While on vacation last week I was a guest teacher in my friend’s advanced biology class. They were doing a unit on evolutionary biology and their teacher, my friend, had asked them to conceptualize a pathogen that would be evolutionarily successful. They had been learning about the “trade off hypothesis” (1) which is the idea that for an organism to be an evolutionary success it must balance virulence (harm inflicted on a host) with ability to transfer to a maximal number of hosts. For example, a pathogen that was highly virulent would cause a huge amount of harm to the host, in some cases killing them, and thus creating a dead end in its evolutionary goal-> to make as many copies of itself as possible (we will ignore the ability for the continued infectivity of bodies after death for this purpose), verses pathogens that take on the goal of minimal virulence for increased transmission, for this I like to think of rhinovirus which causes the common cold. Sure you feel a little sick when you get a cold (its virulence) but not sick enough to avoid interacting in the world and spreading the virus.
While visiting the classroom I decided to tell them about two historical pathogens that had wreaked havoc on the world in the not so distant past: Polio and smallpox, in order to illustrate different evolutionary strategies taken by each virus and why we were able to easily eradicate one (smallpox), while its taken us longer on the other (poliovirus).
Smallpox had plagued mankind for millennia (it was endemic in parts of Asia as far back as the 1st century CE) and it was incredibly virulent (mortality rates ranged from 30-50%) . Most of the students had heard about smallpox but didn’t know the details of its infection, or how it spread (respiratory); what was funny to me was that the students all assumed that the mortality rate was much higher (a lot guessing around 90%) and I had to explain to them that a mortality rate of 30-50% was indeed very high and that a 90% mortality rate would be an evolutionary dead end for any virus. The last wild type smallpox case was in 1977 in Somalia (2).
The reason the campaign against smallpox was so effective was not only because there was an effective vaccine, but also due to the nature of the virus itself. Smallpox does not have an asymptomatic carrier state, i.e. you are only able to spread it once you start experiencing symptoms. The incubation period is 10-14 days, during which time you are not infectious, then you progress to a pre-eruptive stage lasting 2-4 days which comes with symptoms of high fever, headache, myalgias, nausea and vomiting not unlike the flu. When i asked the students what they would do if they started feeling like this most of them answered, i would stay home in bed, which is exactly the point. Smallpox is so virulent that people will stay home and avoid going out into the world and spreading the illness. The point at which smallpox reaches its peak infectivity is during the rash stage and at that point the cat is out of the proverbial bag. Another characteristic of smallpox that made it relatively easy to eradicate was that its only hosts were humans. Unlike other viruses (such as ebola, or rabies) there are no other organisms that variola infects and there is no independent vector spreading the disease (as with plague). Finally, the vaccine for smallpox worked, and it worked well. In fact if someone has been exposed to the virus, if they receive the vaccine within 3 days they are likely to either not become ill, or experience a much less severe form of the illness. I used this example to illustrate to the students why a highly virulent virus would not necessarily be the most evolutionarily beneficial strategy (all info 2).
Contrast smallpox with polio where 90-95% of infections are asymptomatic, which means that people are shedding the virus without knowing it. Another thing that shocked students was how low the paralysis rates were (along the lines of 0.1% of infection). They had assumed that because they had all heard about how horrible poliovirus was that the virulence must be so much higher (3). I explained to them that this asymptomatic infection was one of the reasons why it was so difficult to eradicate poliovirus, i also explained that the nature of the vaccine itself contributed to the persistence of the virus (though we are now finally approaching true eradication). Polio dropped from 350,000 cases in 1988 to 1,000 in 2014, a monumental improvement due to the Global Polio Eradication Initiative (started in 1988). The initial goal of the Global Polio Eradication Initiative was to eradicate polio by 2000, the organization is spearheaded by WHO, Rotary international, CBC, UNICEF and The gates foundation. They used four strategies to attain this goal, first they instituted routine infant immunization programs globally, then they added additional immunization campaigns for age groups (say everyone under 5 for example) regardless of whether or not they’d already been immunized. They had active surveillance for paralysis and any time there was an outbreak they would travel to the location and re-immunize the population with OPV which stopped the spread (3).
