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PubMed2006

Arthritis associated with Strongyloides stercoralis infection in HLA B-27-positive African.

A 44-year old West-African living in Germany since 18 years presented because of persistent painful swelling of both ankle joints and diffuse lymphoedema of feet occurring after a trip to Morocco. Laboratory tests revealed inflammation and eosinophilia. HLA-B27 was positive. Antinuclear antibodies and rheuma factors were not found. There was no evidence of an infection with bacteria or viruses known to cause arthritis. Filariasis was excluded. Microscopy of fresh stool revealed larvae of Strongyloides stercoralis. Symptoms resolved after specific antihelminthic therapy with ivermectin 0.2 mg kg(-1) day(-1) for 2 days and non-steroidal anti-inflammatorials. Reactive arthritis is known to be caused by various bacterial agents. In some individuals, arthritis may be due to helminths, such as S. stercoralis. Patients with strongyloidiasis may respond to non-steroidal anti-inflammatorials but must not undergo treatment with corticosteroids before having received antihelminthic therapy because immunosuppression may result in life-threatening strongyloides hyperinfection syndrome.

Adult↗
PubMed1987

Strongyloides stercoralis hyperinfection in a patient with the acquired immune deficiency syndrome.

Severe infections with Strongyloides stercoralis occur in immunocompromised patients. Strongyloides hyperinfection syndrome complicated by gram-negative bacteremia and meningitis in a bisexual man with the acquired immune deficiency syndrome (AIDS) is described. Increased awareness of this infection, which may also be sexually transmitted, is recommended when caring for patients with AIDS who are homosexual, or have resided in areas endemic for strongyloidiasis. Multiple stool examinations should be performed routinely for such patients. Examination of sputum for the parasite is recommended if pneumonia is present. Prompt diagnosis and therapy are essential for prevention of fatal dissemination.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Strongyloides stercoralis: identification of a protease that facilitates penetration of skin by the infective larvae.

Host invasion and tissue migration of several helminths have been linked to the expression and release of parasite-derived proteases. One of the most remarkable examples of tissue migration is that of larvae of the nematode parasite Strongyloides stercoralis, which can move through tissue at speeds of up to 10 cm per hour. We have shown the Strongyloides L3 larvae secrete a potent histolytic metalloprotease to facilitate their rapid migration. This protease has elastase activity and catalyzes the degradation of a model of dermal extracellular matrix. The importance of this enzyme in the pathogenesis of strongyloidiasis is underscored by the observation that invasion by larvae of skin in vitro is prevented by metalloprotease inhibitors. These results substantiate the role of proteases as virulence factors in strongyloidiasis, as well as other related parasitic infections, and suggest new approaches to therapy.

Animals↗
PubMed1995

Migration route of Strongyloides venezuelensis in rodents.

Infective larvae of Strongyloides venezuelensis were injected into the medial aspect of the thigh of Wistar rats and ddy mice to investigate their distribution within their hosts with the passage of time. The parasite migrated subcutaneously or intramuscularly towards the upper body and gradually arrived in the lung from 45 h post infection (p.i.) in rats and from 42 h p.i. in mice. After the larvae passed through the trachea, they first appeared in the small intestine at 60 h p.i., probably via the oesophagus and stomach. In comparison to the rats, more larvae were recovered from the mice at all times, and a higher concentration of larval localization was observed in the mice. The present study has established a good model of larval migration of S. venezuelensis in rodents, with the migration route apparently different from of Strongyloides ratti, another species found in rodents.

Animals↗
PubMed1996

Efficacy of an in-feed formulation of ivermectin against adult worms and somatic larvae of Strongyloides ransomi.

The efficacy of an in-feed formulation (IVOMEC premix) containing 0.6% ivermectin was tested against Strongyloides ransomi in swine. The efficacy of ivermectin against patent infections of S. ransomi when given via the feed at 2 ppm for 7 days (Days 0-7) to provide 100 mcg ivermectin kg-1 body weight day-1 was evaluated in a study with 16 3-month-old male castrated piglets. Seven days prior to treatment each piglet was infected subcutaneously with 2500 infective larvae of S. ransomi. Fecal egg counts were carried out on Days -7, 0, 7 and 14, and worm counts on Day 14. Efficacy was 100% in all treated piglets. Two trials involving 40 pregnant gilts were carried out to evaluate the efficacy of ivermectin against the somatic larval stages of S. ransomi when given at a daily dose of 100 mcg kg-1 body weight for 7 days starting on Days 66, 78, 92 or 103 of pregnancy. The gilts were each experimentally infected with three subcutaneous injections of 250,000 infective larvae, with the last infection given between 12 and 30 days prior to commencement of treatment. Gilts were confirmed free of pre-existing intestinal stages of S. ransomi prior to ivermectin treatment. Fecal nematode egg counts were carried out in gilts/sows and piglets subsequently born. The Strongyloides larvae present in sow milk 1, 2 and 7 days post partum were counted. Fourteen days post natum, worm counts were performed in four randomly selected piglets for each litter. IVOMEC premix given to pregnant gilts prevented shedding of larvae in sow milk, egg output in feces and the establishment of S. ransomi in piglets.

