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1224         Part ten  Prevention and Therapy of Immunological Diseases



            On tHe HOrIZOn                                     REFERENCES
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           century, they are likely to be even more valuable in the next century.  pneumococcal conjugate vaccine on drug-resistant Streptococcus
          •  Emerging infections capable of severe morbidity (e.g., Zika virus) or   pneumoniae. N Engl J Med 2006;354:1455–63.
           mortality (e.g., Ebola virus and avian influenza virus A/H7N9) continue   2.  Munoz FM, Bond NH, Maccato M, et al. Safety and immunogenicity of
           to emerge and threaten global human health with alarming regularity.  tetanus diphtheria and acellular pertussis (Tdap) immunization during
          •  Having rapid vaccine platforms “on the shelf”—to enable quick produc-  pregnancy in mothers and infants: a randomized clinical trial. JAMA
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           testing—is critical to timely and effective responses to outbreaks that   3.  Zaman K, Roy E, Arifeen SE, et al. Effectiveness of maternal influenza
           may spread globally very rapidly as a result of international air travel.  immunization in mothers and infants. N Engl J Med 2008;359:1555–64.
          •  Several older technologies for vaccine production (e.g., egg-based   4.  Steinhoff MC, Omer SB, Roy E, et al. Influenza immunization in
           production of influenza antigens) or immune response assessment   pregnancy–antibody responses in mothers and infants. N Engl J Med
           (e.g., hemagglutination inhibition assays) will be replaced by newer,   2010;362:1644–6.
           improved methods (e.g., cell culture–derived recombinant antigens
           and automated high-throughput neutralization assays).  5.  Mysorekar IU, Diamond MS. Modeling Zika Virus Infection in
          •  There will  be increased application  of new molecular adjuvants    Pregnancy. N Engl J Med 2016.
           (e.g., CD40L, Toll-like receptor-5 [TLR-5], or interleukin-12 [IL-12]) that   6.  Brasil P, Pereira JP Jr, Raja Gabaglia C, et al. Zika Virus Infection in
           target specific biochemical pathways to direct and shape the cascade   Pregnant Women in Rio de Janeiro - Preliminary Report. N Engl J Med
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          •  The worsening problem of antibacterial resistance is inspiring new   Defects–Reviewing the Evidence for Causality. N Engl J Med
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           resistant, hospital-acquired infections through vaccination—that is, it   8.  Driggers RW, Ho CY, Korhonen EM, et al. Zika Virus Infection with
           is better to prevent an infection caused by a highly resistant microbe   Prolonged Maternal Viremia and Fetal Brain Abnormalities. N Engl J
           than to try to treat it.                               Med 2016;374:2142–51.
                                                                9.  Pilishvili T, Lexau C, Farley MM, et al. Sustained reductions in invasive
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                                                               10.  Pilishvili T, Bennett NM. Pneumococcal disease prevention among adults:
        obtained in Guinea, where the epidemic persisted somewhat   Strategies for the use of pneumococcal vaccines. Am J Prev Med
        longer than it did in Sierra Leone or Liberia. 83,84  Even though   2015;49:S383–90.
        the progression of candidate Ebola vaccines to field trials was   11.  DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose
        rapid (and impressive), the experience with the timing of the   versus standard-dose influenza vaccine in older adults. N Engl J Med
        availability of the Ebola vaccine for efficacy testing and field use   2014;371:635–45.
        versus the waning arc of the Ebola epidemic points to a recurring   12.  Dunning AJ, DiazGranados CA, Voloshen T, et al. Correlates of Protection
        concern. This same concern also arose during the 2009 influenza   against Influenza in the Elderly: Results from an Influenza Vaccine
        A pandemic—namely, when major epidemics of highly infectious   Efficacy Trial. Clin Vaccine Immunol 2016;23:228–35.
        and lethal infectious diseases occur, can protective vaccines be   13.  Black S. Safety and effectiveness of MF-59 adjuvanted influenza vaccines
                                                                  in children and adults. Vaccine 2015;33(Suppl. 2):B3–5.
        developed quickly enough to have an impact and save  lives?   14.  FDA approves first seasonal influenza vaccine containing an adjuvant.
        Some who have raised this concern have suggested that one   U.S. Food and Drug Administration. Available at: http://www.fda.gov/
        solution is to prepare a library and/or repository of vaccines or   NewsEvents/Newsroom/PressAnnouncements/ucm474295.htm. [Accessed
        platforms for all possible epidemic pathogens in advance so as   30 May 2016].
        to ensure readiness.                                   15.  Hopkins D. The Greatest Killer, Smallpox in History. Chicago, IL:
           A major international effort to develop a malaria vaccine has   University of Chicago Press Books; 2002.
        been ongoing for many years, and recent efficacy trials have   16.  Smallpox: A great and terrible scourge. NIH. Available at: https://
        produced encouraging results. 85,86                       www.nlm.nih.gov/exhibition/smallpox/sp_variolation.html. [Accessed 30
           Along with  HIV/AIDS and  malaria, TB is  one of the   May 2016].
        three top infectious killers each year and remains a major   17.  Willis NJ. Edward Jenner and the eradication of smallpox. Scott Med J
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        target for development of a vaccine to reduce mortality and     18.  An Inquiry into the Causes and Effects of the Variolae Vaccinae A Disease
        morbidity. 87-89                                          Discovered in Some of the Western Counties of England, Particularly
           In the past decade, Bordetella pertussis infection, or whooping   Gloucestershire, and Known by the Name of the Cow Pox. Public
        cough, cases in the United States have increased to levels not   domain; 1798. Available at: http://www.bartleby.com/38/4/1.html.
        observed since the 1950s. The transition from the previously   [Accessed 30 May 2016].
        used whole-cell pertussis vaccine to the current acellular pertussis   19.  Wolfe RM, Sharp LK. Anti-vaccinationists past and present. BMJ
        vaccine is thought to be responsible. Although the older vaccine   2002;325:430–2.
        was more reactogenic, it was also more protective. Pertussis   20.  Memoli MJ, Shaw PA, Han A, et al. Evaluation of Antihemagglutinin and
        vaccine developers and public health officials are working to   Antineuraminidase Antibodies as Correlates of Protection in an Influenza
        develop new vaccines and to determine the correlates of protective   A/H1N1 Virus Healthy Human Challenge Model. MBio
                                                                  2016;7(2):e00417–16.
        efficacy and are considering the best options to reduce the   21.  Kirkpatrick BD, Whitehead SS, Pierce KK, et al. The live attenuated
        incidence of pertussis. 90                                dengue vaccine TV003 elicits complete protection against dengue in a
                                                                  human challenge model. Sci Transl Med 2016;8:330ra36.
        Please check your eBook at https://expertconsult.inkling.com/   22.  Bernstein DI, Atmar RL, Lyon GM, et al. Norovirus vaccine against
        for self-assessment questions. See inside cover for registration   experimental human GII.4 virus illness: a challenge study in healthy
        details.                                                  adults. J Infect Dis 2015;211:870–8.
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