Implications of finding poliovirus in sewers of Brazil and Israel

Poliovirus by Jason RobertsWild poliovirus has been detected in the sewers of Brazil and Israel. Fortunately, no cases of poliomyelitis have been reported in either country. Why is poliovirus present in these countries and what are the implications for the eradication effort?

Wild type poliovirus (e.g. not vaccine-derived virus) was detected in sewage samples that had been collected in March 2014 at Viracopos International Airport in the State of Sao Paulo. Wild type poliovirus had not been detected in Brazil since 1989 when the last case of poliomyelitis was reported in that country, and has not been found since March 2014.

Sequence analysis of the RNA genome of the wild type poliovirus found in the Brazilian sewer indicates that it is closely related to an isolate from a case of poliomyelitis in Equatorial Guinea. It seems likely that this virus was carried to Brazil in the intestine of an infected person who did not have symptoms of paralytic disease (only 1 in 100 poliovirus infections lead to paralysis). This individual might have traveled from Equatorial Guinea to the Brazilian airport where use of the bathroom lead to introduction of poliovirus into the sewer.

There have been 8 reported cases of poliomyelitis in Equatorial Guinea in 2014, from which we can extrapolate that there have been approximately 800 infected individuals. Given the number of cases of poliomyelitis that have been reported globally over the past 20 years, it is surprising that virus has not been detected previously in Brazilian sewage, especially at the airport. I suspect that wild type poliovirus would be detected in sewage in the US, given the number of individuals who enter that country each day. However the US does not conduct routine surveillance for poliovirus in sewage.

Brazil utilizes the Sabin vaccine to control poliomyelitis, and in the past 8 years over 95% immunization coverage has been achieved. The Sabin vaccine is taken orally and replicates in the intestine where it induces mucosal immunity. The intestine of Brazilians do not support the replication of wild type poliovirus, which is why the presence of wild type virus in sewage is not a threat – it is unlikely to spread in the population.

The isolation* of wild type poliovirus from sewage and from stool samples in Israel is a far more serious matter. As with Brazil, there have been no reported cases of poliomyelitis in Israel since 1989. Yet ten different sites in central and south Israel have been persistently positive for wild type poliovirus since February 2013. Wild type poliovirus has been found intermittently at 8 of 47 different sampled sites in southern and central Israel, and in stool from healthy persons collected in July 2013.

Two major lineages of wild type polioviruses currently circulate in endemic countries: the South Asian (SOAS) lineage in Pakistan and Afghanistan, andthe West African lineage in Nigeria. Nucleotide sequence analysis of the wild type poliovirus isolates from Israel indicate that they are closely related to the South Asian lineage, and in particular to polioviruses that circulated in Pakistan in 2012 and in Egypt in 2012. Molecular clock analysis of the sequences indicate that poliovirus was probably transmitted in 2012 from Pakistan into Egypt and Israel, and then spread in the latter country.

The central point of poliovirus circulation is within Bedouin communities in the south of Israel. The main virus reservoir within this community is children less than 9 years of age who had been immunized with inactivated poliovirus vaccine (IPV). This vaccine has been exclusively used in Israel since 2005, with overall vaccination coverage between 92-95%, and 81-100% within individual districts. The last nine birth cohorts in this country have been immunized solely with IPV.

The response to isolation of wild type poliovirus in Israeli sewers was to complete IPV immunization of all children in the south, raising coverage to above 99%. Then from August 2013 onwards, all children up to the age of nine years old were given a dose of bivalent oral poliovirus vaccine (OPV) containing types 1 and 3 poliovirus. All children who received OPV had previously been immunized with IPV, a strategy that prevents vaccine-associated poliomyelitis.

The finding of sustained circulation of wild type poliovirus in Israel shows that the virus can circulate silently in a population that has been well immunized with IPV. Such circulation occurs because IPV does not sufficiently protect the intestinal tract against poliovirus infection. However poliomyelitis does not occur in such populations because IPV-induced antibodies in the blood prevent virus invasion into the central nervous system. The US now exclusively uses IPV and it is likely that wild polioviruses are present in US sewage, although as mentioned above the US does not search for poliovirus in sewage. Silent circulation of wild type poliovirus in countries that use IPV poses a threat to other countries where immunization coverage is low.

