Uptake of lumbar puncture and mortality among patients with advanced human immunodeficiency virus disease who screened for serum cryptococcal-antigen in Africa.

Background: The World Health Organization (WHO) recommends lumbar puncture (LP) procedures to assess the diagnosis of cryptococcal meningitis (CM) among patients with advanced human immunodeficiency virus (HIV) disease (AHD) with positive serum cryptococcal antigen (CrAg) and do not have evidence of CM.

Aim: To estimate pooled prevalence of uptake of LP, CM and mortality among patients with AHD.

Methods: PubMed, Cochrane Library and EMBASE were searched for articles published between January 2011 and December 2024. LP uptake was defined as percentage of people who underwent LP procedures among those with AHD (CD4 ≤ 200 cells/mm³ or WHO stage III/IV) and positive serum CrAg. Using random effects models, we computed the pooled estimate of LP uptake, CM and mortality and 95%CI. Stratified analyses were used to compare uptake of LP between studies that involved multiple vs single sites, and mortality analyses between patients with positive and negative serum CrAg were performed. Sensitivity analysis on LP uptake was done by excluding prospective cohort studies that reported 100% uptake.

Results: A total of 32 studies with 46890 people with AHD screened for serum CrAg and 2730 (5.8%) had positive serum CrAg. Overall, pooled prevalence of LP uptake was 67.7% (95%CI: 54.0-81.5). The overall pooled prevalence of CM was 54.3% (95%CI: 39.7-69.0), and mortality was 6.2% (95% CI: 4.5-8.0). There is disparities in the pooled prevalence of LP uptake with studies involving multiple sites having lower prevalence compared to those that involved single sites (54.8% vs 84.7%, P = 0.004). By excluding prospective cohort studies that reported 100% uptake, the overall LP uptake was 54.5% (95%CI: 38.8-70.1). The pooled prevalence of CM was significantly lower among studies that involved multiple sites compared to those that involved single sites (6.8% vs 8.1%, P ≤ 0.001). Mortality was significantly twice as high among patients who had positive serum CrAg compared to those who had negative serum CrAg [risk ratio = 2.0 (95%CI: 1.6-2.5), P ≤ 0.001].

Conclusion: Nearly three to five in 10 people with AHD with positive serum CrAg did not have LP procedures done, indicating significant gaps in identifying patients with CM. Establishing a confirmed diagnosis of CM is critical to avoid exposing patients to subtherapeutic levels of antifungals preemptively. Capacity to perform LP and patient refusals are among the reasons for not performing the procedure. Capacity building in training health care providers to perform LP procedures and professional counselling to obtain patient consent are critical for appropriate treatment to reduce mortality associated with CM infection.