We may be witnessing the last stand of the wild poliovirus (WPV). In 2015, approximately 70 cases of WPV were reported in only two countries – Pakistan and Afghanistan, representing approximately 0.02 % of the global polio burden in 1988, the year the Global Polio Eradication Initiative (GPEI) was launched [1]. As of the end of February, only five cases had been reported in 2016, and all in Pakistan [2]. Polio is not a ‘tropical disease’ and therefore represented a major problem in many developed countries until the 1960s. For example, in 1952, there were 58,000 cases of paralytic polio in the United States, resulting in 3,145 deaths and 22,000 people left with varying degrees of paralysis [3].

WPV is transmitted via the fecal-oral route and, therefore, thrives in environments where sanitation is poor. There are three types of WPV – 1, 2, and 3 – all of which can cause severe paralysis or death. However, for every 200 people infected (mostly children), only one develops paralysis, 20 have non-specific symptoms, and 180 are asymptomatic [4]. This creates challenges for surveillance as the virus may circulate undetected. There has been no case of WPV2 since October 1999 and it was officially declared eradicated in September 2015; WPV3 has not been detected since November 2012.

The most common polio vaccine used worldwide is the trivalent oral polio vaccine (OPV), which contains three types of live, attenuated (weakened) vaccine-viruses. OPV induces immunity against all three types of WPV in the gut of a vaccinated child, thus preventing the viruses from entering the bloodstream and the nervous system to cause paralysis. In most countries, three or four vaccine doses are adequate to protect a child from infection. However, in areas where water quality, sanitation, and hygiene are poor, children may require ten or more doses because the many other viruses and bacteria that infect their gut interfere with the body’s ability to mount an effective immune response, as was the case in the last reservoirs of polio in India – impoverished and densely populated districts of Bihar and Uttar Pradesh States [5]. Therefore, vaccines that target just one (‘monovalent’) or two (‘bivalent’) of the virus strains and induce higher levels of immunity than the trivalent vaccine were developed [6].

Vaccine-associated paralytic poliomyelitis occurs in an estimated 1 in 2.7 million children receiving their first OPV dose, which is why most upper-income countries have switched to the injectable, inactivated (dead) polio vaccine, which induces immunity in the bloodstream. Additionally, after a child is vaccinated, some of the vaccine-virus may be genetically altered during replication upon excretion, and is subsequently termed a vaccine-derived poliovirus. On rare occasions, there are enough susceptible children for the excreted viruses to begin circulating and cause paralytic cases in populations with low immunity; these viruses are called circulating vaccine-derived polioviruses (cVDPV) [7].

The GPEI was launched in 1988, when approximately 350,000 children were paralyzed by polio every year [8]. Initial progress was rapid; the last case of WPV in the WHO region of the Americas occurred in 1993 and the last case in the Western Pacific region (which includes China) occurred in 1997 [9]. However, the initial target of the GPEI to eradicate polio from the world by the year 2000 was not achieved [10]. Progress was slow for the subsequent decade; the number of cases reported in 2010 was higher than in 2000 and 20 countries were still reporting polio.

Since 2010, although deadlines for interrupting WPV transmission were missed in 2012 and 2015, significant progress has been made, including elimination in India and Nigeria. Globally, WPV cases declined from 1,352 in 2010 to 74 in just two countries in 2015 (WHO data 2 March 2016) [11]. The African continent has been WPV-free since August 2014.

Figure 1 shows the number of reported cases of WPV in Afghanistan, Pakistan, Nigeria, and non-endemic countries between 2011 and 2015 (data from [2]).

The GPEI is led by five partners that comprise the Polio Oversight Board, namely the World Health Organization, UNICEF, Rotary International, the US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation. The Independent Monitoring Board (IMB) was convened in late 2010 at the request of the World Health Assembly to monitor and guide progress towards eradication.

We are on the cusp of a polio-free world; however, several challenges need to be overcome in order to meet the deadline set by the Polio Oversight Board to interrupt WPV transmission in 2016. This commentary will discuss these major barriers, and briefly illustrate the paths through which these issues could be overcome.

The title of the IMB’s most recent report was “Now is the Time for Peak Performance” [19]. Indeed, the current low season of transmission (through May 2016) is the time to implement high-quality campaigns that achieve the greatest possible vaccination coverage, especially in areas such as southern Afghanistan, where large proportions of children are missed during campaigns.

The combined use of OPV and inactivated polio vaccine in campaigns is likely to boost population immunity and should be employed routinely in endemic countries and others that are vulnerable to reintroduction of WPV (e.g. Nigeria, Cameroon, Chad, Somalia, and Yemen).

Environmental surveillance should be rapidly expanded throughout Pakistan and Afghanistan coupled with rigorous outbreak response action when positive samples are found. Since WPV causes paralysis in less than 1 % of infected children, an ‘orphan’ virus may circulate undetected by routine acute flaccid paralysis surveillance [20]. In addition, surveillance ‘blackspots’ need to be addressed in countries where international surveillance indicators are not met.

High-level political commitment is essential at the national level to ensure accountability for campaign quality by provincial governors in Afghanistan and state governments in Pakistan and Nigeria. However, at the frontline, the polio campaign needs to be politically neutral to avoid negative responses from anti-government elements.

The rest of the world cannot be complacent. Reintroduction of WPV led to a major outbreak in Somalia in 2013 after a ban by armed militants led to half a million children going unimmunized for three years. Recent clusters of vaccine-derived poliovirus in countries as diverse as Ukraine, Myanmar, and Madagascar indicate low population immunity.