An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how?

Abstract

Parasitology cambridge.org/par Review Cite this article: Archer J, LaCourse JE, Webster BL, Stothard JRussell (2020). An update on non-invasive urine diagnostics for human-infecting parasitic helminths: what more could be done and how? Parasitology 147, 873-888. https://doi. AbstractReliable diagnosis of human helminth infection(s) is essential for ongoing disease surveillance and disease elimination. Current WHO-recommended diagnostic assays are unreliable in lowendemic near-elimination settings and typically involve the invasive, onerous and potentially hazardous sampling of bodily fluids such as stool and blood, as well as tissue via biopsy. In contrast, diagnosis by use of non-invasive urine sampling is generally painless, more convenient and low risk. It negates the need for specialist staff, can usually be obtained immediately upon request and is better accepted by patients. In some instances, urine-based diagnostic assays have also been shown to provide a more reliable diagnosis of infection when compared to traditional methods that require alternative and more invasive bodily samples, particularly in low-endemicity settings. Given these relative benefits, we identify and review current research literature to evaluate whether non-invasive urine sampling is currently exploited to its full potential in the development of diagnostic tools for human helminthiases. Though further development, assessment and validation are needed before their routine use in control programmes, low-cost, rapid and reliable assays capable of detecting transrenal helminthderived antigens and cell-free DNA show excellent promise for future use at the point-ofcare in high-, medium-and even low-endemicity elimination settings.

Analytical and Clinical Assessment of a Portable, Isothermal Recombinase Polymerase Amplification (RPA) Assay for the Molecular Diagnosis of Urogenital Schistosomiasis

“…Although a range of promising Schistosoma antigen-detecting and anti- Schistosoma antibody-detecting immunodiagnostic assays are under development, only a few of these can currently be carried out at the point-of-care and, of those that can, none of these are currently able to reliably detect low levels of infection with S. haematobium with high specificity [ 28 , 30 , 31 , 32 ]. Alternatively, molecular diagnosis using polymerase chain reaction (PCR) or quantitative PCR (qPCR) to detect and amplify S. haematobium -specific DNA within urine samples has been shown to be extremely sensitive and specific [ 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. PCR assays, and crucial preliminary steps needed to isolate DNA from urine samples, however, require expensive and fragile technical equipment, suitable laboratory infrastructure and trained laboratory personnel—all rarely available within schistosomiasis-endemic areas, thus impeding the use of these methods at the point-of-care [ 40 , 41 , 42 ].…”

“…For these reasons, a variety of alternative and portable DNA amplification technologies have been developed for diagnostic purposes, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), the latter of which has been used to detect trace levels of S. haematobium ova-derived DNA within laboratory-prepared samples as well as in clinical urine samples [ 43 , 44 , 45 , 46 ]. Unlike PCR, the RPA assay uses a low-temperature isothermal reaction, requires only minimal equipment and takes comparatively far less time to carry out [ 34 , 40 ]. In addition, the RPA can be performed using lyophilised reagents that do not require a cold chain and also by using a crude DNA extraction process that can be easily prepared under field conditions, rendering the RPA well suited for point-of-care use within schistosomiasis-endemic areas [ 46 ].…”

Context-Specific Procedures for the Diagnosis of Human Schistosomiasis – A Mini Review

“…Additional clinical diagnostic methods such as clinical markers (e.g. haematuria), physical examinations and imaging techniques, including the recent developments in portable and affordable ultrasound machines, are beyond the scope of this review and have been described in detail elsewhere (2,(5)(6)(7)(8).…”

“…For the detection and quantification of Schistosoma-specific DNA, several NAATs have been described for different types of clinical samples, including serum, stool and urine (54)(55)(56)(57)(58)(59)(60)(61). In particular those that apply urine samples are of interest as this type of sample can be easily and non-invasively acquired (6,56,58,59,61). Although the described NAATs are mostly in-house assays, some are becoming commercially available (62,63).…”

Intestinal Schistosomiasis and Giardiasis Co-Infection in Sub-Saharan Africa: Can a One Health Approach Improve Control of Each Waterborne Parasite Simultaneously?

“…Identification of ova in concentrated faecal smear via Kato-Katz technique [62,71] Detection of circulating cathodic antigen (CCA) or circulating anodic antigen (CAA) in urine samples using ELISA or lateral-flow test strips [72,73] Detection and amplification of species-specific DNA in faecal samples using PCR/qPCR [74], (LAMP and RPA assays have also been developed [71,[75][76][77]).…”