Serotype-specific epidemiological patterns of inapparent versus symptomatic primary dengue virus infections: a 17-year cohort study in Nicaragua

IF 36.4 1区医学 Q1 INFECTIOUS DISEASES

Lancet Infectious Diseases Pub Date : 2024-10-25 DOI:10.1016/s1473-3099(24)00566-8

Sandra Bos, José Victor Zambrana, Elias Duarte, Aaron L Graber, Julia Huffaker, Carlos Montenegro, Lakshmanane Premkumar, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris

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引用次数: 0

Abstract

Background

Dengue is the most prevalent mosquito-borne viral disease and a major public health problem worldwide. Most primary infections with the four dengue virus serotypes (DENV1–4) are inapparent; nonetheless, whether the distribution of symptomatic versus inapparent infections by serotype varies remains unknown. Here, we present (1) the evaluation of a DENV1–4 envelope domain III multiplex microsphere-based assay (EDIII-MMBA) to serotype inapparent primary infections and (2) its application leveraging 17 years of prospective sample collection from the Nicaraguan Pediatric Dengue Cohort Study (PDCS).

Methods

We analysed primary DENV infections in the PDCS from 2004 to 2022 detected by inhibition ELISA (iELISA) or RT-PCR. First, we evaluated the performance of the EDIII-MMBA for serotyping with samples characterised by RT-PCR or focus reduction neutralisation test. Next, we analysed a subset of inapparent primary DENV infections in the PDCS with the EDIII-MMBA to evaluate the epidemiology of inapparent infections. Remaining infections were inferred using stochastic imputation, taking year and neighbourhood into account. Infection incidence and percentage of inapparent, symptomatic, and severe infections were analysed by serotype.

Findings

Between Aug 30, 2004, and March 10, 2022, a total of 5931 DENV-naive participants were followed in the PDCS. There were 1626 primary infections (382 symptomatic, 1244 inapparent) detected by iELISA or RT-PCR over the study period. The EDIII-MMBA demonstrated excellent overall accuracy (100%, 95% CI 95·8–100) for serotyping inapparent primary DENV infections when evaluated against gold-standard serotyping methods. Of the 1244 inapparent infections, we analysed 574 (46%) using the EDIII-MMBA. We found that the majority of primary infections were inapparent, with DENV3 exhibiting the highest likelihood of symptomatic (pooled odds ratio compared with DENV1: 2·13, 95% CI 1·28–3·56) and severe (6·75, 2·01–22·62) primary infections, whereas DENV2 was similar to DENV1 in both analyses. Considerable within-year and between-year variation in serotype distribution between symptomatic and inapparent infections and circulation of serotypes undetected in symptomatic cases were observed in multiple years.

Interpretation

Our study indicates that case surveillance skews the perceived epidemiological footprint of DENV. We reveal a more complex and intricate pattern of serotype distribution in inapparent infections. The substantial differences in infection outcomes by serotype emphasises the need for vaccines with balanced immunogenicity and efficacy across serotypes.

Funding

National Institute of Allergy and Infectious Diseases (National Institutes of Health) and Bill & Melinda Gates Foundation.

Translation

For the Spanish translation of the abstract see Supplementary Materials section.

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无症状与有症状原发性登革热病毒感染的血清型特异性流行病学模式：尼加拉瓜一项为期 17 年的队列研究

背景登革热是最流行的蚊媒病毒性疾病，也是全球主要的公共卫生问题。四种登革热病毒血清型（DENV1-4）的大多数原发感染是不明显的；然而，有症状感染与不明显感染的分布是否因血清型而异仍是未知数。在此，我们介绍了：（1）对基于微球的 DENV1-4 包膜域 III 多重检测法（EDIII-MMBA）进行评估，以确定不明显的原发性感染血清型；（2）利用尼加拉瓜儿科登革热队列研究（PDCS）17 年的前瞻性样本收集对该检测法进行应用。首先，我们评估了 EDIII-MMBA 通过 RT-PCR 或病灶还原中和试验对样本进行血清分型的性能。接着，我们用EDIII-MMBA分析了PDCS中不明显的原发性DENV感染，以评估不明显感染的流行病学。剩余的感染病例采用随机估算法进行推断，并将年份和邻近地区考虑在内。研究结果2004年8月30日至2022年3月10日期间，PDCS共对5931名未感染过DENV的参与者进行了随访。在研究期间，通过iELISA或RT-PCR检测到1626例原发性感染（382例有症状，1244例无症状）。与金标准血清分型方法相比，EDIII-MMBA在对不明显的原发性DENV感染进行血清分型时表现出了极高的总体准确性（100%，95% CI 95-8-100）。在 1244 例不明显的感染中，我们使用 EDIII-MMBA 分析了 574 例（46%）。我们发现，大多数原发性感染都是不明显的，其中 DENV3 出现无症状（与 DENV1 相比的汇总几率比：2-13，95% CI 1-28-3-56）和严重（6-75，2-01-22-62）原发性感染的可能性最大，而 DENV2 在这两项分析中的表现与 DENV1 相似。我们的研究表明，病例监测歪曲了人们对 DENV 流行病学足迹的认识。我们揭示了隐性感染中血清型分布更为复杂和错综复杂的模式。不同血清型的感染结果存在巨大差异，这强调了我们需要在不同血清型之间平衡免疫原性和有效性的疫苗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Lancet Infectious Diseases 医学-传染病学

CiteScore

60.90

自引率

0.70%

发文量

1064

审稿时长

6-12 weeks

期刊介绍： The Lancet Infectious Diseases was launched in August, 2001, and is a lively monthly journal of original research, review, opinion, and news covering international issues relevant to clinical infectious diseases specialists worldwide.The infectious diseases journal aims to be a world-leading publication, featuring original research that advocates change or sheds light on clinical practices related to infectious diseases. The journal prioritizes articles with the potential to impact clinical practice or influence perspectives. Content covers a wide range of topics, including anti-infective therapy and immunization, bacterial, viral, fungal, and parasitic infections, emerging infectious diseases, HIV/AIDS, malaria, tuberculosis, mycobacterial infections, infection control, infectious diseases epidemiology, neglected tropical diseases, and travel medicine. Informative reviews on any subject linked to infectious diseases and human health are also welcomed.