Publications & Reports

Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection.

Lindi Masson, Kelly B Arnold, Francesca Little, Koleka Mlisana, David A Lewis, Nonhlanhla Mkhize, Hoyam Gamieldien, Sinaye Ngcapu, Leigh Johnson, Douglas A Lauffenburger, Quarraisha Abdool Karim, Salim S Abdool Karim, Jo-Ann S Passmore
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, University of KwaZulu Natal, Durban, South Africa.


BACKGROUND: Untreated sexually transmitted infections (STIs) and bacterial vaginosis (BV) cause genital inflammation and increase the risk of HIV infection. WHO-recommended syndromic STI and BV management is severely limited as many women with asymptomatic infections go untreated. The purpose of this cross-sectional study was to evaluate genital cytokine profiles as a biomarker of STIs and BV to identify women with asymptomatic, treatable infections. METHODS: Concentrations of 42 cytokines in cervicovaginal lavages from 227 HIV-uninfected women were measured using Luminex. All women were screened for BV by microscopy and STIs using molecular assays. Multivariate analyses were used to identify cytokine profiles associated with STIs/BV. RESULTS: A multivariate profile of seven cytokines (interleukin (IL)-1alpha, IL-1beta, tumour necrosis factor-beta, IL-4, fractalkine, macrophage-derived chemokine, and interferon-gamma) most accurately predicted the presence of a treatable genital condition, with 77% classification accuracy and 75% cross-validation accuracy (sensitivity 72%; specificity 81%, positive predictive value (PPV) 86%, negative predictive value (NPV) 64%). Concomitant increased IL-1beta and decreased IP-10 concentrations predicted the presence of a treatable genital condition without a substantial reduction in predictive value (sensitivity 77%, specificity 72%, PPV 82% and NPV 65%), correctly classifying 75% of the women. This approach performed substantially better than clinical signs (sensitivity 19%, specificity 92%, PPV 79% and NPV 40%). CONCLUSIONS: Supplementing syndromic management with an assessment of IL-1beta and IP-10 as biomarkers of genital inflammation may improve STI/BV management for women, enabling more effective treatment of asymptomatic infections and potentially reducing their risk of HIV infection.


  • Journal: Sexually Transmitted Infections
  • Published: 01/05/2016
  • Volume: 92
  • Issue: 3
  • Pagination: 186-193