# Genital Immune, Mucosal, and Viral Effects of Female Genital Schistosomiasis in Tanzania

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $637,595

## Abstract

Project Summary/Abstract
Female genital schistosomiasis (FGS), caused by the parasitic worm Schistosoma haematobium, affects 40
million girls and women in Africa. Parasite eggs migrate through mucosal tissue, inducing a host immune
reaction that leads to erosions and mucosal breaches of the female genital tract with symptoms including
genital discharge, bleeding, pain, and infertility. Chronic genital tract damage and symptoms persist after
praziquantel therapy in ~70% of women, even though praziquantel effectively kills parasite worms, reduces
excretion of eggs in urine, and resolves most tissue pathology in the bladder. In contrast, parasite eggs remain
trapped in genital tissue post-treatment where, from autopsy studies, they are known to induce a mucosal
immune response characterized by granuloma formation and fibrosis. FGS is a neglected tropical disease and
there are important knowledge gaps in our understanding of its cellular and molecular pathophysiology. We do
not know the profiles or functions of immune cells that respond to S. haematobium eggs in genital tissue, the
effects of FGS on the epithelial cell barrier, and if FGS-related cellular and molecular changes increase
susceptibility to viral genital tract infections. The rationale for this proposal is that addressing these knowledge
gaps could lead to targeted immunomodulatory, tissue reparative, or viral suppressive interventions to restore
damaged genital mucosa. Based on our preliminary data, our central hypothesis is that S. haematobium eggs
in the genital mucosa modulate cervical immunity and decrease anti-viral immune cells, cause breakdowns in
the epithelial barrier, and increase recurrences of HSV-2, resulting in the morbidity and persistent symptoms of
FGS even after praziquantel therapy. To test this hypothesis, we will study 90 women with S. haematobium
infection and 90 controls without. Women with S. haematobium will receive praziquantel treatment at baseline
and during 12 months of follow up if persistent or recurrent S. haematobium is detected. We will pursue three
specific aims: 1) Define the genital mucosal immune cell composition in S. haematobium infection, before and
after praziquantel; 2) Determine the molecular mechanisms linked to breakdown of genital epithelial integrity in
women with S. haematobium infection; and 3) Quantify the effect of S. haematobium infection on the
frequency, intensity, and duration of genital HSV-2 reactivation. In the first aim, we will collect cervical cells by
brush and characterize cells by flow and mass cytometry. In the second aim, we will isolate epithelial cells
collected by cervical brush and perform RNA-Seq to elucidate genes and pathways specific to epithelial
integrity. In the third aim, we will quantify HSV-2 viral shedding over one month in women from the cohort who
are HSV-2 seropositive (n=90). In an exploratory analysis, we will also examine the vaginal virome by
metagenomic sequencing. The proposed research is signific...

## Key facts

- **NIH application ID:** 10423450
- **Project number:** 1R01AI168306-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Jennifer Alzos Downs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $637,595
- **Award type:** 1
- **Project period:** 2022-03-25 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10423450

## Citation

> US National Institutes of Health, RePORTER application 10423450, Genital Immune, Mucosal, and Viral Effects of Female Genital Schistosomiasis in Tanzania (1R01AI168306-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10423450. Licensed CC0.

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