Association of currentSchistosoma mansoni, S. japonicum,andS. mekongiinfection status and intensity with periportal fibrosis: a systematic review and meta-analysis

Abstract

Background: Periportal fibrosis (PPF) is a severe morbidity caused by both current and past exposure to intestinal schistosomes. We assessed the association between current/active infection status and intensity of Schistosoma mansoni, S. japonicum, or S. mekongi with PPF. Methods: We systematically searched the Cochrane Central Register of Controlled Trials, Embase, Global Health, Global Index Medicus and Medline on August 24, 2022. A meta-analysis to derive pooled effect sizes for concurrently measured current schistosome infection status and intensity against author-defined PPF was conducted using inverse-variance weighted random effects. Subgroup analyses by study characteristics and risk of bias assessments using a modified National Institute of Health Risk of Bias Tool were completed. The protocol was prospectively registered on PROSPERO (CRD42022333919). Findings: We identified 2646 records; 37 studies were included in the systematic review and 30 studies in the meta-analysis. S. mansoni was most studied (91.89%; 34/37). PPF was heterogeneously defined with the Niamey ultrasound protocol commonly used for diagnosis. Individuals with any current infection were 2.50 (95% CI:1.71-3.66) times more likely to have PPF compared to uninfected individuals with high heterogeneity (I2 statistic 94.80%). Subgroup analyses showed there was no association when only ultrasound patterns or modified Niamey Protocols were used. There was no association in studies conducted in sub-Saharan Africa after 2002 when mass drug administration became widespread, or in studies with a low risk of bias. No significant association was found between schistosome infection intensity and PPF. Interpretation: World Health Organization guidelines use current schistosome infection intensity as a proxy for schistosomiasis-related morbidity. This study supports that only current infection status was tenuously associated with PPF. Guidelines are needed to better monitor schistosomiasis-related morbidities. Funding: NDPH Pump Priming Fund, Wellcome Trust-ISSF (204826/Z/16/Z), John Fell Fund, Robertson Foundation, and UKRI EPSRC (EP/X021793/1).