Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA; Département d'Anesthésie et Réanimation Chirurgicale, Groupe Hospitalier Bichat Claude Bernard, Université de Paris, Assistance Publique Hôpitaux de Paris, Paris, France; Unit of Antibodies in Therapy and Pathology, Pasteur Institut, UMR 1222 INSERM, Paris, France.
Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institute of Health, Rockville, MD, USA.
Antiviral Res. 2019 Dec;172:104638. doi: 10.1016/j.antiviral.2019.104638. Epub 2019 Oct 28.
Real-time RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) is considered the gold standard for Zika virus (ZIKV) infection diagnosis, despite its low sensitivity. Diagnosis using recommended serologic cutoffs in co-circulating Flaviviruses areas maybe inadequate due to in-vitro cross-reactivities of Flaviviruses-specific antibodies. We evaluated Zika diagnosis in symptomatic patients using serial RT-PCR and develop a classification model using serial Dengue virus (DENV) and ZIKV serologies.
A prospective longitudinal multicentric study in Southern Mexico (NCT02831699) enrolled symptomatic and non-symptomatic participants. In the classification model, true positives were symptomatic (using a modified World Health Organization/Pan American Health Organization definition) with RT-PCR positive for ZIKV or DENV. True negatives were non-symptomatic with negative RT-PCR. Serial serology measurements were used to predict disease status.
Analyzing ZIKV and DENV RT-PCR at 3 timepoints between days 3 and 13 of symptom onset detected 25% more cases than a single RT-PCR analysis between day 0 and 6. When considering sensitivity and specificity together, the serial serology model predicted all categories of disease and negatives better than manufactures cutoffs. Their cutoffs optimized sensitivity or specificity but not both.
We demonstrated the importance of serial RT-PCR and antibody measurements to diagnose arbovirus infection in symptomatic patients living in regions with co-circulating flaviviruses.
实时 RT-PCR（逆转录聚合酶链反应）被认为是寨卡病毒（ZIKV）感染诊断的金标准，尽管其灵敏度较低。在流行黄病毒的地区，使用推荐的血清学截断值进行诊断可能不够充分，因为黄病毒特异性抗体存在体外交叉反应性。我们使用连续 RT-PCR 评估了有症状患者的寨卡诊断，并使用连续登革热病毒（DENV）和 ZIKV 血清学建立了分类模型。
在墨西哥南部进行的一项前瞻性纵向多中心研究（NCT02831699）纳入了有症状和无症状的参与者。在分类模型中，真阳性是指有症状（使用世界卫生组织/泛美卫生组织的改良定义）且 RT-PCR 检测到 ZIKV 或 DENV 阳性的患者。真阴性是指无症状且 RT-PCR 阴性的患者。连续的血清学测量用于预测疾病状态。
在症状出现后的第 3 天至第 13 天之间分析 ZIKV 和 DENV 的 RT-PCR，比在第 0 天至第 6 天之间进行单次 RT-PCR 分析检测到 25%更多的病例。当同时考虑灵敏度和特异性时，连续血清学模型预测所有疾病类别和阴性结果的准确性都优于制造商的截断值。它们的截断值优化了灵敏度或特异性，但不能同时优化。
我们证明了在有流行黄病毒的地区，对有症状的患者进行连续 RT-PCR 和抗体测量对于诊断虫媒病毒感染非常重要。