These findings indicate that immunization with IPV will not lead to eradication of wild type poliovirus. This observation is problematic because the World Health Organization has recommended a gradual shift from OPV to IPV. In the past I have also supported such a transition, but I have also remained cautious about the ability of IPV to immunize the human gut. The experience in Israel confirms my suspicions.

The US shifted from using OPV to IPV because the associated vaccine-associated poliomyelitis was not acceptable in a country with no paralytic disease caused by wild type poliovirus. Now it seems that eradication cannot be achieved with IPV. What can be done about this conundrum? OPV should be used to eradicate remaining pools of wild type poliovirus in endemic countries (Nigeria, Afghanistan, Pakistan). At the same time environmental surveillance must be done in all countries that exclusively use IPV. If wild type poliovirus is found in the sewage of such countries, then introduction of OPV, in children previously immunized with IPV, should be considered to eliminate the reservoir of will type virus. It will be important to observe the effect of the distribution of OPV in Israel on the circulation of wild type poliovirus.

*Infectious poliovirus was isolated by adding sewer and stool filtrates to monolayers of L20B cells, which are mouse fibroblasts that produce the cellular receptor for poliovirus. These cells were produced in my laboratory, and are useful for isolating polioviruses because they are not susceptible to infection with non-polio enteroviruses. I am pleased to be able to contribute to efforts to control poliomyelitis.

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


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.

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.


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


TWiV 110: CSI virology

Alan DoveHosts: Vincent Racaniello, Dickson DespommierAlan Dove, and Rich Condit

On episode #110 of the podcast This Week in Virology, Vincent, Alan, Rich, and Dickson discuss bacteria that can utilize arsenic in place of phosphorus, the passing of Frank Fenner, polio outbreak in The Congo, solving criminal cases of HIV transmission, and classifying viruses by capsid structure.

Click the arrow above to play, or right-click to download TWiV #110 (68 MB .mp3, 93 minutes).

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

Links for this episode:

Weekly Science Picks

Dickson – CDC’s West Nile virus case count for 2010
Rich –
The red bees of Red Hook
Alan – Arsenic-based life at XKCD
Vincent –
PLoS iPad app

Send your virology questions and comments (email or mp3 file) to or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at and tag them with twiv.

Poliovirus vaccine safety

Albert SabinThe contamination of the rotavirus vaccine Rotarix with porcine circovirus 1 DNA was revealed by deep sequencing. The same technique was also used to demonstrate that oral poliovirus vaccine does not contain viruses that can cause poliomyelitis.

The oral poliovirus vaccine strains developed by Albert Sabin (pictured) were licensed in the United States in 1962, and over the next 37 years immunization with these vaccines lead to the eradication of poliomyelitis in this country. During that period, the vaccine was responsible for 5-10 cases of poliomyelitis each year, either in recipients of the vaccine or in their contacts. Some of these individuals have sued the manufacturers of the vaccine, claiming that they made a defective product.

OPV contains three different poliovirus strains which were selected by Sabin because they do not cause poliomyelitis. We call such vaccine strains avirulent or attenuated. The mutations in the genetic information of the virus that prevent the development of paralysis have been identified. Unfortunately, these mutations are unstable. After oral administration, OPV replicates in the intestinal tract. During this phase the vaccine viruses undergo genetic change and eventually lose the mutations that made them avirulent. As a consequence, nearly every infant who receives OPV sheds in the feces polioviruses that are significantly more neurovirulent than those that were ingested.

Vaccine-associated poliomyelitis is caused by vaccine revertants that accumulate in the alimentary tract of immunized individuals. These neurovirulent viruses arise not because the vaccine is improperly prepared, but as a consequence of mutation during replication in the intestine. Proving this point to lay juries has been difficult. Now deep sequencing of poliovirus vaccine can show whether or not vaccine preparations are contaminated with neurovirulent viruses.

Deep sequence analysis of OPV manufactured by Bharat Biotech was done to detect mutations associated with neurovirulence. There are four mutations in the genome of type 1, two in the genome of type 2, and three in the genome of type 3 that are important for the attenuated property of the vaccine. The base present at each of these positions in the neurovirulent wild type viruses, and in the vaccine strains, is shown in the table.

