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).

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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

Learning vaccinology from an immunization record

vrr-immunization-recordLast week on TWiV #26 Rich Condit and I were reminiscing about the possibility that we had received the virus SV40 along with our polio immunizations. That discussion prompted me to examine my immunization record for poliovaccine that my Mother had given to me in the early 1990s. She was cleaning out her house and decided that I should have it – a little memento for someone who has studied poliovirus for most of his career. Can we learn anything of value from this old immunization record?

The first lesson comes from the earliest date on the card, September 1963. I was ten years old – why was I receiving poliovaccine at that advanced age? A child born today in the US is given poliovaccine at 2, 4, and 6-18 months, and then at 4-6 years of age. I was immunized in 1955-56 with the first batches of inactivated poliovirus vaccine, IPV, created by Jonas Salk. Although IPV was used in mass immunization campaigns in the US and reduced the incidence of polio from a peak of 21,000 cases in 1952 to 2,500 in 1960, many felt that it did not confer lifelong immunity and would not lead to eradication of the disease. Hilary Koprowski, Herald Cox, and Albert Sabin all believed that an infectious poliovirus vaccine, which mimicked a natural infection, was needed. Sabin’s oral poliovirus vaccine (OPV) was licensed in the US in 1961, and once again American children stood in line for mass immunizations. OPV is taken by mouth, and I remember clearly waiting in the school auditorium in front of rows of tables covered with small paper cups. Inside each one was a pink sugar cube – the color a consequence of the vaccine which had been poured on it. I ate the sugar cube three times – September 1963, and then April and May of 1964.

If I had been immunized with IPV in the 1950s, wouldn’t the immunological memory block infection with OPV? No, because immunization with IPV did not confer protection of the alimentary tract, which is the initial site of replication of the OPV strains.

There are three columns on the card labeled type I, type II, and type III, which refer to the serotypes of poliovirus that had been poured on the sugar cubes. These monovalent poliovirus vaccines were stopgap measures, used only until approval came in 1964 for a single vaccine containing all three viral serotypes – trivalent OPV. The use of monovalent type 1 OPV resumed a few years ago in Egypt, because of the rarity of polio caused by the other serotypes.

Notice the order in which I received the three monovalent vaccines – type I first, followed by type III, and then type II. This sequence was initially used to prevent the type II virus from interfering with the subsequent replication of the type III strain. Later in 1964, the Advisory Committee on OPV recommended that the order of administration be changed to type II, I, and III. It was believed that giving type II vaccine first would diminish the risk of paralysis associated with types I and III.

Finally, note where the vaccine was administered – Edith A. Bogert School. Why didn’t I receive it in a doctor’s office? Because in mass immunization campaigns, vaccine is most efficiently given in locations where millions of children can be inoculated in a short time. We no longer use this approach – in developed countries new vaccines are incorporated into routine immunization schedules and dispensed in doctors’ offices. Mass immunization campaigns are deployed when it is necessary to quickly stop the chain of transmission. They are still used countries where polio is endemic, such as India, Pakistan, and Afghanistan.

That’s quite a bit to learn from a very small piece of paper. Maybe that’s why my Mother saved it for me.

Poliovirus vaccine litigation

polio-litigationThe oral poliovirus vaccine strains (OPV) developed by Albert Sabin 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.” My experience as an expert witness in a recent poliovirus vaccine litigation illustrates how difficult it can be for a jury to understand complex scientific issues in cases where there typically is no dispute that the product caused the injury.

My most recent experience involved a case in New York that began early in May 1979, when the plaintiff’s daughter received her second dose of Orimune (the trade name for the live, oral trivalent poliovirus vaccine previously produced by Lederle Laboratories). Approximately 6 weeks later, the plaintiff developed severe back pain and then permanent paralysis of both legs. I will focus on one of the many claims of his lawsuit against Lederle Laboratories: that the vaccine failed to comply with the release standards previously set by the Food and Drug Administration (FDA) for monkey neurovirulence testing, which must be conducted on each monovalent lot, or “monopool,” of vaccine. (OPV is no longer used in the United States for routine immunizations, and the FDA’s regulations on testing the vaccine have been repealed.)

The Sabin poliovirus vaccine strains are prepared by separately growing each of the three viral serotypes in primary monkey kidney cells. Before the vaccines can be released, they are tested by both the manufacturer and the FDA for neurovirulence by injecting samples of the monopools directly into the brains and spinal cords of monkeys. Three weeks after inoculation, the animals are sacrificed, and histological sections are prepared and examined by a pathologist for evidence of cell damage caused by poliovirus. The lesions are scored on a scale of 0 to 4, depending on the extent of cell destruction caused by poliovirus. Each monkey is then given a neurovirulence score, which is expressed as ‘severity’ (the lesion score at the site of inoculation) and ‘spread’ (the lesion score distal to the site of inoculation). These scores are then compared with all the values historically obtained in monkey neurovirulence testing conducted using a reference strain of poliovirus.  The FDA’s regulations allowed the monopools to be used in the further manufacture of vaccine only if their neurovirulence in monkeys did not exceed the neurovirulence of the reference preparation.

