title: Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: a cross-sectional study.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa.
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa Department of Medical Microbiology, University of KwaZulu Natal, Durban, South Africa National Health Laboratory Services, South Africa.
authors.forename: Koleka
authors.initials: K
authors.lastname: Mlisana
authors.affiliation: Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa.
authors.forename: Lise
authors.initials: L
authors.lastname: Werner
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa National Institute of Communicable Diseases, Johannesburg, South Africa.
authors.forename: Nonhlanhla N
authors.initials: NN
authors.lastname: Mkhize
authors.affiliation: Division 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.
authors.forename: Katharina
authors.initials: K
authors.lastname: Ronacher
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa.
authors.forename: Hoyam
authors.initials: H
authors.lastname: Gamieldien
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Williamson
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa.
authors.forename: Lyle R
authors.initials: LR
authors.lastname: Mckinnon
authors.affiliation: Division 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.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Walzl
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa Columbia University, New York, New York, USA.
authors.forename: Quarraisha
authors.initials: Q
authors.lastname: Abdool Karim
authors.affiliation: Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa Columbia University, New York, New York, USA.
authors.forename: Salim S
authors.initials: SS
authors.lastname: Abdool Karim
authors.affiliation: Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Medical School, Cape Town, South Africa Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa National Health Laboratory Services, South Africa.
authors.forename: Jo-Ann S
authors.initials: JA
authors.lastname: Passmore
mesh_terms: D000293:Adolescent; D000328:Adult; D001769:Blood / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000302:isolation & purification; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000032:analysis* / Q000097:blood*; D005260:Female; D018258:Herpesvirus 2, Human / Q000302:isolation & purification; D006801:Humans; D008875:Middle Aged; D009344:Neisseria gonorrhoeae / Q000302:isolation & purification; D012749:Sexually Transmitted Diseases / Q000473:pathology*; D014246:Trichomonas vaginalis / Q000302:isolation & purification; D014621:Vagina / Q000276:immunology*; D016585:Vaginosis, Bacterial / Q000473:pathology*; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: BACTERIAL VAGINOSIS; CHLAMYDIA TRACHOMATIS; GENITAL TRACT INFECT; INFLAMMATION; NEISSERIA GONORRHOEA