Administration, Oral↗
PubMed2006

Expression of IL-4 receptor on non-bone marrow-derived cells is necessary for the timely elimination of Strongyloides venezuelensis in mice, but not for intestinal IL-4 production.

In rodents and in humans, Strongyloides infection induces an immune response which is predominantly Th2 in nature. In an attempt to understand the role of the IL-4R/STAT6 signaling pathway, the pathway activated by the Th2 cytokines IL-4 and IL-13, in the induction of protection during Strongyloides venezuelensis infection, we have carried out experiments in mice lacking the IL-4Ralpha chain. Experiments were also carried out in STAT6 (STAT6(-/-)) and IL-12-deficient (IL-12(-/-)) mice for comparison. There was enhancement of IL-13 and abolition of IFN-gamma production in the small intestine of 7 day-infected IL-12(-/-) animals but worm elimination proceeded with very similar kinetics to those of wild-type mice. In IL-4Ralpha- or STAT6-deficient mice, there was a delay in parasite elimination and a large number of S. venezuelensis adult worms was still present in the small intestine 14 days after infection. Moreover, IgE production was completely abolished in IL-4Ralpha- or STAT6-deficient mice but tissue eosinophilia was normally induced by the parasite infection in deficient mice. Bone marrow transfer experiments showed that worm elimination occurred when a functional IL-4 receptor was present only in non-bone marrow-derived cells but not when IL-4R was only expressed in bone marrow cells. The induction of IL-4, but not IL-13, occurred independently of IL-4R. We believe these results are the first direct evidence that the mechanism responsible for the timely elimination of S. venezuelensis is dependent on the activation of IL-4R and STAT6. Moreover, a functional protective response is dependent on the expression of IL-4Ralpha on non-bone marrow-derived cells.

Animals↗
PubMed2005

Identification of an astacin-like metallo-proteinase transcript from the infective larvae of Strongyloides stercoralis.

Strongyloides stercoralis, an important nematode pathogen of humans, is transmitted by contact with soil contaminated with the microscopic larvae of the parasite. We determined the cDNA sequence and deduced amino acid structure of a metallo-proteinase that is abundantly transcribed expressed by infective stage larvae of S. stercoralis. This deduced structure of the enzyme revealed a multi-domain protein that included an NH2-terminal peptidase. This peptidase consisted of a signal peptide, a pro-enzyme region, and a mature peptidase domain that included the metal ion co-ordinating motifs, HETSHALGVIH and SIMHY ("Met-turn"), characteristic of the catalytic active site of members of the metzincin superfamily of zinc metallo-endopeptidases. It was phylogenetically and structurally similar to astacin from the digestive gland of the crayfish Astacus astacus, to the HCH-1 peptidase of Caenorhabditis elegans required for hatching and migration of a post-embryonic neuroblast, and to the morphogenetically important peptidases, bone morphogenetic protein-1 (BMP-1) and Drosophila tolloid. In addition, the Strongyloides enzyme, designated strongylastacin, includes a central epidermal growth factor (EGF) domain followed by a carboxyl CUB (complement sub component C1r/C1s/embryonic sea urchin protein Uegf/bone morphogenetic protein) domain. Inspection of the dbEST database revealed the presence of at least 9 transcript clusters that are related to greater or lesser extent to strongylastacin; based on these expressed sequence tags, strongylastacin was expressed only in the infective third stage larvae, whereas other transcript clusters were expressed both in filariform and rhabditiform stages or only in the rhabditiform stage. Based on the deduced sequence, structure, and expression profile, strongylastacin is the probable candidate for the zinc-dependent metalloprotease, Ss40, known to be deployed by larvae of S. stercoralis to penetrate human skin to initiate infection.

Amino Acid Motifs↗
PubMed2006

Strongyloides stercoralis hyperinfection in systemic lupus erythematosus and the antiphospholipid syndrome.

