Krueger Whitney S, Khuntirat Benjawan, Yoon In-Kyu, Blair Patrick J, Chittagarnpitch Malinee, Putnam Shannon D, Supawat Krongkaew, Gibbons Robert V, Bhuddari Darunee, Pattamadilok Sirima, Sawanpanyalert Pathom, Heil Gary L, Gray Gregory C
College of Public Health and Health Professions and Emerging Pathogens Institute, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2013 Aug 16;8(8):e72196. doi: 10.1371/journal.pone.0072196. eCollection 2013.
In 2008, 800 rural Thai adults living within Kamphaeng Phet Province were enrolled in a prospective cohort study of zoonotic influenza transmission. Serological analyses of enrollment sera suggested this cohort had experienced subclinical avian influenza virus (AIV) infections with H9N2 and H5N1 viruses.
After enrollment, participants were contacted weekly for 24 mos for acute influenza-like illnesses (ILI). Cohort members confirmed to have influenza A infections were enrolled with their household contacts in a family transmission study involving paired sera and respiratory swab collections. Cohort members also provided sera at 12 and 24 months after enrollment. Serologic and real-time RT-PCR assays were performed against avian, swine, and human influenza viruses.
Over the 2 yrs of follow-up, 81 ILI investigations in the cohort were conducted; 31 (38%) were identified as influenza A infections by qRT-PCR. Eighty-three household contacts were enrolled; 12 (14%) reported ILIs, and 11 (92%) of those were identified as influenza infections. A number of subjects were found to have slightly elevated antibodies against avian-like A/Hong Kong/1073/1999(H9N2) virus: 21 subjects (2.7%) at 12-months and 40 subjects (5.1%) at 24-months. Among these, two largely asymptomatic acute infections with H9N2 virus were detected by >4-fold increases in annual serologic titers (final titers 1:80). While controlling for age and influenza vaccine receipt, moderate poultry exposure was significantly associated with elevated H9N2 titers (adjusted OR = 2.3; 95% CI, 1.04-5.2) at the 24-month encounter. One subject had an elevated titer (1:20) against H5N1 during follow-up.
From 2008-10, evidence for AIV infections was sparse among this rural population. Subclinical H9N2 AIV infections likely occurred, but serological results were confounded by antibody cross-reactions. There is a critical need for improved serological diagnostics to more accurately detect subclinical AIV infections in humans.
2008年，来自泰国彭世洛府的800名农村成年人参与了一项关于人畜共患流感传播的前瞻性队列研究。对入组时采集的血清进行的血清学分析表明，该队列曾经历过H9N2和H5N1病毒的亚临床禽流感病毒（AIV）感染。
入组后，每周与参与者联系，持续24个月，以了解急性流感样疾病（ILI）情况。确诊为甲型流感感染的队列成员与其家庭接触者一起纳入一项家庭传播研究，该研究涉及配对血清和呼吸道拭子采集。队列成员还在入组后12个月和24个月时提供血清。针对禽、猪和人流感病毒进行了血清学和实时RT-PCR检测。
在2年的随访期间，对该队列进行了81次ILI调查；通过qRT-PCR鉴定出31例（38%）为甲型流感感染。83名家庭接触者入组；12人（14%）报告有ILI，其中11人（92%）被鉴定为流感感染。发现一些受试者针对禽源样A/香港/1073/1999（H9N2）病毒的抗体略有升高：12个月时为21名受试者（2.7%），24个月时为40名受试者（5.1%）。其中，通过年度血清学滴度增加4倍以上（最终滴度1:80）检测到两例基本无症状的H9N2病毒急性感染。在控制年龄和流感疫苗接种情况后，在24个月随访时，适度的家禽接触与H9N2滴度升高显著相关（调整后的OR = 2.3；95% CI，1.04 - 5.2）。一名受试者在随访期间针对H5N1的滴度升高（1:20）。
2008年至2010年期间，该农村人群中AIV感染的证据稀少。可能发生了亚临床H9N2 AIV感染，但血清学结果因抗体交叉反应而混淆。迫切需要改进血清学诊断方法，以更准确地检测人类的亚临床AIV感染。
