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R M Genta

Publications and source records attributed to R M Genta.

At least 145 records · Page 8Linked to original sources

Dysregulation of strongyloidiasis: a new hypothesis.

Few other human parasites are associated with such a diverse spectrum of clinical manifestations as Strongyloides stercoralis, yet the basic biological behavior of this unusually versatile worm, particularly with respect to its ability to cause severe disseminated disease in certain hosts, is poorly understood. The current uncritical acceptance of the theory that cell-mediated immunity controls autoinfection has stifled research in other directions. After reviewing what is and is not known about the parasite's behavior in its host, this article explores some of the mechanisms that could be involved in the regulation of the parasite population. Taking the provocative viewpoint that the parasite, not the host, is mainly responsible for the maintenance of a balanced relationship between the two, I propose a new theory that corticosteroids may act on the intraintestinal larvae as molting hormones and directly promote the development of disseminated disease.

Adrenal Cortex Hormones↗

Idiopathic myointimal hyperplasia of mesenteric veins.

Nonthrombotic occlusion or stenosis of the mesenteric veins is a rare cause of intestinal ischemia that usually occurs in association with systemic vasculitis. The current report includes four male patients with segmental ischemic colitis caused by idiopathic myointimal hyperplasia in the small mesenteric veins and their intramural branches; neither vasculitis nor arterial involvement were present. Three of the four patients were less than or equal to 38 years of age; the fourth was 67. All four patients were previously healthy and had no history of drug use of any kind. Clinical findings included abdominal pain, diarrhea, bloody stools, and colonic strictures discovered by barium enema. The intima of the mesenteric and intestinal mural veins was focally thickened by a marked increase in cells and matrix between the endothelium and internal elastic lamina, whereas the vessel walls external to the thickened intima appeared normal. Histochemistry and immunoreactivity with antibodies to muscle-specific actins (HHF-35) disclosed that the intimal thickening was caused by proliferation of smooth muscle cells in a proteoglycan matrix. All patients recovered completely after segmental resection of the ischemic portion of the colon and had no recurrence of intestinal symptoms on follow-up of up to 7 years. These unusual venous lesions do not appear to have been previously described; their etiology and pathogenesis remain unknown.

Adult↗

Seroepidemiology of Strongyloides infection in the Southeast Asian refugee population in Canada.

As part of a screening and treatment program for intestinal parasite infections offered to newly arrived Southeast Asian refugees in Canada between July 1982 and February 1983, a total of 232 sera were tested for Strongyloides infection using an enzyme-linked immunosorbent assay (immunoglobulin G). These results were compared with coprologic results and eosinophil counts. The seroprevalence was 76.6% (131 of 171) among Kampucheans, 55.6% (15 of 27) among Laotians, and 11.8% (4 of 34) among Vietnamese. A statistically significant relation (p less than 0.001) was found between Strongyloides serology and Strongyloides infection on stool examination (prevalence, 24.7%) among Kampucheans. Eosinophilia (greater than or equal to 10%) was found to be significantly associated with both infection measures. Using coprologic results as the "gold standard," the properties of the serologic test were estimated to be: sensitivity (95%), specificity (29%), positive predictive value (30%), and negative predictive value (95%). These estimates should be regarded as minimal values, as stool examination for Strongyloides infection can be an unreliable diagnostic reference. Further evaluation of the discrepancies observed between coprologic and serologic testing is required to determine the usefulness of these tests in epidemiologic studies.

Adolescent↗

Opportunistic Strongyloides stercoralis infection in lymphoma patients. Report of a case and review of the literature.

Strongyloides stercoralis is an intestinal parasite that may cause fatal opportunistic infections in immunocompromised patients. Herein is reported a patient who developed fatal disseminated strongyloidiasis 6 weeks after the initiation of chemotherapy for a large cell lymphoma of the small intestine. After reviewing the clinical and epidemiologic features of 16 other cases of disseminated strongyloidiasis in patients with malignant lymphomas, the currently available laboratory methods for the diagnosis of this parasite are outlined. Because uncomplicated infections are treatable, candidates for chemotherapy or immunosuppression with a relevant geographic history should be screened for S. stercoralis prior to the initiation of the treatment.

Antibodies↗

Prominence of IgG4 antibodies in the human responses to Strongyloides stercoralis infection.

