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Recombinant cDNA clones for immunodiagnosis of strongyloidiasis.

Because diagnosis of strongyloidiasis by stool examination is unreliable and because of the potential for serious disease in Strongyloides infections, there is need for improved diagnostic aids to facilitate recognition and treatment of this parasitic infection. Serologic testing, when available, requires antigen preparation from infected primates or dogs that can be difficult to maintain. Several recombinant clones from a cDNA library prepared from the infective stage of Strongyloides stercoralis were characterized. Serologic results indicate that the recombinant proteins were equally or more reactive than the larval somatic antigen. No cross-reactivity with recombinant antigen 5a was found with sera from patients with filarial or intestinal nematode infections. Recombinant antigens 5a and 12a detected parasite-specific IgE and IgG4 antibodies in Strongyloides-infected patients. Sequence analysis showed these antigens to be rich in proline and charged amino acids. Lack of homology from database searches suggests that the antigens are unique. These recombinant antigens should be useful in diagnostic and epidemiologic studies of strongyloidiasis.

Amino Acid Sequence↗

Strongyloidiasis in immunosuppressed patients.

An increasing number of severe, even fatal cases of strongyloidiasis in patients on immunosuppressive drugs are being reported. During a 26 month period, three severe cases of Strongyloides stercoralis infestation were diagnosed in patients who were on steroid therapy. These cases are of special interest because of the following factors. Firstly, all the patients lived in a nonendemic metropolitan area. Secondly, a single stool specimen from one patient contained several distinct developmental stages of the parasite's life cycle. This finding appears to be unique considering the fact that the patient had not been administered a purgative or anthelminthic. Lastly, a surviving renal transplant patient continues to have persistent strongyloidiasis despite repeated Mintezol (thiabendazole) therapy.

Adult↗

Efficacy of ivermectin in the treatment of strongyloidiasis complicating AIDS.

Nine adult male homosexuals who were infected with the human immunodeficiency virus (five with AIDS-defining conditions) and harbored Strongyloides stercoralis received ivermectin on a compassionate basis for persistent intestinal infection. Hyperinfection was present in all cases. Ivermectin was given either as a single oral dose (200 micrograms/kg) or on a multidose schedule (200 micrograms/kg.d) on days 1, 2, 15, and 16. All seven patients who received multiple doses showed sustained clinical and parasitological cure, whereas one of two patients who received single-dose therapy relapsed promptly and fatally. Remissions have been maintained for at least 7 months and up to 3 years of follow-up. Ivermectin appears promising in the treatment of strongyloidiasis in patients with AIDS. Because of the risk of hyperinfection and/or disseminated disease, multidose courses are warranted. We are not aware of other reports describing the efficacy of antiparasitic drugs for strongyloidiasis in patients with AIDS.

AIDS-Related Opportunistic Infections↗

Biology and immunology of human strongyloidiasis.

Strongyloidiasis is an important human parasitic infection primarily because of its potential for serious and even lethal disease in immunosuppressed patients. Certain features of the biology of Strongyloides stercoralis, such as the ability to autoinfect the host, help explain why the parasite is dangerous. Characteristics of the parasite can also be exploited in parasitological diagnosis of infection with the Baermann concentration procedure and by culture. Use of filariform larval antigens in ELISA or immunofluorescent-antibody tests now provide reliable serological tests for diagnosis, and, in most patients, antibody levels decline one to two years after successful treatment. Immediate hypersensitivity is a prominent component of the immune response to strongyloides infection and may play a role in the pathogenesis of disease as well as in protection. An IgE-mediated skin test appears to be useful in diagnosis. Animal models used for immunologic studies of other intestinal helminths have lacked relevance to human strongyloidiasis. Features of the human disease, however, including hyperinfection syndrome, can be produced by S. stercoralis in the Patas monkey and in dogs.

Animals↗

Serum IgG reactivity with 41-, 31-, and 28-kDa larval proteins of Strongyloides stercoralis in individuals with strongyloidiasis.

