World Polio Day

gold poliovirus

Image credit: Jason Roberts

As a virologist who has worked on poliovirus since 1979, I would be remiss if I did not note that today, 24 October, is World Polio Day. World Polio Day was established by Rotary International over a decade ago to commemorate the birth of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis.

The polio eradication effort has made impressive progress towards eliminating polio from the planet. In 1988 it was estimated that there were a total of 350,000 cases of poliomyelitis (probably an underestimate); as of this writing there have been 301 cases in 2013, which is unfortunately already more than in all of 2012 (223). Some setbacks to the program include an outbreak in the Horn of Africa, the finding of wild poliovirus (but no paralytic cases) in Israel, and two suspected cases in Syria. Transmission of wild poliovirus has never been interrupted in three countries: Afghanistan, Nigeria, and Pakistan. The good news is that India remains polio-free, a remarkable achievement.

Currently the eradication effort mainly utilizes the Sabin oral poliovirus vaccine strains (OPV). These vaccines are taken orally and replicate in the intestine, followed by entry into the bloodstream. They induce antiviral immunity in both the intestine and the blood. However, a drawback to using the Sabin vaccines is that the viruses revert to neurovirulence during replication in the intestine. As a consequence, virulent polioviruses are shed in the feces. These can cause poliomyelitis, either in the vaccine recipient or in unimmunized contacts. As wild polioviruses are eliminated, vaccine-derived polioviruses will continue to circulate, necessitating ‘vaccinating against the vaccine’. As a consequence, WHO has proposed a switch to the inactivated poliovirus vaccine, IPV, which if prepared properly cannot cause poliomyelitis.

A very good question is whether the use of IPV can lead to elimination of poliovirus from the planet. Consider the following scenario: at some point in the future the use of Sabin vaccines is discontinued, and all polio immunizations are done with IPV. Vaccine-derived polioviruses will still be present, and possibly also wild polioviruses. As shown by the recent detection of poliovirus in Israel, poliovirus can replicate in the intestines of individuals who have been immunized with IPV. Therefore, in a post-OPV world, immunization with IPV will still allow circulation of vaccine-derived polioviruses. As long as immunization continues at a high rate, there should be no cases of paralytic disease – but we already know that high immunization coverage is difficult to maintain. How long will we need to immunize with IPV before circulation of vaccine-derived polioviruses will stop?

Below are links to resources on polio, provided by David Gold at Global Health Strategies:

  • An expert panel including Dr. Bruce Aylward, WHO’s Assistant Director-General for Polio, will discuss the status of eradication today at Rotary International’s ‘Making History‘ event. Help share and watch live at 6:30 PM ET.
  • Look out for A Shot to Save the World, a documentary about Jonas Salk’s vaccine discovery, airing on the Smithsonian Channel today at 8:00 pm ET/PT.
  • President-elect of the Asia Pacific Pediatric Association Naveen Thacker wrote an opinion piece on India’s incredible achievements against polio, and the benefits and lessons India’s experience offers. Help share his piece.
  • Check out a video by footballer Leo Messi (tweet), a blog post by Paralympian polio-survivor Dennis Ogbe (tweet), a Vaccines Today blog post by Ramesh Ferris (tweet) and an Impatient Optimists post on other ways to get involved today.
  • Pakistan: Thanks to the work of heroic vaccinators, Pakistan has eliminated polio from much of the country. This year, 74% of cases, and 93% during the high season, have occurred in one region: the Federally Administered Tribal Areas (FATA) of northern Pakistan. North Waziristan, in FATA, has been inaccessible since June 2012, and has reported 14 wild polio cases this year in an increasingly severe outbreak. The program is intensifying immunizations in neighboring areas to prevent spread, but continued inaccessibility in this region poses a serious risk to the global effort.
  • Nigeria: Challenges persist in northern Nigeria, particularly in Borno and Kano, but other traditional reservoir areas appear to be largely polio-free — reminders that success is possible. Of particular importance, the northwest of the country, from which polio has historically spread into West Africa, has not had any cases this year. Read and help share a recent Science article (available with free registration) that takes an in-depth look at Nigeria’s eradication efforts.
  • Afghanistan: Afghanistan’s traditionally endemic Southern Region remains polio-free, with all cases this year linked to cross-border transmission with Pakistan. Next month will mark one year since the last case was recorded in the Southern Region.
  • Horn of Africa: GPEI partners responded rapidly to the outbreak, and we’re seeing signs of progress: there have been no confirmed cases in the Banadir region of Somalia, the epicenter of the outbreak, or in Kenya, since August. The number of unimmunized individuals in the region still poses a major risk for further spread. Outbreak response will continue aggressively into 2014.
  • Possible Polio Cases Detected in Syria: Syria reported a cluster of possible polio cases on 17 October that is currently being investigated. The country has been polio-free since 1999, but is considered at high risk for polio due to declining immunization rates. Syria’s Ministry of Health is preparing an urgent response across the country, aiming to conduct the first campaign by the end of October. Supplementary immunization activities are being planned in neighboring countries, including Lebanon, Jordan, Egypt, southern Turkey and western Iraq. The GPEI has a history of eliminating polio in areas of insecurity. Drawing from past successful efforts in insecure areas, including El Salvador and Angola, the Strategic Plan outlines approaches to eliminating polio in areas of conflict that are informing Syria’s response.
  • IMB Report: The International Monitoring Board (IMB), tasked with assessing the GPEI effort each quarter, met earlier this month to review the program’s progress, challenges and risks in endemic countries, the Horn of Africa and Israel. The IMB’s report from this meeting will be available here on Friday, 25 October

