Schistosome infection was associated with delayed HIV disease progression in HIV seroconverters in Tanzania. Of 172 HIV seroconverters followed for a median of 3.4 years, 63 (36.6%) had evidence of pre-HIV schistosome infection. Those with schistosome infection had a significantly lower risk of reaching CD4<350 cells/μL or death, with an 82% reduction in this risk compared to those without schistosome infection. Schistosome infection at HIV acquisition may delay HIV disease progression potentially through induction of Treg and Th17 cells, maintaining functional CD8 T-cells and reducing immune activation. However, the study had limitations such as many lost to follow ups and inability to measure

1. Impact of schistosome infection on long-term
HIV/AIDS outcomes
Soledad Colombe, Richard Machemba, Baltazar Mtenga, Peter Lutonja, Samuel
E. Kalluvya, Claudia J. de Dood, Pytsje T. Hoekstra, Govert J. van Dam, Paul L. A.
M. Corstjens, Mark Urassa, John M. Changalucha, Jim Todd, Jennifer A. Downs
AIDS outcomes. PLoS Negl Trop Dis 12(7) (2018)
MRC/UVRI & LSHTM Journal Club (11/01/2019) Presentation
Dr ludoviko Zirimenya
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2. CELL-MEDIATED IMMUNITY
• Mediated by T lymphocytes, macrophages and NK cells
• The cell-mediated immune system is involved in the elimination of:
• Intracellular pathogens and infected cells (mainly viruses, mycobacteria and
fungi)
• Tumour cells
• Foreign grafts.
• The thymus plays an important role in cell-mediated immunity
because it is the site of T cell maturation.
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3. • CD 4+ Cell Differentiation and
effector function
• Knochelmann et al (2018)
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4. Effects of Tregs on other cell types
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5. Background
• Estimated 6 of 36.7 million global HIV infections are schistosome co-
infected
• Multiple studies have reported interactions between infection with
Schistosoma spp. and HIV-1 in humans.
• Schistosome infection is a risk factor for HIV-1 acquisition in women, but not in
men (Downs et al, 2017)
• ~3-fold increased odds of HIV-1 infection in women with schistosome
infections (Kjetland et al, 2006) (Downs et al, 2012) (Brodish et al 2016)
• Increased HIV-1 RNA viral load set-points in both men and women who were
infected with Schistosoma spp. at time of HIV-1 seroconversion (Downs et al,
2017)
• Treatment of Schistosoma mansoni is associated with a decrease in HIV-1 viral
load in co-infected individuals (Kallestrup et al 2005)
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6. Study Objective
• To investigate the impact of schistosome infection at the time of HIV-
1 seroconversion on the speed of HIV-1 disease progression, as
measured by the outcome CD4+ T-cell (CD4) counts <350 cells/μL
and/or death
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7. Methods
• Study setting and design
• TAZAMA project, a community-based longitudinal open HIV-testing cohort in
Kisesa, north west Tanzania
• Follow-up.
• The follow-up period spanned from date of seroconversion to March 15th
2017. The date of seroconversion was approximated as the mid-point
between the last negative DBS and the first positive test
• Schistosome infection status.
• This was made by measurement of schistosome Circulating Anodic Antigen
(CAA) in DBS collected during two successive sero-discordant sero-survey
visits.
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8. Laboratory testing
• Dried blood spots.
• DBS were collected by finger prick with a fingerstick lancet onto a Whatman
Protein Saver 903 card (GE Healthcare Bio-Sciences, Pittsburgh, PA)
• HIV-1 testing.
• HIV-1 infection was confirmed by two different tests in accordance with
current national HIV guidelines at each time point.
• Schistosoma spp. testing.
• DBS were tested for schistosome CAA at Leiden University Medical Center
• Positive test for schistosome infection was when a person's DBS collected both at the last
sero-survey where he/she tested negative for HIV 1 and the first sero survey where
he/she tested positive for HIV 1 were CAA Positive.
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9. Statistical analysis
• Analysis included all individuals who HIV-1 seroconverted between
September 2006 and February 2016.
• The outcome of interest was defined as a composite endpoint: either
CD4 count <350cells/μL or death.
• All results were expressed with 95% confidence intervals (CIs) and
statistical significance was set at P < 0.05 (two-tailed).
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10. Results
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11. Table 1. Demographics of the TAZAMA HIV-1 seroconverters, by schistosome infection status
at time of HIV-1 seroconversion.
Colombe S, Machemba R, Mtenga B, Lutonja P, Kalluvya SE, et al. (2018) Impact of schistosome infection on long-term HIV/AIDS
outcomes. PLOS Neglected Tropical Diseases 12(7): e0006613. https://doi.org/10.1371/journal.pntd.0006613
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006613

