Pelvic inflammatory disease risk following negative results from chlamydia nucleic acid amplification tests (NAATs) versus non-NAATs in Denmark: A retrospective cohort

BackgroundNucleic Acid Amplification Tests (NAATs) are the recommended test type for diagnosing Chlamydia trachomatis (chlamydia). However, less sensitive diagnostic methods—including direct immunofluorescence (IF) and enzyme-linked immunoassay (ELISA)—remain in use in lower resourced settings. We estimate the risk of pelvic inflammatory disease (PID) following undiagnosed infection in women tested with non-NAATs and estimate the health gain from using accurate diagnostic tests.Methods and findingsWe used Denmark’s national Chlamydia Study dataset to extract all chlamydia tests performed in women aged 15–34 years (1998–2001). Tests were categorised as non-NAAT (IF/ELISA) or NAAT and limited to each woman’s first test in the study period. We linked test data to hospital presentations for PID within 12 months from the Danish National Patient Register. The study included 272,105 women with a chlamydia test, just under half (44.78%, n = 121,857) were tested using NAATs. Overall, 6.38% (n = 17,353) tested positive for chlamydia and 0.64% (n = 1,732) were diagnosed with PID within 12 months. The risk of PID following a positive chlamydia test did not differ by test type (NAAT 0.81% [95% CI 0.61–1.00], non-NAAT 0.78% [0.59–0.96]). The risk of PID following a negative test was significantly lower in women tested with NAATs compared to non-NAATs (0.55% [0.51–0.59] compared to 0.69% [0.64–0.73]; adjusted odds ratio (AOR) 0.83 [0.75–0.93]). We estimate that 18% of chlamydia infections in women tested with a non-NAAT were undiagnosed and that the risk of progression from undiagnosed chlamydia infection to PID within 12 months was 9.52% (9.30–9.68). Using non-NAATs could lead to an excess 120 cases of PID per 100,000 women tested compared to using NAATs. The key limitations of this study are under ascertainment of PID cases, misclassification bias in chlamydia and PID exposure status, bias to the association between clinical presentation and test type and the presence of unmeasured confounders (including other sexually transmitted infection [STI] diagnoses and clinical indication for chlamydia test).ConclusionThis retrospective observational study estimates the positive impact on women’s reproductive health from using accurate chlamydia diagnostic tests and provides further evidence for restricting the use of inferior tests. Women with a negative chlamydia test have a 17% higher adjusted risk of PID by 12 months if they are tested using a non-NAAT compared to a NAAT.

背景
核酸扩增试验（Nucleic Acid Amplification Tests，NAATs）是推荐用于诊断沙眼衣原体（Chlamydia trachomatis，下称衣原体）感染的检测手段。然而，灵敏度较低的诊断检测方法——包括直接免疫荧光法（direct immunofluorescence，IF）与酶联免疫吸附试验（enzyme-linked immunoassay，ELISA）——仍在资源相对匮乏的地区沿用。本研究旨在评估接受非NAATs检测的女性中，未被确诊的衣原体感染者发生盆腔炎性疾病（pelvic inflammatory disease，PID）的风险，并评估采用精准诊断检测手段所能带来的健康收益。

方法与结果
我们使用丹麦全国衣原体研究数据集，提取了1998年至2001年间15~34岁女性的所有衣原体检测数据。将检测手段分为非NAAT（IF/ELISA）与NAAT两类，且仅纳入研究周期内每位女性的首次检测结果。我们将检测数据与丹麦全国患者登记系统中12个月内因盆腔炎性疾病就诊的记录进行关联。本研究共纳入272105名接受衣原体检测的女性，其中近半数（44.78%，n=121857）采用NAATs进行检测。总体而言，6.38%（n=17353）的受试者衣原体检测结果呈阳性，且0.64%（n=1732）的受试者在12个月内被诊断为盆腔炎性疾病。衣原体检测阳性后发生PID的风险未因检测手段不同而存在显著差异：NAAT组为0.81%（95%置信区间0.61~1.00），非NAAT组为0.78%（0.59~0.96）。而检测结果为阴性的女性中，NAAT组受试者12个月内发生PID的风险显著低于非NAAT组（0.55%[0.51~0.59]相较于0.69%[0.64~0.73]；校正比值比（adjusted odds ratio，AOR）为0.83[0.75~0.93]。本研究估算，接受非NAATs检测的女性中，有18%的衣原体感染未被确诊，且未确诊的衣原体感染者在12个月内进展为PID的风险为9.52%（9.30~9.68）。与采用NAATs相比，每10万名接受检测的女性中，使用非NAATs会额外导致120例PID病例。本研究的主要局限性包括：PID病例的确诊不足、衣原体感染与PID暴露状态的分类偏倚、临床就诊与检测类型间关联的偏倚，以及存在未测量的混杂因素（包括其他性传播感染（sexually transmitted infection，STI）诊断及衣原体检测的临床指征）。

结论
本项回顾性观察研究评估了采用精准衣原体检测手段对女性生殖健康的积极影响，并为限制低效检测手段的使用提供了进一步证据。与采用NAATs检测的女性相比，接受非NAATs检测且衣原体结果为阴性的女性，在12个月内发生PID的校正后风险高出17%。