The plaintiff claimed that one of the two type 3 monopools that were likely part of his daughter’s vaccine was excessively neurovirulent. In particular, the plaintiff argued that the FDA’s intraspinal neurovirulence test on one of these type 3 pools revealed a single monkey with a severity-spread score of 3-3. No monkeys with a 3-3 score had been observed on Lederle’s intraspinal test of this vaccine monopool. Plaintiff claimed that this monovalent pool should not have been released under the FDA’s standards, because a monkey with a severity-spread score of 3-3 had never been observed previously on intraspinal testing of the reference strain.

From a scientific point of view, the plaintiff’s claims are, in my view, insupportable.

First, claims about the type component of the vaccine do not appear to be scientifically relevant unless the plaintiff’s polio was caused by type 3 poliovirus.  In this case, type 3 poliovirus was isolated in the plaintiff’s stool shortly after the onset of paralysis, demonstrating that type 3 virus was replicating in his digestive tract.  But complement fixation tests conducted on blood samples also demonstrated a vigorous antibody response to type 2 poliovirus before any response was detected to type 3 poliovirus.  From this evidence, I do not think that it can be said that the plaintiff’s infection of his spinal cord was caused by type 3 virus, as opposed to type 2 virus. The jury reached a different conclusion which in my view is not supported by the scientific evidence.

Second, a single monkey with a 3-3 neurovirulence score appears to have played an important role in this case, but that ignores the fact that there are almost always wide variations that result in “outliers” whenever biological assays are involved.  We have studied poliovirus infection of mice in my laboratory, for example, and outliers are common – the one mouse in twenty that becomes ill or dies, while the others remain well. Other investigators have shown that poliovirus recovered from the spinal cord of an outlier monkey – one with a 3-3 neurovirulence score – does not produce these results when re-injected in a different group of monkeys. The monkey with a 3-3 score observed in the government’s test of one monopool of type 3 poliovirus vaccine is clearly an outlier. The other 14 monkeys in the intraspinal test had very low scores, and Lederle’s neurovirulence test did not produce a monkey with a 3-3 score. I conclude that the neurovirulence test on this type 3 monopool clearly did not exceed that of the reference virus – there is no scientifically valid justification for arguing otherwise.

If you don’t believe in outliers, there is another way to look at this issue: does a monkey with a 3-3 score in the neurovirulence test mean that the lot of vaccine is more likely to cause paralysis in humans? We cannot carry out such an experiment prospectively, but we can do the next best thing – compare the results of the monkey neurovirulence test with the rate of vaccine-associated poliomyelitis. In the entire history of the monkey neurovirulence test – from 1962-1999 – some monopools of vaccine periodically had one or two monkeys with a 3-3 neurovirulence score, and others did not. Nevertheless, the rate of vaccine-associated paralytic disease remained remarkably constant over this time: 5-10 cases per year. There were no spikes in the years when the “3-3” vaccines were in distribution. The conclusion is clear: no lot of vaccine is associated with an increase in the number of paralytic cases in any year.

Why do the Sabin vaccine strains cause paralytic disease in some recipients and contacts? Albert Sabin derived these vaccine strains by serially passing neurovirulent isolates in different cell types, empirically identifying viral mutants with a reduced capacity to cause disease. There are few mutations responsible for the reduced neurovirulence of the Sabin strains – 5 for type 1, and 2 each for the type 1 and type 2 strains. These mutations rapidly revert during multiplication of the vaccine viruses in the human gut, and that occurs in every recipient of the vaccine. Within several days, the recipient sheds viruses that no longer bear the mutations that Sabin so painstakingly selected. These excreted revertants, when tested in monkeys, are more neurovirulent than the vaccine that was fed to the recipient.

Given the high reversion rate of the poliovirus vaccine in the human intestine, it is hard to understand why the vaccine is so safe in practice. Put another way, why do some individuals contract poliomyelitis after exposure to the vaccine, while the vast majority to not? Their paralytic disease is caused by neurovirulent revertant viruses, but why these individuals are more susceptible than the general population is unknown. One hypothesis is that they have a sub-optimal, innate immune response to infection, which allows unchecked multiplication of the revertant viruses and eventual invasion of the brain and spinal cord.

The timing of the plaintiff’s paralysis in the New York case is highly revealing. He reported the first symptoms of paralysis 6 weeks after his daughter received the vaccine. There is a 12-15 day incubation period between the time when poliovirus is ingested and the first appearance of paralytic symptoms. Working backwards, it is likely that the plaintiff was infected by his daughter’s vaccine during the first week of June – nearly four weeks after administration of Orimune to the infant. By this time, all the type 3 viruses that the baby was excreting had reverted to greater neurovirulence. The results of the monkey neurovirulence tests on the vaccine that was fed, therefore, have no relevance to the virus that infected the plaintiff. No matter what scores had been obtained on the monpools by the FDA or by the manufacturer, the excreted virus would have all reverted to neurovirulence long before the plaintiff’s infection.

