Effect of Schistosomiasis Mansoni on HIV Susceptibility and Female Genital Immunology

NCT ID: NCT02878564

Last Updated: 2016-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-03-31

Study Completion Date

2016-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Schistosomiasis Mansoni HIV

Keywords

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Schistosomiasis mansoni HIV susceptibility Genital immunology Mucosal immunology HIV entry assay Adult women

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Praziquantel

Intervention Type DRUG

40 mg/kg, PO (orally administered tablets)

Interventions

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Praziquantel

40 mg/kg, PO (orally administered tablets)

Intervention Type DRUG

Other Intervention Names

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Agopraz, bromoxel, biltricide

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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UVRI-IAVI HIV Vaccine Program, Uganda

UNKNOWN

Sponsor Role collaborator

University of Toronto

OTHER

Sponsor Role lead

Responsible Party

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Rupert Kaul

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Rupert Kaul, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

University of Toronto

Locations

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UVRI-IAVI HIV Vaccine program

Entebbe, Wakiso, Uganda

Site Status

Countries

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Uganda

References

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Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, Abou M, Westmacott GR, McCorrister S, Kwatampora J, Nyanga B, Kimani J, Masson L, Liebenberg LJ, Abdool Karim SS, Passmore JA, Lauffenburger DA, Kaul R, McKinnon LR. Increased levels of inflammatory cytokines in the female reproductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol. 2016 Jan;9(1):194-205. doi: 10.1038/mi.2015.51. Epub 2015 Jun 24.

Reference Type BACKGROUND
PMID: 26104913 (View on PubMed)

Downs JA, van Dam GJ, Changalucha JM, Corstjens PL, Peck RN, de Dood CJ, Bang H, Andreasen A, Kalluvya SE, van Lieshout L, Johnson WD Jr, Fitzgerald DW. Association of Schistosomiasis and HIV infection in Tanzania. Am J Trop Med Hyg. 2012 Nov;87(5):868-73. doi: 10.4269/ajtmh.2012.12-0395. Epub 2012 Oct 1.

Reference Type BACKGROUND
PMID: 23033399 (View on PubMed)

Chenine AL, Shai-Kobiler E, Steele LN, Ong H, Augostini P, Song R, Lee SJ, Autissier P, Ruprecht RM, Secor WE. Acute Schistosoma mansoni infection increases susceptibility to systemic SHIV clade C infection in rhesus macaques after mucosal virus exposure. PLoS Negl Trop Dis. 2008 Jul 23;2(7):e265. doi: 10.1371/journal.pntd.0000265.

Reference Type BACKGROUND
PMID: 18648516 (View on PubMed)

Joag VR, McKinnon LR, Liu J, Kidane ST, Yudin MH, Nyanga B, Kimwaki S, Besel KE, Obila JO, Huibner S, Oyugi JO, Arthos J, Anzala O, Kimani J, Ostrowski MA; Toronto HIV Research Group; Kaul R. Identification of preferential CD4+ T-cell targets for HIV infection in the cervix. Mucosal Immunol. 2016 Jan;9(1):1-12. doi: 10.1038/mi.2015.28. Epub 2015 Apr 15.

Reference Type BACKGROUND
PMID: 25872482 (View on PubMed)

Other Identifiers

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UT-Schisto

Identifier Type: -

Identifier Source: org_study_id