Proteins from a deoxycholate-soluble extract of Strongyloides stercoralis infective larvae were separated by SDS-PAGE, blotted onto nitrocellulose paper, and reacted with sera from individuals with confirmed S. stercoralis infections (n = 100), suspected S. stercoralis infections in whom no larvae could be detected (n = 27), and other nematode infections (40 with Wuchereria bancrofti, 20 with Onchocerca volvulus, 20 with Necator americanus, and 20 with mixed Ascaris lumbricoides and Trichuris trichiura infections). Immunodominant proteins of approximately 41, 31, and 28 kDa were recognized by IgG in 91%, 88%, and 90%, respectively, of sera from those with confirmed strongyloidiasis; in 100%, 100%, and 93% of sera from those with suspected strongyloidiasis; and in 9%, 12%, and 14% of sera from those infected with other nematodes. IgG reactivity to each of these proteins was a more specific means of immunodiagnosis than the currently used indirect ELISA; the methods were equally sensitive.

Animals↗

Strongyloides stercoralis: the first rodent model for uncomplicated and hyperinfective strongyloidiasis, the Mongolian gerbil (Meriones unguiculatus).

Strongyloidiasis is the most common endemic helminthiasis in several of the world's industrialized nations, yet relatively little is known about its basic biology and immunobiology because a practical rodent model for the investigation of this clinically important parasitism is lacking. This study reports such a model for use in the investigation of Strongyloides stercoralis infection. Normal male gerbils infected subcutaneously with 1000 infective filariform larvae harbored moderate numbers (83.6 +/- 27.6) of adult worms at 35 days after infection, and a low-grade infection persisted for at least 131 days mimicking the chronicity of human infections. Gerbils treated weekly with 2 mg of methylprednisolone acetate developed hyperinfective strongyloidiasis with up to 8000 autoinfective larvae occurring in these animals at postinfection day 21. Autoinfection never occurred in normal (untreated) gerbils.

Animals↗

Endemic strongyloidiasis on the Spanish Mediterranean coast.

Diagnosis and treatment of Strongyloides stercoralis infection can be difficult, and a high degree of clinical suspicion in patients who have visited an endemic area is required. We describe the epidemiology and clinical features of 152 prospectively identified cases of strongyloidiasis in an European region, and identify risk factors for the development of severe forms of the disease. This was a prospective study of all patients admitted to a single institution over an 8-year period. Patients (n=152) were mainly elderly male farmers (79%) who had acquired the disease by working barefoot in contact with soil and ingesting non-drinking water. Eosinophilia was a sensitive marker for the infection (82%). Twenty patients (13%) developed severe forms of the illness and six patients (4%) died. A significant association was found between severe forms of strongyloidiasis and steroid usage (OR 9.0, 95%CI 2.1-37.6), immunodebilitating illness (OR 10.1, 95%CI 3.2-32.3) and other immunosuppressive therapy (OR 13.7, 95%CI 2.9-58.7), but by logistic regression analysis, only immunodebilitating disease was as a risk factor (OR 2.1, 95%CI 1.78-2.43). S. stercolaris infection is endemic in the Spanish Mediterranean coast. The frequent development of severe forms of the disease, with a high mortality, makes early recognition and treatment essential.

Aged↗

Case report: reactive hemophagocytic syndrome associated with disseminated strongyloidiasis.

The reactive hemophagocytic syndrome is a condition characterized by systemic proliferation of benign hemophagocytic histiocytes, fever, cytopenia, abnormal liver function, and frequently coagulopathy and hepatosplenomegaly. Its occurrence has been documented in association with viral, bacterial, fungal and parasitic infections; a wide spectrum of malignant neoplasms; some miscellaneous disorders; and phenytoin. Disseminated strongyloidiasis is reported in a patients with systemic lupus erythematosus treated with corticosteroids in whom a reactive hemophagocytic syndrome developed and who finally died. This reactive hemophagocytic syndrome is reported for the first time in strongyloidiasis and may not have been recognized in former patients.

Adult↗

Disseminated strongyloidiasis in a World War II Veteran with metastatic undifferentiated carcinoma of neuroendocrine type.

This case of disseminated strongyloidiasis illustrates the need for a high index of suspicion and effective screening for this pathogen in certain high-risk patient populations before giving immunosuppressive therapy. A complete travel and military history should be obtained. In the United States, persons with a history of military service in endemic areas, emigrants from endemic areas, patients in institutions, and residents of the Southeast should have careful evaluation for strongyloidiasis. Eosinophilia may or may not be present. Stool examinations are not sufficient to rule out the diagnosis. When available, the ELISA screening test for serodiagnosis may be useful. Duodenal aspirates or bronchoalveolar lavage may be necessary to confirm the diagnosis.

Adrenal Cortex Hormones↗

Clinical and imaging features of pulmonary strongyloidiasis.

