The search for serological assays in Strongyloides infection

The global burden of infections due to soil-transmitted helminths (STHs), affecting nearly 1.5 billion individuals, is a cause of concern.[1] STH infections comprise mainly with those of hookworms, Trichuris trichiura, and Strongyloides. Strongyloidiasis alone accounts for approximately 600 million cases.[2] Among the STHs, strongyloidiasis carries the risk of dissemination and fatal outcomes if not controlled in a timely manner. The estimation of the disease burden and the development of suitable treatment and control measures depend critically on the timely and precise diagnosis of the infection.[3] The diagnosis of strongyloidiasis heavily relies on microscopic examination of stool samples. In this context, recent emphasis is being given to a very pertinent issue of the misidentification of Strongyloides eggs with those of hookworm and other hookworm-like helminths.[4] Parasite misidentification in cases of strongyloidiasis has led to its inclusion in the targets of the Neglected Tropical Diseases (NTD) Roadmap 2030 by the World Health Organization (WHO).[5] Despite the fact, that there is no gold standard for the diagnosis of strongyloidiasis.[6] The standard that is routinely followed is the demonstration of the parasite in samples. Tests based on microscopic examination of stool samples, even if backed up by culture techniques such as agar plate culture and the Baermann method, have low sensitivity. This is mostly due to the irregular yield of larvae in cases of chronic strongyloidiasis.[6] In addition, the burden of 50% of cases of strongyloidiasis being asymptomatic cannot be overemphasized. In this regard, serological techniques have high sensitivity besides being easy to perform. They also provide quick results. However, cross-reactivity with other parasites such as Ascaris, microfilaria, schistosomes, along with low specificity, are problems.[7] It has been seen that the sensitivity of serological tests for strongyloidiasis varies from 49% to 81%, depending on the sources of the antigen that have been used.[6] The specificity of these methods can range from 83% for Strongyloides stercoralis larval antigen, 95% for S. ratti, and even higher for Strongyloides venezuelensis. However, they overestimate the incidence of the disease as these serological estimations are unable to differentiate between past and present infections.[6,8] Immunological responses to Strongyloides infection include expression of Immunoglobulin (Ig) A, IgE, IgM, and IgG (G1, G2, G3, and G4). Among the IgG responses, IgG2 and IgG4 are mostly involved. Of the available studies on serological methods for strongyloidiasis, majority are on IgG estimation, and very few studies are on IgG4. A combination of both IgG and IgG4 or IgE and IgG4 testing have been suggested to improve the diagnostic accuracy of strongyloidiasis through these serological methods.[7] There has been a dearth of studies on the burden of strongyloidiasis globally. Interestingly, Brazil and Thailand have most extensively studied the prevalence of strongyloidiasis, as per the global literature. The role of serological tests for strongyloidiasis is not only limited to epidemiological estimations but also it has been suggested that those cases of Strongyloides infection with a low serological response should have combined serological and stool examination tests for better monitoring of treatment.[9] The study by Namhong et al., from Thailand, included in the current issue of the journal “Tropical Parasitology” is an attempt to develop a serological assay in enzyme-linked immune-sorbent assay format for screening of strongyloidiasis,[10] which is a welcome step in the search toward better affordable tests. There is a need to develop accurate serological assays for case diagnosis, especially for screening and disease mapping. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.