We propose an ultrasensitive rapid diagnostic test (RDT) to detect exposure to pulmonary flukes of the genus Paragonimus. Paragonimiasis affects an estimated 21 mi l l ion people and remains amongst the most neglected of all neglected tropical diseases (NTDs). This trematode is acquired upon ingestion of raw or undercooked freshwater crustaceans and migrates to the lungs where it forms cysts. Treatment is straightforward (praziquantel) but diagnosis is not. The classical methodâ detection of Paragonimus eggs in sputum or stool â requires rarely available microscopy expertise, is slow throughput, and is limited to egg-producing adult flukes. With an effective drug at hand but no convenient diagnostic, a highly sensitive RDT is the missing piece to enable efficient clinical management of paragonimiasis. A paragonimiasis RDT is all the more needed when considering that many paragonimiasis symptoms resemble those of TB or lung cancer, including hemoptysis (blood in sputum), persistent cough, weight loss, and cysts in CT scans. Misdiagnosis is common and patients are incorrectly put on ineffective antibiotic regimens or toxic cancer chemotherapy, with serious consequences. This project combines two innovations: (a) the re ce nt di scovery of novel paragonimiasis bi omarkers by re searchers at Washi ngton Uni versi ty, who identified a list of 25 immunoreactive Paragonimus proteins. The two most promising antigens are myoglobin 1 and cysteine protease 6 (CP-6). On the basis of Western blots obtained with a small set of sera, antibodies to myoglobin 1 (total IgG) and CP-6 (IgG4 subtype) detect paragonimiasis with 100% sensitivity and 100% specificity, when using other trematode and nematode infections as comparators. (b) we have developed goldnanoshells, a novel plasmonic nanoparticle designed to increase the analytical sensitivity of RDTs, and applied them to over 20 different analytes. We have expertise with detecting IgG and IgG4 responses through our work on other helminth proteins (loa loa SXP-1 (loiasis), Wuchereria bancrofti Wb123 (lymphatic filariasis), and Onchocerca volvulus Ov16 (river blindness)). The human benefit of our RDT will be significant: (a) this will be the first commercial assay for paragonimiasis, (b) the RDT will further assist the differential diagnosis of tuberculosis, lung cancer, and other pulmonary diseases, (c) while high prevalence areas in Asia stand to benefit most from a new test, the assay would also be useful in the USA, despite low infection rates, as witnessed by the CDCâs interest in this project.
Public Health Relevance Statement: Project Narrative Flukes of the genus âParagonimusâ are food-borne parasites that migrate from the intestine to the lungs, where they cause clinical signs similar to those of tuberculosis and lung cancer: blood in sputum, chronic cough, weight loss, cysts in X-ray, etc. Despite an estimated 21 million people infected (mostly in Asia) there are no convenient commercial diagnostics to detect this disease. Here we propose the first commercial rapid diagnostic test to detect Paragonimus infections, a disease that can be easily cured if diagnosed properly.
Project Terms: Adult; Affect; Antibiotics; Antibodies; Antigens; Area; Asia; base; Biological Assay; Biological Markers; Blood; Body Weight decreased; Caspase; Centers for Disease Control and Prevention (U.S.); Chemotherapy-Oncologic Procedure; Chronic; Clinical; Clinical Management; Clinical Sensitivity; Collection; Conduct Clinical Trials; cost effective; Coughing; Country; Crustacea; Cyst; design; Detection; Diagnosis; Diagnostic; Diagnostic tests; Differential Diagnosis; Disease; egg; Exposure to; Feces; Filaria bancrofti; Filarial Elephantiases; foodborne; Fresh Water; Future; genome sequencing; Goals; Gold; Hand; Helminth Proteins; Helminths; Hemoptysis; High Prevalence; Human; IgG4; Immunoglobulin G; immunoreactivity; Individual; Infection; Ingestion; innovation; interest; Intervention; Intestines; Ions; Life; Loa loa; Loiasis; Lung; Lung diseases; Malignant neoplasm of lung; Measures; medical schools; Methods; Microscopy; Myoglobin; nanoparticle; nanoshell; neglect; neglected tropical diseases; Nematode infections; novel; Ocular Onchocerciasis; Onchocerca volvulus; Paragonimiasis; Paragonimus; Parasites; Patients; Performance; Pharmaceutical Preparations; plasmonics; point of care; Praziquantel; Procedures; Proteins; Reader; Receiver Operating Characteristics; Regimen; Reproducibility; Resources; response; Roentgen Rays; Sampling; Secure; Sensitivity and Specificity; Specificity; Sputum; Symptoms; Technology; Test Result; Testing; Trematoda; Trematode Infections; Tropical Climate; Tuberculosis; undercooked; Universities; Washington; Western Blotting; Work; X-Ray Computed T
