Schistosomiasis Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a disease of the lung blood vessels that results in right heart failure. PAH is thought to occur in about 5% to 10% of patients with hepatosplenic schistosomiasis, particularly due to S. mansoni. The lung blood vessel injury may result from a combination of embolization of eggs through portocaval shunts into the lungs causing localized Type 2 inflammatory response and vessel remodeling, triggering of autonomous pathology that becomes independent of the antigen, and high cardiac output as seen in portopulmonary hypertension. The condition is likely underdiagnosed as there is little systematic screening, and risk factors for developing PAH are not known. Screening is done by echocardiography, and formal diagnosis requires invasive right heart catheterization. Patients with Schistosoma-associated PAH show reduced functional capacity and can be treated with pulmonary vasodilators, which improves symptoms and may improve survival. There are animal models of this disease that might help in understanding disease pathogenesis and identify novel targets to screen and treatment. Pathogenic mechanisms include Type 2 immunity and activation and signaling in the TGF-β pathway. There are still major uncertainties regarding Schistosoma-associated PAH development, course and treatment.

Keywords: TGF-beta; hepatosplenic; neglected tropical disease; pulmonary hypertension; schistosomiasis; type 2 inflammation.

Figure 1

(A) Relationship of chronic schistosomiasis to disease complications including SchPAH (B). Combined criteria for the diagnosis of SchPAH. Notes (1): It is possible for patients to develop SchPAH without HSS (2). The hemodynamic criteria are per the most recent, 6th World Symposium guidelines (Nice-2018; see Simonneau et al. ERJ 2019 [reference (19)].

Figure 2

Current understanding of the epidemiology of schistosomiasis, HSS and SchPAH. With exceptions (see text), most patients who ultimately develop SchPAH have the S. mansoni species (accounting for about 50% of the worldwide burden of disease) and HSS resulting in portal hypertension. Please note that there is uncertainty (as discussed in the text) regarding the percentages for the prevalence of HSS among those with schistosomiasis, and the prevalence of SchPAH among those with HSS.

Figure 3

Examples of HSS (A). An example of bleeding esophageal varices: note the bulging esophageal mucosa indicative of underlying varicies, with signs of active bleeding (Picture taken by ES in the endoscopy unit, University of Zambia Teaching Hospital, Lusaka, Zambia.). (B) Periportal fibrosis detected by ultrasound (red arrows). Reproduced from reference (39), with addition of the red arrows by the present authors to clarify the location of the pathology.

Figure 4

Overview of the diagnostic workup for SchPAH. The current hemodynamic criteria are from the 6th World Symposium on Pulmonary Hypertension [Nice-2018; see Simonneau et al. ERJ 2019, reference (19)].

Figure 5

Mouse models (A). Cercariae infection model (B). Intraperitoneal sensitization followed by intravenous augmentation model.

Figure 6

Schematics of the chain of signaling and cellular events leading to SchPAH (A). Signaling events (B). Cellular events.