recovered from vaccinated jirds. This model of protective immunity in a Brugia-susceptible small rodent may provide a useful system for identification of molecularly defined filarial-protective immunogens.

The present study examined the potential role of IL-1 and TNF in granuloma formation. Mice were given i.v. injections of Schistosoma mansoni eggs or Sephadex beads to induce synchronous immune T cell-mediated (hypersensitivity type) or nonimmune (foreign-body type) granulomas, respectively. Granuloma macrophages isolated at 2, 4, 8, 16, and 32 days of granuloma formation were evaluated for their capacity to produce IL-1 and TNF in response to 1 microgram/ml LPS. This was related to circulating levels of the acute phase protein, serum amyloid P (SAP) and expression of Ia Ag by monocytes and macrophages. Macrophages from nonimmune bead lesions were generally weak producers of IL-1 and TNF. In contrast, those from T cell-mediated egg lesions produced significant levels of both monokines. Moreover, there was a clear pattern of sequential monokine production such that IL-1 was produced in greatest amounts early (2 to 4 days), whereas TNF was produced later (8 to 16 days). Levels of SAP showed an initial sharp rise following particle embolization, then decreased rapidly in bead injected animals. However, mice with immune granulomas showed a prolonged elevation in SAP levels that corresponded to the period of maximal IL-1 production (2 to 4 days). Macrophage/monocyte Ia Ag expression was greatest at 8 to 16 days, corresponding to the period of TNF production. Bead injected animals showed low levels of Ia expression over the study period. These findings suggest that IL-1 may be important in the early recruitment stages of granuloma formation while TNF may take part in later maintenance or effector functions. The extent of production of both is likely influenced by the local or systemic milieu of lymphokines.

An epidemiological study was conducted as an initial phase of a longitudinal study on the immunology of Schistosoma haematobium in Upper Egypt. The study area was confined to three villages in Qena governorate, a region endemic solely for S. haematobium. In a cross-sectional survey in two of these villages, the overall prevalence of infection was 28.7% (29.9% at Khozam and 26.9% at El Ayaisha) based on urine examination of the family members in every third household. S. haematobium infection was found in all age groups including infants below 1 year of age. The age distribution of those infected showed the classical rise in the percent infected, reaching a peak of 57-63% in the 11- to 15-year age group followed by a rapid decline and stable low prevalence below 28% in adult years. Males consistently had higher prevalence rates than females at all ages with the profiles of the age prevalence curves strikingly similar. In the two villages, significantly (P less than 0.05) higher infection rates were found in farmers compared to those in other occupations. The overall prevalence of infection in school children (5-16 years old) in the three villages was 61.1% based on the examination of one urine sample. Almost 10% greater prevalence was found when four consecutive daily urines were examined compared to one in the same study group sampled 1 month apart. There was a rapid increase in prevalence with age, reaching a maximum at age 10 with relatively little fluctuation to age 16 years. When comparing the age prevalence data with the intensity of infection expressed as either mean or median age excretion per milliliter urine, it was found that both were parallel and rose sharply from age 5-10 years, but the latter significantly declined several years prior to any perceptible diminution in prevalence.

A 42-year-old American male researcher contracted schistosomiasis from environmental sources in the course of his observations on human behavior in Upper Egypt. After a long asymptomatic period, he developed various symptoms and Schistosoma haematobium was found in a urine examination. After treatment with Metrifonate, urine examination became negative. However, abdominal pain persisted and most diagnostic tests were negative. Colonoscopic examination and biopsy of the mucosa revealed schistosomiasis. Treatment with Praziquantel was thoroughly effective in clearing the persistent Schistosoma haematobium infection. It is necessary to maintain a high index of suspicion in cases of potential schistosomiasis. The availability of nontoxic treatment is discussed.

The present study examines the kinetics of arachidonic acid (AA) metabolism by murine macrophages isolated from sites of experimentally induced pulmonary granulomatous inflammation. Macrophages of T-cell-mediated hypersensitivity lesions induced by Schistosoma mansoni eggs (SE-GM) and non-T-cell-mediated foreign-body-type lesions (FB-GM) induced by Sephadex beads were examined. Overall, macrophages from both types of lesions produced mainly lipoxygenase pathway metabolites, leukotrienes, and monohydroxyeicosatetraenoic acids (mono-HETEs). Early after induction (4 days [4D]), SE-GM showed an augmented zymosan-stimulated AA release and metabolism compared to resident peritoneal macrophages. Macrophages from mature lesions (8-32D) showed constitutive synthesis of metabolites and were refractory to zymosan stimulation. Both SE-GM and FB-GM showed augmented AA uptake incorporating a large proportion into neutral lipids. A direct comparison of SE-GM and FB-GM revealed that the T-cell-mediated lesion produced lesser amounts of prostaglandins and leukotrienes and showed reduced incorporation of AA into phosphatidylcholine. These data suggest that AA metabolism by granuloma macrophages is sequentially modified during recruitment and activation at sites of chronic inflammation.