The participation of the four subclasses of IgG in the humoral response to Strongyloides stercoralis was assessed by analyzing total and parasite-specific responses of each IgG subclass in 20 patients with uncomplicated strongyloidiasis and 21 immunocompromised patients with extraintestinal disease. The total component of each subclass was normal in most patients. IgG4 antibodies (measured by ELISA) were the most prominent parasite-specific response in both groups. Specific IgG2 and IgG4 responses were significantly more elevated in immunocompetent than in immunosuppressed patients. When the reactivity of each IgG subclass was analyzed by immunoblotting on SDS-PAGE-separated larval antigens, IgG4 recognized more antigens than did any other subclass. No parasite antigens were selectively recognized by either clinical group. Thus the continuous antigenic stimulation of chronic strongyloidiasis may result in an enhanced IgG4 subclass response. However, no presence or absence of humoral responses specific for filariform larval antigens was associated with the extraintestinal dissemination of the parasite.

Adult↗

Filaroides hirthi infection in two related dogs.

Filaroides hirthi infection was diagnosed in 2 related Yorkshire Terriers. Dog 1 had a chronic nonproductive cough, but results of fecal flotation examination were negative. Dog 2 was a 1-year-old female progeny of dog 1. Both dogs came from the same kennel and were raised together for 8 weeks. Dog 2 had generalized demodicosis accompanied by secondary bacterial infection and had been treated with corticosteroids. Dog 2 also was given 68 micrograms of ivermectin, PO, and then 50 mg of fenbendazole/kg, PO, q 24 h for 14 days. After the 14-day treatment, results of 3 fecal examinations were negative for Filaroides sp and other parasites, and the dog improved without complications. Fecal examination of the other dogs in the kennel were negative for F hirthi.

Animals↗

Cutaneous manifestations of strongyloidiasis.

Strongyloides stercoralis is a small intestinal nematode that has the ability to multiply within the human host. Because of the potential opportunistic behavior of this parasite, immunocompromised patients may develop fatal disseminated infections. Chronic strongyloidiasis may last decades and give rise to various dermatologic lesions, the most characteristic of which is larva currens, a serpiginous creeping urticarial eruption caused by the intradermal migration of the infective filariform larvae. Rarely recognized is the presence of widespread petechiae and purpura that may develop in patients with disseminated infections. A 64-year-old immunosuppressed man developed fatal extraintestinal S stercoralis infection with extensive purpura associated with massive invasion of the skin by migrating larvae.

Animals↗

Effect of Strongyloides ratti on small bowel function in normal and immunosuppressed host rats.

Although Strongyloides stercoralis is a common parasite, little is known about its effect on intestinal function. Published clinical studies are difficult to evaluate and compare because of the inability to differentiate the effects of the parasite load from that of various other coexisting features such as bacterial overgrowth, multiparasitism, malnutrition, or tropical sprue. Using a rat model where these problems do not occur, we found that Strongyloides ratti did not inhibit intestinal function in the healthy rat. In fact, in normal rats S. ratti appeared to increase ileal sucrase activity. In contrast, in the methylprednisolone-treated rat, S. ratti produced a decrease in lactase and sucrase activity and an increase in alkaline phosphatase activity. S. ratti had no effect on 3-O-methylglucose uptake or D-xylose absorption in either group. These results suggest that S. ratti has little effect on small bowel function in a healthy rat but can cause minor alterations in intestinal function in an immunosuppressed, methylprednisolone-treated, malnourished host. These results are also consistent with clinical observations seen with S. stercoralis in humans and with another nematode, Ascaris suus, in the pig model.

Alkaline Phosphatase↗

Predictive value of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of strongyloidiasis.

Strongyloides stercoralis is an opportunistic parasite of increasing importance in immunocompromised hosts. Current parasitologic methods for diagnosis are unsatisfactory, and the serologic screening of candidates for immunosuppression and other individuals at risk might prevent fatal disseminated infections. The predictive value of an enzyme-linked immunosorbent assay (ELISA) using S. stercoralis antigens has been evaluated on 268 infected patients, 571 noninfected controls, and 78 individuals with other parasitic infections. A positive test was accurate in predicting the presence of S. stercoralis in 97% of the cases, while a negative test was associated with absence of infection in 95% of the patients. Possible cross-reactivity occurred in some patients with Loa loa filariasis and Ascaris lumbricoides. The authors conclude that the ELISA is a reliable and cost-effective method for the screening of patients at risk, and its results can be used to determine the appropriateness of more in-depth parasitologic evaluation.

