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.     

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.     

Epidemiological and clinical interaction between HTLV-1 and Strongyloides stercoralis

Strongyloides stercoralis is the most common human parasitic nematode that is able to complete a life cycle and proliferate within its host. The majority of patients with strongyloidiasis have an asymptomatic infection or mild disease. However, when autoinfection occurs, a high number of infecting larvae can gain access to the bloodstream by penetrating the colonic mucosa leading to a severe hyperinfection and the development of disseminated strongyloidiasis. The human T cell lymphotropic virus type 1 (HTLV-1) predominantly infects T cells and induces spontaneous lymphocyte proliferation and secretion of high levels of type 1 cytokines. Strongyloides stercoralis patients with HTLV-1 co-infection have a modified immunological responses against parasite antigens and co-infection has clinical implications for strongyloidiasis. The high production of IFN-gamma observed in patients co-infected with HTLV-1 and Strongyloides stercoralis decreases the production of IL-4, IL-5, IL-13 and IgE, molecules that participate in the host defence mechanism against helminths. Moreover, there is a decrease in the efficacy of treatment of Strongyloides stercoralis in patients co-infected with HTLV-1. Alterations in the immune response against Strongyloides stercoralis and the decrease in the efficacy of anti-parasitic drugs are responsible for the increased prevalence of Strongyloides stercoralis among HTLV-1 infected subjects and make HTLV-1 infection the most important risk factor for disseminated strongyloidiasis.     

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.     

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.     

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.     

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.     

Syndrome of inappropriate secretion of antidiuretic hormone and nonpalpable purpura in a woman with Strongyloides stercoralis hyperinfection

Strongyloidiasis stercoralis hyperinfection presenting as vasculitic-like skin lesions is rare. An autoinfection cycle allows intestinal strongyloidiasis, usually a benign infection, to persist for many decades. We report a woman with disseminated S stercoralis infection presenting as nonpalpable purpuric skin rash and syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Upon admission, she was treated with corticosteroids for her vasculitic skin lesions, which then worsened her status. When the diagnosis was recognized, steroids were stopped, thiabendazole treatment was instituted, and she gradually recovered. Serious or fatal infection can occur in patients with strongyloidiasis who were treated with immunosuppressive drugs. Stool specimen screening and/or serological tests for S stercoralis infection in patients who require immunosuppressive therapy helps to prevent complications before embarking on such treatment. Unexplained hyponatremia, severe hypoalbuminemia without proteinuria, and unusual skin rashes, especially over the lower aspect of the abdomen and upper aspects of the thighs, in persons living in areas endemic to S stercoralis should raise suspicion of S stercoralis infection.     

Association of a sex-related difference of Strongyloides stercoralis-specific IgG4 antibody titer with the efficacy of treatment of strongyloidiasis

It is difficult to completely eradicate strongyloidiasis, a human intestinal nematode infection with Strongyloides stercoralis with drugs, especially in males. To find host factors involved in the response to treatment, patients infected with S. stercoralis were examined for S. stercoralis-specific antibody titers and the effect of treatment with albendazole on these titers were determined. The cure rate was slightly but not significantly lower in males than in females (P = 0.108). However, a significantly higher titer of S. stercoralis-specific IgG4 antibody was observed in males than in females (P = 0.0097), and the S. stercoralis-specific IgG4 antibody titer was significantly higher in the male non-cured group than in the cured group (P = 0.035). These results suggest that elevation of the S. stercoralis-specific IgG4 antibody titer is associated with resistance to treatment of S. stercoralis infection, especially in males.     

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.     

Strongyloides stercoralis: a cause of morbidity and mortality for indigenous people in Central Australia

Background: Strongyloides stercoralis may cause a complicated infection in immunocompromised patients, which has a high case fatality rate. Death generally results from sepsis with enteric pathogens. Globally, infection with the human T‐cell lymphotropic virus type 1 (HTLV‐1) is a major risk factor for this syndrome. Both S. stercoralis and HTLV‐1 are endemic to Central Australia. Aims: The aim of the study was to determine whether complicated strongyloidiasis occurs in association with HTLV‐1 infection in Central Australia. Methods: A retrospective audit of all cases of complicated strongyloidiasis presenting to Alice Springs Hospital between January 2000 and December 2006 was carried out. Diagnosis was defined as definite or probable according to whether diagnosis was made by faecal studies or serology respectively. The medical records, investigations and outcomes of patients who met predetermined criteria for a diagnosis of complicated strongyloidiasis were reviewed. Results: Eighteen indigenous patients met the criteria for complicated strongyloidiasis (definite 9, probable 9). Seven of 11 patients tested were HTLV‐1 seropositive. At diagnosis, no treatment was documented for nine patients (definite 4, probable 5), three received a single dose of ivermectin and one a single dose of albendazole. Fifteen patients (83%) died because of sepsis (definite 7, probable 8). Pathogens isolated and their foci of infection included Klebsiella pneumoniae pneumonia (4), bloodstream infection with Enterococcus spp. (2), K. pneumoniae peritonitis (1) and streptococcal meningitis (1). Conclusion: Complicated strongyloidiasis occurs in association with HTLV‐1 infection in central Australia. This finding has significant implications for the management of S. stercoralis in the region.     