 

Jeffrey Almond on vaccine development

Dr. Jeffrey Almond began his career as an academic virologist studying influenza virus, then moved to poliovirus. He made major contributions to our understanding of the molecular basis of poliovirus attenuation and reversion to virulence. After 20 years in academics he moved to Sanofi Pasteur, where he is currently Vice President, discovery research and external R&D.

I interviewed Jeffrey Almond, Ph.D., in Manchester UK at the 2013 meeting of the Society for General Microbiology. We spoke about the eradication of poliovirus, challenges in making a universal influenza vaccine, a dengue virus vaccine developed by Sanofi Pasteur, and moving from academia to industry.

 

TWiV 227: Lacks security and bad poultry

On episode #227 of the science show This Week in Virology, the complete TWiV team reviews the controversial publication of the HeLa cell genome, a missing vial of Guanarito virus in a BSL-4 facility, and human infections with avian influenza H7N9 virus.

You can find TWiV #227 at www.microbe.tv/twiv.

WHO will switch to type 2 inactivated poliovirus vaccine

Poliovirus by Jason RobertsThe World Health Organization’s campaign to eradicate poliomyelitis made impressive inroads in 2012: only 212 cases were reported, compared with 620 the previous year; moreover, India remained polio-free. The dark side of this story is that as wild polio is eliminated, vaccine-associated poliomyelitis moves in to take its place. The landmark decision by WHO to replace the infectious, type 2 Sabin poliovaccine with inactivated vaccine is an important step towards eliminating vaccine-associated polio.

A known side effect of the Sabin poliovirus vaccines, which are taken orally and replicate in the intestine, is vaccine-associated poliomyelitis. During the years that the Sabin poliovirus vaccines (also called oral poliovirus vaccine, or OPV) were used in the US, cases of poliomyelitis caused by vaccine-derived polioviruses (VDPV) occurred at a rate of about 1 per 1.4 million vaccine doses, or 7-8 per year. Once the disease was eradicated from the US in 1979, the only cases of polio were caused by VDPVs. For this reason the US switched to the Salk inactivated poliovirus vaccine (IPV) in 2000.

The main vaccine used by WHO in the global eradication effort has been a trivalent preparation comprising all three serotypes. When type 2 poliovirus was eradicated in 1999, many countries began immunizing only against types 1 and 3 poliovirus. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. This switch, together with poor routine immunization coverage in some areas, has lead to polio outbreaks caused by cVDPV2 in countries such as Pakistan.

Alan Dove and I suggested in 1997 that it would be necessary to switch from OPV to IPV to achieve polio eradication. However, WHO did not agree with our position:

Dove and Racaniello believe that the reliance of the WHO on the live Sabin oral poliovirus vaccine (OPV) means that there will be a continuing threat of release of potentially pathogenic virus into the environment. They therefore recommend a switch to the inactivated polio vaccine (IPV). In response, Hull and Aylward explain why a switch from OPV is not necessary and describe the studies being sponsored by the WHO to determine how and when immunization can safely be ended.

I remember well the words of DA Henderson, the architect of smallpox eradication, when I proposed a switch to IPV at a conference in 2001:

There is no way it is going to come about and as an end-game strategy it is dreaming to believe that this is reasonable. So, it is just not on.