OBJECTIVE: The Strongyloides stercoralis hyperinfection syndrome (SHS) may develop in individuals with asymptomatic infection receiving immunosuppressive treatment. This report summarizes current knowledge regarding SHS in patients with systemic lupus erythematosus (SLE) and associated antiphospholipid syndrome (APS). METHODS: Two patients with active SLE and associated APS presenting with SHS are reported. Additional cases of strongyloidiasis in SLE were identified and reviewed. RESULTS: Patient 1: A 34-year-old woman with SLE and APS characterized by active glomerulonephritis, stroke, and several hospital-acquired infections presented with vomiting and diffuse abdominal pain. Intestinal vasculitis was suspected, and treatment with methylprednisolone and cyclophosphamide was given. Response was partial. A gastric biopsy revealed S. stercoralis larvae. She received ivermectin and eventually recovered. Patient 2: A 37-year-old man with active glomerulonephritis and APS with recurrent thrombosis presented with digital necrosis. Necrotizing vasculitis was suspected and treated with immunosupressants. He suddenly developed respiratory failure secondary to alveolar hemorrhage and bronchoalveolar lavage was performed. The patient developed Gram-negative septic shock and died. The postmortem result of bronchoalveolar lavage yielded Strongyloides larvae. Nine cases of strongyloidiasis and the SHS in SLE patients reported in the literature were identified and reviewed. Five of these patients died; none had associated APS. CONCLUSIONS: These cases suggest that the SHS can exacerbate SLE and APS, predisposing to Gram-negative sepsis and death. Immunocompromised patients need an early diagnosis and specific treatment of parasitic diseases and their complications. The SHS should be considered in the differential diagnosis of lupus complications in patients from endemic areas.

Adult↗
PubMed2003

Larvicidal effects of several chemicals on Strongyloides infective larvae.

The larvicidal effects of 11 anthelmintics, 7 pesticides and 4 disinfectants were evaluated with infective larvae of Strongyloides papillosus (SPL) and Strongyloides venezuelensis (SVZ). The lethal concentrations against SPL and SVZ were found to be similar. Three chemicals (dichlorvos, levamisole and trichlorfon) showed highest larvicidal effects. The 50% lethal concentration (LC(50)) values for the three compounds against SPL larvae were 0.08, 0.24, and 0.59 ppm, respectively.

Animals↗
PubMed2002

Strongyloides stercoralis: high worm population density leads to autoinfection in the jird (Meriones unguiculatus).

At 28 days post-infection autoinfective third-stage larvae (L3a) of Strongyloides stercoralis occurred in jirds infected with 10,000 infective third-stage (L3i). Previously in the jird model of strongyloidiasis, autoinfection had been seen in immunologically immature or immunosuppressed jirds only. The heavily infected jirds described herein had a strong anti-L3i immune response at the same time the living L3a were found in their tissues. This was demonstrated by the rapid killing of L3i in subcutaneously implanted diffusion chambers. No decrease of intestinal motility was observed in these heavily infected jirds, indicating that an increased time for development was not the explanation for the presence of L3a. These larvae were found only in jirds when concomitantly a large number of first-stage larvae (L1) occurred in the intestines. We suggest that the development of L3a in the adult jird model is a rare event and thus, autoinfection occurs only when the intestinal population of L1 is very large, as was the case in the heavily infected jirds. Index Descriptors and Abbreviations. Nematode; Strongyloides stercoralis; Mongolian gerbil; Meriones unguiculatus; autoinfection; larval development; L3i, infective third-stage larva(e); L3i+, tissue migrating third-stage larva(e); L3a, autoinfective third-stage larva(e); L1, first-stage larva(e); PI, post-infection.

Animals↗
PubMed2000

The small subunit ribosomal RNA sequence of Strongyloides stercoralis.

The published small subunit rRNA (ssrRNA) gene sequences for Strongyloides ratti and Strongyloides stercoralis are remarkably divergent, particularly in the 5' 400 bases of the approximately 1700 base pair (bp) sequences. This level of divergence between species nominally in the same genus was unprecedented. We have redetermined the ssrRNA sequence of S. stercoralis and find that the published sequence is a chimaera of parasite and fungal segments. The true sequence for S. stercoralis ssrRNA is very similar to that of S. ratti.

Animals↗
PubMed2000

The neurons of class ALD mediate thermotaxis in the parasitic nematode, Strongyloides stercoralis.

