Postzone phenomenon resulting in a false-negative cerebral spinal fluid cryptococcal antigen lateral flow assay

Yadava, Sanjay; Fazili, Tasaduq

doi:10.1097/qad.0000000000002157

Cited by 7 publications

(16 citation statements)

References 9 publications

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“…In addition, it is worth cautioning that a negative test does not exclude the possibility of cryptococcal infection; and false-negative reactions may be attributed to other interfering factors (eg, post-zone phenomenon, also known as the ‘hook’ effect, the presence of immunocomplexes preventing release of glucuronoxylomannan antigen) or in cats with localized disease. 2 , 3 , 16 , 26 , 39 , 40 In the case presented herein, the manufacturer of the Meridian Premier Cryptococcal Antigen EIA test kit initiated an urgent voluntary medical device recall of three test kit lots between 17 December 2018 through 30 April 2020 (United States Food and Drug Administration Class 2 Device Recall: PREMIER Cryptococcal Antigen enzyme immunoassay [Recall number. Z-0732-2019], lot numbers: 602096K089, 602096K090, 602096K091).…”

Section: Discussionmentioning

confidence: 99%

Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results

McEwan

Sykes

2022

Journal of Feline Medicine and Surgery Open Reports

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Case summary An indoor-only 6-year-old spayed female domestic cat was evaluated for a history of stertorous respiration. Skull radiographs revealed increased soft tissue density within the caudal aspect of the left nasal cavity. CT and rhinoscopy revealed a mass lesion in the choana, plus a smaller lesion, nearly completely occluding flow through the nasal passages. Rhinoscopy was used to collect a biopsy specimen from a fleshy, tan–yellow mass visualized in the caudal nasopharynx. Histopathology was diagnostic for Cryptococcus species infection and systemic antifungal therapy with fluconazole was initiated. Following a series of discordant results, serum samples were submitted to a veterinary diagnostic laboratory that utilized a cryptococcal antigen latex agglutination system with pretreatment of serum with pronase. Twenty-three months after the initial diagnosis, the cat’s serum cryptococcal antigen titer declined to 1:5 and the cat has responded well to continuing treatment. Relevance and novel information This case illustrates challenges associated with discordant test results for cryptococcal antigen among laboratories. Discordancies may be due to differences in assay design, or the underlying disease state itself, or whether serum is pre-treated with pronase; with some tests relying on the training and experience of the operator if the cryptococcal antigen detection test requires a subjective interpretation. It also resolves some confusion in the literature related to the assay types available and terminology used to describe them, and emphasizes the importance of considering cryptococcosis as an important differential for cats with upper respiratory signs, without nasal discharge, even if the cat is kept exclusively indoors.

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Section: Discussionmentioning

confidence: 99%

Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results

McEwan

Sykes

2022

Journal of Feline Medicine and Surgery Open Reports

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“…Case Reports in Infectious Diseases inflammation-induced vasospasms, and thrombosis presenting as lacunar infarctions often in the thalamus, internal capsule, basal ganglia, and rarely the brainstem, as occurred in this patient [19]. e LFA, LA, and EIA have been shown to have sensitivities and specificities as high as 100% in detecting cryptococcal antigen in the CSF [20].…”

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confidence: 53%

“…A complication of chronic cerebral meningitis is lacunar cerebral infarctions. Infection can lead to vasculitis, inflammation-induced vasospasms, and thrombosis presenting as lacunar infarctions often in the thalamus, internal capsule, basal ganglia, and rarely the brainstem, as occurred in this patient [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

False-Negative CSF Cryptococcal Antigen with Cryptococcus gattii Meningoencephalitis in Southeastern United States: A Case Report and Literature Review

Esperti¹,

Stoelting²,

Mangano³

et al. 2020

Case Reports in Infectious Diseases

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A 70-year-old immunocompetent male in South Carolina was admitted secondary to altered mental status and headache without focal neurological deficits. Head CT was negative. Lumbar puncture (LP) revealed normal glucose, elevated protein, and lymphocytosis. Opening pressure was 15 cm of H20. CSF lateral flow assay was negative for cryptococcal antigen; CSF cultures showed no growth. The patient rapidly improved on acyclovir and was diagnosed with presumed viral meningitis, as viral PCR and fungal culture were pending at time of discharge. The patient’s condition quickly worsened and the patient returned one day later with right arm weakness and dysarthria. Brain MRI revealed T2/flair signal abnormalities in the left frontal lobe with associated parenchymal enhancement. Repeat LP revealed increasing white blood cell count with a worsening lymphocytosis and decreasing glucose, and opening pressure remained normal. CSF fungal culture from the first admission grew Cryptococcus gattii, and repeated CSF cryptococcal antigen and culture returned positive. The patient was started on IV steroids, induction Amphotericin and Fluconazole, followed by maintenance oral Fluconazole. The patient’s clinical course was complicated by a brainstem lacunar infarction, which led to demise. We present this case of Cryptococcus gattii meningoencephalitis to highlight the risk factors, characteristics, and challenges in diagnosis and treatment of an emerging disease in the Southeastern United States.

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“…Six were in the CSF and in HIV-infected patients. [15][16][17][18] However, the only specimens tested were CSF. A retrospective study of patients with culture-confirmed CM showed that the CrAg LFA had 100% sensitivity in the serum.…”

Section: Discussionmentioning

confidence: 99%

<p>False-Negative Serum Cryptococcal Antigen Lateral Flow Immunoassay Result for a Patient with Disseminated Cryptococcal Disease</p>

Xu¹,

Xia²,

Ni³

2020

IDR

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Cryptococcus neoformans (C. neoformans) is an opportunistic fungal pathogen to humans, which can be acquired from environmental sources. Its most important virulence factor is its polysaccharide capsule, which can be used for diagnostic tests that identify the cryptococcal antigen (CrAg). The CrAg lateral flow assay (LFA) is a dipstick immunochromatographic assay with high sensitivity and specificity; however, several false-negative cases have been reported. Here, we present a case of a false-negative serum CrAg LFA, in which the blood culture from a matched sample was positive for C. neoformans, thus demonstrating the postzone phenomenon.

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Postzone phenomenon resulting in a false-negative cerebral spinal fluid cryptococcal antigen lateral flow assay

Cited by 7 publications

References 9 publications

Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results

Nasopharyngeal cryptococcosis in a cat: interlaboratory variation in cryptococcal antigen assay test results

False-Negative CSF Cryptococcal Antigen with Cryptococcus gattii Meningoencephalitis in Southeastern United States: A Case Report and Literature Review

<p>False-Negative Serum Cryptococcal Antigen Lateral Flow Immunoassay Result for a Patient with Disseminated Cryptococcal Disease</p>

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