Application of enzyme immunoassay for postchemotherapy evaluation of human strongyloidiasis

doi:10.1016/0732-8893(94)90129-5

Diagnostic Microbiology and Infectious Disease

Volume 18, Issue 1, January 1994, Pages 19-23

https://doi.org/10.1016/0732-8893(94)90129-5 Get rights and content

Abstract

Posttherapy evaluation of strongyloidiasis is frequently difficult because coprologic examination is not sensitive enough for diagnosis of chronic infection. In the present study, anti-Strongyloides enzyme-linked immunosorbent assay antibodies were monitored before and after treatment with thiabendazole and pyrvinium pamoate in 199 patients with chronic strongyloidiasis in Okinawa, Japan. A significant decrease in antibody levels was observed in patients who became negative for fecal larvae after the treatment, whereas the antibody levels did not show a significant change after the treatment in patients who were still harboring the parasite. In the group coprologically negative in the follow-up examination, however, many individuals did not show a significant fall in antibody titers after treatment, which suggests that these cases were equivocal for complete cure. By the subsequent fecal reexamination performed on the equivocal cases, ∼20% were additionally found to be still harboring the parasite. These results indicate that serologic testing is useful to check whether a real cure has been achieved among the patients in whose fecal samples the presence of larvae has not been demonstrated after treatment.

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There are more references available in the full text version of this article.

Cited by (51)

Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial
2019, The Lancet Infectious Diseases
Citation Excerpt :
Although cross-reactivity with other helminth infections is possible, serological specificity is close to 100% when antibody concentrations are above defined cutoff values.10 Serology is also suitable for post-treatment monitoring, and criteria to define response to treatment with this method have been assessed by diagnostic studies.11–13 Evidence before this study
Strongyloides stercoralis infection is a neglected condition that places people who are immunocompromised at risk of hyperinfection and death. Ivermectin is the drug of choice for the treatment of S stercoralis infection, but there is no definitive evidence on the optimal dose. This trial aimed to assess whether multiple doses of ivermectin were superior to a single dose for the treatment of non-disseminated strongyloidiasis.
Our study was designed as a multicentre, open-label, phase 3, randomised controlled superiority trial. Participants were enrolled in four centres in Italy, three in Spain, and two in the UK, and recruiting sites were predominantly hospitals. Eligible patients were older than 5 years, weighed more than 15 kg, were residents in an area not endemic for S stercoralis, and either were positive for S stercoralis in faecal tests and on serology (any titre) or had a positive serological test with high titres, irrespective of the result of faecal tests. Patients were randomly assigned (1:1) using a computer-generated, blinded allocation sequence (with randomly mixed block sizes of six, eight, and ten participants) to receive either one dose of ivermectin 200 μg/kg or four doses of ivermectin 200 μg/kg (given on days 1, 2, 15, and 16). The primary endpoint was the proportion of participants with clearance of S stercoralis infection at 12 months, which was assessed in all randomly assigned participants who were not lost to follow-up (modified full-analysis set) and in participants in the modified full-analysis set who did not deviate from the assigned treatment regimen (per-protocol set). All participants were included in the safety analysis. The trial was registered with ClinicalTrials.gov, NCT01570504, and is now closed for recruitment.
Of the 351 patients assessed for eligibility, 309 recruited between March 26, 2013, and May 3, 2017, were randomly assigned to one dose (n=155) or four doses (n=154) of ivermectin. At 12 months in the modified full-analysis set, 86% (95% CI 79 to 91; 102 of 118 participants) had responded to treatment in the single-dose group compared with 85% (77 to 90; 96 of 113 participants) in the four-dose group (risk difference 1·48%, 95% CI −7·55 to 10·52; p=0·75); similar results were observed in the per-protocol set. Adverse events were generally of mild intensity and more frequent in the multiple-dose than in the single-dose group. The trial was terminated early due to futility.
Multiple doses of ivermectin did not show higher efficacy and was tolerated less than a single dose. A single dose should therefore be preferred for the treatment of non-disseminated strongyloidiasis.
There was no funding source for this study.
Use of dried blood spots to define antibody response to the Strongyloides stercoralis recombinant antigen NIE
2014, Acta Tropica
Citation Excerpt :
Several other studies show a consistent decrease in Strongyloides antibody titre following treatment with follow up periods ranging from 6 to 24 months (Biggs et al., 2009; Karunajeewa et al., 2006; Kobayashi et al., 1994; Loutfy et al., 2002). A serologic follow up period of 6–12 months has been proposed as a reasonable evaluation of treatment efficacy (Loutfy et al., 2002; Requena-Méndez et al., 2013), although serorevision may take longer among patients with very high starting titres (Kobayashi et al., 1994). Of note however, most of these serologic follow up studies have been undertaken in non-endemic settings, where the risk of re-infection is minimal.
An approach to improve the diagnosis of Strongyloides stercoralis infection is the use of serologic assays utilising the NIE antigen from S. stercoralis, with good diagnostic sensitivity and excellent specificity reported. Detection of antibody eluted from dried blood spots (DBS) has shown utility in large-scale seroepidemiological studies for a range of conditions and is appealing for use with children where sample collection is difficult. We adapted an existing NIE-enzyme linked immunosorbent assay (ELISA) for the testing of strongyloides antibody response on DBS, and evaluated it in a population screening and mass drug administration programme (MDA) for strongyloidiasis conducted in an Australian indigenous community. Study participants were treated with 200 μg/kg ivermectin (>15 kg) or 3× 400 mg albendazole (<15 kg). The sensitivity of the NIE DBS-ELISA was determined by receiver operator characteristic (ROC) analysis to be 85.7%. A total of 214 DBS were collected from 184 participants across two screening and MDA encounters. A total of 27 of 164 participants (16.5%) tested positive for S. stercoralis NIE-DBS prior to MDA treatment, and 6 of 50 participants (12.0%) tested positive after treatment. These prevalence values are similar to those documented by standard serology in the same community. For 30 participants where a DBS was collected at both MDA 1 and 2, a significant decline in ELISA values was evident post treatment (0.12–0.02, p = 0.0012). These results are in agreement with previous studies documenting the high seroprevalence of S. stercoralis in remote Australian Indigenous communities, and suggest that collection of dried blood spots may be a useful approach for field diagnosis of S. stercoralis seroprevalence.
Prevention of strongyloides hyperinfection syndrome: A rheumatological point of view
2009, European Journal of Internal Medicine
Strongyloides stercoralis (S.stercoralis) is a parasite that infects humans and in conditions of immunodeficiency may disseminate, causing the potentially fatal strongyloides hyperinfection syndrome (SHS). The aim of this review was to investigate the literature evidence on the prophylaxis of SHS in immunosuppressed patients with rheumatological disorders.
The MEDLINE database (from 1966 to 2008) was searched using the following terms: “strongyloidiasis”, “disseminated strongyloidiasis”, “Strongyloides stercoralis”, “Strongyloides stercoralis dissemination”, “strongyloides hyperinfection syndrome”, “treatment”, “prophylaxis”, “prevention”, “immunocompromised”, “immunodepression”, “immunosuppressed”, “immunosuppression”, “corticosteroids”, “glucocorticoids”, “lupus erythematosus”, “rheumatoid arthritis”, “rheumatic diseases”. A search of the therapeutic studies using the same set of terms was carried out.
No study on the prophylaxis of SHS restricted to rheumatic immunosuppressed patients was identified. However, two articles have been published on the prophylaxis of strongyloidiasis in other immunosuppressed patients. Additionally, 13 studies dealing with different therapeutical options for strongyloidiasis were identified and presented.
Since there is no evidence on the prophylaxis of SHS in immunosuppressed rheumatic patients, the suggested regimen for that prophylaxis may rely on the results obtained from therapeutical studies. Ivermectin has the best safety profile, lower cost and best efficacy and should be the drug of choice for the prophylaxis of SHS in such patients. Although a definitive prophylactic regimen has not been defined, the option for 200 µg/kg/day for 2 days, repeated within 2 weeks, seems to be a reasonable approach. Such regimen should be repeated every 6 months in case of persisting immunosuppression in permanent residents of endemic areas.
Secondary Strongyloides stercoralis prophylaxis in patients with human T-cell lymphotropic virus type 1 infection: report of two cases
2009, International Journal of Infectious Diseases
Citation Excerpt :
A potentially promising method for determining response to treatment is following sequential serology, most commonly the ELISA. Antibody titers decrease after therapy, and the ratio of pre- and post-treatment antibody levels, using a cut-off of <0.6, can be used to document response.14 Although this method has been useful to determine response to therapy in some studies,15,16 it is unclear if serology can determine complete eradication of strongyloides.
Secondary ivermectin prophylaxis for strongyloidiasis in two patients with human T-cell lymphotropic virus type 1 (HTLV-1)-associated malignancies and fully treated complicated strongyloidiasis is described. Treatment was well tolerated and neither patient developed further manifestations of hyperinfection. As treatment failure for complicated strongyloidiasis has been documented in severely immunosuppressed patients, secondary prophylaxis may be indicated.
Strongyloides stercoralis hyperinfection presenting as acute respiratory failure and Gram-negative sepsis in a patient with astrocytoma
2009, International Journal of Infectious Diseases
Citation Excerpt :
In one case of refractory disseminated strongyloidiasis, combined albendazole and ivermectin has been successful.20 Antistrongyloides antibody titers can also confirm the adequacy of treatment and need to be repeated after three months.21 Strongyloidiasis hyperinfection syndrome carries a high mortality approaching 100%; mortality with therapy can exceed 25%.22,23
In developing countries, Strongyloides stercoralis infection is a common cause of morbidity and mortality. Death from strongyloidosis can result from hyperinfection or disseminated disease. Infections due to S. stercoralis are unusual in Saudi Arabia and are usually diagnosed in immigrants from endemic areas. We report a case in which S. stercoralis was isolated from the sputum of a patient with Gram-negative sepsis and respiratory failure, and review the salient features of this disease. A high index of suspicion should be maintained by clinicians treating patients in endemic areas presenting with new-onset wheezing, acute respiratory distress and/or Gram-negative sepsis to prevent the serious complications of Strongyloides hyperinfection and dissemination.
Evidence-based clinical guidelines for immigrants and refugees
2011, CMAJ. Canadian Medical Association Journal
Citation Excerpt :
The National Reference Centre for Parasitology in Montréal, which performs serologic testing for both parasites in Canada, estimates that its enzyme immunoassays have 100% sensitivity and 88% specificity for Strongyloides stercoralis and 96% sensitivity and 82% specificity for Schistosoma mansoni. Several studies have reported levels of antibodies to Strongyloides declining after treatment,48,340–343 which suggests that serologic positivity is indicative of current infection; however, this has not been a universal finding.315 Levels of antibodies to Schistosoma do not appear to decline after treatment.317