Immediate and delayed hypersensitivity responses to schistosome adult worm skin test antigen were assessed in 418 farmers in Dakahlia Governorate, Egypt. All were from a population frame being epidemiologically evaluated for bilharzial urinary bladder cancer and thus were all 20 years old or older. A control, group of 108 adult urban dwellers without antecedent or current history of schistosomiasis were also tested. Ninety eight percent (411/418) of farmers and 35% (38/108) of controls showed reaginic hypersensitivity to 20 micrograms protein antigen. While 43% (180/418) of farmers and 4.6% (5/108) of controls showed positive delayed responses. Schistosoma haematobium eggs were found in 6% on urine cytology smears (Papanicolaou) and in 5% by Nuclepore filtration. A subsample of 97 individuals showed 21% to have S. haematobium eggs in urine by a traditional sedimentation technique. Immediate skin tests were equally positive in egg positive or egg negative farmers but delayed responses were 55% positive in the former and 26% in the latter. It is suggested that the delayed hypersensitivity skin test may be more specific and useful in epidemiologic surveys. The changing prevalence of S. haematobium infections in the Nile Delta is briefly discussed.

Percutaneous needle biopsy of the kidney on eight nephrotic patients with Schistosoma mansoni and chronic Salmonella paratyphi A infection showed diffuse proliferative glomerular change in all biopsies. Capillary basement membrane was normal. Diffuse granular deposits were detected in the glomerular mesangial cells by direct staining with fluorescein labelled anti-IgG anti-IgM. No fluorescence was obtained with rabbit anti-Salmonella paratyphi A. After treatment with ampicillin and niridazole, a reduction of cellular proliferation and mesangial matrix expansion was observed. Simultaneously following treatment there occurred a dramatic clinical improvement with cessation of proteinuria and a return of plasma protein levels and serum complement (C3) to normal values.

The present work deals with the development of an improved animal model to study the association of salmonellosis and schistosomiasis. The animal chosen was the hamster, Mesocricetus auratus, which can be readily infected with Schistosoma mansoni. Normal hamsters and schistosome-infected hamsters (SIH) were given approximately 2.0 x 10(7) Salmonella paratyphi A intracardially. It was found that S. mansoni infections enhanced and prolonged the growth of S. paratyphi A in hamsters. Animals with dual infections had increased mortality in comparison with those infected with just bacteria or parasite during the 50 days post-bacterial challenge. Further studies showed that in SIH, S. paratyphi A persisted in various organs for up to 8 weeks post infection. In contrast, concurrent Leishmania donovani infections have no effect on S. paratyphi A infections. Significant numbers of bacteria were cultured from well-washed schistosome worms recovered from SIH 6--8 weeks post-bacterial challenge. These findings suggest that a direct physical relationship between the bacteria and worms facilitates the establishment and growth of S. paratyphi A in vivo, and that a deficit in host immune response is not a major factor involved in the enhanced growth of S. paratyphi A.

As part of a series of epidemiological and ecological studies of leishmaniasis in Jordan, we have made functional studies of four isolates from human lesions and from ear lesions of three field-collected Psammomys obesus. Primary isolates were subcultured, frozen stabilates prepared and BALB/c mouse infectivity experiments initiated. Each mouse was inoculated with 4-8 x 10(4) promastigotes into a hind footpad. Quantitative evaluation of the footpads showed enlargement three to four weeks postinoculation. Amastigotes were readily identified in smears from footpad lesions and promastigotes in culture. At 47 days, liver and spleen samples grew out promastigotes. Biochemical characterization of these seven isolates was made by isozyme analysis using cellulose acetate membrane electrophoresis of fructokinase, phosphoglucose isomerase, phosphoglucomutase, aspartate aminotransferase, malate dehydrogenase, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. Reference isolates used for comparison were Leishmania major, L. tropica minor, L. donovani, L. aethiopica and L. m. mexicana. All seven Jordan isolates showed enzyme electromorphs identical to L. major, confirming our ecological/epidemiological studies that P. obesus is a major reservoir for human cutaneous leishmaniasis in Jordan.

Renal biopsies were studied by light and immunofluorescent microscopy in 13 young individuals with uncomplicated Schistosoma haematobium infections. Slight mesangial cell proliferation and matrix increase were found in three biopsies and focal interstitial inflammatory infiltrates were noted in six. However extensive IgG (nine cases) and IgM (seven cases) granular deposits were found in the mesangial areas. C3 was found in only three of these cases. Clq, fibrinogen, IgA and IgE were not found deposited except for one case with IgE. Schistosome antigen was identified in mesangial areas in four biopsies after acid treatment of the sections. It appears the immune complexes are deposited consistently in the renal glomeruli in S. haematobium infections but their role in inducing clinical renal disease is minimal.

Twenty-two male BALB/c mice were used in this investigation. A pellet of dry 9,10-dimethyl-1,2-benzanthracene powder was implanted in the submandibular salivary gland. Fifteen epidermoid carcinomas and four sarcomas were induced within a period ranging from 7 to 15 weeks. Epidermoid carcinomas were sucessfully transplanted into syngeneic mice.