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Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Macromolecular Chemistry".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 16502

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Special Issue Editor

Prof. Dr. Adriana Erica Miele

E-Mail Website1 Website2
Guest Editor

1. Department of Biochemical Sciences, Sapienza University of Rome, Rome, Italy
2. Institut des Sciences Analytiques, UMR 5280 CNRS UCBL, University of Lyon, Villeurbanne, France
Interests: molecular parasitology; host-parasite interactions; extracellular matrix; structural biochemistry; structural bioinformatics

Special Issue Information

Dear Colleagues,

NTDs globally affect 1/5 of the entire world population but are disproportionally anchored in tropical and subtropical areas, where access to health services is often limited.

The vast majority of NTDs is represented by vector-borne or food-borne parasitic diseases. Usually, NTDs affecting humans are co-endemic, and most of them also have the same early acute symptoms, thus leading to difficulties in precise early diagnosis. Moreover, the clinically available diagnostic tests detect a specific disease at a mid-to-late stage, when most of the chronic/late symptoms have arisen.

Most of the time, field hospitals and dispensaries first give the prophylaxis treatment for the most common parasitic disease in the area and then perform a true diagnosis, thus increasing the risk of complications and mistreatment.

Therefore, there is a great need for cheap and easy-to-use diagnostic tests, the so-called POC, to implement the mass drug administration (MDA) programs of the World Health Organization (WHO).

In this Special Issue we would like to focus on: (i) The research for unique biomarkers in NTDs; (ii) the methodology for biomarkers validation; (iii) the pathway leading from translational research to POC implementation.

Contributions are welcome from researchers working in academia, public research organizations, NGOs, research and field hospitals, and biotech and private companies.

Prof. Dr. Adriana Miele
Guest Editor

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Keywords

tropical parasitic diseases
biomarkers
excreted/secreted molecules
diagnostic tests

Published Papers (5 papers)

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Research

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15 pages, 1399 KiB

Open AccessArticle

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

by John Archer, Rebecca Barksby, Tom Pennance, Penelope Rostron, Faki Bakar, Stefanie Knopp, Fiona Allan, Fatma Kabole, Said M. Ali, Shaali M. Ame, David Rollinson and Bonnie L. Webster

Molecules 2020, 25(18), 4175; https://doi.org/10.3390/molecules25184175 - 11 Sep 2020

Cited by 20 | Viewed by 3923

Abstract

Accurate diagnosis of urogenital schistosomiasis is crucial for disease surveillance and control. Routine diagnostic methods, however, lack sensitivity when assessing patients with low levels of infection still able to maintain pathogen transmission. Therefore, there is a need for highly sensitive diagnostic tools that can be used at the point-of-care in endemic areas. Recombinase polymerase amplification (RPA) is a rapid and sensitive diagnostic tool that has been used to diagnose several pathogens at the point-of-care. Here, the analytical performance of a previously developed RPA assay (RT-ShDra1-RPA) targeting the Schistosoma haematobium Dra1 genomic region was assessed using commercially synthesised S. haematobium Dra1 copies and laboratory-prepared samples spiked with S. haematobium eggs. Clinical performance was also assessed by comparing diagnostic outcomes with that of a reference diagnostic standard, urine-egg microscopy. The RT-ShDra1-RPA was able to detect 1 × 10¹ copies of commercially synthesised Dra1 DNA as well as one S. haematobium egg within laboratory-spiked ddH₂O samples. When compared with urine-egg microscopy, the overall sensitivity and specificity of the RT-ShDra1-RPA assay was 93.7% (±88.7–96.9) and 100% (±69.1–100), respectively. Positive and negative predictive values were 100% (±97.5–100) and 50% (±27.2–72.8), respectively. The RT-ShDra1-RPA therefore shows promise as a rapid and highly sensitive diagnostic tool able to diagnose urogenital schistosomiasis at the point-of-care. Full article

(This article belongs to the Special Issue Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation)

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17 pages, 3186 KiB

Open AccessArticle

Development of a Molecular Snail Xenomonitoring Assay to Detect Schistosoma haematobium and Schistosoma bovis Infections in their Bulinus Snail Hosts

by Tom Pennance, John Archer, Elena Birgitta Lugli, Penny Rostron, Felix Llanwarne, Said Mohammed Ali, Amour Khamis Amour, Khamis Rashid Suleiman, Sarah Li, David Rollinson, Jo Cable, Stefanie Knopp, Fiona Allan, Shaali Makame Ame and Bonnie Lee Webster

Molecules 2020, 25(17), 4011; https://doi.org/10.3390/molecules25174011 - 02 Sep 2020

Cited by 17 | Viewed by 4002

Abstract

Schistosomiasis, a neglected tropical disease of medical and veterinary importance, transmitted through specific freshwater snail intermediate hosts, is targeted for elimination in several endemic regions in sub-Saharan Africa. Multi-disciplinary methods are required for both human and environmental diagnostics to certify schistosomiasis elimination when eventually reached. Molecular xenomonitoring protocols, a DNA-based detection method for screening disease vectors, have been developed and trialed for parasites transmitted by hematophagous insects, such as filarial worms and trypanosomes, yet few have been extensively trialed or proven reliable for the intermediate host snails transmitting schistosomes. Here, previously published universal and Schistosoma-specific internal transcribed spacer (ITS) rDNA primers were adapted into a triplex PCR primer assay that allowed for simple, robust, and rapid detection of Schistosoma haematobium and Schistosoma bovis in Bulinus snails. We showed this two-step protocol could sensitively detect DNA of a single larval schistosome from experimentally infected snails and demonstrate its functionality for detecting S. haematobium infections in wild-caught snails from Zanzibar. Such surveillance tools are a necessity for succeeding in and certifying the 2030 control and elimination goals set by the World Health Organization. Full article

