Wednesday, August 20, 2014

PNAS: A Vaccine Evading Variant Poliovirus

Syrian kid being vaccinated against polio

Photo Credit WHO

 

# 8975

 

For those born after 1960, it is probably difficult to understand the kind of fear that Polio generated in the United States and around the world during the 1950s.  While only one infection in a hundred resulted in paralysis or death, polio was extremely infectious, and the United States routinely saw between 18,000 and 25,000 paralytic cases each year – mostly among young children.

 

Hospital wards were filled with paralyzed children trapped in iron lungs (a grim technology many younger adults have no memory of), which were used to keep them alive. The following short film clip may be hard for some to look at, but is a reminder of how things were . . . not so very long ago.

 

 image

 

In 1954  the first major field trials of the Salk vaccine took place, and the following year – after review of the data - a national vaccination campaign was launched. By 1957, after two years of vaccination - the number of new polio cases in the United States dropped to under 6,000, and by 1964 that number had dropped to just 121 cases.

image

 

There was suddenly tremendous optimism that modern science had within its power to eliminate even the worst childhood scourges, and indeed over the next decade tremendous progress was made against the lesser threats of measles, mumps, pertussis and chickenpox.

 

But, as we’ve seen with the recent resurgence of measles, mumps, and pertussis – and the steady decline in the effectiveness of once powerful antibiotics – mankind’s victories over diseases are sometimes fleeting.

 

Polio – which just a few short years ago seemed on the verge of global eradication – has also made a comeback.  So much so that last May we saw the WHO Declare Polio Spread A Public Health Emergency Of International Concern

 

As a result, new, strict polio vaccination requirements are being implemented for those countries with `active polio’.

 

In 2010 there was a particularly severe outbreak of polio in the Republic Of Congo (ROC), primarily in and around the port city of Pointe Noire (see WHO GAR update).  This outbreak was unusual in several respects:

  • The median age of victims was 20 (not under 5 as is normally the case)
  • The fatality rate – normally in the single digits – was 47%
  • Cases occurred among previously vaccinated adults

 

Yesterday, the journal PNAS published a study by an international group of researchers (including such familiar names as Christian Drosten  and Marion Koopmans) that examined this particular strain of polio, and found genetic changes in it that allowed it to evade the protective effects of the inactivated polio vaccine.

 

Robustness against serum neutralization of a poliovirus type 1 from a lethal epidemic of poliomyelitis in the Republic of Congo in 2010

Jan Felix Drexler, Gilda Grard, Alexander N. Lukashev, Liubov I. Kozlovskaya, Sindy Böttcher, Gökhan Uslu, Johan Reimerink, Anatoly P. Gmyl, Raphaël Taty-Taty, Sonia Etenna Lekana-Douki, Dieudonné Nkoghe, Anna M. Eis-Hübinger, Sabine Diedrich, Marion Koopmans, Eric M. Leroy, and Christian Drosten

Significance

In 2010, a large outbreak of poliomyelitis involving 445 laboratory-confirmed cases occurred in the Republic of Congo. The 47% case-fatality rate was unusually high. Outbreak severity was attributed to low immunization coverage but vaccine-mediated immunity against the outbreak virus was never investigated. We isolated the poliovirus type 1 responsible for the outbreak and located its evolutionary origins to Southeast Asia. Fatal cases showed evidence for previous vaccination against polioviruses and the outbreak virus was refractive against neutralization by monoclonal and vaccine-derived antibodies. This pointed to immune escape contributing to the severity of the outbreak. Sustained vaccination regimens in polio-free regions, together with clinical and environmental poliovirus surveillance will be necessary to combat antigenetically variant polioviruses in the poliomyelitis eradication endgame.

 

While people who had previously received the weaker inactivated poliovirus vaccine (IPV) were more vulnerable to this variant poliovirus, those who had recently received the live-attenuated Oral Polio Vaccine (OPV) were still protected. 

 

This discovery – of essentially a `mutated’ strain of polio – shows that the poliovirus can evolve over time.  While this particular variant appears to have been stamped out, the authors worry that more variants could appear in the future, complicating attempts to eradicate this virus.

 

In the battle against infectious diseases we’ve seen many wonderful advances made over the past century: Vaccines, antibiotics, even monoclonal antibodies. But no matter how sophisticated our response, the old adage – that nature always bats last – carries with it more than just a grain truth.  

 

A reminder that a loss of focus, or a break in vigilance, and even once defeated enemies can come back to bite us.