AdenoPlus point-of-care test for diagnosing adenoviral conjunctivitis

Study component

Description

Objectives/hypotheses

To compare the sensitivity and specificity of the AdenoPlus test with those of both viral cell culture with confirmatory immunofluorescence assay and polymerase chain reaction in detecting the presence of adenovirus in tear fluid.

Study design

Prospective diagnostic accuracy study (n=128).

Tear samples were collected from 1 affected eye of each patient. The AdenoPlus test results were analysed by an independent, masked healthcare professional^a.

Reference tests used: CC‑IFA for AdenoPlus, PCR for AdenoPlus, both CC‑IFA and PCR for AdenoPlus, and PCR for cell culture respectively.

Setting

Multicentre study at 8 private ophthalmology practices and academic centres in the USA during June 2009–June 2011.

Inclusion/exclusion criteria

The enrolment criteria included onset of symptoms (red eye) within 7 days, a history of spread of infection from 1 eye to the other or recent upper respiratory infection, the presence of follicles or a preauricular node, and symptoms of discharge, eyelash matting, itching, or foreign body sensation. Patients with a corneal ulcer, trauma, allergy to Dacron, or recent medication use were excluded.

Primary outcomes

Sensitivity, specificity, PPV, NPV, and overall agreement.

Statistical methods

Not stated.

Conclusions

AdenoPlus is sensitive and specific for detecting adenoviral conjunctivitis.

Abbreviations: CC‑IFA, cell culture with confirmatory immunofluorescence assay; NPV, negative predictive value; n, number of patients; PCR, polymerase chain reaction; PPV, positive predictive value.

^aNo further information about the mask. It was unclear whether 'masked' means that the person who analysed the AdenoPlus results was blinded to the patient's clinical symptoms and signs.

Patients included

A total of 128 sequential patients with a clinical diagnosis of acute viral conjunctivitis, aged from 5 to 90 years; 76 females (59%) and 52 males (41%).

Outcomes

Of the 128 patients enrolled, the results were positive by either CC‑IFA or PCR in 36 patients. Positive results were found in 29 patients by both CC‑IFA and PCR.

When compared with CC‑IFA, AdenoPlus showed a sensitivity of 90% (28/31), a specificity of 96% (93/97), a NPV of 97% (93/96), a PPV of 88% (28/32), and an overall agreement of 95% (121/128).

When compared with PCR, AdenoPlus showed a sensitivity of 85% (29/34), a specificity of 98% (89/91), a NPV of 95% (89/94), a PPV of 94% (29/31), and an overall agreement of 94% (118/125).

When compared with both CC‑IFA and PCR, AdenoPlus showed a sensitivity of 93% (27/29) and specificity of 98% (88/90).

When compared with PCR, CC‑IFA showed a sensitivity of 85% (29/34), a specificity of 99% (90/91), a NPV of 95% (90/95), a PPV of 97% (29/30), and an overall agreement of 95% (119/125).

Abbreviations: CC‑IFA, cell culture with confirmatory immunofluorescence assay; NPV, negative predictive value; n, number of patients; PCR, polymerase chain reaction; PPV, positive predictive value.

Study component

Description

Objectives/hypotheses

To estimate the diagnostic accuracy of the AdenoPlus point‑of‑care adenoviral test compared with PCR in an ophthalmic accident and emergency service.

Study design

Cross‑sectional, diagnostic accuracy study.

AdenoPlus testing was carried out on the more severely affected eye of each patient. PCR analysis was also done on a swab taken from the same eye. AdenoPlus and PCR results were interpreted by personnel masked to the results of the other testing type^a. Sensitivity and specificity for the AdenoPlus test were calculated using PCR results as the reference standard.

Setting

A walk‑in ophthalmic A&E in the UK. Year and duration unclear.

Inclusion/exclusion criteria

Patients presenting to the walk‑in ophthalmic A&E, who had a preliminary diagnosis of adenoviral conjunctivitis based on their clinical signs and symptoms, were eligible for entry into this study. The clinical signs and symptoms that elicited suspicion of adenoviral infection were recorded according to a prospectively designed checklist. These patients were seen and recruited by either an experienced specialist ophthalmic nurse practitioner or an ophthalmologist of at least Specialty Trainee Year 3 level. Patients were recruited consecutively, but guidelines were not given as to the threshold of severity at which patients should be included; so the decision to include a potentially eligible patient was made by the attending clinician.

Exclusion: patients who declined AdenoPlus testing; patients aged under 16 years; those who had an onset of symptoms more than 2 weeks before presentation; anyone who had a concurrent corneal ulcer of any form; those who had a history of recent trauma to the eye; and those who had an allergy to Dacron.

