背景:在(亚)热带低资源环境中,尽管进行了初步治疗,但仍持续存在的发热性疾病是常见的临床挑战。我们的目的是回顾“长期发烧”(持续发热疾病,PFI)并量化诊断选择有限的选定被忽视的目标疾病的相对贡献,经常被忽视,导致抗生素处方不足,或需要长期和潜在的毒性治疗。
方法:我们使用PRISMA指南对亚热带低收入和中等收入国家(LMICs)成人和儿童PFI感染性病因的文章进行了系统评价。目标疾病清单,包括被忽视的寄生虫和人畜共患细菌(例如,利什曼原虫和布鲁氏菌),由传染病和热带医学专家鉴定,并在搜索中优先考虑。由于完善的流行病学和诊断选择,疟疾和结核病(TB)未被列为目标疾病。四名共同研究者在评估偏倚风险的同时,从已确定的文章中独立提取数据。
结果:纳入了来自52个国家的196篇文章,117来自非洲(33个国家),71来自亚洲(16个国家),和8来自中美洲和南美洲(3个国家)。在几乎一半的文章中,目标疾病被报道为PFI的原因,最常见的立克次体病(包括斑疹伤寒),复发性发热(RF-borreliosis),布鲁氏菌病,肠热,钩端螺旋体病,Q发热和利什曼病。其中,RF-borreliosis是迄今为止非洲最常见的疾病,特别是在东非。立克次体病(包括斑疹伤寒)在非洲和亚洲都经常被描述。利什曼病,弓形虫病和阿米巴病是最常见的寄生虫病。非目标疾病和非热带生物(肺炎链球菌,大肠杆菌,和非伤寒沙门氏菌属)记录在五分之一的文章中。
结论:在亚/热带LMIC中面临PFI的临床医生应考虑广泛的鉴别诊断,包括肠道热和人畜共患细菌疾病(例如,立克次体病,RF-borreliosis和布鲁氏菌病),或寄生虫感染(例如,利什曼病)取决于地理和综合症。如果没有足够的诊断能力,针对相关细胞内细菌的抗生素试验,如多西环素或阿奇霉素,可以考虑。
BACKGROUND: Febrile illnesses that persist despite initial treatment are common clinical challenges in (sub)tropical low-resource settings. Our aim is to review infectious etiologies of \"prolonged fevers\" (persistent febrile illnesses, PFI) and to quantify relative contributions of selected neglected target diseases with limited diagnostic options, often overlooked, causing inadequate antibiotic prescriptions, or requiring prolonged and potentially toxic treatments.
METHODS: We performed a systematic review of articles addressing the infectious etiologies of PFI in adults and children in sub-/tropical low- and middle-income countries (LMICs) using the PRISMA guidelines. A list of target diseases, including neglected parasites and zoonotic bacteria (e.g., Leishmania and Brucella), were identified by infectious diseases and tropical medicine specialists and prioritized in the search. Malaria and tuberculosis (TB) were not included as target diseases due to well-established epidemiology and diagnostic options. Four co-investigators independently extracted data from the identified articles while assessing for risk of bias.
RESULTS: 196 articles from 52 countries were included, 117 from Africa (33 countries), 71 from Asia (16 countries), and 8 from Central and -South America (3 countries). Target diseases were reported as the cause of PFI in almost half of the articles, most frequently rickettsioses (including scrub typhus), relapsing fever borreliosis (RF-borreliosis), brucellosis, enteric fever, leptospirosis, Q fever and leishmaniasis. Among those, RF-borreliosis was by far the most frequently reported disease in Africa, particularly in Eastern Africa. Rickettsioses (including scrub typhus) were often described in both Africa and Asia. Leishmaniasis, toxoplasmosis and amoebiasis were the most frequent parasitic etiologies. Non-target diseases and non-tropical organisms (Streptococcus pneumoniae, Escherichia coli, and non-typhoidal Salmonella spp) were documented in a fifth of articles.
CONCLUSIONS: Clinicians faced with PFI in sub-/tropical LMICs should consider a wide differential diagnosis including enteric fever and zoonotic bacterial diseases (e.g., rickettsiosis, RF-borreliosis and brucellosis), or parasite infections (e.g., leishmaniasis) depending on geography and syndromes. In the absence of adequate diagnostic capacity, a trial of antibiotics targeting relevant intra-cellular bacteria, such as doxycycline or azithromycin, may be considered.