Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study
Acute Undifferentiated Febrile Illness in Rural Cambodia: A 3-Year Prospective Observational Study
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DOI：
10.1371/journal.pone.0095868
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发表时间：
2014-04-22
期刊：
影响因子：
3.7
通讯作者：
Menard, Didier
中科院分区：
文献类型：
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作者：
Mueller, Tara C.;Siv, Sovannaroth;Menard, Didier
在过去十年中，柬埔寨成功地实施了疟疾控制，导致报告病例大幅减少。疟疾快速诊断试验(RDT)的广泛使用揭示了疟疾阴性发热病例的很大负担，外围一级卫生设施没有针对这些病例的临床管理指南。作为制定此类指南的第一步，设计了一项为期3年的横断面前瞻性观察性研究，以调查柬埔寨急性疟疾阴性发热疾病的原因。从2008年1月至2010年12月，从柬埔寨东部和西部的三个卫生中心招募了1193名发烧患者和282名非发烧患者。现场由卫生中心工作人员进行疟疾RDTs和常规临床检查。采集静脉血和鼻咽部拭子，进行分子诊断试验。血液培养和血液涂片也取自所有发烧的人。对疟疾寄生虫、钩端螺旋体、立克次体、钩端螺旋体、登革热和流感病毒进行了分子检测。在73.3%(874/1193)的发热患者样本中至少发现一种病原体。检出病原菌以间日疟原虫(33.4%)、恶性疟原虫(26.5%)、致病性钩端螺旋体(9.4%)、流感病毒(8.9%)、登革病毒(6.3%)、恙虫病原虫(3.9%)、立克次体(0.2%)和诺氏钩端螺旋体(0.1%)为主。在对照组中，40.4%的人发现了潜在的病原体，最常见的是疟疾寄生虫和钩端螺旋体。RDT阴性疟疾病例的临床诊断对病原体和适当治疗的预测性很差。需要更多的研究来了解它们对临床疾病和流行病学的影响，以及多西环素等疗法的可能作用，因为这些病原体中的许多都是在非发烧的受试者中发现的。
In the past decade, malaria control has been successfully implemented in Cambodia, leading to a substantial decrease in reported cases. Wide-spread use of malaria rapid diagnostic tests (RDTs) has revealed a large burden of malaria-negative fever cases, for which no clinical management guidelines exist at peripheral level health facilities. As a first step towards developing such guidelines, a 3-year cross-sectional prospective observational study was designed to investigate the causes of acute malaria-negative febrile illness in Cambodia. From January 2008 to December 2010, 1193 febrile patients and 282 non-febrile individuals were recruited from three health centers in eastern and western Cambodia. Malaria RDTs and routine clinical examination were performed on site by health center staff. Venous samples and nasopharyngeal throat swabs were collected and analysed by molecular diagnostic tests. Blood cultures and blood smears were also taken from all febrile individuals. Molecular testing was applied for malaria parasites, Leptospira, Rickettsia, O. tsutsugamushi, Dengue-and Influenza virus. At least one pathogen was identified in 73.3% (874/1193) of febrile patient samples. Most frequent pathogens detected were P. vivax (33.4%), P. falciparum (26.5%), pathogenic Leptospira (9.4%), Influenza viruses (8.9%), Dengue viruses (6.3%), O. tsutsugamushi (3.9%), Rickettsia (0.2%), and P. knowlesi (0.1%). In the control group, a potential pathogen was identified in 40.4%, most commonly malaria parasites and Leptospira. Clinic-based diagnosis of malaria RDT-negative cases was poorly predictive for pathogen and appropriate treatment. Additional investigations are needed to understand their impact on clinical disease and epidemiology, and the possible role of therapies such as doxycycline, since many of these pathogens were seen in non-febrile subjects.