{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:39:30Z","timestamp":1788842370071,"version":"build-2803163510"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T00:00:00Z","timestamp":1633392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cardiovasc. Med."],"abstract":"<jats:p>Schistosomiasis, especially due to <jats:italic>Schistosoma mansoni<\/jats:italic>, is a well-recognized cause of pulmonary arterial hypertension (PAH). The high prevalence of this helminthiasis makes schistosome-related PAH (Sch-PAH) one of the most common causes of this disorder worldwide. The pathogenic mechanisms underlying Sch-PAH remain largely unknown. Available evidence suggests that schistosome eggs reach the lung via portocaval shunts formed as a consequence of portal hypertension due to hepatosplenic schistosomiasis. Once deposited into the lungs, the eggs elicit an immune response resulting in periovular granuloma formation. Immune mediators drive transforming growth factor-\u03b2 (TGF-\u03b2) release, which gives rise to pulmonary vascular inflammation with subsequent remodeling and development of angiomatoid and plexiform lesions. These mechanisms elicited by the eggs seem to become autonomous and the vascular lesions progress independently of the antigen. Portopulmonary hypertension, which pathogenesis is still uncertain, may also play a role in the genesis of Sch-PAH. Recently, there have been substantial advances in the diagnosis and treatment of PAH, but it remains a difficult condition to recognize and manage, and patients still die prematurely from right-heart failure. Echocardiography is used for screening, and the formal diagnosis requires right-heart catheterization. The experience in treating Sch-PAH is largely limited to the phosphodiesterase type 5 inhibitors, with evidence suggesting that these vasodilators improve symptoms and may also improve survival. Considering the great deal of uncertainty about Sch-PAH pathogenesis, course, and treatment, the aim of this review is to summarize current knowledge on this condition emphasizing its pathogenesis.<\/jats:p>","DOI":"10.3389\/fcvm.2021.724254","type":"journal-article","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T10:42:40Z","timestamp":1633430560000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Schistosome-Associated Pulmonary Arterial Hypertension: A Review Emphasizing Pathogenesis"],"prefix":"10.3389","volume":"8","author":[{"given":"Teresa Cristina Abreu","family":"Ferrari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Cristina Lopes","family":"Albricker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ina Morais","family":"Gon\u00e7alves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e1udia Maria Vilas","family":"Freire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,5]]},"reference":[{"key":"B1","first-page":"401","article-title":"2014 Guidelines of Taiwan Society of Cardiology (TSOC) for the management of pulmonary arterial hypertension","volume":"30","author":"Hsu","year":"2014","journal-title":"Acta Cardiol Sin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.3390\/diseases6020038","article-title":"Pulmonary arterial hypertension: pathophysiology and treatment","volume":"6","author":"Lan","year":"2018","journal-title":"Diseases."},{"key":"B3","doi-asserted-by":"publisher","first-page":"S1767","DOI":"10.21037\/jtd.2019.09.14","article-title":"Pharmacotherapy for pulmonary arterial hypertension","volume":"11","author":"Parikh","year":"2019","journal-title":"J Thorac Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1055\/s-0039-1692452","article-title":"Pulmonary arterial hypertension and therapeutic interventions","volume":"28","author":"Ishak Gabra","year":"2019","journal-title":"Int J Angiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur Respir J."},{"key":"B6","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1136\/heartjnl-2016-309870","article-title":"Cardiac manifestations of parasitic diseases","volume":"103","author":"Nunes","year":"2017","journal-title":"Heart."},{"key":"B7","doi-asserted-by":"publisher","first-page":"608883","DOI":"10.3389\/fimmu.2020.608883","article-title":"Schistosomiasis pulmonary arterial hypertension","volume":"11","author":"Sibomana","year":"2020","journal-title":"Front Immunol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e20190418","DOI":"10.1590\/0037-8682-0418-2019","article-title":"Demographic and clinical characteristics of pulmonary arterial hypertension caused by schistosomiasis are indistinguishable from other etiologies","volume":"53","author":"Mendes","year":"2020","journal-title":"Rev Soc Bras Med Trop."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1161\/CIRCULATIONAHA.113.003072","article-title":"TGF-\u03b2 signaling promotes pulmonary hypertension caused by Schistosoma mansoni","volume":"128","author":"Graham","year":"2013","journal-title":"Circulation"},{"key":"B10","doi-asserted-by":"publisher","first-page":"14","DOI":"10.21542\/gcsp.2017.14","article-title":"Nitric oxide and pulmonary arterial hypertension","volume":"2017","author":"Chester","year":"2017","journal-title":"Glob Cardiol Sci Pract."