Strongyloides stercoralis, a skin-penetrating nematode parasite of homeotherms, migrates to warmth. In nematodes, the amphids, anteriorly positioned, paired sensilla, each contain a bundle of sensory neurons. In the amphids of the free-living nematode Caenorhabditis elegans, a pair of neurons, each of which ends in a cluster of microvilli-like projections, are known to be the primary thermoreceptors, and have been named the finger cells (class AFD). A similar neuron pair in the amphids of the parasite Haemonchus contortus is also known to be thermosensory. Strongyloides stercoralis lacks finger cells but, in its amphids, it has a pair of neurons whose dendrites end in a multi-layered complex of lamellae, the so-called lamellar cells (class ALD). Consequently, it was hypothesised that these lamellar cells might mediate thermotaxis by the skin-penetrating infective larva of this species. To investigate this, first stage S. stercoralis larvae were anaesthetised and the paired ALD class neurons were ablated with a laser microbeam. The larvae were then cultured to the infective third stage (L3) and assayed for thermotaxis on a thermal gradient. L3 with ablated ALD class neuron pairs showed significantly reduced thermotaxis compared with control groups. The thermoreceptive function of the ALD class neurons (i) associates this neuron pair with the host-finding process of S. stercoralis and (ii) demonstrates a functional similarity with the neurons of class AFD in C. elegans. The structural and positional characteristics of the ALD neurons suggest that these neurons may, in fact, be homologous with one pair of flattened dendritic processes known as wing cells (AWC) in C. elegans, while their florid development and thermosensory function suggest homology with the finger cells (AFD) of that nematode.

Animals↗
PubMed2003

[Bronchial nodules produced by Strongyloides stercoralis as the cause of bronchial obstruction].

Infection by Strongyloides stercoralis can cause asthma-like symptoms through mechanisms that have not yet been clarified. A 55-year-old male farm worker with a 2-year history of illness diagnosed as asthma and treated unsuccessfully with bronchodilators and corticosteroids was referred to our hospital with severe dyspnea. The initial chest radiograph showed mild air trapping, and pulmonary function tests detected airway obstruction that did not respond to salbutamol. Bronchoscopy revealed multiple nodules protruding into the airway lumen. S. stercoralis larvae were detected in bronchoalveolar lavage fluid and stool samples. Although treatment with albendazole was initiated, the patient's condition worsened over the next 3 days, hemoptysis presented, and the process ended in death. Autopsy demonstrated Strongyloides larvae in the bronchial nodules. Infection by S. stercoralis should be considered in the differential diagnosis of asthmatic-like symptoms refractory to treatment. In such cases nodules may be responsible for obstruction.

Animals↗
PubMed2000

Chemokinetic behavior of the infective third-stage larvae of Strongyloides ratti on a sodium chloride gradient.

The movements of the infective third-stage larvae (L3) of a rodent parasitic nematode Strongyloides ratti were examined on a sodium chloride (NaCl) gradient set up on agarose plates. The movements of larvae were followed by observing their tracks on the surface of the agarose. The direction of movement depended on the NaCl concentration at the point of their initial placement on the gradient. Larvae placed at between 230 and 370 mM NaCl tended to migrate towards areas of lower concentration. On the other hand, when placed at concentrations less than 20 mM NaCl, larvae tended to migrate initially towards higher concentrations but did not linger in areas where the concentration was over approximately 80 mM NaCl. It seems that S. ratti L3, tested in vitro, prefer regions with a concentration of NaCl below 80 mM NaCl. Two typical chemokinetic behaviors are seen; a unidirectional avoidance movement when initially placed in unfavorable environmental conditions and a random dispersal movement when placed within an area of favorable conditions. Track patterns were straight in the avoidance movement but included multiple changes of direction and loops in the dispersal movement. This study introduces an assay system suitable for studying chemokinetic behavior of larvae of Strongyloides ratti.

Animals↗
PubMed1989

The course of infection in rats given small primary doses of Strongyloides ratti and S. venezuelensis.

