Authors

Discussion

Background: Periportal fibrosis (PPF) is a severe morbidity caused by exposure to intestinal schistosome infections. In the context of repeated mass drug administration, it is unknown whether PPF correlates with schistosome infection. We aimed to assess the association between current infection status and intensity of S. mansoni, S. japonicum, or S. mekongi and periportal fibrosis (PPF). 

Methods: In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, Global Health, Global Index Medicus and Medline on May 18, 2022, for studies of original research. Only studies that actively diagnosed current schistosome infection at the time of PPF measurement were included and underwent a risk of bias assessment. A meta-analysis of data extracted from published reports was conducted when the findings of more than three studies could be combined. Pooled effect sizes for binary PPF outcomes against current schistosome infection status were calculated using inverse-variance weighted random effects meta-analysis. The protocol was prospectively registered on 19th May 2022 with PROSPERO (CRD42022333919).

Findings:  We identified 2646 references; 37 were included in the systematic review and 28  were used to calculate pooled effect sizes across 16777 participants. PPF was heterogeneously defined; with the Niamey protocol most often used to guide ultrasound assessments. Individuals with any current schistosome infection were 2·42 (95% CI:1·65-3·55) times more likely to have PPF but heterogeneity was high (I2 statistic 94·35%).  This association was not observed in studies with a low risk of bias. Subgroup analyses showed significant differences between study design, PPF outcome classifications, and studies that followed an ultrasound protocol and those that modified it. No significant association was found between a secondary outcome of schistosome infection intensity and PPF status. 

Interpretation: Guidelines use current schistosome infection as a proxy for PPF morbidity. This study supports that current infection status but not intensity is associated with an increased likelihood of having PPF. Further work is needed to identify associations of current infection status with different severity stages of PPF to develop effective guidelines for morbidity.