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.12688\/f1000research.14984.1","article-title":"Recent advances in pulmonary arterial hypertension","volume":"7","author":"Wilkins","year":"2018","journal-title":"F1000Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.1016\/S0140-6736(06)69440-3","article-title":"Human schistosomiasis","volume":"368","author":"Gryseels","year":"2006","journal-title":"Lancet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.idc.2012.03.004","article-title":"Schistosomiasis","volume":"26","author":"Gryseels","year":"2012","journal-title":"Infect Dis Clin North Am."},{"key":"B14","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1016\/S0140-6736(13)61949-2","article-title":"Human schistosomiasis","volume":"383","author":"Colley","year":"2014","journal-title":"Lancet."},{"key":"B15","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1038\/s41572-018-0013-8","article-title":"Schistosomiasis","volume":"4","author":"McManus","year":"2018","journal-title":"Nat Rev Dis Primers."},{"key":"B16","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/978-1-4614-8100-3_6","article-title":"Neuroschistosomiasis","volume-title":"Neglected Tropical Diseases and Conditions of the Nervous System","author":"Ferrari","year":"2014"},{"key":"B17","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/S1474-4422(11)70170-3","article-title":"Neuroschistosomiasis: clinical symptoms and pathogenesis","volume":"10","author":"Ferrari","year":"2011","journal-title":"Lancet Neurol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1086\/678507","article-title":"Schistosomiasis associated pulmonary hypertension","volume":"4","author":"Papamatheakis","year":"2014","journal-title":"Pulm Circ."},{"key":"B19","first-page":"66","article-title":"Pulmonary arterial hypertension due to bilharziasis. Apropos of a case due to Schistosoma haematobium having been cured by praziquantel","volume":"83","author":"Bour\u00e9e","year":"1990","journal-title":"Bull Soc Pathol Exot."},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1111\/j.1469-0691.2010.03308.x","article-title":"Pulmonary vascular disease associated with parasitic infection \u2013 the role of schistosomiasis","volume":"17","author":"Kolosionek","year":"2011","journal-title":"Clin Microbiol Infect"},{"key":"B21","doi-asserted-by":"publisher","first-page":"5","DOI":"10.21542\/gcsp.2019.5","article-title":"Schistosome infection and its effect on pulmonary circulation","volume":"2019","author":"Butrous","year":"2019","journal-title":"Glob Cardiol Sci Pract."},{"key":"B22","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1097\/MCP.0000000000000300","article-title":"Pulmonary arterial hypertension in schistosomiasis","volume":"22","author":"Gavilanes","year":"2016","journal-title":"Curr Opin Pulm Med"},{"key":"B23","volume-title":"Ultrasound in Schistosomiasis: A Practical Guide to the Standardized Use of Ultrasonography for the Assessment of Schistosomiasis-Related Morbidity","author":"Richter","year":"2000"},{"key":"B24","doi-asserted-by":"publisher","first-page":"j5492","DOI":"10.1136\/bmj.j5492","article-title":"Pulmonary arterial hypertension: pathogenesis and clinical management","volume":"360","author":"Thenappan","year":"2018","journal-title":"BMJ."},{"key":"B25","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1161\/CIRCRESAHA.113.301141","article-title":"Inflammation and immunity in the pathogenesis of pulmonary arterial hypertension","volume":"115","author":"Rabinovitch","year":"2014","journal-title":"Circ Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1378\/chest.10-0048","article-title":"Schistosomiasis-associated pulmonary hypertension pulmonary vascular disease: the global perspective","volume":"137","author":"Graham","year":"2010","journal-title":"Chest."},{"key":"B27","doi-asserted-by":"publisher","first-page":"356","DOI":"10.4103\/2045-8932.114764","article-title":"Schistosomiasis causes remodeling of pulmonary vessels in the lung in a heterogeneous localized manner: detailed study","volume":"3","author":"Kolosionek","year":"2013","journal-title":"Pulm Circ."},{"key":"B28","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1086\/675983","article-title":"Schistosomiasis and the pulmonary vasculature (2013 Grover Conference series)","volume":"4","author":"Graham","year":"2014","journal-title":"Pulm Circ."},{"key":"B29","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1164\/rccm.201410-1820OC","article-title":"The causal role of IL-4 and IL-13 in Schistosoma mansoni pulmonary hypertension","volume":"192","author":"Kumar","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"15494","DOI":"10.1038\/ncomms15494","article-title":"TGF-\u03b2 activation by bone marrow-derived thrombospondin-1 causes schistosoma- and hypoxia-induced pulmonary hypertension","volume":"8","author":"Kumar","year":"2017","journal-title":"Nat Commun."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2045894019889775","DOI":"10.1177\/2045894019889775","article-title":"Hot topics in the mechanisms of pulmonary arterial hypertension disease: cancer-like pathobiology, the role of the adventitia, systemic involvement, and right ventricular failure","volume":"9","author":"Spiekerkoetter","year":"2019","journal-title":"Pulm Circ."},{"key":"B32","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1586\/ers.11.17","article-title":"Viral infection and pulmonary hypertension: is there an association?","volume":"5","author":"Cool","year":"2011","journal-title":"Expert Rev Respir Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/j.1469-0691.2010.03285.x","article-title":"Inflammation, immunological reaction and role of infection in pulmonary hypertension","volume":"17","author":"Pullamsetti","year":"2011","journal-title":"Clin Microbiol Infect."