Impairment of host immune response against strongyloides stercoralis by human T cell lymphotropic virus type 1 infection

A large-scale study was undertaken to clarify the prevalence rate of strongyloidiasis in Okinawa, Japan and to evaluate the relationship between strongyloidiasis and infection with human T cell lymphotropic virus type 1 (HTLV-1). The prevalence rate of Strongyloides stercoralis and HTLV-1 infection were 6.3% and 14.0%, respectively. Among 2,185 patients more than 50 years of age, the rate of S. stercoralis infection was significantly higher in patients with HTLV-1 infection compared with patients without HTLV-1 infection. In 252 patients treated with ivermectin, serum IgE levels and peripheral eosinophil counts were significantly lower in HTLV-1 co-infected patients compared with patients without HTLV-1 infection. In addition, the anthelmintic effect was significantly lower in patients with HTLV-1 infection compared with patients without HTLV-1 infection. Our prospective study demonstrated a prevalence rate for strongyloidiasis and HTLV-1 infections, and clearly demonstrated that co-infection with HTLV-1 impaired the immune response against S. stercoralis.     

HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis

Eosinophils, immunoglobulin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interferon (IFN)-gamma and interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-gamma and IL-5 (P = 0.01; rs = - 0.37) and between IFN-gamma and parasite specific IgE (P = 0.01; rs = - 0.39), and a direct relationship between IFN-gamma and IL-10 (P = 0.04; rs = 0.35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection.     

Severe and treatment resistant strongyloidiasis--indicator of HTLV-I infection.

The association between severe and persistent strongyloidiasis with human T cell lymphotropic virus type I (HTLV-1) infection is well documented in reports from HTLV-1 endemic regions like Japan and Jamaica. But there are no reports from non-endemic areas like India. We report a case of severe intestinal strongyloidiasis in a 45-year old Keralite man, living in Sikkim. Despite standard treatment with many courses of albendazole, his stool persistently showed Strongyloides stercoralis larvae. In the absence of other immunosuppressive conditions, human T cell lymphotropic virus type I infection was considered and determined positive. Subsequently, treatment with 2 courses of ivermectin achieved eradication of the infection. On follow-up, 3 years later, his stools again revealed Strongyloides stercoralis larvae.     

Case study: Fatal strongyloidiasis associated with human T-cell lymphotropic virus type 1 infection.

A case of fatal strongyloidiasis associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection is described in a 45-year-old West Indian man living in an area endemic for both strongyloidiasis and HTLV-1 infection. Clinical presentation was typical with severe diarrhea, vomiting, and progressive weight loss. Stool microscopy revealed Strongyloides stercoralis rhabditiform larvae. Despite treatment with thiabendazole, the patient died. Autopsy findings revealed severe ileocolitis due to Strongyloides larvae, right subdiaphragmatic pyogenic abscess, and severe pleuritis of the right lower lobe of the lung. This case illustrates that despite effective antihelmintic therapy, mortality is still high in patients with the hyperinfective state of S. stercoralis. Thus, in patients in areas endemic for both Strongyloides infection and HTLV-1, or in immigrants from these areas, repeated stool microscopy is indicated in patients positive for HTLV-1.     

Atypical clinical presentation of strongyloidiasis in a patient co-infected with human T cell lymphotrophic virus type I

Alterations in the immunologic response induced by human T cell lymphotrophic virus type I (HTLV-I) predispose the development of disseminated strongyloidiasis. We report a case of an atypical clinical presentation of strongyloidiasis in a patient co-infected with HTLV-I causing scrotal and perineal pain and infertility. Strongyloides stercoralis was found in the analysis of the sperm and specific therapy for strongyloidiasis was associated with disappearance of the symptoms.     

Human T-cell lymphotropic virus-I in Latin America

HTLV-1 infection is endemic in several Latin American countries. HTLV-1-associated myelophathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia lymphoma (ATLL) are emerging diseases in the region. Documented risk factors for acquiring the virus include breast-feeding, contaminated blood transfusion, and sexual intercourse, all of which are amenable to prevention efforts. Strongyloides stercoralis hyperinfection syndrome and therapeutic failure in apparently healthy patients with nondisseminated strongyloidiasis may be markers of HTLV-1 infection. HTLV-1 co-infection may adversely effect the clinical course of scabies and HIV disease. The new enzyme-linked immunosorbent assays (ELISA) are sensitive and specific, and Western blot technology is reliable for differentiating HTLV-1 from less common HTLV-2. HTLV-1 screening of blood donors and individuals with any disorder that suggests infection has become a necessity in Latin America to prevent the spread of this important emerging pathogen.     