In my view, the scientific evidence overwhelmingly indicates that the neurovirulence of the vaccine in this case was acceptable. I believe that I explained the science clearly to the jury; nevertheless, they found the defendant released vaccine that violated the FDA’s monkey neurovirulence standards and that posed a greater risk than the risk that is inherent in all OPV. This case illustrates that complex scientific issues that we struggle with in the laboratory are most difficult to grasp by jurors. Indeed, one could argue that using a lay jury to decide scientific issues is an imperfect solution. Perhaps cases like this should be resolved by truly expert panels of scientists who are in a better position to evaluate the evidence presented.

Oral polio vaccine has an inherent risk that public health authorities deemed to be acceptable, given the extraordinary benefits of the vaccine. However, in a sense, the ~400 individuals who contracted vaccine-associated polio from 1962-1999 paid a price for the greater good of the population. For this reason alone they deserved compensation, which is what they now receive under the National Childhood Vaccine Injury Act.  Compensation for these individuals is given without the need to castigate life-saving vaccines likes OPV.

Bacteriophages in viral vaccines

bacteriophage-sockWhen live, attenuated poliovirus vaccine was used in the US, its production and testing was regulated by the Food and Drug Administration. Guidelines for preparing and testing the vaccine can be found in the Code of Federal Regulationsthe codification of the rules published in the Federal Register by the executive departments and agencies of the Federal Government. While reading the 1991 regulations for OPV, I came across the following curious statement:

Each seed virus used for vaccine manufacture shall be prepared from an acceptable strain in monkey kidney cell cultures, derived from animals…or in a cell culture of a type determined to be suitable by the Director…The seed virus used in vaccine manufactures shall be demonstrated to be free of extraneous microbial agents except for the unavoidable bacteriophage.

Some live human virus vaccines have been shown to contain bacterial viruses. Why would there be ‘unavoidable bacteriophage’ in seed virus and vaccines? If you know the answer, post it in the comments section, and I’ll explain fully tomorrow. I’ll also tell you why this has been an all-poliovirus week at virology blog.

Polio among the Amish

amishThe last outbreak of poliomyelitis in the United States occurred in 1979, when a type 1 strain imported from the Netherlands caused 13 paralytic cases among unvaccinated Amish communities in three states. Twenty years later, use of the live, attenuated poliovirus vaccine (OPV) was discontinued in the United States, and was replaced with the inactivated vaccine, IPV.  How do we explain the 2005 outbreak of polio in an Amish community in Minnesota?

The infant in this case was five months old when it was hospitalized for fever, irritability, bloody diarrhea, and recurrent infections. Vaccine-derived poliovirus (VDPV) type 1 was isolated from a stool specimen, but paralysis did not occur. VDPVs are excreted by individuals who receive OPV; they have been shown to circulate for long periods and cause outbreaks of paralytic disease in undervaccinated populations. Similar VDPVs were subsequently isolated from four other children in the same Amish community, none of whom were ill. A total of 8 out of  23 children tested had virologic or serologic evidence of type 1 poliovirus infection.

Sequence analysis of the VDPVs was used to estimate that the virus had probably circulated for 2 months in the community before infecting the infant. Such estimates are based on the known rate of sequence change in the poliovirus genome as it moves through the human population. The origin of the VDPV was not identified, despite extensive virological and serological studies of other communites in the US and Canada which might have had contact with the individuals in Minnesota. The source of the virus is probably a recipient of OPV outside of the US and Canada – these countries stopped using this vaccine in 2000 and 1995-96, respectively.

The infant was subsequently diagnosed with severe combined immunodeficiency, a disease characterized by defects in B and T cell immunity and frequent infections. Poliovirus was detected in her stool until January 2006, after which the immunodeficiency was corrected by bone marrow transplant and the virus was eliminated.

All previous outbreaks of poliomyelitis caused by VDVP were in undervaccinated communities in underdeveloped countries. The outbreak in Minnesota underscores the need to maintain high vaccination coverage: until OPV is replaced with IPV globally, circulating VDPVs pose a threat to unimmunized individuals. The outbreak is a harbinger of what could occur in countries where immunization with OPV is halted after the eradication of poliomyelitis. As the number of susceptible newborns increases, circulating VDVPs could spark an outbreak of poliomyelitis.  Another reason for switching to IPV rather than stopping immunization altogether.

James P. Alexander, Kristen Ehresmann, Jane Seward, Gary Wax, Kathleen Harriman, Susan Fuller, Elizabeth A. Cebelinski, Qi Chen, Jaume Jorba, Olen M. Kew, Mark A. Pallansch, M. Steven Oberste, Mark Schleiss, Jeffrey P. Davis, Bryna Warshawsky, Susan Squires, Harry F. Hull (2009). Transmission of Imported Vaccine‐Derived Poliovirus in an Undervaccinated Community in Minnesota The Journal of Infectious Diseases, 199 (3), 391-397 DOI: 10.1086/596052