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Diagnostic Microbiology and Infectious Disease

Abstract

References (19)

Serodiagnosis of human strongyloidiasis by an enzyme-linked immunosorbent assay

Trans R Soc Trop Med Hyg

Treatment of strongyloidiasis with thiabendazole: an analysis of toxicity and effectiveness

Trans R Soc Trop Med Hyg

Clinical studies in human strongyloidiasis. I. Semeiology

Gastroenterology

Detection of antibodies in strongyloidiasis by enzyme-linked immunosorbent assay (ELISA)

Trans R Soc Trop Med Hyg

A new method to detect Strongyloides stervoralis from human stool

J Trop Med

The indirect fluorescent antibody test for the serodiagnosis of strongyloidiasis

J Trop Med Hyg

Cutaneous larva migrans in Northern Kordofan, Sudan: a preliminary report

J Trop Med Hyg

Drug Treatment in Intestinal Helminthiases

Antibodies to Strongyloides stercoralis larval surface antigens in chronic strongyloidiasis

Lab Invest

Cited by (51)

Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial

Use of dried blood spots to define antibody response to the Strongyloides stercoralis recombinant antigen NIE

Prevention of strongyloides hyperinfection syndrome: A rheumatological point of view

Secondary Strongyloides stercoralis prophylaxis in patients with human T-cell lymphotropic virus type 1 infection: report of two cases

Strongyloides stercoralis hyperinfection presenting as acute respiratory failure and Gram-negative sepsis in a patient with astrocytoma

Evidence-based clinical guidelines for immigrants and refugees