Gut reaction: the impact of intestinal infections on polio vaccination
Could gut infections be making the standard polio vaccine ineffective in children in low-income countries? Edward Parker, a PhD student at Imperial College London is trying to find out, as he explains in his article commended in the 2014 Max Perutz Science Writing Award.
The Global Polio Eradication Initiative was never meant to last this long.
In 1988, when the campaign was launched, there was considerable optimism that polio would not see the end of the century. Although this deadline has long since passed, the progress made by the eradication initiative should not be underestimated: in what is arguably the greatest onslaught against a disease in history, polio has been reduced from an infection with a global distribution, responsible for 350,000 cases of paralysis each year, to one that is on the brink of extinction. Just 223 cases of the disease were reported in 2012 ― the lowest number on record.
But polio is a wily foe. Despite exhaustive vaccination campaigns, the virus has never been eliminated in Pakistan, Afghanistan, and Nigeria. What’s more, polio has recently been on the move. After cases in Ethiopia, Somalia, Cameroon, Equatorial Guinea, Syria, and Iraq, in May 2014 the World Health Organization declared the spread of polio to be an international public health emergency.
Why has polio proven so resilient in the face of eradication efforts? Certainly, the problem is far from straightforward. The eradication campaign has had to contend with huge logistical challenges, civil unrest, vaccine boycotts, and a recent upsurge in violence against healthcare workers.
There are also limitations to the key weapon of the campaign’s armoury: the oral poliovirus vaccine (OPV). First developed by Albert Sabin in the late 1950s, OPV is, in many ways, an ideal vaccine. It is cheap, easy to administer (just a few drops on the tongue will do), and capable of protecting against each of the three types of poliovirus.
However, since the earliest trials of OPV, it has been apparent that children living in tropical, low-income countries are less likely to respond to immunisation than those in industrialised settings. While each dose of OPV will protect roughly 65 per cent of children from type 1 paralytic disease in high-income countries, the same vaccine protects just 13 per cent of children in India.
It is this phenomenon that my research is concerned with. Unfortunately, there is unlikely to be a simple explanation. Malnutrition, interference by maternal antibodies, and deficiencies in micronutrients may all contribute to the impaired performance of OPV in low-income countries. However, there is a good reason to suspect that intestinal pathogens may be important, and it is this possibility that I am investigating.
The hypothesis is certainly persuasive: infants living in tropical countries are exposed to a multitude of intestinal infections. If these infections activate the gut’s immune system at the time of immunisation, the vaccine viruses may be unable to induce a proper immune response. Like attempting to make a safety announcement at a rock concert, the message will simply be lost in the noise.
We are not the first group to consider the issue. In fact, at the First International Conference on Live Poliovirus Vaccines, held in 1959, Sabin himself presented several cases in which the response to his new vaccine seemed to be impeded in individuals infected with other intestinal viruses at the time of vaccination.
However, more recent studies have failed to paint a clear picture ― while some have supported the interfering influence of intestinal pathogens, others have refuted these effects, and in the last decade or so, the question has dropped out of fashion.
But the tools of science are ever changing. Lab techniques developed in the past few years have opened up new ways of exploring the relationship between intestinal pathogens and OPV. With this in mind, I donned my lab coat and ― working alongside collaborators in southern India ― put to use a new molecular test that enables more than 30 different pathogens to be detected in stool samples in a matter of hours (to put this in context, in Sabin’s day, the detection of a single virus could take up to two weeks).
Using this tool, we are examining the frequency of intestinal viruses, bacteria, and larger parasites (such as nematode worms) among Indian infants at the time of vaccination. In doing so, we hope to gain a detailed picture of the extent to which individuals who fail to respond to OPV experience a greater burden of infections.
The implications of this research extend beyond polio. Like OPV, oral vaccines against rotavirus and cholera have proven to be less dependable in low-income countries. Our immune response to these vaccines may well be shaped by similar factors.
More than half a century has now passed since the first doses of OPV were administered. Despite considerable effort, we remain unsure as to why the vaccine performs better in some regions than others. What is clear is that OPV and other oral vaccines face unique obstacles precisely where they are needed most.
Each step we make towards understanding the nature of these obstacles is a step towards overcoming them.