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Biomedical subjects

A A Gam

Publications and source records attributed to A A Gam.

At least 19 recordsLinked to original sources
PubMed1998

Interferon-gamma and interleukin-4 responses in relation to serum IgE levels in persons infected with human T lymphotropic virus type I and Strongyloides stercoralis.

Possible immunologic interaction between infection with human T lymphotropic virus type 1 (HTLV-1), a retrovirus, and the intestinal parasite Strongyloides stercoralis was investigated in persons infected with one or both agents. This was done by examining the cytokine responses of peripheral blood mononuclear cells (PBMC) to mitogens and Strongyloides antigen. PBMC of subjects infected with HTLV-1 spontaneously produced interferon (IFN)-gamma with levels that correlated inversely with serum IgE levels. HTLV-1-infected subjects also had poor interleukin (IL)-4 responses to mitogenic stimulation, unlike persons without HTLV-1 infection. It is postulated that the IFN-gamma produced by activated T cells in some HTLV-1-infected persons acts to down-regulate IL-4 with consequent reduction of serum IgE levels. The impaired IgE responses and other effects of IL-4 down-regulation may be contributing factors to more severe disease and impaired response to treatment of strongyloidiasis in some HTLV-1-infected persons.

Animals↗
PubMed1998

Recombinant cDNA clones for immunodiagnosis of strongyloidiasis.

Because diagnosis of strongyloidiasis by stool examination is unreliable and because of the potential for serious disease in Strongyloides infections, there is need for improved diagnostic aids to facilitate recognition and treatment of this parasitic infection. Serologic testing, when available, requires antigen preparation from infected primates or dogs that can be difficult to maintain. Several recombinant clones from a cDNA library prepared from the infective stage of Strongyloides stercoralis were characterized. Serologic results indicate that the recombinant proteins were equally or more reactive than the larval somatic antigen. No cross-reactivity with recombinant antigen 5a was found with sera from patients with filarial or intestinal nematode infections. Recombinant antigens 5a and 12a detected parasite-specific IgE and IgG4 antibodies in Strongyloides-infected patients. Sequence analysis showed these antigens to be rich in proline and charged amino acids. Lack of homology from database searches suggests that the antigens are unique. These recombinant antigens should be useful in diagnostic and epidemiologic studies of strongyloidiasis.

Amino Acid Sequence↗
PubMed1998

Splenic cytokine responses in Indian kala-azar before and after treatment.

Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma; n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute.

Adolescent↗
PubMed1997

Molecular differences between several species of Strongyloides and comparison of selected isolates of S. stercoralis using a polymerase chain reaction-linked restriction fragment length polymorphism approach.

The relationships between the parasitic nematodes of medical importance belonging to the genus Strongyloides was studied using a polymerase chain reaction (PCR)-linked restriction fragment length polymorphism approach. We used several human and dog isolates of S. stercoralis, a monkey isolate of S. fulleborni, and S. ratti, a rodent parasite. The molecular analysis was based on amplification of the internal transcribed spacer and the 5' portion of the 23S-like rRNA gene followed by restriction enzyme digests. The length of the PCR product was specific to each species and varied around 1.5 kilobase pairs. Using nine restriction enzymes, we were able to analyze both interspecific and intraspecific variations. With four restriction enzymes (Taq I, Dde I, Dra I, and Mwo I), human isolates of S. stercoralis from different parts of the world showed identical patterns and could be differentiated from the dog isolate of S. stercoralis. Interspecific differences were readily observed with these and other enzymes. In addition to providing new information on the genomic characteristics of Strongyloides parasites, the results suggest that this technique could be useful for diagnostic and epidemiologic investigations.

Animals↗
PubMed1996

Conservation of low-copy gene loci in Old World leishmanias identifies mechanisms of parasite evolution and diagnostic markers.