12. ….Result…..
• 63/172 (36.6%) sero-converters had a pre-HIV-seroconversion
positive test for Schistosoma.
• 43/172 (25.0%) had both samples positive for Schistosoma
• 172 HIV-1 sero-converters were followed for a median of 3.4[2.3±5.4]
years
• 42 occurrences of the outcome (defined as either reaching CD4 count
<350cells/μL or death)
• Outcome incidence was significantly lower in HIV-1 sero-converters
infected with Schistosoma spp. compared to those non infected with
Schistosoma spp.
• Sub-distribution Hazard Ratio (SHR) = 0.31 [0.12,0.84], p = 0.021
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13. Fig 1. Cumulative incidence function of the composite outcome CD4+ T-cell counts &lt;350
cells/μL and/or death, controlling for ART initiation, by schistosome infection status at time of
HIV-1 seroconversion.
Colombe S, Machemba R, Mtenga B, Lutonja P, Kalluvya SE, et al. (2018) Impact of schistosome infection on long-term HIV/AIDS
outcomes. PLOS Neglected Tropical Diseases 12(7): e0006613. https://doi.org/10.1371/journal.pntd.0006613
https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0006613

14. ….Result
• The impact of schistosome infection on time to outcome was still
statistically significant and protective:
• 82% reduction in risk of reaching a CD4 count <350 or death in HIV-1
seroconverters infected with schistosomes compared to those free of
schistosomes (SHR = 0.18 [0.068,0.50], p = 0.001) at time of seroconversion.
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15. Discussion
• People with schistosome
infection at the time of HIV-
seroconversion develop adverse
HIV outcomes more slowly than
those without.
• Schistosome infection at the time
of HIV-1 acquisition may delay
HIV-1 disease progression.
• Complex interactions between HIV-1 and
schistosome co-infections that may be modulated
over time
• One possible immunologic mechanism is the induction
of Th17 and T reg cells by chronic schistosome infection,
leading to delayed HIV-1 disease progression.
• Treg numbers have been associated with decreased
markers of immune activation (Falivene et al, 2015)
• Individuals with chronic schistosome infection have
increased peripheral blood percentages and absolute
numbers of Th17 cells and T regulatory cells as compared
to uninfected individuals (Mbow et al, 2012) (Larkin et al,
2012)
• Maintaining long-term functional anti-viral CD8+ T-cells.
(Falivene et al, 2015)
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16. Potential roles for Tregs in the natural history of HIV infection.
Mathieu F. Chevalier, and Laurence Weiss Blood
2013;121:29-37
©2013 by American Society of Hematology

17. Limitations
• The sero-surveys were
conducted every 3 years, which
only allowed approximation of
seroconversion dates
• Assumption that schistosome
infection status at
seroconversion was correlated
to the infection status at the last
HIV-1 negative sero-survey and
first HIV-1 positive sero-survey.
• Inability to test for viral loads, or
additional immunologic markers to
provide further insight
• Study assumption that all lost to
follow ups died was extreme
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18. My thoughts
• Reduced study power due to a high number of lost to follow ups
• 75 sero-converters who were lost-to-follow-up
• Researchers did not specify if the laboratory persons that measured
outcome were unaware of participants’ exposure status
• ?Bias
• Researchers did not mention if there were any cross overs
• Participants that were Schistosoma negative that turned schistosoma positive
• May have lead of over estimation of the association
• Objective measurement of all possible confounders
• Exposure to STI
• HAART Adherence
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