Enzyme-Linked Immunosorbent Assay↗

Pulmonary microcalcifications associated with Strongyloides stercoralis infection.

Diffuse alveolar deposits of calcium phosphate have been identified in the lungs of two prednisolone-treated beagles with chronic S stercoralis infection. Such lesions have not previously been described in dogs and have not been found in humans in association with either strongyloidiasis or prolonged steroid therapy. S stercoralis infections in the industrialized world are frequently found in patients on maintenance regimens of corticosteroids. We suggest that the possibility that pulmonary calcifications represent an unsuspected complication in these patients should be investigated.

Animals↗

Endemic strongyloidiasis in northern Italy: clinical and immunological aspects.

One hundred and eighteen cases of S. stercoralis infection were detected by stool examination among 4203 patients seen over a period of three years at the Division of Infectious Diseases (IRCCS, San Matteo, University of Pavia) of a University Hospital in Northern Italy. Because chronic strongyloidiasis is often asymptomatic, a 3 per cent prevalence in this selected population indicates that the parasitosis may be much more frequent in the general population of the area. Parasite-specific humoral responses were studied in 48 patients. Strongyloides-specific IgG and IgA antibodies were found by ELISA in the serum of 40 (83.3 per cent) and 43 (89.5 per cent) patients, respectively, and specific IgE antibodies were detected by RAST in 39 (81.3 per cent). The specific IgG antigen recognition patterns of these patients were compared by immunoblotting with those of North and South American and Thai patients, and differences among the groups suggested the existence of separate geographic strains of S. stercoralis. This was further supported by the virtual absence in our patients of the larva currens, a common and highly characteristic sign of strongyloidiasis in subjects infected in southeast Asia. More awareness of the epidemiologic and clinical features of strongyloidiasis, with the use of serologic tests to screen candidates for immunosuppression, may result in the early detection of chronic uncomplicated strongyloidiasis and in the prevention of fatal opportunistic hyperinfections.

Adult↗

Strongyloidiasis in US veterans of the Vietnam and other wars.

The prevalence of strongyloidiasis among American veterans of the Vietnam and other wars was evaluated by testing several groups of veterans for serum IgG antibodies against Strongyloides stercoralis antigens, using an enzyme-linked immunosorbent assay. Of 493 Vietnam veterans, eight (1.6%) were seropositive. Of 60 patients with abdominal symptoms and/or elevated eosinophilia (greater than 0.08 [greater than 8%]) admitted to the Cincinnati Veterans Administration Medical Center, 12 (5%) were seropositive. Of 147 residents of a Veterans Administration-operated nursing home, six (4%) were seropositive. All infected patients in the latter two groups were World War II veterans. The usefulness of the enzyme-linked immunosorbent assay as a screening tool for at-risk groups is suggested by the finding that S stercoralis larvae were demonstrated in most seropositive patients when a sufficient number of fresh stools were examined.

Adult↗

Parasite-specific humoral responses in different clinical forms of strongyloidiasis.

Total IgE, specific IgE and IgG antibodies directed against Strongyloides stercoralis antigens were measured in the serum of 8 asymptomatic individuals with parasitologically proven strongyloidiasis, 10 patients with symptomatic strongyloidiasis and 8 with a severe form of the disease. No correlation was found between any of the immunological quantities evaluated and the clinical form of strongyloidiasis. We suggest that other responses may be involved in determining clinical manifestations of this parasitosis.

Antibodies, Helminth↗

Demonstration and partial characterization of parasite-specific immunoglobulin A responses in human strongyloidiasis.

