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PubMed2006

Eosinophils can function as antigen-presenting cells to induce primary and secondary immune responses to Strongyloides stercoralis.

Several studies have demonstrated roles for eosinophils during innate and adaptive immune responses to helminth infections. However, evidence that eosinophils are capable of initiating an immune response to parasite antigens is lacking. The goal of the present in vitro study was to investigate the potential of eosinophils to serve as antigen-presenting cells (APC) and initiate an immune response to parasite antigens. Purified eosinophils were exposed to soluble Strongyloides stercoralis antigens, and the expression of various surface markers involved in cell activation was examined. Antigen-exposed eosinophils showed a sixfold increase in expression levels of CD69 and major histocompatibility complex (MHC) class II, a fourfold increase in levels of T-cell costimulatory molecule CD86, and a twofold decrease in levels of CD62L compared to eosinophils cultured in medium containing granulocyte-macrophage colony-stimulating factor. The ability of eosinophils to present antigen to T cells was determined by culturing them with T cells in vitro. Eosinophils pulsed with antigen stimulated antigen-specific primed T cells and CD4+ T cells to increase interleukin-5 (IL-5) production. The blocking of MHC class II expression on eosinophils inhibited their ability to induce IL-5 production by CD4+ T cells in culture. Antigen-pulsed eosinophils were able to prime naïve T cells and CD4+ T cells in culture and polarized them into Th2 cells producing IL-5 similar to that induced by antigen-loaded dendritic cells. These results demonstrate that eosinophils are capable of activating antigen-specific Th2 cells inducing the release of cytokines and assist in the priming of naïve T cells to initiate Th2 responses against infection. This study highlights the potential of eosinophils to actively induce immune responses against infection by amplifying antigen-specific Th2-cell responses.

Animals↗
PubMed2003

Specificity and mechanism of immunoglobulin M (IgM)- and IgG-dependent protective immunity to larval Strongyloides stercoralis in mice.

Protective immunity in mice to the infective third-stage larvae (L3) of Strongyloides stercoralis was shown to be dependent on immunoglobulin M (IgM), complement activation, and granulocytes. The objectives of the present study were to determine whether IgG was also a protective antibody isotype and to define the specificity and the mechanism by which IgG functions. Purified IgG recovered from mice 3 weeks after a booster immunization with live L3 was shown to transfer high levels of protective immunity to naïve mice. IgG transferred into mice treated to block complement activation or to eliminate granulocytes failed to kill the challenge larvae. Transfer of immune IgG into IL-5 knockout (KO) mice, which are deficient in eosinophils, resulted in larval attrition, while transfer into FcRgamma KO mice did not result in larval killing. These findings suggest that IgG from mice immunized with live L3 requires complement activation and neutrophils for killing of L3 through an antibody-dependent cellular cytotoxicity (ADCC) mechanism. This is in contrast to the results of investigations using IgM from mice immunized with live L3 and IgG from mice immunized with larval antigens soluble in deoxycholate in which protective immunity was shown to be ADCC independent. Western blot analyses with immune IgM and IgG identified few antigens recognized by all protective antibody isotypes. Results from immunoelectron microscopy demonstrated that the protective antibodies bound to different regions in the L3. It was therefore concluded that while IgM and IgG antibodies are both protective against larval S. stercoralis, they recognize different antigens and utilize different killing mechanisms.

Animals↗
PubMed2004

Platelet-activating factor receptor deficiency delays elimination of adult worms but reduces fecundity in Strongyloides venezuelensis-infected mice.

We describe the parasitological kinetics and histopathological and immunological alterations in platelet-activating factor receptor-deficient (PAFR(-/-)) and wild-type mice after a single Strongyloides venezuelensis infection (subcutaneous inoculation of 500 L3 larvae). There was no difference in the numbers of worms that reached and became established in the small intestines of PAFR(-/-) and wild-type mice. However, at 12 days after infection, significantly more worms were recovered from PAFR(-/-) mice. Although PAFR(-/-) infected mice showed a delay in elimination of adult worms, worms established in the small intestine of these mice produced a significantly lower number of eggs due to a reduction in worm fecundity. There were also significant reductions in the number of circulating and tissue eosinophils and tumor necrosis factor levels in the small intestines of PAFR(-/-) mice infected for 7 days compared to the number and level in wild-type mice. Histological analysis confirmed the reduced inflammatory process and revealed that the PAFR(-/-) mice had a smaller number of goblet cells. The concentrations of the type 2 cytokines interleukin-4 (IL-4), IL-5, and IL-10 were lower in small intestine homogenates and in supernatants of antigen-stimulated lymphocytes from spleens or mesenteric lymph nodes of PAFR(-/-) mice than in the corresponding preparations from wild-type mice. Thus, in S. venezuelensis-infected PAFR(-/-) mice, decreased intestinal inflammation is associated with enhanced worm survival but decreased fecundity. We suggest that although a Th2-predominant inflammatory response decreases worm survival, the worm may use factors produced during this response to facilitate egg output and reproduction. PAFR-mediated responses appear to modulate these host-derived signals that are important for worm fecundity.

