TWiV 373: The distinguished virology career of Julius S. Youngner

On episode #373 of the science show This Week in Virology, Vincent speaks with Julius about his long career in virology, including his crucial work as part of the team at the University of Pittsburgh that developed the Salk inactivated poliovirus vaccine.

You can find TWiV #373 at Or you can watch the video below.

Oral polio vaccine-associated paralysis in a child despite previous immunization with inactivated virus

Poliovirus by Jason Roberts

Poliovirus by Jason Roberts

Vaccine-associated poliomyelitis caused by the oral poliovirus vaccine is rare, but its occurrence in a healthy, immunocompetent 6-month old child was highly unusual because the child had been previously immunized with two doses of the injected, inactivated poliovirus vaccine (IPV).

The three poliovirus vaccine strains developed by Albert Sabin (OPV, oral poliovirus vaccine) contain mutations which prevent them from causing paralytic disease. When the vaccine is ingested, the viruses replicate in the intestine, and immunity to infection develops. While replicating in the intestinal tract, the vaccine viruses undergo mutation, and 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 the Sabin vaccine.

To prevent vaccine-associated poliomyelitis, in 1997 the US switched to an immunization schedule consisting of two doses of IPV followed by one dose of OPV. The US then switched to using IPV exclusively in 2000. The child in this case essentially had a polio immunization course similar to that utilized in the US from 1997-2000: two doses of IPV, one dose of OPV. Why did the child develop poliomyelitis?

One clue comes from the fact that after the switch to an IPV-OPV schedule in 1997, there were still three cases of VAPP in 1998 and three in 1999. Another hint comes from a study of immune responses in children given multiple doses of IPV. Most of the children receiving two doses of IPV produced antibodies against types 1 and 2 poliovirus (92 and 94%), but only 74% of children produced antibodies against type 3 poliovirus.

The final piece of information needed to solve this puzzle is that the child in this case had vaccine-associated poliovirus caused by the type 3 strain, which was isolated from his feces.

Therefore, the child in this case most likely did not produce sufficient antibodies to type 3 poliovirus after receiving the two doses of IPV. As a consequence, when he was given OPV, he developed type 3 vaccine-associated poliomyelitis.

This case of VAPP could have been prevented: the child was born in Canada, and as customary in that country since 1995, he received two doses of IPV. At 5 months of age the child and his family visited China, where his parents decided to continue his immunizations according to the local schedule. China still uses OPV, so that is what the child received.

India has been free of polio for three years

Poliovirus cutaway

Image credit: Jason Roberts

Three years ago today, on 13 January 2011, the last case of poliomyelitis was reported in India. This achievement represents a remarkable turnaround for a country 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 in India. Being polio-free for three years is certainly a cause for celebration, but not for becoming complacent. Immunization efforts in India must not decline, because wild-type and vaccine-derived polioviruses continue to circulate and pose a threat to any unimmunized individual.

Wild polioviruses – those that have always been circulating in nature – continue to cause disease in Afghanistan and Pakistan, two countries close to India. Pakistan reported 58 polio cases in 2012, and 85 so far in 2013; for Afghanistan the numbers are 37 and 12. But distant countries can also transmit polio: recent outbreaks in the Horn of Africa and in Syria originated in Nigeria and Pakistan, respectively.

Perhaps a greater threat are vaccine-derived polioviruses. The Sabin poliovirus vaccines, which have so far been the mainstay of the polio eradication effort, comprise infectious viruses that are taken orally. Upon replication in the intestinal tract, the vaccine strains confer immunity to infection, but they also revert and become capable of causing paralysis. Such vaccine-derived polioviruses circulate and can cause outbreaks of polio. Because India has been using Sabin poliovirus vaccines intensely for many years, there is no doubt that vaccine-derived polioviruses are circulating in that country. If polio vaccine coverage drops, there will be outbreaks of polio caused by vaccine-derived strains. Even if wild polioviruses disappeared from the globe, as long as Sabin vaccines are used, vaccine-derived polioviruses will circulate. The solution to this conundrum is to switch to Salk’s inactivated poliovirus vaccine and wait for the Sabin-derived strains to disappear. This switch is now part of the WHO’s eradication plan (it wasn’t always), but it will not be easy: Salk vaccine must be injected, and therefore requires trained health care personnel; administering Sabin vaccine requires no special skills. But we cannot simply stop immunizing with Sabin vaccine – that is a recipe for outbreaks of polio.

According to the World Health Organization, being free of wild polio for three years means that the virus is probably no longer endemic in India. However, WHO does not certify individual countries as polio-free; rather it declares a WHO region polio-free when all countries in the Region have not reported a case of wild polio for 3 years in the face of highly active surveillance. The Americas, the Western Pacific, and European regions have been declared polio-free by WHO. India is part of the South-East Asia region, which also includes Bangladesh, Bhutan, Democratic People’s Republic of Korea, Indonesia, Maldives, Myanmar, Nepal, Sri Lanka, Thailand, and Timor-Leste, none of which have reported a case of polio for 3 years. WHO will decide in March whether to declare this region polio-free. That would leave the regions of Africa and the Eastern Mediterranean as the last known reservoirs of wild poliovirus.