Rickettsial infections in Malaysia

描述（由申请人提供）：非疟疾性急性发热性疾病（AFI）在世界范围内比疟疾引起更高的发病率和死亡率。由于临床表现重叠以及缺乏和/或获得确证性诊断测试的机会有限，非疟疾性AFI的负担未得到充分重视。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，由于几个原因，这些感染尤其成问题。首先，有限的研究表明立克次体感染可能是东南亚一些地区AFI最常见的原因。其次，确认立克次体病特别困难，因为这些细胞内细菌感染内皮细胞，因此，既不容易培养，也不丰富的血液样本。最后，广谱抗菌药物，经验用于AFI，如青霉素和头孢菌素，对立克次体无效。虽然1912年在马来西亚首次发现了丛林斑疹伤寒，鼠斑疹伤寒在周边国家流行，但马来西亚卫生部在过去20年里几乎没有报告立克次体病病例。病例稀少的部分原因可能是

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.