Vaccines: now and then...

1. What is a challenge trial? It’s actually a pretty good idea with some interesting ethical questions attached. In a nutshell, volunteers with their full consent allow researchers to purposefully infect them with Covid-19. Advantages of this type of trial compared with our usual trials, is that we know exactly when the volunteer was exposed to the virus relative to when they received a vaccine. This greatly speeds up and simplifies accrual of good data about the efficacy of any vaccine. The obvious ethical consideration is, is it ever OK to knowingly give a healthy person an infection that could be morbid or mortal? The consensus right now in the U.S. is that this is not ethical and challenge trials are not taking place. There is certainly precedent for this approach as human challenge studies have been previously used to develop vaccines for typhoid, cholera and malaria. Resistance to the idea in the U.S. may also be influenced by the dark history of challenge trials done to Black persons with syphilis without their knowledge or consent in the notorious Tuskeegee experiments that were completely unethical. In England, folks feel differently about a transparent process with competent, consenting adults, and are currently allowing a Covid challenge trial to move forward.

 “Deliberately infecting volunteers with a known human pathogen is never undertaken lightly,” said Professor Peter Openshaw, co-investigator on the British study. “However, such studies are enormously informative about a disease, even one so well studied as Covid-19.” In the first phase of the U.K. challenge study, researchers will expose 90 paid volunteers aged 18 to 30 to the virus using nasal drops in an effort to determine the smallest level of exposure needed to cause Covid-19. The virus will be grown in the lab to control purity and assure similar dosing to all volunteers. The research will be conducted at the Royal Free Hospital in London, which has a specially designed biosafety area to contain the disease. Volunteers will quarantine for 2 ? weeks and then be monitored for at least a year to ensure they don’t suffer any long-term effects. The British government is investing $43 million in this trial.

 I think ethical issues are raised around the topic of paying volunteers to participate. One might argue that by offering money, a volunteer’s decision-making is being swayed by money, and one might take that a step further and suggest that the trial takes advantage of poorer people who are more likely to need the money offered by the trial. I could not find out how much money the volunteers will be paid. Danica Marcos, a British graduate student said, “So many people (are) struggling right now, and I want this pandemic to be over. Every day that goes on, more cases are going on, more people are dying. And if this vaccine trial could mean that this period of trauma for the whole world will be over sooner, I want to help. I want to be a part of that.” It’s hard to argue with that kind of spirit!

2. “Why are vaccines so important to population health management?”

Here is an article I wrote in March 2019 – one year before the onset of the Covid-19 pandemic. Interesting to read one year later…

 If you stroll through one of the many quaint, small graveyards that dot the New England landscape, you can’t help but notice the large number of small gravestones. These small fading memorials to beloved children who died at the age of one, or two or six reflect the unstoppable ravages of infectious diseases such as measles, mumps, rubella, diphtheria, pertussis, plague, tetanus, influenza, hemophilus influenza B, typhoid, cholera, rabies, yellow fever and polio. There were no vaccines to prevent these illnesses and no medicines to save these children once they were infected. Doctors could do nothing, other than attempt to console grieving parents.

 Here are a few relevant current headlines:

•  The CDC is currently reporting on 5 measles outbreaks in 10 states with 159 cases reported. The majority of children were unvaccinated.
• A measles outbreak hit Washington state. As of February 14, there were 53 confirmed cases in Clark County.
• In Massachusetts, a third child just died of influenza as of February 19.

Humans have lived with and died from infectious diseases since the dawn of time. However, over the past 230 years we have developed many vaccines to protect ourselves against those diseases - truly a remarkable medical achievement. Incredibly, today we are able to vaccinate our children, teenagers and adults against the majority of lethal infectious diseases. 

