Maternal behavior in wolf spiders: the role of abdominal hairs.

Newly emerged, juvenile wolf spiders do not settle on clothed or shaved areas of their mother's abdomen until after a period of days. Spiny, knobbed hairs, peculiar to adult female lycosids, apparently provide the stimulus and means for attachment by the inner layer of spiderlings. Innervated long, smooth hairs are mechanoreceptors which probably serve in other aspects of brood care.

Role of lipoxygenase products in murine pulmonary granuloma formation.

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.

Dynamics of arachidonic acid metabolism in macrophages from delayed-type hypersensitivity (Schistosoma mansoni egg) and foreign-body-type granulomas.

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.

Tuberculous meningitis: E-rosette-forming T lymphocytes in cerebrospinal fluid.

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.

Differential recognition of two cloned Brugia malayi antigens by antibody class.

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.

Onchocerca volvulus heat shock protein 70 is a major immunogen in amicrofilaremic individuals from a filariasis-endemic area.

Infestation with organisms causing lymphatic filariasis (i.e. Wuchereria bancrofti and Brugia malayi) results in a variety of clinical presentations. It is possible that some of the variation is due to differences in host response to parasite. To determine whether individuals who live in an endemic area but differ in their clinical manifestations respond to different filarial antigens, we screened Onchocerca volvulus expression libraries with sera from a number of individuals belonging to different clinical groups. The results of the study demonstrate that there are indeed differences in the recognition of three cloned filarial antigens and that this differential recognition is related to clinical symptomatology. The most striking finding is that an Onchocerca volvulus protein homologous to the 70 kDa Xenopus laevis heat shock protein is primarily recognized by individuals who are amicrofilaremic. Further analysis is required to determine whether these antigens play any role in the pathogenesis of filarial infection or have any potential value in protective immunity.

Water contact and Schistosoma haematobium infection: a case study from an upper Egyptian village.

The quantitative relationship between water contact and Schistosoma haematobium infection was studied in a cohort of male school children aged 6-17 in El Ayaisha village, Upper Egypt, during a two-year study. An exposure index (total body minutes, TBM) was used to identify the activities responsible for exposure to cercariae-infested water and to examine the relationship between water contact and infection. Results show that 65% of all contacts and 86% of all TBM were due to swimming in the Nile and canals and that swimming was the most important exposure and contamination activity. Using multivariate analysis, several sites, study periods, residence groups and mostly canal contacts were significantly correlated with egg-counts. Positive relationships could also be identified using egg-counts with water contact data from preceding study periods, indicating the influence of pre-existing infections, prepatency and seasonality of water contact and transmission. TBM were usually more significantly correlated with egg-counts than frequency and duration of contact. The relevance of the findings for control programmes and the use of school children and the exposure index for water contact studies are discussed.

Anisakis larval type I in fresh salmon.

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.

Schistosoma haematobium in Upper Egypt: analysis of dispersion patterns.

Statistical methods analyzing changes in dispersion patterns of parasites among hosts were applied to Schistosoma haematobium egg excretion data from a five-year study of a cohort of 1,400 boys in 3 villages in Upper Egypt. Despite significant changes in mean density of the parasites in the first 4 years, the degree of aggregation of S. haematobium among the cohort did not change markedly in analysis of egg count data obtained semiannually. Two other related measures of dispersion, mean crowding and patchiness, were also obtained and compared to prevalence and mean intensity, the components determining mean density of schistosomes among hosts. Anti-schistosomal chemotherapy with metrifonate in the cohort did not succeed in appreciably reducing the mean density of S. haematobium over a one-year follow-up. The dispersion pattern of S. haematobium among the study group was not markedly altered. Prevalence and mean intensity were useful indicators of changes in the degree of aggregation of S. haematobium among hosts. The inability of chemotherapy to provide a persistent decline in the mean density parameter is reflected in the rise of mean intensity and prevalence of S. haematobium 1 year post-therapy. It is suggested that analysis of quantifiable changes in dispersion patterns of S. haematobium among their hosts can be a useful aid in planning and assessment of control strategies.

Ultrastructural observations on the fate of Brugia malayi in jirds previously vaccinated with irradiated infective stage larvae.

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.

Brugia malayi: vaccination of jirds with 60cobalt-attenuated infective stage larvae protects against homologous challenge.

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.

Renal amyloidosis with nephrotic syndrome in two patients with schistosomiasis mansoni and chronic salmonellosis.

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.

Nephrotic syndrome in Schistosomiasis mansoni complicated by chronic salmonellosis.

Thirteen patients with concomitant chronic salmonellosis and schistosomiasis and with the nephrotic syndrome were studied. Of the seven patients' sera examined, all had markedly low complement C3 and near normal C4 levels. This indirectly suggests an active role of Salmonella endotoxin in the etiology of the nephrosis.

Laboratory and field evaluation of a direct filtration technique for recovery of schistosome cercariae.

The use of cercariometry in epidemiological studies has been limited by turbidity, difficulty of recovering cercariae at low concentrations in natural waters, and by complex apparatus that requires a power source. The technique of differential filtration developed by Theron has been modified and tested in the laboratory and in the field in Upper Egypt for detection of Schistosoma haematobium cercariae. A recovery filter with a pore size of 30 micrometer was found to give the best results. The recovery rate in the laboratory was 51% on filtration of 5-liter samples of formalin-treated water, and 19-30% with 10- and 20-liter samples. This moderate efficiency is offset by simplicity of the technique, rapid filtration, and ease of reading the recovery filter, permitting sampling of large volumes of water in the field by persons with little training. Average densities of 0.024 cercariae per liter of water were found at the Nile and 0.029 cercariae per liter in the irrigation canals. Most cercariae were recovered between 0.700 and 0900 hours.

Treatment of complicated schistosomiasis mansoni with oxamniquine.

Twenty male patients (mean age 23 years) with Schistosoma mansoni infections (mean egg count 429 +/- 311/g feces) were each treated with oxamniquine orally in a single daily dose of 20 mg/kg for 3 consecutive days. Seventeen patients had hepatosplenomegaly, two of these had ascites. Three patients had diffuse colonic polyposis, one of these had ascites. Except for one who developed mild hematemesis 3 days after treatment, all patients tolerated the drug very well. However, 11 patients developed a fever 24 to 48 hours after completing treatment, which lasted for 2-3 days and coincided with increased excretion of schistosomal antigens in urine. Three months after completing therapy, all except one young patient ceased to have live egge in the stools or rectal tissue. Six months after treatment, three patients with colonic polyposis showed marked clinical improvement and sigmoidoscopic and barium enema examination demonstrated almost complete disappearance of all polyps.

Schistosoma mansoni tropomyosin: production and purification of the recombinant protein and studies on its immunodiagnostic potential.

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.

Hepatic amebiasis: diagnostic counterimmunoelectrophoresis and metronidazole (flagyl) therapy.

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.

Interaction of Salmonella paratyphi A and Schistosoma mansoni in hamsters.

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.

Salmonella paratyphi A in hamsters concurrently infected with Schistosoma mansoni.

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.

A longitudinal study of Schistosoma haematobium infection in Qena governorate, Upper Egypt. 1. Initial epidemiological findings.

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.