Diagnostics utilized for CM in Group 3.

Meningitis affects over 2.5 million people worldwide, primarily within resource-limited regions of the meningitis belt of Africa. In 2017, we implemented a cryptococcal meningitis (CM) diagnosis and treatment program (CM-DTP) designed to improve CM outcomes. In 2021, a meningitis diagnosis and treatment program (MEN-DTP) began to include all etiologies of meningitis to assess the impact of expanded diagnosis and treatment of meningitis. We conducted a retrospective study utilizing clinical records from 1443 adult patients admitted to Lira Regional Referral Hospital (LRRH) over three time periods between 2015–2024. Group 1 included 321 patients in a historical control group; Group 2 consisted of 890 patients during the CM-DTP and Group 3 included 232 patients during the MEN-DTP. Group 1 received routine meningitis care, Group 2 received testing and treatment focused on CM, and Group 3 received expanded diagnostic testing, including gram stain, culture, PCR- and antigen-based testing. Meningitis diagnosis and in-hospital mortality outcomes were assessed to evaluate our programs. A confirmed meningitis etiology was found in 13.7% in Group 1, 20.7% in Group 2, and 42.2% in Group 3. In Group 3, confirmed etiologies were identified based on culture (n = 30), Pastorex LA (n = 23), BioFire PCR (n = 56), GeneXpert Ultra (n = 14), and serum or CSF CrAg LFA (n = 53). Overall, more confirmed etiologies of meningitis were identified among people living with HIV (PLWH) (n = 319) compared to those without HIV (n = 22) in Group 3. Antibiotic use increased with pre-admission antibiotic use doubling from Group 1 to Group 3 (10.6% to 27.2%). Compared to Group 1, mortality improved in Groups 2 and 3. Overall, PLWH had increased mortality compared to those without HIV (32.4% vs. 13.3%). Introduction of molecular diagnostics increased meningitis diagnoses and improved outcomes, particularly in those with CM. MEN-DTP increased confirmed diagnoses, yet half remained undiagnosed, supporting investigation of deep sequencing technologies.脑膜炎在全球范围内影响超过250万人，主要集中于非洲脑膜炎带的资源匮乏地区。2017年，我们启动了隐球菌性脑膜炎（cryptococcal meningitis, CM）诊疗项目（CM-DTP），旨在改善隐球菌性脑膜炎的诊疗结局。2021年，脑膜炎诊疗项目（MEN-DTP）开始覆盖所有病因类型的脑膜炎，以评估扩大脑膜炎诊疗范围的实际影响。我们针对2015年至2024年间三个时间段内，在利拉区域转诊医院（Lira Regional Referral Hospital, LRRH）收治的1443名成年患者的临床病历开展了一项回顾性研究。其中第1组为321例历史对照患者；第2组为CM-DTP实施期间的890例患者；第3组为MEN-DTP实施期间的232例患者。第1组患者接受常规脑膜炎诊疗；第2组接受针对隐球菌性脑膜炎的专项检测与治疗；第3组则接受扩展诊断检测，包括革兰染色、病原培养、聚合酶链式反应（PCR）及抗原检测。本研究以脑膜炎确诊情况及住院死亡率作为结局指标，以评估前述诊疗项目的实施效果。第1组的脑膜炎明确病因检出率为13.7%，第2组为20.7%，第3组为42.2%。第3组中，明确病因的检测依据包括：病原培养（n=30）、Pastorex LA（n=23）、BioFire PCR（n=56）、GeneXpert Ultra（n=14），以及血清或脑脊液（cerebrospinal fluid, CSF）CrAg LFA（n=53）。整体而言，第3组中人类免疫缺陷病毒感染者（people living with HIV, PLWH）的脑膜炎明确病因检出例数（n=319）显著高于非感染者（n=22）。入院前抗生素使用比例从第1组到第3组翻倍增长（10.6%升至27.2%）。与第1组相比，第2组和第3组的住院死亡率均有所改善。整体而言，人类免疫缺陷病毒感染者的死亡率（32.4%）高于非感染者（13.3%）。分子诊断技术的应用提升了脑膜炎确诊率并改善了诊疗结局，尤其在隐球菌性脑膜炎患者中效果显著。MEN-DTP项目提升了脑膜炎明确病因的检出率，但仍有半数患者未得到明确诊断，这提示亟需开展深度测序技术的相关研究。