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Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: a cross-sectional study
  1. Lindi Masson1,2,
  2. Koleka Mlisana2,3,4,
  3. Francesca Little5,
  4. Lise Werner2,
  5. Nonhlanhla N Mkhize1,6,
  6. Katharina Ronacher7,
  7. Hoyam Gamieldien1,
  8. Carolyn Williamson1,2,
  9. Lyle R Mckinnon2,
  10. Gerhard Walzl7,
  11. Quarraisha Abdool Karim2,8,
  12. Salim S Abdool Karim2,8,
  13. Jo-Ann S Passmore1,2,4
  1. 1Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa
  2. 2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa
  3. 3Department of Medical Microbiology, University of KwaZulu Natal, Durban, South Africa
  4. 4National Health Laboratory Services, South Africa
  5. 5Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
  6. 6National Institute of Communicable Diseases, Johannesburg, South Africa
  7. 7Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, DST/NRF Centre of Excellence for Biomedical Tuberculosis Research and MRC Centre for Molecular and Cellular Biology, Stellenbosch University, Cape Town, South Africa
  8. 8Columbia University, New York, New York, USA
  1. Correspondence to Dr Jo-Ann Passmore, Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, Falmouth Building Level 3, University of Cape Town Medical School, Anzio Road, Observatory, Cape Town 7925, South Africa; Jo-ann.Passmore{at}uct.ac.za

Abstract

Objectives Sexually transmitted infections (STI) and bacterial vaginosis (BV) cause female genital tract inflammation. This inflammation, which is often present in the absence of symptoms, is associated with increased susceptibility to HIV infection. We aimed to evaluate genital cytokine profiles and the degree of inflammation associated with common STIs and BV.

Methods HIV-uninfected women (n=227) were screened for BV, Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus type 2 (HSV-2), and Trichomonas vaginalis. Concentrations of 42 cytokines in cervicovaginal lavages and 13 cytokines in plasma were measured using Luminex. Changes in cytokine profiles were evaluated using Mann–Whitney U test, logistic regression and factor analysis. p Values were adjusted for multiple comparisons using a false discovery rate step-down procedure.

Results Women with chlamydia or gonorrhoea had the highest genital cytokine concentrations, with 17/42 and 14/42 cytokines upregulated compared with women with no infection, respectively. BV was associated with elevated proinflammatory cytokine concentrations, but lower chemokine and haematopoietic cytokine concentrations. HSV-2 reactivation was associated with lower levels of inflammation, while trichomoniasis did not cause significant differences in genital cytokine concentrations. Genital infections did not influence plasma cytokine concentrations. Although certain STIs, in particular chlamydia and gonorrhoea, were associated with high genital cytokine concentrations, only 19% of women with an STI/BV had clinical signs.

Conclusions Chlamydia was associated with the highest genital cytokine levels, followed by gonorrhoea, HSV-2, trichomoniasis, and BV. In regions where HIV is prevalent and STIs are managed syndromically, better STI/BV screening is urgently needed, as certain infections were found to be highly inflammatory.

  • GENITAL TRACT INFECT
  • INFLAMMATION
  • BACTERIAL VAGINOSIS
  • CHLAMYDIA TRACHOMATIS
  • NEISSERIA GONORRHOEA

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