(This article belongs to the Special Issue Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation)

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14 pages, 4718 KiB

Open AccessArticle

Pilot Evaluation of Two Fasciola hepatica Biomarkers for Supporting Triclabendazole (TCBZ) Efficacy Diagnostics

by Clare F. Collett, Russell M. Morphew, David Timson, Helen C. Phillips and Peter M. Brophy

Molecules 2020, 25(15), 3477; https://doi.org/10.3390/molecules25153477 - 30 Jul 2020

Cited by 2 | Viewed by 3194

Abstract

Fasciola hepatica, the causative agent of fasciolosis, is a global threat to public health, animal welfare, agricultural productivity, and food security. In the ongoing absence of a commercial vaccine, independent emergences of anthelmintic-resistant parasite populations worldwide are threatening the sustainability of the few flukicides presently available, and particularly triclabendazole (TCBZ) as the drug of choice. Consequently, prognoses for future fasciolosis control and sustained TCBZ application necessitate improvements in diagnostic tools to identify anthelmintic efficacy. Previously, we have shown that proteomic fingerprinting of F. hepatica excretory/secretory (ES) products offered new biomarkers associated with in vitro TCBZ-sulfoxide (SO) recovery or death. In the current paper, two of these biomarkers (calreticulin (CRT) and triose phosphate isomerase (TPI)) were recombinantly expressed and evaluated to measure TCBZ efficacy via a novel approach to decipher fluke molecular phenotypes independently of molecular parasite resistance mechanism(s), which are still not fully characterised or understood. Our findings confirmed the immunoreactivity and diagnostic potential of the present target antigens by sera from TCBZ-susceptible (TCBZ-S) and TCBZ-resistant (TCBZ-R) F. hepatica experimentally infected sheep. Full article

(This article belongs to the Special Issue Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation)

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Review

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6 pages, 213 KiB

Open AccessReview

Mycetoma and Chromoblastomycosis: Perspective for Diagnosis Improvement Using Biomarkers

by Anne-Lise Bienvenu and Stephane Picot

Molecules 2020, 25(11), 2594; https://doi.org/10.3390/molecules25112594 - 02 Jun 2020

Cited by 10 | Viewed by 2467

Abstract

Background: Mycetoma and chromoblastomycosis are both chronic subcutaneous infectious diseases that pose an obstacle to socioeconomic development. Besides the therapeutic issue, the diagnosis of most neglected tropical diseases (NTD) is challenging. Confirmation using direct microscopy and culture, recognized as WHO essential diagnostic tests, are limited to specialized facilities. In this context, there is a need for simple user-friendly diagnostic tests to be used in endemic villages. Methods: This review discuss the available biomarkers that could help to improve the diagnostic capacity for mycetoma and chromoblastomycosis in a theoretical and practical perspective. Results: A lack of research in this area has to be deplored, mainly for mycetoma. Biomarkers based on the immune response (pattern of leucocytes, antibody detection), the dermal involvement (extracellular matrix monitoring, protein expression), and the presence of the infectious agent (protein detection) are potential candidates for the detection or follow-up of infection. Conclusion: Confirmatory diagnosis based on specific diagnostic biomarkers will be the basis for the optimal treatment of mycetoma and chromoblastomycosis. It will be part of the global management of NTDs under the umbrella of stewardship activities. Full article

(This article belongs to the Special Issue Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation)

Other

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6 pages, 472 KiB

Open AccessBrief Report

Diminished Prolinemia in Chronic Chagasic Patients: A New Clue for Disease Pathology?

by Sandra Carla Rocha, Ana Rosa Pérez, Juan Beloscar, Oscar Bottasso and Ariel Mariano Silber

Molecules 2019, 24(17), 3167; https://doi.org/10.3390/molecules24173167 - 30 Aug 2019

Cited by 4 | Viewed by 2352

Abstract

Trypanosoma cruzi, the etiological agent of Chagas disease, is dependent on proline for a variety of processes, such as energy metabolism, host cell invasion, differentiation, and resistance to osmotic, metabolic, and oxidative stress. On this basis, we investigated a possible relationship between prolinemia and severity of T. cruzi infection in chronic patients, as reported here. The study population consisted of 112 subjects, separated into 83 chronically T. cruzi-infected patients and 29 age-matched healthy volunteers (control) of both sexes, recruited at the Chagas Disease Service from the Department of Cardiology, Hospital Provincial del Centenario de Rosario (Rosario, Argentina). Chagasic patients were separated into three groups: chronic asymptomatic, mild/moderate, and severe chronic chagasic cardiomyopathy (CCC) subjects. We observed a significant decrease of 11.7% in prolinemia in chagasic patients when compared to controls. Further analysis within the three groups of chagasic patients also revealed a statistically significant decrease of prolinemia in severe CCC patients compared to controls, showing a relative difference of 13.6% in proline concentrations. These data point to the possibility that collagen—which participates in the healing process of cardiac tissue—and proline metabolism in the myocardium could constitute new factors affecting the evolution of Chagas disease. Full article

(This article belongs to the Special Issue Biomarkers for Early Detection of Neglected Tropical Diseases (NTDs): Discovery, Validation and POC (Point-of-Care) Devices Implementation)

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