# Host genetic background influences the severity of disease in Schistosoma haematobium infections

## TL;DR

This study shows that a specific genetic variant increases the risk of severe bladder disease caused by a parasitic infection in humans.

## Contribution

First evidence linking a TNF-α promoter polymorphism to severe urogenital schistosomiasis in humans.

## Key findings

- Carriers of the G mutant allele at rs3093660 have a five-fold increased risk of severe urogenital schistosomiasis.
- Higher TNF-α and ECP levels correlate with Schistosoma haematobium infection severity.
- Bladder thickening was the most common morbidity observed in infected individuals.

## Abstract

Host genetic factors influence the severity of infectious diseases, including schistosomiasis, which are major public-health burdens in Africa. While the role of host genetic background in Schistosoma mansoni infection has been clearly established, this link remains poorly explored for S. haematobium infections (Sh). Therefore, this study aims to investigate the relationship between genetic background and morbidity associated with urogenital schistosomiasis using a candidate gene approach. We analyzed urine samples from 334 Beninese men, measuring urinary eosinophil cationic protein (ECP) by ELISA as a marker for bladder inflammation. Abdominopelvic ultrasonography was performed in a subgroup of 146 participants (69 Sh-positive and 77 Sh-negative) to assess morbidities associated with Schistosoma infection. Blood samples were analyzed for TNF-α levels by ELISA and for TNF-α promoter polymorphisms by sequencing to assess associations between genetic variation and morbidity. Results showed that 25.4% of Sh+ had significantly higher mean TNF-α (U = 5888; p = 0.0098) and ECP (U = 912.5; p < 0.0001) levels than Sh−. Positive correlations were observed between egg count and both ECP (Tau = 0.4016; p < 0.0001) and TNF-α levels (Tau = 0.2238; p = 0.014). Morbidity mainly included bladder irregularities (6%), thickening (29%), and kidney dilation (6%). The G mutant allele on the rs3093660 marker was significantly associated with morbidity (χ2 = 4.47; p = 0.034; OR = 5.09 [95% CI: 1.04–24.9]). Our results suggest, for the first time, that carriers of the G mutant allele at rs3093660 marker have a five-fold increased risk of developing severe urogenital schistosomiasis.