Serological diagnosis of soil-transmitted helminth (Ascaris, Trichuris and hookworm) infections: A scoping review

Abstract

Background: The World Health Organization emphasizes the importance of integrated monitoring and evaluation in neglected tropical disease (NTD) control programs. Serological assays offer a potential solution for integrated diagnosis of NTDs, particularly for those requiring mass drug administration (MDA) as primary control and elimination strategy. This scoping review aims (i) to provide an overview of assays using serum or plasma to detect infections with soil-transmitted helminths (STHs) in both humans and animals, (ii) to examine the methodologies used in this research field and (iii) to discuss advancements in serological diagnosis of STHs to guide prevention and control programs in veterinary and human medicine.

Methodology: We conducted a systematic search in the Ovid MEDLINE, Embase and Cochrane Library databases, supplemented by a Google search using predefined keywords to identify commercially available serological assays. Additionally, we performed a patent search through Espacenet.

Principal findings: We identified 85 relevant literature records spanning over 50 years, with a notable increased interest in serological assay development in recent years. Most of the research efforts concentrated on diagnosing Ascaris infections in both humans and pigs, primarily using ELISA and western blot technologies. Almost all records targeted antibodies as analytes, employing proteins and peptides as analyte detection agents. Approximately 60% of sample sets described pertained to human samples. No commercially available tests for Trichuris or hookworms were identified, while for Ascaris, there are at least seven different ELISAs on the market.

Conclusions: While a substantial number of assays are employed in epidemiological research, the current state of serological diagnosis for guiding STH prevention and control programs is limited. Only two assays designed for pigs are used to inform efficient deworming practices in pig populations. Regarding human diagnosis, none of the existing assays has undergone extensive large-scale validation or integration into routine diagnostics for MDA programs.

Fig 1. Flow chart of the literature search and screening procedure.

STH: soil-transmitted helminth, HW: hookworm.

Fig 2. Target species and year of publication of the 85 records included in our review.

HW: hookworm, STH: soil-transmitted helminth. S3 Info provides an overview of the 85 records used to create the figures.

Fig 3. Characteristics of the assays used for serodiagnosis of STHs.

The number of records by technology principle applied (panel A), target analyte detected (panel B) and analyte detection agent used (panel C). The target analyte refers to the specific analyte that a test is designed to detect or measure, while the analyte detection agent refers to the product used in the test to investigate the presence of the target analyte. The color indicates the STH species targeted in each record. In cases where a record applied multiple options, the records was included in the count of all relevant options. FAT: fluorescent antibody test, ELISA: enzyme-linked immunosorbent assay, MFI: multiplex flow immunoassay, qSAT: quantitative suspension array technology, SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis, REIA: reverse enzyme immunoassay, RIA: radioimmunoassay, Ab: antibody, Ig: immunoglobulin, IC: immunecomplex, ES: excretory/secretory, HW: hookworm, STH: soil-transmitted helminth. S3 Info provides an overview of the 85 records used to create the figures.

Fig 4. Characteristics of test species and human sample sets.

Panel A displays the proportion of sample sets that involved a particular test species. Panel B indicates the size of the human sample sets. Panel C provides insights into the origin of the human sample sets. Certain sample sets were re-used and therefore reported in multiple records, resulting in multiple counts in panels A and B. To create panel C, we considered that a reported sample set might contain samples from different origins (e.g., positive samples from Africa, negative samples from Europe), and treated these as distinct human sample sets in our origin analysis. S3 Info provides an overview of the 85 records used in the analyses.

Fig 5. Summary of advancements in the serological diagnosis of soil-transmitted helminthiases.

Assays/records are listed based on the described analyte detection agent. The icons represent the species comprising the reported sample sets. A comprehensive description of the four stages can be found in Table 3 and S5 Info provides a systematic overview of the records used to create this figure.