Determinants of attenuation

The results of sequence analysis show that the Bharat vaccine does not contain any of the ‘wild type’ bases at these nine positions. Any vaccine-associated poliomyelitis associated with this vaccine is not a consequence of faulty production, but the fact that vaccine strains mutate during replication in the human gut.

There have been many lawsuits involving vaccine-associated poliomyelitis in which plaintiffs claim that the OPV was incorrectly manufactured, leading to a product of unacceptably high neurovirulence. Deep sequencing analysis of these lots of vaccine could have resolved this claim in a way that a lay jury could understand.

Is bivalent poliovirus vaccine a good idea?

polio-immunizationA new bivalent poliovirus vaccine, consisting of infectious, attenuated type 1 and type 3 strains, has been deployed in Afghanistan. The use of this vaccine was recommended by the Advisory Committee on Poliomyelitis Eradication, the global technical advisory body of the Global Polio Eradication Initiative. Considering the polio experience in Nigeria, the elimination of type 2 poliovirus from the vaccine might have serious consequences.

There are three serotypes of poliovirus, all of which can cause poliomyelitis. Infection with one serotype of the virus does not confer protection against the other two; therefore poliovirus vaccines have always included all three serotypes (they are trivalent). The attenuated vaccine that is used in the eradication effort is an infectious vaccine. The vaccine is ingested, the viruses replicate in the intestine, and immunity develops. Viruses of all three serotypes undergo genetic changes during replication in the alimentary tract. As a consequence, the vaccine recipient excretes polioviruses that can cause paralysis. These so-called vaccine-derived polioviruses (VDPV) can cause outbreaks of poliomyelitis in non-immune people, as described in Polio among the Amish.

Poliovirus type 2 was declared eradicated from the globe by the World Health Organization in 1999. When type 2 poliovirus was eliminated, many countries began using monovalent type 1 and type 3 vaccines: one vaccine for type 1 and another for type 3. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. Not unexpectedly, there was an outbreak of type 2 poliovirus in Nigeria in 2006. The surprise was that the outbreak was caused by a poliovirus type 2 vaccine strain.

Before 2003, the year that Nigeria began a boycott of polio immunization, the trivalent polio vaccine was used. Immunization resumed with monovalent types 1 and 3 vaccine in 2004. Therefore the source of the VDPV type 2 is most likely the trivalent vaccine used before 2003.

The press release at announcing the bivalent vaccine proclaims:

Of the three wild polioviruses (known as types 1, 2 and 3), type 2 has not been seen anywhere in the world since 1999.

The statement ignores the fact that there is vaccine-derived type 2 poliovirus in the world – and it can cause polio as well as ‘wild’ poliovirus. Such strains have been isolated in Nigeria as recently as October 2009. Why isn’t the type 2 vaccine being used in Afghanistan when it is very likely that vaccine-derived type 2 poliovirus is still circulating? Just because we haven’t isolated type 2 poliovirus recently doesn’t mean that it’s gone. No type 2 poliomyelitis was detected in 1999, yet the vaccine-derived virus was silently circulating in humans.

What will be the WHO response to an outbreak of type 2 polio in Afghanistan? They will probably deploy trivalent vaccine, as was done in Nigeria in 2006. But this approach will simply lead to another cycle of eradication and emergence of type 2 polio. It’s time to begin using inactivated poliovirus vaccine, which I’ve been dreaming about for some time.

Poliovirus type 2 returns

polio-immunizationThe global battle to eradicate poliomyelitis is already 9 years behind schedule. To make matters worse, type 2 poliovirus, which was declared eradicated in 1999, has returned.

There are three serotypes of poliovirus, each of which causes poliomyelitis. The vaccine used by WHO in the global eradication effort is a trivalent preparation comprising all three serotypes. When type 2 poliovirus was eliminated, many countries began using monovalent type 1 and type 3 vaccines: one vaccine for type 1 and another for type 3. As a consequence of this immunization strategy, population immunity to type 2 poliovirus declined. But if type 2 poliovirus was eradicated, where has it come from?

It came from the poliovirus vaccine.