Primary outcomes

Sensitivity and specificity.

Statistical methods

Not stated.

Conclusions

The AdenoPlus test has a high specificity in the diagnosis of adenoviral conjunctivitis, but in this study the authors could not reproduce the high sensitivity that was previously published.

Abbreviations: A&E, accident and emergency department; n, number of patients; PCR, polymerase chain reaction.

^aThe PCR result was automatically generated (including results for herpes simplex and Chlamydia trachomatis), but occasionally manually entered into the database by qualified biomedical staff masked to the result of the AdenoPlus test. AdenoPlus test results were analysed by an independent member of clinical staff (ophthalmologist of at least Specialty Training Year 3 level or specialist ophthalmic nurse practitioner) masked to the PCR results who had no previous contact with the patient or the clinical notes.

Patients included

A total of 109 consecutive patients presenting to an emergency eye unit with a clinical picture of acute adenoviral conjunctivitis and meeting the inclusion criteria of the study.

Of these 109 patients, 55 were male (50.5%) and 54 were female (49.5%). The mean age was 40 years (range 16–85 years). In terms of severity, 38% of patients had bilateral conjunctivitis, and the median number of symptoms and signs listed by each patient was 6 (IQR 5 to 8).

Outcomes

Using PCR as the reference standard, the sensitivity of the AdenoPlus swab in detecting adenovirus was 39.5% (17/43; 95% CI 25 to 56), specificity was 95.5% (63/66; 95% CI 87 to 99), PPV was 85% (95% CI 62.11 to 96.79), and NPV 70.79% (95% CI 60.19 to 79.95). The authors report the positive (8.7; 95% CI 2.71 to 27.9) and negative (0.63; 95% CI 0.49 to 0.81) likelihood ratios incorrectly as PPV and NPV. No adverse events from doing the AdenoPlus or PCR test were reported.

Abbreviations: CI, confidence interval; IQR, interquartile range; NPV, negative predictive value; n, number of patients; PCR, polymerase chain reaction; PPV, positive predictive value.

Study component

Description

Objectives/hypotheses

To assess the clinical characteristics (signs and symptoms) and incidence of adenovirus conjunctivitis in patients who present with signs and symptoms of acute conjunctivitis.

Study design

Cross sectional epidemiology study.

Setting

Data from the 334 patients recruited from 16 sites (3 to 60 patients per site) in France (database extraction date not reported). All sites but 1 were hospital ophthalmology departments. Study year and duration unclear.

Inclusion/exclusion criteria

Before inclusion, patients had to give oral consent.

To participate in the study, patients had to present with acute signs and symptoms of conjunctivitis lasting for less than 7 days. The minimum age was 1 year.

Exclusion criteria: patients who had already used local antiviral therapies, topical steroids or immuno‑modulators; had a history of sensitivity to corn starch, talcum powder or Dacron (sampling fleece components); previous enrolment in the study and direct involvement or family link with the study site.

Primary outcomes

The percentage of AdenoPlus test positives or negatives.

Statistical methods

Not stated.

Patients included

Patients with acute signs and symptoms of conjunctivitis for less than 7 days: 334.

Mean age 42 years (range 5–89 years). Most (81%) of the 334 patients were 18–65 years of age, 13% of the patients were over 65 years of age and 6% were under the age of 18 years. Female: 57%.

Results

Of the users, 74% rated the ease of doing the AdenoPlus test as good or acceptable and 61% of the patients judged that the test was good or excellent.

The percentage of AdenoPlus positive results was 36% (121/334) among the tested patients. Two invalid AdenoPlus test results have been reported (0.6%; no further information about this was provided).

In 89% of the 334 patients, the investigators believed the conjunctivitis was of viral origin. The authors stated that 49% of the investigators had their clinical assessment confirmed by the test. No further details were available that would allow clear interpretation of the results reported.

Of the 334 patients, 7.2% had protocol deviations at inclusion, mostly for using topical corticosteroids.

Conclusions

More than one‑third of patients who presented with signs and symptoms of acute conjunctivitis suspected as being viral were actually diagnosed with adenoviral conjunctivitis using AdenoPlus.

The patients testing positive for adenovirus presented more signs and symptoms compared with the other patients, although none of them were definitive signs of the disease.

The investigator's initial clinical assessment was not confirmed in half of the patients.

In real‑life conditions, the AdenoPlus test may be a useful tool in helping early differential diagnosis in patients with conjunctivitis signs and symptoms lasting for 7 days or less.