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ABSTRACT |
 TOP ABSTRACT INTRODUCTIONSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONREFERENCES |
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONREFERENCES |
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A close relationship between strongyloidiasis and HTLV-1 has been reported in disease-endemic areas.1–3 In addition, a high prevalence rate of infection with S. stercoralis and a high rate of therapeutic failure have been noted in HTLV-1 carriers.4–6 Furthermore, severe forms of strongyloidiasis have been documented in patients with HTLV-1 infection.7,8 These reports have indicated that HTLV-1 has strong immunologic implications in patients with S. stercoralis infection. It has also been reported that Th2 type of immune response is predominant in S. stercoralis infection and that serum IgE levels are low in patients coinfected with S. stercoralis and HTLV-1.9,10
However, there have been few prospective studies evaluating the relationship between strongyloidiasis and HTLV-1 infections. With this background, we have conducted a prospective inpatient survey to examine the prevalence rate of strongyloidiasis and HTLV-1 infection, and to evaluate the relationship between these infections. In addition, we also analyzed serum IgE levels and peripheral eosinophil counts to evaluate immune response in patients with strongyloidiasis who were treated with ivermectin.
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SUBJECTS, MATERIALS, AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients for assessment of the therapeutic effect of ivermectin. These patients had mild-to-moderate strongyloidiasis for a period 11 years from 1990 to 2001. Before entry to this study, each patient was informed of the orphan-drug study, its purpose, and potential side effects. The study included 252 patients with strongyloidiasis who were treated with ivermectin (administered orally at a dose of 100 µg/kg, and the same dose was repeated two weeks later).
Assays to detect HTLV-1 infection and S. stercoralis infection. Serum antibody to HTLV-1 was prospectively measured in all patients by the gelatin particle agglutination method,11 and infection of S. stercoralis was prospectively diagnosed using the agar plate culture method.12 Written informed consent for examination was obtained from all patients. In patients where the therapeutic effect of ivermectin was assessed, total serum IgE levels were determined by latex nephelometry and peripheral eosinophils were counted by May-Giemsa staining.
Definition of the effect of anthelmintic treatment. The effect of anthelmintic treatment was assessed once 1–4 weeks after the administration of ivermectin and a second time 12 months after the initial treatment. In the assessment of the anthelmintic effect, as tested by the agar plate culture method, patients whose stool was negative for S. stercoralis at 12 months after the initial treatment were considered cured.
Statistical analysis. The chi-square test was used to assess differences between sex and between HTLV-1 positive and negative patients. The Mann-Whitney U test was used to compare serum IgE levels and peripheral eosinophil counts between HTLV-1-positive patients and HTLV-1-negative patients.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONREFERENCES |
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). The prevalence rate of S. stercoralis infection gradually increased with age (Table 1).
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). The prevalence rate of HTLV-1 infection gradually increased with age (Table 2).
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). In addition, the prevalence rate of HTLV-1 infection was significantly higher in patients with S. stercoralis infection (32.0%) compared with patients without S. stercoralis infection (16.6%) (P < 0.0001) (Table 4). The differences were more pronounced in female patients than in male patients (Table 4).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS, MATERIALS, AND METHODSRESULTSDISCUSSIONREFERENCES |
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In the present study, the infection rate of S. stercoralis was 6.3% and most patients were more than 50 years of age. The increased rate of strongyloidiasis in patients more than 50 years of age was probably due to the cumulative risk of infection over time. The prevalence of S. stercoralis infection was significantly higher in males compared with females. This result was similar to those of previous reports.13,14 Hayashi and others reported that in the Yaeyama District in Okinawa, Japan, residents worked barefoot in rice paddies and used human excreta as fertilizer until 1965.13 In addition, since male farmers were primarily responsible for distributing human feces in fields, it was assumed that males were more readily exposed to S. stercoralis.13
Human T cell lymphotropic virus type 1 is transmitted by three routes: the first is vertical (in the breast milk or trans-placental), the second is horizontal (sexual), and the third is parenteral (blood transfusion or intravenous drug use).15 In accordance with a previous report,13 the prevalence of HTLV-1 infection was significantly higher in females compared with males, suggesting that horizontal (sexual) transmission played a role in HTLV-1 infection. As demonstrated in the present study, the low prevalence rate of HTLV-1 infection in younger patients might be due to improved public health, as well as a better knowledge of routes of HTLV-1 transmission. In the present study, serum antibody to HTLV-1 was measured by the gelatin particle agglutination method. It has been reported that the specificity and sensitivity of the gelatin particle agglutination test are higher compared with those of the particle agglutination test and indirect immunofluorescence assay.11