The trivalent vaccine that is used in the eradication effort is an infectious vaccine. The vaccine is ingested, the viruses replicate in the intestine, and immunity develops. Viruses of all three serotypes undergo genetic changes during replication in the alimentary tract. As a consequence, the vaccine recipient excretes neurovirulent polioviruses. These so-called vaccine-derived polioviruses (VDPV) can cause outbreaks of poliomyelitis in non-immune people, as described in Polio among the Amish.

The outbreak of type 2 poliovirus in Nigeria began in 2006. There have been 126 cases of paralytic disease reported so far in 2009. Before 2003, the year that Nigeria began a boycott of polio immunization, the trivalent vaccine was used. Immunization resumed with monovalent types 1 and 3 vaccine in 2004. Therefore the source of the VDPV type 2 is most likely the trivalent vaccine used before 2003.

The resurrection of type 2 polio highlights the difficulties involved in using an infectious viral vaccine to eradicate the disease. In reality, type 2 poliovirus was not eradicated in 1999, because that virus was still present in the trivalent vaccine that was being used. Clearly the virus was still circulating in humans, despite the fact that no type 2 poliomyelitis was observed.

In response to the type 2 outbreak in Nigeria, trivalent vaccine is being used again. It’s not difficult to imagine that this will lead to another cycle of eradication and emergence of type 2 polio. What’s the solution to this apparently endless circle? Use inactivated poliovirus vaccine, which I’ve been dreaming about for some time.

Roberts, L. (2007). Vaccine-Related Polio Outbreak in Nigeria Raises Concerns Science, 317 (5846), 1842-1842 DOI: 10.1126/science.317.5846.1842

Roberts, L. (2009). Type 2 Poliovirus Back From The Dead in Nigeria Science, 325 (5941), 660-661 DOI: 10.1126/science.325_660

Jegede, A. (2007). What Led to the Nigerian Boycott of the Polio Vaccination Campaign? PLoS Medicine, 4 (3) DOI: 10.1371/journal.pmed.0040073

Polio returns to Minnesota

amishPoliovirus has been isolated from a patient who died last month in Minnesota. Is this incident related to the outbreak of polio in an Amish community in the same state four years ago?

Here are the facts about this case that have been released by the Minnesota Department of Health: the patient, an adult, had paralytic polio, but it is not known if this played a role in death. Apparently the patient had multiple health problems, including a weakened immune system. The virus isolated from this patient is related to the infectious, orally administered poliovirus vaccine, OPV. They speculate that the patient was infected with OPV over nine years ago, because the use of this vaccine in the US was discontinued in 2000.

The fact that OPV use was discontinued 9 years ago in the US does not prove that this patient was infected with a vaccine virus at that time. The only way to answer this question would be to determine the nucleotide sequence of poliovirus isolated from the patient. From this information the number of years that the vaccine-derived virus has been replicating in humans could be determined. However, no sequence information has been reported by the Department of Health. It is likely that the patient was infected with poliovirus at any time in the last 9 years. If in fact the patient had an immunodeficiency, then infection could have persisted for at least nine years, as has been reported in other immunodeficient patients. However, it seems unlikely that the virus would replicate for 9 years in this individual, and then cause paralytic disease only recently.

I believe this individual was a member of a Minnesota Amish community and was therefore not immunized with OPV as an infant. The patient was probably infected recently with a strain of poliovirus derived from OPV. Because OPV has not been used in the US since 2000 and in Canada since 1995-96, the infecting virus was either imported from another country, where OPV is still used, or shed by an immunodeficient individual in the US. Such patients excrete poliovirus for years in the absence of clinical symptoms. A similar scenario has been invoked to explain poliovirus infection in 2005 of children in a Minnesota Amish community.

We will find out whether this speculation is correct when the Centers for Disease Control and Prevention release the complete data on this case.

You might be wondering why poliovirus has been isolated on two separate occasions in Minnesota. It so happens that the former Minnesota State epidemiologist was Dr. Harry Hull,  who previously worked on the polio eradication campaign at the World Health Organization. When he arrived in Minnesota after his WHO stint, he installed an excellent polio surveillance system in the state which remains in place to this day.

Odoom, J., Yunus, Z., Dunn, G., Minor, P., & Martin, J. (2008). Changes in Population Dynamics during Long-Term Evolution of Sabin Type 1 Poliovirus in an Immunodeficient Patient Journal of Virology, 82 (18), 9179-9190 DOI: 10.1128/JVI.00468-08