PARAGONIMUS

 BACKGROUND

Hardly anyone in the Western world has heard of Paragonimus, yet this parasite affects 21 million people in Southeast Asia. Paragonimus is a slug-like looking worm that is acquired upon ingesting raw crustaceans. It migrates from the digestive tract to the lung, where it induces chronic cough, chest pain, and hemoptysis (coughing up blood). About nine species of Paragonimus are known to cause human paragonimiasis, with P. westermani causing the majority of disease in Asia. In Africa, Central and South America, and North America, the prevalent species are, respectively, P. africanus, P. mexicanus, and P. kellicotti. While treatment with praziquantel is straightforward, diagnosis is challenging. The traditional method – detecting Paragonimus eggs in sputum or stool – requires microscopy expertise, is low-throughput, and only detects egg-producing adult flukes, with a clinical sensitivity of around 50%.

With an effective drug at hand but no convenient diagnostic, a sensitive and specific RDT is the missing piece to enable efficient clinical management of paragonimiasis. Early and accurate diagnosis of Paragonimus infection allows for the appropriate antiparasitic treatment, reducing the risk of severe complications and preventing the spread of the parasite, particularly in endemic areas. Accurately diagnosing paragonimiasis is crucial as its symptoms closely mimic those of tuberculosis (TB) and lung cancer. Misdiagnosis can lead to inappropriate treatments, such as unnecessary TB medications or invasive procedures intended for lung cancer, which are ineffective against paragonimiasis and can even cause harm. Against this backdrop, our goal was to develop a sensitive and specific serological rapid diagnostic test (RDT) to detect exposure to pulmonary flukes of the genus Paragonimus.

A NEW RAPID TEST FOR PARAGONIMUS

Under an NIH SBIR Phase I grant, we collected 93 samples of Paragonimiasis patients in the Philippines, 10 of which were positive for P. kellicotti and 83 positives for P. westermani, and used that sample set to develop two prototype tests capable of detecting IgG4 antibodies raised by the human host against two proteins (antigens) expressed by Paragonimus species. Both tests were evaluated for sensitivity using the 93 Paragonimus positive samples collected in the Philippines, as well as for specificity using 45 negative samples from uninfected US donors from the San Diego Blood Bank. The test based on Antigen 1 (A1) was 50% sensitive and 100% specific, whereas the test based on Antigen 2 (A2) was 71% sensitive and 98% specific. The two tests were complementary to each other, insofar as A1 detected 5 out of 27 clinical samples that were not detected with A2. Therefore, if one were to combine the two antigens in a single test line, the theoretical sensitivity would be 76% (71/93) with a specificity of 98% (44/45). 

In light of these promising sensitivity and specificity data, future work will aim at combining the two antigens in a single test strip and proceed to a multi-center laboratory and field evaluation of the new Paragonimus test. Once manufactured at scale, the new test will enable efficient clinical management of paragonimiasis and allow more precise differential diagnosis of paragonimiasis versus tuberculosis and/or lung cancer.