Why does HIV infection not lead to disseminated strongyloidiasis?

We investigated the hypothesis that host immunosuppression due to advancing human immunodeficiency virus (HIV) disease favors the direct development of infective larvae of Strongyloides stercoralis, which may facilitate hyperinfection and, hence, disseminated strongyloidiasis. To do this, we sought correlations between the immune status of the subjects and the development of S. stercoralis infections. Among 35 adults, there were significant negative rank correlations between CD4+ cell counts and the proportions of free-living male and female worms. Thus, in individuals with preserved immune function, direct development of S. stercoralis is favored, whereas, in individuals with lesser immune function, indirect development is relatively more common. These results may explain the notable absence of disseminated strongyloidiasis in advanced HIV disease. Because disseminated infection requires the direct development of infective larvae in the gut, the observed favoring of indirect development in individuals immunosuppressed by advancing HIV disease is not consistent with the promotion of disseminated infection.     

Prevalence of Strongyloides stercoralis infection among HIV-positive immigrants attending two Italian hospitals, from 2000 to 2009

In patients with Strongyloides stercoralis infection, a dysregulation of host immunity can lead to hyperinfection syndrome (HS) and disseminated strongyloidiasis (DS), characterized by high fatality rate. HS has been reported in HIV-positive patients following use of corticosteroids or during immune reconstitution inflammatory syndrome (IRIS). A retrospective study was conducted to estimate the prevalence of S. stercoralis infection among HIV-positive immigrants, attending two Italian hospitals. From January 2000 to August 2009, 138 HIV-positive immigrants were systematically screened for strongyloidiasis, as a part of their routine care, with an indirect immunofluorescent antibody test (IFAT) developed at the Centre for Tropical Diseases, Sacro Cuore Hospital of Negrar, Verona. The majority were also submitted to stool examination. Fifteen (11%) resulted infected by S. stercoralis, of whom four (27%) had a negative serology (diagnosis made with stool examination). A higher eosinophil count (0·94 versus 0·24×10(9)/l, P<0·01) and more frequent gastrointestinal and cutaneous symptoms (odds ratio: 4·8 and 5·8, respectively) were found in patients with strongyloidiasis compared with controls. The IFAT is more sensitive than direct parasitological methods. The proportion of false negative results was higher than expected based on the theoretical test sensitivity. Considering the high prevalence detected and the apparent, lower sensitivity of serology, we propose a systematic screening for Strongyloides infection, with both serology and stool culture, for all HIV-positive immigrants coming from endemic areas.     

Atypical gastric presentation of strongyloidiasis in HIV-infected patient—case report

Strongyloides stercoralis is an intestinal helminth of systemic distribution, which, once in its host, has the ability to perpetuate itself through an autoinfection cycle, leading to chronic infection. In healthy hosts, the parasite usually does not cause any symptoms, or only mild symptoms that are limited mainly to the small intestine. However, in immunocompromised hosts, uncontrolled multiplication with massive infection may occur, causing hyperinfection syndrome or disseminated strongyloidiasis, which are both associated with high morbidity and mortality. There are few reports of gastric involvement, particularly presenting as ulcer in the stomach. We report a case of gastric ulcer caused by S. stercoralis in HIV-infected patient.     

Endoscopic and histopathological study on the duodenum of Strongyloides stercoralis hyperinfection

AIM： To investigate endoscopic and histopathological findings in the duodenum of patients with Strongyloides stercoralis （S. stercoralis） hyperinfection. METHODS： Over a period of 23 years （1984-2006）, we investigated 25 patients with S. stercoralis hyperinfection who had had an esophagogastroduodenoscopy before undergoing treatment for strongyloidiasis. The clinical and endoscopic findings were analyzed retrospectively. RESULTS： Twenty-four （96%） of the patients investigated were under immunocompromised condition which was mainly due to a human T lymphotropic virus type 1 （HTLV-1） infection. The abnormal endoscopic findings, mainly edematous mucosa, white villi and erythematous mucosa, were observed in 23 （92%） patients. The degree of duodenitis including villous atrophy/destruction and inflammatory cell infiltration corresponded to the severity of the endoscopic findings. The histopathologic yield for identifying larvae was 71.4% by duodenal biopsy. The endoscopic findings of duodenitis were more severe in patients whose biopsies were positive for larvae than those whose biopsies were negative （Endoscopic severity score： 4.86 ± 2.47 vs 2.71 ±1.38, P 〈 0.05）. CONCLUSION： Our study clearly demonstrates that, in addition to stool analysis, endoscopic observation and biopsies are very important. We also emphasize that S. stercoralis and HTLV-1 infections should be ruled out before immunosuppressive therapy is administered in endemic regions.     