Genome plasticity has been hypothesized to be a driving force behind parasite speciation. We have evaluated divergence in single and low-copy genes in terms of locus organization, chromosomal localization and gene expression in Leishmania infantum, L. major, L. tropica and three widely divergent geographic isolates of L. donovani. Seventeen genes of low to moderate copy number (1-4 copies/haploid genome) were analyzed to identify restriction fragment length polymorphisms (RFLPs) providing heritable markers distinguishing Old World (OW) leishmanias. These RFLP markers were conserved in parasite isolates from primary infections demonstrating their utility as diagnostic tools. The species designations established by RFLP analysis of field isolates was confirmed by use of monoclonal antibodies. All 17 genes were present in each OW leishmania analyzed except LSIP (A45), which was absent from L. infantum. The 17 genes were found to be distributed among 9 distinct chromosomes. However, in spite of variations in chromosome karyotypes among the various OW leishmanias, individual gene probes localized to a similar sized chromosome from each isolate. These observations coupled with a molecular tree derived from RFLP data suggest that the OW leishmanias comprise a monophyletic lineage, with species associated with cutaneous disease exhibiting the greatest level of divergence. Data from this study supports previous observations that species causing cutaneous and visceral disease have diverged primarily by nucleotide substitutions. Such nucleotide divergence may not only lead to changes in protein function and antigenicity, but may also alter gene regulation programs as exemplified by the finding that the LdI-9-5 and LdE-6-1 genes were expressed only in visceralizing leishmanias.

Animals↗
PubMed1995

Ss40: the zinc endopeptidase secreted by infective larvae of Strongyloides stercoralis.

Infective larvae of a pathogenic nematode of humans, Strongyloides stercoralis, release a potent zinc endopeptidase activity which has a broad substrate specificity for constituents of extracellular dermal matrix, including elastin. Specific inhibitors of zinc endopeptidases prevent the penetration of mammalian skin by S. stercoralis larvae. We now report the molecular size and isoelectric point of the S. stercoralis zinc endopeptidase at 40 kDa, pI 5 by zymogram analysis. The activity was not influenced by incubation with beta-mercaptoethanol at 22 degrees C, but was inactivated by incubation at 100 degrees C for 2 min. The enzyme, which we term Ss40, is immunogenic and stimulates humoral IgG antibodies during infection of humans; the activity was immunoprecipitable from ES with pooled infection sera. In addition, a HPLC-enriched Ss40 preparation stimulated the release of histamine from peripheral blood leukocytes of S. stercoralis-infected persons, suggesting that Ss40 is allergenic in humans.

Animals↗
PubMed1995

Age-prevalence and household clustering of Strongyloides stercoralis infection in Jamaica.

The epidemiology of Strongyloides stercoralis was studied in families of clinical (reference) cases and their neighbours at endemic foci in Jamaica. Thirteen foci were studied based on the place of residence of a reference case. For each household of a reference case, the 4 most proximal neighbourhood households (spatial controls) were included in the study. Out of 312 persons contacted 244 were followed up using questionnaires, stool examination and serology. Prevalence of infection based on stool examination was 3.5% and on ELISA 24.2%. Prevalence increased with age but was not related to gender. Reference cases were significantly older than the general study population. The prevalence of infection based on both serology and stool examination was significantly higher in reference than in neighbouring households (the reference cases, themselves, were not included in the analysis). Furthermore, prevalence of infection was highest among persons who shared a bedroom with a reference case and decreased significantly with increasing spatial separation. This is indicative of close contact transmission which has not been previously shown for a geohelminth, but which is common among microparasites.

Adolescent↗
PubMed1994

Immunoepidemiologic studies of Strongyloides stercoralis and human T lymphotropic virus type I infections in Jamaica.

Epidemiologic investigations of Strongyloides stercoralis and human T lymphotropic virus type I (HTLV-I) infections were conducted. Of 312 persons contacted, 209 (67%) provided blood and stool samples. Prevalences of S. stercoralis and HTLV-I antibodies were 26.8% and 8.1% (n = 198), respectively, and S. stercoralis larvae were detected in 4%. HTLV-I antibodies were significantly more common in persons positive for S. stercoralis larvae (10 [58.8%] of 17) compared with seropositive larva-negative (4 [8.9%] of 45) or seronegative persons (9 [6.2%] of 145) (P < .002). IgE levels increased with age in S. stercoralis-seropositive persons who were HTLV-I negative (P < .002). However, there was an age-related depression of serum IgE in HTLV-I-positive positive persons (P < .003) that was sufficient to annul the IgE level-raising effect of S. stercoralis seropositivity. The data provide evidence that HTLV-I infection is associated with increased frequency of larvae in the stool of S. stercoralis-infected persons and suggest that the mechanism may involve suppression of the IgE response.

