# Phasing out India ink: the case for the CrAg LFA in modern practice

**Authors:** Sejal Morjaria, Derick Iturralde, Brenden Clarck, N. Esther Babady

PMC · DOI: 10.1128/spectrum.01531-25 · Microbiology Spectrum · 2025-12-05

## TL;DR

This paper argues for replacing the outdated India ink test with the more accurate CrAg LFA for diagnosing cryptococcal meningitis.

## Contribution

The study provides evidence supporting the replacement of India ink with CrAg LFA for improved diagnostic accuracy.

## Key findings

- India ink had 42.9% sensitivity compared to 100% for CrAg LFA and multiplex PCR.
- CrAg LFA and PCR offer superior sensitivity, ease of use, and reproducibility.
- Replacing India ink can improve detection and patient outcomes in immunocompromised individuals.

## Abstract

Cryptococcal meningitis remains a life-threatening infection, particularly in immunocompromised patients, and timely, accurate diagnosis is essential. In a retrospective review of 489 cerebrospinal fluid samples at a tertiary cancer center, the India ink stain demonstrated low sensitivity (42.9%) compared to lateral flow antigen (100%) and multiplex PCR (100%) methods. These findings support replacing the outdated, labor-intensive India ink test with more accurate, rapid diagnostics to improve detection and patient outcomes.

The India ink test has historically been a cornerstone of cryptococcal diagnosis, but its low sensitivity and reliance on subjective interpretation make it increasingly obsolete in modern practice. Continued reliance on India ink risks delayed or missed diagnoses, particularly in immunocompromised patients where early detection is critical. In contrast, the cryptococcal antigen lateral flow assay (CrAg LFA) and other modern diagnostics provide superior sensitivity, ease of use, and reproducibility. Phasing out India ink in favor of the CrAg LFA is essential to align clinical practice with contemporary diagnostic standards and to improve patient outcomes.

## Linked entities

- **Diseases:** cryptococcal meningitis (MONDO:0005723)

## Full-text entities

- **Genes:** AGAP3 (ArfGAP with GTPase domain, ankyrin repeat and PH domain 3) [NCBI Gene 116988] {aka AGAP-3, CENTG3, CRAG, MRIP-1, cnt-g3}
- **Diseases:** Cryptococcal meningitis (MESH:D016919), infection (MESH:D007239), cancer (MESH:D009369)
- **Chemicals:** cryptococcal antigen (-), India ink (MESH:C028433)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

19 references — full list in the complete paper: https://tomesphere.com/paper/PMC12772231/full.md

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Source: https://tomesphere.com/paper/PMC12772231