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Inflammatory cytokine biomarkers to identify women with asymptomatic sexually transmitted infections and bacterial vaginosis who are at high risk of HIV infection
  1. Lindi Masson1,2,
  2. Kelly B Arnold3,
  3. Francesca Little4,
  4. Koleka Mlisana2,5,
  5. David A Lewis6,7,8,
  6. Nonhlanhla Mkhize8,
  7. Hoyam Gamieldien1,
  8. Sinaye Ngcapu2,
  9. Leigh Johnson9,
  10. Douglas A Lauffenburger3,
  11. Quarraisha Abdool Karim2,10,
  12. Salim S Abdool Karim2,10,
  13. Jo-Ann S Passmore1,2,11
  1. 1Institute 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, University of KwaZulu Natal, Durban, South Africa
  3. 3Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  4. 4Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa
  5. 5School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal
  6. 6Western Sydney Sexual Health Centre, Parramatta, Australia
  7. 7Centre for Infectious Diseases and Microbiology & Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, Australia
  8. 8National Institute for Communicable Diseases, Sandringham, Johannesburg, South Africa
  9. 9Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa
  10. 10Columbia University, New York, New York, USA
  11. 11National Health Laboratory Services, South Africa
  1. Correspondence to Dr Lindi Masson, Institute of Infectious Diseases and Molecular Medicine, Division of Medical Virology, Falmouth Building Level 3, University of Cape Town Medical School, Anzio Road, Observatory, 7925, Cape Town, South Africa; Lindi.Masson{at}gmail.com

Abstract

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)-1α, IL-1β, tumour necrosis factor-β, IL-4, fractalkine, macrophage-derived chemokine, and interferon-γ) 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-1β 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-1β 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.

  • BACTERIAL VAGINOSIS
  • WOMEN
  • DIAGNOSIS
  • GENITAL TRACT INFECT
  • INFLAMMATION

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