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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.

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

SUBMITTER: Masson L

PROVIDER: S-EPMC6801014 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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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.

Masson Lindi L Arnold Kelly B KB Little Francesca F Mlisana Koleka K Lewis David A DA Mkhize Nonhlanhla N Gamieldien Hoyam H Ngcapu Sinaye S Johnson Leigh L Lauffenburger Douglas A DA Abdool Karim Quarraisha Q Abdool Karim Salim S SS Passmore Jo-Ann S JA

Sexually transmitted infections 20151028 3

<h4>Background</h4>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.<h4>Methods</h4>Concentrations of 42 cy ...[more]

PMID: 26511781

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Project description:BackgroundEstimates of sexually transmitted infection (STI) prevalence are essential for efforts to prevent and control STIs. Few large STI prevalence studies exist, especially for low- and middle-income countries (LMICs). Our primary objective was to estimate the prevalence of chlamydia, gonorrhea, trichomoniasis, syphilis, herpes simplex virus type 2 (HSV-2), and bacterial vaginosis (BV) among women in sub-Saharan Africa by age, region, and population type.Methods and findingsWe analyzed individual-level data from 18 HIV prevention studies (cohort studies and randomized controlled trials; conducted during 1993-2011), representing >37,000 women, that tested participants for ?1 selected STIs or BV at baseline. We used a 2-stage meta-analysis to combine data. After calculating the proportion of participants with each infection and standard error by study, we used a random-effects model to obtain a summary mean prevalence of each infection and 95% confidence interval (CI) across ages, regions, and population types. Despite substantial study heterogeneity for some STIs/populations, several patterns emerged. Across the three primary region/population groups (South Africa community-based, Southern/Eastern Africa community-based, and Eastern Africa higher-risk), prevalence was higher among 15-24-year-old than 25-49-year-old women for all STIs except HSV-2. In general, higher-risk populations had greater prevalence of gonorrhea and syphilis than clinic/community-based populations. For chlamydia, prevalence among 15-24-year-olds was 10.3% (95% CI: 7.4%, 14.1%; I2 = 75.7%) among women specifically recruited from higher-risk settings for HIV in Eastern Africa and was 15.1% (95% CI: 12.7%, 17.8%; I2 = 82.3%) in South African clinic/community-based populations. Among clinic/community-based populations, prevalence was generally greater in South Africa than in Southern/Eastern Africa for most STIs; for gonorrhea, prevalence among 15-24-year-olds was 4.6% (95% CI: 3.3%, 6.4%; I2 = 82.8%) in South Africa and was 1.7% (95% CI: 1.2%, 2.6%; I2 = 55.2%) in Southern/Eastern Africa. Across the three primary region/population groups, HSV-2 and BV prevalence was high among 25-49-year-olds (ranging from 70% to 83% and 33% to 44%, respectively). The main study limitation is that the data are not from random samples of the target populations.ConclusionsCombining data from 18 HIV prevention studies, our findings highlight important features of STI/BV epidemiology among sub-Saharan African women. This methodology can be used where routine STI surveillance is limited and offers a new approach to obtaining critical information on STI and BV prevalence in LMICs.

Dataset Information

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

Publications

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

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