John Bartlett's Take on Critical Infectious Disease Topics: Part 2

Antibiotics, Bioterrorism, and Vaccines

John G. Bartlett, MD


March 30, 2017

Polio vaccination. Studies of the immune response have demonstrated boosting with fractional doses, indicating that the polio vaccine can induce adequate protection with lower-than-standard doses. This is of potential interest in areas where the supply is inadequate,[32] because reducing the dose to extend supplies could have more general application.

HBV vaccine. Use of the HBV vaccine in infants and neonates has substantially decreased new infections. An estimated 63 million new cases of HBV infection and 17 million HBV-related deaths have been prevented.[33] This is a remarkable achievement, and is largely responsible for the progress toward the global elimination of HBV infection.

World Health Organization (WHO) vaccine priorities. The experience with the Ebola virus resulted in three candidate vaccines, but timing and testing were, in retrospect, too little and too late.[34] As a result, WHO and National Institutes of Health (NIH) are emphasizing earlier and more aggressive responses to major emerging pathogens likely to cause severe outbreaks.[35] The priority list includes the following (in no particular order):

  • Crimean Congo hemorrhagic fever virus

  • Filoviruses (including Ebola and Marburg viruses)

  • The emerging coronaviruses (including MERS and SARS-Co-V)

  • Lassa fever virus

  • Nipah virus

  • Riff Valley fever virus

  • Vaccines for "any new severe infectious disease"

Other conditions considered priorities include chikungunya, severe fever with thrombocytopenia syndrome, and epidemics associated with neurologic complications, such as the Zika virus. Notably absent from the list is a dengue virus vaccine.

The antimosquito vector virus vaccine. This is a very early-stage vaccine being tested at the NIH for potential use in the prevention of mosquito-borne infections, which include dengue fever, West Nile virus, Zika virus, and chikungunya.[35]

Clostridium difficile infection. Large-scale trials are testing the utility of several different products for the prevention of C difficile, with particular emphasis on elderly patients. Some of these trials are far enough along to provide future guidance. These trials are generally conducted with elderly patients using data that consistently show a substantial age-associated risk.[36]

Pertussis. Experience with the current vaccine has shown that in the past 10 years, more than 25,000 cases of pertussis in the United States can be ascribed to failure of the acellular vaccine, vaccine refusal, or waning immunity. Specifically, antigenic response is shown in 86% of recipients at 1 year, but in only 4% at 8 years.

Herpes zoster. The good news is that there is a new subunit herpes zoster vaccine that is showing good antigenic response in elderly patients, with 97% efficacy in preventing zoster pertussis in elderly patients and sustained antibody levels lasting more than 3 years.[37]

Measles. This highly contagious disease was declared eliminated in 2000, but since then, 23 outbreaks have occurred, involving about 1500 patients, about 200 of whom were known to have been vaccinated and 804 of whom were known not to have been previously vaccinated. This issue is politically charged, but it appears that immune protection is time-dependent.[38]

Pneumococcal vaccine. This is another vaccine controversy. The CDC currently recommends, on the basis of a trial done in the Netherlands,[39] Prevnar 13 for adults older than 65 years. However, a strong case has been made for the older 23-valent polysaccharide pneumococcal vaccine. The contention is that the Dutch data showed efficacy in preventing the 13 serotypes in the vaccine, but failed to show a reduction in all-cause CAP or pneumonia mortality.

More important, the Dutch study is viewed by some experts as irrelevant to the United States. Because pediatric vaccines have provided substantial herd immunity, the validity of data from other countries (including the Netherlands), with different pediatric vaccine policies, is diminished. Thus, many clinicians continue to recommend the older 23-valent pneumococcal vaccine in this population.[40] The cost for Prevnar 13 is also significantly higher than the older vaccine.

Influenza vaccine. Fluad is a three-valent influenza vaccine with an adjuvant (MF58) to enhance antigenic protection against all three anticipated strains of seasonal influenza in older adults.[41] This appears to be a better immunogen for older adults than other influenza vaccines without adjuvant, according to a controlled trial with 7082 adults older than 65 years.[42] It is probably too late for this season, but a recommendation for the adjuvant vaccine could be important for the epidemic strains anticipated next year.


The author thanks Dr Tom Inglesby, Dr Matt Watson, and colleagues for valuable input on the topic of bioterrorism.


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