Immunocompromised group differences in the presentation of intestinal strongyloidiasis

The hospital records of 213 outpatients from Bangkok, Thailand, infected with Strongyloides stercoralis as determined by stool inspections were examined retrospectively for the different clinical presentations ascribed to patients with HIV, those with chronic illness, those who used immunosuppressant drugs and relatively healthy subjects. For HIV patients with strongyloidiasis, the most common symptoms were chronic diarrhea, fever, persistent coughing and loss of weight, but only the first three symptoms were significantly different from other immunocompromised hosts. For healthy patients with strongyloidiasis, acute diarrhea and abdominal pain were the most frequent symptoms. Moreover, the peripheral eosinophil blood count was significantly lower (P=0.004) in the HIV patients than in any of the other subsets. Males were more common than females across all categories. While the average age of all subjects was 48.3+/-16.4 years, the strongyloidiasis patients with chronic illness were significantly older (56.8+/-13.5 years) than those in the other groups. This study may suggest that strongyloidiasis is commonly found in geriatric males, and that the patients most at risk for S. stercoralis infection are HIV patients. This is the first report of the different clinical presentations of intestinal strongyloidiasis in various groups of patients with impaired immunity.     

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.     

Parasitological and immunological diagnosis of Strongyloides stercoralis in patients with gastrointestinal cancer

This study examined the frequency of Strongyloides stercoralis infection in patients with gastrointestinal cancer through parasitological and immunological tests. A total of 77 patients were evaluated, 33 with gastrointestinal cancer and 44 controls with other types of cancers. All the patients were undergoing chemotherapy and 14 (18.2%) were receiving concomitant radiotherapy. For a parasitological diagnosis, we applied the Baermann and Lutz methods. The immunological diagnosis involved the indirect fluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA) to detect IgG antibodies using Strongyloides ratti antigens. The frequency of positive S. stercoralis in gastrointestinal cancer diagnosed by parasitological methods was 3 cases (9.1%), by serology it was 8 cases (24.2%). In the control group 1 case (2.3%) of S. stercoralis was diagnosed by parasitological methods and 2 cases (4.5%) by immunological tests (p<0.05). Patients with gastrointestinal cancer had a 6.7-fold greater chance of testing positive for S. stercoralis infection. Our data highlight the importance of parasitological and immunological diagnosis for S. stercoralis in patients with gastrointestinal cancer living in endemic areas of strongyloidiasis, since they have a higher risk of becoming infected with S. stercoralis than patients with other types of cancer.     

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.     

Hematologic and biochemical changes associated with human T lymphotropic virus type 1 infection in Jamaica: a report from the population-based blood donors study.

OBJECTIVE: We investigated changes in hematologic and biochemical parameters associated with human T lymphotropic virus type 1 (HTLV-1) infection, antibody titer, and provirus load. Additionally, on a subset of participants, we assessed the epidemiologic relationship of HTLV-1 with Strongyloides stercoralis. METHODS: Among volunteer blood donors in Jamaica, HTLV-1 carriers (n=482) were frequency matched with HTLV-1 negative subjects (n=355) by age (+/-5 years), sex, and date of blood donation (+/-3 months). HTLV-1 antibody titer, provirus load, S. stercoralis IgG antibodies, complete blood cell count, blood chemistry, and urinalysis parameters were measured. RESULTS: HTLV-1 carriers, compared with HTLV-1-negative individuals, had elevated levels of cleaved lymphocytes (24.5% vs. 16.4%), any lymphocyte abnormalities (atypical, cleaved, and reactive lymphocytes combined, 45.7% vs. 35.4%), and gamma-glutamyl transferase levels (21.2 vs. 19.6 IU/L), as well as lower eosinophil count (2.6% vs. 3.1%). Among carriers, HTLV-1 antibody titer (n=482) was inversely correlated with mean corpuscular volume (r=-0.10) and positively correlated with levels of total protein (r=0.16), phosphorus (r=0.12), and lactate dehydrogenase (r=0.24). HTLV-1-provirus load (n=326) was higher among carriers with cleaved lymphocytes and any lymphocyte abnormalities. Provirus load was inversely correlated with hemoglobin (r=-0.11), mean corpuscular volume (r=-0.15), neutrophil (r=-0.12), and eosinophil (r=-0.19) levels and was positively correlated with lactate dehydrogenase levels (r=0.12). Provirus load was significantly higher among male than female subjects. S. stercoralis antibodies were detected in 35 (12.1%) of 288 participants but were not associated with HTLV-1 status, antibody titer, or provirus load. CONCLUSIONS: Markers of HTLV-1 infection (infection status, antibody titer, and provirus load) are associated with hematologic and biochemical alterations, such as lymphocyte abnormalities, anemia, decreased eosinophils, and elevated lactate dehydrogenase levels.     