 A brief history of vaccine development

Our adventures and achievements in vaccine development began in the late 1700s and continue to this day.  Some important milestones include:

• 1790s -- Dr. Edward Jenner developed the first vaccine for smallpox
• 1885 – Rabies vaccine
• 1896 – Typhoid and cholera vaccines
• 1897 – Plague vaccine
• 1918 – Influenza epidemic claimed XX million lives
• 1923 – Diphtheria vaccine
• 1926 – Pertussis vaccine
• 1926 -- Tetanus
• 1927 -- BCG vaccine against tuberculosis
• 1935 – Yellow fever
• 1936 -- Influenza
• 1955 – Polio vaccine
• 1963 – Measles
• 1967 – Mumps
• 1969 -- Rubella
• 1970 – Anthrax
• 1974 – Meningococcal
• 1977 – Last documented case of smallpox in Somalia after international campaign to eradicate the disease.
• 1977 – Pneumococcal
• 1981 -- Hepatitis B
• 1985 – H. Influenzae type B (HIB)
• 1989 -- Typhoid
• 1993 – Cholera
• 1995 -- Varicella
• 1996 – Hepatitis A
• 1999 – Rotavirus
• 2005 -- Meningococcal
• 2006 -- Zoster
• 2006 – Human Papillomavirus (HPV)
• 2019 -- A new malaria vaccine that is partially effective could help reduce the 300 million annual infections and deaths of 1 million children annually.
• 2019 -- Active exploration of an HIV vaccine

 Troubling skepticism puts this medical miracle at risk

For a vaccination program to protect a population against an infectious disease, 85-95% of the population must be vaccinated. This creates what is known as “herd immunity”, protecting the small number of individuals who cannot receive a vaccine. Since the advent of vaccines with Dr. Jenner in the 18th century, some fraction of the population remains skeptical, suspicious and unwilling to participate in vaccination. This long fascinating chapter in the history of science shows that, like sunspots, the numbers of people against vaccinations wax and wane over time for unclear reasons. 

 In the recent past in the United States, many people believed (and many still do) that vaccines, especially the measles, mumps, rubella (MMR) vaccine “cause” autism. Though there was never a shred of scientific evidence to support this claim, the idea took root and even today we are witnessing a resurgence of measles as we have lost the “herd immunity” that exists when 85-95% of the population gets vaccinated.

 Currently, all states require parents to vaccinate their children in order to attend school. This requirement applies to private schools as well as public schools. But all states also allow parents an exemption from vaccination on religious grounds and currently 17 states allow exemptions based on “personal or philosophical reasons” against vaccines. This recent outbreak of measles in the United States is causing some public health entities to reconsider this liberal attitude towards vaccine exemptions. And in case you had any doubt as to the lethality of measles, as recently as 1991, a deadly measles outbreak in Philadelphia took the lives of nine children.

 In defense of medical science

In my opinion, people who do not believe in the benefits of vaccines, or in the science of climate change, or for that matter even in science itself, represent a risk not only to the health of their own children, but also create a risk to elderly and immune compromised patients of any age who become susceptible to transmissible infections in public places as our herd immunity is lost. The good news is that using updated aggregated claims and EHR data, an ACO or health care entity or payor can identify which patients have gaps in vaccine status. Based on that gaps list, care managers or other staff can easily do the outreach to get those patients in for their needed vaccines. ACOs can also leverage their efficiency by using automated outreach methods including auto phone dialing, text and e-mails. Information technology goes a long way towards solving the problem of helping the unvaccinated population.  ACOs can also develop educational strategies for their patients, including the parents of their pediatric patients.

 My hope is that ACOs, academic medical centers, departments of public health and the medical community ourselves will recommit to educating the public about the safety and benefits of modern vaccines that have the power to save us from terrible suffering and untimely death. We should not have to see more small gravestones in our cemeteries because we declined to believe in science…

 Sources:

1. Health Affairs: The History of Vaccines and Immunization: Familiar Patterns, New Challenges Alexandra Minna Stern, Howard Markel

https://doi.org/10.1377/hlthaff.24.3.611

2. History of Vaccination, Stanley Plotkin, Proceedings of the National Academy of Sciences, 2014 Aug 26; 111(34): 12283–12287.  10.1073/pnas.1400472111

3. Centers for Disease Control and Prevention, www.cdc.gov