The present prospective study clearly demonstrates that there was a strong relationship between HTLV-1 infection and S. stercoralis infection. The prevalence rate of S. stercoralis infection was significantly higher in patients with HTLV-1 infection compared with patients without HTLV-1 infection. Previous studies have demonstrated similar results in Okinawa, Japan.1,13
In the present study, the eradication rate with ivermectin administrated at a dose of 100 µg/kg was significantly lower in patients with HTLV-1 infection compared with patients without HTLV-1 infection. At the beginning of this study, we decided to use a dose of 100 µg/kg per dose instead of 200 µg/kg to reduce the occurrence of any side effects of related to ivermectin. In addition, because it has been suggested that ivermectin is ineffective against larvae and eggs within human tissues, and because it takes two weeks from the time of a percutaneous infection of S. stercoralis until S. stercoralis is discharged into the feces, we administered ivermectin again two weeks later. However, as demonstrated in the present study, the anthelmintic rate of ivermectin at a dose of 100 µg/kg was low, especially in patients with HTLV-1 infection. Therefore, since 2002, we have increased the single dose amount of ivermectin from 100 µg/kg per dose to 200 µg/kg per dose. In accordance with the present study, higher rates of therapeutic failure with ivermectin or thiabendazole against S. stercoralis in patients with HTLV-1 infection have been reported.4,16
The development of strongyloidiasis in HTLV-1-infected individuals is due to two factors: impairment of the immune mechanism against S. stercoralis and decreased efficacy of anti-helminth drugs in patients co-infected with HTLV-1 and helminthes. The reasons for the decreased efficacy of anti-heminth drugs in patients infected with both S. stercoralis and HTLV-1 are not clear, but because the immune mechanisms against S. stercoralis are decreased in patients infected with HTLV-1, it is likely that the efficacy of the drugs also depends on intact immune responses.3
In S. stercoralis infection, a Th2 type immune response is predominant. However, patients infected with HTLV-1 have spontaneous T lymphocyte proliferation and infected T lymphocytes produce high levels of interferon-
, which are associated with the Th1 type of immune response. In contrast, HTLV-1-infected T lymphocytes produce low levels of interleukin-4, as well as interleukin-5, which play an important role in the Th2 type immune response.10,17 However, as demonstrated in the present study, patients co-infected with HTLV-1 had significantly lower levels of serum IgE and peripheral eosinophil counts compared with patients without HTLV-1 infection. In accordance with this evidence, in the present study, the prevalence rate of S. stercoralis infection and the rate of therapeutic failure were high in patients with HTLV-1 infection compared with patients without HTLV-1 infection. Since the Th2 type immune response is necessary for defense against helminthes, and eosionophils and IgE have important roles against helminthes,9,18 these results suggest that co-infection with HTLV-1 may impair the Th2 type of immune response in patients infected with S. stercoralis.
In conclusion, our prospective study clearly demonstrates the relationship between S. stercoralis infection and HTLV-1 infection. Since impairment of the immune response to S. stercoralis was evident in patients co-infected with HTLV-1, new strategies to eradicate S. stercoralis should be established in future studies.
Received August 4, 2005. Accepted for publication October 9, 2005.
* Address correspondence to Tetsuo Hirata, Control and Prevention of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. E-mail: h400314{at}med.u-ryukyu.ac.jp 
Authors’ addresses: Tetsuo Hirata, Nobufumi Uchima, Akira Hokama, and Jiro Fujita, Control and Prevention of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan, Telephone: 81-98-895-1144, Fax: 81-98-895-1414, E-mails: h400314{at}med.u-ryukyu.ac.jp, nuchima-gi{at}umin.ac.jp, hokama-a{at}med.u-ryukyu.ac.jp, and fujita{at}med.u-ryukyu.ac.jp. Ka-zuto Kishimoto, Nagisa Kinjo, and Fukunori Kinjo, Department of Endoscopy, Ryukyu University Hospital, 207 Uehara, Nishihara, Okinawa 903-0215, Japan, Telephone: 81-98-895-1144, Fax: 81-98-895-1414, E-mails: kk691031{at}yahoo.co.jp, nagisa-k{at}med.u-ryukyu.ac.jp and kinjofuk{at}med.u-ryukyu.ac.jp. Osamu Zaha, Department of Internal Medicine, Nakagami Hospital, 6-25-5 Chibana, Okinawa city, Okinawa, Japan, Telephone: 81-98-939-1300, Fax: 81-98-937-8699, E-mail: zaha-o{at}nakagami.or.jp. Hiroshi Sakugawa, Department of Blood transfusion Medicine, Ryukyu University Hospital, 207 Uehara, Nishihara, Okinawa 903-0215, Japan, Telephone: 81-98-895-1144, Fax: 81-98-895-1414, E-mail: b987607{at}med.u-ryukyu.ac.jp.
Reprint requests: Tetsuo Hirata, Control and Prevention of Infectious Diseases, Department of Medicine and Therapeutics, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan, E-mail: h400314{at}med.u-ryukyu.ac.jp
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