Epidemiological aspects of Strongyloides stercoralis infection in Okinawa, Japan.

The epidemiology of Strongyloides stercoralis infection was compared among three localities with various prevalences of human T lymphotropic virus type 1 (HTLV-1) infection in Okinawa Prefecture, Japan, using agar-plate culture of faeces. The prevalence of S. stercoralis infection is much higher in Gusukube, where HTLV-1 infection is rare, than in Yomitan, where this viral infection is common. In all localities the parasite prevalence is significantly higher in males than in females, whereas the prevalence of HTLV-1 infection is much higher in females. These epidemiological facts suggest that infection by S. stercoralis occurs independently of that by HTLV-1.     

Strongyloides stercoralis infection in an HIV positive patient--a case report from RIMS, Imphal, Manipur

Strongyloides stercoralis, a nematode parasite in human 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. We report a case of a 33 year old male HIV positive patient admitted on 2/6/08 in male medical ward, Regional Institute of Medical Sciences, Imphal, Manipur with complaints of loose stools, pain abdomen, nausea, vomiting, generalized weakness, loss of appetite and loss of weight for past one month with fever off and on. Stool examination reveals larvae of Strongyloides stercoralis. The patient was successfully treated with Ivermectin 200 microgm/kg daily for 2 days.     

Helminthic infection down-regulates type 1 immune responses in human T cell lymphotropic virus type 1 (HTLV-1) carriers and is more prevalent in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis

Human T cell lymphotropic virus type 1 (HTLV-1) infection is associated with an exacerbated type 1 immune response and secretion of high levels of proinflammatory cytokines. In contrast, helminthic infection induces a type 2 immune response. In the present study, the cytokine profile in HTLV-1 carriers coinfected with helminths (Strongyloides stercoralis and/or Schistosoma mansoni) was compared with that in HTLV-1 carriers not coinfected with helminths. Levels of interferon (IFN)- gamma were higher in HTLV-1 carriers not coinfected with helminths than in HTLV-1 carriers coinfected with helminths (P<.05). The overall frequency of IFN- gamma -expressing CD8+ and CD4+ cells was decreased in HTLV-1 carriers coinfected with helminths (P<.05). The percentage of interleukin (IL)-5- and IL-10-expressing T cells in HTLV-1 carriers coinfected with helminths was higher than that in HTLV-1 carriers not coinfected with helminths (P<.05). Moreover, we found that the prevalence of helminthic infection was 7-fold higher in HTLV-1 carriers than in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (P<.05). These data show that helminthic infection decreases activation of type 1 cells, which may influence the clinical outcome of HTLV-1 infection.     

Eosinophil-selective mediators in human strongyloidiasis

Strongyloides stercoralis infection is characterized by the production of IgE and eosinophils in peripheral blood. Experimental studies have demonstrated that eosinophils play an important role in protection against Strongyloides stercoralis, but the mechanisms regulating eosinophils are not known. In this study we have focused on analysing the molecules that selectively regulate eosinophil migration, namely eotaxin and interleukin-5 (IL-5), using an enzyme-linked immunosorbent assay in patients with strongyloidiasis. Serum expression of eotaxin and IL-5 were significantly increased in patients compared with the control group. This rise suggests that selective mediators of the eosinophil can have a role in immunity against S. stercoralis in human infection.     

Comparative studies on the efficacy of three anthelminthics on treatment of human strongyloidiasis in Okinawa, Japan

A study was undertaken to compare the efficacy of three drugs in the treatment of uncomplicated strongyloidiasis in Okinawa, Japan. Two hundred and eleven patients with confirmed Strongyloides stercoralis infection were given either ivermectin, 6 mg in a single dose, albendazole, 400 mg/day for 3 days or pyrvinium pamoate, 5 mg/kg/day for 3 days. For each treatment, the same regimen was repeated once 2 weeks later. Efficacy was evaluated at 2 weeks, 6 months and 12 months after the second course of treatment. Each follow-up examination included a parasitological examination of z stool specimens, using the agar-plate culture method. Coprological cure was obtained in 65 of the 67 patients treated with ivermectin (97.0%), in 65 of the 84 patients treated with albendazole (77.4%) and only in 14 of the 60 patients who were given pyrvinium pamoate (23.3%). The cure rates were lower in males and in the patients with concurrent HTLV-1 infection. An epidemiological feature of Strongyloides infection in recent Okinawa might allow workers to evaluate the exact efficacy of the treatment for an extended period, over a year, without the possibility of reinfection from the environment.     

