Research Spotlight

Tenforde, M.W., Talbot, H.K., Trabue, C.H., Gaglani, M., McNeal, T.M., Monto, A.S., Martin, E.T., Zimmerman, R.K., Silveira, F., Middleton, D.B., Olson, S.M., Garten Kondor, R.J., Barnes, J.R., Ferdinands, J.M. and Patel, M.M. (2020). “Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020.” J Infect Dis Dec 30;jiaa800. [Epub ahead of print].

Full text of this article.

BACKGROUND: Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. METHODS: We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. RESULTS: 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. CONCLUSIONS: In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

Tenforde, M.W., Kondor, R.J.G., Chung, J.R., Zimmerman, R.K., Nowalk, M.P., Jackson, M.L., Jackson, L.A., Monto, A.S., Martin, E.T., Belongia, E.A., McLean, H.Q., Gaglani, M., Rao, A., Kim, S.S., Stark, T.J., Barnes, J.R., Wentworth, D., Patel, M.M. and Flannery, B. (2020). “Effect of antigenic drift on influenza vaccine effectiveness in the United States – 2019-2020.” Clin Infect Dis Dec 25;ciaa1884. [Epub ahead of print].

Full text of this article.

BACKGROUND: At the start of the 2019-2020 influenza season, concern arose that circulating B/Victoria viruses of the globally emerging clade V1A.3 were antigenically drifted from the strain included in the vaccine. Intense B/Victoria activity was followed by circulation of genetically diverse A(H1N1)pdm09 viruses, that were also antigenically drifted. We measured vaccine effectiveness (VE) in the United States against illness from these emerging viruses. METHODS: We enrolled outpatients aged ≥6 months with acute respiratory illness at five sites. Respiratory specimens were tested for influenza by reverse-transcriptase polymerase chain reaction (RT-PCR). Using the test-negative design, we determined influenza VE by virus sub-type/lineage and genetic subclades by comparing odds of vaccination in influenza cases versus test-negative controls. RESULTS: Among 8,845 enrollees, 2,722 (31%) tested positive for influenza, including 1,209 (44%) for B/Victoria and 1,405 (51%) for A(H1N1)pdm09. Effectiveness against any influenza illness was 39% (95% confidence interval [CI]: 32-44), 45% (95%CI: 37-52) against B/Victoria and 30% (95%CI: 21-39) against A(H1N1)pdm09 associated illness. Vaccination offered no protection against A(H1N1)pdm09 viruses with antigenically drifted clade 6B.1A 183P-5A+156K HA genes (VE 7%; 95%CI: -14 to 23%) which predominated after January. CONCLUSIONS: Vaccination provided protection against influenza illness, mainly due to infections from B/Victoria viruses. Vaccine protection against illness from A(H1N1)pdm09 was lower than historically observed effectiveness of 40-60%, due to late-season vaccine mismatch following emergence of antigenically drifted viruses. The effect of drift on vaccine protection is not easy to predict and, even in drifted years, significant protection can be observed.

Struyvenberg, M.R., de Groof, A.J., Kahn, A., Weusten, B., Fleischer, D.E., Ganguly, E.K., Konda, V.J.A., Lightdale, C.J., Pleskow, D.K., Sethi, A., Smith, M.S., Trindade, A.J., Wallace, M.B., Wolfsen, H.C., Tearney, G.J., Meijer, S.L., Leggett, C.L., Bergman, J. and Curvers, W.L. (2020). “Multicenter study on the diagnostic performance of multiframe volumetric laser endomicroscopy targets for Barrett’s esophagus neoplasia with histopathology correlation.” Dis Esophagus 33(12).

Full text of this article.

