Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology

October 26, 2016 updated by: Rupert Kaul, University of Toronto

Effect of Schistosomiasis Mansoni and Its Treatment on HIV Susceptibility and Female Genital Immunology

The aim of this study is to assess the impact of Schistosoma mansoni infection and its treatment on genital immunology and HIV susceptibility in Ugandan women.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Schistosomiasis mansoni is a water-borne disease caused by helminth Schistosoma mansoni (S. mansoni), in which adult worms deposit eggs in mesenteric blood vessels. Schistomiasis prevalence in the fishing communities in East Africa, and particularly in the Lake Victoria region, exceeds 60% and there is overlap in this region with a high prevalence of HIV (29%).

A recent epidemiological study found an association between S. mansoni and HIV infection in adult women residing near Lake Victoria in Tanzania. Furthermore, in primate studies S. mansoni infection was shown to increase susceptibility to SIV infection after rectal (but not intravenous) challenge, implying that S. mansoni might increase HIV susceptibility by altering local mucosal (gut) immunology.

While S. mansoni does not directly infect the genital tract, we hypothesize that the inflammation it causes in the gut may be associated with mucosal inflammation at other sites through activation of common mucosal homing integrins such as a4b7. Therefore in this study we propose to explore whether S. mansoni increases inflammation and/or HIV susceptibility in the endocervix of adult women.

HIV-uninfected adult women from Entebbe, Uganda will be screened for schistosomiasis using a commercial CCA rapid test kit, and infected women who fulfill the study eligibility criteria will be recruited into the study. Kato-Katz microscopy analysis will be performed to assess egg shedding at baseline. Additionally, urine microscopy will be done to screen for Schistosoma hematobium (which can directly involve the genital mucosa). Schistosomiasis treatment will be provided to all participants according to Ugandan clinical guidelines.

Endocervical cytobrush, vaginal SoftCup and blood samples will be collected at three time points; at baseline and 4 and 8 weeks after schistosomiasis treatment, at the same stage of the menstrual cycle. Using an ex vivo HIV entry assay and mucosal cytokine and microbiome analyses we will quantify the effect of S. mansoni and its treatment on cervical HIV susceptibility and genital inflammation.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Uganda
    • Wakiso
      • Entebbe, Wakiso, Uganda
        • UVRI-IAVI HIV Vaccine program

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Positive (score above "trace") on a urine CCA rapid test
  • Willing to be treated with praziquantel
  • Willing to give informed consent, and answer short questionnaires on economic status, and sexual risk behavior.
  • Willing to comply with the requirements of the protocol
  • HIV and classical STI (see below) negative

Exclusion Criteria:

  • HIV infected
  • Malaria infected
  • Pregnant.
  • Irregular menstrual cycle, or actively menstruating at the time of genital sampling.
  • Tested positive for classical STIs (syphilis, gonorrhea, chlamydia, Trichomonas vaginalis) or having genital ulcers
  • Prior hysterectomy
  • Deemed by physician to be unlikely to complete study protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Praziquantel treatment
Participants will be HIV-uninfected women with asymptomatic Schistosoma mansoni infection; the study will examine the impact of standard praziquantel therapy (40 mg/kg po single dose) on genital immunology and HIV susceptibility.
Drug: Praziquantel
40 mg/kg, PO (orally administered tablets)
Other Names:
  • Agopraz, bromoxel, biltricide

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time Frame: 1 month.
The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
1 month.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time Frame: 1 month.
The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
1 month.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the percentage of blood CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time Frame: 1 and 2 months.
The percentage of blood CD4+ T cells infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
1 and 2 months.
Change in the phenotype of endocervical and blood CD4+ T cells after treatment of schistosomiasis.
Time Frame: 1 and 2 months.
Surface expression of CCR5, CD69, CD38, HLA-DR, a4b7, CCR7 and CD45RA by endocervical and blood CD4 T will be assessed using flow cytometry.
1 and 2 months.
Change in genital proinflammatory cytokine levels after treatment of schistosomiasis.
Time Frame: 1 and 2 months.
A predefined genital inflammation score based on genital levels of pro-inflammatory cytokines and chemokines [as per Arnold K et al, Muc Immunol, 2015] will be assessed.
1 and 2 months.
Change in the cervico-vaginal microbiome after treatment of schistosomiasis.
Time Frame: 1 and 2 months.
The cervico-vaginal microbiome will be assessed by 16s rRNA sequencing before and after schistosomiasis therapy.
1 and 2 months.
Change in the cervico-vaginal proteome after treatment of schistosomiasis.
Time Frame: 1 and 2 months.
The genital proteome will be assessed by mass spectrometry before and after schistosomiasis therapy.
1 and 2 months.
Change in the percentage of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time Frame: 2 months.
The percentage of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
2 months.
Change in the number of endocervical CD4+ T cells susceptible to HIV pseudovirus entry after treatment of schistosomiasis.
Time Frame: 2 months.
The number of endocervical CD4+ T cells per cytobrush infected ex vivo by an HIV pseudovirus construct, as quantified by flow cytometry.
2 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Toronto

Collaborators

UVRI-IAVI HIV Vaccine Program, Uganda

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2016

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2016

Study Registration Dates

First Submitted

August 15, 2016

First Submitted That Met QC Criteria

August 19, 2016

First Posted (Estimate)

August 25, 2016

Study Record Updates

Last Update Posted (Estimate)

October 27, 2016

Last Update Submitted That Met QC Criteria

October 26, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UT-Schisto

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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