Disseminated infection due to strongyloides stercoralis in AIDS patients. A report of 2 cases

Strongyloides stercoralis is an intestinal nematode that infects humans worldwide. Infected patients with severe involvement of cellular immunity may develop a syndrome characterized by the dissemination of larvae throughout the body. Extraintestinal strongyloidiasis has been infrequently reported and despite the prevalence of the helminth in tropical and developing countries there are few cases reported in AIDS patients. Most patients with disseminated strongyloidiasis present with fever, cough, diarrhea and shortness of breath. Chest radiographs usually show diffuse infiltrates. The diagnosis has been made by finding the helminth in respiratory secretions or stool. Enteric organisms like Escherichia coli can often be isolated in the blood or cerebrospinal fluid. We report two cases of disseminated strongyloidiasis in AIDS patients, in which stercoralis larvae were detected in sputum and stool samples.     

Influence of human T-cell lymphocytotropic virus type 1 infection on serologic and skin tests for strongyloidiasis.

The aim of this study was to determine whether human T-cell lymphocytotropic virus type 1 (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific IgE levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44% and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis.     

Efficient control of Leishmania and Strongyloides despite partial suppression of nematode-induced Th2 response in co-infected mice

Endemic regions for the pathogenic nematode Strongyloides and parasitic protist Leishmania overlap and therefore co-infections with both parasites frequently occur. As the Th2 and Th1 immune responses necessary to efficiently control Strongyloides and Leishmania infections are known to counterregulate each other, we analysed the outcome of co-infection in the murine system. Here, we show that Leishmania major-specific Th1 responses partially suppressed the nematode-induced Th2 response in co-infected mice. Despite this modulation, successful expulsion of gut dwelling Strongyloides was not suppressed in mice with pre-existing or subsequent Leishmania infection. A pre-existing Strongyloides infection, in contrast, did not interfere with efficient type-1 responses but even increased pro-inflammatory cytokine production. Also, control of L. major infections was not affected by pre-existing nematode infection. Taken together, we provide evidence that simultaneous presence of helminth and protist parasites did not interfere with efficient host defence in our co-infection model.     

Disseminated strongyloidiasis with uncommon manifestations in Greece

Strongyloidiasis is a human intestinal parasitosis caused by the nematode Strongyloides stercoralis. In most cases the infection is subclinical, but rarely, disseminated strongyloidiasis may occur in debilitated or immunocompromised patients, and in those who receive immunosuppressive agents. In this report, we describe an unusual case of severe disseminated strongyloidiasis, with intestinal, pulmonary and neurological manifestations, in a previously healthy male. The onset of the disease was acute with headache and neck stiffness, due to subarachnoid-ventricular haemorrhage. During a protracted clinical course the patient developed diarrhoea, abdominal pain, recurrent paralytic ileus, pneumonitis and respiratory distress, malabsorption and weight loss, diagnosis was delayed due to the complicated course and rarity of the disease. The diagnosis finally established during evaluation for malabsorption by demonstrating larvae of S. stercoralis in the jejunal mucosal biopsy and faeces. Response to mebendazole treatment was prompt with complete recovery and resolution of all systemic manifestations. Early diagnosis and treatment of strongyloidiasis in the intestinal phase is critical in the prevention of dissemination, which may prove lethal due to life-threatening complications.     

Treatment of experimental infection by Strongyloides venezuelensis in rats, with the use of injectable ivermectin and levamisole

For the therapy of human strongyloidiasis, are necessary effective drugs to eliminate both larvae and adult worm parasitism, which may also be used by parenteral route, to obviate the particular conditions presented by many patients. A study based on the experimental infection by Strongyloides venezuelensis in rats was done, administering injectable ivermectin or levamisole. Both drugs were shown to be active, when used in single doses of 0.2 to 0.5 mg/kg of ivermectin, or 26 mg/kg for levamisole. Ivermectin was slightly more effective as far as larval stage of the infection is concerned, and the same happened for levamisole for the adult worm stage. Promising perspectives are visualized to improve the therapy of patients with serious disseminated infection by Strongyloides stercoralis.