Assessing the performance of TRX and DUF148 antigens for detection of prepatent Guinea worm ( <i>Dracunculus medinensis</i> ) infection in dogs
Bibliographic record
Abstract
Abstract Guinea worm (GW, Dracunculus medinensis ) is a nematode that causes a painful and debilitating neglected tropical disease in humans. The GW Eradication Program has decreased human infections by >99% over the last 40 years. However, GW emergence in animal hosts, particularly dogs, has hampered eradication efforts. Currently, there is no method for diagnosing GW infection in animals during the prepatent period, before the adult female worms emerge. Previous works have identified two GW proteins, TRX and DUF148, as immunoreactive antigens with GW-positive human and dog sera. This study developed and validated indirect enzyme-linked immunosorbent assays (ELISA) using each antigen alone or in a combination of both antigens. Using serum samples from experimentally exposed dogs, TRX and DUF148 showed reactivity at 9- and 11-weeks post-exposure, respectively. In an experimentally infected ferret, TRX and DUF148 showed reactivity at 13- and 15-weeks post-exposure, respectively. These antigens were further validated using sera of dogs from endemic villages in Chad (n=47) and shelter dogs from the non-endemic United States (n=492). DUF148 showed better reactivity and sensitivity of 76.6.% in detecting GW infection in prepatent sera compared to TRX. However, DUF148 cross-reacted with one serum sample from Brugia pahangi experimental infection and several shelter dog sera. The anti-DUF148 titer was significantly higher in the shelter dogs positive for gastrointestinal nematodes than in negative dogs. To mitigate this cross-reaction, we produced 3 peptides of DUF148. Peptide 3 from the C-terminal was more reactive with prepatent sera and had a sensitivity of 83%; however, the specificity was not superior to DUF148 whole antigen. The antibody response to DUF148 in Chad dogs with the history of GW emergence waned overtime but was detectable until two years post-GW-emergence. Our findings could facilitate the development of diagnostic methods for early detection of GW infection in dogs in endemic countries. Authors summary Dracunculiasis or Guinea worm (GW) disease is a neglected tropical disease caused by the nematode Dracunculus medinensis and is targeted for eradication by the World Health Organization. The main challenge for the eradication program is the emergence of animal infections, especially dogs. Diagnostic tests are needed to find infected dogs during the prepatent period to better control infection and prevent the spread of GW. Previous studies have found two immunoreactive GW proteins, TRX and DUF148. In this study, we validated these antigens to detect infection in before GW emergence. Using sera of dogs from endemic areas of Chad, we found that DUF148 was more reactive and had promising sensitivity to detect the prepatent infection in an indirect ELISA assay. However, DUF148 also showed cross-reaction with some sera of dogs from the Unites States, a non-endemic area for GW. To mitigate this cross-reactivity, we performed ELISA using shorter peptides. We found peptide 3 that covers the C-terminal of the protein is the immunogenic part of DUF148. However, peptide 3 ELISA did not outperform whole antigen ELISA. This study confirms the applicability of DUF148 ELISA in detecting prepatent infections in dogs and could assist the GW Eradication Program.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".