Systematic Reviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Virol. Jun 25, 2025; 14(2): 106973
Published online Jun 25, 2025. doi: 10.5501/wjv.v14.i2.106973
Uptake of lumbar puncture and mortality among patients with advanced human immunodeficiency virus disease who screened for serum cryptococcal-antigen in Africa
Haji Mbwana Ally, Hafidha Mhando Bakari, Jackline Vicent Mbishi, Zuhura Mbwana Ally, Mariam Salim Mbwana, Lynn Moshi, Rahma Musoke, Swalehe Mustafa Salim, Hassan Fredrick Fussi, Aboubakar Omar Mustafa, John Bartlet, Habib Omari Ramadhani
Haji Mbwana Ally, Department of Medicine, Kilimanjaro Christian Medical Center, Moshi 25116, Kilimanjaro, Tanzania
Hafidha Mhando Bakari, Department of Literature, Communication and Publishing, University of Dar es Salaam, Dar es Salaam 16103, Tanzania
Jackline Vicent Mbishi, Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar es Salaam 11102, Tanzania
Zuhura Mbwana Ally, Department of Medicine, District Hospital, Tanga 21628, Tanzania
Mariam Salim Mbwana, Department of Medicine, Primary Health Care Insitute, Iringa 51108, Tanzania
Lynn Moshi, Department of Obstetric and Gynecology, Aga Khan Hospital, Dar es Salaam 14112, Tanzania
Rahma Musoke, Department of Research, Water Mission, Dar es Salaam 14112, Tanzania
Swalehe Mustafa Salim, Department of Research, Canada Youth Group, Dar es Salaam 15103, Tanzania
Hassan Fredrick Fussi, Department of Medicine, District Hospital, Dar es Salaam 15103, Tanzania
Aboubakar Omar Mustafa, Department of Pharmacy, Tanga Regional Referral Hospital, Tanga 21101, Tanzania
John Bartlet, Duke University Medical Center Durham, Durham, NC 27708, United States
Habib Omari Ramadhani, Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Co-first authors: Haji Mbwana Ally and Hafidha Mhando Bakari.
Author contributions: Ally HM and Bakari HM were responsible for writing original draft; Ally HM, Bakari HM, Mbishi JV, Fussi HF, and Ramadhani HO were responsible for methodology; Ally HM, Bakari HM, Mbwana MS, Moshi L, Musoke R, Mustafa AO, and Ramadhani HO were responsible for validation; Ally HM, Bakari HM, and Ramadhani HO were responsible for conceptualization; Ally HM, Ally ZM, Mbwana MS, Moshi L, Musoke R, Mustafa AO, and Ramadhani HO were responsible for data curation; Ally HM, Mbishi JV, and Ramadhani HO were responsible for formal analysis; Mbishi JV was responsible for visualization; Fussi HF and Ramadhani HO were responsible for supervision; Ally HM, Bakari HM, Mbishi JV, Ally ZM, Mbwana MS, Moshi L, Musoke R, Salim SM, Fussi HF, Mustafa AO, Bartlet J, and Ramadhani HO were responsible for writing review and editing; all authors reviewed this manuscript, provided feedback, and approved the manuscript in its final form.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Habib Omari Ramadhani, MD, PhD, Department of Medicine, Institute of Human Virology, University of Maryland School of Medicine, 725 W Lombard Street, Baltimore, MD 21201, United States. homari@ihv.umaryland.edu
Received: March 12, 2025
Revised: April 21, 2025
Accepted: June 7, 2025
Published online: June 25, 2025
Processing time: 103 Days and 15.5 Hours
Abstract
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.

Keywords: Lumbar puncture uptake; Cryptococcal antigen; Advanced human immunodeficiency virus disease; Mortality; Africa

Core Tip: There is limited data on the compliance of the World Health Organization guideline on the management of patients with advanced human immunodeficiency virus disease (AHD). This systematic review and meta-analysis analyzed 46890 people with AHD screened for serum cryptococcal antigen (CrAg) from 32 studies conducted in Africa between 2011 and 2024. Of those screened, 2730 tested positive for serum CrAg. The uptake of lumbar puncture (LP) procedure among those with positive serum CrAg was between 55% and 68%. Mortality was higher among those with positive serum CrAg compared to those with negative serum CrAg. In Africa, among people with AHD who screened positive for CrAg, uptake of LP procedure is low, indicating gaps in the diagnosis of cryptococcal meningitis.