Adult↗
PubMed1994

A randomized trial of single- and two-dose ivermectin versus thiabendazole for treatment of strongyloidiasis.

A randomized trial is described comparing ivermectin and thiabendazole for treatment of chronic infection with Strongyloides stercoralis. Subjects received ivermectin (200 micrograms/kg) in a single dose, ivermectin (200 micrograms/kg) on 2 consecutive days, or thiabendazole (50 mg/kg/day) twice daily for 3 consecutive days. Most subjects (94%) had intermittent symptoms, including urticaria, epigastric pain, and diarrhea. Stools were examined 7 days and 1, 3, 6, 10, and 22 months after treatment. Fifty-three subjects completed at least 3 months of follow-up. Only 1 of 34 and 2 of 19 ivermectin and thiabendazole subjects, respectively, had a stool positive for larvae after treatment. Symptoms were relieved in all 3 groups and eosinophil levels returned to normal in 90% of all subjects by 12 months. Nearly 95% of thiabendazole subjects had short-term adverse effects during therapy versus only 18% of those treated with ivermectin. One dose of ivermectin provides safety and efficacy equivalent to thiabendazole with a much lower prevalence of side effects and, consequently, better compliance.

Adolescent↗
PubMed1992

Cutaneous leishmaniasis: review of 59 cases seen at the National Institutes of Health.

Fifty-nine cases of cutaneous leishmaniasis seen at the National Institutes of Health in Bethesda, Maryland, are reviewed. The group of patients involved was unique in that the majority were American civilians, their disease was acquired in many different endemic areas of the world, and their illnesses represented all points on the clinical spectrum of cutaneous disease. The majority of American patients acquired leishmaniasis while engaging in activities related to their occupations. Cutaneous disease acquired in the New World usually consisted of one or two lesions, while multiple lesions often characterized Old World infections with Leishmania major. Patients with chronic relapsing or diffuse cutaneous leishmaniasis were native to endemic areas and were infected at an early age. Even the localized form of cutaneous leishmaniasis was often extensive and difficult to treat. Diagnosis with culture and identification of the parasite to the subspecies level is instrumental in the selection of optimal therapy. Cutaneous leishmaniasis may be encountered increasingly often in the United States because of the frequent international travel of U.S. residents and the influx of immigrants from endemic areas of the world.

Adolescent↗
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↗
PubMed1989

Leishmania mexicana mexicana: quantitative analysis of the intracellular cycle.

The complete intracellular cycle of the Leishmania mexicana mexicana G. S. strain was quantified in human macrophages and in the mouse IC-21 macrophage line utilizing a culture system that allows the direct observation of individual intracellular parasites. A wide range of pre-replicative lag periods exists, implying that promastigotes may be in any phase of their DNA synthetic cycle when phagocytosed by the macrophage. Amastigotes replicated 2-3 times, after which the host cell died and liberated amastigotes that were taken up by other macrophages and continued to replicate. The mean amastigote population-doubling time in human macrophages (17.5 h) was not statistically different from promastigotes growing in axenic culture (16.4 h), but was nearly 2-fold less than amastigotes growing in mouse-derived IC-21 macrophages (33.7 h). These observations are markedly different from cover-glass culture assays of Leishmania-macrophage interactions and provide an unambiguous description of the intracellular cycle of Leishmania mexicana mexicana.

Animals↗
PubMed1989

Diffuse cutaneous leishmaniasis in Mexico.

In Mexico, 6 cases of diffuse cutaneous leishmaniasis (DCL) were found in widely separated geographic regions. Information was also available on 2 other cases. In addition to the typical clinical features, half of the patients had evidence of nasopharyngeal mucosal involvement. All isolates from the DCL patients were identified as Leishmania mexicana mexicana by isoenzyme analysis and monoclonal antibody typing. In 1 region of Tabasco state where DCL was found, uncomplicated cutaneous leishmaniasis appeared to be highly endemic, and isolates from a few such patients were identified as L. mexicana mexicana. An incidental finding was the recovery of an isolate of L. braziliensis braziliensis from a patient with chiclero ulcer in Oaxaca state. The clinical and epidemiological significance of the reported cases are discussed.