Volumetric laser endomicroscopy (VLE) has been shown to improve detection of early neoplasia in Barrett’s esophagus (BE). However, diagnostic performance using histopathology-correlated VLE regions of interest (ROIs) has not been adequately studied. We evaluated the diagnostic accuracy of VLE assessors for identification of early BE neoplasia in histopathology-correlated VLE ROIs. In total, 191 ROIs (120 nondysplastic and 71 neoplastic) from 50 BE patients were evaluated in a random order using a web-based module. All ROIs contained histopathology correlations enabled by VLE laser marking. Assessors were blinded to endoscopic BE images and histology. ROIs were first scored as nondysplastic or neoplastic. Level of confidence was assigned to the predicted diagnosis. Outcome measures were: (i) diagnostic performance of VLE assessors for identification of BE neoplasia in all VLE ROIs, defined as accuracy, sensitivity, and specificity; (ii) diagnostic performance of VLE assessors for only high level of confidence predictions; and (iii) interobserver agreement. Accuracy, sensitivity, and specificity for BE neoplasia identification were 79% (confidence interval [CI], 75-83), 75% (CI, 71-79), and 81% (CI, 76-86), respectively. When neoplasia was identified with a high level of confidence, accuracy, sensitivity, and specificity were 88%, 83%, and 90%, respectively. The overall strength of interobserver agreement was fair (k = 0.29). VLE assessors can identify BE neoplasia with reasonable diagnostic accuracy in histopathology-correlated VLE ROIs, and accuracy is enhanced when BE neoplasia is identified with high level of confidence. Future work should focus on renewed VLE image reviewing criteria and real-time automatic assessment of VLE scans.

Souza, R.F. and Spechler, S.J. (2021). “Advances in Biomarkers for Risk Stratification in Barrett’s Esophagus.” Gastrointest Endosc Clin N Am 31(1): 105-115.

Full text of this article.

Dysplasia currently is the primary biomarker used to risk stratify patients with Barrett’s esophagus, but dysplasia has a number of considerable limitations in this regard. Thus, investigators over the years have explored innumerable alternative molecular biomarkers for risk stratification in Barrett’s esophagus. This report focuses only on those biomarkers that appear most promising based on the availability of multiple published studies corroborating good results, and on the commercial availability of the test. These promising biomarkers include p53 immunostaining, TissueCypher, BarreGEN, and wide-area transepithelial sampling with computer-assisted 3-dimensional analysis (WATS(3D)).

Smith, E.R., Fry, A.M., Hicks, L.A., Fleming-Dutra, K.E., Flannery, B., Ferdinands, J., Rolfes, M.A., Martin, E.T., Monto, A.S., Zimmerman, R.K., Nowalk, M.P., Jackson, M.L., McLean, H.Q., Olson, S.C., Gaglani, M. and Patel, M.M. (2020). “Reducing Antibiotic Use in Ambulatory Care Through Influenza Vaccination.” Clin Infect Dis 71(11): e726-e734.

Full text of this article.

BACKGROUND: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI. METHODS: We enrolled outpatients aged ≥6 months with ARI from 50-60 US clinics during 5 winters (2013-2018) and tested for influenza with RT-PCR; results were unavailable for clinical decision making and clinical influenza testing was infrequent. We collected antibiotic prescriptions and diagnosis codes for ARI syndromes. We calculated vaccine effectiveness (VE) by comparing vaccination odds among influenza-positive cases with test-negative controls. We estimated ARI visits and antibiotic prescriptions averted by influenza vaccination using estimates of VE, coverage, and prevalence of antibiotic prescriptions and influenza. RESULTS: Among 37 487 ARI outpatients, 9659 (26%) were influenza positive. Overall, 36% of ARI and 26% of influenza-positive patients were prescribed antibiotics. The top 3 prevalent ARI syndromes included: viral upper respiratory tract infection (47%), pharyngitis (18%), and allergy or asthma (11%). Among patients testing positive for influenza, 77% did not receive an ICD-CM diagnostic code for influenza. Overall, VE against influenza-associated ARI was 35% (95% CI, 32-39%). Vaccination prevented 5.6% of all ARI syndromes, ranging from 2.8% (sinusitis) to 11% (clinical influenza). Influenza vaccination averted 1 in 25 (3.8%; 95% CI, 3.6-4.1%) antibiotic prescriptions among ARI outpatients during influenza seasons. CONCLUSIONS: Vaccination and accurate influenza diagnosis may curb unnecessary antibiotic use and reduce the global threat of antibiotic resistance.