Risk factors for strongyloidiasis. A case-control study

Although infection with Strongyloides stercoralis is usually only mildly symptomatic, it can persist for many years and occasionally progress to the hyperinfection syndrome, with a resultant high mortality rate. We studied factors associated with S stercoralis infection by comparing 28 domestic cases of S stercoralis infection with 76 controls with negative stool samples for ova and parasites. The relative risk (RR) of S stercoralis infection was increased for white patients (RR = 5.6), men (RR = 3.9), and patients who had recently used corticosteroids (RR = 3.3), had a hematologic malignancy (RR = 5.28) or had prior gastric surgery (RR = 11.5). These risk factors might be for initial infection, persistence of infection, or both. Although they are not necessarily causal, knowledge of them may lead to earlier recognition of this dangerous and treatable disease.     

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.     

An inverse relationship between autoimmune liver diseases and Strongyloides stercoralis infection

A case-control study was undertaken to describe the prevalence of Strongyloides stercoralis infection among patients with autoimmune liver diseases, such as primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). This study covered 4,117 patients who were admitted to hospitals in Okinawa, Japan, between 1988 and 2006. During this period, 538 patients had the following chronic liver diseases: PBC, AIH, PSC, chronic viral hepatitis group, and alcoholic liver disease. The other 3,579 patients who were hospitalized and underwent parasitologic tests served as controls. The frequency of S. stercoralis infection in the autoimmune liver diseases group (1.0%) was lower than that found in the control group (7.0%; P = 0.0063). None of the female patients with PBC born before 1955 had S. stercoralis infection, which was also statistically significant (P = 0.045). We hypothesized that immunomodulation by S. stercoralis infection may lower the incidence of autoimmune liver disease.     

Strongyloidiasis: challenges in diagnosis and management in non-endemic Kuwait

Among immunocompromised individuals, hyper-infection with Strongyloides stercoralis may occur and lead to fatal strongyloidiasis. To clinicians and laboratory diagnosticians in non-endemic countries such as Kuwait, this severe infection poses a particular problem. The clinical histories and signs and symptoms of four Kuwaiti cases of S. stercoralis hyper-infection were reviewed. Each of the four was found not only to have lived in an area where S. stercoralis was endemic but also to have been treated with immunosuppressive steroids (for medical problems unrelated to the nematode infection). When they presented with undiagnosed hyper-infections their clinical features were confusing. Three of the cases, all with low eosinophil counts, died but the other, who was treated with thiabendazole, survived. In the light of these observations, healthy medical examinees who had recently moved from endemic zones were checked for asymptomatic S. stercoralis infection, both by stool examination and ELISA-based serology. Of 381 stool samples investigated over a 3-month period, 183 (48%) were found positive for helminths, 7% for S. stercoralis. Of 198 individuals from endemic zones who were screened after another medical examination, 71 (35.8%) were found positive for intestinal helminth parasites, including one (1.45%) infected with S. stercoralis. Although ELISA appear reliable in making a presumptive diagnosis of strongylodiasis, the results of such assays are not very specific and are best interpreted in conjunction with the patient's clinical status. The concurrent administration of anthelminthics to patients prescribed steroids who, because they live or have lived in an area where S. stercoralis is endemic, are at risk of infection with the nematode, should be considered.     

A luciferase immunoprecipitation systems assay enhances the sensitivity and specificity of diagnosis of Strongyloides stercoralis infection

BACKGROUND: We investigated whether luciferase immunoprecipitation systems (LIPS) can be the basis for a more rapid, specific, and standardized assay for the diagnosis of Strongyloides stercoralis infection. METHODS: A LIPS assay was developed based on immunoglobulin (Ig) G or IgG4 antibody to a recombinant Strongyloides antigen (NIE) and was compared with an NIE enzyme-linked immunosorbent assay (ELISA). A second antigen, S. stercoralis immunoreactive antigen (SsIR), was tested alone and in combination with NIE. The assays were tested using serum samples from patients with parasitologically proven S. stercoralis or filarial infections and from healthy, uninfected control subjects. RESULTS: The NIE LIPS assay based on IgG antibody easily differentiated between S. stercoralis-infected and uninfected patients (P< .0001) and demonstrated improved specificity compared with the NIE ELISA (100% vs. 95%). Serum from filaria-infected patients did not cross-react when tested with the NIE LIPS assay. When SsIR was used in combination with NIE in the LIPS format, sensitivity and specificity improved to 100%, with a 7-fold difference between positive and negative values. No advantage was found in using a LIPS assay based on IgG4. At posttreatment follow-up, a significant decline in antibody titers was detected using the NIE ELISA (P< .0017) and the NIE LIPS assay (P< .0001). CONCLUSIONS: LIPS addresses several limitations of current ELISAs and represents a major advance in the diagnosis of S. stercoralis infection.     

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.     

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 a patient with rheumatoid arthritis and type 2 diabetes mellitus: a case-based review

Clinical Rheumatology - Strongyloides stercoralis (S. stercoralis), a human intestinal nematode, can lead to hyper/disseminated (HD) infection in patients treated with corticosteroids. Here, we...     

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.     

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.     

Disseminated Strongyloides stercoralis infection. Association with ectopic ACTH syndrome and depressed cell-mediated immunity.

