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

 

Poliovirus silently (and not so silently) spreads

Poliovirus by Jason RobertsPoliovirus has been found in sewage in Israel. The virus detected is not vaccine-derived poliovirus; it is wild-type 1 poliovirus, the strain that occurs naturally in the wild and which the World Health Organization is trying very hard to eradicate from the planet.

As part of the global effort to eradicate poliovirus, environmental samples from many countries are routinely examined for the presence of the virus. Wild type poliovirus was detected in 30 sewage sample from 10 different sites, collected from 3 February to 30 June 2013 in Israel. No cases of paralytic disease have been detected in that country. This is not a surprising finding because only roughly one in 100 individuals infected with poliovirus develop paralysis.

During poliovirus infection, the virus replicates in the gastrointestinal tract and is shed in the feces. Most of the poliovirus-positive sewage samples were from southern Israel. Finding the virus at multiple sites suggests that the virus has been in the population for an extended period of time and that multiple individuals are shedding virus.

Why is wild type virus circulating in Israel? Poliovirus vaccine coverage in Israel is high but it is never 100%, and non-immunized individuals are hosts for the virus. Another explanation is related the the use of inactivated poliovirus vaccine (IPV) in Israel. Immunization with IPV, which is administered intramuscularly, does not protect the alimentary tract from infection. Therefore poliovirus can replicate in the intestine of immunized individuals, but once the virus reaches the blood its spread is blocked by anti-viral antibodies.

An interesting question is whether there is wild type poliovirus in the United States. I suspect that if we looked for poliovirus in our sewage, we would find it. However we no longer carry out surveillance of sewage for poliovirus and therefore we do not know if it is present.

Genetic analysis of wild type poliovirus from Israel suggests that it is related to the strain found in December 2012 in sewers in Cairo, Egypt. That virus in turn is closely related to virus from Pakistan, one of three countries from which wild type poliovirus has not been eradicated (the others are Nigeria and Afghanistan).

There is an ongoing outbreak of poliomyelitis in the Horn of Africa, with 65 cases in Somalia and 8 cases in Kenya. The virus causing that outbreak came from Nigeria. Somalia and Kenya had been free of polio since 2007 and 2011, respectively.

WHO has concluded that the risk of further international spread of wild type poliovirus from Israel as moderate to high. As long as there are individuals who are not immune, there will be a risk of poliovirus infection, in part due to the silent infections caused by the virus.