Infectious Diseases Data Observatory (IDDO), University of Oxford, NDMRB, Old Road Campus, Oxford, OX3 7FZ, UK.
Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK.
BMC Med. 2020 Sep 21;18(1):299. doi: 10.1186/s12916-020-01745-0.
In the absence of definitive diagnosis, healthcare providers are likely to prescribe empirical antibacterials to those who test negative for malaria. This problem is of critical importance in Southern Asia (SA) and South-eastern Asia (SEA) where high levels of antimicrobial consumption and high prevalence of antimicrobial resistance have been reported. To improve management and guide further diagnostic test development, better understanding is needed of the true causative agents of fever and their geographical variability.
We conducted a systematic review of published literature (1980-2015) to characterise the spectrum of pathogens causing non-malarial febrile illness in SA and SEA. We searched six databases in English and French languages: MEDLINE, EMBASE, Global Health (CABI) database, WHO Global Health Library, PASCAL, and Bulletin de la Société Française de Parasitologie (BDSP). Selection criteria included reporting on an infection or infections with a confirmed diagnosis, defined as pathogens detected in or cultured from samples from normally sterile sites, or serological evidence of current or past infection.
A total of 29,558 records from 19 countries in SA and SEA were screened, of which 2410 (8.1%) met the selection criteria. Bacterial aetiologies were reported in 1235 (51.2%) articles, viral in 846 (35.1%), parasitic in 132 (5.5%), and fungal in 54 (2.2%), and 143 (6.0%) articles reported more than one pathogen group. In descending order of frequency, Salmonella Typhi, Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, and coagulase negative Staphylococcus were the commonly reported bacteria, while dengue virus, chikungunya virus, Japanese encephalitis virus, hepatitis B virus, and hepatitis C virus were common viral pathogens reported. Reports of rarely reported or emerging pathogens included a case report of Borrelia burgdorferi (Lyme disease) in India in 2010 and reports of Nipah virus in Singapore and India.
This review summarises the reported non-malaria pathogens that may cause febrile illness in SA and SEA. The findings emphasise the need of standardising the reporting of aetiological studies to develop effective, evidence-based fever management and improved surveillance. Research and development of diagnostic tools would benefit from up-to-date epidemiological reporting of the regional diversities of non-malaria fever aetiologies.
PROSPERO registration, CRD42016049281.
在无法明确诊断的情况下，对于检测结果为疟疾阴性的患者，医疗保健提供者可能会经验性地开出抗菌药物。在南亚（SA）和东南亚（SEA）地区，这种情况非常重要，因为那里报告了高水平的抗生素使用和高比例的抗生素耐药性。为了改善管理并指导进一步的诊断测试开发，需要更好地了解引起发热的真正病原体及其地理变异性。
我们对已发表的文献（1980-2015 年）进行了系统回顾，以描述导致 SA 和 SEA 地区非疟疾性发热的病原体谱。我们在英语和法语语言的六个数据库中进行了搜索：MEDLINE、EMBASE、全球卫生（CABI）数据库、世界卫生组织全球卫生图书馆、PASCAL 和 Bulletin de la Société Française de Parasitologie（BDSP）。选择标准包括报告已确诊的感染或感染，定义为从正常无菌部位的样本中检测到或培养出的病原体，或当前或过去感染的血清学证据。
共筛选了来自 19 个 SA 和 SEA 国家的 29558 条记录，其中 2410 条（8.1%）符合选择标准。1235 篇（51.2%）文章报告了细菌病因，846 篇（35.1%）报告了病毒病因，132 篇（5.5%）报告了寄生虫病因，54 篇（2.2%）报告了真菌病因，143 篇（6.0%）报告了超过一种病原体群。按频率降序排列，伤寒沙门氏菌、大肠杆菌、金黄色葡萄球菌、肺炎克雷伯菌和凝固酶阴性葡萄球菌是常见的细菌，而登革热病毒、基孔肯雅病毒、日本脑炎病毒、乙型肝炎病毒和丙型肝炎病毒是常见的病毒病原体。罕见或新兴病原体的报告包括 2010 年印度报告的伯氏疏螺旋体（莱姆病）病例，以及新加坡和印度报告的尼帕病毒。
本综述总结了可能导致 SA 和 SEA 地区发热的报告非疟疾病原体。研究结果强调需要标准化病因研究报告，以制定有效的、基于证据的发热管理和改进监测。诊断工具的研究和开发将受益于区域性非疟疾发热病因的最新流行病学报告。
PROSPERO 注册，CRD42016049281。
