Related Experiment Video
Updated: Apr 26, 2026
The α-test: Rapid Cell-free CD4 Enumeration Using Whole Saliva
Published on: May 16, 2012
Performance of cryptococcal antigen lateral flow assay using saliva in Ugandans with CD4 <100
Richard Kwizera1, Joyce Nguna1, Agnes Kiragga1
1Infectious Diseases Institute, Makerere University, Kampala, Uganda.
Background:
Cryptococcal meningitis can best be diagnosed by cerebrospinal fluid India ink microscopy, cryptococcal antigen detection, or culture. These require invasive lumbar punctures. The utility of cryptococcal antigen detection in saliva is unknown. We evaluated the diagnostic performance of the point-of-care cryptococcal antigen lateral flow assay (CrAg LFA) in saliva.
Methods:
We screened HIV-infected, antiretroviral therapy naïve persons with symptomatic meningitis (n = 130) and asymptomatic persons with CD4+<100 cells/µL entering into HIV care (n = 399) in Kampala, Uganda. The diagnostic performance of testing saliva was compared to serum/plasma cryptococcal antigen as the reference standard.
Results:
The saliva lateral flow assay performance was overall more sensitive in symptomatic patients (88%) than in asymptomatic patients (27%). The specificity of saliva lateral flow assay was excellent at 97.8% in the symptomatic patients and 100% in asymptomatic patients. The degree of accuracy of saliva in diagnosing cryptococcosis and the level of agreement between the two sample types was better in symptomatic patients (C-statistic 92.9, κ-0.82) than in asymptomatic patients (C-statistic 63.5, κ-0.41). Persons with false negative salvia CrAg tests had lower levels of peripheral blood CrAg titers (P<0.001).
Conclusion:
There was poor diagnostic performance in testing saliva for cryptococcal antigen, particularly among asymptomatic persons screened for preemptive treatment of cryptococcosis.
Insights
Saliva testing for cryptococcal antigen using a lateral flow assay showed poor accuracy, especially in asymptomatic individuals. This limits its use for diagnosing cryptococcal meningitis, particularly for preemptive treatment screening.
Area of Science:
- Infectious Diseases
- Diagnostics
- Point-of-Care Testing
Background:
- Cryptococcal meningitis diagnosis relies on invasive cerebrospinal fluid analysis.
- The diagnostic value of salivary cryptococcal antigen detection remains unestablished.
- Point-of-care assays offer potential for rapid diagnostics.
Purpose of the Study:
- To evaluate the diagnostic performance of a saliva-based cryptococcal antigen lateral flow assay (CrAg LFA).
- To compare saliva CrAg LFA results against serum/plasma cryptococcal antigen reference standards.
Main Methods:
- The study involved HIV-infected, antiretroviral therapy-naïve individuals in Kampala, Uganda.
- Symptomatic meningitis patients (n=130) and asymptomatic individuals with CD4+<100 cells/µL (n=399) were screened.
- Diagnostic performance was assessed by comparing saliva CrAg LFA to serum/plasma CrAg testing.
Main Results:
- Saliva CrAg LFA demonstrated higher sensitivity in symptomatic patients (88%) versus asymptomatic patients (27%).
- Specificity was excellent in both groups (97.8% symptomatic, 100% asymptomatic).
- Diagnostic accuracy and agreement were significantly better in symptomatic individuals.
Conclusions:
- Saliva CrAg LFA exhibited poor diagnostic performance, particularly in asymptomatic individuals.
- The assay is not recommended for screening asymptomatic populations for preemptive cryptococcosis treatment.
- Further research may be needed to improve saliva-based diagnostics for cryptococcal antigen.