Animals↗
PubMed2005

DNA immunization with Na+-K+ ATPase (Sseat-6) induces protective immunity to larval Strongyloides stercoralis in mice.

Strongyloides stercoralis causes chronic asymptomatic infections which can be maintained in the human host for many decades. Identification and treatment of S. stercoralis-infected individuals is required because immunosuppression can lead to fatal hyperinfection. In this study, human immunoglobulin G (IgG) that had previously been shown to transfer protective immunity to mice was used to identify potential protective antigens. Three antigens or genes from S. stercoralis larvae were identified as tropomyosin (Sstmy-1), Na+-K+ ATPase (Sseat-6), and LEC-5 (Sslec-5). The genes were cloned into plasmids for DNA immunization, and mice were immunized intradermally with the three plasmids individually in combination with a plasmid containing murine granulocyte-macrophage colony-stimulating factor. Only Na+-K+ ATPase induced a significant reduction in larval survival after DNA immunization. Immunization with a combination of all three plasmids, including Na+-K+ ATPase, did not induce protective immunity. Serum from mice immunized with DNA encoding Na+-K+ ATPase was transferred to naive mice and resulted in partial protective immunity. Therefore, DNA immunization with Na+-K+ ATPase induces protective immunity in mice, and it is the first identified vaccine candidate against infection with larval S. stercoralis.

Animals↗
PubMed2006

Mixed pulmonary infection with Strongyloides stercoralis and Blastomyces dermatitidis.

We report the first case of mixed pulmonary infection with Strongyloides stercoralis and Blastomyces dermatitidis. Histopathology from the lung biopsy showed structures consistent with B. dermatitidis and S. stercoralis. A parasitology exam from a bronchi alveolar lavage yielded an immature rhabditiform larva and female worm. Fungal cultures grew B. dermatitidis.

Animals↗
PubMed2006

Use of enzyme-linked immunosorbent assay and dipstick assay for detection of Strongyloides stercoralis infection in humans.

A homemade enzyme-linked immunosorbent assay (ELISA) (Academic Medical Center ELISA [AMC-ELISA]) and a dipstick assay for the detection of anti-Strongyloides stercoralis antibodies in serum were developed and evaluated together with two commercially available ELISAs (IVD-ELISA [IVD Research, Inc.] and Bordier-ELISA [Bordier Affinity Products SA]) for their use in the serodiagnosis of imported strongyloidiasis. Both commercially available ELISAs have not been evaluated previously. The sensitivities of the assays were evaluated using sera from 90 patients with parasitologically proven intestinal strongyloidiasis and from 9 patients with clinical larva currens. The sensitivities of the AMC-ELISA, dipstick assay, IVD-ELISA, and Bordier-ELISA were 93, 91, 89, and 83%, respectively, for intestinal strongyloidiasis. In all tests, eight of nine sera from patients with larva currens were positive. The specificity was assessed using a large serum bank of 220 sera from patients with various parasitic, bacterial, viral, and fungal infectious diseases; sera containing autoimmune antibodies; and sera from healthy blood donors. The specificities of AMC-ELISA, dipstick assay, IVD-ELISA, and Bordier-ELISA were 95.0, 97.7, 97.2, and 97.2%, respectively. Our data suggest that all four assays are sensitive and specific tests for the diagnosis of both intestinal and cutaneous strongyloidiasis.

Animals↗
PubMed1986

Elucidation of Strongyloides stercoralis by bacterial-colony displacement.

Two cases of unsuspected Strongyloides stercoralis infection were elucidated by the displacement of bacterial colonies on primary plating media. Observation of primary plates inoculated for the diagnosis of bacterial pneumonia or gastroenteritis revealed that normal flora colonies had been moved and were aligned in a pathway, or track. This unusual colony alignment prompted us to request a stool for the examination of parasites, and S. stercoralis was found. It was concluded that the parasite is capable of motility on agar surfaces, resulting in the displacement of bacterial colonies that make up the normal flora.

