Transient Ascaris suum larval migration induces intractable chronic pulmonary disease and anemia in mice.

Yifan Wu,Maria Elena Bottazzi,Jill E Weatherhead,Morgan Knight,Ana Clara Gazzinelli-Guimaraes,Grace Adeniyi-Ipadeola,Evan Li,Li-Zhen Song,Ricardo Fujiwara,Alan R Burns,Keke C Fairfax

doi:10.1371/journal.pntd.0010050

Abstract

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host's lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through the host lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that a single episode of Ascaris larval migration through the host lungs leads to permanent lung damage with systemic effects. Remote episodes of ascariasis may drive non-communicable lung diseases such as asthma, chronic obstructive pulmonary disease (COPD), and chronic anemia in parasite endemic regions.

Highlights

Ascariasis is the most common helminth infection globally, affecting approximately 500 million people living in low- and middle-income countries (LMIC) and is associated with significant global morbidity, equating to nearly 800,000 disability-adjusted life years (DALYs)[1,2,3]
Our work demonstrates that transient Ascaris spp. larval migration through the lungs has significant long-term consequences including changes in lung structure and function as well as vascular damage causing chronic lung disease and anemia
We propose that Ascaris spp. larval migration through the host lungs is a risk factor for the development of chronic lung disease and anemia in parasite-endemic regions globally

Summary

Introduction

Ascariasis is the most common helminth infection globally, affecting approximately 500 million people living in low- and middle-income countries (LMIC) and is associated with significant global morbidity, equating to nearly 800,000 disability-adjusted life years (DALYs)[1,2,3]. Children become infected with either Ascaris lumbricoides, human roundworm, or Ascaris suum, porcine roundworm, via oral ingestion of eggs that are ubiquitous within the environment. Ascaris spp. larvae hatch in the intestines and migrate to the liver followed by the lungs via the systemic circulation. The mature larvae move through the alveolar epithelium, ascend the bronchotracheal tree and are swallowed back into the intestines where they develop into adult worms[6,7]. Completion of the two month larval migration cycle is essential for the parasite to develop into adult worms in the intestines[8]. The immunomodulatory properties of Ascaris adult worms permit long-term occupancy in the host intestinal lumen up to two years [9,10]

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Discussion

Conclusion