There are two kinds of vaccine, an injectable killed virus (introduced first) and an oral attenuated viral vaccine. The oral vaccine was thought to be better because it induced a stronger immunity particularly in the gut (where poliovirus replicates first), it was easy to administer (all it required was a drop of vaccine on the tongue), and it was 10 times less expensive than the injectable variety. Essentially the perfect vaccine for a global program. One of the downsides of the oral polio vaccine is the fact that it causes paralysis in 1 in 2.5 million administrations (3). Which sounds like great odds until you factor in that there are 6 Billion people in the world and that someone who becomes infected with the active virus starts to shed it in their stool. Then you have a localized polio outbreak which is exactly what happened in The Dominican Republic and Haiti in 2000. In that outbreak there were 21 cases of paralysis and 2 deaths which were later found to be attributed to a vaccine derived strain of polio (4). My own uncle developed polio after receiving the oral polio vaccine in the late 60s (he later made a full recovery) but he accounted to me how one morning my grandmother told him to straighten up (She’d noticed his gait was crooked) and he found he was unable to. A better form of the inactivated vaccine (given as part of the tetanus/pertussis vaccine) became available in the 1980s and by 2000 everyone in the US had switched over to the inactivated, injectable form (4).
The question of the social justice of the continued use of the oral polio vaccine is interesting. OPV provides better immunity to poliovirus overall and decreases the spread when administered in an outbreak (however the ability of the vaccine to work is limited by the presence of healthy gut tissue able to mount an immune response which is limited in areas of chronic diarrhea and enteritis (3)) and is easy to administer, however the conversion to active form of the virus is a serious problem as it propagates the infection. As part of the The Polio Eradication & Endgame Strategic Plan 2013-2018 WHO is in the process of phasing out routine OPV (oral polio vaccine) in favor of the Inactivated, injectable variety (5). Polio has represented a formidable foe to global health, due in part to its evolutionary strategies. Each year as the number of cases of poliomyelitis drop we look forward to a time when we can finally say we were able to eradicate it, we’re not there yet.
- “Virulence Evolution”: http://public.wsu.edu/~broosien/VirulenceEvolution.html
- Up To date article on smallpox http://www.uptodate.com/contents/the-epidemiology-pathogenesis-and-clinical-manifestations-of-smallpox
- Up To date article on poliovirus http://www.uptodate.com/contents/global-poliomyelitis-eradication and http://www.uptodate.com/contents/polio-and-infectious-diseases-of-the-anterior-horn
I wanted to be the first to let you guys know that we will be now be updating our blog every 2 weeks with Global health topics and miscellaneous concerns. The goal is to have a new blog post out on the 1st and 3rd week of every month, starting with this post.
I am very excited to see how much interest we can gather for our global health endeavors. To that extent, I am also eager to recruit guest bloggers outside of our global health pathway residents, at BMC or otherwise, to blog about topics relevant to global health. Please subscribe to our blog, give us feedback and help us build a bigger online presence.
Now, back to your previously scheduled blogging.
If you haven’t already guessed, we’ve all returned from our global health trip to India, safe and sound. Even better, I did not contract dengue fever (this time).
Our trip was enlightening and exciting. Coming back to my home country and observing medical care in India, after a year away in the US, gave me a new perspective on things. It deepened my interests in cost-effective care, and my desire to practice equitable health.
We had a number of intense discussions and debates on topics ranging from the actual definition of global health, the stakeholders that determine global health funding and care delivery, disease profiles and historical trends of diseases, and, the future of global health.
It was a grounding experience, that has left me with the essentials to begin to carve out a path towards my intended career in global health. For this, and many other reasons, I hope future residency applicants interested in a career in global health, choose BMC.
But I digress.
One of the things I’ve decided from this trip, is that I need to choose my words and actions carefully. The term used to describe what I thought was global health has changed frequently. Terms such as global health, local health and international health have been throw around in the past, and, in our discussions. I believe that what I intend to practice, is equitable health. I want to be able to provide equal opportunities in health care, i.e, to attempt to level the playing ground wherever help is needed to achieve that.
I am interested in a career in equitable health focused on obtaining renal replacement therapy where it is inaccessible. I envision that I will one day learn to place peritoneal dialysis catheters to start peritoneal dialysis in resource-limited settings, and eventually develop peritoneal dialysis centers that are self-sustained by the people that live in that country/region. I plan on spending the next few years of residency and fellowship, trying to figure out the best way to make this possible.
I will have more information on this, and other global health endeavors in nephrology, in the coming months.
For now, I will leave you with a picture of us on a swing in my home in Trichy
From left to right: My grandmother; Andrea; Jocelyn; Ed; Me (Yuvaram)
Until next time!
P.S: My next topic will be Part 2 of the Medical Education System
Starting next month, the residents in the BMC IM global health pathway will be publishing pieces every two weeks on topics in global health. Should be quite enjoyable!
A group of Haitian medical students that my NGO works with produced this short, well-designed video that neatly captures key questions anyone should ask themselves before performing a volunteer medical experience. It’s great to hear what these partners of ours find most important.