A patient with disseminated Strongyloides stercoralis was evaluated to elucidate host factors that may have led to the development of this infection. The patient was found to have oat cell carcinoma with hypercortisolism produced by tumor adrenocorticotropic hormone. His serum contained a potent inhibitor of lymphocyte blastogenesis. This patient's high level of endogenous cortisol may have impaired lymphocyte function and thereby facilitated infection with S stercoralis.     

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.     

Increased detection rate of Strongyloides stercoralis by repeated stool examinations using the agar plate culture method

To clarify the efficacy of repeated stool examinations by the agar plate culture method for the detection of Strongyloides stercoralis infection, 4,071 stool samples collected from 2,406 patients > 50 years of age in Ryukyu University Hospital were examined. The cumulative detection rate of S. stercoralis infection was 4.7% (112/2,406). At the first, second, third, and beyond fourth examinations, the detection rates were 3.6% (86/2,406), 1.5% (12/786), 2.6% (10/392), and 2.0% (4/198), respectively. From these results, the cumulative detection rate was estimated to be 7.4% when three stool samples were examined for all patients. Our study showed that repeated stool examinations increase the sensitivity of detection of S. stercoralis infection.     

Is there an association between positive Strongyloides stercoralis serology and diabetes mellitus?

The purpose of this study was to determine the frequency of association between positive Strongyloides stercoralis serology and diabetes mellitus. A total of 78 diabetic patients and 42 controls were evaluated. For a parasitological diagnosis, Baermann and Hoffman et al.'s methods were applied. The immunological diagnosis involved the indirect fluorescence antibody test, ELISA and Western blotting to detect IgG antibodies. The frequency of positive S. stercoralis serology in diabetics was 23% versus 7.1% in the control group (P<0.05). The odds ratio for diabetics was 3.9 (CI, 1.6-15.9, P<0.05). Diabetic patients with HbA(1c)< or =7 had a greater chance of testing negatively for S. stercoralis infection (OR: 1.5, P>0.05). Provided there are related cases of disseminated strongyloidiasis in diabetics and there is a higher frequency of asymptomaticity of the infection in this group, the immunological screening of these patients at risk could prevent severe and fatal outcomes of the disease.     

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.     

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.     

Global prevalence of strongyloidiasis: critical review with epidemiologic insights into the prevention of disseminated disease

Opportunistic disseminated strongyloidiasis is an important cause of morbidity and mortality in immunocompromised patients. However, the worldwide prevalence of Strongyloides stercoralis is difficult to determine because adequate data are lacking. In this paper more than 100 epidemiologic studies reporting on the prevalence of S. stercoralis among various populations on five continents are critically reviewed. Analysis of this information indicates that the following groups of people may be at risk: residents of an emigrants from any developing country and southern, eastern, and central Europe; travelers and veterans returning from endemic areas; natives and residents of the Appalachian region in the United States and local endemic areas in other countries; and institutionalized persons. Because disseminated infections may be prevented by early treatment of asymptomatic chronic infections, screening programs are recommended to detect latent S. stercoralis infection before the initiation of chemotherapy or immunosuppression in patients at risk. Serologic tests are sensitive and specific but are not yet widely available. Thus strong suspicion based on clinical and epidemiologic clues in conjunction with repeated stool examinations remains the best way to rule out S. stercoralis infection in these groups.     

Clinical presentation and diagnostic sensitivity of laboratory tests for Strongyloides stercoralis in travellers compared with immigrants in a non-endemic country

OBJECTIVES: To assess whether the clinical and laboratory methods for diagnosing Strongyloides stercoralis infection in non-endemic countries is different between those who are chronically exposed and those who travel. METHODS: Analysis of laboratory and clinical data from 204 patients having S. stercoralis infection at the Hospital for Tropical Diseases, London. RESULTS: Sixty-four travellers and 128 immigrants from endemic countries had laboratory-proven strongyloides. In those with microscopically proven disease, serology was 73% sensitive in travellers and 98% sensitive in immigrants (P < 0.001). There was no difference in the eosinophil count between the two groups with 19% having a normal count. Patterns of symptoms varied between the groups, and around one-third were asymptomatic in both groups. Serology was of limited use in follow-up. CONCLUSIONS: Eosinophil count and stool microscopy are insufficiently sensitive to be used alone for screening strongyloides. The sensitivity of serology is good in immigrants with chronic infection, but lower in travellers.     

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.     

Severe strongyloidiasis during interferon plus ribavirin therapy for chronic HCV infection

Ribavirin is a nucleoside analogue, recently introduced in hepatitis C virus (HCV) therapy, that has postulated immunomodulatory and immunosuppressive action. Strongyloidiasis is an helmintic infection caused by Strongyloides stercoralis, endemic in tropical countries. Severe strongyloidiasis has been demonstrated after immunosuppression by corticosteroids evolving some fatal cases. Here, we describe two cases of severe strongyloidiasis coincident with ribavirin plus interferon therapy for treating HCV infection. The review of our monotherapy protocol with interferon did not disclose any case of symptomatic strongyloidiasis pointing to a possible role of ribavirin in modifying immune response to S. stercoralis. We propose a careful screening for S. stercoralis before initiating ribavirin therapy or even empiric antihelmintic treatment.