WHO assessment of experimental Ebola virus vaccines

The World Health Organization held a conference to assess the status of testing and eventual licensing of two candidate Ebola virus vaccines. The agenda and list of participants and the final report are available. I was interested in the following list of key expected milestones:

October 2014:
Mechanisms for evaluating and sharing data in real time must be prepared and agreed upon and the remainder of the phase 1 trials must be started

October–November 2014:
Agreed common protocols (including for phase 2 studies) across different sites must be developed

October–November 2014:
Preparation of sites in affected countries for phase 2 b should start as soon as possible

November–December 2014:
Initial safety data from phase 1 trials will be available

January 2015:
GMP (Good Manufacturing Practices) grade vaccine doses will be available for phase 2 as soon as possible

January–February 2015:
Phase 2 studies to be approved and initiated in affected and non-affected countries (as appropriate)

As soon as possible after data on efficacy become available:
Planning for large-scale vaccination, including systems for vaccine financing, allocation, and use.

I wonder how a phase 2 study will be conducted, the goal of which is to determine if it is effective and further evaluate its safety. Will this be done in west Africa, where protection against Ebola virus infection can be assessed? If so, will there be controls who receive placebo?

If indeed an Ebola virus vaccine is our best hope in limiting the current outbreak, it won’t be distributed for a while, according to the optimistic expectations of WHO – assuming all proceeds on time, and that the results are favorable.

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.

WHO report on human cases of avian influenza A(H7N9) infection

The World Health Organization has been publishing weekly reports on the avian influenza A(H7N9) outbreak which include the geographical location of each case, the cumulative number of cases, and the epidemiological curve. Go to this page at the WHO website for an archive of the weekly reports (there you will also find other useful information on the H7N9 outbreak). Images for report #3 of 24 April 2013 are reproduced below. Click each image for a larger view.


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.

TWiV 188: Haggis, single malt, and viruses

On episode #188 of the science show This Week in Virology, Vincent travels to Scotland to meet with members of the Centre for Virus Research at the University of Glasgow to discuss their work on hepatitis C virus and jaagsiekte sheep retrovirus.

You can find TWiV #188 at www.microbe.tv/twiv.