Pleural Fluid Adenosine Deaminase (Pfada) in the Diagnosis of Tuberculous Effusions in a Low Incidence Population

Arnold, David; Bhatnagar, Rahul; Fairbanks, Lynette D.; Zahan-Evans, Natalie; Clive, Amelia O; Morley, Anna; Medford, Andrew R L; Maskell, Nicholas

doi:10.1371/journal.pone.0113047

Cited by 21 publications

(14 citation statements)

References 25 publications

(27 reference statements)

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“…Specificity of ADA in low prevalence areas has also been estimated. In a study done in north-western Europe, 338 patients with effusions were analyzed, and when an ADA cut-off of 35 U/L was used in combination with lymphocytic effusions, sensitivity was 90.9% and specificity was 98.9% [6]. In our study, pleural fluid CBNAAT was found to be positive in only 32% of cases, and rifampicin resistance was seen in 8.3%.…”

Section: Discussionmentioning

confidence: 48%

The Role of Genexpert in the Diagnosis of Tubercular Pleural Effusion in India

Chakraborty

Ramaswamy

Shivananjiah

et al. 2019

Advances in Respiratory Medicine

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Introduction: Tubercular pleural effusion is the second most common extrapulmonary form of tuberculosis in India. Developing nations like India face several health challenges and with limited resources, appropriate planning and channelization of the same is the need of the hour. Material and methods: The objective of the study was to determine the role of cartridge-based nucleic acid amplification test (CBNAAT) in the diagnosis of tubercular pleural effusion (TPE) and also to study if any association exists between CBNAAT and pleural fluid adenosine deaminase (ADA) and lymphocyte counts. Clinically suspected TPE, lymphocyte predominant (≥ 70%) exudates (according to the Lights criteria) with ADA ≥ 40 U/L and microbiologically confirmed pulmonary tuberculosis patients with a co-existent pleural effusion were included. Pleural fluid CBNAAT was performed on all the samples. Results: Out of a total of 75 patients, 57 were males and 18 were females. A lymphocyte predominance of ≥ 70% was seen in 73 subjects (97%). Mean ADA was 61.7 U/L ± 16.2 (SD). Pleural fluid CBNAAT was positive for Mycobacterium tuberculosis (MTB) in 24 patients (32%). Out of these patients, rifampicin resistance was detected in 2 individuals (8.3%). Sputum smear for acid fast bacilli (AFB) was positive in 3 (4%) patients, whereas in sputum CBNAAT MTB was detected in 8 (10.6%) persons. Association between pleural fluid ADA, lymphocyte count and CBNAAT positivity was evaluated by Student T-test. There was a significant association between higher ADA levels and CBNAAT (p value = 0.001). Conclusions: Pleural fluid CBNAAT, owing to its low sensitivity, should not be included in the diagnostic protocol of TPE in high prevalence areas. A high ADA ≥ 40 U/L in combination with Light's criteria to define exudates, with lymphocyte predominance is sufficient evidence to diagnose TPE and initiate anti-tubercular therapy, thereby deferring the need to perform an invasive pleural biopsy.

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Section: Discussionmentioning

confidence: 48%

The Role of Genexpert in the Diagnosis of Tubercular Pleural Effusion in India

Chakraborty

Ramaswamy

Shivananjiah

et al. 2019

Advances in Respiratory Medicine

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“…Indeed, the paucibacillary aspect of tuberculous pleural effusion renders diagnosis difficult. Even in low incidence populations, pleural fluid measurement of ADA showed a high negative predictive value of 99.7% and a good sensitivity of 85.7% . Specifically, ADA2 is elevated in tuberculous pleural effusion and a reduction in ADA2 correlates with treatment response .…”

Section: The Human Adenosine Deaminase Enzymes: a Historical Perspectivementioning

confidence: 97%

“…Even in low incidence populations, pleural fluid measurement of ADA showed a high negative predictive value of 99.7% and a good sensitivity of 85.7%. 30 Specifically, ADA2 is elevated in tuberculous pleural effusion and a reduction in ADA2 correlates with treatment response. 27 ADA2 is produced by live MTB-infected macrophages.…”

Section: The Discovery Of Ada2 and The Genes That Encode It In Invementioning

confidence: 99%

Human adenosine deaminase 2 deficiency: A multi‐faceted inborn error of immunity

Moens

Hershfield

Arts

et al. 2018

Immunological Reviews

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Human adenosine deaminase 1 deficiency was described in the 1970s to cause severe combined immunodeficiency. The residual adenosine deaminase activity in these patients was attributed to adenosine deaminase 2. Human adenosine deaminase type 2 deficiency (DADA2), due to biallelic deleterious mutations in the ADA2 gene, is the first described monogenic type of small‐ and medium‐size vessel vasculitis. The phenotype of DADA2 also includes lymphoproliferation, cytopenia, and variable degrees of immunodeficiency. The physiological role of ADA2 is still enigmatic hence the pathophysiology of the condition is unclear. Preliminary data showed that in the absence of ADA2, macrophage differentiation is skewed to a pro‐inflammatory M1 subset, which is detrimental for endothelial integrity. The inflammatory phenotype responds well to anti‐TNF therapy with etanercept and that is the first‐line treatment for prevention of severe vascular events including strokes. The classic immunosuppressive drugs are not successful in controlling the disease activity. However, hematopoietic stem cell transplantation (HSCT) has been shown to be a definitive cure in DADA2 patients who present with a severe cytopenia. HSCT can also cure the vascular phenotype and is the treatment modality for patients’ refractory to anti‐cytokine therapies. In this review, we describe what is currently known about the molecular mechanisms of DADA2. Further research on the pathophysiology of this multifaceted condition is needed to fine‐tune and steer future therapeutic strategies.

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“…They also demonstrated the levels were higher with advanced stage of disease and there remains a significant relationship between Fibulin 3 and survival (Pass et al, 2012). Further studies on Fibulin-3 have not been able to replicate these results, more recently Creaney et al demonstrated Fibulin 3 to be of low specificity for mesothelioma where a large number of patients with benign aetiology showing elevated levels of Fibulin 3 (Creaney et al, 2014).…”

Section: Fibulinmentioning

confidence: 99%