A conversation on smallpox and vaccination with Dr. William Foege

I can hardly do Dr. William Foege justice with a short introduction. He is one of the scientists who led the global smallpox eradication efforts. He developed the concept of ring vaccination, which targeted vaccination to those individuals around a known case of smallpox. This concept really made eradication possible, as it eliminated the need for universal vaccination.  Following the success of the smallpox campaign, he has worked tirelessly to increase global vaccination rates.  He led the effort to provide low-cost treatments for river blindness, resulting in an immense reduction in that disease in Africa. To read some of his amazing stories of his time in the field, check out his autobiography and chronicle of smallpox’s demise, “House on Fire: The Fight to Eradicate Smallpox.” He’s currently a fellow at the Gates Foundation after serving with the Carter Foundation and spending time as the director of the CDC. I could go on and on about his positions and awards, but suffice it to say, he’s a man who knows his stuff.

Dr. Foege was generous enough to answer my questions on vaccination and on smallpox in particular, after I ran across a particularly egregious anti-vaccine article which suggested that use of the vaccine actually increased smallpox cases, and did nothing to eradicate the virus. He also discusses what vaccine supporters can do to promote vaccination.

TS: You have certainly encountered resistance to vaccination in your day, and much misinformation about and fear of vaccinations. How did you overcome this misinformation and fear when working to eradicate smallpox, and later in your career to increase rates of vaccination overall in the developing world?

WF: The first anti-vaccination movements appeared immediately after Edward Jenner introduced smallpox vaccine in 1796.  I start from the premise that parents want to do the right thing for their children, and when they don’t it is because of misinformation rather than evil intent.  While resistance was found in many countries, the fear of smallpox overcame many of the problems.  When people observed a decreased risk of the disease in those vaccinated it was a powerful message.  Now parents don’t always see the disease impact and therefore have a harder time weighing risks.

An overwhelming concern in recent years has been the concern about autism.  We know the studies are good showing no increased risk in children who have been vaccinated, but parents are often left with the first impression when that concern was voiced some years ago and have no way of following the literature.  They have been poorly served by Andrew Wakefield.  We now know that his article in the Lancet was more than poor science.  He fabricated and received money from a lawyer.  He lost his license and yet he continues to give talks to parents looking for an answer to autism.  So he not only lost his license but he lost his way.

The research, by the way, is pointing to something that happens in the second trimester of pregnancy as a cause of autism, not something that happens after birth.

TS: Unfortunately, there is rampant misinformation today even in developed countries. A common anti-vaccine message is that “vaccines didn’t reduce” measles, polio, etc. A recent post even claims that “Small pox had greatly declined before the vaccine, increased after the vaccine in westernized countries, and was effectively eradicated in third-world countries due to the surveillance and containment quarantine program. The small pox vaccine was actually flawed, deadly, and ineffective, killing many and inflicting even more with serious adverse reactions. Small pox eventually exterminated itself when people had access to clean water, good food, clean living conditions, and proper hygiene.” (Source) As one who led smallpox eradication efforts in Africa and India, can you address the claim that what led to the elimination of smallpox was hygiene and quarantine rather than vaccination?

WF: I would never speak against clean water, good food, clean living conditions and proper hygiene, but that is not what eradicated smallpox.  Smallpox was almost a universal disease in Europe at the time the vaccine was developed in 1796.  Even in the 20th century there were an estimated 300 million deaths from smallpox worldwide.  The surveillance/containment strategy was based on using vaccine and getting it to the people at immediate risk because they were in the vicinity of people with smallpox.  Quarantine of smallpox patients in their homes was part of the strategy in order to reduce the number of people they could expose.  Visitors were allowed into their homes but only after being vaccinated.  The science of vaccine preventing smallpox is so abundantly clear that it is difficult to imagine one looking at the evidence and reaching the conclusions cited above.  The same is true of measles and polio.  Measles killed large numbers of children in Africa and Asia before vaccine was introduced.  The number of measles deaths was over 3 million a year in the early 1960’s and has been reduced by over 90% with the introduction of vaccine.  The people who ascribe the reductions of cases in measles, polio and smallpox to hygiene provide proof to Mark Twain’s comment that people who don’t read have no advantage over people who can’t read.

TS: Another common anti-vaccine claim is that “herd immunity is a myth.”  Would smallpox eradication have succeeded if this was the case? 

WF: Herd immunity is a complex subject.  There is no percentage of protection that will automatically protect others.  For example, 90% smallpox vaccination in a state such as Bihar, India, would still allow more susceptible people per square mile than 10% smallpox vaccination in most of the United States.  Measles virus is so contagious that it seeks out susceptible children with tenacity.  Introduce a person with smallpox to a room of susceptible children and only about a third will have smallpox one incubation period later.  Do the same with a case of measles and 80% will have the disease one incubation period later.

However, the concept is correct that increasing the number of persons protected in the population will decrease the chances that an organism will be passed on.  Not only is the vaccinated person protected but they can’t pass on the disease to others.  At high levels of coverage the remaining population receives great protection.  With surveillance/containment in smallpox eradication, our objective was to vaccinate all contacts of a person with smallpox and in that sense attempt to get 100% of close contacts protected, a form of herd immunity in a small defined group.

TS: You were instrumental in increasing vaccination rates in developing countries in years past. What are your thoughts on those who sit in a position of privilege in the U.S., eschewing vaccines and declaring vaccine-preventable diseases “harmless” while many of them have never seen a case of polio or measles?

