Department of Internal Medicine, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone.
Ministry of Health and Sanitation, Government of Sierra Leone, Freetown, Sierra Leone.
BMC Infect Dis. 2020 Feb 14;20(1):141. doi: 10.1186/s12879-020-4862-x.
The global annual estimate for cryptococcal disease-related deaths exceeds 180,000, with three fourth occurring in sub-Saharan Africa. The World Health Organization (WHO) recommends cryptococcal antigen (CrAg) screening in all HIV patients with CD4 count < 100/μl. As there is no previous published study on the burden and impact of cryptococcal disease in Sierra Leone, research is needed to inform public health policies. We aimed to establish the seroprevalence and mortality of cryptococcal disease in adults with advanced HIV attending an urban tertiary hospital in Sierra Leone.
A prospective cohort study design was used to screen consecutive adult (18 years or older) HIV patients at Connaught Hospital in Freetown, Sierra Leone with CD4 count below 100 cells/mm from January to April 2018. Participants received a blood CrAg lateral flow assay (IMMY, Oklahoma, USA). All participants with a positive serum CrAg had lumbar puncture and cerebrospinal fluid (CSF) CrAg assay, and those with cryptococcal diseases had fluconazole monotherapy with 8 weeks followed up. Data were entered into Excel and analysed in Stata version 13.0. Proportions, median and interquartile ranges were used to summarise the data. Fisher's exact test was used to compare categorical variables.
A total of 170 patients, with median age of 36 (IQR 30-43) and median CD4 count of 45 cells/mm (IQR 23-63) were screened. At the time of enrolment, 54% were inpatients, 51% were newly diagnosed with HIV, and 56% were either ART-naïve or newly initiated (≤ 30 days). Eight participants had a positive blood CrAg, giving a prevalence of 4.7% (95% CI: 2.4-9.2%). Of those with a positive CrAg, CSF CrAg was positive in five (62.5%). Five (62.5%) CrAg-positive participants died within the first month, while the remaining three were alive and established on ART at 8 weeks.
A substantial prevalence of cryptococcal antigenaemia and poor outcome of cryptococcal disease were demonstrated in our study. The high mortality suggests a need for the HIV programme to formulate and implement policies on screening and pre-emptive fluconazole therapy for all adults with advanced HIV in Sierra Leone, and advocate for affordable access to effective antifungal therapies.
全球每年因隐球菌病相关死亡人数超过 18 万,其中四分之三发生在撒哈拉以南非洲。世界卫生组织(WHO)建议对所有 CD4 计数<100/μl 的 HIV 患者进行隐球菌抗原(CrAg)筛查。由于塞拉利昂以前没有关于隐球菌病负担和影响的发表研究,因此需要开展研究为公共卫生政策提供信息。我们旨在确定在塞拉利昂一家市级三级医院就诊的晚期 HIV 成人中隐球菌病的血清流行率和死亡率。
采用前瞻性队列研究设计,于 2018 年 1 月至 4 月期间在塞拉利昂弗里敦的康诺特医院筛查连续入组的 CD4 计数<100 个细胞/mm 的成人(18 岁或以上)HIV 患者。参与者接受 IMMY(美国俄克拉荷马州)侧向流隐球菌抗原检测。所有血清 CrAg 阳性的参与者均进行腰椎穿刺和脑脊液(CSF)CrAg 检测,确诊为隐球菌病的患者接受氟康唑单药治疗 8 周并进行随访。数据输入 Excel 并在 Stata 版本 13.0 中进行分析。使用比例、中位数和四分位数范围来总结数据。使用 Fisher 确切检验比较分类变量。
共筛查了 170 名患者,中位年龄为 36 岁(IQR 30-43),中位 CD4 计数为 45 个细胞/mm(IQR 23-63)。入组时,54%为住院患者,51%为新诊断的 HIV 患者,56%为初次接受抗逆转录病毒治疗(≤30 天)。8 名参与者的血液 CrAg 检测呈阳性,阳性率为 4.7%(95%CI:2.4-9.2%)。CrAg 阳性者中有 5 人(62.5%)CSF CrAg 阳性。5 名(62.5%)CrAg 阳性患者在第一个月内死亡,其余 3 名在 8 周时存活并开始接受 ART 治疗。
本研究表明,隐球菌抗原血症的患病率相当高,且隐球菌病的预后较差。高死亡率表明 HIV 规划需要制定和实施政策,对塞拉利昂所有晚期 HIV 成人进行筛查和预防性氟康唑治疗,并倡导获得负担得起的有效抗真菌治疗。