Vaccines: A tool for the post-antibiotic era?

In honor of World Immunization Week this week, I recently read two books by Paul Offit: Vaccinated: One Man's Quest to Defeat the World's Deadliest Diseases and The Cutter Incident: How America’s First Polio Vaccine Led to the Growing Vaccine Crisis. Both are excellent. Vaccinated is essentially a biography of Maurice Hilleman, but it also reviews how several of the important vaccines currently in use were developed and marketed. The Cutter Incident tells the story of incompletely inactivated lots of polio vaccine manufactured by Cutter Laboratories, which caused 40,000 cases of polio nationwide in 1955, including 200 cases of paralysis and 10 deaths. There are many pearls and much wisdom to be found in the pages of these two books; I recommend reading them.

Certainly the utility of vaccines is well demonstrated and their development and application is one of the major accomplishments of modern medicine. In the US alone the improvement of population health as vaccines have become available is remarkable. Globally, it has been estimated that vaccines prevent nearly 6 million deaths annually worldwide.

The books got me thinking about future potential vaccines. In one passage, Offit recounts the development of a pneumococcal vaccine and quotes Robert Austrian talking about the rationale for his work:

The only alternative then to protect those at high risk of early death is to prevent them from becoming ill.

This beautiful and simple idea -- a medical and public health truism if ever there was one ("an ounce of prevention is worth a pound of cure") -- strikes me as relevant to HAI and antibiotic resistant infections. Think what healthcare might be like if there were vaccines for many of the bacterial infections that are currently problematic and often resistant to antibiotics, like Staphylococcus aureus, Clostridium difficile, and Neisseria gonorrhoeae.

Several antibacterial vaccines are available, including ones for pertussis, tetanus, diphtheria, meningococcus, pneumococcus, Haemophilus influenzae type b (Hib) disease, cholera, typhoid, and anthrax. However, there are reasons that vaccines for S. aureus, C. diff, and N. gonorrhoeae (as well as others) don't yet exist. For one, the immunology can be complex, as Offit explains in the discussion of the pneumococcal vaccine. Proctor describes the situation for Staph aureus in a recent review, as do Fowler and Proctor in another review. Also, the cost of developing, testing, and licensing can be steep relative to the profits of a licensed, marketed vaccine. Yet another issue is the specter of adverse events, both real and perceived. On this point, Offit notes that

. . . a technology that would clearly save lives sits on the shelf. "We could make a group B strep vaccine tomorrow," said one senior pharmaceutical company scientist. "But it would have to be given to pregnant women and we couldn't handle the liability." 

Dempsey et al offers a recent, interesting, and partially validating study to this view of a potential group B strep (GBS) vaccine. Such issues are difficult.

That being said, perhaps vaccines should be emphasized more in the conversation regarding antibiotic resistance. I've wondered in the past about the effectiveness of developing new antibiotics when there seems to be little reason to believe, given the past track record, that they will be used responsibly. A new generation of antibiotic drugs could become useless within a few years if effective antibiotic stewardship isn't practiced globally. Vaccines, if they could be made, may offer protection against what may soon be untreatable infections. Or put differently, perhaps vaccines could be an important tool in a post-antibiotic era.

Of course, there are issues to be better understood and addressed. Recent work illustrates that Bordetella pertussis is evolving in response to the vaccine, raising the possibility that future vaccines may be associated with similar dynamics. Also, vaccines to human commensals like Staphylococcus aureus might promote overgrowth of other commensal organisms. Studies have investigated this for the case of Streptococcus vaccination and MRSA colonization and infection. Moreover, it's unclear whether people would really embrace more vaccinations given the current and recent climate surrounding vaccines.

Regardless, one seldom hears about vaccines in the conversation about antibiotic resistance. It seems like funding should address making new vaccines as well as development of new antibiotic drugs -- because Robert Austrian was right. 

(image source: CDC/PHIL)

Life in a post-antibiotic era: A scary time

The global emergence of pathogens resistant to a range of antimicrobial treatment is a reality threatening the foundations of modern medicine. The WHO, CDC, ministries of health, and NGOs around the world now warn of a post-antibiotic era:

If current trends continue unabated, the future is easy to predict. Some experts say we are moving back to the pre-antibiotic era. No. This will be a post-antibiotic era. In terms of new replacement antibiotics, the pipeline is virtually dry, especially for gram-negative bacteria. The cupboard is nearly bare. . . A post-antibiotic era means, in effect, an end to modern medicine as we know it. Things as common as strep throat or a child’s scratched knee could once again kill. Some sophisticated interventions, like hip replacements, organ transplants, cancer chemotherapy, and care of preterm infants, would become far more difficult or even too dangerous to undertake.

(Dr Margaret Chan, Director-General of the World Health Organization, 2012)

The implications of this potential are astonishing, both in terms of health and economics. According to a recent CDC report, already each year in the US at least 2 million people acquire serious bacterial infections resistant to one or more antibiotics. More than 23,000 people die each year as a direct result of these infections, and many more succumb from conditions complicated by resistant infections. As resistance becomes more prevalent, these numbers will only increase.

While the total economic cost of antibiotic resistance to the US economy has been difficult to calculate, estimates quoted in the CDC report are as high as $20 billion in excess direct healthcare costs, with additional costs to society for lost productivity as high as $35 billion a year (in 2008 dollars). Other nations suffer similar or worse impacts. We can only expect that the costs will increase as infections resistant to antibiotics increase in incidence. 

I recently came across a report from the World Economic Forum, Global Risks 2013, that explores the issue of antibiotic resistance from a global economic perspective. The study frames many of the issues thoughtfully, and proposes some macro-level actions. Getting the issue before world leaders who have the power to do something in response to the threat, such as the members of the WEF, is a good first step. Although not a topic on the agenda for this week's meeting, hopefully, some of the conversation in Davos will include how to make progress against the threat of antibiotic resistance. A sustainable global approach might avert the looming disaster. A post-antibiotic era must be averted.    

(image source: Wikipedia)