WF: It would be nice to be protected from both the diseases and the small risks of vaccine.  But it doesn’t work.  The social contract requires that we all participate or the diseases will come back.  Every pregnant woman in this country should be aware that their child will not have Congenital Rubella Syndrome.  Why?  Because other children have been vaccinated against rubella and while they get no direct benefit, they have stopped the transmission of the virus to a fetus.  It is a social contribution they can be proud of providing.  Parents who withhold vaccines from their children are doing their children a disservice. They put others at risk if their children get a vaccine-preventable disease and they have also put their children at increased risk if they want to travel abroad as students or later as adults.  It has turned out to be a heavy burden for parents who have lost their children in recent measles outbreaks.  Indigenous measles has disappeared in this country so every case can be traced to importations.  But we have continuous importations and at times we have had large outbreaks because of the many children are unvaccinated.

TS: In your campaigns against smallpox, for global vaccinations, and for the distribution of ivermectin to treat river blindness, it seems like you have frequently played the role of diplomat in addition to scientist/physician: bringing together people from opposing “turfs” to come to a mutually beneficial understanding and outcome. Do you have any advice for those of us working on raising vaccine awareness in the current U.S. climate, and how we can work to better play the role of diplomat as well?

WF: First, know what we all want.  Our children to be healthy.  Both sides can’t be right (although as Lincoln pointed out they could both be wrong!) so what information is needed to reach a decision?  Immunization rates have improved on Vashon Island because parents got together to try and understand why the difference of opinion.  My belief is that Andrew Wakefield so poisoned the well that the facts have to be explained before there can be common ground.

I often tell students that health leadership today is found not in a title but in a person that can make a coalition work effectively.  We need many coalitions to discuss this at local levels to discover what do the anti-vaccination people need in the way of information.  There has been a movement by some pediatricians to say they can’t care for children who are not immunized.  I understand the feeling but feel those are exactly the children who need care because they already have a strike against them because of parents not understanding the science.

You can make a great contribution by making the science clear, encouraging feedback and providing reassurance to the parents who need support.  Autism is such a difficult burden for parents that they want answers.  They need help in getting what is known about the science.  They are not helped by erroneous information.


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Is there such a thing as an “evolution-proof” drug?

Eleven years ago, two scientists made a bet. One scientist wagered that a new type of antimicrobial agent, called antimicrobial peptides, would not elicit resistance from bacterial populations which were treated with the drugs. Antimicrobial peptides are short proteins (typically 15-50 amino acids in length) that are often positively charged. They are also a part of our body’s own innate immune system, and present in other species from bacteria to plants. It is thought that these peptides work primarily by disrupting the integrity of the bacterial cell, often by poking holes in them. Sometimes they work with the host to ramp up the immune response and overwhelm the invading microbe. Because the peptides are frequently targeted at the bacterial cell wall structure, it was thought that resistance to these drugs would require a fundamental change in membrane structure, making it an exceedingly rare event. Therefore, these antimicrobial peptides might make an excellent weapon in the fight against multiply drug-resistant bacteria.

Additionally, the remarkable diversity of these peptides, combined with the presence of multiple types of peptides with different mechanisms of action present at the infection site, rendered unlikely the evolution of resistance to these molecules (or so some reasoning went). However, evolutionary biologists have pointed out that therapeutic use of these peptides would differ from natural exposure: concentration would be significantly higher, and a larger number of microbes would be exposed. Additionally, resistance to these peptides has been detailed in a few instances. For example, resistance to antimicrobial peptides has been shown to be essential for virulence in Staphylococcus aureus and Salmonella species, but we didn’t *witness* that resistance develop–therefore, it might simply be that those species have physiological properties that render them naturally resistant to many of these peptides, and were never susceptible in the first place.

The doubter of resistance, and the bet instigator, was Michael Zasloff of Georgetown University, who wrote in a 2002 review of antimicrobial peptides:

Studies both in the laboratory and in the clinic confirm that emergence of resistance against antimicrobial peptides is less probable than observed for conventional antibiotics, and provides the impetus to develop antimicrobial peptides, both natural and laboratory conceived, into therapeutically useful agents.

Certainly in the short term, resistance may be unlikely to evolve for reasons described above. However, if these peptides are used over an extended period of time, could the mutations necessary to confer resistance accumulate? This was the question asked in a new study by Dr. Zasloff along with colleagues Gabriel Perron and Graham Bell. Following publication of his 2002 paper where he called evolution of resistance to these peptides “improbable,” Bell challenged Zasloff to test this theory. Zasloff took him up on the offer, and they published their results in Proceedings of the Royal Society

The result?

Zasloff had egg on his face. Resistance not only evolved, but it evolved independently in almost every instance they tested (using E. coli and Pseudomonas species), taking only 600-700 generations–a relative blip in microbial time. Oops.

Well, everything old is new again. A very similar claim has been making the rounds recently, originating from the press release for a new paper claiming to have found bacteria’s “Achilles’ heel,” advancing the claim that “Because new drugs will not need to enter the bacteria itself, we hope that the bacteria will not be able to develop drug resistance in future.”  A grand claim, but history suggests otherwise. It was argued that bacteria could not evolve resistance to bacteriophage, as the ancient interaction between viruses and their bacterial hosts certainly must have already exploited and overcome any available defense. Now a plethora of resistance mechanisms are known.

Alexander Fleming, who won the 1945 Nobel Prize in Physiology or Medicine, tried to sound the warning that the usefulness of antibiotics would be short-lived as bacteria adapted, but his warnings were (and still are?) largely ignored. There is no “magic bullet;” there are only temporary solutions, and we should have learned by now not to underestimate our bacterial companions.

Part of this post previously published here.