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Peer-reviewedCC BY 4.0Arquivos de Neuro-Psiquiatria

Revisiting the use of adenosine deaminase in cerebrospinal fluid analysis for infectious meningoencephalitis

2 more authors
8 affiliations
  1. 1Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Doenças Infecciosas e Parasitárias, Laboratório de Investigação Médica em Protozoologia, Bacteriologia e Resistência Antimicrobiana (LIM 49), São Paulo SP Brazil.
  2. 2Hospital São José de Doenças Infecciosas, Fortaleza CE Brazil.
  3. 3Centro Universitário Christus, Fortaleza CE Brazil.
  4. 4Universidade Federal do Ceará, Fortaleza CE Brazil.
  5. 5Instituto de Bioestatística de Ciência e Tecnologia, Belém PA Brazil.
  6. 6Secretaria de Saúde do Estado do Ceará, Fortaleza CE Brazil.
  7. 7Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Serviço de Controle de Infecção Hospitalar, São Paulo SP Brazil.
  8. 8Hospital Sírio-Libanês, Serviço de Controle de Infecção Hospitalar, São Paulo SP Brazil.

Abstract

Background: Adenosine deaminase (ADA) levels in the cerebrospinal fluid have neither been validated as a reliable diagnostic marker nor sufficiently studied in patients with tropical diseases and human immunodeficiency virus (HIV) infection.

Objective: To investigate cerebrospinal fluid (CSF)ADA levels in different central nervous system (CNS) infections, define a cutoff value, and assess correlations between CSF-ADA and other laboratory parameters.

Methods: In 206 patients whose CSF-ADA levels were measured, we analyzed data on baseline characteristics, diagnoses, CSF-ADA levels, and additional laboratory parameters. These CSF-ADA levels were compared according to microbiological diagnosis, and correlations with other CSF and blood parameters were analyzed.

Results: Compared with the non-CNS infectious control group ( n = 40), 2 subgroups showed significantly higher CSF-ADA levels: Mycobacterium tuberculosis ( n = 45, p < 0.0001) and Neisseria meningitidis ( n = 11, p = 0.0400). The identified cutoff values were 5.5 and 7.3 IU/L for M. tuberculosis and CNS coinfections, respectively. For M. tuberculosis , sensitivity was 61.2% and specificity was 72.4%, whereas coinfections demonstrated 50% of sensitivity and 82.8% of specificity. The CSF-ADA levels correlated positively with CSF protein (Spearman rank correlation coefficient [rs] = 0.3009, p < 0.0003) and weakly correlated negatively with CSF glucose (rs = -0.1895, p < 0.0254). Patients with M. tuberculosis infection exhibited significantly higher CSF-ADA levels, as reflected by the mean, median, and standard deviation, than those with other infectious etiologies combined ( n = 121) and those with bacterial and viral infections analyzed separately ( p < 0.05). When stratified according to HIV status, a significant difference in CSF-ADA levels was observed only among patients with varicella-zoster virus infection ( p = 0.0428).

Conclusion: The CSF-ADA levels were elevated in tuberculous and meningococcal meningitis. Higher cutoff values may occur in CNS coinfections. Therefore, CSF-ADA may serve as a supportive diagnostic tool in cases of suspected TBM, meningococcal meningitis, and CNS coinfections.

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BibTeX
@article{farias2026revisiting,
  title = {{Revisiting the use of adenosine deaminase in cerebrospinal fluid analysis for infectious meningoencephalitis}},
  author = {Luis Arthur Brasil Gadelha Farias and Osvaldo Mariano Viana Neto and Ednaldo Pereira Lima Sobrinho and Giuliana de Fátima Lima Morais and Nathalia Camila Maciel Jenkins and Deborah Nayara Santos de Farias and Bruno Cavalcante Fales de Brito Alves and Aldenise de Olinda Castro and Alex de Assis Santos dos Santos and Paulo Germano de Carvalho and Tania Mara Silva Coelho and Silvia Figueiredo Costa and Maura Salaroli de Oliveira and Lauro Vieira Perdigão Neto},
  journal = {Arquivos de Neuro-Psiquiatria},
  year = {2026},
  month = oct,
  doi = {10.1055/s-0046-1829158},
  url = {https://doi.org/10.1055/s-0046-1829158},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Revisiting the use of adenosine deaminase in cerebrospinal fluid analysis for infectious meningoencephalitis
AU  - Luis Arthur Brasil Gadelha Farias
AU  - Osvaldo Mariano Viana Neto
AU  - Ednaldo Pereira Lima Sobrinho
AU  - Giuliana de Fátima Lima Morais
AU  - Nathalia Camila Maciel Jenkins
AU  - Deborah Nayara Santos de Farias
AU  - Bruno Cavalcante Fales de Brito Alves
AU  - Aldenise de Olinda Castro
AU  - Alex de Assis Santos dos Santos
AU  - Paulo Germano de Carvalho
AU  - Tania Mara Silva Coelho
AU  - Silvia Figueiredo Costa
AU  - Maura Salaroli de Oliveira
AU  - Lauro Vieira Perdigão Neto
PY  - 2026
DA  - 2026/10/27
JO  - Arquivos de Neuro-Psiquiatria
DO  - 10.1055/s-0046-1829158
UR  - https://doi.org/10.1055/s-0046-1829158
AB  - Background: Adenosine deaminase (ADA) levels in the cerebrospinal fluid have neither been validated as a reliable diagnostic marker nor sufficiently studied in patients with tropical diseases and human immunodeficiency virus (HIV) infection.  Objective: To investigate cerebrospinal fluid (CSF)ADA levels in different central nervous system (CNS) infections, define a cutoff value, and assess correlations between CSF-ADA and other laboratory parameters.  Methods: In 206 patients whose CSF-ADA levels were measured, we analyzed data on baseline characteristics, diagnoses, CSF-ADA levels, and additional laboratory parameters. These CSF-ADA levels were compared according to microbiological diagnosis, and correlations with other CSF and blood parameters were analyzed.  Results: Compared with the non-CNS infectious control group ( n = 40), 2 subgroups showed significantly higher CSF-ADA levels: Mycobacterium tuberculosis ( n = 45, p < 0.0001) and Neisseria meningitidis ( n = 11, p = 0.0400). The identified cutoff values were 5.5 and 7.3 IU/L for M. tuberculosis and CNS coinfections, respectively. For M. tuberculosis , sensitivity was 61.2% and specificity was 72.4%, whereas coinfections demonstrated 50% of sensitivity and 82.8% of specificity. The CSF-ADA levels correlated positively with CSF protein (Spearman rank correlation coefficient [rs] = 0.3009, p < 0.0003) and weakly correlated negatively with CSF glucose (rs = -0.1895, p < 0.0254). Patients with M. tuberculosis infection exhibited significantly higher CSF-ADA levels, as reflected by the mean, median, and standard deviation, than those with other infectious etiologies combined ( n = 121) and those with bacterial and viral infections analyzed separately ( p < 0.05). When stratified according to HIV status, a significant difference in CSF-ADA levels was observed only among patients with varicella-zoster virus infection ( p = 0.0428).  Conclusion: The CSF-ADA levels were elevated in tuberculous and meningococcal meningitis. Higher cutoff values may occur in CNS coinfections. Therefore, CSF-ADA may serve as a supportive diagnostic tool in cases of suspected TBM, meningococcal meningitis, and CNS coinfections.
SN  - 0004-282X
SN  - 1678-4227
ER  -