Adolescent↗
PubMed1988

Antigens from the surface and excretions/secretions of the filariform larva of Strongyloides stercoralis.

The surface and excretory/secretory (ES) antigens of the infective, filariform larva (L3) of Strongyloides stercoralis were identified. These studies provide a basis for the purification of these proteins as diagnostic allergens for human strongyloidiasis. The Mr values of the surface and ES molecules were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, fluorography, or silver staining following the recovery of these molecules after the radiolabelling of living parasites. At least 10 surface proteins were radioiodinated extrinsically using chloroglycoluril as the catalyst for iodination, and then extracted with detergents and/or beta-mercaptoethanol. Several surface molecules of the L3 were immunogenic in humans, as determined by immunoprecipitation with sera (IHS) from infected patients. About 30 proteins were present in the ES preparation. Many ES antigens were labelled biosynthetically during the culture of larvae in media supplemented with either [35S]methionine or [14C]glucose. Furthermore, several of the surface proteins of the L3 were found with the ES antigens recoverable by culturing larvae in vitro. About 10 of the ES proteins were immunogenic as determined by immunoaffinity chromatography using IHS; and two of these antigens with Mr 50,000 and 90,000 incorporated [35S]methionine during culture of larvae. Moreover, some ES proteins were allergenic when tested in an in vitro assay of histamine release from basophils from infected humans or monkeys. The isotype of the homocytophilic antibodies involved in this immediate hypersensitivity assay, which is the basis of a diagnostic skin test for human strongyloidiasis, appears to be IgE.

Animals↗
PubMed1988

The immune response to nematode parasites: modulation of mast cell numbers and function during Strongyloides stercoralis infections in nonhuman primates.

Mucosal mast cell numbers are modulated in the intestines of rodents during parasitic infections. These mast cells can degranulate in response to worm antigens, and this event has been suggested to play a protective role for the host. To examine whether mast cells in higher animals play a role in protecting from disseminated parasitic disease, mast cell numbers and responsiveness to parasite antigens were evaluated in 5 Erythrocebus patas infected with the human intestinal nematode Strongyloides stercoralis. Initial infection and subsequent challenge infections were associated with increase in jejunal histamine and mast cell numbers, and these mast cells could release histamine in response to parasite antigens. Jejunal mast cell numbers returned to normal during a chronic phase of infection. The cells lost their ability to respond to antigenic stimulation following limited steroid treatment. Subsequent activation of chronic infections to fatal disseminated disease by more prolonged steroid treatment was associated with a marked decrease in jejunal mast cell numbers and histamine. In one animal which succumbed to severe disease without steroid treatment, jejunal mast cells were refractory to worm antigens.

Animals↗
PubMed1987

American trypanosomiasis (Chagas' disease) in Central American immigrants.

A survey was conducted to determine the prevalence of infection with Trypanosoma cruzi, the protozoan etiologic agent of American trypanosomiasis (Chagas' disease), among Nicaraguan and Salvadoran immigrants living in the Washington, D.C., area. The serum samples of study subjects were tested for reactivity with T. cruzi antigens in an enzyme-linked immunosorbent assay, and also tested for antibody specific for the 72 and 90 kilodalton (kDa) surface glycoproteins of the parasite in an immunoprecipitation and electrophoresis procedure. Xenodiagnosis using reduviid bugs to detect parasites, and clinical evaluations for cardiac and gastrointestinal disease were performed in patients in whom results of both serologic tests were positive. Of 205 subjects studied, 4.9 percent were infected with T. cruzi, and parasites were isolated from 50 percent of those in whom xenodiagnosis was attempted. No significant cardiac or gastrointestinal abnormalities were detected in the six infected patients who were evaluated clinically. These findings suggest that a sizable proportion of persons in this immigrant group are infected with this organism. Thus, routine serologic testing for antibody to T. cruzi may be warranted in immigrants from these countries, especially in view of the potentially serious consequences of infection with this parasite, and also because of the risk of transmission of T. cruzi by blood transfusion.

Chagas Disease↗