Strongyloides stercoralis hyperinfection in a carrier of HTLV-I virus with evidence of selective immunosuppression.

A patient with near fatal Strongyloides hyperinfection syndrome is briefly described. Investigation for possible risk factors for this parasitic infection disclosed that he was a carrier of human T-cell leukemia virus type I (HTLV-I), but without evidence of disease due to this retrovirus. Over the next few years, the patient's serum antibody levels of IgG to S. stercoralis larvae declined and became undetectable despite continued infection with the parasite. Repeated courses of appropriate treatment cleared the parasitic infection only temporarily. The patient was also found to have undetectable total serum IgE and a negative immediate hypersensitivity skin test to S. stercoralis antigens. Five of six other patients with HTLV-I-associated disease and with or without strongyloidiasis were also found to have very low total serum IgE levels. It is postulated that HTLV-I infection in certain individuals may selectively impair immune responses that are critical in controlling strongyloidiasis.     

Low prevalence of human T cell lymphotropic virus type 1 infection in patients with gastric cancer

BACKGROUND AND AIM: There have been few studies on the association between human T cell lymphotropic virus type 1 (HTLV-1) infection and cancer risk. It is still controversial whether or not HTLV-1 infection affects the incidence of several cancers. With this background, we aimed to evaluate the relationship between HTLV-1 infection and the occurrence of several types of cancers. METHODS: Subjects were 699 patients with cancer aged 50 years and older diagnosed between 1991 and 2004 at the Department of Medicine and Therapeutics, Ryukyu University Hospital, Okinawa, Japan, and 1365 control patients without cancer. The association between HTLV-1 infection and cancer (biliary tract, pancreatic, esophageal, gastric, colorectal, liver, and lung cancers) was analyzed by logistic regression analysis adjusted for age and sex. RESULTS: The infection rate of HTLV-1 in patients with gastric cancer was significantly lower than in controls (P = 0.01, adjusted odds ratio 0.46). The infection rate of HTLV-1 was not associated with increased or decreased risk of cancers other than gastric cancer. CONCLUSION: Our study indicated that the prevalence of HTLV-1 infection in patients with gastric cancer appears to be significantly lower than that in control patients.     

Detection of opportunistic and non-opportunistic intestinal parasites and liver flukes in HIV-positive and HIV-negative subjects

We assessed the frequency and distribution of infection with opportunistic and non-opportunistic intestinal parasites and the liver fluke, Opisthorchis viverrini, in HIV-seropositive and HIV-seronegative subjects. Age- and sex-matched HIV-seropositive (n = 78) and HIV-seronegative patients (n = 78) from two hospitals in Khon Kaen Province, Thailand, participated in this study from November 1998 to August 2000. These subjects were divided according to the presence of diarrhea and CD4 counts. A single stool sample was obtained and analyzed by using specific techniques. Opisthorchis viverrini, was the most common parasite (19.2%) in each group. The prevalence rates of Cryptosporidium spp (11.5%) and Strongyloides stercoralis (17.9%) in the HIV-seropositive group were significantly (p < 0.05) higher than those in the HIV-seronegative group (1.0% for Cryptosporidium spp and 7.7% for S. stercoralis infections). The prevalences of these two parasites were 28% for Cryptosporidium spp and 20% for S. stercoralis in HIV-seropositives with diarrhea and CD4 counts lower than 100 cells/mm3, and were higher compared with patients without diarrhea or with high CD4 counts. These results suggest that infection with these parasites increases during HIV infection. The epidemiological distribution of Cryptosporidium and S. stercoralis may have implications for AIDS-related diseases.     

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.