Aged↗
PubMed1996

Patterns of detection of Strongyloides stercoralis in stool specimens: implications for diagnosis and clinical trials.

Reported efficacies of drugs used to treat Strongyloides stercoralis infection vary widely. Because diagnostic methods are insensitive, therapeutic trials generally require multiple negative posttreatment stool specimens as evidence of drug efficacy. However, only a single positive stool specimen is usually required for study enrollment. To determine the reproducibility of detection of S. stercoralis larvae in the stool, 108 asymptomatic infected men submitted 25 g of fresh stool once a week for eight consecutive weeks for examination by the Baermann technique. During the 8-week study, 239 (27.7%) of 864 stool specimens were positive for S. stercoralis. Rates of detection of larvae in the stool specimens ranged from eight of eight specimens in 3 (2.8%) men to none of eight specimens in 36 (33.3%) men. Of 43 men for whom S. stercoralis was detected in at least two of the first four stool specimens, only 1 (2.3%) man tested negative on all of the next four specimens. In comparison, of 29 men who had detectable larvae in only one of the first four specimens, 22 (75.9%) tested negative on all of the next four samples. Thus, if these 29 men had been enrolled in a therapeutic trial between the first and second sets of four specimens, the efficacy of a drug with no activity against this parasite would have been estimated to be 76%. These data suggest that patterns of S. stercoralis detection vary widely among infected persons and that intermittent larval shedding can lead to inflated estimates of drug efficacy. Before a patient is entered in a clinical trial of drug efficacy, four consecutive stool specimens should be examined for S. stercoralis; only persons with two or more positive specimens should be enrolled.

Adolescent↗
PubMed1999

First-glance diagnosis of Strongyloides stercoralis autoinfection by stool microscopy.

We report a case of autoinfection due to Strongyloides stercoralis in a 27-year-old Ethiopian AIDS patient living in Germany for nearly 3 years. This case was diagnosed on the basis of a single-view field in microscopy of a freshly obtained formalin-fixed stool specimen showing both rhabditiform and filariform larvae. The diagnosis of autoinfection by microscopy is discussed in detail.

Adult↗
PubMed1973

Hyperinfection syndrome with Strongyloides stercoralis in malignant lymphoma.

Hyperinfection with Strongyloides stercoralis occurred in three patients with malignant lymphoma. The probable cause in each case was alteration of the immune responses either as a result of the malignant lymphoma or by the treatment given. Though thiabendazole (Mintezol) has produced reasonable results in the treatment of the hyperinfection syndrome, preliminary data suggest that the new broad-spectrum anthelmintic levamisole (Ketrax) is more effective. All patients who live or have lived in an area where strongyloidiasis is endemic should be investigated to detect the presence of the nematode before and during treatment with drugs with immunosuppressive properties. In view of the high mortality with S. stercoralis hyperinfection, vigorous therapy should be instituted before the use of immunosuppressive drugs.

Adult↗
PubMed2005

Strongyloides stercolaris infection mimicking a malignant tumour in a non-immunocompromised patient. Diagnosis by bronchoalveolar cytology.

Autoinfective strongyloidiasis is often fatal in immunosuppressed patients or in immunocomprised hosts. An interesting case of Strongyloides stercolaris hyperinfection was seen in an immunocompetent patient. This report describes a case of fatal strogyloidiasis in a 79 year old man, who had suffered gastrointestinal discomfort for years, and who presented because of respiratory illness. A chest radiograph showed an irregular mass close to the mediastinum and interstitial infiltrates, but blood eosinophilia was not observed. Cytological examination of the samples obtained from bronchial aspiration and brushing identified several filariform larvae. Thus, cytology was essential for the correct diagnosis in this patient and is a very reliable method to diagnose lung parasitosis.

Aged↗
PubMed2000

Strongyloides stercoralis: ultrastructural study of newly hatched larvae within human duodenal mucosa.

