Rickettsial infections in Malaysia

描述（由申请人提供）：非疟疾性急性发热性疾病（AFI）在世界范围内引起的发病率和死亡率高于疟疾。非疟疾性AFI的负担被低估，因为重叠的临床表现和缺乏和/或有限的获得确认性诊断测试。最常见的原因包括登革热、伤寒和副伤寒、钩端螺旋体病和立克次体感染，这些疾病由于几个原因而特别成问题。首先，有限的研究表明立克次体感染可能是东南亚某些地区AFI最常见的原因。其次，确认立克次体病是特别困难的，因为这些细胞内细菌感染内皮细胞，因此，既不易培养，也不丰富的血液样本。最后，经验性地用于AFI的广谱抗菌药物，如青霉素和头孢菌素，对立克次体无效。虽然丛林斑疹伤寒于1912年首次在马来西亚被发现，鼠斑疹伤寒在周边国家流行，但在过去20年中，马来西亚卫生部几乎没有报告立克次体病病例。案件少的部分原因可能是 缺乏可用的检测来急性诊断这些感染，因为20世纪80年代的一项研究和最近的血清调查证实，马来西亚经常（2 - 9%的献血者和12 - 44%的发热患者住院）存在抗立克次体抗体。虽然登革热的流行引起了相当大的关注，但大多数参加登革热样发热性疾病（马来西亚卫生部倡导的临床标准）研究的患者被发现没有登革热，其疾病的病因往往仍未确定。我们推测，在马来西亚沙巴及周边地区，相当一部分非疟疾、非登革热的AFI是由未确诊的立克次体感染引起的。为了验证这一假设，我们建议使用血清，全血，血沉棕黄层，焦痂标本从前瞻性招募急性未分化发热性疾病的患者队列，以确定和表征可疑的立克次体感染。我们提出以下具体目标：目标1。证明在马来西亚沙巴非疟疾性急性发热性疾病患者中立克次体感染的发生率并描述其流行病学。目标二。目的明确我国斑疹热、斑疹伤寒群立克次体感染和恙虫病的种或菌株亚结构。 马来西亚，沙巴。这项工作将记录在马来西亚沙巴发生的立克次体感染，描绘其相关的流行病学特征，并确定该地区目前存在的物种和菌株。此外，我们将为后续详细的前瞻性研究提供所需的初步数据，这些研究可以更全面地确定马来西亚立克次体病与其他AFI原因的发病率和患病率，从而为管理非疟疾AFI提供合理的科学依据。

DESCRIPTION (provided by applicant): Non-malarial acute febrile illness (AFI) causes greater morbidity and mortality world-wide than malaria. The burden of non-malarial AFI is underappreciated, because of overlapping clinical presentations and lack of and/or limited access to confirmatory diagnostic tests. The most frequent causes include dengue, typhoid and paratyphoid fever, leptospirosis, and rickettsial infections, which are particularly problematic fo several reasons. First, limited studies suggest rickettsial infections may be the most common cause of AFI in some regions of Southeast Asia. Second, confirming rickettsioses is particularly difficult because these intra-cellular bacteria infect endothelial cells and, therefore, are neithe readily-cultivable nor abundant in samples of blood. Finally, the broad-spectrum, antimicrobial agents used empirically for AFI, such as penicillins and cephalosporins, are ineffective against rickettsiae. Although scrub typhus was first recognized in Malaysia in 1912 and murine typhus is endemic in surrounding countries, almost no cases of rickettsial disease were reported by the Malaysian Ministry of Health over the last 2 decades. The paucity of cases is likely due in part to the lack of available tests to diagnose these infections acutely, since a study from the 1980s and more recent serosurveys confirm the frequent (2 to 9% of blood donors and 12 to 44% of febrile patients presenting to hospital) presence of anti-rickettsial antibodies in Malaysia. Although epidemics of dengue attract considerable attention, most patients enrolled in studies of dengue-like febrile illness (clinical criteria advocated by the Malaysian Ministry of Health) are found to not have dengue and the etiology of their illness often remains undetermined. We hypothesize that a substantial proportion of the non-malaria, non-dengue AFI in Sabah, Malaysia and surrounding regions results from undiagnosed rickettsial infections. To test this hypothesis, we propose to use serum, whole blood, buffy coat, and eschar specimens from a cohort of patients enrolled prospectively with acute undifferentiated febrile illness to identify ad characterize unsuspected rickettsial infections. We propose the following specific aims: Aim 1. To demonstrate the occurrence and describe the epidemiology of rickettsial infections among patients with non-malarial acute febrile illness in Sabah, Malaysia. Aim 2. To define the species or strain substructure of spotted fever and typhus group rickettsial infections and scrub typhus in Sabah, Malaysia. This work will document the occurrence of rickettsial infections in Sabah, Malaysia, delineate their associated epidemiological features, and define the species and strains that are now present in this region. Additionally, we will generate preliminary data needed for subsequent detailed prospective studies that can more fully define the incidence and prevalence of rickettsial disease versus other causes of AFI in Malaysia and, thereby, provide a rational scientific basis for managing non-malarial AFI.