Diagnostic Tests to Support Late-Stage Control Programs for Schistosomiasis and Soil-Transmitted Helminthiases

Abstract

Global efforts to address schistosomiasis and soil-transmitted helminthiases (STH) include deworming programs for school-aged children that are made possible by large-scale drug donations. Decisions on these mass drug administration (MDA) programs currently rely on microscopic examination of clinical specimens to determine the presence of parasite eggs. However, microscopy-based methods are not sensitive to the low-intensity infections that characterize populations that have undergone MDA. Thus, there has been increasing recognition within the schistosomiasis and STH communities of the need for improved diagnostic tools to support late-stage control program decisions, such as when to stop or reduce MDA. Failure to adequately address the need for new diagnostics could jeopardize achievement of the 2020 London Declaration goals. In this report, we assess diagnostic needs and landscape potential solutions and determine appropriate strategies to improve diagnostic testing to support control and elimination programs. Based upon literature reviews and previous input from experts in the schistosomiasis and STH communities, we prioritized two diagnostic use cases for further exploration: to inform MDA-stopping decisions and post-MDA surveillance. To this end, PATH has refined target product profiles (TPPs) for schistosomiasis and STH diagnostics that are applicable to these use cases. We evaluated the limitations of current diagnostic methods with regards to these use cases and identified candidate biomarkers and diagnostics with potential application as new tools. Based on this analysis, there is a need to develop antigen-detecting rapid diagnostic tests (RDTs) with simplified, field-deployable sample preparation for schistosomiasis. Additionally, there is a need for diagnostic tests that are more sensitive than the current methods for STH, which may include either a field-deployable molecular test or a simple, low-cost, rapid antigen-detecting test.

Parasites and allergy: Observations from Africa

“…Secondly, misclassification of helminth status may have occurred since many of these studies relied on the examination of a single parasitological sample using microscopy, which is not very sensitive . Misclassification of allergy‐related outcomes may have occurred since most studies relied on self‐reported allergy‐related outcomes from a questionnaire rather than doctor‐diagnosed outcomes.…”

“…Secondly, misclassification of helminth status may have occurred since many of these studies relied on the examination of a single parasitological sample using microscopy, which is not very sensitive. 42 Lastly, there is evidence that the risk of allergy-related outcomes is established early in life, 44 yet most investigations shown in Table 1 were conducted among school-age children or adults. Therefore, it is possible that helminths at this point in life may have a limited role in modifying the risk or the clinical manifestation of allergy-related outcomes.…”

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

“…As such, just one human harbouring even a low level of infection, which was not entirely cleared following treatment, is sufficient to re-infect a population of freshwater snails and therefore the human population post-MDA [ 1 , 22 , 23 , 24 ]. As control programmes progress, reliable and robust diagnostic tools which can be easily and rapidly carried out at the point-of-care and are able to detect low levels of infection within individuals able to maintain pathogen transmission are therefore needed to achieve and sustain elimination [ 20 , 25 , 26 , 27 , 28 , 29 ].…”

“…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 ].…”

Selecting targets for the diagnosis of Schistosoma mansoni infection: An integrative approach using multi-omic and immunoinformatics data

“…Part of this failure could be attributed to the absence of an accurate method of diagnosis that is able to determine the real prevalence of the disease in populations, and that could monitor the success of interventions and assess healing after therapeutic intervention [ 2 – 4 ]. Parasitological tests are still the most widely used diagnostic methods of schistosomiasis control programs [ 5 , 6 ], and of these, the Kato-Katz technique is the most used due to its low cost, abillity to detect different helminths infection and greater sensibility in áreas high intensity infections [ 7 – 9 ]. However, low parasite burdens require examination of more slides or association of the parasitological tests with serological and molecular techniques to have an accurate diagnosis of the disease.…”