We evaluated 20 patients with pulmonary strongyloidiasis for risk factors, clinical and imaging manifestations, complications, treatment, and outcome. Eighteen (90%) had risk factors for strongyloidiasis including steroid use, age greater than 65, chronic lung disease, use of histamine blockers, or chronic debilitating illness. Pulmonary signs and symptoms, including cough, shortness of breath, wheezing, and hemoptysis, were present in 19 (95%); adult respiratory distress syndrome (ARDS) developed in 9 (45%). Pulmonary infiltrates occurred in 18 (90%). Gastrointestinal signs and symptoms were also common. Peripheral blood eosinophilia occurred in 15 (75%). Twelve (60%) had secondary infection, and 3 (15%) had bacterial lung abscesses. All were treated with thiabendazole, 25 mg/kg twice daily; on average, patients without ARDS were treated for 3 days, versus 7 days for those with ARDS. Seventy percent responded to therapy; 30% died. Preexisting chronic lung disease and ARDS were statistically significant predictors of a poor prognosis.

Adolescent↗

Bacterial complications of strongyloidiasis: Streptococcus bovis meningitis.

We report the case of a 64-year-old veteran who had Streptococcus bovis meningitis as a result of a long latent Strongyloides infection that became acute when he was treated with prednisone. We reviewed 38 reported cases of serious bacterial infections associated with strongyloidiasis. Patients most frequently had nonspecific gastrointestinal symptoms. Of these 38 patients, 21 (55%) had meningitis, and 28 (73%) had bacteremia that was polymicrobial in 3 cases (8%). Other sites of infection included lung, bone marrow, ascites, mitral valve, and lymph node. Most infections were due to enteric gram-negative bacteria. There is one previously reported case of S bovis meningitis. Thirty-four of the patients (89%) were immunosuppressed; 21 of these (55%) were taking pharmacologic doses of adrenal corticosteroids. Thirty-three of the 38 (87%) patients died. Patients with enteric bacterial infection without an obvious cause should be tested for the presence of strongyloidiasis.

Animals↗

Marked eosinophilia in an immunosuppressed patient with strongyloidiasis.

Strongyloidiasis in immunocompromised patients is typically associated with a fulminant clinical course and little eosinophilia. We describe an immunocompromised patient with strongyloidiasis in whom the infection was only minimally symptomatic in association with a dramatic increase in eosinophil count.

Adult↗

[A case report of meningitis and sepsis due to Enterococcus faecium complicated with strongyloidiasis].

A 80 year-old male was transferred to our department on 18th Aug. 1988, for high fever and clouding of the consciousness. He had been treated with steroid hormone (betamethasone 3.0 mg/day for 15 days) for his uveitis. Enterococcus faecium was isolated from both blood and spinal fluid, and then Strongyloides sterocoralis was revealed both in the sputum and stool. Anti-Human T-cell leukemia virus 1 (HTLV-1) antibody was also positive serologically. At first, beta-lactam antibiotics were used for the treatment of purulent meningitis and sepsis, but after performing sensitivity tests for E. faecium, the antibiotics were changed to rifampicin (RFP), fosfomycin (FOM) and ofloxacin (OFLX) for their excellent activity against the organism. After the clinical symptoms, subsided, thiabendazole was used for disseminated strongyloidiasis in daily doses of 2,500 mg for six days initially. The drug was used three times with two week intervals. Both bacterial and parasite infections subsided and no recurrence has been noticed until now. This is the first case of meningitis caused by E. facium complicated with strongyloidiasis.

Aged↗

[Clinical study of albendazole therapy for strongyloidiasis].

We reported the efficacy of albendazole (ABZ) for the treatment of 27 patients with strongyloidiasis. Twenty-seven patients, 23 males and 4 females, received 200 mg of ABZ one hour before breakfast and supper for 3 days and this treatment was repeated 2 weeks later. The following results were obtained: 1) The eradication rate at 2 weeks after the initial treatment was 70.4% (19 of 27 patients) and 2 weeks after the second course was 66.7% (16 of 24 patients). 2) One patients (3.7%) complained of abdominal pain after the first treatment. Four patients (14.8%) complained of headache (n = 2), nausea (n = 1) and exanthema (n = 1) after the second treatment. But all symptoms were mild and required no treatment and subsided in a few days. 3) Positive rate of HTLV-1 antibody was 45.8% in the patients. As described above, side effects occurred in some cases, although they were mild and transient. From these results, it can be concluded that on increased dose of ABZ could be much more favorable for the treatment of strongyloidiasis.

