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Research Article

A Honduran Prevalence Study on Soil-Transmitted Helminths Highlights Serological Antibodies to Tm-WAP49 as a Diagnostic Marker for Exposure to Human Trichuriasis

Neima Briggs Department of Internal Medicine (Infectious Diseases), Yale University School of Medicine, New Haven, Connecticut;
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut;

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Leroy Versteeg Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;

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Rojelio Mejia Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;

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Jeroen Pollet Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;

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Maria Jose Villar Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;

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Bin Zhan Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;

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Graeme Segal McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas;

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Stephanie Novak McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas;

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Patricia Lenihan McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas;

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Paul Musgrave McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas;

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Viviana Ellis McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, Texas;

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Carol Florencia Coello Santa Ana Clinic, Houston Shoulder to Shoulder Foundation, Houston, Texas;

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K. Jagannadha Sastry Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas;

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Joe Craft Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut;
Department of Internal Medicine (Rheumatology, Allergy and Immunology), Yale University School of Medicine, New Haven, Connecticut;

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Peter J. Hotez Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas;
Department of Biology, Baylor University, Waco, Texas;
James A. Baker III Institute for Public Policy, Rice University, Houston, Texas;
Hagler Institute for Advanced Study, Texas A&M University, College Station, Texas

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Maria Elena Bottazzi Texas Children’s Hospital Center for Vaccine Development, Department of Pediatric Tropical Medicine, National School of Tropical Medicine, Baylor College of Medicine, Houston, Texas;
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas;
Department of Biology, Baylor University, Waco, Texas;

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DOI:
https://doi.org/10.4269/ajtmh.24-0514
Volume/Issue:
Ahead of Print
Open access
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Soil-transmitted helminth (STH) infections rank among the most prevalent communicable diseases of humans, yet detection of these parasites is mostly restricted to identifying active infection through fecal examinations. Currently, there are no commercial diagnostic tools to identify a prior whipworm or hookworm exposure, and the few serological assays for roundworm infection have not been well validated for crossreactivity or infections in humans. Such diagnostic restrictions limit the range of scientific and clinical questions that surround STH exposures and their implicated relationship to chronic diseases, such as autoimmunity, allergy, and cancer. The goal of this investigation was to evaluate the diagnostic potential of 13 STH recombinant proteins. As there are no gold standard tests to verify positive STH antisera, we used sera from active STH-infected individuals in Honduras (measured by quantitative real-time polymerase chain reaction of helminth DNA in stool) and compared antibody recognition by both ELISA and western blot with nonendemic control sera from age-matched individuals in the United States split into screening and validation cohorts. One recombinant protein, rTm-WAP49, shows potential as a whipworm diagnostic tool by receiver-operator characteristic analysis (area under the curve = 0.997, P <0.001) and indirect ELISA with sensitivity of 100% and specificity of 91% as defined by mean plus two SDs from the nonendemic screening cohort. We found discrepancies in serological recognition of previously tested STH antigens, highlighting the need to consider different technologies before down selection of a promising diagnostic candidate and screen multiple endemic populations before widely accepting an STH serological assay.

Author Notes

Financial support: N. Briggs was supported by a training grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (Award no. T32 AI007517); the American Society of Tropical Medicine Benjamin H. Kean Travel Fellowship in Tropical Medicine; and the Robert E. Leet and Clara Guthrie Patterson Trust Mentored Research Award from Bank of America, Private Bank, Trustee. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Disclosures: P. J. Hotez and M. E. Bottazzi are inventor patent holders on various vaccines against neglected diseases, including vaccines against hookworm and roundworm. Honduras human samples were collected and maintained in accordance with the Baylor College of Medicine Institutional Review Board (H-33704), with corresponding approval by the University of Texas Health Science Center at Houston Institutional Review Board (HSC-MS-14–0035) and the National Autonomous University of Honduras Committee of Ethics Investigation (01–2014). Human samples from the United States used as negative controls were collected and maintained in accordance with the Baylor College of Medicine Institutional Review Board (H-35471). All human research was conducted in compliance with applicable U.S. and Honduran federal statutes and regulations relating to human research.

Current contact information: Neima Briggs and Joe Craft, Yale University, New Haven, CT, E-mails: neima.briggs@yale.edu and joseph.craft@yale.edu. Leroy Versteeg, Rojelio Mejia, Jeroen Pollet, Maria Jose Villar, Bin Zhan, Peter J. Hotez, and Maria Elena Bottazzi, Baylor College of Medicine, Houston, TX, E-mails: leroy.versteeg@bcm.edu, rojelio.mejia@bcm.edu, jeroen.pollet@bcm.edu, mariajose.villarmondragon@bcm.edu, bzhan@bcm.edu, hotez@bcm.edu, and bottazzi@bcm.edu. Graeme Segal, University of Washington, Seattle, WA, E-mail: graeme.segal@seattlechildrens.org. Stephanie Novak, Baylor Scott & White Health Pediatrics, Southlake, TX, E-mail: stephanie.novak@bswhealth.org. Patricia Lenihan, The University of Texas Health Science Center at Houston, Houston, TX, E-mail: plenihan9@gmail.com. Paul Musgrave, Legacy Health, Portland, OR, E-mail: phmusgra@lhs.org. Viviana Ellis, Legacy Women’s Health OBGYN, San Antonio, TX, E-mail: vcellis12@gmail.com. Carol Florencia Coello, Houston Shoulder to Shoulder Foundation, Houston, TX, E-mail: arcacolo@hotmail.com. K. Jagannadha Sastry, The University of Texas MD Anderson Cancer Center, Houston, TX, E-mail: jsastry@mdanderson.org.

Address correspondence to Neima Briggs, Yale University, 1 Gilbert St., TAC S530, New Haven, CT 06519, E-mail: neima.briggs@yale.edu or Maria Elena Bottazzi, Baylor College of Medicine, 1102 Bates St., 550, Houston, TX 77030, E-mail: bottazzi@bcm.edu
Copyright:
© The author(s) 2025
Received:
28 Jul 2024
|
Accepted:
20 Nov 2024
|
Published Online:
11 Feb 2025
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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