Chest
Volume 137, Issue 6, Supplement, June 2010, Pages 20S-29S
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PULMONARY VASCULAR DISEASE: THE GLOBAL PERSPECTIVE
Schistosomiasis-Associated Pulmonary Hypertension: Pulmonary Vascular Disease: The Global Perspective

https://doi.org/10.1378/chest.10-0048Get rights and content

Inflammation is likely a critical underlying etiology in many forms of severe pulmonary hypertension (PH), and schistosomiasis-associated PH, one of the most common causes of PH worldwide, is likely driven by the host response to parasite antigens. More than 200 million people are infected with schistosomiasis, the third most common parasitic disease, and approximately 1% of those chronically infected develop PH. Acute cutaneous infection causes inflammation at the site of parasite penetration followed by a subacute immune complex-mediated hypersensitivity response as the parasite migrates through the lungs. Chronic schistosomiasis infection induces a granulomatous inflammation around ova deposited in the tissue. In particular, Schistosoma mansoni migrates to the portal venous system and causes preportal fibrosis in a subset of individuals and appears to be a prerequisite for PH. Portal hypertension facilitates shunting of ova from the portal system to the pulmonary arterial tree, resulting in localized periovular pulmonary granulomas. The pulmonary vascular remodeling is likely a direct consequence of the host inflammatory response, and portopulmonary hypertension may be a significant contributor. New specific therapies available for PH have not been widely tested in patients with schistosomiasis and often are unavailable for those infected in resource-poor areas of the world where schistosomiasis is endemic. Furthermore, the current PH therapies in general target vasodilation rather than vascular remodeling and inflammation. Further research is needed into the pathogenic mechanism by which this parasitic infection results in pulmonary vascular remodeling and PH, which also may be informative regarding the etiology of other types of PH.

Section snippets

Case Presentation

The patient was a woman aged 31 years when she presented at Procape Hospital in Recife, the capital of the State of Pernambuco in northeast Brazil. She had a history of multiple unexplained syncopal episodes beginning at age 17. At the time of presentation, she complained of significant progressive shortness of breath with minimal exertion (World Health Organization functional class III), palpitations, and intermittent chest pain. She had never smoked or used anorexigens. She was born and grew

The Global Impact of Schistosomiasis

Schistosomiasis is the third most common parasitic disease after malaria and amebiasis, affecting about 200 to 300 million people in 74 countries, 85% of whom live in sub-Saharan Africa. Almost 500 to 800 million people are at risk for acquiring the infection that accounts for > 250,000 deaths per year. It causes up to 4.5 million disability-adjusted life year losses annually due to factors such as anemia, pain, diarrhea, exercise intolerance, and undernutrition that results from chronic

Schistosome, the Parasite

Schistosomiasis is an ancient and chronic disease of humans, nonhuman primates, other mammals, and birds. It is also known as bilharzia, or snail fever, and is caused by several species of the genus Schistosoma. These parasites are flatworm flukes of the trematoda class. The main species to infect humans is Schistosoma mansoni (also known as Manson blood fluke or swamp fever). The worm has two hosts in its life cycle (Fig 217) and involves many steps.18, 19 Snails of the Biomphalaria genus are

Acute Schistosomiasis Infection

After penetration, the cercariae may remain in the skin for 1 to 2 days. At the site of penetration, the parasite leaves behind an itchy punctate rash, called cercarial dermatitis, that self-resolves after the parasite leaves. The cercaria accesses the bloodstream through the postcapillary venules and undergoes transformation into schistosomulum prior to becoming an adult worm. Migration through the venous system continues, and the parasite reaches the lungs. At this stage, schistosomiasis

Portal Fibrosis: A Potential Precursor to Chronic Pulmonary Disease

A minority of the eggs released by the reproducing adult worms remain within the host. For S mansoni and S japonicum, the retained ova remain within the portal venous system, either in the intestinal mucosa or in the small portal veins within the liver. Within the liver, the ova become niduses for periovular epitheloid granulomatous reactions as the immune system attempts to encapsulate the parasite. Although these lesions result in eventual egg destruction, they also lead to tissue destruction

Pulmonary Periovular Granulomas and Vascular Remodeling: What Is the Link?

In patients with portal hypertension, Schistosoma eggs embolize into the lungs where they lodge in small muscular arteries and induce isolated granulomas. Andrade and Andrade41 reported that among 78 persons with hepatosplenic schistosomiasis, 72% had periovular granulomas. One-third had numerous periovular granulomas involving the alveolar tissue and the pulmonary arterioles. The cellular components of the pulmonary granulomas include eosinophils, macrophages, leukocytes, and fibroblasts as

PH and Schistosomiasis-Specific Treatment Options

It is apparent that schistosomiasis relies on persistent, recurrent, high-egg-burden chronic infection. The cycle can be interrupted with sanitation and education measures to prevent fresh water exposure to infectious cercariae. However, several cultural and economic hurdles prevent the successful implementation of these preventive measures. These difficulties underlie the global impact of schistosomiasis. Furthermore, patients with recurrent hemoptysis due to hepatosplenic disease in

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Bandeira has received speaking fees from Pfizer. Dr Butrous owns Shares in Pfizer Ltd and has participated in speaking activities and industry advisory committees. Drs Graham, Bandeira, Morrell, Butrous, and Tuder have disclosed that they are affiliated with the Pulmonary Vascular Research Institute.

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      Citation Excerpt :

      As expected, we developed a consistent model of schistosomiasis, which manifested marked lung accumulation of S. mansoni eggs in the chronic phase of infection. In schistosomiasis, the development of lung granulomatous inflammation is directly linked to the retention of eggs in the pulmonary circulation, which migrates from the portal system to the lung parenchyma from portocaval shunts [52,53]. Thus, eggs trapped in the lungs trigger an intense inflammatory response that drives granulomatous lung disease [52,54], which was consistently associated to reduced weight gain, increased lung mass, intense and diffuse inflammatory infiltrate, vascular congestion, and extensive microstructural lung remodeling evidenced by alveolar collapse, septal thickening, expansion of the connective stroma and tissue fibrosis.

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    Funding/Support: This work was supported by the Cardiovascular Medical Research Fund.

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).

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