Apparently I was not dreaming: in May 2012 the 65th World Health Assembly requested that the Director-General “coordinate with all relevant partners, including vaccine manufacturers, to promote the research, production and supply of vaccines, in particular inactivated polio vaccines, in order to enhance their affordability, effectiveness and accessibility”. Later last year the Strategic Advisory Group of Experts on immunization (SAGE) called for a global switch from trivalent to bivalent OPV, eliminating the type 2 component. To ensure that circulating type 2 VDPVs do not pose a threat, SAGE also recommended that all countries introduce at least one dose of inactivated poliovaccine. This decision was announced in the 4 January 2013 Weekly Epidemiological Record (pdf).

The fact that WHO believes it is necessary to switch from type 2 OPV to IPV surely means that in the future, when types 1 and 3 polioviruses are eradicated, types 1 and 3 OPV will be replaced with IPV. This is the correct endgame strategy for eradicating polio. Once circulating VDPVs are no longer detectable on the planet – something that will probably not happen before 2020 – then we may safely stop immunization with IPV.

Poliovirus image courtesy of Jason Roberts.

Vaccine-associated poliomyelitis in Pakistan

Poliovirus by Jason RobertsAn outbreak of ten cases of poliomyelitis caused by circulating vaccine-derivied poliovirus type 2 (cVDPV2) is ongoing in Pakistan, centered in the Kila Abdulla/Pishin area of Baluchistan. The same virus strain has spread to the neighboring Kandahar province in Afghanistan, where two paralytic cases have been reported. Vaccine-derived poliomyelitis is a well-known consequence of immunization with the Sabin poliovirus vaccine.

There are three serotypes of poliovirus, each of which causes poliomyelitis. The three vaccine strains developed by Albert Sabin (OPV, oral poliovirus vaccine) contain mutations which prevent them from causing paralytic disease. When the vaccine is taken orally, the viruses replicate in the intestine, and immunity to infection develops. While replicating in the intestinal tract, the vaccine viruses undergo genetic changes. As a consequence, the OPV recipients excrete neurovirulent polioviruses. These so-called vaccine-derived polioviruses (VDPV) can cause poliomyelitis in the recipient of the vaccine or in a contact. During the years that the Sabin poliovirus vaccines were used in the US, cases of poliomyelitis caused by VDPV occurred at a rate of about 1 per 1.4 million vaccine doses, or 7-8 per year. Once the disease was eradicated from the US in 1979, the only cases of polio were caused by VDPVs. For this reason the US switched to the Salk (inactivated) poliovirus vaccine in 2000.

Because VDPVs are excreted in the feces, they can spread in communities. These circulating VDPVs, or cVDPVs, can cause outbreaks of poliomyelitis in under-immunized populations. Examples include outbreaks of poliomyelitis in an Amish community and in Nigeria in 2009 caused by cVDPV2. Nigeria employed trivalent OPV before 2003, the year that this country began a boycott of polio immunization. Because type 2 poliovirus had been eradicated from the globe in 1999, when immunization in Nigeria resumed in 2004, monovalent types 1 and 3 vaccine were used. The source of the VDPV type 2 in Nigeria was the trivalent vaccine used before 2003.

For many years the vaccine used by WHO in the global eradication effort was a trivalent preparation comprising all three serotypes. When type 2 poliovirus was eliminated, many countries began immunizing only against types 1 and 3 poliovirus. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. This has likely lead to the emergence of cVDPV2 in Pakistan, together with poor routine immunization coverage.

The resurrection of poliovirus type 2 highlights the difficulties in eradicating a pathogen using a vaccine that can readily mutate to cause the disease that it is designed to prevent. As wild type polioviruses are eliminated, the only remaining polio will be caused by the vaccine. If immunization is then stopped, as planned by WHO, there will likely be outbreaks of polio caused by cVDPV of all three serotypes. The solution to this conundrum is to switch to the inactivated vaccine until cVDPVs disappear from the planet.

Exacerbating the polio situation in Pakistan was the murder in the past week of nine immunization workers in several provinces. The Taliban, which carried out the executions, accused them of being spies. This accusation originates from the CIA operation in 2011 in which a Pakistani doctor ran an immunization program in Abbottabad in an attempt to obtain DNA samples from the Bin Laden family. As a result of this violence, immunization campaigns in Balochistan have been suspended. Coupled with the previous refusal of many parents to have their children immunized, this action makes it likely that poliovirus will spread more extensively in the country, making eradication even more difficult.

Poliovirus image courtesy of Jason Roberts.