Adult↗

Evaluation of an indirect immunofluorescence assay for strongyloidiasis as a tool for diagnosis and follow-up.

The diagnostic accuracy of an indirect immunofluorescence antibody test (IFAT) for Strongyloides stercoralis at different serum antibody titers was evaluated. To assess diagnostic sensitivity, sera from 156 patients with known strongyloidiasis were collected. Negative control sera were obtained from a composite group of 427 subjects (blood donors and hospitalized patients). With an area under the receiver-operating characteristic plot of 0.98, the IFAT showed a high level of diagnostic accuracy for strongyloidiasis. An antibody titer of > or = 1:20, with 97% sensitivity and 98% specificity, was identified as the diagnostic threshold with the best overall performance. Cross-reactions were evaluated with 41 additional samples from patients with other known helminth infections, and the IFAT detected low-titer positivity in only one subject with filariasis. A positive IFAT result at an antibody dilution of > or = 1:80 was virtually 100% specific, with 71% sensitivity. To test the usefulness of the IFAT as a monitoring tool, the changes in specific-antibody titers after treatment in a group of 155 patients were evaluated. Seroreversion or a decrease in antibody titer of twofold or more was observed in 60% of the patients. Response to treatment was directly correlated to the initial antibody titer, and a baseline titer of > or = 1:80 was identified as the best predictor of response. In conclusion, a positive IFAT result at an antibody dilution of >/=1:20 is the optimal cutoff for screening. A titer of > or = 1:80, with virtually no false-positive result, is a reliable cutoff for a serological assessment of treatment efficacy and for inclusion in clinical trials.

Aged↗

Diagnostic implications of parasite-specific immune responses in immunocompromised patients with strongyloidiasis.

Parasite-specific humoral and cellular immune responses were evaluated in in nine immunosuppressed patients with Strongyloides stercoralis infection. Four patients had the disseminated form of the disease, and five had serious manifestations without evidence of hyperinfection. All patients had high levels of immunoglobulin G (IgG) antibodies directed against S. stercoralis larval antigens as detected by the enzyme-linked immunosorbent assay. Seven patients had both elevated total serum IgE and parasite-specific IgE antibodies detected by a modified radioimmunoassay. The hyperinfected patients differed significantly from the nonhyperinfected group in total and specific IgE levels and peripheral eosinophilia but not in specific IgG levels. None of the patients tested exhibited significant in vitro lymphoproliferative responses to parasite antigens. Our results indicated that the possibility of a protective role of IgE and eosinophils in strongyloidiasis deserves further investigation. In addition, we suggest that the enzyme-linked immunosorbent assay for specific IgG antibodies may have an important place in the diagnosis of strongyloidiasis in immunocompetent as well as in immunocompromised patients.

Adult↗

Interrelation of strongyloidiasis and tuberculosis.

A 31 year old man from Gambia, resident in the United Kingdom for two years, presented with a two month history of unproductive cough, malaise, weight loss, non-specific abdominal pain, and episodic diarrhoea. Acid alcohol fast bacilli were identified in his sputum, together with Strongyloides stercoralis larvae and Giardia lamblia cysts in his stools. This case illustrates that latent strongyloidiasis can become overt in the presence of tuberculosis, and the diagnosis of strongyloidiasis must be borne in mind in patients who have previously resided in endemic regions.

Adult↗

Nephrotic syndrome in strongyloidiasis: remission after eradication with anthelmintic agents.

Strongyloides stercoralis infection is known to be important because of its potential for life-threatening disseminated infection in immunosuppressed hosts. Apart from direct invasion into nearly every organ in systemic infection, evidence suggests that immunological reaction also plays a role in the pathogenesis of the disease, including both uncomplicated and disseminated infections. However, Strongyloides-related glomerulonephritis has not been well documented. We present a case of steroid- and cyclophosphamide-resistant nephrotic syndrome complicated by disseminated strongyloidiasis which responded to anthelmintic agents. The remission of nephrotic syndrome after treatment of Strongyloides infection strongly suggests the possibility of Strongyloides-associated glomerulonephritis. Nephrotic patients in endemic areas of Strongyloides infection should have the differential white cell count checked. Strongyloides infection should be ruled out in patients with eosinophilia before immunosuppressants are initiated to prevent the complication of disseminated strongyloidiasis.

Adult↗