By using an enzyme-linked immunosorbent assay, serum immunoglobulin A (IgA) responses directed against Strongyloides stercoralis larvae antigens were measured in 104 presumably immunocompetent individuals with chronic uncomplicated strongyloidiasis and in 15 immunocompromised patients with S. stercoralis infection. Fifty healthy North American adults and 18 patients with other helminthic parasites served as controls. All 50 healthy controls were negative for antibody responses (mean absorbance +/- standard deviation = 0.0724 +/- 0.040). The mean absorbance of the 18 parasitized controls was 0.230 +/- 0.087; two individuals parasitized by Ascaris lumbricoides showed positive antibody responses. The mean absorbance of the immunocompetent patients with strongyloidiasis was 0.680 +/- 0.364, with 91 subjects (87.5%) having a positive value (greater than 0.300). Of the immunocompromised patients (mean absorbance +/- standard deviation = 0.735 +/- 0.538), 11 (73%) had a positive antibody response test. When the IgA responses of these two groups were compared, they were not significantly different. There was no correlation between the levels of total serum IgA and the concentration of specific IgA in the infected patients. Both IgA and IgG immunoreactive bands were detected on immunoblots of sodium dodecyl sulfate-polyacrylamide gel electrophoresis-separated larval antigen protein blots. Nineteen bands were recognized by IgG, and 13 were recognized by IgA from sera of infected patients. Several bands displayed specific IgG or IgA reactivity. The present work shows that most patients with strongyloidiasis mount specific IgA responses against filariform larval antigens. These responses are, for the most part, directed against antigens that are different from those recognized by IgG. The lack of correlation between the magnitude of the specific serum IgA responses and the clinical aspects of the infection suggests that these antibodies may not play a central role in the regulation of this parasitosis.

Antibody Specificity↗

Strongyloides stercoralis: parasitological, immunological and pathological observations in immunosuppressed dogs.

Four specific pathogen-free, two to three-month-old, laboratory-raised beagles were infected with Strongyloides stercoralis and monitored by thrice-weekly faecal examinations. Larvae were not detected in the faeces after the 11th week. During the 14th week, daily oral prednisolone (2.2 mg/kg) was given. This led to weak recrudescence of the infection. During the 21st week, the daily dose of prednisolone was doubled and thereafter two of the four dogs developed severe hyperinfective strongyloidiasis with their adult worm populations markedly exceeding the number of larvae inoculated, as did one dog which remained asymptomatic. One dog died during the 15th week, i.e., before there was time for a marked increase in the parasite population. Three of the four dogs provided evidence of disseminated infection with adult worms occurring in ectopic sites. Parasite-specific cellular and humoral immune responses were monitored weekly. All dogs developed a significant rise in specific IgM titres lasting until the fifth week. From the fourth week, all dogs had detectable parasite-specific IgG antibody levels that persisted throughout the experiment in spite of the immunosuppression. Strongyloides-induced lymphocytic responses in vitro were demonstrated in three dogs from the second to the fifth week of infection, but returned to pre-infection levels thereafter. All animals were necropsied. Relevant pathological lesions were found in the small intestine, the colon and the lungs. Larvae were seen in such ectopic sites as mesenteric nodes and prostate. The observations provide further evidence that canine S. stercoralis infections can be manipulated to reproduce with great fidelity the parasitological and clinico-pathological events occurring in human disseminated strongyloidiasis.

Animals↗

Strongyloides stercoralis: immunobiological considerations on an unusual worm.

In the highly competitive world of parasites, where survival is indissolubly tied to the presence of suitable hosts in the same ecological niche, Strongyloides stercoralis occupies a unique position. This versatile nematode has developed a successful relationship with two ecosystems, the terrestrial environment and the mammalian body, by becoming facultatively independent of either (Box 1). It requires external maturation for transmission, but it also has the ability to multiply within a single host. It prefers man, but may infect apes, monkeys, dogs and cats. As a human parasite, S. stercoralis establishes self-perpetuating intestinal colonies and negotiates their survival with the host's defense mechanisms. In this article, Robert Genta reviews the immunobiological aspects of this unusual relationship.

Journal Article↗

Diagnostic implications of parasite-specific immune responses in immunocompromised patients with strongyloidiasis.

Parasite-specific humoral and cellular immune responses were evaluated in in nine immunosuppressed patients with Strongyloides stercoralis infection. Four patients had the disseminated form of the disease, and five had serious manifestations without evidence of hyperinfection. All patients had high levels of immunoglobulin G (IgG) antibodies directed against S. stercoralis larval antigens as detected by the enzyme-linked immunosorbent assay. Seven patients had both elevated total serum IgE and parasite-specific IgE antibodies detected by a modified radioimmunoassay. The hyperinfected patients differed significantly from the nonhyperinfected group in total and specific IgE levels and peripheral eosinophilia but not in specific IgG levels. None of the patients tested exhibited significant in vitro lymphoproliferative responses to parasite antigens. Our results indicated that the possibility of a protective role of IgE and eosinophils in strongyloidiasis deserves further investigation. In addition, we suggest that the enzyme-linked immunosorbent assay for specific IgG antibodies may have an important place in the diagnosis of strongyloidiasis in immunocompetent as well as in immunocompromised patients.

Adult↗