Virology class at Montana State University

In August this year I received the following note from Michele Hardy, Professor of Immunology and Infectious Diseases at Montana State University:

I’m writing to ask if you’d be willing to participate in my  undergraduate/graduate virology course this fall.   We have several guests per semester that we Skype in to talk with students.  I was thinking of you as a guest to talk with them about poliovirus, but also about your role in TWiV.  It’s not a lecture format, instead teams of students will research your work and come up with a set of questions that we would provide to you in advance.  In the past they’ve asked specifically about research areas, but also are really interested in what people’s backgrounds are, how they got to be where they are now, etc. We give them pretty much free reign to ask whatever they want to, whether it’s virus-specific or not.  Our goal is to get them excited about virology and so we don’t put restrictions on what they’re allowed to talk about.  Sometimes they stick to the questions they submit, others they take whatever direction the discussion goes.  There are ~60 students, 8-10 of them are graduate students.  We encourage them to listen to TWiV a few times a semester so I think they’ll be excited to talk with you.  Thanks for considering this, I look forward to hearing from you.

This past Monday I joined the class via Skype. The questions ranged from how I became interested in and use social media, to polio eradication. Listen to our conversation by clicking the arrow below.

Click arrow to play | Download (35 MB .mp3, 48 min)

Update: Received a nice thank you card from the class:

Bozeman class 2012

World Polio Day

Today, 24 October 2012, is World Polio Day:

World Polio Day (October 24) was established by Rotary International over a decade ago to commemorate the birth of Jonas Salk, who led the first team to develop a vaccine against poliomyelitis. Use of this inactivated poliovirus vaccine and subsequent widespread use of the oral poliovirus vaccine developed by Albert Sabin led to establishment of the Global Polio Eradication Initiative (GPEI) in 1988. Since then, GPEI has reduced polio worldwide by 99%.

The polio eradication effort has made huge inroads towards eliminating polio from the planet. In 1988 it was estimated that there were a total of 350,000 cases of poliomyelitis (probably an underestimate); as of this writing there have been 174 cases in 2012. India has been polio-free for over one year, a remarkable achievement. Only three countries have never seen a break in wild poliovirus transmission: Afghanistan, Nigeria, and Pakistan. Continued surveillance and extensive immunization efforts will be needed to remove the last pockets of the disease from these countries.

Because only 1% of poliovirus infections lead to paralytic disease, the 174 polio cases in 2012 translates to 17,400 infections. The virus clearly has the ability to circulate undetected, which can be a problem if surveillance drops. Another thorny issue is how to deal with immunization once the disease has been eradicated. The vaccine strains used for immunization revert to virulence during replication in the human intestine, with the consequence that immunized individuals shed virulent poliovirus into the environment. These viruses will pose a threat to non-immune individuals. How long these vaccine-derived neurovirulent strains will persist in the population is unknown. Therefore we cannot simply stop vaccinating against polio once the disease is eradicated. It will likely be necessary to immunize globally with the non-infectious inactivated poliovirus vaccine until vaccine derived polioviruses are no longer detected.

Related: World Polio Day

Can India remain polio-free?

global polio 2012India has been free of polio for over one year. This is a remarkable accomplishment, considering that just 30 years ago the country recorded 200,000 cases of the disease annually, or one every three minutes. With polio endemic in two neighboring countries, Pakistan and Afghanistan, and in the more distant Nigeria (figure), can India remain free of the disease? According to Shahnaz Wazir Ali, the Pakistani Prime Minister’s focal person for polio, there is little risk for export of the virus from Pakistan:

The likeliness of polio virus being exported to India from Pakistan is very low, and historically, it has not happened. Those who travel from India to Pakistan are mostly adults. There are rarely any babies. So the chances are low.

It is correct that polio has not traveled from Pakistan to India during the modern era of virus detection (1980 to the present). However, the same genotypes of types 1 and 3 poliovirus have circulated in both countries, implying sharing of viruses some time in recent history. Therefore Ali cannot conclude that export of virus to India ‘has not happened’.

Poliovirus continues to circulate in Pakistan, which shares a border with India: there were 198 cases in that country in 2011, the most of any in the world, and 16 cases so far in 2012. Remember that most poliovirus infections are asymptomatic, so the number of paralytic cases is far lower than the actual number of infections. The ratio of paralytic cases to infections varies according to the viral serotype: 1:200, 1:1800, and 1:1200 for types 1, 2, and 3 respectively. Furthermore, poliovirus has been known to spread from Pakistan from other countries. An outbreak of polio in Xinjiang, China, in 2011 was caused by virus imported from Sindh, Pakistan. There were 21 paralytic cases caused by poliovirus type 1, over half of which occurred in individuals 19-53 years old. The outbreak was halted by immunization but the region remains at risk for importation from Pakistan.

