The intermediate state of HTLV-1 infection, often found in individuals dually infected with Strongyloides stercoralis (S. stercoralis) and HTLV-1, is assumed to be a preleukemic state of adult T-cell leukemia (ATL). To investigate the e ects of S. stercoralis superinfection on the natural history of HTLV-1 infection, we characterized peripheral blood samples of these individuals in Okinawa, Japan, an endemic area for both HTLV-1 and S. stercoralis and we studied e ects of the parasite antigen on T-cells. The dually infected individuals showed a signi®cantly higher provirus load and an increase in CD4 + 25 + T cell population, with a signi®cant, positive correlation. This increase was attributable to polyclonal expansion of HTLV-1-infected cells, as demonstrated by inverse-long PCR analysis of the integration sites. S. stercoralis antigen activated the IL-2 promoter in reporter gene assays, induced production of IL-2 by PBMC in vitro, and supported growth of IL-2 dependent cell lines immortalized by HTLV-1 infection or the transduction of Tax. Taken collectively, these results indicate that S. stercoralis infection induces polyclonal expansion of HTLV-1-infected cells by activating the IL-2/IL-2R system in dually infected carriers, an event which may be a precipitating factor for ATL and in¯ammatory diseases.
Parasitological diagnosis based on the faecal examination is frequently difficult in cases of chronic, low-level S. stercoralis infection. Even when a newly developed sensitive method (an agar plate culture) is applied, it is essential to examine faecal samples repeatedly to achieve a correct diagnosis. Additionally, it is important to note that a negative result does not necessarily indicate the unequivocal absence of the infection. On the other hand, several serological tests which have recently been developed for strongyloidiasis have proven reliable when used to complement parasitological examination. We have developed two serological tests, ELISA and GPAT, to demonstrate Strongyloides infection and possible applications of the serological tests for diagnosis, mass-screening, epidemiological study and postchemotherapy evaluation of strongyloidiasis were reviewed based on our recent studies.
An indirect agglutination test using recently developed gelatin particles was assessed to determine its applicability as a screening test for mass examination for strongyloidiasis. 1199 individuals in Sashiki Town, Okinawa Island, were screened by the test and 34.7% were determined to be antibody positive. Follow-up examination of the persons whose sera showed positive antibody responses demonstrated the presence of faecal larvae in 41.7%. The calculated infection rate (14.5%) was similar (14.1%) to that indicated by another survey using the micro-enzyme-linked immunosorbent assay (micro-ELISA), conducted simultaneously among the inhabitants. The indirect agglutination test was simple to perform in a short time and without specialized equipment. Additionally, the gelatin particles have many advantages as an antigen carrier, e.g. in handling, reading of the resulting pattern, and stable, long-term preservation. The test was considered to be more convenient than the micro-ELISA for mass screening for strongyloidiasis.
Abstract. Strongyloidiasis, a human intestinal infection with Strongyloides stercoralis, is difficult to treat with drugs. The factors influencing this phenomenon remain unclear. To determine the host factors involved in response to treatment, 46 patients with strongyloidiasis were treated with albendazole, followed-up for 1 year, and separated into two groups: cured and non-cured. Serum levels of specific IgA, IgE, IgG, IgG1, and IgG4 antibodies were estimated using S. stercoralis antigen. Significantly higher titers of IgG4 antibody were observed in the non-cured group than in the cured group (P ϭ 0.016). A total of 88 patients were typed for HLA-DRB1 alleles and analyzed for serum levels of antibody. The S. stercoralis-specific IgG4 antibody titers were significantly higher in the HLA-DRB1*0901-positive group than in the negative group (corrected P ϭ 0.044). These results suggest that HLA-DRB1*0901 is a possible genetic marker for resistance to treatment of S. stercoralis that is associated with elevation of S. stercoralis-specific IgG4 antibody titer.Strongyloidiasis is a human intestinal nematode infection caused by Strongyloides stercoralis. It causes chronic bowel problems, especially in immunocompromised hosts, in which systemic migration of larvae provokes a serious illness due to the unique life cycle of autoinfection of this nematode. 1 It is difficult to completely disrupt this process with drugs against S. stercoralis. 1,2 In Japan, there are many patients with persistent infection in the Southern Islands and Okinawa. 2,3 The factors involved in resistance to treatment remain unknown. Several protocols for treatment have been used, but the efficacy of chemotherapy is not always sufficient to achieve complete treatment. 2,3 In general, there are 2 factors determining the effectiveness of antimicrobial drugs. The first is its pharmacologic effect, including specific cytotoxicity and pharmacokinetics. The other factor is host immunity.The purpose of this study was to determine the factors related to host immunity that influence resistance to treatment of S. stercoralis infection. We examined the HLA-DRB1 gene because its shows the most genetic polymorphism in HLA. Here we show that an increased S. stercoralis-specific IgG4 antibody titer is associated with resistance to treatment, and that patients with HLA-DRB1*0901 produce higher levels of specific IgG4 antibody.
MATERIALS AND METHODSStudy population. The efficacy of treatment was evaluated in 46 patients with S. stercoralis infection (29 males and 17 females). The mean ages were 66.4 and 67.1 years, respectively. The frequency of HLA-DRB1 alleles were determined in 88 patients (59 males and 29 females, mean ages ϭ 64.9 and 65.1 years, respectively), including 29 patients who were evaluated for efficacy of treatment. All patients in this study were diagnosed with S. stercoralis infection by an agar plate fecal culture as described 4 at the 1994 annual regional health examination performed in Okinawa prefecture, Japan. Informed consent was obtained fr...
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