Infectious Disease

Jackson, M. L., C. H. Phillips, J. Benoit, L. A. Jackson, M. Gaglani, K. Murthy, H. Q. McLean, E. A. Belongia, R. Malosh, R. Zimmerman and B. Flannery (2018). “Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons.” Vaccine 36(4): 467-472.

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BACKGROUND: In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. METHODS: We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. RESULTS: Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6months to 9years (33 to 70 per 1000) and lowest in adults aged 18-49years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14). DISCUSSION: Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.

Flannery, B., C. Smith, R. J. Garten, M. Z. Levine, J. R. Chung, M. L. Jackson, L. A. Jackson, A. S. Monto, E. T. Martin, E. A. Belongia, H. Q. McLean, M. Gaglani, K. Murthy, R. Zimmerman, M. P. Nowalk, M. R. Griffin, H. Keipp Talbot, J. J. Treanor, D. E. Wentworth and A. M. Fry (2018). “Influence of Birth Cohort on Effectiveness of 2015-2016 Influenza Vaccine Against Medically Attended Illness Due to 2009 Pandemic Influenza A(H1N1) Virus in the United States.” J Infect Dis. Jan 18. [Epub ahead of print].

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Background: The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE). Methods: We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 x [1 – adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients. Results: A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged >/=6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined. Conclusion: Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses.

Deshpande, D., S. Srivastava, P. Bendet, K. R. Martin, K. N. Cirrincione, P. S. Lee, J. G. Pasipanodya, K. Dheda and T. Gumbo (2018). “Antibacterial and Sterilizing Effect of Benzylpenicillin in Tuberculosis.” Antimicrob Agents Chemother 62(2).

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The modern chemotherapy era started with Fleming’s discovery of benzylpenicillin. He demonstrated that benzylpenicillin did not kill Mycobacterium tuberculosis In this study, we found that >64 mg/liter of static benzylpenicillin concentrations killed 1.16 to 1.43 log10 CFU/ml below starting inoculum of extracellular and intracellular M. tuberculosis over 7 days. When we added the beta-lactamase inhibitor avibactam, benzylpenicillin maximal kill (Emax) of extracellular log-phase-growth M. tuberculosis was 6.80 +/- 0.45 log10 CFU/ml at a 50% effective concentration (EC50) of 15.11 +/- 2.31 mg/liter, while for intracellular M. tuberculosis it was 2.42 +/- 0.14 log10 CFU/ml at an EC50 of 6.70 +/- 0.56 mg/liter. The median penicillin (plus avibactam) MIC against South African clinical M. tuberculosis strains (80% either multidrug or extensively drug resistant) was 2 mg/liter. We mimicked human-like benzylpenicillin and avibactam concentration-time profiles in the hollow-fiber model of tuberculosis (HFS-TB). The percent time above the MIC was linked to effect, with an optimal exposure of >/=65%. At optimal exposure in the HFS-TB, the bactericidal activity in log-phase-growth M. tuberculosis was 1.44 log10 CFU/ml/day, while 3.28 log10 CFU/ml of intracellular M. tuberculosis was killed over 3 weeks. In an 8-week HFS-TB study of nonreplicating persistent M. tuberculosis, penicillin-avibactam alone and the drug combination of isoniazid, rifampin, and pyrazinamide both killed >7.0 log10 CFU/ml. Monte Carlo simulations of 10,000 preterm infants with disseminated disease identified an optimal dose of 10,000 U/kg (of body weight)/h, while for pregnant women or nonpregnant adults with pulmonary tuberculosis the optimal dose was 25,000 U/kg/h, by continuous intravenous infusion. Penicillin-avibactam should be examined for effect in pregnant women and infants with drug-resistant tuberculosis, to replace injectable ototoxic and teratogenic second-line drugs.

Block, T. M., H. Alter, N. Brown, A. Brownstein, C. Brosgart, K. M. Chang, P. J. Chen, C. Cohen, H. El-Serag, J. Feld, R. Gish, J. Glenn, T. F. Greten, J. T. Guo, Y. Hoshida, K. V. Kowdley, W. Li, A. S. Lok, B. McMahon, A. Mehta, R. Perrillo, C. M. Rice, J. Rinaudo, R. F. Schinazi and K. Shetty (2018). “Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop.” Antiviral Res 150: 93-100.

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In early 2017, the Hepatitis B Foundation invited 30 experts in the fields of hepatitis B and liver cancer research to identify projects they deemed important to the goal of finding a cure for chronic hepatitis B and D and the diseases with which these viral infections are associated. They were also asked to identify general categories of research and to prioritize sub-project topics within those areas. The experts generally agreed on broadly defined areas of research, but there was usually little difference between the highest and lowest scoring projects; for the most part, all programs described in this document were considered valuable and necessary. An executive summary of this discussion was recently published (Alter et al., Hepatology 2017). The present manuscript reports the areas of research identified by the workshop participants, provides a brief rationale for their selection, and attempts to express differences among the priorities assigned to each area of research, when such distinctions were expressed.

Jackson, M. L., C. H. Phillips, J. Benoit, L. A. Jackson, M. Gaglani, K. Murthy, H. Q. McLean, E. A. Belongia, R. Malosh, R. Zimmerman and B. Flannery (2017). “Burden of medically attended influenza infection and cases averted by vaccination – United States, 2013/14 through 2015/16 influenza seasons.” Vaccine.

Full text of this article.

BACKGROUND: In addition to preventing hospitalizations and deaths due to influenza, influenza vaccination programs can reduce the burden of outpatient visits for influenza. We estimated the incidence of medically-attended influenza at three geographically diverse sites in the United States, and the cases averted by vaccination, for the 2013/14 through 2015/16 influenza seasons. METHODS: We defined surveillance populations at three sites from the United States Influenza Vaccine Effectiveness Network. Among these populations, we identified outpatient visits laboratory-confirmed influenza via active surveillance, and identified all outpatient visits for acute respiratory illness from healthcare databases. We extrapolated the total number of outpatient visits for influenza from the proportion of surveillance visits with a positive influenza test. We combined estimates of incidence, vaccine coverage, and vaccine effectiveness to estimate outpatient visits averted by vaccination. RESULTS: Across the three sites and seasons, incidence of medically attended influenza ranged from 14 to 54 per 1000 population. Incidence was highest in children aged 6months to 9years (33 to 70 per 1000) and lowest in adults aged 18-49years (21 to 27 per 1000). Cases averted ranged from 9 per 1000 vaccinees (Washington, 2014/15) to 28 per 1000 (Wisconsin, 2013/14). DISCUSSION: Seasonal influenza epidemics cause a considerable burden of outpatient medical visits. The United States influenza vaccination program has caused meaningful reductions in outpatient visits for influenza, even in years when the vaccine is not well-matched to the dominant circulating influenza strain.