Date Published: July 9, 2018
Publisher: Public Library of Science
Author(s): Chatanun Eamudomkarn, Paiboon Sithithaworn, Christine Kamamia, Anna Yakovleva, Jiraporn Sithithaworn, Sasithorn Kaewkes, Anchalee Techasen, Watcharin Loilome, Puangrat Yongvanit, Chompunoot Wangboon, Prasert Saichua, Makoto Itoh, Jeffrey M. Bethony, Carolina Barillas-Mury.
The diagnosis of strongyloidiasis by coprological methods has a low sensitivity, underestimating the prevalence of Strongyloides stercoralis in endemic areas. Serodiagnostic tests for strongyloidiasis have shown robust diagnostic properties. However, these methods require a blood draw, an invasive and labor-intensive sample collection method, especially in the resource-limited settings where S. stercoralis is endemic. Our study examines a urine-based assay for strongyloidiasis and compares its diagnostic accuracy with coprological and serological methods. Receiver operating characteristic (ROC) curve analyses determined the diagnostic sensitivity (D-Sn) and specificity (D-Sp) of the urine ELISA, as well as estimates its positive predictive value and diagnostic risk. The likelihood ratios of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for each diagnostic positivity threshold. The urine ELISA assay correlated significantly with the serological ELISA assay for strongyloidiasis, with a D-Sn of 92.7% and a D-Sp of 40.7%, when compared to coprological methods. Moreover, the urine ELISA IgG test had a detection rate of 69%, which far exceeds the coprological method (28%). The likelihood of a positive diagnosis of strongyloidiasis by the urine ELISA IgG test increased significantly with increasing units of IgG detected in urine. The urine ELISA IgG assay for strongyloidiasis assay has a diagnostic accuracy comparable to serological assay, both of which are more sensitive than coprological methods. Since the collection of urine is easy and non-invasive, the urine ELISA IgG assay for strongyloidiasis could be used to screen populations at risk for strongyloidiasis in S. stercoralis endemic areas.
Strongyloidiasis is a neglected tropical disease (NTD), with transmission occurring in tropical and subtropical regions of the world, including the subtropical regions of the United States (Southeastern USA) [1–3]. People acquire an infection via penetration of the skin by infective larvae whereupon the larvae enter the blood circulation, reaching the lungs and subsequently the gastrointestinal tract where they mature to adult worms. The life cycle of S. stercoralis, however, is unique among soil-transmitted helminths (STHs) in several key respects. Strongyloides stercoralis filariform larvae can autoinfect its human host by re-entering via enteral circulation without shedding larvae into the soil. With both irregular and minimal S. stercoralis larval output in human feces, conventional microscopic methods often fail to detect chronic asymptomatic strongyloidiasis. Despite the regular daily collection of stool samples which were also subjected to fecal concentration techniques, coprological tests by the Baermann and Koga agar plate culture (ACP) have been found to lack significant diagnostic sensitivity (4). Hence, improved methods for the detection of S. stercoralis infection are urgently needed not only for people at increased risk from chronic strongyloidiasis (e.g., candidates for transplantation, people undertaking chemotherapy, or people on systemic corticosteroids) [1,4], but also people residing in S. stercoralis endemic areas, such as northeast Thailand, where the current study takes place.
The present studies showed that urine and serum ELISA tests for the detection of strongyloidiasis were similar in terms of sensitivity, specificity, and predictive diagnostic values (Odds Ratios). Based on the same sample population, the percent positive for both the urine and serum ELISAs for strongyloidiasis were comparable (68.5% and 65.8%, respectively), while the percent positive for strongyloidiasis by coprological examine was less than half (27.5%) of those for urine and serum tests. In fact, an additional 81 individuals were determined to be positive for strongyloidiasis by urine or serum ELISA that went undetected by the coprological exam. These results show that coprological examination is less sensitive to diagnose strongyloidiasis than urine or serum ELISA. This is in keeping with reports by Siddiqui and Berk , who reported that conventional coprological examination fails to detect S. stercoralis larvae in up to 70% of cases. It should be noted that the detection rate for coprological methods can be increased from 18.6% to 24.4% for S. stercoralis when repeated fecal samples (usually around 3 days) are combined with the results of APCT and the Baermann method . Moreover, APCT increased sensitivity to 85% when it used with repeated fecal samples . However, three fecal samples are a time-consuming, laborious, and not always a feasible method to screen populations resident in areas where S stercoralis is endemic. Our study shows that IgG excreted into urine against a crude larval S. ratti antigen extract correlated extremely well with IgG level in serum and can also be used to detect strongyloidiasis. By virtue of its increased sensitivity and ease of collecting urine samples, we advise that the urine ELISA for strongyloidiasis be routinely introduced to screen population for strongyloidiasis in S. stercoralis endemic areas. Chronic strongyloidiasis is often asymptomatic and non-severe, but when left untreated individuals, remain at lifelong risk of hyperinfection syndrome or disseminated strongyloidiasis, both of which can be lethal. Successful identification and treatment of chronic strongylodiasis is therefore critical and this can be accomplished during screening programs of populations .