School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda.
Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, P.O Box 7072, Uganda.
BMC Health Serv Res. 2022 Mar 4;22(1):301. doi: 10.1186/s12913-022-07624-z.
Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities.
We conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap.
We evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/μL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0-75.7) of patients' records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4-86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3-64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0-27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7-92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6-30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening.
There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation.
无症状隐球菌抗原血症（CrAg）患者在检测呈阳性后的一个月内会发展为脑膜炎。预防性抗真菌治疗可以预防隐球菌性脑膜炎（CM）的进展。2016 年 4 月，乌干达在 206 家提供抗逆转录病毒治疗的大容量卫生机构启动了全国性的 CrAg 筛查计划。我们报告了对 CrAg 筛查级联的评估，重点是关联护理、氟康唑治疗 10 周和 6 个月随访，以及在部分机构启动抗逆转录病毒治疗。
在该计划实施一年后，我们对七个城市和七个农村设施中 CD4<100 的 359 名患者进行了回顾性、横断面调查。我们量化了在六个月随访期间，患者通过 CrAg 筛查级联的各个步骤的数量。我们将级联完成定义为在最初的 10 周内开具预防性氟康唑处方。我们对实验室人员和诊所工作人员进行了半结构化访谈，以评估 CrAg 筛查计划的功能。数据使用 REDCap 收集。
我们评估了 2016 年 4 月至 2017 年 3 月期间的 359 份患者记录；大多数（358/359，99.7%）来自政府所有的卫生机构，超过一半（193/359，53.8%）的患者的基线 CD4 细胞计数<50 个/μL。总体而言，在 359 份患者记录中，有 255 份（71.0%，95%置信区间，66.0-75.7%）进行了 CrAg 筛查，其中城市设施的比例较高（170/209（81.3%，95%置信区间，75.4-86.4%）高于农村设施（85/150（56.7%，95%置信区间，48.3-64.7%））。在接受 CrAg 筛查的患者中，有 56/255（22.0%，95%置信区间，17.0-27.5%）的患者有隐球菌抗原血症，其中 47/56（83.9%，95%置信区间，71.7-92.4%）的患者开始预防性氟康唑治疗，其中 8/47（17.0%，95%置信区间，7.6-30.8%）在 6 个月随访时仍在接受抗真菌治疗。在有抗原血症的患者中，有 70%（39/56）至少有一个中枢神经系统症状。在开始接受抗逆转录病毒治疗的患者中，几乎有 40%的患者在 CrAg 筛查前开始接受抗逆转录病毒治疗。15/26（58%）的人员报告设备/用品不足是该计划的障碍，而 13/26（50%）的人员报告需要关于 CM 和 CrAg 筛查的培训。
在开始氟康唑治疗后，患者的随访存在严重差距。在进行 CrAg 筛查之前，几乎有 40%的患者开始接受抗逆转录病毒治疗。抗原血症较高的患者出现中枢神经系统症状可能与晚期出现有关。在进行更全面的评估后，需要解决这些差距。
