Infectious Disease

McLean, H. Q., H. Caspard, M. R. Griffin, K. A. Poehling, M. Gaglani, E. A. Belongia, H. K. Talbot, T. R. Peters, K. Murthy and C. S. Ambrose (2017). “Effectiveness of live attenuated influenza vaccine and inactivated influenza vaccine in children during the 2014-2015 season.” Vaccine 35(20): 2685-2693.

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BACKGROUND: A clinical study found that live attenuated influenza vaccine (LAIV) was superior to inactivated influenza vaccine (IIV) against drifted A(H3N2) viruses in children. During the 2014-2015 influenza season, widespread circulation of antigenically and genetically drifted A(H3N2) viruses provided an opportunity to evaluate subtype-specific vaccine effectiveness (VE) of quadrivalent LAIV (LAIV4) and IIV in children. METHODS: Children (2-17years) with febrile acute respiratory illness <5days' duration were enrolled at 4 outpatient sites in the United States during the 2014-2015 influenza season. Nasal swabs were tested for influenza by reverse transcription polymerase chain reaction; vaccination dates were obtained from medical records or immunization registries. VE was estimated using a test-negative design comparing odds of vaccination among influenza cases and test-negative controls with adjustment for potential confounders. RESULTS: Among 1696 children enrolled, 1511 (89%) were included in the analysis. Influenza was detected in 427 (28%) children; 317 had influenza A(H3N2) and 110 had influenza B. Most influenza isolates were characterized as a drifted strain of influenza A(H3N2) or a drifted strain of B/Yamagata. For LAIV4, adjusted VE was 50% (95% confidence interval [CI], 27-66%) against any influenza, 30% (95% CI, -6% to 54%) against influenza A(H3N2), and 87% (95% CI, 63-96%) against type B. For IIV, adjusted VE was 39% (95% CI, 18-54%) against any influenza, 40% (95% CI, 16-58%) against A(H3N2), and 29% (95% CI, -15% to 56%) against type B. Odds of influenza for LAIV4 versus IIV recipients were similar against influenza A(H3N2) (odds ratio [OR], 1.17; 95% CI, 0.73-1.86) and lower against influenza B (OR, 0.18; 95% CI, 0.06-0.55). CONCLUSIONS: LAIV4 and IIV provided similar protection against a new antigenic variant A(H3N2). LAIV4 provided significantly greater protection than IIV against a drifted influenza B strain.

Perrillo, R. P. (2017). “HBV Reactivation During DAA Treatment of Chronic Hepatitis C: A Hidden Danger of an Otherwise Major Success Story.” Hepatology: 2017 Mar [Epub ahead of print].

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It has been estimated that 250 million and 170 million people worldwide are infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. Co-infection is relatively common in regions where both viruses are endemic and transmission is facilitated by common routes of exposure. In a recent study of 1287 New York City residents with hepatitis C, most of whom were born in United States, 62% had resolved HBV infection and 6% were HBsAg positive. Dual infection with HBV and HCV leads to accelerated liver disease and a higher risk for cirrhosis and hepatocellular carcinoma. Treatment of coinfected patients is controversial, but it is a common practice to treat the virus that genomic testing reveals to be dominant. The intracellular interactions of the two viruses are unclear. Cross sectional studies have shown that co-infected individuals often have high levels of HCV RNA, low or non-detectable HBV DNA, anti-HBe reactivity, and lower levels of HBsAg when compared to HBV mono infection. Thus, HCV is most often the primary target of antiviral therapy. However, longitudinal studies have demonstrated that the levels of HBV DNA and HCV RNA may fluctuate with time suggesting that competitive interactions between the two viruses is more dynamic than previously thought.

Moore, L., C. J. Kramer, S. Delcoix-Lopes and A. M. Modrykamien (2017). “Comparison of Cisatracurium Versus Atracurium in Early ARDS.” Respir Care: 2017 Mar [Epub ahead of print].

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BACKGROUND: Administration of cisatracurium in severe ARDS decreases in-hospital mortality. Whether clinical outcomes are cisatracurium-specific or related with all neuromuscular blockers is unknown. This study aimed to compare outcomes in severe ARDS patients treated with cisatracurium versus atracurium. METHODS: Patients admitted in ICUs with a diagnosis of severe ARDS and treated with neuromuscular blocking agents within 72 h of diagnosis were included. Subjects treated with cisatracurium versus atracurium were compared. The primary outcome was improvement in oxygenation, defined as the difference of PaO2 /FIO2 at 72 h post-initiation of neuromuscular blocking agents. Secondary outcomes were ventilator-free days at day 28, ICU and hospital lengths of stay, and hospital mortality. RESULTS: Seventy-six subjects with ARDS were included in the study. Eighteen subjects (24%) were treated with atracurium, whereas 58 (76%) were treated with cisatracurium. Equivalent dosages of sedation and analgesia as well as use of brain function monitoring technology were similar between both groups. There were no differences in clinical outcomes. Specifically, improvement of PaO2 /FIO2 was a median (interquartile range [IQR]) of 65 (25-162) in the atracurium group and 66 (IQR 16-147) in the cisatracurium group (P = .65). Ventilator-free days at day 28 were 13 d (IQR 0-22 d) and 15 d (IQR 8-21 d) in the atracurium and cisatracurium groups, respectively (P = .72). ICU length or stay was 18 d (IQR 8-34 d) in the atracurium group and 15 d (IQR 9-22 d) in the cisatracurium group (P = .34). In-hospital mortality was 50% for the atracurium population and 62% for the cisatracurium group (P = .42) CONCLUSIONS: Among subjects with early severe ARDS, the utilization of atracurium versus cisatracurium within 72 h of admission was not associated with significant differences in clinical outcomes.

Magombedze, G., T. Shiri, S. Eda and J. R. Stabel (2017). “Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data.” Sci Rep 7: 44765.

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Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-gamma, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-gamma/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.

Emmett, M. (2016). “Stewart versus traditional approach to acid-base disorders.” Anesth Analg 123(4): 1063-1064.

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Undoubtedly, the Stewart methodology (and the “base excess” approach) can be used to diagnose metabolic acidbase disorders, but it has no advantage over the classic physiologic methodology advanced by Schwartz and Relman2 and Narins and Emmett.3 The “Stewart Approach” is a more complicated and less-intuitive framework for diagnosing and understanding acid-base physiology/pathophysiology. Dr Story describes an intubated cirrhotic patient (who had received generous intravenous saline expansion) with the following laboratory results: Na: 133; Cl: 110; lactate: 5 (all mmol/L); albumin: 22 g/L; arterial blood gas—pH 7.20; Pco2 40; HCO3 15. Potassium and venous HCO3 (or total CO2) were not reported.