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1161\/HYPERTENSIONAHA.119.14294","article-title":"Altered gut microbiome profile in patients with pulmonary arterial hypertension","volume":"75","author":"Kim","year":"2020","journal-title":"Hypertension."},{"key":"B35","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1002\/lt.23485","article-title":"Portopulmonary hypertension: an update","volume":"18","author":"Safdar","year":"2012","journal-title":"Liver Transpl."},{"key":"B36","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1186\/s12890-015-0115-y","article-title":"Pulmonary artery enlargement in schistosomiasis associated pulmonary arterial hypertension","volume":"15","author":"Hoette","year":"2015","journal-title":"BMC Pulm Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1378\/chest.14-1036","article-title":"Pulmonary arterial hypertension in the southern hemisphere: results from a registry of incident Brazilian cases","volume":"147","author":"Alves","year":"2015","journal-title":"Chest."},{"key":"B38","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.jacc.2010.03.065","article-title":"Survival in schistosomiasis-associated pulmonary arterial hypertension","volume":"56","author":"dos Santos Fernandes","year":"2010","journal-title":"J Am Coll Cardiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"315","DOI":"10.4269\/ajtmh.19-0866","article-title":"Nationwide remapping of Schistosoma mansoni infection in Rwanda using circulating cathodic antigen rapid test: taking steps toward elimination","volume":"103","author":"Ruberanziza","year":"2020","journal-title":"Am J Trop Med Hyg."},{"key":"B40","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1097\/MCP.0b013e3283645966","article-title":"Enhancing the accuracy of echocardiography in the diagnosis of pulmonary arterial hypertension: looking at the heart to learn about the lungs","volume":"19","author":"Mazurek","year":"2013","journal-title":"Curr Opin Pulm Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1186\/1750-1172-8-97","article-title":"Pulmonary arterial hypertension","volume":"8","author":"Montani","year":"2013","journal-title":"Orphanet J Rare Dis."},{"key":"B42","doi-asserted-by":"publisher","first-page":"G11","DOI":"10.1530\/ERP-17-0071","article-title":"Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography","volume":"5","author":"Augustine","year":"2018","journal-title":"Echo Res Pract."},{"key":"B43","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.ijcard.2018.08.084","article-title":"Risk stratification strategy and assessment of disease progression in patients with pulmonary arterial hypertension: updated recommendations from the cologne consensus conference 2018","author":"Leuchte","year":"2018","journal-title":"Int J Cardiol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1801904","DOI":"10.1183\/13993003.01904-2018","article-title":"Diagnosis of pulmonary hypertension","volume":"53","author":"Frost","year":"2019","journal-title":"Eur Respir J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/eurheartj\/ehv317","article-title":"2015 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT)","volume":"37","author":"Gali\u00e8","year":"2016","journal-title":"Eur Heart J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1590\/s0066-782x2012005000071","article-title":"Hemodynamic profile of severity at pulmonary vasoreactivity test in schistosomiasis patients","volume":"99","author":"Japyass\u00fa","year":"2012","journal-title":"Arq Bras Cardiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1800307","DOI":"10.1183\/13993003.00307-2018","article-title":"Survival of patients with schistosomiasis-associated pulmonary arterial hypertension in the modern management era","volume":"51","author":"Fernandes","year":"2018","journal-title":"Eur Respir J."},{"key":"B48","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1055\/s-0039-1692140","article-title":"Novel therapeutic approaches of pulmonary arterial hypertension","volume":"28","author":"Tyagi","year":"2019","journal-title":"Int J Angiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s12170-020-00663-3","article-title":"Management of pulmonary arterial hypertension","volume":"15","author":"Mayeux","year":"2021","journal-title":"Curr Cardiovasc Risk Rep."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1056\/NEJMoa2024277","article-title":"Sotatercept for the treatment of pulmonary arterial hypertension","volume":"384","author":"Humbert","year":"2021","journal-title":"N Engl J Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1586\/ers.11.58","article-title":"Schistosomiasis and pulmonary hypertension","volume":"5","author":"Fernandes","year":"2011","journal-title":"Expert Rev Respir Med."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.724254\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T10:42:48Z","timestamp":1633430568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2021.724254\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":51,"alternative-id":["10.3389\/fcvm.2021.724254"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2021.724254","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,5]]},"article-number":"724254"}}