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

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.

• Authors: 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
• Journal: Sexually transmitted infections (Sex Transm Infect) Vol. 92 Issue 3 Pg. 186-93 (May 2016) ISSN: 1472-3263 [Electronic] England
• PMID: 26511781 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Chemical References

• Biomarkers
• Cell Cycle Proteins
• Chemokine CXCL10
• Cytokines
• Interleukin-1beta
• TSPY1 protein, human

Topics

• Adolescent
• Biomarkers (analysis)
• Cell Cycle Proteins (genetics)
• Cervix Uteri (chemistry)
• Chemokine CXCL10 (analysis)
• Cross-Sectional Studies
• Cytokines (analysis)
• Female
• HIV Infections (etiology, prevention & control)
• Humans
• Interleukin-1beta (analysis)
• Logistic Models
• Middle Aged
• Predictive Value of Tests
• ROC Curve
• Sensitivity and Specificity
• Sexually Transmitted Diseases (complications, diagnosis)
• Therapeutic Irrigation
• Vagina (chemistry)
• Vaginosis, Bacterial (complications, diagnosis)
• Young Adult