Development of exact doses (less than 100) of Strongyloides venezuelensis third-stage larvae in adult Wistar rats was insignificant (mean proportion of 0.076 of the dose at day 8, n = 16) compared with a homogonic strain of S. ratti (0.538, n = 6; 0.726, n = 6) and heterogonic S. ratti (0.681, n = 6). Newly-weaned Wistars allowed development of a mean proportion of S. venezuelensis of 0.298 (n = 4) compared with 0.013 (n = 4) of the same sample of larvae in adult hosts. Experiments with 75Se-labelled larvae established that S. venezuelensis effectively failed to migrate from skin to intestine in adult animals, while mean proportions of 0.141 (n = 5) and 0.138 (n = 4) of the label was found in the intestines of newly-weaned rats 72 h after skin application. Labelled larvae of homogonic S. ratti migrated equally well in both age groups of host (0.350 and 0.358 in 12- and 3-week-olds respectively). Adult S. venezuelensis transferred surgically to the intestines of previously uninfected full-grown Wistars survived over a 21-day period to the same extent as either strain of S. ratti. Resistance of Wistar rats to S. venezuelensis therefore appears to affect the migratory stage preferentially. S. venezuelensis developed better in mature PVG inbred rats (mean = 0.301, n = 20). Studies of S. ratti showed that infections of both strains initiated by exact (less than 100) doses in Wistar rats had decayed to insignificance between days 26 and 32. The rate of loss of adults of the heterogonic strain was significantly greater than that for the homogonic. The egg content of worms declined as infection progressed and rats were idiosyncratic in their influence on parasite reproduction from the earliest time of sampling (8 d). It was established that 'autoinfection' was an unlikely feature of the biology of homogonic S. ratti following the surgical transfer of 450 first-stage larvae to the intestines of 8 adult Wistar rats. No evidence of infection appeared in the guts of these animals 8 days post-transfer. The significance of these results in terms of the biology of Strongyloides spp. naturally occurring in the rat is discussed.

Animals↗
PubMed1994

Development in vitro of free-living infective larvae to the parasitic stage of Strongyloides venezuelensis by temperature shift.

Free-living infective larvae Strongyloides venezuelensis were cultured in Dulbecco's modified Eagle's medium at 25 and 37 degrees C, and development to the parasitic stage was evaluated using morphological, protein and antigenicity criteria. Few larvae cultured at 25 degrees C showed development whereas, in most of the larvae cultured at 37 degrees C, there appeared characteristic changes such as a bulb-like head and droplets under the cuticle with an increase of body width of the larvae. The results obtained from two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) revealed that the protein spot patterns of the larvae cultured at 25 and 37 degrees C were differentiated by 17 specific spots. In addition, Western blot analysis combined with 2D-PAGE for reaction with serum obtained from an infected rat revealed that protein spots showing immunodominant antigen at 37 degrees C were almost the same as those of the larvae recovered from the rats rather than those of the larvae at 25 degrees C. These results strongly suggested that a temperature shift from 25 to 37 degrees C has an important role in the development of free-living infective larvae to the parasitic stage of S. venezuelensis. The culture system established in the present study was useful for biological and biochemical studies in the development from/of the free-living to the parasitic stage of Strongyloides species.

Animals↗
PubMed2000

Natural killer-cell lymphocytosis and strongyloides infection.

We report a case of strongyloides infection in a 72-year-old man presenting with acute angio-oedema and urticaria. He was also found to have natural killer cell (NK) large granular lymphocytosis (LGL). We discuss the possible relationship between the strongyloides infection and the NK-LGL lymphocytosis.

Aged↗
PubMed1998

[Strongyloides stercoralis infection in a patient with AIDS and non-Hodgkin lymphoma].

HISTORY AND CLINICAL FINDINGS: The patient, now 50 years old, an immigrant miner from the former Yugoslavia who was known to have AIDS, was in 1992 found to have non-Hodgkin lymphoma of the oesophagus and given five cycles of multiple chemotherapy (CHOP) with complete remission. Subsequently he complained of retrosternal pain, dysphagia, dry cough and upper abdominal discomfort. On admission he had slight fever of 39.1 degrees C, but physical examination was unremarkable. LABORATORY TESTS: Blood count revealed an eosinophilia of 41%. IgE concentration was raised to 432IU/ml. The CD4+ T-cell count was reduced to 10/microliter, that of CD8+ to 89/microliter. ADDITIONAL TESTS: Blood culture, fecal and sputum samples and bronchoalveolar lavage demonstrated Mycobacterium avium intracellulare. TREATMENT AND COURSE: Treatment of the disseminated atypical mycobacterial infection was started with clarithromycin, rifabutin, ciprofloxacin and ethambutol. There was no improvement of the upper abdominal discomfort, but the fever subsided. Oesophagogastroscopy excluded recurrence of the lymphoma. Biopsy and examination of the duodenal juice revealed worms and larvae of Strongyloides stercoralis. Stool samples contained no mycobacteria, but strongyloides larvae were demonstrated. Albendazole was given (2 x 400 mg daily for 6 days, followed by a maintenance dose of 1 x 400 mg daily). Repeat endoscopy and stool sample after a month no longer showed any parasites. CONCLUSION: Even in Western Europe, persons coming from endemic areas who, as this patient, have various risk factors that may facilitate the occurrence of strongyloidiasis. With early diagnosis and treatment albendazole is an efficacious drug.

AIDS-Related Opportunistic Infections↗