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Monday, 19th of January 2009 Print


To date, the world has seen eight outbreaks of circulating vaccine derived poliovirus, cVDPV, in Hispaniola, Indonesia, Egypt, Madagascar (×2), Philippines, China and Cambodia. This includes the very large Egyptian outbreak, from 1988 to 1993, an outbreak confirmed years later by retrospective examination of lab samples originally mistaken for wild poliovirus. As of this writing, January 2009, Nigeria is home to an outbreak of Type 2 VDPV that has continued for more than a year.

In this article from PLOS, Wringe and colleagues review the virological and epidemiological evidence on VDPV with special attention to case to infection ratios, paying particular attention to the large VDPV epidemics in Hispaniola, Indonesia and Egypt.

Wringe and colleagues do not minimize the importance of VDPV:

'To describe the problem of vaccine-derived polio as 114 virologically-confirmed cases, worldwide, over some twenty years, gives a very different impression than a description which suggests a minimum of hundreds of thousands, and more likely several million infections by vaccine-derived viruses, some of which became endemic in large populations. It is also possible that other vaccine-derived virus lineages have circulated for limited time periods, but failed to cause any clinical cases and were thus unrecognized[61]. The risk of VDPV appearance and the incidence and spread of these infections will be important considerations for policies relating to the cessation of OPV, for future surveillance needs, and for planning for outbreak control in the future, including stockpiling vaccines.'

These findings have important implications for the future of polio vaccination policy. One solution to VDPV is stockpiling of monovalent OPV. But is the solution a problem if mOPV runs the risk of generating fresh VDPV? Can we eliminate the risk of VDPV without recourse to IPV?

Full text is at http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003433


2, 3)          VDPV CASE REPORTS

Over 30 countries have gone over from OPV or joint IPV/OPV administration to the exclusive use of IPV, which generates neither VDPV nor vaccine associated paralytic polio (VAPP). One of those countries, Spain, recently reported a case of VDPV contracted in Morocco but detected in Spain. That case, and a case from China, form the subject of the second and the third contributions.
Those with special interests in the Egyptian outbreak can read the report online at http://jvi.asm.org/cgi/content/full/77/15/8366?view=long&pmid=12857906#R43


Neal Nathanson points out knowledge gaps in our understanding of polio. His last two points, summarized in the abstract below, are pertinent to the previous discussion.

N Nathanson, The pathogenesis of poliomyelitis: what we don't know.

Adv Virus Res. 2008;71:1-50

Department of Microbiology and Neurology, School of Medicine, University of Pennsylvania, Philadelphia, PA

Poliomyelitis has long served as a model for studies of viral pathogenesis, but there remain many important gaps in our understanding of this disease. It is the intent of this review to highlight these residual but important questions, in light of a possible future moratorium on research with polioviruses. Salient questions include: (1) What cells in the gastrointestinal tract are initially infected and act as the source of excreted virus? (2) What is the receptor used by mouse-adapted strains of poliovirus and how can some polioviruses use both mouse and primate receptors? (3) What determines species differences in susceptibility of the gastrointestinal tract to polioviruses? Why cannot PVR transgenic mice be infected by the natural enteric route? (4) Why are neuroadapted polioviruses unable to infect nonneural cells? (5) What is the role of postentry blocks in replication as determinants of neurovirulence? (6) What route(s) does poliovirus take to enter the central nervous system and how does it cross the blood-brain barrier? (7) Why does poliovirus preferentially attack lower motor neurons in contrast to many other neuronal types within the central nervous system? (8) Does cellular immunity play any role in recovery from acute infection or in vaccine-induced protection? (9) In which cells does poliovirus persist in patients with gamma-globulin deficiencies? (10) Is there any evidence that poliovirus genomes can persist in immunocompetent hosts? (11) Why has type 2 poliovirus been eradicated while types 1 and 3 have not? (12) Can transmission of vaccine-derived polioviruses be prevented with inactivated poliovirus vaccine? (13) What is the best strategy to control and eliminate vaccine-derived polioviruses?


In this paper, summarized below, Wagner and Earn look at possible solutions to the problem of cVDPV. Their conclusions are in highlight.
Wagner BG, Earn DJ, Bull Math Biol. 2008 Jan;70(1):253-80

Department of Mathematics and Statistics, McMaster University, 1280 Main Street West, Hamilton, ON L8S 4K1, Canada. wagnerb@math.mcmaster.ca

Poliomyelitis vaccination via live Oral Polio Vaccine (OPV) suffers from the inherent problem of reversion: the vaccine may, upon replication in the human gut, mutate back to virulence and transmissibility resulting in circulating vaccine derived polio viruses (cVDPVs). We formulate a general mathematical model to assess the impact of cVDPVs on prospects for polio eradication. We find that for OPV coverage levels below a certain threshold, cVDPVs have a small impact in comparison to the expected endemic level of the disease in the absence of reversion. Above this threshold, the model predicts a small but significant endemic level of the disease, even where standard models predict eradication. In light of this, we consider and analyze three alternative eradication strategies involving a transition from continuous OPV vaccination to either continuous Inactivated Polio Vaccine (IPV), pulsed OPV vaccination, or a one-time IPV pulse vaccination. Stochastic modeling shows continuous IPV vaccination is effective at achieving eradication for moderate coverage levels, while pulsed OPV is effective if higher coverage levels are maintained. The one-time pulse IPV method may also be a viable strategy, especially in terms of the number of vaccinations required and time to eradication, provided that a sufficiently large pulse is practically feasible. More investigation is needed regarding the frequency of revertant virus infection resulting directly from vaccination, the ability of IPV to induce gut immunity, and the potential role of spatial transmission dynamics in eradication efforts.


Good reading.