AIM: To investigate the ultrastructural features of the newly hatched larvae of Strongyloides stercoralis in human duodenal mucosa. METHODS: Duodenal biopsies from an AIDS patient were studied by transmission electron microscopy to investigate morphology, location, and host-worm relations of newly hatched larvae. RESULTS: Newly hatched larvae were found in the Lieberkuhn crypts within the tunnels formed by migration of parthenogenic females. Delimiting enterocytes were compressed. Release of larvae into the gut lumen was also documented. It was shown that both a thin and a thick membrane surrounded the eggs and larvae, as a tegument derived respectively from parasite and host. Segmentary spike-like waves, caused by contractures of worm body musculature, were observed on the surface of newly hatched larvae, and their intestinal lumen was closed and empty, with no budding microvilli. Immaturity of the cuticle and some degree immaturity of amphidial neurones were found, but there was no evidence of either immaturity or signs of damage to other structures. CONCLUSIONS: Newly hatched larvae of S stercoralis appear to be a non-feeding immature stage capable of active movement through the epithelium, causing mechanical damage. The tegument resulting from the thin and the thick membrane may protect the parasite and reduce any disadvantage caused by immaturity.

AIDS-Related Opportunistic Infections↗
PubMed1992

Strongyloides stercoralis hyperinfection in a patient with angioimmunoblastic lymphadenopathy.

A 29 year old Bengali male patient on chemotherapy for angioimmunoblastic lymphadenopathy developed Strongyloides hyperinfection syndrome 3 months after being treated with a single 3 day course of thiabendazole. His complicated hospitalization and successful management are described. Prevention of this potentially fatal disease in immunocompromised patients by early diagnosis and proper management of intestinal strongyloidiasis is emphasized.

Adult↗
PubMed2005

HIV infection associated with Strongyloides stercoralis colitis resulting in Streptococcus bovis bacteraemia and meningitis.

We report the case of an HIV infected patient with Streptococcus bovis bacteraemia and meningitis associated with gastrointestinal Strongyloides stercoralis infection. To our knowledge, this has been reported once previously and serves as a reminder to actively exclude asymptomatic S stercoralis infection in HIV infected individuals presenting with bacteraemia.

AIDS-Related Opportunistic Infections↗
PubMed1985

Efficacy of ivermectin against somatic Strongyloides ransomi larvae.

The efficacy of ivermectin against the somatic larval stages of Strongyloides ransomi was evaluated in three trials involving 35 pregnant gilts harbouring induced infections. Treatment at a rate of 300 micrograms/kg bodyweight subcutaneously, four to 16 days before farrowing, was highly effective as judged by counts of larvae in milk and worm burdens of piglets.

Animals↗
PubMedDate not supplied

[Malabsorption syndrome due to Strongyloides stercoralis associated with Loeffler syndrome in a 29-year-old woman].

We report a case of chronic infection by Strongyloides stercoralis in a 29-year-old Colombian woman who had been living in Spain for 2 years. The patient had recurrent abdominal pain and malabsorption syndrome. The diagnosis was made through intestinal biopsy in upper gastrointestinal endoscopy. Transport of the parasite through the lung parenchyma (Loeffler syndrome) was visible on simple chest X-ray. Bronchoalveolar lavage, bronchoalveolar aspirate and repeated stool examination were negative.

Adult↗
PubMedDate not supplied

Diagnosis of Strongyloides stercoralis in a peritoneal effusion from an HIV-seropositive man. A case report.

BACKGROUND: Strongyloides stercoralis, a nematode parasite in humans with free-living and autoinfective cycles, is often an asymptomatic infection of the upper small intestine. If the host becomes immunocompromised, autoinfection may increase the intestinal worm burden and lead to disseminated strongyloidiasis. The parthenogenetic adult female larvae can remain embedded in the mucosa of the small intestine for years, producing eggs that develop into either rhabditiform, noninfective larvae or filariform, infective larvae. Manifestations of dissemination occur when the filariform larvae penetrate the intestinal wall and migrate into the blood. Pulmonary involvement is common, and the central nervous system may be affected. Blood eosinophilia is typical, and gram-negative sepsis from enteric bacteria may occur. Much less commonly described is invasion of the peritoneal cavity with peritoneal effusion. CASE: A 49-year-old man who came to the United States from Liberia 4 years earlier presented with sudden onset of severe abdominal distention, generalized weakness and marked pedal edema. Diagnostic paracentesis showed numerous filariform larvae of S stercoralis. Stool examination confirmed the presence of both rhabditiform and filariform larvae. Subsequently the patient was found to be HIV seropositive, with a CD4 lymphocyte count of 59. CONCLUSION: Early detection of S stercoralis may alter the often-fatal course of infection. The present case is the second reported one in the English-language literature of the diagnosis of S stercoralis in ascitic fluid.

AIDS-Related Opportunistic Infections↗