Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year.
Symptomatic versus inapparent outcome in repeat dengue virus infections is influenced by the time interval between infections and study year.
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DOI：
10.1371/journal.pntd.0002357
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发表时间：
2013
影响因子：
3.8
通讯作者：
Harris E
中科院分区：
文献类型：
--
作者：
Montoya M;Gresh L;Mercado JC;Williams KL;Vargas MJ;Gutierrez G;Kuan G;Gordon A;Balmaseda A;Harris E
四种登革热病毒血清型（DENV 1 -4）在全球传播，比任何其他虫媒病毒引起的人类疾病都多。登革热可表现为一系列临床表现，从未分化发热到登革热，再到严重的危及生命的综合征。然而，大多数DENV感染是不明显的。然而，对不明显与有症状的DENV感染结果的决定因素知之甚少。在这里，我们分析了2004年至2011年在尼加拉瓜马那瓜进行的前瞻性儿科队列研究中的2,000多例DENV感染。在研究健康中心捕获症状病例，并使用血清学方法每年检查配对的健康年度样本以识别隐性DENV感染。总体而言，隐性和症状性DENV感染按性别平均分布。与隐性感染相比，有症状的DENV感染的平均感染年龄高1.2岁。尽管不明显与症状性结局在感染数量（首次、第二次或第三次/第二次DENV感染后）方面没有差异，但在所有DENV感染中观察到症状性DENV感染比例在整个研究年中存在显著差异。在重复DENV感染的参与者中，第一次隐性DENV感染和第二次隐性感染之间的时间间隔明显短于第一次隐性感染和第二次症状性感染之间的时间间隔。在随后的感染中没有观察到这种差异。使用分别测量总抗DENV抗体和病毒型特异性中和抗体的两种不同血清学技术证实了该结果。综上所述，这些发现表明，在这项研究中，年龄，研究年份和连续DENV感染之间的时间间隔影响不明显与症状性感染的结果，而性别和感染数量没有显着影响。此外，这些结果表明，由DENV首次感染诱导的针对第二次症状性感染的交叉保护窗口约为2年。这些发现对于登革热流行建模和疫苗开发具有重要意义。蚊媒登革热病毒（DENV）的四种血清型每年感染估计1亿人，导致数千万登革热病例和数十万严重疾病病例。然而，DENV感染并不总是导致临床症状，并且大部分DENV感染是不明显的。在这里，我们研究了影响登革病毒感染是否不明显或有症状的因素。从尼加拉瓜马那瓜正在进行的儿童前瞻性队列研究中收集了7年期间超过2，000例DENV感染（1，600例隐性感染和1，400例有症状感染）的数据。我们表明，无论一个人是第一次，第二次还是第三次感染不同的DENV血清型，症状感染的比例是相似的。然而，症状性感染的比例在研究年份之间差异很大，与隐性感染相比，症状性感染倾向于发生在年龄较大的儿童中。我们还表明，如果第二次登革病毒感染发生在第一次感染后的10年内，第二次感染更有可能是不明显的。然而，如果第一次和第二次DENV感染之间的时间间隔较长，这种保护作用就会减弱，感染可能会有症状。这些发现对于登革热流行的建模和新疫苗的开发非常重要。
Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first infection with DENV against a second symptomatic infection is approximately 2 years. These findings are important for modeling dengue epidemics and development of vaccines. The four serotypes of the mosquito-borne dengue virus (DENV) infect an estimated 100 million humans annually, resulting in tens of millions of dengue cases and hundreds of thousands of cases of severe disease. However, infection with DENV does not always lead to clinical signs, and a large proportion of DENV infections are inapparent. Here, we studied the factors that influence whether a DENV infection is inapparent or symptomatic. Data from over 2,000 DENV infections (∼1,600 inapparent and ∼400 symptomatic) were collected during 7 years from an ongoing prospective cohort study of children in Managua, Nicaragua. We show that whether a person is infected for the first, the second, or the third time with different DENV serotypes, the proportion of symptomatic infections is similar. However, the proportion of symptomatic infection varied substantially across study years, and symptomatic infections tended to happen in older children when compared to inapparent infections. We also show that if a second DENV infection happens within a period of ∼2 years after the first infection, the second infection is more likely to be inapparent. However, if the time interval between first and second DENV infections is longer, this protection wanes and the infection is likely to be symptomatic. These findings are important for the modeling of dengue epidemics and the development of new vaccines.
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影响因子：
3.8
作者：
Dussart, Philippe;Baril, Laurence;da Costa Vasconcelos, Pedro Fernando
通讯作者：
da Costa Vasconcelos, Pedro Fernando
影响因子：
5
作者：
Endy, TP;Chunsuttiwat, S;Ennis, FA
通讯作者：
Ennis, FA
DOI：
10.4269/ajtmh.1988.38.172
发表时间：
1988-01-01
影响因子：
3.3
作者：
BURKE, DS;NISALAK, A;SCOTT, RM
通讯作者：
SCOTT, RM
DOI：
10.4269/ajtmh.2007.77.910
发表时间：
2007-11-01
影响因子：
3.3
作者：
Gibbons, Robert V.;Kalanarooj, Siripen;Srikiatkhachorn, Anon
通讯作者：
Srikiatkhachorn, Anon
影响因子：
3.7
作者：
Ansarah-Sobrinho, Camilo;Nelson, Steevenson;Jost, Christiane A.;Whitehead, Stephen S.;Pierson, Theodore C.
通讯作者：
Pierson, Theodore C.