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. 2025 Jan 24;20(1):e0313453.
doi: 10.1371/journal.pone.0313453. eCollection 2025.

Systematic review on the compliance of WHO guidelines in the management of patients with advanced HIV disease in Africa: The case of cryptococcal antigen screening

Zuhura Mbwana Ally  1 , Jackline Vicent Mbishi  2 , Mariam Salim Mbwana  3 , Hafidha Mhando Bakari  4 , Swalehe Mustafa Salim  5 , Zarin Nudar Rodoshi  6 , Muhidin Ibrahim Hundisa  7 , Rebecca Mesfin Sileshi  8 , Biruk Demisse Ayalew  8 , Rahma Musoke  9 , Lynn Moshi  10 , Yousef Elias Fakhoury  11 , Haji Mbwana Ally  12 , Habib Omari Ramadhani  12
Affiliations

Systematic review on the compliance of WHO guidelines in the management of patients with advanced HIV disease in Africa: The case of cryptococcal antigen screening

Zuhura Mbwana Ally et al. PLoS One. .

Abstract

Background: The World Health Organization (WHO) recommended cryptococcal antigen (CrAg) screening for people presenting with advanced HIV disease (AHD) and for those with positive CrAg without evidence of meningitis to initiate preemptive antifungal medication. Data on the implementation of WHO recommendations regarding CrAg screening is limited. We estimated pooled prevalence of CrAg screening uptake, cryptococcal antigenemia, lumbar puncture, cryptococcal meningitis and initiation of preemptive antifungal medication from available eligible published studies conducted in Africa.

Methods: PubMed, Cochrane Library and Embase were searched for articles published between January 2011 and December 2023. CrAg uptake was defined as percentage of eligible people (CD4 ≤ 200 cells/mm3 or WHO stage III/IV) who received cryptococcal antigen testing. Stratified analysis to compare uptake and cryptococcal antigenemia between studies that involved multiple vs single sites was performed. Using random effects models, we computed the pooled estimate of CrAg screening uptake, cryptococcal antigenemia, lumbar puncture, cryptococcal meningitis, preemptive antifungals treatment and 95% confidence intervals (CIs).

Results: Ten studies with 18,820 individuals with AHD were analyzed. Overall, the pooled estimate of CrAg screening uptake was 57.1% (95% CI: 41.4-72.7). CrAg screening uptake was significantly lower among studies that involved multiple sites compared to those that involved single site, (47.3% vs 73.3%; p<0.001). Overall, the pooled prevalence of cryptococcal antigenemia was 9.6% (95% CI:6.4-12.9). Cryptococcal antigenemia was significantly lower among studies that involved multiple sites compared to those that involved single site, (9.1% vs 10.4%; p<0.001). Among those who tested positive for CrAg, 84.6% (95% CI: 54.1-99.0) received preemptive antifungal treatment, though nearly 25% did not undergo lumbar puncture, highlighting gaps in diagnostic follow-up. Six studies evaluated CrAg positive patients with lumbar puncture and the overall prevalence of lumbar puncture was 74.9% (48.0-94.8). The overall prevalence of cryptococcal meningitis was 58.1% (46.6-69.6).

Conclusions: Not screening for CrAg among people with AHD and failure to initiate antifungal medications among eligible patients with cryptococcal antigenemia presents a significant missed opportunity. Emphasis on improving CrAg screening is critical given its proven cost-effective benefits.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. PRISMA flow diagram of the included studies for meta-analysis of on the compliance of WHO guidelines in the management of patients with advanced HIV disease in Africa.
Fig 2
Fig 2. Overall prevalence of CrAg screening uptake among people living with HIV in Africa.
Fig 3
Fig 3. Influential analysis on the overall prevalence of CrAg screening uptake among people living with HIV in Africa.
Fig 4
Fig 4. Overall prevalence of cryptococcal antigenemia among people living with HIV in Africa.
Fig 5
Fig 5. Influential analysis on the overall prevalence of cryptococcal antigenemia among people living with HIV in Africa.
See this image and copyright information in PMC

References

    1. Castelnuovo B, Manabe YC, Kiragga A, Kamya M, Easterbrook P, Kambugu A. Cause-specific mortality and the contribution of immune reconstitution inflammatory syndrome in the first 3 years after antiretroviral therapy initiation in an urban African cohort. Clin Infect Dis 2009; 49(6): 965–72. doi: 10.1086/605500 - DOI - PubMed
    1. Rajasingham R, Govender NP, Jordan A, et al.. The global burden of HIV-associated cryptococcal infection in adults in 2020: a modelling analysis. Lancet Infect Dis 2022; 22(12): 1748–55. doi: 10.1016/S1473-3099(22)00499-6 - DOI - PMC - PubMed
    1. Rajasingham R, Smith RM, Park BJ, et al.. Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis. Lancet Infect Dis 2017; 17(8): 873–81. doi: 10.1016/S1473-3099(17)30243-8 - DOI - PMC - PubMed
    1. Wykowski J, Galagan SR, Govere S, et al.. Cryptococcal antigenemia is associated with meningitis or death in HIV-infected adults with CD4 100–200 cells/mm(3). BMC Infect Dis 2020; 20(1): 61. doi: 10.1186/s12879-020-4798-1 - DOI - PMC - PubMed
    1. Ford N, Shubber Z, Jarvis JN, et al.. CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis. Clin Infect Dis 2018; 66(suppl_2): S152–s9. doi: 10.1093/cid/cix1143 - DOI - PMC - PubMed

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