Poliovirus also continues to circulate in Afghanistan, which lies on the northwestern border of Pakistan. Eighty cases of paralytic disease were reported in this country in 2011, and 7 so far in 2012. It has been difficult to control polio in the southern provinces of Kandahar and Helmand due to ongoing armed activities. There is active migration between the southern regions of Afghanistan and Pakistan which has lead to a steady exchange of polioviruses between the two countries.

There many other examples of polio spread from one country to another in recent years. Following cessation of polio immunization in 2003, virus spread from Nigeria to many countries in Africa as well as to Indonesia. From India poliovirus has spread to Nepal, Angola (2005 and 2007), and Tajikistan and then to Russia (2010), in all cases causing substantial outbreaks of the disease.

The message is clear: poliovirus spreads easily among countries, and it is often spread by infected adults, not children. Because poliovirus infection is frequently asymptomatic, such spread cannot be detected by simply examining travelers for signs of paralysis.

For these reasons I am skeptical of Ali’s reassurance that the virus is not likely to spread from Pakistan to India. If adults mainly travel from India to Pakistan, as she says, they could well be infected and import the virus back home before it is detected. Furthermore, adults could bring the virus to India from other countries where poliovirus continues to circulate, although that is not Pakistan’s concern.

Because Pakistan remains a major reservoir of poliovirus, it is a good sign that the country is acknowledging the possibility that they might export the virus to India. The best way to avoid this scenario would be to intensify their immunization programs and eliminate the virus. Apparently Ali has been speaking with Indian officials to learn how they accomplished this goal:

We got to know what actually took India to become polio-free. We have understood the scale and efforts that we require to make Pakistan polio-free.

 

India polio-free for one year

Year in polio 2011A year has passed since the last reported case of poliomyelitis in India, which occurred on 13 January 2011 in a two year old girl in Howrah, West Bengal. If no additional cases are reported in the next few weeks (some samples are currently being tested for the virus), then it will mark the first time that India has been polio free for one year.

This achievement represents a remarkable turnaround for India, where control of the disease had for years been extremely difficult. As recently as 2009 there were 741 confirmed cases of polio caused by wild-type virus (as opposed to vaccine-derived virus) in India. The tide turned in 2010 with only 42 confirmed polio cases, and in calendar year 2011 there was just one. That is why the 2011 map marking locations of confirmed wild polio cases in India (see figure) shows only one red dot (paralysis caused by type 1 poliovirus) in the country. The blue dots indicate cases caused by type 3 poliovirus.

The challenge now is to keep India free of polio. The map shows why this will be difficult – there are many red dots (cases of type 1 polio) in neighboring Pakistan and Afghanistan. Poliovirus does not respect national borders – China had been free of polio since 1999, but now there are red dots in that country. That outbreak was imported from Pakistan. Even the polio cases in more distant countries such as Africa constitute a threat. As long as there is polio somewhere, all countries must maintain extensive immunization programs. Whether or not that will happen depends upon money, determination, and allowing immunization campaigns to proceed without interruption.

Once polio was eradicated from the United States, the only poliomyelitis was caused by the Sabin vaccine. Consequently this country switched to the use of inactivated vaccine in 2000. As other countries eliminate the disease, vaccine-associated poliomyelitis will become more prominent. If eradication of polio is achieved, the world will have to switch to using inactivated poliovaccine.

Related:

Wild poliovirus in China
Dreaming of inactivated poliovaccine
Poliomyelitis after a twelve year incubation period
Poliovirus vaccine litigation

 

TWiV 149: Live at ICAAC in the Windy City

twiv at icaacHosts: Vincent Racaniello, Rich Condit, Mark Pallansch, and Trine Tsouderos

Vincent, Rich, Mark, and Trine discuss science and medicine in journalism and the eradication of poliovirus at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).

Click the arrow above to play, or right-click to download TWiV 149 (62 MB .mp3, 86 minutes).

Subscribe to TWiV (free) in iTunes , at the Zune Marketplace, by the RSS feed, by email, or listen on your mobile device with the Microbeworld app.

Links for this episode:

Weekly Science Picks

Rich – Parachute use to prevent death (Brit Med J)
Vincent –
Ian Lipkin’s Op-Ed on Contagion and a review of the movie (both NY Times)

Listener Pick of the Week

MichaelBacteria billboard for Contagion (YouTube)

This episdode of TWiV is sponsored by Wiley-Blackwell, the leading scientific publisher of books, scholarly journals, major reference works and databases. This month they are offering 25%-off all Microbiology and Virology books. To take advantage of this offer go to www.wiley.com/go/microbeworld.

Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv, or call them in to 908-312-0760. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.